Utilization of smart breeding tools and techniques for crop improvement.
\\n\\n
Released this past November, the list is based on data collected from the Web of Science and highlights some of the world’s most influential scientific minds by naming the researchers whose publications over the previous decade have included a high number of Highly Cited Papers placing them among the top 1% most-cited.
\\n\\nWe wish to congratulate all of the researchers named and especially our authors on this amazing accomplishment! We are happy and proud to share in their success!
\\n"}]',published:!0,mainMedia:null},components:[{type:"htmlEditorComponent",content:'IntechOpen is proud to announce that 179 of our authors have made the Clarivate™ Highly Cited Researchers List for 2020, ranking them among the top 1% most-cited.
\n\nThroughout the years, the list has named a total of 252 IntechOpen authors as Highly Cited. Of those researchers, 69 have been featured on the list multiple times.
\n\n\n\nReleased this past November, the list is based on data collected from the Web of Science and highlights some of the world’s most influential scientific minds by naming the researchers whose publications over the previous decade have included a high number of Highly Cited Papers placing them among the top 1% most-cited.
\n\nWe wish to congratulate all of the researchers named and especially our authors on this amazing accomplishment! We are happy and proud to share in their success!
\n'}],latestNews:[{slug:"stanford-university-identifies-top-2-scientists-over-1-000-are-intechopen-authors-and-editors-20210122",title:"Stanford University Identifies Top 2% Scientists, Over 1,000 are IntechOpen Authors and Editors"},{slug:"intechopen-authors-included-in-the-highly-cited-researchers-list-for-2020-20210121",title:"IntechOpen Authors Included in the Highly Cited Researchers List for 2020"},{slug:"intechopen-maintains-position-as-the-world-s-largest-oa-book-publisher-20201218",title:"IntechOpen Maintains Position as the World’s Largest OA Book Publisher"},{slug:"all-intechopen-books-available-on-perlego-20201215",title:"All IntechOpen Books Available on Perlego"},{slug:"oiv-awards-recognizes-intechopen-s-editors-20201127",title:"OIV Awards Recognizes IntechOpen's Editors"},{slug:"intechopen-joins-crossref-s-initiative-for-open-abstracts-i4oa-to-boost-the-discovery-of-research-20201005",title:"IntechOpen joins Crossref's Initiative for Open Abstracts (I4OA) to Boost the Discovery of Research"},{slug:"intechopen-hits-milestone-5-000-open-access-books-published-20200908",title:"IntechOpen hits milestone: 5,000 Open Access books published!"},{slug:"intechopen-books-hosted-on-the-mathworks-book-program-20200819",title:"IntechOpen Books Hosted on the MathWorks Book Program"}]},book:{item:{type:"book",id:"1803",leadTitle:null,fullTitle:"Quality Assurance and Management",title:"Quality Assurance and Management",subtitle:null,reviewType:"peer-reviewed",abstract:"The purpose of this book is to present new concepts, state-of-the-art techniques and advances in quality related research. Novel ideas and current developments in the field of quality assurance and related topics are presented in different chapters, which are organized according to application areas. Initial chapters present basic ideas and historical perspectives on quality, while subsequent chapters present quality assurance applications in education, healthcare, medicine, software development, service industry, and other technical areas. This book is a valuable contribution to the literature in the field of quality assurance and quality management. 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The book is imagined as a comprehensive approach that will include all related topics and detailed information starting from production to consumption, composition of herbs and spices, and their contribution and mechanisms for treating various ailments, helping readers in making correct food choices for betterment of health and contribution towards a healthy society.
",isbn:"978-1-83969-609-1",printIsbn:"978-1-83969-608-4",pdfIsbn:"978-1-83969-610-7",doi:null,price:0,priceEur:0,priceUsd:0,slug:null,numberOfPages:0,isOpenForSubmission:!0,hash:"f95ecdf9c56db9567aa29b880dba5836",bookSignature:"Dr. Rabia Shabir Ahmad",publishedDate:null,coverURL:"https://cdn.intechopen.com/books/images_new/10907.jpg",keywords:"Herb, Spice, Functional Food, Essential Oil, Antioxidant, Health Benefit, Garlic, Cinnamon, Black Cumin, Tamarind, Curcumin, Clove",numberOfDownloads:null,numberOfWosCitations:0,numberOfCrossrefCitations:null,numberOfDimensionsCitations:null,numberOfTotalCitations:null,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"March 1st 2021",dateEndSecondStepPublish:"March 29th 2021",dateEndThirdStepPublish:"May 28th 2021",dateEndFourthStepPublish:"August 16th 2021",dateEndFifthStepPublish:"October 15th 2021",remainingDaysToSecondStep:"a month",secondStepPassed:!1,currentStepOfPublishingProcess:2,editedByType:null,kuFlag:!1,biosketch:"Dr. Rabia Shabir Ahmad won various research projects funded by Higher Education Commission (HEC) and was honored to receive the highest funded project under the National Research Programme for Universities (NRPU). 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She played an important role in the establishment and development of the Institute of Home and Food Science at GC University, Faisalabad, and developed and taught courses to graduate and post-graduate level students both in food science and technology, and human nutrition and dietetics. During her stay at the Government College University Faisalabad, she won various HEC-funded research projects and was also honored to receive the highest funded project under the NRPU scheme from HEC. Along with her teaching and research supervising responsibilities, she has also been working as the reviewer of several journals, and has published numerous research papers in highly impacted international and national journals. 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Venkateswarlu",coverURL:"https://cdn.intechopen.com/books/images_new/371.jpg",editedByType:"Edited by",editors:[{id:"58592",title:"Dr.",name:"Arun",surname:"Shanker",slug:"arun-shanker",fullName:"Arun Shanker"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"878",title:"Phytochemicals",subtitle:"A Global Perspective of Their Role in Nutrition and Health",isOpenForSubmission:!1,hash:"ec77671f63975ef2d16192897deb6835",slug:"phytochemicals-a-global-perspective-of-their-role-in-nutrition-and-health",bookSignature:"Venketeshwer Rao",coverURL:"https://cdn.intechopen.com/books/images_new/878.jpg",editedByType:"Edited by",editors:[{id:"82663",title:"Dr.",name:"Venketeshwer",surname:"Rao",slug:"venketeshwer-rao",fullName:"Venketeshwer Rao"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"4816",title:"Face Recognition",subtitle:null,isOpenForSubmission:!1,hash:"146063b5359146b7718ea86bad47c8eb",slug:"face_recognition",bookSignature:"Kresimir Delac and Mislav Grgic",coverURL:"https://cdn.intechopen.com/books/images_new/4816.jpg",editedByType:"Edited by",editors:[{id:"528",title:"Dr.",name:"Kresimir",surname:"Delac",slug:"kresimir-delac",fullName:"Kresimir Delac"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}]},chapter:{item:{type:"chapter",id:"49115",title:"Skull Base Endoscopic-Assisted Surgery",doi:"10.5772/60588",slug:"skull-base-endoscopic-assisted-surgery",body:'The neuroendoscopic technique has its roots in the early 20th century, applied at the beginning to treat hydrocephalus with cauterization or removal of the choroid plexus [1, 2]. Pure endonasal endoscopic resection of pituitary tumors became more popular in the 1990s, and skull base endoscopy has made timid advances since then. Increased development in skull base endoscopy occurred just before 2005 [3]. The new generation of neuroendoscopes allowed neurosurgeons to use them in the subarachnoid space and to use their excellent light quality and optical resolution in the depth during microsurgical procedures [1, 4].
Nowadays the neuroendoscope is used in different intracranial procedures as the main visualization tool or as an additional device. In modern skull base surgery, it has a significant supplementary value and has been used more and more frequently for different pathologies and in diverse occasions. Some advantages of the neuroendoscope for the skull base surgery are as follows:
Very good illumination
The possibility to demonstrate structures from a different angle (“look around the corner”)
Less invasiveness by reduction of approach size and retraction of structures
Different from intraventricular endoscopy, there are no preformed cavities in skull base surgery, and the need of retraction of structures is not infrequent. Vestibular schwannomas, cerebellopontine angle meningiomas, trigeminal neuralgia, epidermoid tumors, hemifacial spasms, and aneurysms are some of the skull base pathologies in which the endoscope can be helpful giving additional information on the target. The possibility of introduction of the tip of the endoscope into deep areas and the use of different angle scopes widening the field of view permit the reduction of surgical trauma during the approach, by reduced retraction of structures.
The endoscopic-assisted technique is becoming a very powerful method to be added to the armamentarium of neurosurgical technologies in skull base surgeries. This chapter provides a broad overview of the role of this technique in a wide spectrum of skull base diseases, starting with a historical perspective of the evolution of the use of the endoscope in skull base surgery and followed by the exploration in depth of the principles and techniques of the different surgical methods. In addition, the topic of “minimally invasive” skull base surgery using “keyhole” approaches and finally the learning curve and complications associated with the application of these new techniques is discussed.
The name endoscope comes from two Greek words — endon that means within and skopein that means to view [5]. Along the years, this visualization instrument has been used to look inside every natural opening and cavity in the human body.
At the beginning, the direct visualization inside of the bladder, female genital organs, or the digestive tract using a speculum was restricted to a few centimeters. The view into deeper cavities was restricted by the difficulty of illumination and poor visual quality. The son of Italian immigrants and born in Mainz, Germany, in 1773, physician Philipp Bozzini constructed at the beginning of the 19th century what may be considered as a rudimental endoscope. This equipment consisted of a speculum with two chambers — one for the transmission of light and the other one for the visualization. Bozzini called this instrument “Lichtleiter” what in German means “light conductor” [2].
After several improvements and developments of this equipment in Germany and Austria, the serial production of cystoscopes began in the United States at the beginning of the 20th century. The initial use of this technique in neurosurgery has its roots in the early 20th century. The urologist Victor Darwin L’Esspinasse and the neurosurgeon Allen Buckner Kanavel used for the first time an endoscope to perform the cauterization of the choroid plexus in two children with hydrocephalus in 1910 [1, 2].
Guiot et al. in Paris documented the first case of a pure transsphenoidal endoscopic resection of a pituitary tumor in 1962. This surgical technique became more popular, however, in the mid-1990s. After a short break, increased development of the endoscopy of the skull base could be observed again at the beginning of the 21st century. These advances were fruit of two important elements present at this time: technology and creativity [3]. Endoscopes with better light quality and capable of exceptional image reproduction allowed an excellent exposition of the deep surgical field in the skull base. New ideas and attempts to solve old problems as the restricted straight-line view of the microscope were responsible for additional discoveries in this field [1, 4].
Endoscopic skull base surgery techniques as the minimally invasive approaches, endoscopic-assisted surgery and full-endoscopic surgery are today in continuous development.
Advances of the neuroendoscopic equipment like the endoscope-integrated near-infrared indocyanine green video angiography for aneurysm surgery and the continuously variable-view rigid endoscope with possibility to alternate the view angle without the necessity of changing the scope just as well contribute to the rapid progress of skull base endoscopy [6-8]. In the same way, the combination with other known methods as robot-assisted neuroendoscopy and neuro-navigated endoscopy propel the progress of this technique.
Skull base surgery comprises the treatment of several pathologies that are located or have their source in the most inferior part of the cranial cavity. Because of the complex anatomy and important structures, approaches and operations in this region have always been challenging. Tumors, aneurysms, and neurovascular conflicts are the most frequent pathologies treated in this area. During the last decades, important developments in the skull base surgery were responsible for substantial reductions in the morbidity and mortality. Advancements of the intraoperative neuromonitoring, microsurgical techniques, and new imaging modalities were some of these developments [9]. The use of the endoscopic technique in this region began later on and is gradually increasing.
Skull base pathologies may be very complex and the decision of the right treatment is not always so evident. In some cases, there is little or no doubt about what should be done. However, in many of these patients, different therapy options or no therapy at all (“wait and see”) should be considered. So that the best advice may be given to a patient, the physician must have the knowledge concerning the natural history of the disease and also be up-to-date about the current and new treatment alternatives [10].
The goal of every medical treatment is of course the well-being of the patient. To achieve that, some objectives as tumor complete resection, partial resection, or simply biopsy for eventually further radio- or chemotherapy should be considered in different situations [11]. The skull base surgery aim should be very well analyzed in every case and the expectations of the patient need to be considered for the final decision of the therapy strategy.
The main objective during the surgery of tumors in this region is the complete removal with preservation of function provoking as little physical and mental pressure as possible to the person being treated. If total resection is not possible or represents a great risk of impairment of important functions as in some cases of sphenoid wing meningiomas, large vestibular schwannomas, or petroclival meningiomas, cytoreductive surgery as preparation for radiotherapy should be considered [12, 13]. In certain cases of elderly or, for example, patients with neurofibromatosis type 2, purely decompression may be the main goal of the operation [12, 14].
In most cases, however, the final goal is to achieve a complete tumor resection, aneurysm clipping, or neurovascular decompression with total neurovascular function preservation and minimal patient stress.
The clinical presentation of skull base pathologies is very variable, depending on the nature and location of the underlying cause. Cranial nerve dysfunction, cerebellar symptoms, hydrocephalus (e.g., in tumors of the posterior cranial fossa obstructing the 4th ventricle), and thunderclap headache (in patients with subarachnoid hemorrhage after aneurysm rupture) are some of the possible presentations. Furthermore, a considerable number of patients with a skull base disease are referred to a neurosurgical department with no complains and an incidental finding. The actual patient’s complains and results expectations should be considered during decision and planning of the most appropriate treatment modality.
As said before, skull base pathologies are much diversified. The ideal image method should be elected depending on the current questions for each case.
Magnetic resonance imaging (MRI) is useful in almost every case due to its magnificent ability to demonstrate soft tissues. The routine T1-, T2-, and T1 with endovenous contrast injection-weighted images should be obtained in all three planes — axial, coronal, and sagittal — so that an accurate study of each case can be carried out. The fluid-attenuated inversion recovery (FLAIR) is a pulse sequence using an inversion recovery technique that nulls fluids. It is very sensitive to edema and some parenchymal abnormalities and can be used to indirectly demonstrate lesions that are not evident in other sequences. Diffusion weighted imaging (DWI) sequences are useful in differentiating epidermoid tumors, that are hyperintense due its solid composition), from arachnoid cysts shown hypointense, demonstrating high diffusivity. Some authors still report about the importance of this sequence during the assessment of clival tumors, particularly in differentiating chordoma from chondrosarcoma [15]. The gradient echo sequence provides information about hemoglobin breakdown products and calcifications [16].
Computed tomography (CT) scan is the image of choice for demonstrating bony structures. Before surgeries involving the internal auditory canal (IAC) or sella, for example, a thin-layer CT scan is mandatory. Also during surgery of sphenoid wing meningioma with bone involvement or when using the supraorbital approach, a CT scan may be valuable. Preoperatively, the evaluation of several aspects is important:
Disposition of the bony labyrinth (vestibule, semicircular canals, and cochlea) before drilling of the IAC and avoiding injury of these structures
Disposition and height of the jugular bulb in relation to the posterior wall of the IAC
Extension of the pneumatization of the mastoid cells during suboccipital craniotomy and opening of the IAC’s posterior wall
Location of the emissary vein during suboccipital craniotomy
Location of the frontal sinus when using the supraorbital approach
Configuration of the sella and sphenoid sinus during surgery of intra-, para-, and suprasellar lesions
Extension of bone infiltration by tumors such as sphenoid wing meningioma and others
Preoperative computed tomography angiography (CT-angiography) is useful in some cases, demonstrating tumor blood supply and patency of sinuses, veins, and arteries. Tridimensional representation of aneurysm configuration and its relationship with parent, branching, and perforating arteries is likewise helpful in selected circumstances when conceiving the surgical strategy.
Angiography is losing ground to CT-angiography and magnetic resonance angiography but is still the gold standard image method for aneurysm, arteriovenous malformation, and dural arteriovenous fistula evaluation before surgery.
Cervical spine x-ray should be performed preoperatively to rule out gross deformities depending on the patient positioning chosen. If there is necessity of extreme rotation, flexion, or extension of the head as in the semi-sitting position, for example, a cervical study prior to surgery may avoid major injuries.
Preoperative planning is a very important “part of the surgery.” Previous and meticulous study of images to understand the individual anatomy of each patient should be performed. Planning of surgery should start with choosing the best craniotomy site and the optimal trajectory to the desired spot. Reachability and view angle using microscope and different angled endoscopes should be taken into consideration. Recognition of anatomical variations and the neurovascular relationship is important to achieve the surgical goal with minimal effort and without undesirable surprises. The comprehension of aneurysm configuration or exact tumor extension when analyzing images before surgery reduces intraoperative time and fulfills surgeon and staff.
There are several situations in skull base surgery in which the use of the endoscope may supplement the traditional microscopic visualization technique. Endoscopy may, in these surgeries, commonly enhance the exposure of the operative field and frequently provide new information for the surgeon [17-22]. In the authors’ experience, benefits of this visualization technique are noted especially in cases in which important neurovascular structures constitute a hindrance for the straight-line view of the microscope or in cases with a narrow surgical corridor and “keyhole” approaches (e.g., supraorbital approach, retrosigmoidal approach, etc.). Situations in which it is important to have a lateral view as in lesions invading the IAC, for example, are another interesting indication for this technique. Because of the high definition images delivered and the proximity of the endoscope tip to the region observed, superior exposition of surface texture may help in differentiating some lesions from normal tissue.
Surgical clipping is still the most complete treatment alternative for intracranial aneurysms [19, 23, 24]. Aneurysm complete exclusion of the circulation after clipping without occlusion of parent, branching, and perforation vessels is the main goal of the surgical therapy. Large series reported incidences of unexpected residual filling and parent artery occlusion after clipping 4–19% and 0.3–12%, respectively [19, 23]. With the continuous advances in endovascular technologies for the treatment of aneurysms, patients undergoing coiling have increased considerably [25]. Reduction of undesirable and preventable events is essential to support that the surgical technique remains as a reliable treatment alternative [19].
The gold standard examination for evaluation after aneurysm clipping is still the intraoperative digital subtraction angiography (DSA). Routine intraoperative DSA is however not available in most centers [19]. New techniques to better expose and understand the aneurysm anatomy and parent and branching vessels’ configuration intraoperatively as the near-infrared indocyanine green video angiography (ICG-VA) and microvascular Doppler sonography (mDs) have been developed. A study in 2010 analyzing both techniques concluded that the methods are complementary and the drawbacks could be compensated by each other. In this report, when both techniques were simultaneously used, 90% of all aneurysms could be correctly evaluated. If only one of these techniques was used, evaluations were correct in about 80% of the cases [23]. These intraoperative techniques have also some weak points. Blood flow assessment in small perforators is not possible using the mDs and illumination deep in the surgical field may be deficient during ICG-VA when small craniotomies are performed [23]. Particularly, because of the straight-line view of the microscope, these techniques have the limited capacity to expose areas behind vessels or the aneurysm sac. To overcome this situation, a mirror or a high-definition image endoscope may be used.
Endoscopy has several advantages (definition, magnification, etc.) in comparison with a simple micromirror during aneurysm surgery. It has been used in different stages of surgery and presented to be safe and effective diminishing unexpected findings as incomplete aneurysm occlusion or parent vessels’ compromise in large series reports [19, 26, 27]. About a lower retraction of the nervous structures and reduced morbidity has also been reported [26].
The decision of whether or not to use the endoscope should be based on the preoperative imaging. If this reveals an intricate anatomy, endoscope set and tower should be prepared for possible application. Intraoperative, insufficient exposure of perforators and/or aneurysm anatomy is an indication for the endoscopic-assisted surgery.
The cerebellopontine angle (CPA) is a complex region of the skull base, with elaborated neurovascular structures and little space. Tumors growing in the CPA tend to disturb cranial nerve functions, brainstem, cerebellum, and eventually cerebrospinal fluid circulation. Different tumors incurring in this location present different behaviors, infiltrating, pushing, or adhering to important structures. Some lesions “create space,” pushing structures and sometimes facilitating the approach. Epidermoid tumors, for example, frequently spread around cranial nerves, arteries, and veins invading recesses and corners making complete tumor resection under the straight line view of the microscope difficult, sometimes impossible. Use of endoscopy additionally to the microscope enables a safe removal of such tumors, reduces the extra retraction of nerves and vessels, and eliminates the necessity of enlarging the craniotomy in some cases [22].
The use of the endoscopic-assisted technique during the removal of epidermoid tumors of the posterior fossa is recommended in almost all cases because of the growing behavior of these lesions.
Vestibular schwannomas are benign tumors that generally arise from the vestibular portion of the vestibulocochlear nerve. The region where this tumor grows (Obersteiner–Redlich zone), where the nerve covering myelin changes from central to peripheral type, is close to the opening of the internal auditory canal (IAC) [28]. Dandy considered, in 1941, that surgery of these tumors was the most difficult of all neurosurgical procedures [29]. Resection of these kinds of lesions is still nowadays frequently not easy. One reason for that is the invasion of tumor in the IAC. Visualization of the whole resection area of intrameatal tumors using the microscope is usually just possible after opening the posterior meatus wall. In several cases, the opening of the IAC is not sufficient by risk of damage to the vestibular system and cochlea. By some patients, with high jugular bulb, the complete opening of the IAC is difficult or, sometimes, nearly impossible. Because of the histological benign behavior of this tumor, complete tumor resection with preservation of neurovascular structures and their function is in most cases the aim of surgery.
The capability of the wide view angle of the endoscope associated to the superb illumination of the field enables a deeper exposure of the IAC and eventually residual tumor after resection under microscope view [18, 30-34].
Endoscopy is indicated in cases with deep intrameatal seated vestibular schwannomas, far medial placed labyrinth structures, and high jugular bulb.
Microvascular decompression (MVD) is an important alternative in the treatment of trigeminal neuralgia and hemifacial spasm. Other neurovascular compression syndromes, such as disabling positional vertigo, tinnitus, and glossopharyngeal neuralgia may also, sometimes, be treated through this surgical option [35]. Several vessels may be responsible for the neurovascular conflict. Arteries and also veins can be compressing the nerve. The neurovascular conflict usually occurs at the root exit or entry zone, but compression of the trigeminal nerve distally in Meckel’s cave has been described as well [35].
The incidence of identification of a neurovascular conflict during MVD using the microscope oscillates between 25% and 98% in large series [35-37]. The reason of the inability to recognize a neurovascular conflict could be a negative exploration, as the probability to find the site of nerve compression increases with the surgeon’s experience [35, 36]. Insufficient visualization of the root exit zone in Meckel’s cave or an incomplete view of the inferior and anterior aspect of the trigeminal nerve were also described as a possible reason for a negative exploration during decompression [35].
The use of endoscopy in MVD surgeries has already been described by some authors in the literature [35, 36, 38, 39]. In these cases, a recognition of 100% of the site of compression was reported [35, 36, 38, 39].
During surgeries of neurovascular compression syndromes, the use of endoscopy is specially indicated in cases with unclear or poor exposure of the neurovascular conflict.
The neurosurgical approach to deep seated intraparenchymal lesions of the cerebellum and particularly of the brainstem should be kept as small as possible to avoid unnecessary injuries. Because of the balloon-like shape frequently assumed by the resection cavity, the whole operative field view is not always possible using the straight-line view of the microscope. In these cases, an incomplete resection of the lesion with the microscopic vision may occur. Bertalanffy et al. described in 1991 about the increased risk of a secondary hemorrhage after incomplete resection of deep-seated brainstem cavernomas. In this series, residual cavernous hemangioma induced bleeding in two cases [40]. The use of an endoscope may be useful decreasing the deficit of the microscope during the exposure of a cavity though a small opening. This technique can help the surgeon, peculiarly in cases of cavernous hemangiomas and hemangioblastomas. The use of endoscopy should be indicated in cases of deep seated brainstem and cerebellum lesions and by the existence of a small resected cavity.
Surgery of skull base meningiomas is challenging. The frequently demanding approach, the close relation with important neurovascular structures, and the possible involvement of bone are some of the adversities found during the surgical treatment of this disease. Not rarely, bone, dura mater, vessels, and cranial nerves are superposed to tumor parts and restrict the straight-line view of the microscope [41]. The endoscopic-assisted microsurgery technique is an advantage for skull base meningioma surgery in the hand of experienced surgeons. Use of different angled endoscopes may reduce craniotomy size, skull base drilling, and brain retraction in selected cases [41].
Reasons for employing the endoscope during surgery of skull base meningiomas are the intricate relationship of tumor with neurovascular structures, deep seated lesions, and inadequate exposure of the anatomy because of an insufficient angle of view, small craniotomy, and preoperative images revealing possible blind corners.
The first step before treatment of a skull base pathology is the individual understanding of the disease, patient’s anatomy, and patient’s expectations. By means of a careful imaging examination and recognition of the relationship of important anatomical structures, possible pathways and eventual pitfalls as well as the understanding of the clinical presentation and patient’s expectation, the decision for the best treatment choices can be made.
Whether or not to use the endoscope initially, during or at the end of surgery for inspection may be determined by the pathology or preoperative image findings. There are different endoscopic-assisted techniques available, and the most appropriate should be chosen depending on the needs of each case. Some of these endoscopic-assisted surgical alternatives for the treatment of skull base pathologies are discussed in the following text.
The endoscopic technique during aneurysm clipping should always be used in combination with the standard microscopic visualization so that benefits of both methods may represent an advantage (Fig. 1). The endoscopic-assisted surgical technique may be used in different situations during aneurysm clipping:
Inspection of the aneurysm anatomic and topographical configuration as well as of its surroundings
Clipping under endoscopic view, when the approach is limited (e.g., supraorbital keyhole approach)
Post-clipping evaluation, checking for complete occlusion, parent vessel, or perforating artery occlusion or restriction [19]
Use of this technique showed to enhance the completeness of aneurysm occlusion and diminish compromise of involved vessels in a large study series [19].
Endoscopic view during inspection of a basilar artery aneurysm before clipping and exposure of the surgical field through the left opto-carotid window and a pterional approach. III, oculomotor nerve; PCA, posterior cerebral artery; SCA, superior cerebellar artery; BA, basilar artery; A, aneurysm sac. (Klinik fuer Neurochirurgie—Universitaet des Saarlandes—Prof. Oertel/Dr. Montibeller)
A novel technique with the endoscopic near-infrared indocyanine green video angiography (ICG-VA) was developed. The aim of this new method is to compensate the weakness of the traditional microscope ICG-VA in the evaluation of vessels located in the depth of the surgical field particularly through small craniotomies. The first results of the comparison of both methods in 40 cases revealed that in 27.5% of cases the endoscopic ICG-VA provided better results for the evaluation of the post-clipping situation. Prevention of neck remnant or branch occlusion could be prevented in four cases, changing the surgical procedure [6].
Endoscopy may help in different situations maximizing the exposure of the surgical field during operations in the CPA. The deepness of this region and the complexity of its neurovascular anatomy represent an obstacle to the straight-line view of the microscope. Use of the endoscope in the CPA should, also because of that, be performed by experienced hands. We advocate that insertion of the endoscope in the posterior fossa should always be performed under microscopic view. After initial orientation, the surgeon’s sight may switch to the endoscopic monitor.
Changes between angled endoscopes should be performed to offer the optimal exposition for different situations. It is very important to pay attention to the direction of the insertion of the endoscope, especially when using angled optics. With the angled view, the direction of movement is not the same of sight. Depending on the angle of the optic used and the angle of view, the trajectory of positioning may eventually not be seen with the endoscope.
Because of the narrowness of this region, lens blurring is a frequent problem encountered during inspection. To prevent this issue, the suction tip can be held close to the endoscope tip. This reduces the moisture and keeps the lenses dry. Cleaning of lenses with warmed-up water also helps to minimize this undesirable situation.
Endoscopy may be useful during surgery of tumors invading the IAC (Fig. 2). Especially those with a deep extension inside the canal. The endoscope revealed to be helpful finding residual tumor in 11.1–48.1% of selected cases after microscopic resection during vestibular schwannoma surgery [18, 21, 31-34, 42]. An advantage could also be seen during surgery of other tumors invading the IAC [17]. The capability to look further inside the IAC even before opening it in comparison with the microscope has been proven in cadaveric studies [30].
Endoscopic view of the opened internal auditory canal after microscopic resection of a small intrameatal vestibular schwannoma at the right side in semi-sitting position. Detection of intrameatal residual tumor (arrow) due the angled view of the 30° endoscope. VIII, vestibulocochlear nerve. (Klinik fuer Neurochirurgie—Universitaet des Saarlandes—Prof. Oertel/Dr. Montibeller)
The recognition of the facial nerve was facilitated and it could be identified in the early stages of the dissection of vestibular schwannomas using the “look around the corner” technique [32].
Identification of opened air cells minimizing the chance for postoperative cerebrospinal fluid fistula may be another advantage of the endoscopic-assisted technique [31, 43].
Because of the extended view delivered through endoscopy, drilling of the posterior wall of the IAC in cases of a medially placed labyrinth or high jugular bulb may be reduced [30, 44].
The advantages of the endoscopic-assisted technique during MVD have been described by many authors [17, 35, 36, 38, 39]. The endoscope may be used to inspect the trigeminal and facial nerve root as well as Meckel’s cave. This technique may help to identify the compression site, find multiple spots of neurovascular contact, and confirm decompression at the end of surgery [17].
Fully endoscopic MVD has also been described with good results [45].
By surgery of tumors of the anterior cranial fossa, the endoscope may also be useful during inspection before and after microscopic resection. Especially in cases of olfactory groove meningiomas, endoscopy may play a role accessing the integrity of the olfactory nerve.
Introduction of the endoscope inside small resection cavities of brainstem or cerebellum may provide an advantage for the inspection of the whole wall of the cavity and rule out bleeding spots or residual tumor after microscopic resection.
Special microsurgical instruments and technique are necessary as well as microsurgical experience. Changing the views between microscope and endoscope requires attention of the surgeon and his assistant. Several modalities of observing the endoscopic and microscopic images at the same time have been described [4]. Alternating between oculars of microscope and the video screen of the endoscopy, numerous variations may be possible. We use the oculars of the microscope for the microscopic image and a video screen placed in front of the surgeon to display the endoscopic image (Fig. 3). The position of equipment and staff in the operating room is very important so that the surgeon is able to move in an ergonomic or user-friendly way maximizing his coordination. An example with a possible distribution is seen in Fig. 4.
Endoscopic-assisted technique showing the introduction of the endoscope in the surgical field by the surgeon under microscopic view (a) and the position of the endoscope screen (b). (Klinik fuer Neurochirurgie—Universitaet des Saarlandes—photograph of the department: Ruediger Koop)
Possible distribution of equipment in the operation theatre providing a user-friendly movement of the surgeon. M: microscope, E: endoscope screen, N: neuronavigation screen. (Dr. Erasmo Barros da Silva Junior)
Neuroendoscopy may offer several advantages in selected cases of skull base surgery in comparison with the microscope. The better illumination of the field due to the proximity of the endoscope tip to the tissue and the high definition images delivered by the new generation equipment offer an excellent visualization of the surgical field. Also, the different perception of tissue texture is observed when both techniques are compared. The expanded view angle and different possible “looks” using a movable instrument is of course also a benefit in some skull base surgeries with a complex anatomy. Reduced tissue mobilization and the necessity of retraction of important structures as well as reduced trauma are a consequence of the different view angle capability of the neuroendoscope when compared with the microscope. Finding additional information at target in some skull base surgeries is obviously a great benefit of the endoscopy. In the authors’ experience, most of this technique during skull base surgery in the actual days may be achieved when using both techniques, microscope and neuroendoscope, together as supplementary and additive devices.
Some disadvantages of the endoscope when compared with the image delivered by the microscope are as follows:
Inferior 3D-perception of the images. Compensated with surgeon’s experience time but cannot be set side by side with the microscope, at least not with the current technology. New 3D-endoscopes are in development and trying to improve this issue.
Distortion of images is another issue that should be considered a disadvantage of the endoscopic images. Especially in deep areas, images get deformed in size. Angled endoscopes also distort the images that are distant from the tip [30].
Time consuming — Gerganov et al. analyzed the additional time for the use of this technique during the removal of vestibular schwannomas and concluded that 15–20 minutes extra time was needed in the operating theater applying the endoscope [13]. We believe it is very difficult to exactly calculate the additional time needed for the use of this technique. Some information given through endoscopy may even shorten the operative time. Particularly, only one case with complete tumor removal instead of leaving remnant tumor behind will justify any additional surgical time. If the endoscopic equipment is prepared and set in standby in every skull base surgery, undesirable waste of time may be avoided.
Some authors also reported about the complications and limitations of this technique [22, 34, 41, 46, 47]. The use of endoscopy during skull surgery may correlate with iatrogenic damage of nerves and vessels [46]. Hori et al. reported about the injury of the facial nerve during inspection with the endoscope in one case of a series [34].
The risk of using this instrument, especially with the 30°, 45°, and 70° angulated optics should be kept in mind. With angulated scopes, it is not always easy to know where the tip of the instrument is and the introduction of this tool in the operative field should be performed under microscopic view.
Vestibular schwannomas, trigeminal schwannomas, epidermoid tumors, hemifacial spasms, cerebellopontine angle meningiomas, anterior fossa meningiomas, and aneurysms between others are some of the skull base pathologies with which the endoscope can be helpful giving some additional information on the target. The neuroendoscope is usually used for inspection of the situs and not as the main source for imaging. In a few selected circumstances, endoscopic-assisted surgery present a benefit in comparison with the microscope and can be used during the preparation of structures, resection of tumors (e.g., intrameatal vestibular schwannoma or epidermoid tumor), or clipping intricate aneurysms.
Endoscopy in microsurgical removal of vestibular schwannomas may be useful, especially in cases with small deep intrameatal tumors and of high-positioned jugular bulb. Inspection of the fundus of the internal auditory canal may permit the identification of eventual remnant tumor.
In epidermoid tumors, endoscopic inspection, and endoscopic-assisted tumor resection are of great value, particularly in the posterior fossa, finding remnant tumor and reaching difficult and delicate areas. In epidermoid tumor surgery of the cerebellopontine angle, when remnants are not visible in a straight line, the endoscope-assisted technique can contribute to safe tumor removal. It also allows the resection of tumor extensions without retracting neurovascular structures or enlarging the craniotomy.
In trigeminal neuralgia, the endoscope may help when the neurovascular conflict cannot be identified using the straight-line view of the microscope.
In aneurysm surgery, endoscopy is especially useful in deep-seated lesions and in aneurysms with suspicion of perforators on their backside. In some cases, additional information on aneurysm occlusion and on the patency of parent, branching, and perforating arteries can be gained.
The possibility of introduction of the tip of the endoscope into deep areas and the use of different angle scopes widening the field of view permit the reduction of surgical trauma during the approach, by reduced retraction of structures. Discovery of additional information at target, however, is certainly the principal advantage of this tool. Novel indications for endoscopy in the skull base surgery are growing fast and different uses of this device are being tested.
The authors thank Mr. Ruediger Koop for the nice pictures exposing the real surgical situations using the endoscopic-assisted technique and Dr. Erasmo Barros da Silva Junior for his attractive illustration of the ergonomic equipment distribution in the operating room.
Joachim Oertel acts as consultant for Karl Storz Company. Thank you for your cooperation!
Land is shrinking but world population is increasing in a rapid phase, so, modern agricultural practice is struggling to meet the level of primary productivity required to feed approximately 10 billion people by 2050 [1]. From last few decades the adverse effects of climate change and higher CO2 concentrations, the consequence of expected impacts on the water-use efficiency of dryland as well as irrigated crop production, potential effects on biosecurity, production, and quality of product through increased the frequency of introduced various abiotic (heat, salinity and drought) and biotic stresses (pests and diseases). In addition, climate change is also expected to cause losses of biodiversity, mainly in more marginal environments. Drought alone is expected to reduce crop productivity in half of the global arable land and it’s estimated around 50% in the next five decades [2]. It has been predicted that, on average, global yields of major economic important crops will be reduced by the unfavorable climatic conditions in wheat (6.0%), rice (3.2%), maize (7.4%) and soybean (3.1%) for every degree celsius increase in global mean temperature [3].
Climate resilience is an ability of the plant/crop to survive and recover from the effects of climate change. Some important practices that may help to adapt the climate change are soil organic carbon build up or carbon sequestration, in-situ moisture conservation, residue incorporation instead of burning, water harvesting and recycling for supplemental irrigation, growing biotic and abiotic resistance/tolerant varieties, location specific agronomic and nutrient management and breeding for multiple traits of interest including quality.
Plant Breeding has always played a pivotal role in human history from revolutionizing agriculture to feed the ever-growing population. The key role of plant breeding in agriculture is to develop a genetically superior genotype/variety, which is suitable for a specific as well as general cultivation of particular environment towards higher production [4]. Realizing the importance of genomic resources to expedite the breeding programs, huge amount of genetic data related to genes and QTLs (Quantitative Trait Loci) are generated after the advent of molecular biology and biotechnology [5]. The progress in precise phenotyping and genotyping offers tremendous opportunities to develop crop varieties that are suit for better changing the climatic conditions, which ameliorate in boosting the plant breeding activities for developing climate resilient varieties/cultivars [6]. Hence, development of climate resilient varieties utilizing Smart breeding tools to ensures the food security in adverse climatic conditions.
The effect of climate on agriculture is related to variability’s in local climates rather than in global climate patterns. The changes in the rainfall patterns, temperature, CO2 level and greenhouse gases resulting in the frequency and severity of extreme events such as flooding, drought, hail, and hurricanes etc. are major hindrance in achieving the food security for ever increasing population [7].
According to Intergovernmental Panel on Climate Change (IPCC), global temperature may be rise from 1.7 to 4.8°C during the twenty-first century and precipitation pattern will also be altered [8]. In recent times, it has been reported that the Yangtze river basin in China has become hotter and it is expected that the temperature will increase up to 2°C by 2050 relative to 1950 [9], and also reduce the rice (41%) and maize (50%) production by the end of the 21st century. This shift in climate will affect the environment, including the soil ecology and thus has the potential to threaten food security through its adverse effects on soil properties and processes [10]. Additionally, the direct and indirect effects of climatic change would lead to alter the nutrient and their bioavailability in soils (Figure 1). The effect of climate changes on biotic and abiotic stresses have already reduced the global agricultural production from 1 to 5% during the past three decades [11].
Adverse effects of climate change on agriculture and food production.
Some important practices that assist to adapt the climate changes for crop production including (i) Building resilience in soil (tillage management, avoid bare soil, fertilizer application after mandatory soil testing, increase soil carbon through organic manure, green manuring, crop rotation or intercropping with legume sequester carbon and biochar), (ii) Adapted cultivars and cropping systems (crop diversification, shallow-deep root and legume-cereal cropping system, improved early/short duration cultivars for tolerant against drought, heat and submergence capturing optimum yields despite climatic stresses), (iii) Rainwater harvesting and recycling (inter-row water harvesting, inter-plot water harvesting, in farm ponds and reservoirs and recycling), (iv) Farm machinery (chisel and para plow to opening the furrows which conserves rain water, laser leveler helps in increasing nutrient as well as water use efficiency), (v) Crop contingency plans (livestock and fishery interventions), (vi) Weather based agro advisories (automatic weather stations establishment at experimental farms and mini-weather observatories records for real time weather parameters such as rainfall, temperature and wind speed, which customized through agro advisories and improve weather literacy among the farmers).
Plant breeding procedures have been constantly evolving to meet the increasing food demand. The art of plant breeding has been practiced in various forms since the start of human civilization. In conventional plant breeding, development of a new cultivar take around 10–14 years and may even exceed this period based on the plant habit, reproductive cycle and complexity of traits involved. The rapid climate change necessitates the development of varieties in a shorter period to tackle with the unpredictable weather parameters. The concept of Smart breeding is an integration of conventional breeding strategies with advanced molecular, genomic and phenomic tools to efficiently and effectively breed the resilient crop cultivars with enhanced yield potential. New breeding approaches such as rapid generation advancement, doubled haploid (DH), marker assisted back crossing (MABC), marker assisted recurrent selection (MARS), genomic selection (GS) etc. have been used to help shorten the breeding cycle along with efficient screening for specific biotic and abiotic stresses. Biotechnology-based breeding technologies (marker-assisted breeding and genetic modifications) will be essential to assist and accelerate genetic gain, but their application requires additional investment in the understanding, genetic characterization and phenotyping for complex adaptive traits to be exploited for climate resilient breeding.
Climate change leading to severe weather fluctuations would also lead to evolution of plant diseases and pests, exposing crops to higher biotic pressure in addition to abiotic stresses. To make crop adaptation feasible in the era of changing climate, there is indispensible need to breed the crop plants with diverse genetic backgrounds. In order to feed the mushrooming population, there is urgent need to use crop wild relatives for developing broader spectrum varieties to tackle various biotic and abiotic stresses. During the era of domestication, selection preferences lead to modern crops with narrow genetic background, resulting in limitation of environmental adaptation and breeding capacity using modern germplasm [12]. Wild relatives and ancestral species relatively possess broader adaptation to environment and climates ultimately higher potential in crop improvement.
Prebreeding activity is a bridge for linking the desirable traits of CWR to the modern cultivar development by providing breeders with wild genetic diversity in a more immediately usable form [13, 14]. Pre-breeding is an opportunity to introgression of desirable genes, from wild species (primary, secondary and tertiary gene pools) into elite breeding lines/cultivars/genotypes, to overcome the linkage drag (Figure 2). Almost all cultivated crop species were originally domesticated from wild plants by humans, due to domestication inherently reduced the genetic variation [15]. The genetic potential of wild relatives has been reported in different crops like rice, wheat, maize, potato, tomato, cotton, tobacco, sugarcane, chickpea and pigeonpea [16, 17, 18, 19, 20, 21].Genomics strategies have been widely utilized in staple crops for transferring major genes (i.e. disease resistance) from wild germplasm to elite cultivars [22]. It is well documented that application of molecular mapping and sequencing to could be useful to unlock the genetic potential of CWR [23]. So, crop wild relatives (CWRs) are good reservoir of untapped genetic diversity, which may not exist in the cultivated gene pool that can be used to improve the numerous trait of interest including resistance/tolerance against diseases, insect-pests, drought, salinity, cold, heat and good agronomic adaption with quality improvement.
Untapped genetic resources/ CWRs towards the germplasm enhancement.
Wild species are used mainly for the introgression of disease and insect resistance into crops although drought, cold, heat and salinity tolerance have also been addressed in some staple crops. This is because most pathogens have faster adaptation to climate rendering cultivars vulnerable to novel deadly diseases [24]. The use of interspecific or intergeneric hybridization for disease resistance introgression is conventional one. Another potential technique to enhance genetic diversity and facilitate crop vigor with adaptation to different environmental niches is creating the polyploidy crops mimicking natural evolution through hybridization [25]. Enriched genes for biotic and abiotic stress resistance of CWR can be studied using comparative pool sequencing of genome assemblies, elucidating the potential genomic segments responsible for adaptation to different ecological niches. These have been explored in wild relatives of many crops including chickpea, barley and maize [26, 27, 28, 29].
To address the diversity within species, pan-genomics based on entire gene repository of a species can reveal the genetic variations such as structure variants (SVs) and single nucleotide polymorphism (SNPs) abundantly found in plants. One such example under SVs is presence/absence variants (PAVs) of Elicitin response (ELR) gene between wild and cultivated potato leads to resistance/susceptibility response to late blight disease [30]. Larger pan-genomes including both wild relatives and cultivars can acquire glut 0f dispensable genes resulting in phenotypic variations; thereby easing out with characterization of the trait associated genomic variants [31]. To tackle the deadly rust diseases in wheat in the context of changing climate, several pan-genomic R genes have been successfully identified and cloned from wild diploid wheat Aegilops tauschii [32].
Considering the risks of introducing foreign alleles into cultivars, other potential technique for developing climate-friendly crops is de novo domestication [33]. As most staple crops are grown majorly in the regions other than where they were originally domesticated with different climatic regimes. Nevertheless, their wild relatives and landraces exhibit better adaptation to local climate in the native regions. In the scenario of climatic change, there is chance to leverage this opportunity to use those underutilized or orphan crops e.g. rise in Sinapis alba (white mustard) acreage replacing the B. napus in Europe for biofuel production [34]. A pipeline strategy has been proposed for domestication of wild germplasm in some orphan crops such as quinoa [35]. In addition to direct planting of non-domesticated crop plants, relatively advance methodology of CRISPR/Cas9 boosts the wild germplasm domestication by editing of domesticated genes e.g. editing in wild tomatoes (Solanum pimpinellifolium) and ground cherry (Physalis pruinosa) mainly focused on flower improvement, plant architecture improvement, fruit size, fruit number and nutritional content [36, 37, 38]. It is evident from such a few successful introgressions of domesticated genes that use of wild germplasm in regular plant breeding is quite promising in countering the effects of climate change on agriculture and hence, food security.
The actual potential of the CWR in plant breeding largely remains underexploited due to linkage drag and frequent breeding barriers with the crops. Introgressiomics approach allows mass scale development of plant material and populations with introgression lines from CWR into the genetic background of crops [39]. This pre-emptive breeding technique could be focused or unfocused depending upon the objective. Besides genetic analysis of traits present in CWR, MAS driven generation of chromosome substitution lines (CSL), introgression lines (IL) or MAGIC populations allow the development of genetically characterized elite material. Genomic tools like high throughput molecular markers facilitate the characterization and development of Introgressiomics populations, which can be easily incorporated into major breeding programs for coping with the accelerating environmental challenges.
After the introgression into domesticated background from CWR, populations such as backcross populations (BC), recombinant inbred lines (RILs), doubled haploids (DH), near isogenic lines (NILs), multiparent advance generation intercross (MAGIC) populations as well as nested association mapping (NAM) populations are developed to study the introgressed gene(s). After mapping their locations on to the genome and it genotypic validation with molecular markers, they are further deployed using Marker assisted selection (MAS). Systematic screening of the huge number of progenies with MAS enhances the efficiency of breeding program (van de Weil 2010). Desirable recombinants can be developed at early generations using larger populations e.g. using marker-assisted backcrossing (MABC), an important QTL was introduced into a new lowland rice background in just 2 rounds of backcrossing [40].
Genomic scans can also reveal candidate domestication and improvement loci as well as post-domestication introgression using CWR [41, 42] to be further harnessed in the scenario of climatic challenges. In case of CWR, high throughput sequencing offers a cheap and rapid way to deploy thousands to millions of markers for mapping purposes [43]. Reduced representation techniques as genotyping by sequencing (GBS) or even nimble exom capture have been exploited to this effect in several CWR species already [42, 44, 45]. These technologies offer rapid marker density as required for rapid fine mapping and can saturate mapping populations in terms of capturing all of the recombinants.
The availability of a reference genome sequence in CWR during recent times greatly boosts the use of high-throughput sequence data. Some large scale genomic sequencing and re-sequencing programs are well underway [27, 46] often with reduced representation methods. Whole genome shotgun sequencing (WGS) techniques can also be utilized to characterize CWR germplasm for climate resilience breeding in major staple crops. E.g. Rice having smaller genome size (430 mb) long with its wild relatives has been re-sequenced using WGS [47, 48, 49]. Already sequenced germplasm collections including Chickpea [50], Rice [48], Soybean [51] and Wheat [52] etc. will provide insights into these diverse gene pools to be exploited in combating various biotic and abiotic challenges during this era of climate change. More recently, a massive scale genomic study of almost 80000 accessions from CIMMYT and ICARDA unraveled unprecedented amount of genetic diversity in 29 wheat species comprising cultivated wheats, CWRs and landraces to be exploited in wheat improvement for range of climate related plant traits [53].
Potentially revolutionary technology in modern plant breeding like genome editing has enabled scientists to alter genome of any organism with unprecedented precision without involvement of any foreign DNA [54]. CWR and their sequence information may serve as a reference library for all kind of diversity. This information on allelic diversity and its phenotype is a vital requirement for many genome editing approaches. In fact, these approaches will allow the use of this information from more distantly related, cross-incompatible CWR and domesticated species to be further utilized in crop improvement [55, 56].
Considering the various direct and indirect impacts of climate change on food production and agriculture along with rapid deterioration of arable land and perplexity of rainfall patterns, all these factors triggering various abiotic stresses such as drought, heat stress and biotic stresses like pest and disease attacks, the sophisticated techniques laden biotechnology toolkit has potential to address these immense challenges of developing the stress tolerant food crop cultivars in this hour of need [57]. With population growing at rapid rate under threatening scenario of climate change, it is high time to shift resilience from conventional breeding along with fertilizers and pesticides to genomics-assisted crop improvement techniques in order to achieve more sustainable and efficient yield gains [58].
Recent advances in biotechnology tools have the potential to understand the function of genes/QTLs that govern the economic traits, and applying this information’s to Smart breeding programs, leading to crop improvement. The advent of molecular markers such as Restriction fragment length polymorphism (RFLP), Rapid Amplified Polymorphic DNA (RAPD), Simple Sequence repeat (SSR), Kompetitive allele specific PCR (KASP), Cleaved amplified polymorphic sequence (CAPS) and especially Single Nucleotide polymorphism (SNP) have revolutionerized the field of plant genetics and facilitated molecular crop breeding [59].
The ultimate goal of crop breeding to develop super-varieties by assembling multiple desirable traits, such as yield related, superior quality, tolerance/resistance against biotic and abiotic stress and good environmental adaption. It is very challenging, difficult and time consuming to combine all traits in single genotypes by traditional breeding, so some alternates need to be compiling all important traits, into single varieties, can be done through marker assisted selection (MAS), which have become an integral component of genotypes/germplasm improvement. The potential benefits of using molecular markers linked to the genes/QTLs of interest in breeding programmes, which have shifted from phenotype-based (traditional breeding) to a combination of phenotype and genotype-based selection, are of great importance to the Smart breeding programme [60].
Breeding programme combine, with MAS strategies have major advantages compared to traditional phenotype-dependent breeding in terms of convenience and efficiency for transferring the genes/QTLs of interest to the plant genome [61]. Selection can be done selectively with the genotypes of molecular markers linked to the target traits, selection in off-season nurseries (reduce breeding cycle), making the technique more cost effective to grow for more generations per year (speed breeding), reduction of required population size because many lines can be discarded in earlier breeding generations after MAS. The most effective and usefulness of MAS approaches, for traits of simple inheritance (qualitative traits controlled by one or a few genes) have been well proven in many important crops [62].
Basically, two major MAS strategies are usually applied in breeding programme, (i) backcrossing for favorable alleles into elite germplasm, i.e. marker-assisted-backcrossing (MABC) and (ii) stacking multiple genes of different sources into elite breeding lines, i.e. marker-assisted gene pyramiding (MAGP). The success of MAS has depends to search the important QTLs for complex traits (controlled by minor genes), which account for a large proportion of phenotypic variation (major QTLs). Successful applications of MABC and MAGP for improving yield or yield component traits by using well characterized major QTLs/genes in important crops [63]. Successful implementation of MAS breeding in broad range of crops including barley, beans, cassava, chickpea, cowpea, groundnut, maize, potato, rice, sorghum, and wheat [64]. Genetic markers associated with agronomic traits can be introgressed into elite crop genetic backgrounds via marker assisted breeding (MAB). It allows stacking of desirable traits into elite varieties to make them better adapted to climatic changes.
With plummeting cost and greater accessibility of high throughput genome sequencing technology, the breadth of genomic data is expanding rapidly. In order to capture diversity of specific gene families within a large group, DNA samples can preferentially be enriched before sequencing. This approach can be adopted to define genetic variation in disease resistance gene repositories in Solanaceae and Triticeae (RNA seq) [65] and gluten gene families I bread wheat (GlutEn Seq) [66].
Sanger sequencing to study plant genomes is unfeasible due to low throughput and high sequencing costs. In 2005, Roche released its revolutionary 454 pyrosequencing platform [67]. Subsequently, several sequencing platforms such as developed by Illumina, ABI, Life technologies, PacBio, Oxford Nanopore and Complete genomics were released commercially, changing the scenario of genome sequencing. Depending on chemistry, second generation sequencing (SGS) approaches are classified as ligation based approaches and synthesis based approaches [68]. To rectify the problems of assembling repetitive genomic regions, long read sequencing offers solution by producing reads spanning the repeat regions [69].
Rapid cost reduction in genome wide genotyping allows large scale assessment of crop species diversity to capture climate related traits. It leverages cheaper sequencing to identify up to millions of SNPs in plant population [70]. High SNP density approach like whole genome resequencing (WGR) & low SNP density approach like reduced representation sequencing (RRS) are majorly used approaches. However, high density genotyping assay “SNP chips” enable large scale genotyping using SNP specific oligonucleotide probes rather than direct sequencing.
The variants identified by genotyping by sequencing (GBS) can be used for conventional QTL analysis and modern approach like genome wide association studies (GWAS). GWAS exploits the past recombinations in a diverse association panels to identity genes lined to phenotypic traits [71]. SNP genotyping have been widely used in many crops including wheat [72] and Maize [73]. Extensive use of GWAS is resulting in our enhanced understanding of genetics of important climate specific traits viz. drought and heat tolerance. In light of reducing sequencing cost and expensive validation of candidate genes, use of WGR to further enhance resolution of mapping studies is likely to become routine task in future [70].
The availability of reference genome assembly rewards us with information about gene content, ability to associate the traits with specific genes with subsequent insights into related biophysical and biochemical roles of gene(s) in the expression of that particular trait [74]. Resequencing of diverse crop cultivars reveals the gene content variation and DNA sequence differences between allelic variants, while sequencing of expressed gene products provides information on where and when genes are functioning. Such information when integrated within breeding pipelines, offers promise to accelerate the development of climate smart crop varieties.
The recent explosion in genomic data is rapidly triggering a fundamental shift to genomic based breeding [75]. The ability to identify and genotype umpteen SNPs at ever reducing costs facilitated expansion of MAS in breeding to plethora of traits and across wider range of crops [76]. A major outcome of availability of high throughput genome wide markers is a move towards population based trait association and breeding i.e. NAM or MAGIC populations to ultimately enhance the trait mapping resolution by greatly increasing the number of recombinations in the population. After identification and validation of the candidate genes, there achieved the deeper understanding of biological mechanism underlying the trait, which can subsequently be improved through MAB or genetic alterations. Furthermore, precise understanding of the molecular basis of traits enables the engineering of novel alleles or mining of potentially desirable alleles from CWR, facilitating further enhancement of the trait.
Genome editing has enabled breeders to precisely add or delete any DNA sequence in the genome and has shown enormous potential to revolutionize the crop improvement in this very decade [70, 77]. Some approaches like transcription activator-like effector nucleases (TALENs) and zinc finger nucleases (ZFNs) have been in the game for more than 2 decades. However, type II clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated protein (Cas) system from Streptococcus pyogenes [78] developed in last decade has been most versatile tool in breeder’s toolkit to introduce desirable or novel traits and accelerate development of climate smart crop varieties.
Usually, a custom-made guide RNA (gRNA) along with Cas9 nuclease is delivered into plant protoplast, where Cas9 produces double strand break (DSB) 3 bp upstream of the NGG motif (protospacer adjacent motif-PAM sequence) [78]. Cellular repair machinery through non-homologous end joining (NHEJ) can lead to frameshift mutation causing a knock-out. Otherwise, a donor DNA template can be provided for precise genetic knock-in through homologous recombination (HR). CRISPR/Cas9 was initially used to disrupt genes related to disease susceptibility in crops such as OsERF922 gene disruption in rice for blast resistance [79] and loss of function in susceptibility gene TaMLO for powdery mildew resistance in wheat [80]. Genome editing has also been used to tackle some abiotic stresses in staple crops like a promoter of a gene AGROS8 was replaced with a stronger one to impart drought tolerance in maize [81].
Due to changing climates, it may be quite beneficial for the farmers to have early maturing varieties, which enables plants to complete crucial developmental periods before the onset of a stress. It has been achieved by disrupting a flower repressing gene SP5G to develop early maturing tomato varieties [82]. For instance, developing climate rice to grow in diverse climates, generally desirable traits are cold, heat and drought tolerance at seedling and reproductive stages [83]. Secondary characters like root and flag leaf traits can be useful to generate cultivars with improved drought and heat tolerance [84]. Here, CRISPR tools could prove to be of great value for exploration of the candidate genes from CWR (O. officinalis, O. nivara and O. glaberrima) for abiotic stress resistance [85].
Genome editing has also huge potential to accelerate the domestication of novel crops form CWR or minor crops with valuable traits for coping with extreme climatic events. This would allow the editing of key genes for domestication in potential new crops for rapid enhancement of currently limited gene pools to maximize the use of germplasm adapted to climate change. Also, multiplexing of CRISPR systems for simultaneous editing of multiple genetic loci can boost the speed and efficiency manifolds. However, there are a number of shortcomings in this approach including off target effects [86], low efficiency of HR, restrictive PAM sequences and regulatory concerns, which paved the way for advent of more sophisticated technologies like DNA free genome editing, base editing and prime editing.
Conventional genome editing using recombinant DNA (rDNA) leads to random host genome integration and can generate undesirable genetic changes or DNA damage [87], along with concerns over genetically modified organism (GMO) regulations with introduction of foreign DNA [88]. DFGE takes care of such critical issues along with reduced risk of off-targets. Initially, it was successfully deployed in rice and tobacco with transfection of protoplast with CRISPR-Cas9 ribonucleoprotein (RNP) [89]. Also, a particle bombardment mediated DFGE approach has been developed in wheat and maize [90, 91].
It is evident that a single base change can cause variation in the elite traits [92], so there required an efficient technique to cause precise and efficient point mutations in plants. CRISPR-Cas9 driven base editing is new approach which accurately transform one DNA base to another without repair template [93]. E.g. Cytidine deaminases convert cytosine (C) to uracil (U), which is treated as thymine (T) in subsequent DNA repair and replication, thus creating C•G to T•A substitution. It has been utilized in wheat, maize and tomato [94] and can be quite useful for gene functional analysis and therefore can assist breeding for better stress adapted varieties.
Another latest milestone in this genome engineering era called prime editing allows introduction of all known 12 base to base conversions in addition to mutations such as insertions and deletions using prime editing guide RNA (pegRNA) [95]. This promising approach opening up numerous possibilities for effectively targeting and modifying desirable genome sequences to accelerate functional genomics and introduction of genes for adaptation to diverse climates can boost breeding for climate smart crop varieties in near future [96].
In this rejuvenated plant mutagenesis breeding era, genome editing can be used in functional genomics for the identification of candidate genes for climate related agronomic, physiological and phonological traits, which can be exploited for crop improvement in adaptation to changing climate. Despite having enormous potential and real world applications of genome editing technologies, the regulatory and ethical concerns may limit it, as happened in a few European countries. In the nutshell, genome editing in complementation with conventional plant breeding can be adopted to develop and deploy climate smart crop varieties in the farmers’ fields.
Advances in phenomics and genomics have generated unprecedented amount of new data, enabling breeders to continuously pushing the crop yields on positive side [97]. Despite success in techniques like genomic selection (GS) in cereals and legumes, lack of predictive accuracy for many complex traits (yield) have revealed their inability to adequately model all relevant factors inherent to such traits due to complexity of the interactions between genetic and environmental components of phenotypic variation [98]. Several mapping studies have shown that such complex traits are controlled by minor genes (polygenes) with small but cumulative effect, hence go undetected while analyzing them in smaller population size.
Relationship between genotype and phenotype is not always linear and small changes on one hierarchical level may have bigger impact on other levels. Many statistical models therefore fail to accurately delineate the non-linear relationships. Additionally, epistatic interactions are hard to detect while mapping genotype to phenotype with linear models due to low power and sheer computational demand [99]. With continuously falling cost of genome sequencing, advent of innovative genetic assays to explore missing heritability and genetic regulation, breeders have access to wide range of high-throughput sensors and imaging techniques for spectrum of traits and field conditions.
Omics technologies (genomics, transcriptomics, proteomics, metabolomics, phenomics, epigenomics and microbiomics) together with approaches to gather information about climate and field environment conditions have become routine in breeding programs now a days. However, ability to accurately predict & select best lines for the specific environment relies on our ability to model these immensely complex systems from web of genomic and phenomic data at hand e.g. multiomics big data. Integrating with phenomics and genomics, AI technologies by assisting with big data, can boost up the development of climate resilient crop varieties with enhanced yield potential and stability and improved tolerance to expected simultaneous environmental stresses (abiotic and biotic).
Accelerated plant breeding for climate resilience is critically dependent upon high resolution, high throughput, field level phenotyping that can effectively screen among better performing breeding lines within larger population across multiple environments [100]. With advent of novel sensors (unmanned air vehicle-UAV), high resolution imagery and new platforms for wide range of traits and conditions, phenomics has been elevating the collection of more phenotypic data over the past decade [101, 102]. High throughput phenotyping (HTP) allows the screening for plant architectural traits and early detection of desirable genotypes. It enables accurate, automated and repeatable measurements for agronomic traits (seedling vigor, flowering time, flower counts, biomass and grain yield, height and leaf erectness, canopy structure) as well as physiological traits (photosynthesis, disease and stress tolerance). HTP methods such as RGB imaging, 3-D scanning, thermal and hyper spectral sensing and fluorescence imaging have been successfully utilized to identify, quantify and monitor plant diseases [103].
By coupling GWAS with high throughput phenotyping facilities, phenomics can be adopted as novel tool for studying plant genetics and genomic characterization enhancing the crop breeding efficiency in era of climate change [104]. Recently, deep learning (DL) has been extensively used to analyze and interpret more phenomic big data, especially for advancing plant image analysis and environmental stress phenotyping [105].
Genomic selection as been extensively used breeding approach for climate resilience in agriculture in last decade, especially for complex polygenic traits. It involves prediction models developed by estimating the combined effect of all existing markers simultaneously on a desirable phenotype. Highly accurate prediction can result into enhanced levels of yields by shortening the breeding cycles. Omics layers (gene expression, metabolite concentration and epistatic signals) can be better predictors of phenotype than SNPs alone due to their molecular proximity to the phenotype. Many such omics layers that explain trait variation have not been made available to the statistical models lowering down its efficacy. Several approaches such as mixed effect linear models and Bayesian models to select only most important predictive SNPs are majorly used.
From the prospective of breeding, by accessing the rich set of omics and environmental data lying between plant genotype and its phenotype, superior and refined impact can be achieved on desirable phenotype. Next gen AI holds promise for GS as acquisition of large scale genomics and phenomics data in addition to molecular layers between them such as transcriptomics, proteomics and epigenomics will facilitate a period, where AI models can identify and explain the complex biological interactions [99].
Next gen AI will surely require knowledge and rationality of breeders as well as farmers to evaluate the efficacy of outcomes. In coming times, agriculture will rely on Next Gen AI methods for making decisions and recommendations from big data (highly heterogeneous and complex) that are representative of environment and system biology based understanding of the behavioral response of plants.
The current pace of yield increase in staple crops like wheat, rice and maize is insufficient to meet the future demand in the wake of climate change [106]. A major limiting factor in plant breeding is the longer generation times of the crops, typically allowing 1–2 generations in a year. Several ‘speeding breeding’ protocols, using extended photoperiods and controlled temperatures have enabled breeders to harvest up to 6 generations per year by reducing the generation time by more than half [107]. Such protocols have been reported in several important crops such as spring wheat (Triticum aestivum) [108], barley (Hordeum vulgare) [109], chickpea (Cicer arietinum), rice (Oryza sativa) [110] and canola (Brassica napus).
Speed breeding can potentially accelerate the discovery and use of allelic diversity in landraces as well as in CWR to be further used in developing climate resilient crop varieties. One such example is recent discovery of new sources of leaf rust resistance after screening of the Vavilov wheat collection using speed breeding along with gene specific molecular markers [111].
Interestingly, speed breeding can also be integrated with advanced technique like gene editing to precisely alter the plant genes for better coping with various biotic and abiotic stresses in threatening climatic changes. In traditional CRISPR gene editing, the sgRNA directs Cas9 enzymes to cut target sequence. ‘CRISPR-ready’ genotypes containing heterologous Cas9 gene can be created. For instance, a transformant harboring a Cas9 transgene can be used a donor to create a stock of elite inbred lines using speed marker-assisted backcrossing. Such an integrated system like ExpressEdit could circumvent the bottlenecks of in vitro manipulation of plant materials also making gene editing fast-tracking [1]. Integration of both the techniques without tissue culture/foreign DNA requires handful of technological breakthroughs with the desirable outcomes being allelic modification, these would bypass genetically modified organism (GMO) label. It has been widely reported that single or multiplex edits can be obtained [112] and could be implemented with some tissue culture free techniques like CRISPR-Cas9 ribonucleoprotein (RNP) complexes in wheat [91] and maize [90].
Genomic selection (GS) unlike MAS uses genome-wide DNA markers in order to predict the genetic gain of breeding individuals for complex traits such as yield [113]. The effect of large number of genetic variants for such a complex traits is captured through linkage disequilibrium (LD) with the genome-wide markers (SNPs), effects of which are determined in large training populations (lines in which marker genotype and trait are measured). Since speed breeding can substantially lowers down the generation periods, it can maximize the benefits by applying genomic selection at every generation to select parents for next generation. Modern genotyping techniques such as rAmpSeq may considerably reduce the genotyping cost for genomic selection [114]. When combined with speed breeding protocol, the approach for stacking of best haplotypes (ones with desirable resistance alleles/desirable edits) could be used rapidly to develop new cultivars [1] with improved performance across multiple traits like coping with adverse climatic variations or any pathogen/insect attack.
Re-domestication of crop plants for capturing the desirable alleles for climate resilience can be sped up by linking it with speed breeding. Re-creation of the polyploids such as groundnut (Arachis hypogea) and banana (Musa spp.) can be benefitted by such approach. Speed breeding could accelerate re-domestication at multiple selection steps after crossing of diploids followed by colchicine application [115]. Ultimately, it will provide access to novel plant traits for developing cultivars of these crops exhibiting disease resistance and stress adaptation. Also, Gene editing and targeted mutagenesis coupled with speed breeding could prove to be more efficient to create healthier foods by biofortification. For instance, the increased content of vitamin B9 in rice and antinutritional glucosinolates from Brassica seeds etc. [1].
Combining all these tools with speed breeding approach would provide rapid access to desirable alleles and novel variation present in CWR and would accelerate the breeding pipelines to develop more climate resilient varieties (Table 1).
Crop species | Target trait/Improved trait | Technology/ Technique used | Reference |
Rice | Submergence tolerance | MAB | [116] |
Rice | Grain number, dense erect panicles and larger grain size | CRISPR/Cas9 | [117] |
Rice | Maintenance of heterosis | CRISPR/Cas9 | [118, 119] |
Wheat | Heat tolerance | GWAS | [120] |
Wheat | Leaf rust, fusarium head blight and stripe rust resistance | Speed breeding | [121, 122, 123, 124] |
Wheat | Powdery mildew-resistant | CRISPR/Cas9 | [80] |
Finger millet | Salt tolerance | RNA sequencing | [125] |
Sorghum | Low and high nitrogen conditions | RNA sequencing | [126] |
Sugarcane | Drought and chilling resistance | CRISPR/Cas9 | [127] |
Maize | Kernel row number | RNA sequencing | [128] |
Maize | High amylopectin content | CRISPR/Cas9 | [129] |
Cotton | Salt and drought tolerance | GWAS | [130] |
Soybean | Salt and drought tolerance | CRISPR/Cas9 | [131, 132] |
Soybean | Salt tolerance | RNA sequencing | [133] |
Chickpea | Drought, salinity, cold and heavy metal stress resistance | RNA sequencing | [134] |
Lentil | Seedling drought stress resistance | RNA sequencing | [135] |
Tomato | High temperature stress responsiveness | GWAS | [136] |
Tomato | Powdery mildew-resistant | CRISPR/Cas9 | [137] |
Tomato | Longer internodes and lighter green leaves with smoother margins | TALEN | [138] |
Tomato | Short (hairy) roots with stunted meristematic, altered branching and increased yield | CRISPR/Cas9 | [139, 140] |
Tomato | Fruits never turn red, altered firmness | CRISPR/Cas9 | [141] |
Broccoli | Dwarf phenotype | CRISPR/Cas9 | [142] |
Watermelon | Albino phenotype | CRISPR/Cas9 | [143] |
Potato | Reduced steroidal glycoalkaloids in leaves and Undetectable level of reducing sugar in tubers | TALEN | [144, 145] |
Mushroom | Reduced browning | CRISPR/Cas9 | [146] |
Banana | Cold and salt resistance | CRISPR/Cas9 | [147] |
Coconut | Root wilt disease | CRISPR/Cas9 | [148] |
Papaya | Drought, heat and cold resistance | CRISPR/Cas9 | [149] |
Apple | Albino phenotype and Blight resistance | CRISPR/Cas9 | [150, 151] |
Utilization of smart breeding tools and techniques for crop improvement.
In the face of ongoing and projected climate change, including higher temperatures and more erratic climate events across extensive regions over the globe, breeding of crop plants with enhanced yield potential and improved resilience to such environments is crucial for global food security. Improved plant varieties that can withstand diseases and pests with efficient use of fewer resources, exhibiting stable yields amidst stressful climate in near future could only help to achieve the goal of climate resilient agriculture. In order to be able to make contribution in climatic resilience, research attention is indispensable for currently underutilized crop species. The concept of smart breeding largely depends upon generating large breeding populations, efficient high throughput phenotyping, big data management tools and downstream molecular techniques to tackle the vulnerability of crop plants to changing climate (Figure 3). The efficient preservation and conservation of plant genetic resources is also a pre requisite for climate smart breeding. Strategies for capturing the novel variation may include the state of the art tools such as gene editing to directly introduce novel alleles found in wild plants into domesticated crop varieties. Generating new crop cultivars with the capability to tolerate multiple stresses can be achieved with increasing information on their basal physiological and genetic mechanisms. The technological improvements in phenotypic and genotypic analysis, as well as the biotechnological and digital revolution could definitely pave the way for developing and deployment of climate smart varieties in coming times.
Compilation of state-of-the-art genomic, phenomic and computational tools comprising smart breeding approach for climatic resilience in agriculture.
The authors declare they have no conflict of interest.
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