Barely three months into the new year and we are happy to announce a monumental milestone reached - 150 million downloads.
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This achievement solidifies IntechOpen’s place as a pioneer in Open Access publishing and the home to some of the most relevant scientific research available through Open Access.
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We are so proud to have worked with so many bright minds throughout the years who have helped us spread knowledge through the power of Open Access and we look forward to continuing to support some of the greatest thinkers of our day.
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Thank you for making IntechOpen your place of learning, sharing, and discovery, and here’s to 150 million more!
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\r\n\tSpinal cord injury represents a relatively frequent clinical scenario that emergency doctors, neuroradiologists, and spine surgeons have to deal with in their daily practice.
\r\n
\r\n\tAlthough there are many publications on this topic, a consensus on the preferred management has not been reached yet. In fact, other than clearly surgical or non-surgical patients, there is a non-negligible number of cases where an interdisciplinary discussion is strictly needed, eventually determining a case-by-case treatment selection.
\r\n
\r\n\tEmergency decompression surgery, often associated with fusion, represents an effective treatment for critical compressions of the spinal cord, while its role in subacute cases is still debated. Different medical managements have been proposed for the acute, subacute, and chronic phases, respectively. Since function preservation is the primary outcome to be pursued, the multidisciplinary case discussion is a fundamental step in the decision-making process. However, a practical guide on the state of the art on spinal cord injury management may result as useful to a large audience of practitioners.
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Dr. Ricciardi serves as a guest editor, editorial board member, and reviewer of many indexed journals such as the Journal of Neurosurgical Sciences and Frontiers in Neurooncology, Life, and Cell. He is a co-chairman for SPINE20, the World Congress on Spine Disorders at the G20 conference in Rome, Italy, and an individual delegate at the European Association of Neurosurgical Societies.",coeditorOneBiosketch:"A neurosurgeon specialized in craniocervical junction diseases and minimally invasive spine surgery. Dr. Lofrese was awarded the European Young Researcher Award (AOSpine) and the Young Neurosurgeon Award (WFNS). He is a member of EUROSPINE, SPINE20, and the European Association of Neurosurgical Societies.",coeditorTwoBiosketch:"Dr. Perna's main fields of study are the pathologies of the spine, with particular attention to spinal deformities, traumatological surgery, and infectious pathologies such as spondylodiscitis. 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1. Introduction
Direct repair is defined as the elimination of DNA and RNA damage using chemical reversion that does not require a nucleotide template, breakage of the phosphodiester backbone or DNA synthesis. As such, the process of direct repair is completely error-free, granting a major advantage in preservation of genetic information. In mammalian cells, direct repair is utilized to repair specific types of DNA and RNA damage caused by ubiquitous alkylating agents. Only two major types of proteins conduct direct repair in mammalian cells, O6-methylguanine-DNA methyltransferase (MGMT or AGT) and ALKBH family Fe(II)/α-ketoglutarate dioxygenases (FeKGDs). In humans and mice, a single direct repair methyltransferase protein exists, MGMT. In contrast, ALKBH FeKGDs represent a family of nine homologs with conserved active site domains. Although the biochemical function of a number of ALKBH proteins and their biological roles require further investigation, several directly repair alkylation damage in DNA and RNA at base-pairing sites.
2. Direct repair substrates—DNA and RNA alkylation damage
Exposure to alkylating agents is major cause of DNA and RNA damage, generating adducts that can compromise genomic integrity. As a result, repair of alkylation adducts is mediated by a variety of DNA repair pathways, some with overlapping substrate specificity. However, direct DNA repair proteins utilize unique mechanisms to specifically eliminate damage at base-pairing sites. The frequency and site of DNA and RNA damage occurrence is dependent on the source and type of alkylating agent exposure, as discussed in this section.
3. Sources of alkylation damage
Alkylating agents are present environmentally and also generated within the cell via oxidative metabolism. They modify DNA and RNA, forming adducts that disrupt replication and transcription, trigger cell cycle checkpoints, and/or initiate apoptosis. If left unrepaired, some adducts formed by alkylation damage can be cytotoxic and/or mutagenic [1-3].
Environmental alkylating agents fall into two primary groups, nitrosoureas that generate primarily O-alkylations and methanesulfonates that cause mostly N-alkylations [1, 3] (Figure 1). These exogenous alkylating agents are present in air, water, plants and food, in the form of nitrosamines, chloro- and bromomethane gases, myosamines and halocarbons [4]. There are also industrially produced alkylating agents, including various chemotherapeutic agents [5, 6].
Figure 1.
Examples of nitrosourea and methanesulfonate alkylating agents. (A) Nitrosourea, SN1, alkylating agents. Abbrevations are as follows: methylnitrosourea (MNU); ethylnitrosourea (ENU); 1,3-bis (2chloroethyl)-1-nitrosourea (BCNU); N-(2-chloroethyl)-N-cyclohexyl-N-nitrosourea- (CCNU); N-methyl-N-nitro-N-nitrosoguanidine (MNNG); N-ethyl-N-nitro-N-nitrosoguanidine (ENNG). (B) Methanesulfonate, SN2, alkylating agents. Abbrevations are as follows: dimethylsufate (DMS); diethylsulfate (DES); methylmethanesulfonate (MMS); ethylmethanesulfonate (EMS). [14]
Enzymes involved in cellular metabolism are responsible for the majority of endogenous alkylating agent damage. Nitrosating agents are generated, resulting in amine nitrosation, and reactive oxygen species (ROS), which cause lipoperoxidation [7]. Additionally, a family of S-adenosyl methionine (SAM) methyltransferase enzymes is involved in more than 40 metabolic reactions using SAM as a methyl donor to modify nucleic acids, proteins and lipids [8, 9]. Four of those SAM methyltransferase enzymes participate in DNA and RNA modification in mammalian cells. DNMT1, DNMT3A, and DNMT3B catalyze methyl group transfer at the C5 position of cytosine in DNA CpG sequences [10], whereas TRDMT1 (DNMT2) methylates the C5 position of cytosine 38 in aspartic acid tRNA [11].
3.1. Types of alkylating agents
Alkylating agents can be categorized by their method of activation. Some alkylating agents react directly with DNA and do not require any activation, whereas many alkylating agents, including many carcinogens, must undergo metabolic activation by the cytochrome P450 system to generate reactive species capable of modifying DNA [3, 12, 13]. In addition, alkylating agents are electrophilic compounds that possess either one or two reactive groups that can interact with the nucleophilic centers of DNA and RNA bases. Alkylating agents that can only react with one nucleophilic center are mono-functional, whereas bi-functional agents can react with two sites in DNA or RNA [1, 13]. Alkylating agents that are mono-functional primarily transfer alkyl groups to ring nitrogens, while agents that react in a bi-functional manner not only react with ring nitrogens, but can form cyclized DNA bases, by reacting with exocylic nitrogen and oxygen groups [13] (Figure 2). In addition to methylating agents, larger alkylating agents also modify nucleic acids—bi-functional ethylating agents can form exocyclic ethano and etheno adducts at nitrogen and oxygen molecules in all DNA and RNA bases. Additionally, bi-functional alkylating agents can produce DNA inter- and/or intrastrand cross-links [13]. Some alkylating agents also react at phosphate residues to generate phosphotriesters, leading to potential single-strand breaks [13] (Figure 2). Two main pathways, characterized as SN1 or SN2, are defined based on the kinetics of the alkylation reaction, leading to the above mentioned modifications of DNA and RNA bases [2].
Figure 2.
(A) Purple arrows indicate sites in DNA most often methylated by SN1 alkylating agents. Green arrows indicate sites commonly modified by SN2 alkylating agents, orange arrows indicate sites in single-stranded DNA. Blue arrows indicate exocyclic amino groups important in formation of cyclized DNA adducts. The location of the major and minor grooves in DNA are indicated. “R” is the attachment of the base to the deoxyribose and phosphodiester backbone. (B) Modified phosphodiester isoforms in the DNA backbone. SN1 alkylating agents generally form more phosphotriester products than SN2 agents. [2,14]
SN1 agents act via a two step reaction involving a unimolecular nucleophilic substitution with a rate-limiting step that generates an intermediate carbonium ion electrophile that reacts with nucleophilic DNA sites. Thus, the reaction kinetics depend only on the formation of the carbonium ion intermediate (first-order). The triganol planar conformation of the sp2 hybridized carbon generated in the carbocation intermediate permits nucleophilic attack from either side, yielding a racemic mixture of reaction products at chiral centers [13] (Figure 3). Though agents that react via an SN1 mechanism produce both N- and O-alkylations, increased amounts of modified oxygens are generated, compared to agents that react via an SN2 mechanism.
Figure 3.
SN1 and SN2 nucleophilic substitution reactions. (A) Example of an SN1 reaction. SN1 reactions are dependent on formation of a carbonium ion intermediate that rate-limiting. Product chiral centres are a racemic mixture because the intermediate can be attacked by either side. (B) Example of an SN2 reaction. Both reactants are required and there is direct attack by the nuclephile in SN2 reactions. Chirality is maintained since a transition state is formed with the chiral center. [2,14]
In contrast, SN2 reaction mechanisms depend on both the alkylating agent and its target to define the kinetics (second-order). Using a one step reaction where both the electrophile and nucleophile are involved in the transition state, SN2 alkylating agents proceed with direct attack by the nucleophile on an electron deficient center. The nucleophile attacks from the back of the electrophile, forming the carbon-nucleophile bond and breaking the carbon-leaving group bond. Simultaneous backside, nucleophilic attack and leaving group departure cause the incoming group to replace the leaving group. Because a transition state is formed with the chiral center, chirality is maintained, leading to a stereocenter (inversion) configuration [13] (Figure 3). Alkylating agents that react via an SN2 mechanism cause primarily N-alkylations.
3.2. DNA and RNA alkylation damage
Modification sites of DNA bases are the same for all alkylating agents and include all the exocyclic nitrogens and oxygens, as well as ring nitrogens without hydrogen. Though all DNA nucleobase oxygen or nitrogen atoms can be alkylated, the type and frequency of specific damage varies depending on the type of alkylating agent, the structure of the substrate, and the position of the damage site [13] (Table 1). Generally, alkylation damage at nitrogen molecules is less mutagenic than oxygen, though both types of alkylation damage are cytotoxic and genotoxic [14].
Common alkylations generated by exogenous alkylating agents include O6-alkylguanine and O4-alkylthymine adducts, as well as N7-alkylguanine, N3-alkyladenine, N1-alkyladenine, and N3-alkylcytosine [13] (Figure 1). Moreover, the frequency of each adduct type depends on whether the DNA and RNA substrates are single- or double-stranded [13] (Table 1). For instance, nitrogen molecules involved in DNA base-pairing are less vulnerable to alkylation damage than the same base nitrogens in a single-stranded region arising during replication and transcription.
\n\t\t
\n\t\t
\n\t\t\t
\n\t\t
\n\t
Table 1.
% of Total DNA alkylation adduct formation in single- and double-strand DNA. Modifications following SN2 alkylating agent methylmethanesulfonate (MMS) or SN1 alkylating agent treatments methylnitrosourea (MNU) or ethylnitrosourea (ENU). Sites where % alkylation is undetermined are indicated as (--) [13].
4. Direct repair proteins
Numerous cellular mechanisms have evolved to deal with various types of DNA damage and each DNA repair pathway is important to maintain genomic integrity. However, most repair mechanisms require DNA synthesis and therefore an intrinsic risk of causing mutation in executing the repair. In contrast, direct repair proteins, MGMT and ALKBH family proteins employ direct reversal mechanisms that result in complete restoration of DNA bases and are thus error-free mechanisms. Moreover, MGMT, ALKBH2, and ALKBH3 repair endogenous and exogenous DNA and RNA alkylation damage at critical base-pairing sites, facilitating proper replication of genetic information or transcription. This section will discuss each of these direct DNA repair enzymes in detail.
Figure 4.
Major mechanisms of alkylation adduct repair. Direct repair pathways are indicated in green. Base and nucleotide excision repair pathways are indicated in blue [2,14].
4.1. Mechanisms of alkylation repair
Multiple mechanisms are employed to rid the genome of alkyl adducts, thereby preventing detrimental effects within the cell (Figure 4). Mismatch repair (MMR), base excision repair (BER) and nucleotide excision repair (NER) and direct repair (DR) pathways all participate in alkylation damage repair [15-24]. Specifically, BER and NER repair small alkylated base damage including 7-methylguanine (7-meG) and 3-methyladenine (3-meA) DNA adducts [25]. Although BER repairs the majority of small alkylated base damage (methyl and ethyl adducts) the NER system can also remove small, as well as bulky adducts larger than ethylated bases [24, 26]. As an alternative to NER, incomplete BER repair intermediates can be processed by homologous recombination (HR) [27]. However, BER, NER and HR repair pathways generate strand breaks during repair of alkyl adducts and could introduce mutations or rearrangements [28]. On the contrary, DR mechanisms, provided by methyltransferase MGMT and ALKBH homologs, eliminate alkylation damage at DNA base-pairing sites, including O6-methylguanine (O6-meG), 1-methyladenine (1-meA) and 3-methylcytosine (3-meC) and do not require a nucleotide template, result in phosphodiester backbone breakage, nor do they require DNA synthesis.
In mammals, methylguanine DNA methyltransferase (MGMT or AGT), can repair two types of DNA adducts: O6-methylguanine (O6-meG) and O4-methylthymine (O4-meT). O6-meG adducts in DNA are extremely mutagenic [29, 30] and also block DNA polymerase extension, which is generally associated with cytotoxicity [31, 32]. The primary mutations observed when there is a failure to repair O6-meG adducts prior to replication are G:CA:T transitions, whereas a failure to repair O4-meT results primarily in T:AC:G transition mutations [29]. In mammals, elimination of O6-meG by MGMT is preferred over O4-meT, but the respective efficiency of each type of reversion is species dependent [29, 33-37].
Removal of O6-meG and O4-meT modifications are achieved via a one-step methyltransferase reaction, wherein MGMT accepts the alkyl adduct from the modified oxygen molecule, onto an internal residue, directly restoring the DNA base and inactivating the protein [38] (Figure 5). In addition to methyl groups, several other alkyl-adducts can also be transferred from guanine to MGMT, including ethyl-, propyl- butyl-, benzyl- and 2-chloroethyl-. However, the efficiency of the reaction is decreased for alkyl adducts greater than methylated bases [39]. Once modified, the protein is targeted for elimination via the proteasome [40].
4.2.1. Protein structure/active site organization
Alkyltransferase proteins are found in eukaryotic and prokaryotic organisms and have been identified in as many as 100 organisms [41]. Though sequences are not highly conserved between human MGMT and Eubacterial, Archea, and Eukaryotic DNA methyltransferase enzymes, structural domains and active site residues are almost identical [42-46].
Figure 5.
Methylguanine methyltransferase (MGMT) activity. (A) MGMT DNA repair substrates (B) MGMT repair reaction. Transfer of the methyl group (orange) from the damaged DNA base to the internal Cys145 (light green) is a suicide reaction, inactivating MGMT. [14]
In human MGMT, a conserved α/β roll structure, containing a three-stranded, anti-parallel β-sheet, followed by two helices, make up the N-terminus (residues 1-85). The MGMT C-terminus (residues 86-207) contains a short, two-stranded, parallel β-sheet, four α-helices and a 310 helix [42, 47]. Found only in humans, a zinc ion stabilizes the interface between the N- and C-termini, binding Cys5, Cys24, His29 and His85 in a tetrahedral conformation to bridge three strands of the N-terminal β-sheet with the coil preceding the 310 helix in the C-terminus [47].
The conserved active site cysteine motif (-PCHR-) is located in the C-terminus contained within the DNA binding channel, and the helix-turn-helix (HTH) DNA binding motif. Residues Try114-Ala121 form the first helix of the HTH motif and residues Ala127-Gly136 form the second, “recognition” helix, which interacts with DNA. Linked by an Asn-hinge (Asn137) that stabilizes the over-lapping turns by binding Val139, Ille143 and the Cys145 thiol, the -PHCR- active site is located near the “recognition” helix [42, 47, 48].
The active site of human MGMT is composed of at least ten residues that participate in substrate binding, enzyme structure and alkyl transfer. Residues Val155-Gly160 and Met134 generate a hydrophobic cleft in the active site loop, while residues Tyr114, His146, Val148, Ser159, and Glu172 participate in active site coordination and alkyl group transfer to residue Cys145. Not unexpectedly, mutation of residue Cys145 results in elimination of alkyl group transfer, however substrate binding is unaffected [49] (Figure 6).
Figure 6.
Structure of human MGMT (PDBid1QNT). The N-termianl p-sheet and C-terminal 310 helix of the α/β roll structure, conserved in AGT proteins are indicated. In humans, a zinc ion stabilizes interaction of MGMT N-and C-termini [46].
4.2.2. Substrate recognition/repair mechanism
In repair, MGMT is unique in that one molecule is responsible for the removal of one O6-meG or O4-meT adduct. Unlike most enzymes with the capacity to catalyze multiple reactions, MGMT catalyzed reactions are stoichiometric and capable of only a single repair reaction [50]. As a result, removal of O6-meG and O4-meT alkyl adducts is dependent on both MGMT and the substrate concentrations (second-order reaction).
The recognition of guanine and thymine base methylation is accomplished by a highly conserved amino acid structure. The hydrophobic cleft of the active site loop and -PCHR- motif within the binding channel allow MGMT to bind to the minor-groove of DNA using residues Ala126, Ala127, Ala129, Gly131, and Gly132, of the HTH “recognition” helix [51, 52], which is followed by necessary conformational changes to orient the damaged base within the active site.
Identified based on bacterial Ada homology and human MGMT structures, following substrate recognition, the target base is repaired using a base flipping mechanism [53-58]. In the MGMT repair reaction, the damaged base undergoes a residue Tyr114-mediated, sterically enforced 3’ phosphate rotation into the active-site pocket. The hydrophobic cleft formed by the active site loop easily accepts the extra-helical base, causing the DNA minor groove to widen [51]. The arginine finger residue, Arg128, intercalates between the DNA bases and interacts with the unpaired cytosine, via a charged hydrogen bond [55], maintaining an appropriate DNA duplex conformation (Figure 6).
Once bound within the MGMT active site, numerous residues participate in the methyltransferase reaction. A hydrogen bond network, conserved in AGTs, is formed between Glu172, His146, water and Cys145. His146 acts as a water-mediated base that deprotonates Cys145, converting Cys145 to a cystine thiolate anion and generating an imidazolium ion that is stabilized by Glu172 [35, 59]. Residues, Val148 and Cys145 carbonyls accept guanine exocyclic amine hydrogen bonds and nitrogen atoms of residues Tyr114 and Ser159 donate protons to N3 and O6 of O6-meG, respectively. The deprotonated Tyr114 residue abstracts a proton from Lys165, simultaneously transferring the alkyl group from the O6 position of guanine to the thiolate anion of the Cys145 residue [35]. Transfer of the alkyl group generates a thioether, S-alkylcysteine, and results in complete restoration of the guanine base, as well as irreversible inactivation of the methyltransferase enzyme (Figure 5). While many DNA repair proteins have a specific requirement for double-stranded DNA, MGMT can also bind to single-stranded DNA [60].
4.2.3. Gene expression/protein regulation
Removal of O6-meG modifications by MGMT has a major role in cell cycle checkpoint control, proliferation, and differentiation [61]. As a result, MGMT is a house-keeping gene that is expressed in all tissues; though expression varies depending on cell type [62]. MGMT expression in an individual cell or tissue type is dependent on a variety of factors, including numerous types of stimuli and promoter regulator elements. However, the relationship between factors that mediate MGMT expression and the regulation of its function is not well-understood. The lack of understanding regarding the consequences of MGMT regulation is illustrated by the fact that MGMT expression is silenced in some cancers, but expression is up-regulated in others [62, 63].
MGMT is a single gene on chromosome 10q26, spanning approximately 300kb [64]. The gene has five exons, but the first is non-coding [65, 66]. The promoter of MGMT is a non-TATA-box promoter that contains a GC-rich CpG island of 780 bp that includes 97 CpG dinucleotides [67]. CpG islands are commonly associated with promoter regions of constitutively expressed genes, from which transcription is initiated from a single promoter site [68-70]. Additionally, the promoter contains six transcription consensus binding sites (SP1, AP1, and AP2), three upstream and three downstream of the transcription start site, a glucocorticoid-responsive element, and a 3’ enhancer element [62, 67, 69, 71]. Though unmethylated in normal cells, promoter CpG island methylation-induced silencing of MGMT is found in various cancer types and MGMT-deficient cell lines and is one mechanism that regulates MGMT expression [72-76]. However, whether MGMT promoter methylation disables transcription factor binding or contributes to chromatin reorganization remains uncertain [71, 75].
In addition to numerous transcription factor binding sites that surround the MGMT promoter transcription start site, the MGMT promoter CpG islands exhibit a chromatin structure that mediates interaction with transcription factors. The MGMT gene is organized around five or more nucleosomes in a manner that positions 300 bp region of the promoter sequence, which contains known MGMT transcription factor binding sites, so that it does not lie within the nucleosomes, and therefore does not maintain a higher-order chromatin structure [62, 72, 77]. Such nucleosomal positioning facilitates an “open” stretch of DNA that enables constitutive interaction of transcription factors with the promoter.
Methylation of the CpG island surrounding the transcription factor binding sites contributes to lack of transcription factor binding, but could also effect nucleosomal positioning of the MGMT promoter [62, 71], suggested by histone H3 Lys9 (H3K9) di-methylation, exhibited in relationship to MGMT silencing [78, 79]. Further, deacetylation of histones H3 and H4 could also be associated nucleosome organization that is more condensed, resulting in transcription inactivation. Therefore, the chromatin structure of the MGMT promoter, as well as CpG island methylation, mediate transcription factor access to the promoter and are important for MGMT expression.
4.2.4. Protein localization and cell type dependence
Immunofluorescence studies indicate MGMT nuclear localization at discrete nuclear regions [80]. Although a nuclear localization signal (NLS) for MGMT has not been identified, the small size of MGMT, 23 kDa, may not require an active translocation signal to traverse nuclear pores [53]. However, a –PKAAR- sequence within the DNA binding domain of MGMT is necessary for DNA interactions to facilitate nuclear retention [81]. The highest MGMT expression levels are found in the liver, where high levels of endogenous nitrosating agents are present, but MGMT is also expressed at high levels in the lung, kidney and colon. MGMT expression is heterogeneous in the brain and the lowest levels are observed in the pancreas, hematopoietic cells, lymphoid tissues [62, 67, 82-86].
4.2.5. Post-translational modification
Once MGMT has transferred a methyl group to its Cys145 residue, no further reactions are catalyzed, so the protein must be eliminated. The degradation of MGMT is an ubiquitination-dependent process that has been evaluated using inactivation of the protein by O6-BzG, BCNU, or NO-generating agents at position Cys145 [40, 87, 88]. Conformational changes in the protein structure after alkyl group transfer target MGMT for ubiquitination and proteasomal degradation [40, 89]. Two sites within MGMT, Lys125 and Lys178, have been identified as ubiquitination targets in B lymphocyte (NCI-H929) or 293T, and myeloid (MV4-11) cells, respectively. Additionally, examination of potential MGMT modification sites using predictive software also identifies Lys104 as an ubiquitination target. Furthermore, predictions also indicate post-translational modification sites for methylation (Arg128, Arg135), acetylation (Lys8, 125, 178, 193), and sumoylation (Lys75, 205, 18, 107), as well as numerous phosphorylation sites (Ser36, 56, 130, 182, 202, 206, 208; Thr37; Tyr91, 115) [90-93], which all merit further consideration. Notably, phosphorylation of residues Thr10 and Thr11 was also noted in HeLa cells [92], and phosphorylation of Ser201 is observed in B lymphocyte cells (DG75 and GM00130), KGI myeloid cells, and HeLa cervical cancer cells. Importantly, crystallographic data suggests that modification of Ser201 could disrupt interaction with DNA [48, 51, 55].
In mammals, repair of cytosine and adenine base methylation at base-pairing positions is specifically associated with the AlkB family dioxygenase proteins [92, 94-96]. Discovered first in Escherichia coli (E. coli) in 1983 [96] alkylation protein B (AlkB) belongs to a super-family of Fe(II)/α-ketoglutarate-dependent dioxygenases (FeKGDs), with roles in histone demethylation [97-99], proline hydroxylation [95] and in the case of AlkB, the ability to directly remove alkyl adducts generated in DNA residues as a result of exposure to SN2 alkylating agents [94, 100]. Originally predicted to act on 1-methyladenine (1-meA) and 3-methylcytosine (3-meC), bacterial AlkB has been shown to repair a variety of DNA and RNA adducts, including 1-meA, 3-meC, 1-meG, 3-meT, 1-etA, as well as aromatic ethyl, 3-etC, and etheno adducts, 1,N6-ethenoadenine (εA) and 3,N4-ethenocytosine (εC) [94, 100-108] (Figure 7).
Figure 7.
ALKBH protein substrates. (A) DNA methyl adducts repaired by ALKBH proteins. (B) DNA etheno adducts repaired by ALKHB proteins.
Using bioinformatics, nine human ALKBH family enzymes, ALKBH1-8 and FTO, were identified, of which only four have been reported to have DNA repair activity, ALKBH1 – ALKBH3 and FTO [109, 110]. Though all of the ALKBH homologs contain conserved catalytic domain residues, none entirely encompass the enzymatic activity of AlkB [15, 103, 104, 111-114]. Removal of alkyl adducts from DNA is only accomplished by three ALKBH proteins, ALKBH1-3, known to remove 1-meA and 3-meC adducts. However, ALKBH1 is reportedly a mitochondrial protein [115], therefore in the nucleus ALKBH2 and ALKBH3 proteins are employed to remove specific adducts in single- or double-stranded DNA or in RNA [104]. Lesions that are repaired by ALKBH proteins generally interfere with base-pairing and block replication and transcription, triggering cell cycle checkpoints and apoptosis [92, 95, 96, 110, 115]. In E. coli AlkB mutants, as well as in Alkbh2- or Alkbh3-deficient mouse embryonic fibroblasts, cells exhibit increased sensitivity to alkylating agents, particularly the SN2 type, and increased mutant frequency [101, 116-119].
4.3.1. Protein structure/active site organization
Similar to MGMT, the sequences of human ALKBH proteins do not contain a high percentage of sequence homology in regions other than active sites and conserved domains, but do have conserved secondary structures [109, 110, 114, 120-122]. In AlkB family proteins, the catalytic core is composed of three major components, the double-stranded β-helix (DSBH), the nucleotide recognition lid (NRL) and the N-terminal extension (NTE) (Figure 8). The DSBH is comprised of eight β-strands in the C-terminal portion that form two β-sheets to create a central core jelly-roll fold. Within the major and minor β-sheets of the DSBH lie conserved catalytic residues RxxxxxR and HxDxnH, respectively [120, 121, 123]. The HxD dyad is near the amino terminal end and is located in a flexible loop that follows the first strand, stacking with the minor β-sheet. The carboxy-terminal histidine of the conserved HxDxnH residues is associated with the beginning of the sixth strand and together these residues coordinate iron (His171, Asp173 and His236—Alkbh2; His191, Asp193 and His258—Alkbh3) [114, 120, 121, 123, 124]. The histidine and aspartic acid residues (Asp248 and Asp254—ALKBH2; Asp269 and Asp275—ALKBH3), conserved in the DSBH minor β-sheet, coordinate Fe(II), α-ketoglutarate and the DNA or RNA repair substrate within the catalytic core. A conserved Arg residue in the C-terminal β-strand (Arg254—ALKBH2 and Arg275—ALKBH3) sets AlkB family proteins apart from other α-ketoglutarate-dependent dioxygenases within the Fe(II)/α-ketoglutarate dioxygenase superfamily, forming the base of the substrate binding pocket [110, 120, 121, 123].
Figure 8.
Structure of human AlkB homolog DNA repair proteins. Two looped structures (flip1 and flip2) generated by anti-parallel β-sheets create the nucleotide recognition lid (NRL) and are involved in DNA base flipping. (A) Structure of ALKBH2 (PDBid3BTX). ALKBH2 double-strand DNA substrate specificity is facilitated by residues in loops L1 and L2. (B) Structure of ALKBH3 (PDBid2IUW). β -sheets 4 and 5 form the β-hairpin motif in ALKBH3. Part of loop 1, involved in ALKBH substrate specificity, was omitted due to electron density problems. [121]
The N-terminal extension (NTE) and Nucleotide Recognition Lid (NRL) are formed by the β-hairpin motifs that extend from the DSBH jelly-roll, forming a substrate binding groove that covers the active site until bound. Ninety residues are contained within two looped structures, forming “flips” that lie between a single β-sheet and two α-helices in the N-terminal portion of the catalytic core [120, 121]. Secondary structures are of similar size, but possess different characteristics important for substrate specificity and DNA activity. In ALKBH2, the first flip is 20 residues that make up a β-hairpin and short α-helix, creating a hydrophobic binding groove. In contrast, the first flip in ALKBH3 is a β-hairpin made up of 17 residues that form a hydrophilic, positively charged binding groove, more suitable for single-stranded DNA or RNA substrates [15, 120]. The characteristics of the second flip are also unique. Flip two of ALKBH2 spans 24 residues that is made up of three β-sheets, with numerous sites for DNA substrate interaction. The orientation of the three β-sheets, which fold back towards the C-terminal end of the first α-helix, is also unique only to ALKBH2 [114, 121]. However, flip 2 of ALKBH3 is only 12 residues and contains a single β-sheet [114]. The N-terminal regions of each ALKBH homolog are more variable and hypothesized to play roles in sub-cellular sorting and protein-protein interactions [114, 115] (Figure 8).
In addition to the conserved catalytic dioxygenase residues, some human ALKBH proteins also contain additional catalytic residues and domains [104, 109, 110, 113, 125] (Figure 9). Structural analysis of bacterial AlkB and human ALKBH homologs provides insight into substrate preferences and repair capabilities. For instance, ALKBH2 contains three unique motifs that facilitate enhanced activity on double-stranded DNA [121]. A long, flexible β-sheet hairpin loop that contains DNA binding residues Arg198, Gly204 and Lys205, a short loop that contains the RKK motif (Arg241-Lys243) and an aromatic finger residue (Phe102) are used to make contacts with both DNA strands, rotate and take the place of the damaged base in duplex DNA molecules. On the other hand, the number and organization of the catalytic domains in ALKBH3 result in differential manipulation of the DNA backbone, explaining the preference for single-strand substrates. Lack of an aromatic finger residue and RKK motif in ALKBH3, the damaged base is squeezed on either side, forcing it to rotate, and the immediate 5’ and 3’ bases to stack against one another. However, structural analysis of ALKBH3 has identified residue Arg122, specifically the arginine side chain length, as important for double-stranded DNA substrate activity, possibly mimicking the base-flipping and stacking activities of ALKBH2 residue Phe102 [114, 121].
Unfortunately, extensive biochemical analysis or structural studies have not been conducted on ALKBH homologs 4-8. However, it is apparent that differences in the number and organization of catalytic residues, as well as secondary structures play a large role in the diversity of ALKBH family protein substrate specificities and enzymatic activities [113]. For instance, although single- or double-strand DNA repair activity has not been established for ALKBH8, the presence of RNA binding and methyltransferase domains in ALKBH8 (Figure 9) suggested that this homolog plays a role in maintenance of methylation patterns. Investigation of such activities led to the identification of ALKBH8 tRNA methyltransferase activity, necessary in the biogenesis of wobble uridine modifications utilized in translational decoding [126, 127].
Figure 9.
AlkB family protein domain alignment. Conserved amino acid sequences and domain function are indicated. The total number of amino acids is indicated to the right of each homolog. [110,113,125]
4.3.2. Substrate recognition/repair mechanism
Initially, it was predicted that AlkB family proteins directly repaired alkylation adducts by hydroxylating methyl groups and removing the resultant hydroxymethyl groups via an oxidative reaction that directly restores the undamaged base [94, 109, 112, 124, 128, 129]. However, specific investigation of the AlkB family dealkylation mechanism [130] determined that the direct repair reaction mediated by AlkB family proteins involves several intermediate steps that had not yet been identified. Regardless, dealkylation catalyzed by AlkB and its human homologs occurs via transformation of α-ketoglutarate into succinate, formaldehyde release, and restoration of the undamaged base [94, 100, 111, 130, 131] (Figure 10).
Figure 10.
ALKBH protein repair reactions. (A) ALKBH methyl adduct repair reaction. (B) ALKBH ethyl adduct repair reaction. (C) ALKBH etheno adduct repair reaction. Repair of ethyl and etheno adducts requires the same co-factors, but displaces acetaldehyde or water and glyoxal as byproducts of the repair reaction, respectively, instead of formaldehyde [100,102,103]
First, Fe(II) and three water molecules must be coordinated within the conserved catalytic core, stimulating α-ketoglutarate (KG) binding in the catalytic pocket. Binding of α-KG into the catalytic pocket chelates Fe(II) by displacing two water molecules to create the Fe(II)/α-KG active-site complex. Ligation of dioxygen to the Fe(II) molecule displaces the remaining water molecule, generating a ferric-superoxido species that undergoes self-redox and nucleophilic attack on the α-keto group. This nucleophilic attack is necessary to decarboxylate α-KG, releasing succinate and generating a ferryl-oxo intermediate. Reorientation of this intermediate facilitates removal of a hydrogen atom from the methyl adduct. Finally, radical rebound hydroxylation of the methylene group results in decomposition of the hydroxymethyl nucleobase, yielding formaldehyde and the repaired nucleobase. Though two co-factors were noted initially, α-ketoglutarate and Fe(II), ascorbate also plays a role, helping to convert the Fe(III) to Fe(II), thereby regenerating the original oxidative state of iron in the Alkbh proteins that permits enzymatic cycling [94, 111, 112, 122, 124, 130].
The major methylated bases repaired by ALKBH proteins are 1-methyladenine (1-meA) and 3-methylcytosine (3-meC), however homologs have also been reported to repair ethylated, and some etheno and exocyclic bases [102-105, 107, 131, 132]. Similar mechanisms are proposed for repair of ethano and exocyclic etheno (ε) adducts, though the final steps of these reactions result in release of acetylaldehyde and glycol, respectively [130] (Figure 10). However, additional biochemical studies are needed to confirm these mechanisms in similar detail to removal of methyl adducts from DNA.
4.3.3. Gene expression/protein regulation
Human AlkB DNA repair homologs, ALKBH2 and ALKBH3 are single genes on chromosomes 12q24 and 11p11, respectively. Expression of human AlkB homologs has been reported in a variety of normal tissue samples, including ALKBH homologs 4-8, despite the lack of DNA repair activity in the literature [133]. Expression of ALKBH family proteins varies depending on cell types. Protein expression levels in the various tissue types vary depending on the homolog evaluated. Little is known of ALKBH protein regulation mechanisms and is an area in need of further study.
4.3.4. Protein localization and cell type dependence
Differences amongst AlkB homolog proteins in their biological roles are partially ascribed to their sub-cellular localizations. ALKBH2 and ALKBH3 homolog proteins are expressed at the highest levels in the testis and ovary, however detectable expression of all AlkB homolog proteins is exhibited in the spleen, pancreas, lung, kidney, prostate and brain [133]. Although ALKBH1 activity is confined to mitochondria [115], immunofluorescence imaging indicates that the protein is cytoplasmic and nuclear [133]. Similarly, AlkB homolog proteins ALKBH3, 4, 6, and 7 are also present in the nucleus and cytoplasm [133], though ALKBH3 is the only homolog reported to possess repair activity [1, 104, 111]. Localization of ALKBH3 in both the nucleus and cytoplasm are consistent with identified interactions with helicase enzymes to facilitate DNA repair [134] and roles in mRNA repair [131]. ALKBH2 is present only in the nucleus and exhibits diffuse as well as localized, punctate staining, supporting pre-established co-localization with PCNA at replication foci during S phase [111, 131, 133], suggesting a role in replication- and transcription-related repair, as well as genome maintenance. On the contrary, AlkB homolog proteins ALKBH5 and 8 are present only in the cytoplasm [133], which supports known ALKBH8 tRNA methyltransferase activity [126, 127].
4.3.5. Post-translational modification
Unlike MGMT, ALKBH proteins are not suicide enzymes and a single protein can catalyze multiple direct repair reactions, requiring only ascorbate to regenerate the Fe(II) active site center [135]. Therefore, immediate degradation of ALKBH proteins following repair is not required, as it is for MGMT. Other possible post-translational modifications in ALKBH2 and ALKBH3 include candidate sites for phosphorylation and acetylation. Mass-spectrometric analysis of a curated database of cell lines revealed that both ALKBH2 and ALKBH3 proteins undergo post-translational modification of specific residues present in various cancer types [92].
Post-translational modifications curated for ALKBH2 include acetylation of residue Lys34 and Lys104 in various colorectal cancer cell types (HCT116, HT29, XY3-92-T and XY3-68-T), as well as phosphorylation of residue Thr252 in esophageal cancer cell line XY2-E111N [92]. Though the exact effects of these modifications are unknown, it is important to state that Lys34 is within the variable region of the N-terminus that is thought to provide protein specificity. Similarly, Lys104 is between two residues that make contact with the complimentary DNA strand during double-strand DNA repair and Thr230 is a residue in the most C-terminal α-helix of the active site [92]. Examination of potential ALKBH2 modification sites using predictive software shows possible post-translational modification sites for methylation (Arg128, 135), sumoylation (Lys75, 205), and ubiquitination (Lys104), along with other possible phosphorylation sites (Ser36, 56, 130, 182, 202, 206, 208; Thr37; Tyr91, 115) [90-93]. All of those possible post-translational modifications merit further consideration.
Post-translational modifications were also present in ALKBH3, corresponding to various disease states. Phosphorylation of Thr126 and Tyr127 residues in the β-hairpin of the NRL, as well as residue Try229 in the ALKBH3 active site, was present in acute myelogenous, chronic myelogenous and/or T-cell leukemia [92]. Additionally, phosphorylation of Tyr127 was exhibited in lung and non-small cell lung cancer cell lines. Phosphorylation of residue Tyr143, which precedes the first residue of the second β-hairpin in the NRL, was also noted in the gastric carcinoma cell line MKN-45, as well as phosphorylation of residues T212 and T214, within the ALKBH3 active site, was found in liver cancer tissue samples [92]. Examination of potential ALKBH3 modification sites using predictive software shows possible post-translational modification sites for acetylation (Lys43, 116, 219, 220), and sumoylation (Lys57, 236), along with other possible phosphorylation sites (Ser32, 50, 187, 192, 208, 265; Thr29, 41; Tyr78, 127, 229) [90-93]. All of those possible post-translational modifications merit further consideration.
5. Biological significance of direct repair in mammalian cells
Normal cells depend on direct repair to eliminate damage that is possibly cytotoxic or mutagenic. Our knowledge of the biological significance of direct repair proteins in mammalian cells is based on the evaluation of effects on cell cytotoxicity, replication, transcription and subsequent mutagenic consequences observed in the absence of each protein of interest. Recent investigations performed in model system organisms, most prominently in mice, to assess the impact of the absence of Mgmt or Alkbh family proteins will be highlighted in this section. These studies also provide insight into the function and importance of direct repair proteins in humans.
5.1. Knock-out animal models
It is important to remember that a number of DNA repair systems are implicated in the elimination of DNA lesions formed by exposure to alkylating agents. Therefore, dysfunction of repair systems can lead to pathologies that include cancer development. However, without use of a model organism to assay the effects, the consequences to the organism as a whole cannot be assessed. Knock-out animal models are a valuable tool for understanding the overall physiological effects of genes on an organism, and provide insight into disease research and therapeutic development.
Murine Mgmt models have been studied by multiple groups to evaluate sensitivity to alkylating agents commonly used in chemotherapeutics [5, 6, 82, 86, 136-139]. Though Mgmt repairs DNA damage that is known to be mutagenic, Mgmt-deficient mice surprisingly lack any overt phenotype. However, these mice are significantly more sensitive to treatment with N-methyl-N-nitrosourea (MNU), 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU), 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)3-nitrosourea (ACNU), streptozotocin, temozolomide, and dacarbazine alkylating agents [5, 136, 137, 139-142]. Mgmt knock-out mice treated with various chemotherapeutic agents also show ablation of hematopoietic tissues at the stem cell level [38, 141, 143] and are prone to development of thymic lymphomas [144]and lung adenomas [82, 138, 144, 145]. Similarly, mouse embryonic stem (ES), embryonic fibroblasts (MEFs) and bone marrow cells deficient in Mgmt also exhibit a significant increase in sensitivity (~10-fold) to MNU and BCNU [83, 141, 146]. However, mice heterozygous for Mgmt do not display a significant reduction in survival following treatment with nitrosoureas or increased tumorigenesis, compared to their wild-type counterparts.
Although in vitro DNA repair activity has been established for ALKBH1, studies conducted in murine models lacking Alkbh1 suggest roles involved in transcription. Mice deficient in Alkbh1 exhibit apoptosis in adult testis, sex-ratio distortion and unilaterial eye defects, as well as impaired differentiation of specific trophoblast lineages in the developing placenta [147, 148]. Though the specific activity and function of ALKBH1 remains to be determined, ALKBH1 biological roles seem linked to spermatogenesis and embryonic development.
On the other hand, Alkbh2- and/or Alkbh3-deficient murine models do not manifest any obvious phenotype or histopathological changes [116, 119, 132]. However, over time mice lacking Alkbh2 accumulate significant levels of 1-meA, confirming a role in removing endogenous DNA alkyl adducts. In a recent study, Alkbh2,Alkbh3,Aag knock-out mice (Aag also known as Mpg, a DNA glycosylase in the BER pathway) were viable, but underwent rapid death when exposed to a chemically-induced colitis treatment [119]. Similarly, primary mouse embryonic fibroblasts (MEFs) derived from mice lacking functional Alkbh2 exhibited significantly increased cytotoxicity and mutagenesis following exposure to the SN2 alkylating agent methyl methanesulfonate (MMS) [116, 118, 119]. Survival of Alkbh3-deficient MEFs exposed to MMS was reduced by ~50% compared to wild type MEF sensitivity, though mutant frequency did not significantly increase [116].
5.2. Replication and transcription defects
Though not all lesions generated by exposure to alkylating agents cause defects in replication and transcription, DNA and RNA adducts that are specifically removed via a direct repair mechanism interfere with replication and transcription machinery. The presence of O6-meG in DNA impedes polymerization by DNA and RNA polymerases [31, 32, 149, 150]. Polymerase beta (β), involved in base excision repair (BER) of alkylation adducts, is completely blocked by O6-meG adducts [150]. Polymerase delta (δ) is able to replicate past, but insertion of the correct base opposite O6-methylguanine is very inefficient. However, these adducts can be bypassed using polymerase eta (η) [149], a member of the Y-family DNA translesion synthesis (TLS) polymerases, but TLS polymerases are notorious for being error-prone. Interestingly, when replicating past O6-meG DNA adducts, TLS polymerase, Polη is twice as efficient at inserting cytosines opposite O6-meG as replicative polymerase, Pol δ [32].
1-meA and 3-meC lesions that are repaired by Alkbh2 and Alkbh3 are at DNA base-pairing positions and hinder proper base insertion [101]. During replication, this can lead to arrest of nucleotide synthesis, resulting in replication fork collapse [151]. Similarly, 1-meA and 3-meC adducts can also cause stalling of transcription. Correspondingly, Alkbh2 co-localizes with replication foci during S-phase [111, 131, 133] and Alkbh3 has a role in removal of alkyl adducts from mRNA [1, 15, 108, 115, 131, 152]. However, a TLS polymerase that is linked to 1-meA and/or 3-meC DNA adduct bypass has not been identified.
5.3. Cell cytotoxicity
Treatment with alkylating agents introduces a variety of adducts into DNA and RNA (Figure 2, Table 1). In the absence of direct repair proteins, those lesions can lead to cell death or damage tolerance, which allows for cell survival, but can introduce mutations into the genome that could have detrimental effects [101, 116, 142, 153]. As exhibited in Mgmt- and Alkbh-deficient murine models, lack of direct repair proteins correlates with a significant increase in cell death following treatment with SN1 or SN2 alkylating agents, respectively [116, 118, 140, 141].
5.4. Mutagenesis
When a modified nucleoside can form at least two hydrogen bonds, transcription and replication templates and translation of messengers are active [13]. O6-meG, 1-meA, and 3-meC are all involved in DNA base-pairing. Modification at O6-meG and 3-meC still allow for formation of two hydrogen bonds, while 1-meA results in only a single hydrogen bond between paired bases [13]. However, the exocyclic amino group of 1-meA can rotate so that both amino group hydrogen molecules can generate the necessary base-pairing bonds, though a slight distortion of the double-strand DNA helix does occur [13]. The addition of a methyl group to O6-G, N1-A, or N3-C interferes with normal replication, and could recruit DNA translesion synthesis (TLS) polymerases to bypass the DNA adducts. The size and organization of the Y-family TLS polymerase active sites is variable and allows for accommodation of numerous adducts. However, not only are TLS polymerases inherently error-prone [154, 155], the number and type of hydrogen bonds that can be made with the modified bases has been altered. Those factors can produce insertion of an erroneous base during bypass that accompanies replication or transcription.
O6-meG mutagenicity has been established in bacterial and mammalian systems [29, 30]. O6-meG is mutagenic and primarily gives rise to G:C→A:T mutations. A mis-insertion of thymine is thought to occur due to mis-identification of O6-meG as adenine, as hydrogen bonding can occur with the N1 and exocyclic amino group of O6-meG [13].
Unfortunately, studies evaluating the mutagenicity of a site-specific 1-meA, 3-meC, 1-meG, or 3-meT adducts have not been conducted in mammalian systems, but studies in E. coli, show that 1-meA adducts are only slightly mutagenic, whereas 3-meC, 1-meG, and 3-meT adducts are much more mutagenic [101]. Work evaluating the anti-mutagenic role of Alkbh2 and Alkbh3 in a murine model showed increased mutant frequency, specifically for mouse embryonic fibroblast (MEF) cells deficient in either Alkbh2 or Alkbh3 [116]. Those Alkbh-deficient cells exhibited increased amounts of C:G→A:T C:G→T:A mutations, respectively. Additionally, when treated with MMS, Alkbh2-deficient MEFs displayed an increased frequency of C:G→T:A and T:A→A:T mutations. Similarly, Alkbh3-deficient MEFs also exhibited an increased frequency of T:A→A:T mutations, as well as an increased frequency of A:T→G:C mutations, in response to MMS treatment. Like O6-meG, misidentification of the modified DNA bases due to the presence of two sites for hydrogen bond formation could arise if 1-meG or 3-meC is recognized as thymine and an adenine is paired with the two remaining hydrogen bond acceptors. Furthermore, T:A→A:T mutations could arise if 3-meT becomes recognized as adenine and a thymine is paired via hydrogen bonds between thymine O4 and O2 and adenine N-3 exocyclic amino group nitrogen. It is likely that 1-meA is rarely mutagenic in E. coli, deficient in AlkB, because 1-meA can utilize the C6 exocyclic amine and N7 as an alternative binding site providing two sites for hydrogen bond formation with thymine N-7 and O4 molecules, using Hoogsteen base-pairing [156].
6. Medical significance of direct repair proteins in humans
Genetic and epigenetic controls that regulate MGMT, ALKBH2, and ALKBH3 gene expression and influence how these proteins directly repair DNA are critical factors that can lead to a better understanding of cancer development. In addition, comprehension of factors that cause variations in the direct DNA repair activities of cancer cells will provide important progress toward formulating cancer therapeutics that target MGMT or ALKBH proteins. Understanding the impact of direct DNA repair proteins will eventually result in treatments that can be tailored to achieve better therapeutic results or to predict treatment and/or disease outcomes.
6.1. Epigenetic and transcriptional regulation
Epigenetic modifications are stable alterations of DNA that are heritable in the short term, but do not involve mutations of the DNA itself, and are mediated by DNA methylation and histone modifications. The stable alterations that are involved in epigenetics have a major role in exerting control on gene expression. Endogenous cell signaling as well as external influences, including diet and other life style choices, can alter gene expression mediated by changes in epigenetic modifications [157, 158]. Methylation of cytosines at transcription factor recognition sites can interfere with binding and/or function and repress transcription of that gene [159, 160]. Alternatively, protein recruitment that binds methyl CpG islands can block transcription machinery or alter chromatin structure [161, 162]. Transcriptional silencing also is connected to histone deacetylation [163, 164]. Methyl CpG binding domain (MBD) family proteins direct histone deacetylases to remove acetyl groups from lysines in the amino terminal histone tails, stabilizing DNA-histone interactions, and condensing chromatin so that transcription factor binding sites are inaccessible.
Though unmethylated in normal cells, transcriptional silencing of MGMT, associated with promoter CpG island methylation has been reported in a variety of cancer cell types and MGMT-deficient cell lines [82, 138]. Additionally, in a glioma mouse model a subpopulation of glioma cells with stem cell properties were identified [165] that are capable of re-establishing tumor growth following temozolomide treatment. Although Mgmt promoter CpG methylation or protein levels were not determined in that study, when MGMT transcript levels were evaluated in glioma patients [166], those with MGMT CpG promoter methylation had increased response to temozolomide, but also maintained a subset of glioma cells with stem cell-like character and MGMT promoter methylation. Interestingly, mRNA levels of DNMT1 and DNMT3b methyltransferases are increased in a number of human glioma patients, but there does not appear to be a link to MGMT expression levels [167]. Moreover, MGMT promoter CpG methylation levels and DNA methyltransferase levels alone do not account for patient response to alkylating agent therapy. However, whether MGMT promoter methylation disables transcription factor binding or contributes to chromatin reorganization remains uncertain [71, 72, 74]. Therefore, regulation of MGMT expression is still unclear and merits intense scrutiny.
The inability to establish direct connections among MGMT expression, CpG methylation, and response to alkylating agent therapy indicates that other mechanisms contribute in regulating MGMT levels. Studies evaluating MGMT expression and microRNAs in patient samples have established a modest inverse correlation between the levels of MGMT transcript and miR-181d [168]. Moreover, expression of mi-181d in A1207 glioblastoma cells, results in abnormal sensitivity to temozolomide. However, expression of MGMT cDNA, restores the survival to levels close to that of the A1207 parental line. These results suggest that identification of other miRNAs involved in regulating MGMT expression will help elucidate the mechanisms that control the gene transcript levels.
In addition to control at the DNA and transcript levels, histone modifications can also control the epigenetic state and direct expression. Acetylated histone H3 and H4 levels also increase in cell lines expressing MGMT, compared to cell lines deficient in MGMT [169], which would facilitate nucleosomal positioning that enables transcription factor interactions. Further, binding of MBD proteins in the MGMT promoter of was greater in MGMT-silenced cells, implicating MBD proteins in recruitment of histone deactylases that remove lysine acetylation from the amino-terminal tails of histones H3 and H4, resulting in more condensed chromatin and transcription inactivation [73, 79, 170]. Therefore, epigenetic and/or enzymatic CpG island methylation at the MGMT promoter influences transcription factor access, as well as chromatin structure that are important for MGMT expression.
ALKBH2 and ALKBH3 both have CpG islands in their promoters, but epigenetic regulation and/or gene silencing has not been reported for either homolog. However, mutations that alter protein expression have been observed [171], but it is likely that methylation of CpG islands near any of the seven transcription factor binding sites in the promoter of ALKBH2 or the single transcription factor binding sites within the promoter region of ALKBH3, would repress transcription factor binding and possibly gene expression. Because data on the function of ALKBH promoters are less abundant compared to those available for the MGMT promoter, examination of the promoter function for those genes is an area that would benefit from further investigation.
6.2. Links to cancer
Dysregulation of numerous DNA repair pathways are involved in tumor development, progression, diagnosis, treatment and prognosis, including direct DNA repair proteins [82, 159, 172-179]. Over-expression of direct repair proteins is generally associated with a protective effect against cell death that would otherwise be induced by alkylating agent treatment. However, down-regulation or silencing of direct repair protein expression is associated with increased mutagenesis that precedes tumorgenesis. Therefore expression profiles could be used to predict potential resistance or enhanced sensitivity to therapeutics.
MGMT has been implicated in many types of human tumors. Numerous MGMT polymorphisms have risk associations with breast, lung, colon, and head and neck cancers [63, 82, 180-186]. Decreased MGMT expression is also found in glioma, lymphoma, retinoblastoma, breast (including triple-negative breast cancer) and prostate cancer [82, 138, 187] [188]. Moreover, lack of MGMT is associated with enhanced outcomes using alkylating agent therapies [5, 62, 67, 82, 86, 138, 139, 180, 181, 183, 189]. Though MGMT silencing occurs in a variety of tumor types, increased levels have also been observed in non-Hodgkin lymphoma, myeloma and glioma, as well as in some colon, pancreatic, breast, and lung cancers [63, 183, 184].
Mutations in ALKBH2 and 3 have been associated with an enhanced expression of these proteins in glioma cells and pediatric brain tumors [171, 190]. Similarly, over-expression of ALKBH3 has been associated with human rectal carcinoma [191] and prostate cancer, as well as, lung adenocarcinoma and non-small-cell lung cancer [134] [192]. On the contrary, down regulation of ALKBH2 has been observed in gastric cancer, promoting growth of gastric cancer cells [193]. Although down regulation of ALKBH2 in gastric cancer cells caused increased proliferation, ALKBH2 silencing in H1299 lung cancer cells had the opposite effect, increasing cisplatin sensitivity. Similarly, ALKBH3 silencing induced senescence and sensitivity to alkylating agents in human adenocarcinoma and prostate cancer cells [134, 193]. Therefore, further study of the role of ALKBH2 and 3 in both normal and tumor cells is necessary to elucidate their biological role(s).
6.3. Therapeutic targets
Understanding the mechanism of proteins involved in various DNA repair pathways is crucial for developing new chemotherapeutic targets and eventually new drugs. DNA alkylating agents and ionizing radiation (IR) are often used as chemotherapeutic treatments because of ability to control the dose administered and area of treatment, as well as the major cytotoxic effects of both agents at high doses. However, in addition to generation of cytotoxic adducts that cause apoptosis, alkylating agents and IR also form adducts that can be mutagenic and as a result can cause initiation of secondary cancers. Although DNA repair deficiencies are associated with increased cancer risk and formation, cancer cells proficient in DNA repair can reduce therapeutic efficacy. Currently, combination cancer treatment regimens are being explored that utilize chemotherapy or IR and target specific DNA repair proteins with pharmacological agents to enhance treatment efficacy and eliminate resistance to treatment regimens exhibited in some patients [189].
6.3.1. MGMT
Chemotherapeutic drugs such as temozolamide (TMZ) and bis-(2-chloroethyl)-nitrosourea (BCNU) generate some lesions repaired via the direct methyltransferase mechanism. Combination treatment with MGMT inhibitors prevents repair and resistance to methylating and chloroethylating agents [1, 38, 137] and has also been shown to reverse cisplatin drug resistance [194].
Understanding cellular regulation of MGMT expression will allow for selective down regulation and sensitization of tumors to alkylating agent chemotherapies. Studies have evaluated manipulation of MGMT expression and protein levels. Initial experiments evaluating MGMT inhibitors identified O6-benzyl guanine (BG) as an efficacious inhibitor of MGMT activity, a single, micromolar dose depleting greater than 99% of MGMT activity in human cells for 24-hours following drug removal [195]. Moreover, treatment with BG lacks any mutagenic or cytotoxic effects [195-197]. Clinical trials combining BG and BCNU treatment have been conducted in colon cancer, sarcoma, melanoma and myeloma, as well as studies evaluating combination of BG and TMZ [138]. Since synthesis of BG, additional BG-like inhibitors have been developed [196], including O6-(4-bromothenyl) guanine, which has been evaluated in patients with glioma [187]. Similarly, targeting of MGMT along with combination of platinum drugs, including cis- and carboplatinum [198], as well as topoisomerase I inhibitors has been investigated in various clinical trials [86].
Another approach to regulate MGMT that holds great, essentially untapped therapeutic potential is strategies utilizing RNA interference-mediated gene silencing to target MGMT [168, 199, 200]. For instance, if anti-sense molecules can specifically target MGMT mRNA translation, and degradation is also inhibited, depletion of MGMT is sustainable for long periods of time [62]. As seen in glioblastoma patients, expression levels of various miRNA markers correlate with prognosis [168, 199, 200]. Therefore, one potential new treatment could use miRNAs, such as miR-181d, to decrease MGMT levels, thus increasing sensitivity to alkylating agents [168]. Similarly, targeting regions of the MGMT promoter that is accessible to transcription factors could interfere with binding and down-regulate MGMT transcription. However, non-specific targeting of MGMT inhibitors in all cells increases chemotherapeutic toxicity. Therefore, mutant forms of MGMT that are resistant to BG-like inhibitors are also being evaluated to limit myelosuppression, affording hematopoietic progenitor cells protection from BG and BCNU or temozolomide treatment [201-204].
6.3.2. Alkbh homologs
Similar to MGMT, the role of ALKBH2 and ALKBH3 in repair of DNA alkylation damage at base-pairing sites is anti-carcinogenic. However, investigations indicate that over-expression of ALKBH proteins in various cancer cell lines shields those cells against methylating agent toxicity and would thereby protect against some chemotherapeutic treatments [134, 171, 192]. Additionally, because loss of ALKBH2 and/or ALKBH3 leads to disruption of replication, inhibition of ALKBH2 and/or ALKBH3 is a strong target for the development of novel chemotherapeutic agents. Some specific inhibitors of these proteins have already been identified [135, 205, 206], as well as generic α-KG/dioxygenase inhibitors including dimethyl oxalylglycine (DMOG) and α-ketoglutarate derivatives such as oxoglutarate. Studies have addressed the application of DNA aptamers as inhibitors of ALKBH proteins [207]. However, to date no studies have been conducted in mammalian models that evaluate the combination of ALKBH inhibitors with chemotherapeutic alkylating agents.
7. Summary
Direct repair proteins represent a unique class of enzymes that remove DNA damage without a dependence on DNA synthesis. In the future, better comprehension of how these proteins function and are produced in cells will lead to understanding their roles in formation of mutations that cause cancer. Eventually, that knowledge will foster the development of drugs to target these proteins and/or to regulate their expression to improve patient outcomes.
\n',keywords:null,chapterPDFUrl:"https://cdn.intechopen.com/pdfs/44566.pdf",chapterXML:"https://mts.intechopen.com/source/xml/44566.xml",downloadPdfUrl:"/chapter/pdf-download/44566",previewPdfUrl:"/chapter/pdf-preview/44566",totalDownloads:3407,totalViews:684,totalCrossrefCites:1,totalDimensionsCites:4,totalAltmetricsMentions:1,introChapter:null,impactScore:1,impactScorePercentile:46,impactScoreQuartile:2,hasAltmetrics:1,dateSubmitted:"April 17th 2012",dateReviewed:"October 16th 2012",datePrePublished:null,datePublished:"May 22nd 2013",dateFinished:"May 7th 2013",readingETA:"0",abstract:null,reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/44566",risUrl:"/chapter/ris/44566",book:{id:"3302",slug:"new-research-directions-in-dna-repair"},signatures:"Stephanie L. Nay and Timothy R. O‘Connor",authors:[{id:"155613",title:"Dr.",name:"Timothy",middleName:null,surname:"O\\'Connor",fullName:"Timothy O\\'Connor",slug:"timothy-o'connor",email:"toconnor@coh.org",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:{name:"City Of Hope National Medical Center",institutionURL:null,country:{name:"United States of America"}}},{id:"157190",title:"BSc.",name:"Stephanie",middleName:null,surname:"Nay",fullName:"Stephanie Nay",slug:"stephanie-nay",email:"snay@coh.org",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:null}],sections:[{id:"sec_1",title:"1. Introduction",level:"1"},{id:"sec_2",title:"2. Direct repair substrates—DNA and RNA alkylation damage",level:"1"},{id:"sec_3",title:"3. Sources of alkylation damage",level:"1"},{id:"sec_3_2",title:"3.1. Types of alkylating agents",level:"2"},{id:"sec_4_2",title:"3.2. DNA and RNA alkylation damage",level:"2"},{id:"sec_6",title:"4. Direct repair proteins",level:"1"},{id:"sec_6_2",title:"4.1. Mechanisms of alkylation repair",level:"2"},{id:"sec_7_2",title:"4.2. Methyl Guanine Methyl Transferase (MGMT) proteins",level:"2"},{id:"sec_7_3",title:"4.2.1. Protein structure/active site organization",level:"3"},{id:"sec_8_3",title:"4.2.2. Substrate recognition/repair mechanism",level:"3"},{id:"sec_9_3",title:"4.2.3. Gene expression/protein regulation",level:"3"},{id:"sec_10_3",title:"4.2.4. Protein localization and cell type dependence",level:"3"},{id:"sec_11_3",title:"4.2.5. Post-translational modification",level:"3"},{id:"sec_13_2",title:"4.3. Alkbh Fe(II)/α-ketoglutarate-dependent dioxygenases",level:"2"},{id:"sec_13_3",title:"4.3.1. Protein structure/active site organization",level:"3"},{id:"sec_14_3",title:"4.3.2. Substrate recognition/repair mechanism",level:"3"},{id:"sec_15_3",title:"4.3.3. Gene expression/protein regulation",level:"3"},{id:"sec_16_3",title:"4.3.4. Protein localization and cell type dependence",level:"3"},{id:"sec_17_3",title:"4.3.5. Post-translational modification",level:"3"},{id:"sec_20",title:"5. Biological significance of direct repair in mammalian cells ",level:"1"},{id:"sec_20_2",title:"5.1. Knock-out animal models",level:"2"},{id:"sec_21_2",title:"5.2. Replication and transcription defects",level:"2"},{id:"sec_22_2",title:"5.3. Cell cytotoxicity",level:"2"},{id:"sec_23_2",title:"5.4. Mutagenesis",level:"2"},{id:"sec_25",title:"6. Medical significance of direct repair proteins in humans",level:"1"},{id:"sec_25_2",title:"6.1. Epigenetic and transcriptional regulation",level:"2"},{id:"sec_26_2",title:"6.2. Links to cancer",level:"2"},{id:"sec_27_2",title:"6.3. Therapeutic targets",level:"2"},{id:"sec_27_3",title:"6.3.1. MGMT",level:"3"},{id:"sec_28_3",title:"6.3.2. Alkbh homologs",level:"3"},{id:"sec_31",title:"7. Summary",level:"1"}],chapterReferences:[{id:"B1",body:'Drablos F, Feyzi E, Aas PA, Vaagbo CB, Kavli B, Bratlie MS, et al. Alkylation damage in DNA and RNA--repair mechanisms and medical significance. DNA Repair (Amst). 2004;3(11):1389-407.'},{id:"B2",body:'Sedgwick B. Repairing DNA-methylation damage. Nat Rev Mol Cell Biol. 2004;5(2):148-57.'},{id:"B3",body:'Hecht SS. DNA adduct formation from tobacco-specific N-nitrosamines. Mutat Res. 1999;424(1-2):127-42.'},{id:"B4",body:'Ballschmiter K. Pattern and sources of naturally produced organohalogens in the marine environment: biogenic formation of organohalogens. Chemosphere. 2003;52(2):313-24.'},{id:"B5",body:'Sanada M, Takagi Y, Ito R, Sekiguchi M. Killing and mutagenic actions of dacarbazine, a chemotherapeutic alkylating agent, on human and mouse cells: effects of Mgmt and Mlh1 mutations. DNA Repair (Amst). 2004;3(4):413-20.'},{id:"B6",body:'Shiraishi A, Sakumi K, Sekiguchi M. Increased susceptibility to chemotherapeutic alkylating agents of mice deficient in DNA repair methyltransferase. Carcinogenesis. 2000;21(10):1879-83.'},{id:"B7",body:'Taverna P, Sedgwick B. Generation of an endogenous DNA-methylating agent by nitrosation in Escherichia coli. J Bacteriol. 1996;178(17):5105-11.'},{id:"B8",body:'Cantoni GL. The nature of the active methyldonor formed enzymatically from L-methionine and adenosinetriphosphate.. J Am Chem Soc. 1952;74(11):2942-3.'},{id:"B9",body:'Cantoni GL, Scarano E. The formation of S-adenosylhomocysteine in enzymatic transmethylation reactions. J Am Chem Soc. 1954;76(18):4744-.'},{id:"B10",body:'Kumar S, Cheng X, Klimasauskas S, Mi S, Posfai J, Roberts RJ, et al. The DNA (cytosine-5) methyltransferases. Nucleic Acids Res. 1994;22(1):1-10.'},{id:"B11",body:'Goll MG, Kirpekar F, Maggert KA, Yoder JA, Hsieh CL, Zhang X, et al. Methylation of tRNAAsp by the DNA methyltransferase homolog Dnmt2. Science. 2006;311(5759):395-8.'},{id:"B12",body:'Patterson LH, Murray GI. Tumour cytochrome P450 and drug activation. Curr Pharm Des. 2002;8(15):1335-47.'},{id:"B13",body:'Singer B, Grunberger D, editors. Molecular Biology of Mutagens and Carcinogens. 1 ed. New York: Plenum; 1983.'},{id:"B14",body:'Friedberg EC, Walker GC, Siede W. DNA Repair and mutagenesis. Washington DC: ASM Press; 1995.'},{id:"B15",body:'Aas PA, Otterlei M, Falnes PO, Vagbo CB, Skorpen F, Akbari M, et al. Human and bacterial oxidative demethylases repair alkylation damage in both RNA and DNA. Nature. 2003;421(6925):859-63.'},{id:"B16",body:'Fu D, Calvo JA, Samson LD. Balancing repair and tolerance of DNA damage caused by alkylating agents. Nat Rev Cancer. 2012;12(2):104-20.'},{id:"B17",body:'Mishina Y, Duguid EM, He C. Direct Reversal of DNA Alkylation Damage. Chem Rev. 2006;106(2):215-32.'},{id:"B18",body:'Baker DJ, Wuenschell G, Xia L, Termini J, Bates SE, Riggs AD, et al. Nucleotide excision repair eliminates unique DNA-protein cross-links from mammalian cells. J Biol Chem. 2007;282(31):22592-604.'},{id:"B19",body:'Bjelland S, Bjoras M, Seeberg E. Excision of 3-methylguanine from alkylated DNA by 3-methyladenine DNA glycosylase I of Escherichia coli. Nucleic Acids Res. 1993;21(9):2045-9.'},{id:"B20",body:'Jones LE, Jr., Ying L, Hofseth AB, Jelezcova E, Sobol RW, Ambs S, et al. Differential effects of reactive nitrogen species on DNA base excision repair initiated by the alkyladenine DNA glycosylase. Carcinogenesis. 2009;30(12):2123-9.'},{id:"B21",body:'Fortini P, Dogliotti E. Base damage and single-strand break repair: mechanisms and functional significance of short- and long-patch repair subpathways. DNA Repair (Amst). 2007;6(4):398-409.'},{id:"B22",body:'Houtgraaf JH, Versmissen J, van der Giessen WJ. A concise review of DNA damage checkpoints and repair in mammalian cells. Cardiovasc Revasc Med. 2006;7(3):165-72.'},{id:"B23",body:'Samson L, Han S, Marquis JC, Rasmussen LJ. Mammalian DNA repair methyltransferases shield O4MeT from nucleotide excision repair. Carcinogenesis. 1997;18(5):919-24.'},{id:"B24",body:'Ziemba A, Derosier LC, Methvin R, Song CY, Clary E, Kahn W, et al. Repair of triplex-directed DNA alkylation by nucleotide excision repair. Nucleic Acids Res. 2001;29(21):4257-63.'},{id:"B25",body:'Ye N, Holmquist GP, O\'Connor TR. Heterogeneous repair of N-methylpurines at the nucleotide level in normal human cells. J Mol Biol. 1998;284(2):269-85.'},{id:"B26",body:'Kondo N, Takahashi A, Ono K, Ohnishi T. DNA damage induced by alkylating agents and repair pathways. Journal of nucleic acids. 2010;2010:543531. Epub 2010/11/30.'},{id:"B27",body:'Sobol RW, Kartalou M, Almeida KH, Joyce DF, Engelward BP, Horton JK, et al. Base excision repair intermediates induce p53-independent cytotoxic and genotoxic responses. J Biol Chem. 2003;278(41):39951-9.'},{id:"B28",body:'Hoeijmakers JH. Genome Maintenance Mechanisms for Preventing Cancer. Nature. 2001(411):366 - 74.'},{id:"B29",body:'Dosanjh MK, Singer B, Essigmann JM. Comparative mutagenesis of O6-methylguanine and O4-methylthymine in Escherichia coli. Biochemistry. 1991;30(28):7027-33. Epub 1991/07/16.'},{id:"B30",body:'Ellison KS, Dogliotti E, Connors TD, Basu AK, Essigmann JM. Site-specific mutagenesis by O6-alkylguanines located in the chromosomes of mammalian cells: influence of the mammalian O6-alkylguanine-DNA alkyltransferase. Proc Natl Acad Sci U S A. 1989;86(22):8620-4.'},{id:"B31",body:'Reha-Krantz LJ, Nonay RL, Day RS, Wilson SH. Replication of O6-methylguanine-containing DNA by repair and replicative DNA polymerases. J Biol Chem. 1996;271(33):20088-95.'},{id:"B32",body:'Voigt JM, Topal MD. O6-methylguanine-induced replication blocks. Carcinogenesis. 1995;16(8):1775-82.'},{id:"B33",body:'Fang Q, Noronha AM, Murphy SP, Wilds CJ, Tubbs JL, Tainer JA, et al. Repair of O6-G-alkyl-O6-G interstrand cross-links by human O6-alkylguanine-DNA. Biochemistry. 2008;47(41):10892-903.'},{id:"B34",body:'Graves RJ, Li BF, Swann PF. Repair of O6-methylguanine, O6-ethylguanine, O6-isopropylguanine and. Carcinogenesis. 1989;10(4):661-6.'},{id:"B35",body:'Jena NR, Shukla PK, Jena HS, Mishra PC, Suhai S. O6-methylguanine repair by O6-alkylguanine-DNA alkyltransferase. J Phys Chem B. 2009;113(51):16285-90.'},{id:"B36",body:'Kawate H, Ihara K, Kohda K, Sakumi K, Sekiguchi M. Mouse methyltransferase for repair of O6-methylguanine and O4-methylthymine in. Carcinogenesis. 1995;16(7):1595-602.'},{id:"B37",body:'Swann PF. Why do O6-alkylguanine and O4-alkylthymine miscode? The relationship between the. Mutat Res. 1990;233(1-2):81-94.'},{id:"B38",body:'Verbeek B, Southgate TD, Gilham DE, Margison GP. O6-Methylguanine-DNA methyltransferase inactivation and chemotherapy. Br Med Bull. 2008;85:17-33.'},{id:"B39",body:'Parkinson JF, Wheeler HT, McDonald KL. Contribution of DNA repair mechanisms to determining chemotherapy response in high-grade glioma. J Clin Neurosci. 2008;15(1):1-8.'},{id:"B40",body:'Srivenugopal KS, Yuan XH, Friedman HS, Ali-Osman F. Ubiquitination-dependent proteolysis of O6-methylguanine-DNA methyltransferase in human and murine tumor cells following inactivation with O6-benzylguanine or 1,3-bis(2-chloroethyl)-1-nitrosourea. Biochemistry. 1996;35(4):1328-34. Epub 1996/01/30.'},{id:"B41",body:'Fang Q, Kanugula S, Pegg AE. Function of domains of human O6-alkylguanine-DNA alkyltransferase. Biochemistry. 2005;44(46):15396-405.'},{id:"B42",body:'Daniels DS, Tainer JA. Conserved structural motifs governing the stoichiometric repair of alkylated DNA. Mutat Res. 2000;460(3-4):151-63.'},{id:"B43",body:'Hashimoto H, Inoue T, Nishioka M, Fujiwara S, Takagi M, Imanaka T, et al. Hyperthermostable protein structure maintained by intra and inter-helix ion-pairs. J Mol Biol. 1999;292(3):707-16.'},{id:"B44",body:'Moore MH, Gulbis JM, Dodson EJ, Demple B, Moody PC. Crystal structure of a suicidal DNA repair protein: the Ada O6-methylguanine-DNA. Embo J. 1994;13(7):1495-501.'},{id:"B45",body:'Roberts A, Pelton JG, Wemmer DE. Structural studies of MJ1529, an O6-methylguanine-DNA methyltransferase. Magn Reson Chem. 2006;44 Spec No:S71-82.'},{id:"B46",body:'Wibley JE, Pegg AE, Moody PC. Crystal structure of the human O(6)-alkylguanine-DNA alkyltransferase. Nucleic Acids Res. 2000;28(2):393-401.'},{id:"B47",body:'Rasimas JJ, Kanugula S, Dalessio PM, Ropson IJ, Fried MG, Pegg AE, et al. Effects of zinc occupancy on human O6-alkylguanine-DNA alkyltransferase. Biochemistry. 2003;42(4):980-90.'},{id:"B48",body:'Daniels DS, Mol CD, Arvai AS, Kanugula S, Pegg AE, Tainer JA. Active and alkylated human AGT structures: a novel zinc site, inhibitor and extrahelical base binding. Embo J. 2000;19(7):1719-30.'},{id:"B49",body:'Crone TM, Pegg AE. A single amino acid change in human O6-alkylguanine-DNA alkyltransferase decreasing sensitivity to inactivation by O6-benzylguanine. Cancer Res. 1993;53(20):4750-3.'},{id:"B50",body:'Lindahl T, Demple B, Robins P. Suicide inactivation of the E. coli O6-methylguanine-DNA methyltransferase. Embo J. 1982;1(11):1359-63.'},{id:"B51",body:'Daniels DS, Woo TT, Luu KX, Noll DM, Clarke ND, Pegg AE, et al. DNA binding and nucleotide flipping by the human DNA repair protein AGT. Nat Struct Mol Biol. 2004;11(8):714-20.'},{id:"B52",body:'Duguid EM-, Rice PA, He C. The structure of the human AGT protein bound to DNA and its implications for. J Mol Biol. 2005;350(4):657-66.'},{id:"B53",body:'Pegg AE. Repair of O(6)-alkylguanine by alkyltransferases. Mutat Res. 2000;462(2-3):83-100.'},{id:"B54",body:'Tubbs JL, Latypov V, Kanugula S, Butt A, Melikishvili M, Kraehenbuehl R, et al. Alkylated DNA damage flipping bridges base and nucleotide excision repair. Nature. 2009;459(7248):808-13.'},{id:"B55",body:'Tubbs JL, Pegg AE, Tainer JA. DNA binding, nucleotide flipping, and the helix-turn-helix motif in base repair. DNA Repair (Amst). 2007;6(8):1100-15.'},{id:"B56",body:'Verdemato PE, Brannigan JA, Damblon C, Zuccotto F, Moody PC, Lian LY. DNA-binding mechanism of the Escherichia coli Ada O(6)-alkylguanine-DNA alkyltransferase. Nucleic Acids Res. 2000;28(19):3710-8.'},{id:"B57",body:'Yang CG, Garcia K, He C. Damage Detection and Base Flipping in Direct DNA Alkylation Repair. Chembiochem. 2009.'},{id:"B58",body:'Zak P, Kleibl K, Laval F. Repair of O(6)-alkylguanine by alkyltransferases. J Biol Chem. 2000;462(2-3):83-100.'},{id:"B59",body:'Yarosh DB, Rice M, Day RS, 3rd, Foote RS, Mitra S. O6-Methylguanine-DNA methyltransferase in human cells. Mutat Res. 1984;131(1):27-36.'},{id:"B60",body:'Fried MG, Kanugula S, Bromberg JL, Pegg AE. The modified human DNA repair enzyme O(6)-methylguanine-DNA methyltransferase is a negative regulator of estrogen receptor-mediated transcription upon alkylation DNA damage. Biochemistry. 2001;21(20):7105-14.'},{id:"B61",body:'Groth P, Auslander S, Majumder MM, Schultz N, Johansson F, Petermann E, et al. Methylated DNA causes a physical block to replication forks independently of damage signalling, O(6)-methylguanine or DNA single-strand breaks and results in DNA damage. J Mol Biol. 2010;402(1):70-82.'},{id:"B62",body:'Pieper RO. Understanding and manipulating O6-methylguanine-DNA methyltransferase expression. Pharmacol Ther. 1997;74(3):285-97.'},{id:"B63",body:'Matsukura S, Miyazaki K, Yakushiji H, Ogawa A, Harimaya K, Nakabeppu Y, et al. Expression and prognostic significance of O6-methylguanine-DNA methyltransferase. Ann Surg Oncol. 2001;8(10):807-16.'},{id:"B64",body:'Natarajan AT, Vermeulen S, Darroudi F, Valentine MB, Brent TP, Mitra S, et al. Chromosomal localization of human O6-methylguanine-DNA methyltransferase (MGMT). Mutagenesis. 1992;7(1):83-5.'},{id:"B65",body:'Nakatsu Y, Hattori K, Hayakawa H, Shimizu K, Sekiguchi M. Organization and expression of the human gene for O6-methylguanine-DNA. Mutat Res. 1993;293(2):119-32.'},{id:"B66",body:'Tano K, Shiota S, Collier J, Foote RS, Mitra S. Isolation and structural characterization of a cDNA clone encoding the human DNA. Proc Natl Acad Sci U S A. 1990;87(2):686-90.'},{id:"B67",body:'Soejima H, Zhao W, Mukai T. Epigenetic silencing of the MGMT gene in cancer. Biochem Cell Biol. 2005;83(4):429-37.'},{id:"B68",body:'Gardiner-Garden M, Frommer M. CpG islands in vertebrate genomes. J Mol Biol. 1987;196(2):261-82.'},{id:"B69",body:'Harris LC, Potter PM, Tano K, Shiota S, Mitra S, Brent TP. Characterization of the promoter region of the human O6-methylguanine-DNA. Nucleic Acids Res. 1991;19(22):6163-7.'},{id:"B70",body:'Takai D, Jones PA. Comprehensive analysis of CpG islands in human chromosomes 21 and 22. Proc Natl Acad Sci U S A. 2002;99(6):3740-5.'},{id:"B71",body:'Pieper RO, Patel S, Ting SA, Futscher BW, Costello JF. Methylation of CpG island transcription factor binding sites is unnecessary for. J Biol Chem. 1996;271(23):13916-24.'},{id:"B72",body:'Costello JF, Futscher BW, Kroes RA, Pieper RO. Methylation-related chromatin structure is associated with exclusion of. Mol Cell Biol. 1994;14(10):6515-21.'},{id:"B73",body:'Pieper RO, Costello JF-, Kroes RA, Futscher BW, Marathi U, Erickson LC. Direct correlation between methylation status and expression of the human. Cancer Commun. 1991;3(8):241-53.'},{id:"B74",body:'Costello JF, Futscher BW, Tano K, Graunke DM, Pieper RO. Graded methylation in the promoter and body of the O6-methylguanine DNA. J Biol Chem. 1994;269(25):17228-37.'},{id:"B75",body:'Qian X, von Wronski MA, Brent TP. Localization of methylation sites in the human O6-methylguanine-DNA. Carcinogenesis. 1995;16(6):1385-90.'},{id:"B76",body:'Silber JR, Blank A, Bobola MS, Mueller BA, Kolstoe DD, Ojemann GA, et al. Lack of the DNA repair protein O6-methylguanine-DNA methyltransferase in. Proc Natl Acad Sci U S A. 1996;93(14):6941-6.'},{id:"B77",body:'Patel SA, Graunke DM, Pieper RO. Aberrant silencing of the CpG island-containing human O6-methylguanine DNA methyltransferase gene is associated with the loss of nucleosome-like positioning. Mol Cell Biol. 1997;17(10):5813-22. Epub 1997/10/07.'},{id:"B78",body:'Nakagawachi T, Soejima H, Urano T, Zhao W, Higashimoto K, Satoh Y, et al. Silencing effect of CpG island hypermethylation and histone modifications on O6-methylguanine-DNA methyltransferase (MGMT) gene expression in human cancer. Oncogene. 2003;22(55):8835-44.'},{id:"B79",body:'Zhao W, Soejima H, Higashimoto K, Nakagawachi T, Urano T, Kudo S, et al. The essential role of histone H3 Lys9 di-methylation and MeCP2 binding in MGMT. J Biochem. 2005;137(3):431-40.'},{id:"B80",body:'Ali RB, Teo AK, Oh HK, Chuang LS, Ayi TC, Li BF. Implication of localization of human DNA repair enzyme O6-methylguanine-DNA. Mol Cell Biol. 1998;18(3):1660-9.'},{id:"B81",body:'Lim A, Li BF. The nuclear targeting and nuclear retention properties of a human DNA repair. Embo J. 1996;15(15):4050-60.'},{id:"B82",body:'Gerson SL. MGMT: its role in cancer aetiology and cancer therapeutics. Nat Rev Cancer. 2004;4(4):296-307.'},{id:"B83",body:'Kaina B, Christmann M, Naumann S, Roos WP. MGMT: key node in the battle against genotoxicity, carcinogenicity and apoptosis. DNA Repair (Amst). 2007;6(8):1079-99.'},{id:"B84",body:'Liu L, Gerson SL. Targeted modulation of MGMT: clinical implications. Clin Cancer Res. 2006;12(2):328-31.'},{id:"B85",body:'Pegg AE, Fang Q, Loktionova NA. Human variants of O6-alkylguanine-DNA alkyltransferase. DNA Repair (Amst). 2007;6(8):1071-8.'},{id:"B86",body:'Sabharwal A, Middleton MR. Exploiting the role of O6-methylguanine-DNA-methyltransferase (MGMT) in cancer therapy. Curr Opin Pharmacol. 2006;6(4):355-63.'},{id:"B87",body:'Srivenugopal KS, Yuan XH, Friedman HS, Ali-Osman F. Inhibition by nitric oxide of the repair protein, O6-methylguanine-DNA-methyltransferase. Biochemistry. 1994;15(3):443-7.'},{id:"B88",body:'Hwang CS, Shemorry A, Varshavsky A. Two proteolytic pathways regulate DNA repair by cotargeting the Mgt1 alkylguanine. Proc Natl Acad Sci U S A. 2009;106(7):2142-7.'},{id:"B89",body:'Srivenugopal KS, Ali-Osman F. The DNA repair protein, O(6)-methylguanine-DNA methyltransferase is a proteolytic. Oncogene. 2002;21(38):5940-5.'},{id:"B90",body:'Li T, Du Y, Wang L, Huang L, Li W, Lu M, et al. Characterization and prediction of lysine (K)-acetyl-transferase specific acetylation sites. Molecular & cellular proteomics : MCP. 2012;11(1):M111 011080. Epub 2011/10/04.'},{id:"B91",body:'Artimo P, Jonnalagedda M, Arnold K, Baratin D, Csardi G, de Castro E, et al. ExPASy: SIB bioinformatics resource portal. Nucleic Acids Res. 2012;40(Web Server issue):W597-603. Epub 2012/06/05.'},{id:"B92",body:'Hornbeck PV, Kornhauser JM, Tkachev S, Zhang B, Skrzypek E, Murray B, et al. PhosphoSitePlus: a comprehensive resource for investigating the structure and function of experimentally determined post-translational modifications in man and mouse. Nucleic Acids Res. 2012;40(Database issue):D261-70. Epub 2011/12/03.'},{id:"B93",body:'Shi SP, Qiu JD, Sun XY, Suo SB, Huang SY, Liang RP. PMeS: prediction of methylation sites based on enhanced feature encoding scheme. PLoS ONE. 2012;7(6):e38772. Epub 2012/06/22.'},{id:"B94",body:'Begley TJ, Samson LD. AlkB mystery solved: oxidative demethylation of N1-methyladenine and N3-methylcytosine adducts by a direct reversal mechanism. Trends Biochem Sci. 2003;28(1):2-5.'},{id:"B95",body:'Flashman E, Davies SL, Yeoh KK, Schofield CJ. Investigating the dependence of the hypoxia-inducible factor hydroxylases (factor inhibiting HIF and prolyl hydroxylase domain 2) on ascorbate and other reducing agents. Biochem J. 2010;427(1):135-42.'},{id:"B96",body:'Kataoka H, Yamamoto Y, Sekiguchi M. A new gene (alkB) of Escherichia coli that controls sensitivity to methyl methane sulfonate. J Bacteriol. 1983;153(3):1301-7.'},{id:"B97",body:'Schneider J, Shilatifard A. Histone demethylation by hydroxylation: chemistry in action. ACS Chem Biol. 2006;1(2):75-81.'},{id:"B98",body:'Tsukada Y, Fang J, Erdjument-Bromage H, Warren ME, Borchers CH, Tempst P, et al. Histone demethylation by a family of JmjC domain-containing proteins. Nature. 2006;439(7078):811-6.'},{id:"B99",body:'Yamane K, Toumazou C, Tsukada Y, Erdjument-Bromage H, Tempst P, Wong J, et al. JHDM2A, a JmjC-containing H3K9 demethylase, facilitates transcription activation by androgen receptor. Cell. 2006;125(3):483-95.'},{id:"B100",body:'Trewick SC, Henshaw TF, Hausinger RP, Lindahl T, Sedgwick B. Oxidative demethylation by Escherichia coli AlkB directly reverts DNA base damage. Nature. 2002;419(6903):174-8.'},{id:"B101",body:'Delaney JC, Essigmann JM. Mutagenesis, genotoxicity, and repair of 1-methyladenine, 3-alkylcytosines, 1-methylguanine, and 3-methylthymine in alkB Escherichia coli. Proc Natl Acad Sci U S A. 2004;101(39):14051-6. Epub 2004/09/24.'},{id:"B102",body:'Delaney JC, Smeester L, Wong C, Frick LE, Taghizadeh K, Wishnok JS, et al. AlkB reverses etheno DNA lesions caused by lipid oxidation in vitro and in vivo. Nat Struct Mol Biol. 2005;12(10):855-60.'},{id:"B103",body:'Falnes PO. Repair of 3-methylthymine and 1-methylguanine lesions by bacterial and human AlkB proteins. Nucleic Acids Res. 2004;32(21):6260-7.'},{id:"B104",body:'Falnes PO, Bjoras M, Aas PA, Sundheim O, Seeberg E. Substrate specificities of bacterial and human AlkB proteins. Nucleic Acids Res. 2004;32(11):3456-61.'},{id:"B105",body:'Frick LE, Delaney JC, Wong C, Drennan CL, Essigmann JM. Alleviation of 1,N6-ethanoadenine genotoxicity by the Escherichia coli adaptive response protein AlkB. Proc Natl Acad Sci U S A. 2007;104(3):755-60.'},{id:"B106",body:'Koivisto P, Robins P, Lindahl T, Sedgwick B. Demethylation of 3-methylthymine in DNA by bacterial and human DNA dioxygenases. J Biol Chem. 2004;279(39):40470-4.'},{id:"B107",body:'Mishina Y, Yang CG, He C. Direct repair of the exocyclic DNA adduct 1,N6-ethenoadenine by the DNA repair AlkB proteins. J Am Chem Soc. 2005;127(42):14594-5.'},{id:"B108",body:'Ougland R, Zhang CM, Liiv A, Johansen RF, Seeberg E, Hou YM, et al. AlkB restores the biological function of mRNA and tRNA inactivated by chemical methylation. Mol Cell. 2004;16(1):107-16.'},{id:"B109",body:'Aravind L, Koonin EV. The DNA-repair protein AlkB, EGL-9, and leprecan define new families of 2-oxoglutarate- and iron-dependent dioxygenases. Genome Biol. 2001;2(3):RESEARCH0007.'},{id:"B110",body:'Kurowski MA, Bhagwat AS, Papaj G, Bujnicki JM. Phylogenomic identification of five new human homologs of the DNA repair enzyme AlkB. BMC Genomics. 2003;4(1):48.'},{id:"B111",body:'Duncan T, Trewick SC, Koivisto P, Bates PA, Lindahl T, Sedgwick B. Reversal of DNA alkylation damage by two human dioxygenases. Proc Natl Acad Sci U S A. 2002;99(26):16660-5.'},{id:"B112",body:'Mishina Y, He C. Oxidative dealkylation DNA repair mediated by the mononuclear non-heme iron AlkB proteins. J Inorg Biochem. 2006;100(4):670-8.'},{id:"B113",body:'Sedgwick B, Robins P, Lindahl T. Direct removal of alkylation damage from DNA by AlkB and related DNA dioxygenases. Methods Enzymol. 2006;408:108-20.'},{id:"B114",body:'Sundheim O, Talstad VA, Vagbo CB, Slupphaug G, Krokan HE. AlkB demethylases flip out in different ways. DNA Repair (Amst). 2008;7(11):1916-23.'},{id:"B115",body:'Westbye MP, Feyzi E, Aas PA, Vagbo CB, Talstad VA, Kavli B, et al. Human AlkB homolog 1 is a mitochondrial protein that demethylates 3-methylcytosine in DNA and RNA. J Biol Chem. 2008;283(36):25046-56.'},{id:"B116",body:'Nay SL, Lee DH, Bates SE, O\'Connor TR. Alkbh2 protects against lethality and mutation in primary mouse embryonic. DNA Repair (Amst). 2012;11(5):502-10.'},{id:"B117",body:'Nieminuszczy J, Mielecki D, Sikora A, Wrzesinski M, Chojnacka A, Krwawicz J, et al. Mutagenic potency of MMS-induced 1meA/3meC lesions in E. coli. Environ Mol Mutagen. 2009;50(9):791-9.'},{id:"B118",body:'Ringvoll J, Nordstrand LM, Vagbo CB, Talstad V, Reite K, Aas PA, et al. Repair deficient mice reveal mABH2 as the primary oxidative demethylase for repairing 1meA and 3meC lesions in DNA. EMBO J. 2006;25(10):2189-98.'},{id:"B119",body:'Calvo JA, Meira LB, Lee CYI, Erkul CA, Abolhassani N, Taghizadeh K, et al. DNA repair is indispensable for survival after acute inflammation. J Clin Invest. 2012;122(7):2680-9.'},{id:"B120",body:'Sundheim O, Vagbo CB, Bjoras M, Sousa MM, Talstad V, Aas PA, et al. Human ABH3 structure and key residues for oxidative demethylation to reverse DNA/RNA damage. EMBO J. 2006;25(14):3389-97.'},{id:"B121",body:'Yang CG, Yi C, Duguid EM, Sullivan CT, Jian X, Rice PA, et al. Crystal structures of DNA/RNA repair enzymes AlkB and ABH2 bound to dsDNA. Nature. 2008;452(7190):961-5.'},{id:"B122",body:'Yi C, Yang CG, He C. A Non-Heme Iron-Mediated Chemical Demethylation in DNA and RNA. Acc Chem Res. 2009;42(4):519-29.'},{id:"B123",body:'Yu B, Edstrom WC, Benach J, Hamuro Y, Weber PC, Gibney BR, et al. Crystal structures of catalytic complexes of the oxidative DNA/RNA repair enzyme AlkB. Nature. 2006;439(7078):879-84.'},{id:"B124",body:'Bleijlevens B, Shivarattan T, Flashman E, Yang Y, Simpson PJ, Koivisto P, et al. Dynamic states of the DNA repair enzyme AlkB regulate product release. EMBO Rep. 2008;9(9):872-7.'},{id:"B125",body:'Sedgwick B, Bates PA, Paik J, Jacobs SC, Lindahl T. Repair of alkylated DNA: recent advances. DNA Repair (Amst). 2007;6(4):429-42.'},{id:"B126",body:'Shimada K, Nakamura M, Anai S, De Velasco M, Tanaka M, Tsujikawa K, et al. A novel human AlkB homologue, ALKBH8, contributes to human bladder cancer progression. Cancer Res. 2009;69(7):3157-64.'},{id:"B127",body:'Songe-Moller L, van den Born E, Leihne V, Vagbo CB, Kristoffersen T, Krokan HE, et al. Mammalian ALKBH8 possesses tRNA methyltransferase activity required for the biogenesis of multiple wobble uridine modifications implicated in translational decoding. Mol Cell Biol. 2010;30(7):1814-27.'},{id:"B128",body:'Falnes PO, Johansen RF, Seeberg E. AlkB-mediated oxidative demethylation reverses DNA damage in Escherichia coli. Nature. 2002;419(6903):178-82.'},{id:"B129",body:'Kataoka H, Sekiguchi M. Molecular cloning and characterization of the alkB gene of Escherichia coli. Mol Gen Genet. 1985;198(2):263-9.'},{id:"B130",body:'Liu H, Llano J, Gauld JW. A DFT study of nucleobase dealkylation by the DNA repair enzyme AlkB. J Phys Chem B. 2009;113(14):4887-98.'},{id:"B131",body:'Lee DH, Jin SG, Cai S, Chen Y, Pfeifer GP, O\'Connor TR. Repair of methylation damage in DNA and RNA by mammalian AlkB homologues. J Biol Chem. 2005;280(47):39448-59.'},{id:"B132",body:'Ringvoll J, Moen MN, Nordstrand LM, Meira LB, Pang B, Bekkelund A, et al. AlkB homologue 2-mediated repair of ethenoadenine lesions in mammalian DNA. Cancer Res. 2008;68(11):4142-9.'},{id:"B133",body:'Tsujikawa K, Koike K, Kitae K, Shinkawa A, Arima H, Suzuki T, et al. Expression and sub-cellular localization of human ABH family molecules. J Cell Mol Med. 2007;11(5):1105-16.'},{id:"B134",body:'Dango S, Mosammaparast N, Sowa M, Xiong L, Wu F, Park K, et al. DNA Unwinding by ASCC3 Helicase Is Coupled to ALKBH3-Dependent DNA Alkylation Repair and Cancer Cell Proliferation. Molecular Cell. 2011(44):373–84.'},{id:"B135",body:'Welford RW, Schlemminger I, McNeill LA, Hewitson KS, Schofield CJ. The selectivity and inhibition of AlkB. J Biol Chem. 2003;278(12):10157-61.'},{id:"B136",body:'Tsuzuki T, Sakumi K, Shiraishi A, Kawate H, Igarashi H, Iwakuma T, et al. Targeted disruption of the DNA repair methyltransferase gene renders mice hypersensitive to alkylating agent. Carcinogenesis. 1996;17(6):1215-20.'},{id:"B137",body:'D\'Atri S, Graziani G, Lacal PM, Nistico V, Gilberti S, Faraoni I, et al. Attenuation of O(6)-methylguanine-DNA methyltransferase activity and mRNA levels by cisplatin and temozolomide in jurkat cells. J Pharmacol Exp Ther. 2000;294(2):664-71.'},{id:"B138",body:'Gerson SL. Clinical relevance of MGMT in the treatment of cancer. J Clin Oncol. 2002;20(9):2388-99.'},{id:"B139",body:'Hansen RJ, Ludeman SM, Paikoff SJ, Pegg AE, Dolan ME. Role of MGMT in Protecting against Cyclophosphamide-Induced Toxicity in Cells and. DNA Repair (Amst). 2007;6(8):1145-54.'},{id:"B140",body:'Glassner BJ, Weeda G, Allan JM, Broekhof JL, Carls NH, Donker I, et al. DNA repair methyltransferase (Mgmt) knockout mice are sensitive to the lethal. Mutagenesis. 1999;14(3):339-47.'},{id:"B141",body:'Roos WP, Christmann M, Fraser ST, Kaina B. Mouse embryonic stem cells are hypersensitive to apoptosis triggered by the DNA damage O(6)-methylguanine due to high E2F1 regulated mismatch repair. Cell Death Differ. 2007;14(8):1422-32.'},{id:"B142",body:'Sakumi K, Shiraishi A, Shimizu S, Tsuzuki T, Ishikawa T, Sekiguchi M. Methylnitrosourea-induced tumorigenesis in MGMT gene knockout mice. Cancer Res. 1997;57(12):2415-8.'},{id:"B143",body:'Bobola MS, Blank A, Berger MS, Silber JR. O6-methylguanine-DNA methyltransferase deficiency in developing brain. DNA Repair (Amst). 2007;6(8):1127-33.'},{id:"B144",body:'Dumenco Ll, Allay E, Norton K, Gerson SL. The prevention of thymic lymphomas in transgenic mice by human. Science. 1993;259(5092):219-22.'},{id:"B145",body:'Horsfield JA, Anagnostou SH, Hu JK, Cho KH, Geisler R, Lieschke G, et al. Cohesin-dependent regulation of Runx genes. Development. 2007;134(14):2639-49.'},{id:"B146",body:'Tominaga Y, Tsuzuki T, Shiraishi A, Kawate H, Sekiguchi M. Alkylation-induced apoptosis of embryonic stem cells in which the gene for DNA-repair, methyltransferase, had been disrupted by gene targeting. Carcinogenesis. 1997;18(5):889-96.'},{id:"B147",body:'Nordstrand L, Svard J, Larsen E, Nilsen A, Ougland R, Furu K, et al. Mice lacking Alkbh1 display sex-ratio distortion and unilateral eye defects. PLoS Biol. 2010;5(11).'},{id:"B148",body:'Pan Z, Sikandar S, Witherspoon M, Dizon D, Nguyen T, Benirschke K, et al. Impaired placental trophoblast lineage differentiation in Alkbh1(-/-) mice. Dev Dyn. 2008;237(2):316-27.'},{id:"B149",body:'Haracska L, Prakash S, Prakash L. Replication past O(6)-methylguanine by yeast and human DNA polymerase eta. Mol Cell Biol. 2000;20(21):8001-7.'},{id:"B150",body:'Singh J, Su L, Snow ET. Replication across O6-methylguanine by human DNA polymerase beta in vitro. Insights into the futile cytotoxic repair and mutagenesis of O6-methylguanine. J Biol Chem. 1996;271(45):28391-8.'},{id:"B151",body:'Andreassen PR, Ho GP, D\'Andrea AD. DNA damage responses and their many interactions with the replication fork. Carcinogenesis. 2006;27(5):883-92.'},{id:"B152",body:'Feyzi E, Sundheim O, Westbye MP, Aas PA, Vagbo CB, Otterlei M, et al. RNA base damage and repair. Curr Pharm Biotechnol. 2007;8(6):326-31.'},{id:"B153",body:'Loechler EL, Green CL, Essigmann JM. In vivo mutagenesis by O6-methylguanine built into a unique site in a viral genome. Proc Natl Acad Sci U S A. 1984;81(20):6271-5.'},{id:"B154",body:'McCulloch SD, Kunkel TA. The fidelity of DNA synthesis by eukaryotic replicative and translesion synthesis. Cell Res. 2008;18(1):148-61.'},{id:"B155",body:'Prakash S, Johnson RE, Prakash L. Eukaryotic translesion synthesis DNA polymerases: specificity of structure and. Annu Rev Biochem. 2005;74:317-53.'},{id:"B156",body:'Yang H, Lam SL. Effect of 1-methyladenine on thermodynamic stabilities of double-helical DNA structures. FEBS Lett. 2009;583(9):1548-53.'},{id:"B157",body:'Rodenhiser D, Mann M. Epigenetics and human disease: translating basic biology into clinical applications. Cmaj. 2006;174(3):341-8.'},{id:"B158",body:'Laird PW, Jaenisch R. The role of DNA methylation in cancer genetic and epigenetics. Annu Rev Genet. 1996;30:441-64.'},{id:"B159",body:'Wang Z, Cummins JM, Shen D, Cahill DP, Jallepalli PV, Wang TL, et al. Three classes of genes mutated in colorectal cancers with chromosomal instability. Cancer Res. 2004;64(9):2998-3001. Epub 2004/05/06.'},{id:"B160",body:'Wiseman H, Halliwell B. Damage to DNA by reactive oxygen and nitrogen species: role in inflammatory disease and progression to cancer. Biochem J. 1996;313 ( Pt 1):17-29.'},{id:"B161",body:'Bird AP, Wolffe AP. Methylation-induced repression--belts, braces, and chromatin. Cell. 1999;99(5):451-4.'},{id:"B162",body:'Hendrich B, Bird A. Identification and characterization of a family of mammalian methyl-CpG binding. Mol Cell Biol. 1998;18(11):6538-47.'},{id:"B163",body:'Jones PL, Veenstra GJ, Wade PA, Vermaak D, Kass SU, Landsberger N, et al. Methylated DNA and MeCP2 recruit histone deacetylase to repress transcription. Nat Genet. 1998;19(2):187-91.'},{id:"B164",body:'Nan X, Ng HH, Johnson CA, Laherty CD, Turner BM, Eisenman RN, et al. Transcriptional repression by the methyl-CpG-binding protein MeCP2 involves a. Nature. 1998;393(6683):386-9.'},{id:"B165",body:'Chen J, Li Y, Yu TS, McKay RM, Burns DK, Kernie SG, et al. A restricted cell population propagates glioblastoma growth after chemotherapy. Nature. 2012;488(7412):522-6. Epub 2012/08/03.'},{id:"B166",body:'Villalva C, Cortes U, Wager M, Tourani JM, Rivet P, Marquant C, et al. O6-Methylguanine-Methyltransferase (MGMT) Promoter Methylation Status in Glioma Stem-Like Cells is Correlated to Temozolomide Sensitivity Under Differentiation-Promoting Conditions. Int J Mol Sci. 2012;13(6):6983-94. Epub 2012/07/28.'},{id:"B167",body:'Kreth S, Thon N, Eigenbrod S, Lutz J, Ledderose C, Egensperger R, et al. O-methylguanine-DNA methyltransferase (MGMT) mRNA expression predicts outcome in malignant glioma independent of MGMT promoter methylation. PLoS ONE. 2011;6(2):e17156. Epub 2011/03/03.'},{id:"B168",body:'Zhang W, Zhang J, Hoadley K, Kushwaha D, Ramakrishnan V, Li S, et al. miR-181d: a predictive glioblastoma biomarker that downregulates MGMT expression. Neuro Oncol. 2012;14(6):712-9.'},{id:"B169",body:'Danam RP, Howell SR, Brent TP, Harris LC. Epigenetic regulation of O6-methylguanine-DNA methyltransferase gene expression. Mol Cancer Ther. 2005;4(1):61-9.'},{id:"B170",body:'Sansom OJ, Maddison K, Clarke AR. Mechanisms of disease: methyl-binding domain proteins as potential therapeutic targets in cancer. Nat Clin Pract Oncol. 2007;4(5):305-15.'},{id:"B171",body:'Cetica V, Genitori L, Giunti L, Sanzo M, Bernini G, Massimino M, et al. Pediatric brain tumors: mutations of two dioxygenases (hABH2 and hABH3) that directly repair alkylation damage. J Neurooncol. 2009;94(2):195-201. Epub 2009/03/18.'},{id:"B172",body:'Caldecott KW. Single-strand break repair and genetic disease. Nat Rev Genet. 2008;9(8):619-31.'},{id:"B173",body:'Chen S, Tang D, Xue K, Xu L, Ma G, Hsu Y, et al. DNA repair gene XRCC1 and XPD polymorphisms and risk of lung cancer in a Chinese population. Carcinogenesis. 2002;23(8):1321-5.'},{id:"B174",body:'Gangawar R, Ahirwar D, Mandhani A, Mittal RD. Impact of nucleotide excision repair ERCC2 and base excision repair APEX1 genes polymorphism and its association with recurrence after adjuvant BCG immunotherapy in bladder cancer patients of North India. Med Oncol. 2010;27(2):159-66. Epub 2009/02/27.'},{id:"B175",body:'Karran P, Offman J, Bignami M. Human mismatch repair, drug-induced DNA damage, and secondary cancer. Biochimie. 2003;85(11):1149-60.'},{id:"B176",body:'Khanna KK, Jackson SP. DNA double-strand breaks: signaling, repair and the cancer connection. Nat Genet. 2001;27(3):247-54.'},{id:"B177",body:'Li X, Heyer WD. Homologous recombination in DNA repair and DNA damage tolerance. Cell Res. 2008;18(1):99-113.'},{id:"B178",body:'Thompson D, Easton DF. Cancer Incidence in BRCA1 mutation carriers. J Natl Cancer Inst. 2002;94(18):1358-65.'},{id:"B179",body:'Wiseman H, Kaur H, Halliwell B. DNA damage and cancer: measurement and mechanism. Cancer Lett. 1995;93(1):113-20.'},{id:"B180",body:'Esteller M, Garcia-Foncillas J, Andion E, Goodman SN, Hidalgo OF, Vanaclocha V, et al. Inactivation of the DNA-repair gene MGMT and the clinical response of gliomas to. N Engl J Med. 2000;343(19):1350-4.'},{id:"B181",body:'Esteller M, Hamilton SR, Burger PC, Baylin SB, Herman JG. Inactivation of the DNA repair gene O6-methylguanine-DNA methyltransferase by. Cancer Res. 1999;59(4):793-7.'},{id:"B182",body:'Kitajima Y, Miyazaki K, Matsukura S, Tanaka M, Sekiguchi M. Loss of expression of DNA repair enzymes MGMT, hMLH1, and hMSH2 during tumor progression in gastric cancer. Gastric Cancer. 2003;6(2):86-95.'},{id:"B183",body:'Sharma S, Salehi F, Scheithauer BW, Rotondo F, Syro LV, Kovacs K. Role of MGMT in tumor development, progression, diagnosis, treatment and. Anticancer Res. 2009;29(10):3759-68.'},{id:"B184",body:'Shen L, Kondo Y, Rosner GL, Xiao L, Hernandez NS, Vilaythong J, et al. MGMT promoter methylation and field defect in sporadic colorectal cancer. J Natl Cancer Inst. 2005;97(18):1330-8.'},{id:"B185",body:'Silber JR, Bobola MS, Ghatan S, Blank A, Kolstoe DD, Berger MS. O6-methylguanine-DNA methyltransferase activity in adult gliomas: relation to. Cancer Res. 1998;58(5):1068-73.'},{id:"B186",body:'Zuo C, Ai L, Ratliff P, Suen JY, Hanna E, Brent TP, et al. O6-methylguanine-DNA methyltransferase gene: epigenetic silencing and prognostic value in head and neck squamous cell carcinoma. Cancer Epidemiol Biomarkers Prev. 2004;13(6):967-75.'},{id:"B187",body:'Hegi ME, Liu L, Herman JG, Stupp R, Wick W, Weller M, et al. Correlation of O6-methylguanine methyltransferase (MGMT) promoter methylation. J Clin Oncol. 2008;26(25):4189-99.'},{id:"B188",body:'Fumagalli C, Pruneri G, Possanzini P, Manzotti M, Barile M, Feroce I, et al. Methylation of O6-methylguanine-DNA methyltransferase (MGMT) promoter gene in triple-negative breast cancer patients. Breast Cancer Res Treat. 2012;134(1):131-7. Epub 2012/01/10.'},{id:"B189",body:'Sanchez-Perez I. DNA repair inhibitors in cancer treatment. Clin Transl Oncol. 2006;8(9):642-6.'},{id:"B190",body:'Lee SY, Luk SK, Chuang CP, Yip SP, To SST, Yung YM. TP53 regulates human AlkB homologue 2 expression in glioma resistance to. Br J Cancer. 2010;103(3):362-9.'},{id:"B191",body:'Choi SY, Jang JH, Kim KR. Analysis of differentially expressed genes in human rectal carcinoma using. Clin Exp Med. 2011;11(4):219-26.'},{id:"B192",body:'Tasaki M, Shimada K, Kimura H, Tsujikawa K, Konishi N. ALKBH3, a human AlkB homologue, contributes to cell survival in human non-small-cell lung cancer. British Journal of Cancer. 2011:1-7.'},{id:"B193",body:'Wu SS, Xu W, Liu S, Chen B, Wang XL, Wang Y, et al. Down-regulation of ALKBH2 increases cisplatin sensitivity in H1299 lung cancer cells. Acta Pharmacologica Sinica. 2011:1-6.'},{id:"B194",body:'Qiu YY, Mirkin BL, Dwivedi RS. Inhibition of DNA methyltransferase reverses cisplatin induced drug resistance in murine neuroblastoma cells. Cancer Detect Prev. 2005;29(5):456-63.'},{id:"B195",body:'Dolan ME, Mitchell RB, Mummert C, Moschel RC, Pegg AE. Effect of O6-benzylguanine analogues on sensitivity of human tumor cells to the. Cancer Res. 1991;51(13):3367-72.'},{id:"B196",body:'Chae MY, Swenn K, Kanugula S, Dolan ME, Pegg AE, Moschel RC. 8-Substituted O6-benzylguanine, substituted 6(4)-(benzyloxy)pyrimidine, and. J Med Chem. 1995;38(2):359-65.'},{id:"B197",body:'Dolan ME, Pegg AE, Dumenco LL, Moschel RC, Gerson SL. Comparison of the inactivation of mammalian and bacterial O6-alkylguanine-DNA. Carcinogenesis. 1991;12(12):2305-9.'},{id:"B198",body:'Sato K, Kitajima Y, Nakagawachi T, Soejima H, Miyoshi A, Koga Y, et al. Cisplatin represses transcriptional activity from the minimal promoter of the. Oncol Rep. 2005;13(5):899-906.'},{id:"B199",body:'Lakomy R, Sana J, Hankeova S, Fadrus P, Kren L, Lzicarova E, et al. MiR-195, miR-196b, miR-181c, miR-21 expression levels and O-6-methylguanine-DNA methyltransferase methylation status are associated with clinical outcome in glioblastoma patients. Cancer Sci. 2011;102(12):2186-90.'},{id:"B200",body:'Zinn P, Sathyan P, Mahajan B, Bruyere J, Hegi ME, Majumder S, et al. A Novel Volume-Age-KPS (VAK) Glioblastoma Classification Identifies a Prognostic Cognate microRNA-Gene Signature. PLoS One. 2012;7(8):e41522.'},{id:"B201",body:'Chinnasamy N, Rafferty JA, Hickson I, Lashford LS, Longhurst SJ, Thatcher N, et al. Chemoprotective gene transfer II: multilineage in vivo protection of haemopoiesis. Gene Ther. 1998;5(6):842-7.'},{id:"B202",body:'Hickson I, Fairbairn LJ, Chinnasamy N, Lashford LS, Thatcher N, Margison GP, et al. Chemoprotective gene transfer I: transduction of human haemopoietic progenitors. Gene Ther. 1998;5(6):835-41.'},{id:"B203",body:'Koc ON, Reese JS, Davis BM, Liu L, Majczenko KJ, Gerson SL. DeltaMGMT-transduced bone marrow infusion increases tolerance to O6-benzylguanine. Hum Gene Ther. 1999;10(6):1021-30.'},{id:"B204",body:'Reese JS, Koc ON, Lee KM, Liu L, Allay JA, Phillips WP, Jr., et al. Retroviral transduction of a mutant methylguanine DNA methyltransferase gene into. Proc Natl Acad Sci U S A. 1996;93(24):14088-93.'},{id:"B205",body:'Karkhanina AA, Mecinovic J, Musheev MU, Krylova SM, Petrov AP, Hewitson KS, et al. Direct analysis of enzyme-catalyzed DNA demethylation. Anal Chem. 2009;81(14):5871-5.'},{id:"B206",body:'Woon EC, Demetriades M, Bagg EAL, Aik WS, Krylova SM, Ma JHY, et al. Dynamic combinatorial mass spectrometry leads to inhibitors of a. J Med Chem. 2012;55(5):2173-84.'},{id:"B207",body:'Krylova SM, Koshkin V, Bagg E, Schofield CJ, Krylov SN. Mechanistic studies on the application of DNA aptamers as inhibitors of. J Med Chem. 2012;55(7):3546-52.'}],footnotes:[],contributors:[{corresp:null,contributorFullName:"Stephanie L. Nay",address:null,affiliation:'
Irell and Manella Graduate School of Biological Sciences, USA
Department of Cancer Biology, Beckman Research Institute, Duarte, CA, USA
'},{corresp:null,contributorFullName:"Timothy R. O‘Connor",address:null,affiliation:'
Department of Cancer Biology, Beckman Research Institute, Duarte, CA, USA
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1. Introduction
Wheat (Triticum aestivum L) is the second most important cereal crop in Kenya after maize and is produced mainly under rainfed conditions on 0.4% of the arable land [1, 2]. The crop has greater potential in the country where it is grown in Agro-ecological zones: UH2-UH3; LH2-LH3) [3]. Annual estimated area under production is 150,000 hectares [4] with a production of 320,000MT in 2019 compared to local consumption of 2,450,000MT [5]. The national demand for wheat and wheat consumption is on the increase, partly due to the high population growth, increased urbanization, and changing diet [6, 7]. The local wheat production has not been able to meet this demand leading to the importation of large quantities to fill the gap between supply and demand [8]. However, this is unlikely to be satisfied partly due to pre-harvest sprouting, lodging, losses caused by re-emerging diseases, insect pests, intermittent droughts [6, 9], inadequate seed systems, and poor crop practices under resource-constrained small scale farming conditions. The crop grows in a considerably wide range of altitudes in the country, maturing between 90−145 days depending on the location and cultivars.
There are various wheat diseases such as fungal, which include stem or black rust, caused by Puccinia graminis f. sp. tritici Erikss and Henning (Pgt), yellow/stripe rust, caused by Puccinia striiformis f. sp. tritici (Pst), leaf/brown rust caused by Puccinia triticina (Pt) and Fusarium caused by Gibberella zeae that infect wheat in Kenya. Other diseases include Septoria leaf and glume blotch caused by S. tritici and S. nodorum, respectively Spot blotch (Bipolaris sorokiniana), Loose smut (Ustilago tritici), Take All (Gaeumannomyces graminis var. tritici) and a viral disease, Barley Yellow Dwarf, causal agent Barley Yellow Dwarf Virus (BYDV) [10].
1.1 Wheat rust diseases in Kenya
Among the wheat diseases, rusts have become the most destructive diseases of wheat in Kenya resulting in yield losses of up to 100% in susceptible cultivars [10, 11]. Breeders have been breeding for wheat rust resistance, since 1908, but up to date, there is no permanent solution to the rust diseases as the pathogens keep on evolving rendering the resistant cultivars ineffective [12]. Since the beginning of the wheat breeding program in Kenya in the 1900s, until early 1980s, stem rust was the most serious disease of the three wheat rusts and therefore was given a high research priority by the breeding program. Consequently, many resistant wheat cultivars were developed and the disease seemed to have been controlled. It was until between 1985 and 1988 that trace amounts of the disease were observed in the experimental plots in Njoro; in 1996, it was recorded in some commercial cultivars in Mau-Narok and Molo, and in the year 2000 all the cultivars had become susceptible [10, 12].
Stem or black rust of wheat, caused by Pgt is known historically for causing severe losses to wheat production and was the most feared disease in various countries where wheat is grown [13]. The common host is wheat with other small grain cereals, durum wheat (Triticum durum), barley (Hordeum vulgare L), Rye (Secale cereael L.), oats (Avena fatua L.), wild barley, goatgrass and forage grasses [14]. Although the disease has been under control through widespread use of resistant cultivars, the re-emergence of a new virulent race, Ug99 [15] first keyed to pathotype TTKS [16] using the North American nomenclature [17] and later as TTKSK after a fifth set of differentials was adapted to further expand the characterization [18]. Prior to the official reporting of the new race, trace amounts of the disease were observed in experimental plots in Njoro between 1985 and 1988, in 1996 the disease was recorded in some commercial cultivars in Mau-Narok and Molo (high altitude areas) in 1996 and in 2000 all the cultivars had become susceptible [10, 12]. This Ug99 race group has evolved and is now composed of 15 races in 14 countries [19, 20, 21] with 12 variants (TTKSK, TTKST, TTTSK, PTKSK, PTKST, TTKTT, TTKTK, TTHSK, PTKTK, TTHST, TTKTT+, TTHTT) present in Kenya reversing the gains made by breeders, posing a new and significant threat to wheat production in the Eastern Africa region [16]. In the year 2016, race TKTTF (Digalu race) was genotyped in Kenya for the first time. A new variant TTKTT+ with additional virulence on Sr8155B1 was detected in 2019 and another new variant, TTHTT detected in Kenya in 2020 [22]. This is an indication that Ug99 race group is spreading faster specifically, in the areas where close to one billion people reside and the majority of this population consumes wheat and its products [23].
Wheat yellow or stripe rust, caused by Pst, is one of the key economical diseases of wheat worldwide [24, 25]. In Kenya, it occurred as early as 1908 and is prevalent in the Rift valley region [12, 26, 27]. Since then it has become a major threat every year as no commercial cultivar is resistant [28, 29]. Serious attacks of the pathogen occur annually and newly introduced resistant cultivars lose their resistance within a short time.
Stripe rust to limits wheat production by affecting the yield and quality of kernels as it develops at an early crop stage when temperatures are favorable for rust development [30]. Stripe rust destroys leaves at jointing to booting growth stages. Consequently, infection of stripe rust on wheat reduces photosynthetic area as early as tillering and jointing stages of development. Stripe rust epidemic has occurred in more than 60 countries in every continent causing yield losses of up to 100% in susceptible cultivars [31]. In East Africa, Kenya, and Ethiopia the epidemics caused yield loss of 67−100% in the year 2010 [25]. In Kenya, wheat is grown throughout the year in different agro-ecological zones, and this increases the concentration of the urediniospores in the air making it difficult to control the disease in susceptible varieties [12, 16]. Yield losses of up to 80% have been estimated but some fields with susceptible cultivars go up to 100% [10, 25].
Stripe rust is a global problem evolving into different races, either from their wild ancestor or their host through introductions [32]. In Kenya and Ethiopia Yr9 and Yr27 based cultivars broke down due to evolution of virulent stripe rust races to these genes resulting to yield losses of up to 40% in commercial cultivars like Paa that carried Yr9 gene [12, 33]. Stripe rust race 134 with virulence for Yr7, 6, 9+ genes were present in Ethiopia, Kenya, Syria, and Yemen [34]. Thirteen races with virulence corresponding to stripe rust resistance genes Yr1, Yr2, Yr3, Yr6, Yr7, Yr8, Yr9, Yr17, Yr25, Yr27, and Avocet S are present in wheat-growing regions of Kenya [35], these races belong to either strain Pst1 or Pst2 which might have been present much earlier than 1982 and 1970.
Wheat leaf rust caused by Pt is the most common and widely distributed of the three wheat rusts and occurs in more regions than stem rust and stripe rust [36, 37]. Leaf rust mostly infects wheat in low to medium altitude wheat-growing areas of Kenya [38, 39]. The earliest epidemics of this rust were reported in Kenya as early as 1908 [26]; therefore, it is considered to be among the major three wheat rusts (stem, yellow and leaf) responsible for depressing crop yields drastically depending on the cultivar because of its high frequency and widespread occurrence. Yield losses attributed to leaf rust have been reported to range from 5–16% on average, and up to 40% in epidemic years [40]. Yield losses are usually the result of lower kernel weights and decreased number of kernels as the pathogen may kill wheat seedlings by elevating respiration rate, reducing photosynthetic area on the leaf surfaces, and lessening translocation of carbohydrates [41]. In Kenya, the disease appears sporadically and has not been a problem for the past 20 years, but it has recently emerged in the wheat fields, and experimental plots, including the Kenya Agricultural and Livestock Research Organization (KALRO), Njoro international screening nursery with severity of over 50% [42]. One of the recent studies [43] reported a high reduction in grain yield and kernel weight in some of the Kenyan wheat cultivars.
Highly effective durable resistance to leaf rust has been difficult to achieve due to the high degree of virulence variation in the Pt population and the rapid selection of races with virulence to effective Lr genes in wheat genotypes [44]. This high degree of specificity has made durable rust resistance in wheat difficult to achieve because the virulence of leaf rust against wheat resistance genes is highly diverse resulting in the existence of many different pathogenic races [37]. For instance, the novel race BBG/BN and its variant BBG/BP overcame the resistance of widely adapted durum cultivars in northwestern Mexico. In Kenya, leaf rust samples collected from wheat-growing areas were found to have virulence for leaf rust resistance genes Lr1, Lr2b, Lr3, Lr9, Lr11, Lr12, Lr14a, Lr14b, Lr18, Lr20, Lr22a, Lr23, Lr24, Lr26, and Lr27. The race for an isolate collected from Ololulung’a, Narok in the South Rift region was designated as LBBTN [45].
1.2 Other wheat diseases in Kenya
Fusarium diseases, mainly Fusarium head blight of wheat (FHB), also called head scab, are caused mainly by the fungus Gibberella zeae (also known as Fusarium graminearum), periodically causes significant yield losses and reduced grain quality. Gibberella zeae also produces mycotoxins [46]. All Kenya wheat cultivars are susceptible to Fusarium infection [47]. Studies done in Kenya show that the prevalence of FHB and yield loss due to FHB varies from trace to 100% [47, 48].
Septoria diseases are caused by S. tritici and S. nodorum [49]. Yield losses attributed to heavy incidences of S. tritici and S. nodorum have been reported to range from 31–53% resulting in shriveled kernels [49]. The occurrence of Septoria diseases in the wheat-growing areas of Kenya is sporadic and severe infection leading to shriveled grain is observed (Wanyera, Personal observation). Some of the foliar fungicides recommended for the control of rust diseases in wheat have been observed to reduce Septoria disease infection when applied at the right time. These foliar fungicides include: (azoxystrobin 200 g/L+ tebuconazole 300 g/L (Stamina 500 SC); benzovindiflupy 30 g/L + azoxystrobin114G/L + propiconazole 132 g/L (Elatus Arc 265.14 SE); difenaconazole 125 g/L + azoxystrobin200g/L (Token 325 SC); (trifloxystrobin250g/Kg/L + tebuconazole 500 g/Kg (Shadow 750 WG).
Spot blotch caused by Bipolaris sorokiniana (Sacc) Shoemaker, perfect stage Cochliobolus sativus (S.Ito & Kurib) also causes black point, root rot, and crown rot in wheat. It is known to occur worldwide in warmer environments and is a serious constraint in wheat production in India, Bangladesh, and Nepal [50]. It is also a serious problem on barley. The disease can attack all parts of the wheat plant (seed, roots, shoots and leaves) causing seed-rot, seedling emergence, reduced yield affecting end-use quality of the harvested grain [51, 52]. Bipolaris sp. is known to reduce seed viability in wheat and also causes a significant reduction in seed quality and flour [53]. Yield loss estimates of 15−25% and 30% have been reported [54] and on barley in Canada [55].
The sudden upsurge of Bipolaris sp. in certain areas of the country has been associated with acid soils. It is estimated that 30% of the soil in the wheat-growing areas is acidic. High infection has been recorded on wheat cultivars Ngamia in Uasin Gishu county (North Rift) and Kenya Nyangumi in Rongai areas of Nakuru county (Central Rift) (Wanyera, Personal observation).
The highland areas of wheat production in Kenya: Molo, Mau Narok (Central Rift), Eldoret and Endebess (North Rift) have a pH of 4.3−5.5 [56]. All wheat cultivars grown in these areas have shown susceptibility to the pathogen but no direct screening has been done. Aluminum toxicity in acid soils has been documented as the primary factor in the reduction of the crop yields [56]. Seed borne nature of the disease has been reported in wheat cultivars in Kenya [57, 58], and studies on disease management revealed that the pathogen can be reduced by the use of seed treatment fungicides [59]. Biological control methods have also been reported [60, 61].
Loose smut caused by Ustilago tritici is seed-borne and common in the wheat-growing areas of the world. Infection occurs during flowering through wind-borne spores. In Kenya, the disease occurs rarely and is mostly observed in recycled wheat seeds.
Take All (Gaeumannomyces graminis var. tritici) is soil and debri-borne, detected mostly in fields that are continuously cultivated with cereals. Both Loose smut and Take All are well managed through use of certified seed, cultural control, and seed treatment fungicides. Some of the recommended seed treatment fungicides are: prothioconazole 100 g/L (Redigo FS100), difenoconazole92g/L + metalaxyl-M 23 g/L (Dividend Extreme 115 FS), and azoxystrobin 141.4 g/L+ propiconazole122.4 g/L (Quilt Excel 263.5 SE) [6].
Apart from fungal diseases, another disease that threatens wheat production in Kenya is the Barley Yellow Dwarf Virus (BYDV), which is an important virus disease of cereals globally and has a wide host range that includes wheat, barley, oats, triticale, and over 150 grass species [51]. The disease was first reported in Kenya in 1984 and causes serious damage in barley, wheat, and oats and estimated losses range from 16.5−54.7% [62, 63]. Cereal aphids are vectors of the barley yellow dwarf and five strains have been known to occur in Kenya: RPV (Rhopalosiphumpadi), RMV (R. maidis), MAV (Sitobionavenae), SGV (Schizaphis graminum), and PAV (R. padi, S. avenae [63]. Outbreaks are frequent, and management practices require use of seed dressing insecticides: Gaucho 350FS (Imidacloprid), Cruiser 350FS (Thiamethoxam), Redigo Deter 350FS (Clothianidin + prothioconazole), Celest Top 312FS (Thiamethoxam + fludioxonil +difenoconozole, and (ii) foliar-applied insecticides (Karate Zeon (Lambda-cyhalothrin), Bulldock star 262.5EC (Betacyfluthrin + Chlorpyrifos), Thunder OD 145 (Imidacloprid + Betacyfluthrin), Keshet 2.5EC (Deltamethrin),Twigathoate 40EC (Dimethoate), Nurelle D 50/505 EC (Cypermethrin + Chlorpyrifos), Alphadime (Alpha-cypermethrin + Dimethoate), Cyclone 505EC (Cypermethrin + Chlorpyrifos), and Pirimor 50WG (Pirimicarb) [6, 64, 65].
Under favorable environmental conditions, infection of the wheat crop with these diseases can reduce quantity and quality of the grain. Disease surveillance is an epidemiological practice by which the spread is monitored to establish patterns of progression and is key in identifying new diseases and races which can be used in risk assessment and resistance breeding. This review highlights the prevalence, distribution of wheat diseases, host plant resistance in the key wheat-growing regions, and future prospects in Kenya.
1.3 Distribution of diseases in wheat-growing regions of Kenya
Surveys were conducted in the farmer fields in the major wheat-growing regions (Central Rift, South Rift, North Rift, and Mount (Mt) Kenya from 2011 to 2019. The objective was to determine the prevalence and distribution of the wheat diseases and host plant resistance in these regions. Farms were randomly picked along the routes, stopping at every 3 to 5 kilometers. Crops were observed for disease symptoms. An International Standardized survey form was used to keep the records on disease incidence and severity, cultivar grown, production area, and growth stage [66], also any other data that was useful. The Global positioning system (GPS) tool was used to collect precise information on latitude, longitude, and elevation of the sampled farms. Stem, yellow, and leaf rust severities were taken using modified Cobb scale, 0−100% where; 0- immune and 100- susceptible [67]. The host plant response to infection was scored as resistant (R), moderately resistant (MR), moderately susceptible (MS), and susceptible(S) [68]. Incidence and severity of other diseases observed during the surveys were also taken using recommended scales. Septoria diseases were assessed using 0−9 scale [49], where 0 = Free from infection and 9 = Very susceptible/severe infection. Similarly, barley yellow dwarf virus was assessed on a scale of 0−9 [69], where 0 = no symptoms and 9 = full symptom expression, and the Fusarium disease score rating system was 0−5 [70]. Tables 1 and 2 show the occurrence (percent infection and severity & plant response) of the diseases in all the wheat-growing regions. Rust diseases are common in the wheat fields and stem rust is widespread in all the regions. This explains the importance of stem rust, Ug99 race group, since its detection in Uganda and spread to the wheat-growing areas of Kenya, throughout eastern Africa, Yemen, Sudan, Iran, Zimbabwe, Tanzania, South Africa, Mozambique, Zimbabwe, and Iraq [15, 16, 22]. The prediction for the rust diseases to spread towards North Africa, Middle East, Asia and beyond, raises serious concerns of major epidemics that could destroy the world’s wheat crop [19].
Year
Region
No. of sampled farms
Sr % Infection (%)
Sr % severity and plant response
Yr infection (%)
Yr % severity and plant response
Lr Infection (%)
Lr% severity (%)
2011
Central Rift
62
70.9
0-100S
17.7
TR -60S
17.7
TR-40S
South Rift
125
68.8
TR-100S
6.4
TR- 20S
17.7
TR-20S
North Rift
73
48.3
TR-90S
10.9
TR- 20S
10.9
TR-20S
Mt. Kenya region
67
68.0
TR- 60S
10.4
0 - 40S
13.4
TR-20S
Total/Mean
327
63.9
11.3
14.9
2012
Central Rift
67
65.7
TR-80S
4.5
5-50S
11.9
5-30S
South Rift
71
5.6
TR-20S
—
—
—
—
North Rift
101
26.7
TR-70S
5.9
5-70S
3.9
10-50S
Mt. Kenya region
39
58.9
TR-50S
5.1%
5-60S
2.6
30S
Total/Mean
278
39.2
3.9
4.6
2013
Central Rift
97
71.0
TR-70S
8.3
TR-50S
6.7
TR-50S
South Rift
104
68.3
TR-100S
3.8
10S–30S
5.8
TR-50S
North Rift
78
33.3
TR-70S
10.3
TR-50S
6.5
TR-50S
Mt. Kenya region
54
25.9
TR-60S
7.4
10S–30S
0
0
Total/Mean
333
49.6
7.5
4.8
2014
Central Rift
92
82.5
TR-80S
6.2
TR -50S
6.2
10S–50S
South Rift
79
72.2
TR-80S
8.9
TR- 60S
—
—
North Rift
95
55.8
TR-80S
6.3
TR- 40S
5.3
0 - 40S
Mt. Kenya region
71
57.7
TR- 60S
15.5
5S - 60S
1.4
0-40S
Total/Mean
342
67.05
4.0
4.0
2015
Central Rift
66
54.54
TR-80S
5.8
5S–40S
1.5
0-30S
South Rift
101
35.6
TR-60S
—
—
—
—
North Rift
106
75.5
TR-50S
8.5
TR-40S
1.9
TR-30S
Mt. Kenya region
63
71.4
TR-60S
—
—
—
—
Total/Mean
336
59.26
3.58
0.85
2016
Central Rift
60
88.3
TR-80S
16.7
TR-60S
3.3
30S–50S
South Rift
81
76.5
TR-70S
4.9
TR-10S
1.2
0-50S
North Rift
98
72.4
TR-80S
13.3
TR-40S
10.2
TR-50S
Mt. Kenya region
61
80.3
TR-90S
1.6
TR
—
—
Total/Mean
300
79.38
9.13
3.68
2017
Central Rift
54
87.03
TR-70S
8.9
0 -30S
—
—
South Rift
79
69.2
TR-100S
3.79
TR- 10S
—
—
North Rift
78
64.1
TR-60S
8.97
TR- 30S
24.4
TR-40S
Mt. Kenya region
38
44.1
TR- 30S
10.5
TR - 40S
—
—
Total/Mean
249
66.11
8.04
6.10
2018
Central Rift
64
74.0
5-50S
10.0
5-60S
10.0
TR-30S
South Rift
85
42.2
5-70S
3.3
10S–30S
1.1
TR-40S
North Rift
89
25.84
5-80S
19.1
5S–60S
24.35
5S–70S
Mt. Kenya region
62
47.9
5-40S
2.81
10S–30S
—
—
Total/Mean
300
47.78
8.80
4.0
2019
Central Rift
56
82.2
TR-50S
2.2
0-40S
—
—
South Rift
87
83.13
TR-80S
1.2
TR
—
—
North Rift
101
22.77
TR-40S
7.92
TR-40S
4.95
TR-20S
Mt. Kenya region
46
63.04
TR-50S
10.86
15S–60S
6.5
5S–30S
Total/Mean
290
62.79
5.62
2.86
Table 1.
Occurrence of wheat rust diseases in the commercial fields in year 2011−2019.
Sr = Stem rust; Yr = Yellow rust; Lr = Leaf rust; TR- trace; S = susceptible; − = no disease observed.
Year
Region
No of sampled farms
Disease incidence (%)
Septoria diseases
Fusarium sp
BYDV
2011
Central Rift
62
16.1
9.6
0
South Rift
125
4
1.6
0.8
North Rift
73
27.4
12.3
0
Mt. Kenya
67
1.5
0
0
2012
Central Rift
67
42.8
8.9
16.4
South Rift
71
46.5
2.8
0
North Rift
101
41.8
0.9
0.9
Mt. Kenya
39
17.9
2.7
0
2013
Central Rift
97
8.2
6.2
2.1
South Rift
104
14.4
0.9
0.9
North Rift
78
28.2
0
0
Mt. Kenya
54
45.3
1.9
0
Table 2.
Occurrence of Septoria diseases, Fusarium sp. and Barley yellow dwarf virus (BYDV) in commercial wheat field year 2011, 2012, and 2013.
Yellow rust, which was first described in 1777, and attacked wheat in Kenya as early as 1908 [26], was observed in low incidences but high severities across all the regions (Table 1). The disease is also a major threat as no cultivar is resistant [28, 29]. Newly introduced resistant varieties lose their resistance within a short time and farmers are forced to spray to save on yields. Serious attacks of the pathogen occur annually and the disease severity increases with altitude [33]. Serious epidemics also occur in the lower latitudes areas. All the wheat-growing areas are prone to disease in low medium and high altitudes areas.
In Kenya, leaf rust has been sporadic and has not been a problem for the past 20 years, but it has recently emerged in the wheat fields (Table 1), and experimental plots, including the international screening nursery with a severity of over 50%. Our cultivars are now at risk given the fact that virulences and new races have been identified in Njoro and also South Rift, Ololulung’a areas (data not shown).
The growing of wheat in diverse agro-ecological zones throughout the year [71, 72] in Kenya creates a significant pool of airborne urediniospores, which coupled with favorable climatic conditions and the presence of host plants, favors rapid build up of inoculum and the occurrence of epidemics. This implies that there is a shift in races present each year, which affects different cultivars of wheat. There is continuous attack, due to the presence of wheat crops throughout the year. The breakdown in resistance could also be attributed to mutations [24]. It is, therefore, a problem to reduce the disease infection in susceptible cultivars and also not possible to grow a profitable crop of wheat without the application of fungicides [10, 16]. Septoria diseases, Fusarium spp., Barley yellow dwarf virus are also becoming more prevalent in the commercial fields (Table 2), year 2011 to 2013. Disease incidence varied from year to year depending on the chemical/spray applied. Data for the occurrence of these diseases from 2014 to 2019 was not shown because it was similar as shown in Table 2.
1.4 Wheat breeding in Kenya
Conventional breeding, which includes testing genotypes in different environments to determine the adaptability of the varieties has been used largely in Kenyan wheat breeding programs to identify resistant varieties [72]. Crop improvement by traditional methods, involves collection, hybridization, and inbreeding that has been practiced since the beginning of 20th Century. However, it has now been realized that these methods are insufficient to make further breakthroughs or cope with the increasing demand for improvement in crop varieties [73]. Some of the limitations of conventional breeding include the exhaustion of the gene pool, low response to biotic and abiotic stress of the introduced materials, and low combining ability, especially with complex characters. In Kenya, diverse agro-ecological zones and favorable environs highly contribute to the emergence of new races. The cultivars grown are at high risk of being infected with diseases, therefore, it is necessary to identify and incorporate genes that confer durable resistance to contain major epidemics [74, 75]. There are various strategies employed to control these diseases in wheat. These include incorporation of genetic resistance into susceptible wheat genotypes, crop management plus use of fungicides. Despite the fact that it takes a long-time, breeding for durable resistance remains to be a cost-effective strategy of minimizing loss due to wheat diseases [76]. Therefore, host resistance is the primary tool to protect wheat crops from wheat fungal rust diseases and other biotic stresses [77]. Breeding for vertical (qualitative) resistance based on major genes and horizontal (quantitative) influenced by several minor genes for wheat disease resistance has been going on in Kenya since wheat introduction in the 19th century. However, due to pathogen evolution, most of the genotypes with qualitative and quantitative resistance become susceptible to the new races, especially wheat rusts pathogens. For instance, wheat cultivars Robin and Eagle 10 released in Kenya as resistant varieties in 2009 and 2010 were overcome by Ug99 variant SrTmp [78, 79]. Durable resistance by selecting resistant wheat varieties has been going on in Kenya for the past decades, most of the varieties released with resistant genes are now ineffective against the evolving wheat rusts pathogens (Table 3).
No
Variety
Region and variety area planted (%)
Central Rift
South Rift
North Rift
Mt.Kenya
2011
2012
2013
2011
2012
2013
2011
2012
2013
2011
2012
2013
1
NjoroBW2
30.4
34.3
24.7
29.6
39.4
42.3
49.0
60.4
57.7
26.2
—
—
2
KS Mwamba
50.4
14.9
12.3
50.4
15.5
20.2
45.2
28.7
26.9
33.8
25.6
25.9
3
Kwale
14.0
20.9
14.4
14.4
9.9
20.2
4.1
1.9
5.1
6.2
23.1
11.4
4
Robin
—
7.5
20.6
—
1.4
—
—
—
7.7
—
—
22.2
5
Mixed
3.2
8.9
10.3
—
—
1.9
1.3
5.9
1.3
—
17.9
7.4
6
Eagle10
1.6
—
—
—
1.4
0.9
—
—
—
—
1.6
7
Others
0.4
13.5
17.7
5.6
32.4
14.5
0.4
3.1
1.3
33.8
33.1
31.5
Table 3.
Commonly grown cultivars in the key wheat-growing regions in the year 2011−2013.
-cultivar not planted.
Kenyan wheat cultivars Robin, NjoroBW2, KS Mwamba, Kwale, Kenya Korongo, Robin, Eagle 10, Kenya Black Hawk 12 (Tables 3 and 4), and Kenya Seed Company cultivars were grown by most farmers in the wheat-growing regions of Kenya.
In 2011, KS Mwamba occupied the largest area in Central and South Rift (50.4%), North Rift (45.2%), and in Mount Kenya region 33.8% (Table 3). In 2012, the area planted with NjoroBW2 increased: 34.3%, 39.4%, 60.4%, while it decreased for KS Mwamba, 14.9%, 15.5%, and 28.7% in Central, South, and North Rift, respectively (Table 3). Cultivar Kwale was highly grown in Central Rift (20.9%), Mt. Kenya (23.1%), and South Rift (20.2%) in 2013. For the cultivars released in 2010 with adult plant resistance (APR) to the wheat stem rust race Ug99, Robin occupied 20.6% in Central Rift, 22.2% in Mt. Kenya, 7.7% in North Rift (2013). Cultivar Eagle 10 occupied 1.6% in Mt. Kenya region and 0.9% in South Rift. Mixed and other unknown cultivars were common across the regions and this could be due to the high cost of certified seed.
In 2014, cultivar Robin was highest in Central Rift (43.3%), South Rift (41.8%), and Mt. Kenya region (43.7%) while cultivar NjoroBW2 was highest in North Rift (64.2%), Central Rift (15.5%), Mt. Kenya (12.7%), and South Rift (8.9%). KS Mwamba was highest in North Rift (16.4%), Central Rift (15.5%), South Rift (11.4%), and Mount Kenya (9.9%). The area under cultivar Kwale was highest in Central Rift (10.3%), followed by South Rift and Mt. Kenya region (7.6% and 7.0%), respectively. The area under cultivar Eagle 10 was only noted in South Rift 18.9% and overall occupied only 4.4% across the region. Mixed and other unknown cultivars were common in Mt. Kenya region: Kenya Ibis occupied 1.2%, Duma (0.6%), mixed cultivars (1.8%).
In 2015, the area planted with NjoroBW2 increased in North Rift from 63.2% in 2014 to 70.6% in 2015 cultivar Robin increased in Mt. Kenya region (66.7%) as opposed to 2014 (43.7%), but decreased in Central Rift from to 21.2%. The area under production in North Rift increased from to 16.5% and decreased in South Rift from 35.6%. Cultivar Eagle 10 was only observed in South Rift (20.8%) of the sampled fields. Cultivars Kenya Wren and Kenya Hawk12 were observed only in the South Rift (1.9%).
The area planted on NjoroBW2 decreased in North Rift to 64.3% Mt. Kenya 49.2% in 2016. Cultivar Eagle 10 was only grown in South Rift (9.9%) and in North Rift (2.0%) of the sampled fields. Cultivars Kenya Wren was grown in South Rift (2.5%) and North Rift (1.0%) while Kenya Hawk12 was grown in the South Rift (6.2%). Kenya Korongo was grown in South Rift (8.3%) and North Rift (1.0%).
In 2017, cultivar NjoroBW2 was popular in North Rift (69.2%), Central Rift (40.7%), and South Rift (32.9%). Robin was popular in Mt. Kenya region (32.4%), followed by South Rift (20.3%), Central Rift (10.7%), and North Rift (7.7%). Kenya Korongo was only popular in the Central Rift (27.8%). Kwale was popular in Central Rift (7.4%), South Rift (6.3%), and Mt. Kenya (5.3%) area under production of the sampled fields. Cultivar NjoroBW2 occupied the largest area in North Rift (69.2%) and Central Rift (40.7%). Cultivar Eagle 10 was recorded in South Rift (13.9%), Central Rift (1.9%), and in North Rift (1.3%) of the sampled fields. While variety Duma was popular in Mt. Kenya region (42.1%) area under production of the sampled fields. Kenya Wren was grown in Central Rift 1.9.3%), South Rift (1.3%), and North Rift (1.0%) while Kenya Black Hawk12 was grown in South Rift (6.2%) and North Rift (1.3%). Kingbird was only grown in South Rift (2.5%) and North Rift (1.3%) area under production of the sampled fields.
In 2018, cultivar NjoroBW2 was popular in all the regions: North Rift (70.8%), Central Rift (44.0%), South Rift (34.4%), and Mt. Kenya region (14.08%). Robin was grown in North Rift (16.0%), Mt. Kenya (14.6%), Central Rift (12.0%), and South Rift (11.8). Kenya Korongo was only popular in the Mt. Kenya region (36.6%) while Kwale was grown in Central Rift (8.0%) and South Rift (4.7%). Variety Eagle 10 was only popular in South Rift (14.0%) area under production of the sampled fields. The area under production of variety Eagle 10 remained the same in the South Rift as the previous year. Kenya Wren was only grown in South Rift (3.5%), Kenya Black Hawk12 was grown in North Rift (2.5%). while Kingbird was grown in South Rift (1.2%) and North Rift (1.3%).
In 2019 cultivar NjoroBW2 was popular in Mt. Kenya (43.5%). North Rift (42.5%), Central Rift (39.28%), South Rift (31.0%). Kenya Korongo was grown in Mt. Kenya (23.9%), Central Rift (16.0%), South Rift (11.5%), and North Rift (7.92%). Cultivar Robin was popular in the Mt. Kenya (23.9%), South Rift (13.8%), and Central Rift (5.4%). Kwale was grown in North Rift (9.9.0%), South Rift (8.0%), Mt. Kenya (6.5%), Central Rift (5.4%) area under production of the sampled fields. Cultivar Eagle 10 was only popular in South Rift (14.9%) and Central Rift (7.1%) area under production of the sampled fields. The Kenya Seed Company cultivars were more popular in the North Rift (24.8%) area under production of the sampled fields.
Over fifty percent of the previously released varieties (Table 4) are now susceptible to the Ug99 race. Robin, Kenya Black Hawk12, Kenya Korongo, Kenya Jacana, and Kenya Kasuko are susceptible to Ug99 races (TTKTK and TTKTT) that were detected on Robin with virulence to SrTmp and virulence to Sr24, respectively. The resistance in Kwale and other genotypes like Kenya Plume (not included) is due to adult plant resistance (APR) genes and others associated with variable levels of disease symptoms, which show recessive inheritance and is expressed primarily during the APR which has been deployed in a breeding program in Kenya [80]. Stem rust resistance gene Sr2 is an APR gene present in some of the Kenyan genotypes such as Kwale, Kenya Swara, Kenya Nyangumi, and Kenya Popo together with other APR genes condition resistance to stem rust [11, 81].
There is a long history of wheat breeding in Kenya as early as 1908, however, the use of molecular breeding tools is very limited thereby hampering the rate of genetic gains achieved. As such, the national breeding program has depended on introductions of wheat lines from international wheat breeding programs including CIMMYT and ICARDA. Understanding the composition and diversity of fungal wheat disease resistance in Kenya wheat germplasm is important for defining breeding strategies and prioritizing trait targets for wheat improvement [82].
Biotechnological approaches in wheat breeding such as double haploid (DH) and mutational breeding have been used to speed up breeding by complementing conventional breeding [72]. DH which shortens the breeding period by a single cycle has been used in Kenya to produce varieties such as K. Ibis. Mutation breeding brings about genetic variation and accelerates the outcome of variety release has been applied at KARLO, Njoro to release varieties NjoroBW2 and K. Heroe by irradiation using gamma rays [72, 83]. Conventional method of gene pyramiding is time-consuming, hence, the incorporation of molecular breeding is efficient in breeding for biotic and abiotic stresses in wheat for quick release of resistant varieties. The use of molecular markers enhances phenotypic selection because it makes it more efficient, effective, reliable, and cost-effective compared to conventional plant breeding, hence improving the latter [84]. There has been some concern about the incorporation of DNA marker technology in many plant-breeding institutions and most institutions can now develop their own markers [85, 86]. Molecular markers such as SSR, AFLP, and KASP markers have been developed to evaluate genotypes for biotic stresses such as diseases in Kenyan varieties [7, 82, 87].
1.5 Control of wheat diseases in Kenya
Other than host plant resistance, cultural and chemical methods have been used to control wheat diseases in Kenya. Cultural control techniques such as growing resistant genotypes, late planting, reduced irrigation, avoidance of excessive nitrogen use, and elimination of volunteer and grass plants can reduce stripe rust severities as they limit exposure time to inoculum [25]. Altering planting date and separating the vulnerable crop from the pathogen in either time or space controls certain airborne disseminated pathogens of wheat [88]. Although the cultural techniques are used, they are either not profitable, conflict with conservation farming, or reduce yield potential [89]. Genetic resistance combined with chemical treatments, although expensive to the poor resource farmers may often be very effective in controlling wheat diseases [90]. Some of the fungicides used by farmers in Kenya are listed in Table 5. The application of seed treatment chemicals such as triadimenol (sterol biosynthesis inhibitors) and carboxin (respiratory inhibitors) and the use of moderately resistant cultivars is effective in controlling wheat diseases as it provides the most efficient use of fungicides at the lowest rates [91, 92]. Reduced chemical applications could also minimize the potential development of resistance to the chemicals [90]. Although wheat diseases have been controlled by timely use of effective chemicals, the cost of chemicals and their application creates a huge burden for growers. In Kenya, large-scale farmers are the only ones who can afford to spray chemicals, but it costs about $ 8 million annually [10]. Fungicides can be used to control fungal diseases, but they cause environmental hazards and lead to fungicide tolerant strains [25]. Re-emergence of new virulent races has reversed the gains made by breeders, posing a new and significant threat to wheat breeding in Kenya [16]. Resistance in the commercial wheat cultivars in Kenya, including those released in the last decade, has been overcome by the new races making it impossible to grow a profitable crop of wheat without the use of fungicides [10, 90].
Recommended fungicides for control/reduction of foliar wheat diseases in Kenya.
* Can control Fusarium Head Blight (FHB) when spayed at flowering**Can control Fusarium Head Blight (FHB) and Septoria diseases GF- Generic fungicide.
During surveys, we noted that farmers who sprayed following the right recommendations of fungicides in Table 5 had good yields compared to those who did not spray or sprayed without following the proper recommendations hence losing the crop to the disease. Majority of the farmers sprayed the fungicides to reduce/suppress disease infections, particularly the rusts, but some sprayed farms were noted to have high disease infections. These are farms that either had been sprayed late or the timing/ chemical concentrations were not right.
1.6 Future of breeding for wheat diseases resistance in Kenya
Despite the occurrence of wheat diseases in Kenya, information on the genetic basis of the diseases and wheat cultivars is limited. Molecular genetic markers have been advanced from phenotypic and protein-based markers to DNA sequence polymorphism, this accelerates the process of plant breeding when coupled with conventional breeding [93]. Since many traits valued by plant breeders are complex and polygenic, it is essential to involve the deliberate combination of various genomic regions from many different individuals in the development of an adapted elite variety [94]. Sequencing polymorphism markers are important in identifying genetic diversity in cultivated and wild genotypes, the source of novel genomic regions, alleles, and traits [95].
In crops, marker-assisted selection (MAS) has been made efficient by designation of markers associated with economic importance, for instance, disease resistance (wheat rust), response to abiotic stress and seed quality [96, 97]. The use of molecular markers enhances phenotypic selection because it makes it more efficient, effective, reliable, and cost-effective compared to conventional plant breeding hence improving the latter [84]. There has been some concern about the incorporation of DNA marker technology in many plant-breeding institutions but most institutions can now develop their own markers [85, 86].
In genetic studies of wheat, genetic markers such as amplified fragment length polymorphism (AFLP), restriction fragment length polymorphism (RFLP), random amplified polymorphic DNA (RAPD), simple sequence repeat (SSR), and single nucleotide polymorphism (SNP) have been used but they are limited in their own ways [98]. These limitations are being overcome by improving already available techniques to form next-generation sequencing (NGS) [98]. With next-generation sequencing (NGS) technologies, SNP markers have been discovered in wheat, which is a good choice due to their abundance in the genome as they are distributed across all the wheat chromosomes [99]. These technologies offer easier means to map polymorphic genetic loci and identify genes for important traits [98]. Microsatellite markers have been used to determine the genetic diversity of wheat stem rust races in Kenya ([100]; Wanyera, unpublished data).
1.6.1 Single nucleotide polymorphism (SNP) markers
Single nucleotide variations in genome sequences of individuals of a population are known as SNPs. They result when DNA sequence differs by a single base and are the most abundant molecular markers in the genome [101]. SNPs and flanking sequences are found by library construction and sequencing or through the screening of readily available sequence databases [102]. Genotyping methods, including DNA chips, allele-specific PCR, and primer extension approaches based on SNPs, are particularly attractive for their high data throughput and for suitability for automation [103]. They are used for a wide range of purposes, including rapid identification of crop cultivars and construction of ultra-high-density genetic maps [103, 104]. SNPs markers have been used in wheat in identifying resistance genes for stripe rust Yr5, leaf rust Lr16, stem rust Sr6, the waxy starch gene Wx-D, and Karnal bunt resistance among others [105, 106, 107].
1.6.2 Kompetitive allele specific PCR (KASP) markers
Application of modern marker-assisted breeding approaches can help accelerate variety development efforts, single nucleotide polymorphisms (SNPs) markers have emerged as powerful tools for many genetic applications mainly due to their low assay cost, high abundance, co-dominant inheritance, high-throughput, and ease of use [101]. Numerous genotyping platforms have therefore been developed for SNP genotyping [108, 109] including KASP (Kompetitive Allele Specific PCR) which is a gel-free and fluorescent-based genotyping platform. KASP is fast emerging as a global benchmark in SNP genotyping [110, 111] developed and validated 70 KASP assays for functional genes controlling economically important traits such as plant height, disease resistance, yield, and quality in bread wheat. KASP markers have been used to determine alleles for important agronomic traits in wheat in East Africa, Kenya, and Ethiopia [82].
1.6.3 Use of sequence-characterized-amplified region (SCAR)
The application of molecular markers in different epidemiological studies is crucial in developing strain-specific markers such as Sequence-characterized-amplified-region (SCAR) markers [112]. The SCAR markers are codominant, while others are dominant single locus which allows for quick and easy PCR amplification-based detection and hence used in the studies of pathogens [113]. The SCAR markers are efficient in testing large samples and useful in tracing the origin and spread of microbial pathogens with the ability for long-distance disposal and invasion like yellow rust [114]. SCAR markers SCAR1265 and SCAR1400 were developed in wheat to identify powdery mildew (B. graminis) gene Pm21, which was located on 6AL/6Vs same locus for gene Yr26 [115]. Species-specific sequence-characterized-amplified-region (SCAR) markers have been used to characterize stripe rust races in Kenya [35].
2. Conclusion
There are high disease incidences and severity of wheat diseases particularly wheat rusts in the farmers’ fields, which is attributed to the use of highly susceptible wheat cultivars and also climate change contributing to emerging of new diseases. For example, the evolution and spread of Ug99 race group and additional races like Digalu race (TKTTF) are spreading very fast causing epidemics subjecting the wheat germplasm to vulnerability.
Other wheat diseases such as Septoria and Fusarium although sporadic are also a major concern in the wheat-growing regions in the country. The increase in the spread of these diseases is largely due to the widespread of cultivars that are highly susceptible. The favorable climatic conditions and additional costs of fungicides qualify the diseases as damaging with a strong impact on wheat production. Varieties with adequate resistance are now being released and continued monitoring of disease virulences throughout the country is necessary to detect shifts in the pathogen population as early as possible and therefore to effect an appropriate breeding strategy. Effective genetic control of the diseases using the state of the art molecular techniques will require a coordinated effort, including race monitoring, collection, and characterization of sources of resistance and resistance breeding.
In Kenya, different research groups consisting of plant breeders, plant pathologists, agronomists, international partners, and farmers are working towards achieving host plant resistance and ways to combat wheat diseases in order to achieve high yields and contribute to food security.
Acknowledgments
The authors wish to acknowledge the technical staff of the Plant Pathology section KALRO, Njoro, for assistance in collating pertinent information for this article.
\n',keywords:"wheat, diseases, challenges, control strategies",chapterPDFUrl:"https://cdn.intechopen.com/pdfs/81085.pdf",chapterXML:"https://mts.intechopen.com/source/xml/81085.xml",downloadPdfUrl:"/chapter/pdf-download/81085",previewPdfUrl:"/chapter/pdf-preview/81085",totalDownloads:52,totalViews:0,totalCrossrefCites:0,dateSubmitted:"January 17th 2022",dateReviewed:"January 25th 2022",datePrePublished:"April 3rd 2022",datePublished:null,dateFinished:"April 3rd 2022",readingETA:"0",abstract:"Wheat (Triticum aestivum L.) is an important cereal and is among the crops that contribute significantly to food security in Kenya. However, wheat diseases are among the biotic factors that affect wheat production. Considerable progress has been made to control wheat diseases through host plant resistance breeding and chemical applications. Frequent changes in the pathogens population still present a major challenge to achieving durable resistance. Disease surveillance and monitoring of the pathogens have revealed the changes in virulence across the region, justifying the need to develop and deploy more efficient and sustainable strategies to manage the diseases. Understanding the genetic variability and composition of the diseases is important for variety release with appropriate resistance gene combinations for sustainable disease management. This review highlights the prevalence, distribution of wheat diseases, host plant resistance in the key wheat-growing regions of Kenya, and future prospects in Kenya.",reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/81085",risUrl:"/chapter/ris/81085",signatures:"Ruth Wanyera and Mercy Wamalwa",book:{id:"11359",type:"book",title:"Wheat",subtitle:null,fullTitle:"Wheat",slug:null,publishedDate:null,bookSignature:"Dr. Mahmood-ur-Rahman Ansari",coverURL:"https://cdn.intechopen.com/books/images_new/11359.jpg",licenceType:"CC BY 3.0",editedByType:null,isbn:"978-1-80355-523-2",printIsbn:"978-1-80355-522-5",pdfIsbn:"978-1-80355-524-9",isAvailableForWebshopOrdering:!0,editors:[{id:"185476",title:"Dr.",name:"Mahmood-ur-Rahman",middleName:null,surname:"Ansari",slug:"mahmood-ur-rahman-ansari",fullName:"Mahmood-ur-Rahman Ansari"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}},authors:null,sections:[{id:"sec_1",title:"1. Introduction",level:"1"},{id:"sec_1_2",title:"1.1 Wheat rust diseases in Kenya",level:"2"},{id:"sec_2_2",title:"1.2 Other wheat diseases in Kenya",level:"2"},{id:"sec_3_2",title:"1.3 Distribution of diseases in wheat-growing regions of Kenya",level:"2"},{id:"sec_4_2",title:"1.4 Wheat breeding in Kenya",level:"2"},{id:"sec_5_2",title:"1.5 Control of wheat diseases in Kenya",level:"2"},{id:"sec_6_2",title:"1.6 Future of breeding for wheat diseases resistance in Kenya",level:"2"},{id:"sec_6_3",title:"1.6.1 Single nucleotide polymorphism (SNP) markers",level:"3"},{id:"sec_7_3",title:"1.6.2 Kompetitive allele specific PCR (KASP) markers",level:"3"},{id:"sec_8_3",title:"1.6.3 Use of sequence-characterized-amplified region (SCAR)",level:"3"},{id:"sec_11",title:"2. Conclusion",level:"1"},{id:"sec_12",title:"Acknowledgments",level:"1"}],chapterReferences:[{id:"B1",body:'Republic of Kenya. National Food and Nutrition Security Policy. Cathedral Road, Nairobi, Kenya: Agricultural Sector Coordination Unit (ASCU), Kilimo House; 2011'},{id:"B2",body:'Kenya Agricultural Research Institute. Strategic Plan. Annual Reports, KARI, Nairobi- Kenya; 2009. pp. 2009-2014'},{id:"B3",body:'Jaetzold R, Schmidt H, Hornetz B, Shisanya C. Farm management Handbook. 2nd ed. Vol. II. Part B Central Kenya. Subpart B1a: Southern Rift Valley. Ministry of Agriculture, Kenya, in Cooperation with the German Agency for Technical Corporation; 2010'},{id:"B4",body:'Economic Review of Agriculture. Ministry of Agriculture. Nairobi, Kenya; 2013. p. 109'},{id:"B5",body:'FAOSTAT. 2019. Available at: http://www.fao.org/faostat/en/#home'},{id:"B6",body:'Kamwaga J, Macharia G, Boyd L, Chiurugwi T, Midgley I, Canales C, et al. Kenya Wheat Production Handbook. Nairobi, Kenya: Kenya Agricultural and Livestock Research Organization; 2016. ISBN 978-9966-30-025-6'},{id:"B7",body:'Macharia G, Waweru B. Wheat in Kenya: Past and twenty-first century breeding. In: Wanyera R, Owuoche J, editors. Wheat Improvement, Management and Utilization. Rijeka: InTech; 2017. ISBN: 978-953-51-3151-9, Online: ISBN: 978-953-51-3152-6'},{id:"B8",body:'FAOSTAT. 2020. Statistical Database of the Food and Agriculture of the United Nations. Available from: http://www.fao.org/faostat/en/#home'},{id:"B9",body:'Kenya Agricultural Research Institute. 2009. Strategic Plan Implementation Frame Work. Annual Reports, KARI, Nairobi, Kenya; 2009-2014'},{id:"B10",body:'Wanyera R, Macharia JK, Kilonzo SM, Kamundia JW. Foliar fungicides to control wheat stem rust, race TTKS (Ug99) in Kenya. Plant Disease. 2009;93:929-932'},{id:"B11",body:'Wamalwa MN, Owuoche J, Ogendo J, Wanyera R. Multi-pathotype testing of selected Kenyan wheat germplasm and Watkin landraces for resistance to wheat stripe rust (Puccinia striiformis f. sp tritici) races. Agronomy. 2019;9(11):770'},{id:"B12",body:'Fetch TG, Park RF, Pretorius ZA, Depauw RM. Stem rust: Its history in Kenya and research to combat a global wheat threat. Canadian Journal of Plant Pathology, (just-accepted). 2021;43:S275-S297. DOI: 10.1080/07060661.2021.1902860'},{id:"B13",body:'Singh VK. Pathophenotyping and genome guided characterization of rust fungi infecting wheat and other cereals-A training manual. In: The Cereal Rusts in History. Vol. 10. 2020'},{id:"B14",body:'Li A, Liu D, Yang W, Kishii M, Mao L. Synthetic hexaploid wheat: Yesterday, today, and tomorrow. Engineering. 2018;4(4):552-558'},{id:"B15",body:'Pretorius ZA, Singh RP, Wagoire WW, Payne TS. Detection of virulence to wheat stem rust resistance gene Sr31 in Puccinia graminis f. sp. tritici in Uganda. Plant Disease. 2000;84:203'},{id:"B16",body:'Wanyera R, Kinyua MG, Jin Y, Singh R, Roelfs AP. The spread of stem rust caused by Puccinia graminis f. sp. tritici, with virulence on Sr31 in wheat in eastern Africa. Plant Disease. 2006;90:113'},{id:"B17",body:'Roelfs AP, Singh RP, Saari EE. Rust Diseases of Wheat: Concepts and Methods of Disease Management. Mexico, D.F: CIMMYT; 1992'},{id:"B18",body:'Jin Y, Szabo LJ, Pretorius ZA, Singh RP, Ward R, Fetch T. Detection of virulence to resistance gene Sr24 within race TTKS of Puccinia graminis f. sp. tritici. Plant Disease. 2008;92:923-926'},{id:"B19",body:'Singh RP, Hodson DP, Jin Y, Lagudah ES, Ayliffe MA, Bhavani S, et al. Emergence and spread of new races of wheat stem rust fungus: Continued threat to food security and prospects of genetic control. Phytopathology. 2015;105:872-884'},{id:"B20",body:'Newcomb M, Olivera PD, Rouse MN, Szabo LJ, Johnson J, Gale S, et al. (2016). Characterization of Kenyan isolates of Puccinia graminis f. sp. tritici from 2008 to 2014 reveals virulence to SrTmp in the Ug99 race group. Phytopathology. 2016;100:986-996'},{id:"B21",body:'Nazari K, Al-Maaroof E, Kurtulus E, Kavaz H, Hodson D, Ozseven I. First report of Ug99 race TTKTT of wheat stem rust (Puccinia graminis f. sp. tritici) in Iraq. Plant Disease. 2021;105(9):2719'},{id:"B22",body:'RustTracker.org. 2020 Pathotype Tracker – Where Is Ug99? Retrieved from: https://rusttracker.cimmyt.org/?page_id=22'},{id:"B23",body:'Olson EL. Broadening the wheat gene pool for stem rust resistance through genomic-assisted introgressions from Aegilops tauschii [PhD thesis]. Kansas State University: Manhattan, Kansas; 2012'},{id:"B24",body:'Hovmøller MS. Sources of seedling and adult plant resistance to Puccinia striiformis f. sp. tritici in European wheat. Plant Breeding. 2007;126:225-233'},{id:"B25",body:'Chen XM. Pathogens which threaten food security: Puccinia striiformis, the wheat stripe rust pathogen. Food Security. 2020;12(2):239-251'},{id:"B26",body:'Thorpe HC. Wheat Breeding in Kenya. Canada: First International wheat Genetics Symposium, University of Manitoba; 1959'},{id:"B27",body:'Wanyera R. The status of rust diseases of wheat in Kenya. In: Breeding for disease resistance with emphasis on durability. In: Daniel DL, editor. Proceedings of a Regional Workshop for Eastern, Central and Southern Africa. Njoro, Kenya. 1994. pp. 222-225'},{id:"B28",body:'Bonthuis H. Survival of stripe rust (Puccinia striiformis) on wheat in the Kenyan highlands and the consequences for virulence. Mededelingen van de Faculteit landbouwwetenschappen. Rijksuniversiteit Gent. 1985;50(4):1109-1117'},{id:"B29",body:'Kenya Agricultural Research Institute. Annual Reports, KARI, Nairobi, Kenya; 1990-2012'},{id:"B30",body:'Braun HJ, Singh RP, Huerta-Espino J, Herrera-Foessel SA, Lan CX, Basnet BR. Global status of yellow rust on wheat and strategies for its short- and long-term control. In: Proceedings of the 2nd International Wheat Stripe Rust Symposium, Regional Cereal Rust Research, Center Izmir, Turkey, 28th April – 1st May 2014. 2014. p. 25'},{id:"B31",body:'Aggarwal R, Kulshreshtha D, Sharma S, Singh VK, Manjunatha C, Bhardwaj SC, et al. Molecular characterization of Indian pathotypes of Puccinia striiformis f. sp. tritici and multigene phylogenetic analysis to establish inter-and intraspecific relationships. Genetics and Molecular Biology. 2018;41:834-842'},{id:"B32",body:'Hartmann FE, Rodríguez de la Vega RC, Carpentier F, Gladieux P, Cornille A, Hood ME, et al. Understanding adaptation, coevolution, host specialization, and mating system in castrating anther-smut fungi by combining population and comparative genomics. Annual Review of Phytopathology. 2019;57:431-457'},{id:"B33",body:'Danial DL, Stubbs RW, Parlevliet JE. Evolution of virulence patterns in yellow rust races and its implications for breeding for resistance in wheat in Kenya. Euphytica. 1994;80:165-170'},{id:"B34",body:'Ding Y, Cuddy WS, Wellings CR, Zhang P, Thach T, Hovmøller MS, et al. Incursions of divergent genotypes, evolution of virulence and host jumps shape a continental clonal population of the stripe rust pathogen Puccinia striiformis. Molecular Ecology. 2021;00:1-19'},{id:"B35",body:'Wamalwa M, Wanyera R, Rodriguez-Algaba J, Boyd L, Owuoche J, Ogendo J, et al. Distribution of Puccinia striiformis f. sp. tritici races and virulence in wheat growing regions of Kenya from 1970 TO 2014. Plant Disease. 2021;PDIS-11'},{id:"B36",body:'Kolmer JA, Long DL, Hughes ME. Physiological specialization of Puccinia triticina on wheat in the United States in 2003. Plant Disease. 2005;89:1201-1206'},{id:"B37",body:'Kolmer J. Leaf rust of wheat: Pathogen biology, variation and host resistance. Forests. 2013;4(1):70-84'},{id:"B38",body:'Roelfs AP, Singh RP, Saari EE. Rust Diseases of Wheat: Concepts and Methods of Disease Management. Mexico, D.F: CIMMYT; 1992'},{id:"B39",body:'Marasas CN, Smale M, Singh RP. The economic impact of productivity maintenance research: Breeding for leaf rust resistance in modern wheat. Agricultural Economics. 2003;29:253-263'},{id:"B40",body:'Bolton MD, Kolmer JA, Garvin DF. Wheat leaf rust caused by Puccinia triticina. Molecular Plant Pathology. 2008;9:563-575'},{id:"B41",body:'Arslan U, Karbulut OA, Yagdi K. Reaction of wheat lines to leaf rust (Puccinia triticina) in Turkey. Bangladesh Journal of Botany. 2007;36(2):163-166'},{id:"B42",body:'Kenya Agricultural Research Institute. Annual Reports. Kenya: Nairobi; 2011'},{id:"B43",body:'Nyamu GA, Owuoche JO, Ojwang PR, Wanyera R. Evaluation of Kenyan wheat (Triticum aestivum L.) genotypes for leaf rust (Puccinia triticina Eriks) at adult plant stage. International Journal Agronomic Agriculture Research. 2017;11(6):66-78'},{id:"B44",body:'Jin Y, Kolmer JA, Long DL. Wheat leaf rust and stem rust in the United States. Australian Journal of Agricultural Research. 2007;58:631-638'},{id:"B45",body:'Wamalwa M, Wanyera R. Characterization of wheat (Triticum aestivum L.) leaf rust (Puccinia triticina) races in Kenya. In: Proceedings of EAAPP Mini-Conference and Stakeholders Open Day 12-15 November 2013. Naivasha, Kenya: RDCoE/Morendat Training Centre; 2014'},{id:"B46",body:'Windels CE. Economic and social impacts of fusarium head blight: Changing farms and rural communities in the northern Great Plains. Phytopathology. 2000;90:17-21'},{id:"B47",body:'Muthomi JW, Oerke EC, Dehne HW, Mutitu EW. Susceptibility of Kenyan wheat varieties to head blight, fungal invasion and Deoxynivalenol accumulation inoculated with fusarium graminearum. Journal of Phytopathology. 2002;150(1):30-36'},{id:"B48",body:'Wagacha JM, Steiner U, Dehne HW, Zuehlke S, Spiteller M, Muthomi JW, et al. Diversity in mycotoxins and fungal species infecting wheat in Nakuru district, Kenya. Journal of Phytopathology. 2010;157:527-535'},{id:"B49",body:'Eyal Z, Scharen AL, Prescott JM, Van Ginkel M. The Septoria Diseases of Wheat Concepts and Methods of Diseases Management. Mexico, D.F: CIMMYT; 1987. ISBN: 968-6127-06-02'},{id:"B50",body:'Gupta PK, Chand R, Vasistha NK, Pandey SP, Kumar U, Mishra VK, et al. Spot blotch disease of wheat: The current status of research on genetics and breeding. Plant Pathology. 2018;67:508-531'},{id:"B51",body:'Wiese MV. Compendium of Wheat Diseases. St. Paul, MN: APS Press; 1987'},{id:"B52",body:'Mathur SB, Cunfer BM. Seed Borne Diseases and Seed Health Testing of Wheat. Copenhagen: Danish Government Institute of Seed Pathology for Developing Countries; 1993. p. 168'},{id:"B53",body:'Mehta YR. Constraints on the integrated management of spot blotch of wheat. In: Duveiller E, Dubin HJ, Reeves J, McNab A, editors. Helminthosporium Blight of Wheat: Spot Blotch and Tan Spot. Mexico, DF: CIMMYT; 1998. pp. 18-27'},{id:"B54",body:'Dubin HJ, van Ginkel M. The status of wheat diseases and disease research in the warmer areas. Wheat for the nontraditional warm areas: a proceedings of the International Conference July 29-August 3 1990 Foz do Iguaçu, Brazil. CIMMYT; 1991. pp. 125-45'},{id:"B55",body:'Ghazvini H, Tekauz A. Virulence diversity in the population of Bipolaris sorokiniana. Plant Disease. 2007;91(7):814-821'},{id:"B56",body:'Nyachiro JM. Development of Aluminum-tolerant bread wheat varieties in Kenya. In: Saunders DA, editor. Wheat for the Non-traditional Warm Areas. Mexico, D.F: CIMMYT; 1990. pp. 486-490'},{id:"B57",body:'Wanyera R, Kinyua MG, Kongsdal O, Hynkemejer A. Detection of seed- bornefungal pathogens infecting some crops in Kenya. In: Korir JK, Gohole LS, Muasya RM, editors. Proceedings of the Stakeholders workshop on Seed Industry in Kenya. Agrotech; 2004. p. 82-88. ISSN: 1727-8155'},{id:"B58",body:'Wanyera R. Seed-health status in wheat varieties Kenya. Proceedings of the First EgertonUniversity/NPBRC-NJORO Symposium in Agricultural Research. For Development (eds. J.N. Nanua, et al.); 2001. p. 249-256'},{id:"B59",body:'Wanyera R. Seed-borne pathogens of wheat in Kenya. Regional Wheat Workshop for Eastern, Central and Southern Africa, 10; University of Stellenbosch, South Africa; 14-18 Sep 1998. In: TRegional Wheat Workshop for Eastern, Central and Southern Africa, 10; University of Stellenbosch, South Africa; 14-18 Sep 1998 Addis Ababa (Ethiopia)CIMMYT C1999 (No. Look under series title. CIMMYT.). Centro Internacional de Mejoramiento de Maiz y Trigo (CIMMYT), Addis Ababa (Ethiopia). 1999'},{id:"B60",body:'Villa-Rodríguez E, Parra-Cota F, Castro-Longoria E, López-Cervantes J, de los Santos-Villalobos S. Bacillus subtilis TE3: A promising biological control agent against Bipolaris sorokiniana, the causal agent of spot blotch in wheat (Triticum turgidum L. subsp. durum). Biological Control. 2019;132:135-143'},{id:"B61",body:'Singh UB, Malviya D, Singh S, Kumar M, Sahu PK, Singh HV, et al. Trichoderma harzianum- and methyl Jasmonate-induced resistance to Bipolaris sorokiniana through enhanced Phenylpropanoid activities in bread wheat (Triticum aestivum L.). Frontiers in Microbiology. 2019;10:3389'},{id:"B62",body:'Wangai AW. Effects of barley yellow dwarf virus on cereals in Kenya. In: Burnett PA, editor. World Perspectives on Barley Yellow Dwarf Virus. Mexico, D.F: CIMMYT; 1990. pp. 391-393'},{id:"B63",body:'Munene M, Nyakwara ZA, Njuguna MN, Maina IN. The occurrence of cereal aphids in Rainfed wheat in Kenya: The problem and possible integrated Pest management strategies. In: Wanyera R, Owuoche J, editors. Wheat Improvement, Management and Utilization. Rijeka: IntechOpen; 2017. DOI: 10.5772/67115. Available from: https://www.intechopen.com/chapters/53906'},{id:"B64",body:'Wanjama JK. Review of wheat aphid as a pest of cereals in the Rift Valley province Kenya. Entomologist Newsletter. 1979;9:2-3'},{id:"B65",body:'Migui SM, Macharia M, Muthangyia PM, Wanjama JK. Evaluation of insecticides for the control of cereal aphids transmitting barley yellow dwarf virus in barley. Pp-203-210. In: Tanner DG, Mwangi W, editors. Seventh Regional Wheat Workshop for Eastern, Central and Southern Africa. Nakuru, Kenya: CIMMYT; 1992'},{id:"B66",body:'Zadoks JC, Chang TT, Konzak CF. A decimal code for the growth stages of cereals. Weed Research. 1974;14:415-421'},{id:"B67",body:'Peterson RF, Campell AB, Hannah AE. A diagrammatic scale for estimating rust intensity of leaves and stems of cereals. Canadian Journal of Research. 1984;26:496-500'},{id:"B68",body:'Roelfs AP, Singh RP, Saari EE. Rust Diseases of Wheat: Concepts and Methods of Disease Management. Mexico, D.F: CIMMYT; 1992'},{id:"B69",body:'Muthangya PM, Macharia M, Wanjama JK. Effects of Imidacloprid seed dressing and foliar aphicide on cereal aphids and BYDV on barley in Kenya. In: Tanner DG, Payne TS, Abdalla OS, editors. The Nineth Regional Wheat Workshop: For Eastern, Central and Southern Africa. 1993'},{id:"B70",body:'James C. A Manual of Assessment Keys for Plant Diseases. No. BOOK. American Phytopathological Society; 1971'},{id:"B71",body:'Green GJ, Martens JW, Ribeiro O. Epidemiology and specialization of wheat and oat stem rusts in Kenya in 1968. Phytopathology. 1970;60:309-314'},{id:"B72",body:'Njau PN, Kimurto PK, Kinyua MG, Okwaro HK, Ogolla JB. Wheat productivity improvement in the drought prone areas of Kenya. African Crop Science Journal. 2006;14(1):49-57'},{id:"B73",body:'Kinyua M, Malinga JN, Wanyama J, Karanja L, Njau P, Leo T, Alomba E (2001) Improvement of wheat for resistance to Russian wheat aphid.'},{id:"B74",body:'Dawit WK, Flath WE, Weber E, Schumann MS, Röderand S, Chen X. Postulation and mapping of seedling stripe rust resistance genes in Ethiopian bread wheat cultivars. Plant Pathology. 2012;94:403-409'},{id:"B75",body:'Kang ZS, Zhao J, Han DJ, Zhang HC, Wang XJ, Wang CF, et al. Status of wheat rust research and control in China. In: BGRI 2010 Technical Workshop, 30-31 May 2010, St Petersburg, Russia. PP; 2010. p. 38'},{id:"B76",body:'Yuen GY, Schoneweis SD. Strategies for managing fusarium head blight and deoxynivalenol accumulation in wheat. International Journal of Food Microbiology. 2007;119(1-2):126-130'},{id:"B77",body:'Loughman A, Fitzgerald JR, Brennan MP, Higgins J, Downer R, Cox D, et al. Roles for fibrinogen, immunoglobulin and complement in platelet activation promoted by Staphylococcus aureus clumping factor A. Molecular Microbiology. 2005;57(3):804-818'},{id:"B78",body:'Njau PN, Wanyera R, Singh D, Singh R, Gethi M. Release of stem rust resistant wheat varieties for commercial production in Kenya. Journal of Agricultural Science and Technology. 2011;A1:587-598'},{id:"B79",body:'Alemu G. Wheat breeding for disease resistance: Review. Journal of Microbiology and Biotechnology. 2019;4(2):000142'},{id:"B80",body:'Spielmeyer W, Sharp PJ, Lagudah ES. Identification and validation of markers linked to broad-spectrum stem rust resistance gene Sr2 in wheat (Triticum aestivum L.). Crop Science. 2003;43:333-336'},{id:"B81",body:'Njau PN, Jin Y, Huerta-Espino J, Keller B, Singh RP. Identification and evaluation of sources of resistance to stem rust race Ug99 in wheat. Plant Disease. 2010;94(4):413-419'},{id:"B82",body:'Wamalwa M, Tadesse Z, Muthui L, Yao N, Zegeye H, Randhawa M, et al. Allelic diversity study of functional genes in East Africa bread wheat highlights opportunities for genetic improvement. Molecular Breeding. 2020;40(11):1-4'},{id:"B83",body:'M’mboyi F, Njau P, Olembo N, Kinyua M, Malinga MJ. Application of Biotechnology to Wheat Improvement in Sub-Saharan Africa: The Case of Kenya. Nairobi, Kenya: African Biotechnology Stakeholders Forum (ABSF); 2010'},{id:"B84",body:'Yang Q, Fang T, Li X, Ma C, Yang S, Kang Z, et al. Improving stripe rust resistance and agronomic performance in three elite wheat cultivars using a combination of phenotypic selection and marker detection of Yr48. Crop Protection. 2021;148:105752'},{id:"B85",body:'Eagles HA, Barian HS, Ogbonnaya FC, Rebetzke GJ, Hollamby GJ, Henry RJ, et al. Implementation of markers in Australian wheat breeding. Austrialian Journal of Agricultural Research. 2001;52:1349-1356'},{id:"B86",body:'Kaur P, Sachan S, Sharma A. Weed competitive ability in wheat: A peek through in its functional significance, present status and future prospects. Physiology and Molecular Biology of Plants. 2021;1:15'},{id:"B87",body:'Malinga J, Kinyua M, Wanjama J, Kamau A, Karanja L, Awala J, et al. Evidence of a new Russian wheat aphid biotype in Kenya adduced from molecular markers. In: 12th Regional Wheat Workshop for Eastern, Central and Southern Africa, Nakuru, Kenya, 22-26 November, 2004. 2005'},{id:"B88",body:'Ellis JG, Lagudah ES, Spielmeyer W, Dodds PN. The past, present and future of breeding rust resistant wheat. Frontiers of Plant Science. 2014;5:641'},{id:"B89",body:'Chen XM. Epidemiology and control of stripe rust (Puccinia striiformis f sp tritici). Canadian Journal of Plant Pathology. 2005;27:314-337'},{id:"B90",body:'Chen XM, Kang ZS, editors. Stripe Rust (719 pages). Dordrecht: Springer; 2017'},{id:"B91",body:'Boshoff WHP, Pretorius ZA, Van BD. Fungicide efficacy and the impact of stripe rust on spring and winter wheat in South Africa. South African Journal of Plant and Soil. 2003;20:11-17'},{id:"B92",body:'Zobir SAM, Ali A, Adzmi F, Sulaiman MR, Ahmad K. A review on Nano pesticides for plant protection synthesized using the supramolecular chemistry of layered hydroxide hosts. 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Molecular Markers for Gene Bank Management. IPGRI Technical Bulletin No. 10. Rome, Italy: International Plant Genetic Resources Institute; 2005'},{id:"B103",body:'Pandurangan S, Workman C, Nilsen K, Kumar S. Introduction to marker-assisted selection in wheat breeding. In: Accelerated Breeding of Cereal Crops. New York, NY: Humana; 2022. pp. 77-117'},{id:"B104",body:'Mondini L, Noorani A, Pagnotta MA. Assessing plant genetic diversity by molecular tools. Diversity. 2009;1:19-35'},{id:"B105",body:'Kassa MT, You FM, Hiebert CW, Pozniak CJ, Fobert PR, Sharpe AG, et al. Highly predictive SNP markers for efficient selection of the wheat leaf rust resistance gene Lr16. BMC Plant Biology. 2017;17(1):1-9'},{id:"B106",body:'Mourad AM, Sallam A, Belamkar V, Wegulo S, Bowden R, Jin Y, et al. Genome-wide association study for identification and validation of novel SNP markers for Sr6 stem rust resistance gene in bread wheat. 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Available from: http://www.intechopen.com/books/plantbreeding/ genomics-assisted-plant-breeding-in-the-21stcenturytechnological-advances-and-progress'},{id:"B111",body:'Rasheed A, Wen W, Gao FM, Zhai S, Jin H, Liu JD. Development and validation of KASP assays for functional genes underpinning key economic traits in wheat. Theoretical and Applied Genetics. 2016;129:1843-1860'},{id:"B112",body:'Hodson DP, Hansen JG, Lassen P, Alemayehu Y, Arista J, Sonder K. Tracking the wheat rust pathogen. In: Proceedings from BGRI Technical Meeting, Beijing, China. 2012. p. 20'},{id:"B113",body:'Naeimi S, Koscsube S. Strain-specific SCAR markers for the detection of Trichoderma harzianum AS12- 2, a biological control agent against Rhizoctonia solani, the causal agent of rice sheath blight. Acta Biology Hungary. 2011;62:73-84'},{id:"B114",body:'Walter S, Ali S, Kemen E, Nazari K, Bahri BA, Enjalbert J, et al. 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Our Values
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Our business values are based on those any scientist applies to their research. We have created a culture of respect and collaboration within a relaxed, friendly and progressive atmosphere, while maintaining academic rigour.
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Integrity - We are consistent and dependable, always striving for precision and accuracy in the true spirit of science.
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Disruptiveness - We are eager for discovery, for new ideas and for progression. We approach our work with creativity and determination, with a clear vision that drives us forward. We look beyond today and strive for a better tomorrow.
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Co-founded by Alex Lazinica and Vedran Kordic: “We are passionate about the advancement of science. As Ph.D. researchers in Vienna, we found it difficult to access the scholarly research we needed. We created IntechOpen with the specific aim of putting the academic needs of the global research community before the business interests of publishers. Our Team is now a global one and includes highly-renowned scientists and publishers, as well as experts in disseminating your research.”
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Sara Uhac, COO
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Sara Uhac was appointed Managing Director of IntechOpen at the beginning of 2014. She directs and controls the company’s operations. Sara joined IntechOpen in 2010 as Head of Journal Publishing, a new strategically underdeveloped department at that time. After obtaining a Master's degree in Media Management, she completed her Ph.D. at the University of Lugano, Switzerland. She holds a BA in Financial Market Management from the Bocconi University in Milan, Italy, where she started her career in the American publishing house Condé Nast and further collaborated with the UK-based publishing company Time Out. Sara was awarded a professional degree in Publishing from Yale University (2012). She is a member of the professional branch association of "Publishers, Designers and Graphic Artists" at the Croatian Chamber of Commerce.
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Adrian Assad De Marco
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Adrian Assad De Marco joined the company as a Director in 2017. With his extensive experience in management, acquired while working for regional and global leaders, he took over direction and control of all the company's publishing processes. Adrian holds a degree in Economy and Management from the University of Zagreb, School of Economics, Croatia. A former sportsman, he continually strives to develop his skills through professional courses and specializations such as NLP (Neuro-linguistic programming).
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IntechOpen Board Members
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Dr Alex Lazinica
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Alex Lazinica is co-founder and Board member of IntechOpen. After obtaining a Master's degree in Mechanical Engineering, he continued his Ph.D. in Robotics at the Vienna University of Technology. There, he worked as a robotics researcher with the university's Intelligent Manufacturing Systems Group, as well as a guest researcher at various European universities, including the Swiss Federal Institute of Technology Lausanne (EPFL). During this time he published more than 20 scientific papers, gave presentations, served as a reviewer for major robotic journals and conferences and, most importantly, co-founded and built the International Journal of Advanced Robotic Systems, the world's first Open Access journal in the field of robotics. Starting this journal was a pivotal point in his career since it proved to be the pathway to the foundation of IntechOpen with its focus on addressing academic researchers’ needs. Alex personifies many of IntechOpen´s key values, including the commitment to developing mutual trust, openness, and a spirit of entrepreneurialism. Today, his focus is on defining the growth and development strategy for the company.
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Integrity - We are consistent and dependable, always striving for precision and accuracy in the true spirit of science.
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Openness - We communicate honestly and transparently. We are open to constructive criticism and committed to learning from it.
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Disruptiveness - We are eager for discovery, for new ideas and for progression. We approach our work with creativity and determination, with a clear vision that drives us forward. We look beyond today and strive for a better tomorrow.
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Our Team
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Co-founded by Alex Lazinica and Vedran Kordic: “We are passionate about the advancement of science. As Ph.D. researchers in Vienna, we found it difficult to access the scholarly research we needed. We created IntechOpen with the specific aim of putting the academic needs of the global research community before the business interests of publishers. Our Team is now a global one and includes highly-renowned scientists and publishers, as well as experts in disseminating your research.”
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But, one thing we have in common is -- we are all scientists at heart!
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Sara Uhac, COO
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Sara Uhac was appointed Managing Director of IntechOpen at the beginning of 2014. She directs and controls the company’s operations. Sara joined IntechOpen in 2010 as Head of Journal Publishing, a new strategically underdeveloped department at that time. After obtaining a Master's degree in Media Management, she completed her Ph.D. at the University of Lugano, Switzerland. She holds a BA in Financial Market Management from the Bocconi University in Milan, Italy, where she started her career in the American publishing house Condé Nast and further collaborated with the UK-based publishing company Time Out. Sara was awarded a professional degree in Publishing from Yale University (2012). She is a member of the professional branch association of "Publishers, Designers and Graphic Artists" at the Croatian Chamber of Commerce.
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Adrian Assad De Marco
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Adrian Assad De Marco joined the company as a Director in 2017. With his extensive experience in management, acquired while working for regional and global leaders, he took over direction and control of all the company's publishing processes. Adrian holds a degree in Economy and Management from the University of Zagreb, School of Economics, Croatia. A former sportsman, he continually strives to develop his skills through professional courses and specializations such as NLP (Neuro-linguistic programming).
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IntechOpen Board Members
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Dr Alex Lazinica
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Alex Lazinica is co-founder and Board member of IntechOpen. After obtaining a Master's degree in Mechanical Engineering, he continued his Ph.D. in Robotics at the Vienna University of Technology. There, he worked as a robotics researcher with the university's Intelligent Manufacturing Systems Group, as well as a guest researcher at various European universities, including the Swiss Federal Institute of Technology Lausanne (EPFL). During this time he published more than 20 scientific papers, gave presentations, served as a reviewer for major robotic journals and conferences and, most importantly, co-founded and built the International Journal of Advanced Robotic Systems, the world's first Open Access journal in the field of robotics. Starting this journal was a pivotal point in his career since it proved to be the pathway to the foundation of IntechOpen with its focus on addressing academic researchers’ needs. Alex personifies many of IntechOpen´s key values, including the commitment to developing mutual trust, openness, and a spirit of entrepreneurialism. Today, his focus is on defining the growth and development strategy for the company.
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From 1985 to 1986, he was a Research Fellow in the Research Institute for Electronic Equipment, ZZU AD, Plovdiv, Bulgaria. In 1986, he joined the Department of Control Systems, Technical University of Sofia at the Plovdiv campus, where he is presently a Full Professor. He has held long-term visiting Professor/Scholar positions at various institutions in South Korea, Turkey, Mexico, Greece, Belgium, UK, and Germany. And he has coauthored one book and authored or coauthored more than 80 research papers in conference proceedings and journals. His current research interests are in the fields of intelligent control and robotics.",institutionString:null,institution:{name:"Technical University of Sofia",country:{name:"Bulgaria"}}},{id:"585",title:"Prof.",name:"Munir",middleName:null,surname:"Merdan",slug:"munir-merdan",fullName:"Munir Merdan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/585/images/system/585.jpg",biography:"Munir Merdan received the M.Sc. degree in mechanical engineering from the Technical University of Sarajevo, Bosnia and Herzegovina, in 2001, and the Ph.D. degree in electrical engineering from the Vienna University of Technology, Vienna, Austria, in 2009.Since 2005, he has been at the Automation and Control Institute, Vienna University of Technology, where he is currently a Senior Researcher. 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Plateau State, Nigeria.",book:{id:"11602",title:"Corporate Social Responsibility",coverURL:"https://cdn.intechopen.com/books/images_new/11602.jpg"},signatures:"Peter Musa Wash, Shida Irwana Omar, Badaruddin Mohamed and Mohd Ismail Isa"},{id:"82786",title:"Discussion of Purchasing Virtual Digital Nature and Tourism",slug:"discussion-of-purchasing-virtual-digital-nature-and-tourism",totalDownloads:5,totalDimensionsCites:0,doi:"10.5772/intechopen.105869",abstract:"This chapter discusses the potential and prospects of consumers purchasing virtual digital nature and smart tourism. During the lockdown period, people experienced a trend toward increased subjective well-being as a result of their familiarity with the digital nature. In order to academically validate these experiences, this study examines how interaction with nature in the digital environment stimulates new consumer behavior in post-pandemic life. The study will apply structural equation modeling (SEM) to 300 data collected through a questionnaire to develop the discussion, with a particular focus on the mediating effects of digital forest bathing. The results show that digital forest bath ing has a mediating effect in stimulating people’s environmentally oriented behavior, and that the more active they are in digital space and interact with others, the more consumers enjoy interacting with nature in cyberspace and, in turn, the more willing they are to commune with digital nature through smart tourism. This can be expected to provide an effective reference for marketing strategies that contribute to the promotion of smart tourism in the age of symbiosis with COVID.",book:{id:"11581",title:"A New Era of Consumer Behavior - Beyond the Pandemic",coverURL:"https://cdn.intechopen.com/books/images_new/11581.jpg"},signatures:"Hiroko Oe and Yasuyuki Yamaoka"},{id:"82777",title:"Sustainability and Social Investment: Community Microhydropower Systems in the Dominican Republic",slug:"sustainability-and-social-investment-community-microhydropower-systems-in-the-dominican-republic",totalDownloads:4,totalDimensionsCites:0,doi:"10.5772/intechopen.105995",abstract:"Sustainability remains an underestimated concept when assessing the impact of philanthropic and social investments in communities due to the difficult task of conciliating human development, economy, and environmental protection. Currently, financial cost-effectiveness is one of the main criteria for decision-making. 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This article contains the experience of the successes and challenges of more than 50 community microhydropower systems, managed by local groups, which are working and demonstrating the meaning of sustainability and the positive nonmonetary impacts of social investing, opening future opportunities to expand the present 5% of private investment.",book:{id:"11476",title:"Globalization and Sustainability - Recent Advances, New Perspectives and Emerging Issues",coverURL:"https://cdn.intechopen.com/books/images_new/11476.jpg"},signatures:"Michela Izzo, Alberto Sánchez and Rafael Fonseca"},{id:"81403",title:"Do the Collaboration Dimensions Pay in Manufacturing Reverse Supply Chain? An Empirical Approach",slug:"do-the-collaboration-dimensions-pay-in-manufacturing-reverse-supply-chain-an-empirical-approach",totalDownloads:10,totalDimensionsCites:0,doi:"10.5772/intechopen.103068",abstract:"The purpose of this paper is to examine empirically the enablers and practices of collaboration in relation to reverse supply chain. The research method used in this research was a quantitative method using a survey approach to empirically test if the following collaboration enables and practices are applicable. The statistical approach was AMOS 26. The findings revealed that, the relationship building and management for implementing collaboration was ranked highest, resource investment and development in reverse supply chain was ranked the next. Furthermore, quick response on returned goods and information sharing with suppliers on the returned products were highest ranked. The research was limited because the study was based in the Gauteng region, which means that a generalised statement cannot be made of the finding, as well there is a need for the study to be industry specific such as electronics, online retailers. The practical implications of the findings are that the enablers and practices are needed for reverse supply practices to achieve its aims. There is lack of research in the reverse collaboration space, this has paper has fulfilled the following gap.",book:{id:"11253",title:"Sustainable Rural Development",coverURL:"https://cdn.intechopen.com/books/images_new/11253.jpg"},signatures:"Ifije Ohiomah, Clinton Aigbavboa and Nita Sukdeo"},{id:"82387",title:"Kept Promises? The Evolution of the EU Financial Contribution to Climate Change",slug:"kept-promises-the-evolution-of-the-eu-financial-contribution-to-climate-change",totalDownloads:11,totalDimensionsCites:0,doi:"10.5772/intechopen.105541",abstract:"The chapter provides an overview of the public climate finance implemented under the UNFCCC by the EU as a whole and its Member States—in the chapter called EUplus—later taken over by SDG 13.a, for the period 2011–2018 (the latest year available). Through the analysis of the UNFCCC Biennial Reports, it is possible not only to highlight the amount allocated to the challenge against climate change, but also to break it down into its two meanings: mitigation and adaptation, as well as to identify the type of channel through which this support has been implemented. In this context, particular attention will be given to the two contribution channels: bilateral and multilateral, highlighting the type of support in different cases. The chapter shows an increase in contributions, especially since 2015, and how support has been increasingly shifted toward adaptation. 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\r\n\tEducation and Human Development is an interdisciplinary research area that aims to shed light on topics related to both learning and development. This Series is intended for researchers, practitioners, and students who are interested in understanding more about these fields and their applications.
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Recently, he expanded his research interest to epidemiology and biostatistics of chronic diseases in Gabon.",institutionString:"Kent State University",institution:{name:"Kent State University",country:{name:"United States of America"}}},{id:"188773",title:"Prof.",name:"Emmanuel",middleName:null,surname:"Drouet",slug:"emmanuel-drouet",fullName:"Emmanuel Drouet",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/188773/images/system/188773.png",biography:"Emmanuel Drouet, PharmD, is a Professor of Virology at the Faculty of Pharmacy, the University Grenoble-Alpes, France. As a head scientist at the Institute of Structural Biology in Grenoble, Dr. Drouet’s research investigates persisting viruses in humans (RNA and DNA viruses) and the balance with our host immune system. He focuses on these viruses’ effects on humans (both their impact on pathology and their symbiotic relationships in humans). He has an excellent track record in the herpesvirus field, and his group is engaged in clinical research in the field of Epstein-Barr virus diseases. He is the editor of the online Encyclopedia of Environment and he coordinates the Universal Health Coverage education program for the BioHealth Computing Schools of the European Institute of Science.",institutionString:null,institution:{name:"Grenoble Alpes University",country:{name:"France"}}},{id:"131400",title:"Prof.",name:"Alfonso J.",middleName:null,surname:"Rodriguez-Morales",slug:"alfonso-j.-rodriguez-morales",fullName:"Alfonso J. Rodriguez-Morales",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/131400/images/system/131400.png",biography:"Dr. Rodriguez-Morales is an expert in tropical and emerging diseases, particularly zoonotic and vector-borne diseases (especially arboviral diseases). He is the president of the Travel Medicine Committee of the Pan-American Infectious Diseases Association (API), as well as the president of the Colombian Association of Infectious Diseases (ACIN). He is a member of the Committee on Tropical Medicine, Zoonoses, and Travel Medicine of ACIN. He is a vice-president of the Latin American Society for Travel Medicine (SLAMVI) and a Member of the Council of the International Society for Infectious Diseases (ISID). Since 2014, he has been recognized as a Senior Researcher, at the Ministry of Science of Colombia. He is a professor at the Faculty of Medicine of the Fundacion Universitaria Autonoma de las Americas, in Pereira, Risaralda, Colombia. He is an External Professor, Master in Research on Tropical Medicine and International Health, Universitat de Barcelona, Spain. He is also a professor at the Master in Clinical Epidemiology and Biostatistics, Universidad Científica del Sur, Lima, Peru. In 2021 he has been awarded the “Raul Isturiz Award” Medal of the API. Also, in 2021, he was awarded with the “Jose Felix Patiño” Asclepius Staff Medal of the Colombian Medical College, due to his scientific contributions to COVID-19 during the pandemic. He is currently the Editor in Chief of the journal Travel Medicine and Infectious Diseases. His Scopus H index is 47 (Google Scholar H index, 68).",institutionString:"Institución Universitaria Visión de las Américas, Colombia",institution:null},{id:"332819",title:"Dr.",name:"Chukwudi Michael",middleName:"Michael",surname:"Egbuche",slug:"chukwudi-michael-egbuche",fullName:"Chukwudi Michael Egbuche",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/332819/images/14624_n.jpg",biography:"I an Dr. Chukwudi Michael Egbuche. I am a Senior Lecturer in the Department of Parasitology and Entomology, Nnamdi Azikiwe University, Awka.",institutionString:null,institution:{name:"Nnamdi Azikiwe University",country:{name:"Nigeria"}}},{id:"284232",title:"Mr.",name:"Nikunj",middleName:"U",surname:"Tandel",slug:"nikunj-tandel",fullName:"Nikunj Tandel",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/284232/images/8275_n.jpg",biography:'Mr. Nikunj Tandel has completed his Master\'s degree in Biotechnology from VIT University, India in the year of 2012. He is having 8 years of research experience especially in the field of malaria epidemiology, immunology, and nanoparticle-based drug delivery system against the infectious diseases, autoimmune disorders and cancer. He has worked for the NIH funded-International Center of Excellence in Malaria Research project "Center for the study of complex malaria in India (CSCMi)" in collaboration with New York University. The preliminary objectives of the study are to understand and develop the evidence-based tools and interventions for the control and prevention of malaria in different sites of the INDIA. Alongside, with the help of next-generation genomics study, the team has studied the antimalarial drug resistance in India. Further, he has extended his research in the development of Humanized mice for the study of liver-stage malaria and identification of molecular marker(s) for the Artemisinin resistance. At present, his research focuses on understanding the role of B cells in the activation of CD8+ T cells in malaria. Received the CSIR-SRF (Senior Research Fellow) award-2018, FIMSA (Federation of Immunological Societies of Asia-Oceania) Travel Bursary award to attend the IUIS-IIS-FIMSA Immunology course-2019',institutionString:"Nirma University",institution:{name:"Nirma University",country:{name:"India"}}},{id:"334383",title:"Ph.D.",name:"Simone",middleName:"Ulrich",surname:"Ulrich Picoli",slug:"simone-ulrich-picoli",fullName:"Simone Ulrich Picoli",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/334383/images/15919_n.jpg",biography:"Graduated in Pharmacy from Universidade Luterana do Brasil (1999), Master in Agricultural and Environmental Microbiology from Federal University of Rio Grande do Sul (2002), Specialization in Clinical Microbiology from Universidade de São Paulo, USP (2007) and PhD in Sciences in Gastroenterology and Hepatology (2012). She is currently an Adjunct Professor at Feevale University in Medicine and Biomedicine courses and a permanent professor of the Academic Master\\'s Degree in Virology. She has experience in the field of Microbiology, with an emphasis on Bacteriology, working mainly on the following topics: bacteriophages, bacterial resistance, clinical microbiology and food microbiology.",institutionString:null,institution:{name:"Universidade Feevale",country:{name:"Brazil"}}},{id:"229220",title:"Dr.",name:"Amjad",middleName:"Islam",surname:"Aqib",slug:"amjad-aqib",fullName:"Amjad Aqib",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/229220/images/system/229220.png",biography:"Dr. Amjad Islam Aqib obtained a DVM and MSc (Hons) from University of Agriculture Faisalabad (UAF), Pakistan, and a PhD from the University of Veterinary and Animal Sciences Lahore, Pakistan. Dr. Aqib joined the Department of Clinical Medicine and Surgery at UAF for one year as an assistant professor where he developed a research laboratory designated for pathogenic bacteria. Since 2018, he has been Assistant Professor/Officer in-charge, Department of Medicine, Manager Research Operations and Development-ORIC, and President One Health Club at Cholistan University of Veterinary and Animal Sciences, Bahawalpur, Pakistan. He has nearly 100 publications to his credit. His research interests include epidemiological patterns and molecular analysis of antimicrobial resistance and modulation and vaccine development against animal pathogens of public health concern.",institutionString:"Cholistan University of Veterinary and Animal Sciences",institution:{name:"University of Agriculture Faisalabad",country:{name:"Pakistan"}}},{id:"333753",title:"Dr.",name:"Rais",middleName:null,surname:"Ahmed",slug:"rais-ahmed",fullName:"Rais Ahmed",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/333753/images/20168_n.jpg",biography:null,institutionString:null,institution:{name:"University of Agriculture Faisalabad",country:{name:"Pakistan"}}},{id:"62900",title:"Prof.",name:"Fethi",middleName:null,surname:"Derbel",slug:"fethi-derbel",fullName:"Fethi Derbel",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/62900/images/system/62900.jpeg",biography:"Professor Fethi Derbel was born in 1960 in Tunisia. He received his medical degree from the Sousse Faculty of Medicine at Sousse, University of Sousse, Tunisia. He completed his surgical residency in General Surgery at the University Hospital Farhat Hached of Sousse and was a member of the Unit of Liver Transplantation in the University of Rennes, France. He then worked in the Department of Surgery at the Sahloul University Hospital in Sousse. Professor Derbel is presently working at the Clinique les Oliviers, Sousse, Tunisia. His hospital activities are mostly concerned with laparoscopic, colorectal, pancreatic, hepatobiliary, and gastric surgery. He is also very interested in hernia surgery and performs ventral hernia repairs and inguinal hernia repairs. He has been a member of the GREPA and Tunisian Hernia Society (THS). During his residency, he managed patients suffering from diabetic foot, and he was very interested in this pathology. For this reason, he decided to coordinate a book project dealing with the diabetic foot. Professor Derbel has published many articles in journals and collaborates intensively with IntechOpen Access Publisher as an editor.",institutionString:"Clinique les Oliviers",institution:null},{id:"300144",title:"Dr.",name:"Meriem",middleName:null,surname:"Braiki",slug:"meriem-braiki",fullName:"Meriem Braiki",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/300144/images/system/300144.jpg",biography:"Dr. Meriem Braiki is a specialist in pediatric surgeon from Tunisia. She was born in 1985. She received her medical degree from the University of Medicine at Sousse, Tunisia. She achieved her surgical residency training periods in Pediatric Surgery departments at University Hospitals in Monastir, Tunis and France.\r\nShe is currently working at the Pediatric surgery department, Sidi Bouzid Hospital, Tunisia. Her hospital activities are mostly concerned with laparoscopic, parietal, urological and digestive surgery. She has published several articles in diffrent journals.",institutionString:"Sidi Bouzid Regional Hospital",institution:null},{id:"229481",title:"Dr.",name:"Erika M.",middleName:"Martins",surname:"de Carvalho",slug:"erika-m.-de-carvalho",fullName:"Erika M. de Carvalho",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/229481/images/6397_n.jpg",biography:null,institutionString:null,institution:{name:"Oswaldo Cruz Foundation",country:{name:"Brazil"}}},{id:"186537",title:"Prof.",name:"Tonay",middleName:null,surname:"Inceboz",slug:"tonay-inceboz",fullName:"Tonay Inceboz",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/186537/images/system/186537.jfif",biography:"I was graduated from Ege University of Medical Faculty (Turkey) in 1988 and completed his Med. PhD degree in Medical Parasitology at the same university. I became an Associate Professor in 2008 and Professor in 2014. I am currently working as a Professor at the Department of Medical Parasitology at Dokuz Eylul University, Izmir, Turkey.\n\nI have given many lectures, presentations in different academic meetings. I have more than 60 articles in peer-reviewed journals, 18 book chapters, 1 book editorship.\n\nMy research interests are Echinococcus granulosus, Echinococcus multilocularis (diagnosis, life cycle, in vitro and in vivo cultivation), and Trichomonas vaginalis (diagnosis, PCR, and in vitro cultivation).",institutionString:"Dokuz Eylül University",institution:{name:"Dokuz Eylül University",country:{name:"Turkey"}}},{id:"71812",title:"Prof.",name:"Hanem Fathy",middleName:"Fathy",surname:"Khater",slug:"hanem-fathy-khater",fullName:"Hanem Fathy Khater",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/71812/images/1167_n.jpg",biography:"Prof. Khater is a Professor of Parasitology at Benha University, Egypt. She studied for her doctoral degree, at the Department of Entomology, College of Agriculture, Food and Natural Resources, University of Missouri, Columbia, USA. She has completed her Ph.D. degrees in Parasitology in Egypt, from where she got the award for “the best scientific Ph.D. dissertation”. She worked at the School of Biological Sciences, Bristol, England, the UK in controlling insects of medical and veterinary importance as a grant from Newton Mosharafa, the British Council. Her research is focused on searching of pesticides against mosquitoes, house flies, lice, green bottle fly, camel nasal botfly, soft and hard ticks, mites, and the diamondback moth as well as control of several parasites using safe and natural materials to avoid drug resistances and environmental contamination.",institutionString:null,institution:{name:"Banha University",country:{name:"Egypt"}}},{id:"99780",title:"Prof.",name:"Omolade",middleName:"Olayinka",surname:"Okwa",slug:"omolade-okwa",fullName:"Omolade Okwa",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/99780/images/system/99780.jpg",biography:"Omolade Olayinka Okwa is presently a Professor of Parasitology at Lagos State University, Nigeria. She has a PhD in Parasitology (1997), an MSc in Cellular Parasitology (1992), and a BSc (Hons) Zoology (1990) all from the University of Ibadan, Nigeria. She teaches parasitology at the undergraduate and postgraduate levels. She was a recipient of a Commonwealth fellowship supported by British Council tenable at the Centre for Entomology and Parasitology (CAEP), Keele University, United Kingdom between 2004 and 2005. She was awarded an Honorary Visiting Research Fellow at the same university from 2005 to 2007. \nShe has been an external examiner to the Department of Veterinary Microbiology and Parasitology, University of Ibadan, MSc programme between 2010 and 2012. She is a member of the Nigerian Society of Experimental Biology (NISEB), Parasitology and Public Health Society of Nigeria (PPSN), Science Association of Nigeria (SAN), Zoological Society of Nigeria (ZSN), and is Vice Chairperson of the Organisation of Women in Science (OWSG), LASU chapter. She served as Head of Department of Zoology and Environmental Biology, Lagos State University from 2007 to 2010 and 2014 to 2016. She is a reviewer for several local and international journals such as Unilag Journal of Science, Libyan Journal of Medicine, Journal of Medicine and Medical Sciences, and Annual Research and Review in Science. \nShe has authored 45 scientific research publications in local and international journals, 8 scientific reviews, 4 books, and 3 book chapters, which includes the books “Malaria Parasites” and “Malaria” which are IntechOpen access publications.",institutionString:"Lagos State University",institution:{name:"Lagos State University",country:{name:"Nigeria"}}},{id:"273100",title:"Dr.",name:"Vijay",middleName:null,surname:"Gayam",slug:"vijay-gayam",fullName:"Vijay Gayam",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/273100/images/system/273100.jpeg",biography:"Dr. Vijay Bhaskar Reddy Gayam is currently practicing as an internist at Interfaith Medical Center in Brooklyn, New York, USA. He is also a Clinical Assistant Professor at the SUNY Downstate University Hospital and Adjunct Professor of Medicine at the American University of Antigua. He is a holder of an M.B.B.S. degree bestowed to him by Osmania Medical College and received his M.D. at Interfaith Medical Center. His career goals thus far have heavily focused on direct patient care, medical education, and clinical research. He currently serves in two leadership capacities; Assistant Program Director of Medicine at Interfaith Medical Center and as a Councilor for the American\r\nFederation for Medical Research. As a true academician and researcher, he has more than 50 papers indexed in international peer-reviewed journals. He has also presented numerous papers in multiple national and international scientific conferences. His areas of research interest include general internal medicine, gastroenterology and hepatology. He serves as an editor, editorial board member and reviewer for multiple international journals. His research on Hepatitis C has been very successful and has led to multiple research awards, including the 'Equity in Prevention and Treatment Award” from the New York Department of Health Viral Hepatitis Symposium (2018) and the 'Presidential Poster Award” awarded to him by the American College of Gastroenterology (2018). He was also awarded 'Outstanding Clinician in General Medicine” by Venus International Foundation for his extensive research expertise and services, perform over and above the standard expected in the advancement of healthcare, patient safety and quality of care.",institutionString:"Interfaith Medical Center",institution:{name:"Interfaith Medical Center",country:{name:"United States of America"}}},{id:"93517",title:"Dr.",name:"Clement",middleName:"Adebajo",surname:"Meseko",slug:"clement-meseko",fullName:"Clement Meseko",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/93517/images/system/93517.jpg",biography:"Dr. Clement Meseko obtained DVM and PhD degree in Veterinary Medicine and Virology respectively. He has worked for over 20 years in both private and public sectors including the academia, contributing to knowledge and control of infectious disease. Through the application of epidemiological skill, classical and molecular virological skills, he investigates viruses of economic and public health importance for the mitigation of the negative impact on people, animal and the environment in the context of Onehealth. \r\nDr. Meseko’s field experience on animal and zoonotic diseases and pathogen dynamics at the human-animal interface over the years shaped his carrier in research and scientific inquiries. He has been part of the investigation of Highly Pathogenic Avian Influenza incursions in sub Saharan Africa and monitors swine Influenza (Pandemic influenza Virus) agro-ecology and potential for interspecies transmission. He has authored and reviewed a number of journal articles and book chapters.",institutionString:"National Veterinary Research Institute",institution:{name:"National Veterinary Research Institute",country:{name:"Nigeria"}}},{id:"158026",title:"Prof.",name:"Shailendra K.",middleName:null,surname:"Saxena",slug:"shailendra-k.-saxena",fullName:"Shailendra K. Saxena",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRET3QAO/Profile_Picture_2022-05-10T10:10:26.jpeg",biography:"Professor Dr. Shailendra K. Saxena is a vice dean and professor at King George's Medical University, Lucknow, India. His research interests involve understanding the molecular mechanisms of host defense during human viral infections and developing new predictive, preventive, and therapeutic strategies for them using Japanese encephalitis virus (JEV), HIV, and emerging viruses as a model via stem cell and cell culture technologies. His research work has been published in various high-impact factor journals (Science, PNAS, Nature Medicine) with a high number of citations. He has received many awards and honors in India and abroad including various Young Scientist Awards, BBSRC India Partnering Award, and Dr. JC Bose National Award of Department of Biotechnology, Min. of Science and Technology, Govt. of India. Dr. Saxena is a fellow of various international societies/academies including the Royal College of Pathologists, United Kingdom; Royal Society of Medicine, London; Royal Society of Biology, United Kingdom; Royal Society of Chemistry, London; and Academy of Translational Medicine Professionals, Austria. He was named a Global Leader in Science by The Scientist. He is also an international opinion leader/expert in vaccination for Japanese encephalitis by IPIC (UK).",institutionString:"King George's Medical University",institution:{name:"King George's Medical University",country:{name:"India"}}},{id:"94928",title:"Dr.",name:"Takuo",middleName:null,surname:"Mizukami",slug:"takuo-mizukami",fullName:"Takuo Mizukami",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/94928/images/6402_n.jpg",biography:null,institutionString:null,institution:{name:"National Institute of Infectious Diseases",country:{name:"Japan"}}},{id:"233433",title:"Dr.",name:"Yulia",middleName:null,surname:"Desheva",slug:"yulia-desheva",fullName:"Yulia Desheva",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/233433/images/system/233433.png",biography:"Dr. Yulia Desheva is a leading researcher at the Institute of Experimental Medicine, St. Petersburg, Russia. She is a professor in the Stomatology Faculty, St. Petersburg State University. She has expertise in the development and evaluation of a wide range of live mucosal vaccines against influenza and bacterial complications. Her research interests include immunity against influenza and COVID-19 and the development of immunization schemes for high-risk individuals.",institutionString:'Federal State Budgetary Scientific Institution "Institute of Experimental Medicine"',institution:null},{id:"238958",title:"Mr.",name:"Atamjit",middleName:null,surname:"Singh",slug:"atamjit-singh",fullName:"Atamjit Singh",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/238958/images/6575_n.jpg",biography:null,institutionString:null,institution:null},{id:"252058",title:"M.Sc.",name:"Juan",middleName:null,surname:"Sulca",slug:"juan-sulca",fullName:"Juan Sulca",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/252058/images/12834_n.jpg",biography:null,institutionString:null,institution:null},{id:"191392",title:"Dr.",name:"Marimuthu",middleName:null,surname:"Govindarajan",slug:"marimuthu-govindarajan",fullName:"Marimuthu Govindarajan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/191392/images/5828_n.jpg",biography:"Dr. M. Govindarajan completed his BSc degree in Zoology at Government Arts College (Autonomous), Kumbakonam, and MSc, MPhil, and PhD degrees at Annamalai University, Annamalai Nagar, Tamil Nadu, India. He is serving as an assistant professor at the Department of Zoology, Annamalai University. His research interests include isolation, identification, and characterization of biologically active molecules from plants and microbes. He has identified more than 20 pure compounds with high mosquitocidal activity and also conducted high-quality research on photochemistry and nanosynthesis. He has published more than 150 studies in journals with impact factor and 2 books in Lambert Academic Publishing, Germany. He serves as an editorial board member in various national and international scientific journals.",institutionString:null,institution:null},{id:"274660",title:"Dr.",name:"Damodar",middleName:null,surname:"Paudel",slug:"damodar-paudel",fullName:"Damodar Paudel",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/274660/images/8176_n.jpg",biography:"I am DrDamodar Paudel,currently working as consultant Physician in Nepal police Hospital.",institutionString:null,institution:null},{id:"241562",title:"Dr.",name:"Melvin",middleName:null,surname:"Sanicas",slug:"melvin-sanicas",fullName:"Melvin Sanicas",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/241562/images/6699_n.jpg",biography:null,institutionString:null,institution:null},{id:"322007",title:"Dr.",name:"Maria Elizbeth",middleName:null,surname:"Alvarez-Sánchez",slug:"maria-elizbeth-alvarez-sanchez",fullName:"Maria Elizbeth Alvarez-Sánchez",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Universidad Autónoma de la Ciudad de México",country:{name:"Mexico"}}},{id:"337443",title:"Dr.",name:"Juan",middleName:null,surname:"A. Gonzalez-Sanchez",slug:"juan-a.-gonzalez-sanchez",fullName:"Juan A. Gonzalez-Sanchez",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Puerto Rico System",country:{name:"United States of America"}}},{id:"337446",title:"Dr.",name:"Maria",middleName:null,surname:"Zavala-Colon",slug:"maria-zavala-colon",fullName:"Maria Zavala-Colon",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Puerto Rico, Medical Sciences Campus",country:{name:"United States of America"}}},{id:"338856",title:"Mrs.",name:"Nur Alvira",middleName:null,surname:"Pascawati",slug:"nur-alvira-pascawati",fullName:"Nur Alvira Pascawati",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Universitas Respati Yogyakarta",country:{name:"Indonesia"}}}]}},subseries:{item:{id:"4",type:"subseries",title:"Fungal Infectious Diseases",keywords:"Emerging Fungal Pathogens, Invasive Infections, Epidemiology, Cell Membrane, Fungal Virulence, Diagnosis, Treatment",scope:"Fungi are ubiquitous and there are almost no non-pathogenic fungi. Fungal infectious illness prevalence and prognosis are determined by the exposure between fungi and host, host immunological state, fungal virulence, and early and accurate diagnosis and treatment. \r\nPatients with both congenital and acquired immunodeficiency are more likely to be infected with opportunistic mycosis. Fungal infectious disease outbreaks are common during the post- disaster rebuilding era, which is characterised by high population density, migration, and poor health and medical conditions.\r\nSystemic or local fungal infection is mainly associated with the fungi directly inhaled or inoculated in the environment during the disaster. The most common fungal infection pathways are human to human (anthropophilic), animal to human (zoophilic), and environment to human (soilophile). Diseases are common as a result of widespread exposure to pathogenic fungus dispersed into the environment. \r\nFungi that are both common and emerging are intertwined. In Southeast Asia, for example, Talaromyces marneffei is an important pathogenic thermally dimorphic fungus that causes systemic mycosis. Widespread fungal infections with complicated and variable clinical manifestations, such as Candida auris infection resistant to several antifungal medicines, Covid-19 associated with Trichoderma, and terbinafine resistant dermatophytosis in India, are among the most serious disorders. \r\nInappropriate local or systemic use of glucocorticoids, as well as their immunosuppressive effects, may lead to changes in fungal infection spectrum and clinical characteristics. Hematogenous candidiasis is a worrisome issue that affects people all over the world, particularly ICU patients. CARD9 deficiency and fungal infection have been major issues in recent years. Invasive aspergillosis is associated with a significant death rate. Special attention should be given to endemic fungal infections, identification of important clinical fungal infections advanced in yeasts, filamentous fungal infections, skin mycobiome and fungal genomes, and immunity to fungal infections.\r\nIn addition, endemic fungal diseases or uncommon fungal infections caused by Mucor irregularis, dermatophytosis, Malassezia, cryptococcosis, chromoblastomycosis, coccidiosis, blastomycosis, histoplasmosis, sporotrichosis, and other fungi, should be monitored. \r\nThis topic includes the research progress on the etiology and pathogenesis of fungal infections, new methods of isolation and identification, rapid detection, drug sensitivity testing, new antifungal drugs, schemes and case series reports. 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International Union of Microbiological Societies (IUMS) Fellow, and International Emerging Infectious Diseases (IEID) Fellow, Centers for Diseases Control and Prevention (CDC), Atlanta, USA. Diploma of Dermatological Scientist, Japanese Society for Investigative Dermatology. Ph.D. of Juntendo University, Japan. Bachelor’s and Master’s degree, Medicine, West China University of Medical Sciences. Chair of Sichuan Medical Association Dermatology Committee. General Secretary of The 19th Annual Meeting of Chinese Society of Dermatology and the Asia Pacific Society for Medical Mycology (2013). In charge of the Annual Medical Mycology Course over 20-years authorized by National Continue Medical Education Committee of China. Member of the board of directors of the Asia-Pacific Society for Medical Mycology (APSMM). Associate editor of Mycopathologia. Vice-chief of the editorial board of Chinses Journal of Mycology, China. 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