Publications by authors named "Amit Kumar Singh"

216 Publications

Genome-wide association mapping reveals key genomic regions for physiological and yield-related traits under salinity stress in wheat (Triticum aestivum L.).

Genomics 2021 Jul 19;113(5):3198-3215. Epub 2021 Jul 19.

ICAR-National Bureau of Plant Genetic Resources, Pusa Campus, New Delhi 110012, India.

A genome-wide association study (GWAS) was conducted using six different multi-locus GWAS models and 35K SNP array to demarcate genomic regions underlying reproductive stage salinity tolerance. Marker-trait association analysis was performed for salt tolerance indices (STI) of 11 morpho-physiological traits, and the actual concentrations of Na and K, and the Na/K ratio in flag leaf. A total of 293 significantly associated quantitative trait nucleotides (QTNs) for 14 morpho-physiological traits were identified. Of these 293 QTNs, 12 major QTNs with R ≥ 10.0% were detected in three or more GWAS models. Novel major QTNs were identified for plant height, number of effective tillers, biomass, grain yield, thousand grain weight, Na and K content, and the Na/K ratio in flag leaf. Moreover, 48 candidate genes were identified from the associated genomic regions. The QTNs identified in this study could potentially be targeted for improving salinity tolerance in wheat.
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http://dx.doi.org/10.1016/j.ygeno.2021.07.014DOI Listing
July 2021

Genetic Dissection of Seedling Root System Architectural Traits in a Diverse Panel of Hexaploid Wheat through Multi-Locus Genome-Wide Association Mapping for Improving Drought Tolerance.

Int J Mol Sci 2021 Jul 2;22(13). Epub 2021 Jul 2.

Department of Agronomy, Kansas State University, Manhattan, KS 66506, USA.

Cultivars with efficient root systems play a major role in enhancing resource use efficiency, particularly water absorption, and thus in drought tolerance. In this study, a diverse wheat association panel of 136 wheat accessions including mini core subset was genotyped using Axiom 35k Breeders' Array to identify genomic regions associated with seedling stage root architecture and shoot traits using multi-locus genome-wide association studies (ML-GWAS). The association panel revealed a wide variation of 1.5- to 50-fold and were grouped into six clusters based on 15 traits. Six different ML-GWAS models revealed 456 significant quantitative trait nucleotides (QTNs) for various traits with phenotypic variance in the range of 0.12-38.60%. Of these, 87 QTNs were repeatedly detected by two or more models and were considered reliable genomic regions for the respective traits. Among these QTNs, eleven were associated with average diameter and nine each for second order lateral root number (SOLRN), root volume (RV) and root length density (RLD). A total of eleven genomic regions were pleiotropic and each controlled two or three traits. Some important candidate genes such as Formin homology 1, Ubiquitin-like domain superfamily and ATP-dependent 6-phosphofructokinase were identified from the associated genomic regions. The genomic regions/genes identified in this study could potentially be targeted for improving root traits and drought tolerance in wheat.
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http://dx.doi.org/10.3390/ijms22137188DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8268147PMC
July 2021

Descriptive Epidemiology of Unintentional Childhood Injuries in India: An ICMR Taskforce Multisite Study.

Indian Pediatr 2021 Jun;58(6):517-524

Ramaiah Medical College, Bangalore, Karnataka.

Background: Children 0-14 years constitute about 31.4% of Indian population, among whom the magnitude and risk factors of childhood injuries have not been adequately studied.

Objective: To study the prevalence of and assess the factors associated with unintentional injuries among children aged 6 month - 18 years in various regions.

Methodology: This multi-centric, cross-sectional, community-based study was conducted at 11 sites across India. States included were Gujarat, Karnataka, Madhya Pradesh, Punjab, Sikkim, Tamil Nadu, Uttarakhand, and West Bengal between March, 2018 and September, 2020. A total of 2341 urban and rural households from each site were selected based on probability proportionate to size. The World Health Organization (WHO) child injury questionnaire adapted to the Indian settings was used after validation. Information on injuries was collected for previous 12 months. Definitions for types (road traffic accidents, falls, burns, poisoning, drowning, animal-related injuries) and severity of injuries was adapted from the WHO study. Information was elicited from parents/primary caregivers. Data were collected electronically, and handled with a management information system.

Results: In the 25751 households studied, there were 31020 children aged 6 months-18 years. A total of 1452 children (66.1% males) had 1535 unintentional injuries (excluding minor injuries) had occurred in the preceding one year. The overall prevalence of unintentional injuries excluding minor injuries was 4.7% (95% CI: 4.4-4.9). The commonest type of injury was fall-related (842, 54.8%) and the least common was drowning (3, 0.2%). Injuries in the home environment accounted for more than 50% of cases.

Conclusions: The findings of the study provide inputs for developing a comprehensive child injury prevention policy in the country. Child safe school with age-appropriate measures, a safe home environment, and road safety measures for children should be a three-pronged approach in minimizing the number and the severity of child injuries both in urban and rural areas.
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June 2021

Evaluation of antidiabetic activity of dietary phenolic compound chlorogenic acid in streptozotocin induced diabetic rats: Molecular docking, molecular dynamics, in silico toxicity, in vitro and in vivo studies.

Comput Biol Med 2021 07 2;134:104462. Epub 2021 May 2.

Department of Biochemistry, University of Allahabad, Prayagraj, 211002, India. Electronic address:

Background: Chlorogenic acid is amongst the well-known polyphenolic compounds being used in human food and beverages. Its presence has been reported in tea leaves, roasted green beans, coffee, cocoa, berry fruits, apples, citrus fruits, and pears.

Objective: The present study aims to elucidate the effectiveness of chlorogenic acid on in silico and in vitro inhibition of glucose metabolising enzymes (α-amylase and α-glucosidase) and on blood-based markers associated with diabetic complications in vivo.

Methods: Docking and molecular dynamics studies were performed using GLIDE (Schrodinger, LLC, NY, 2019-2) and Maestro-Desmond Interoperability Tools, version 4.1 (Schrödinger, NY, 2015), respectively. α-Amylase and α-glucosidase inhibitory activities of chlorogenic acid were measured in vitro. Diabetes was induced in adult Wistar rats by injecting streptozotocin (50 mg/kg). Biochemical assays were performed using standard kits.

Result: The in silico studies for α-amylase and α-glucosidase with chlorogenic acid suggested that the ligand was stable and strongly bound with the above-mentioned proteins. During in vitro studies, chlorogenic acid inhibited both the enzymes in a dose-dependent manner (5-30 μg/mL). In addition, chlorogenic acid treatment for 28 days significantly suppressed the increase in blood glucose, total cholesterol, triglyceride, glutamic oxaloacetic transaminase, glutamic pyruvic transaminase, γ-glutamyl transferase, alkaline phosphatase, total bilirubin, creatinine, urea, uric acid, and feed intake levels in diabetic rats. Chlorogenic acid also caused significant improvement in body weight, serum HDL-cholesterol, total protein, and albumin levels leading to betterment in atherogenic indices related to diabetes-associated cardiovascular risks.

Conclusion: The findings indicated that chlorogenic acid inhibited α-amylase and α-glucosidase and significantly decreased diabetes associated hyperglycemia, hyperlipidemia, and hepatorenal damage, making it a possible functional food ingredient and drug candidate for the management of diabetes and related complications.
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http://dx.doi.org/10.1016/j.compbiomed.2021.104462DOI Listing
July 2021

Chemoenzymatic production of chitooligosaccharides employing ionic liquids and Thermomyces lanuginosus chitinase.

Bioresour Technol 2021 Oct 11;337:125399. Epub 2021 Jun 11.

Department of Microbiology, School of Life Sciences, Central University of Rajasthan, Ajmer 305817, Rajasthan, India. Electronic address:

The aim of this work was to study a two-step chemoenzymatic method for production of short chain chitooligosaccharides. Chitin was chemically pretreated using sulphuric acid, sodium hydroxide and two different ionic liquids, 1-Ethyl-3-methylimidazolium bromide and Trihexyltetradecylphosphonium bis(2,4,4-trimethylpentyl)phosphinate under mild processing conditions. Pretreated chitin was further hydrolyzed employing purified chitinase from Thermomyces lanuginosus ITCC 8895. Trihexyltetradecylphosphonium bis(2,4,4-trimethylpentyl)phosphinate treated chitin appeared amorphous and resulted in generation of 1.10 ± 0.89 mg ml of (GlcNAc) and 1.07 ± 0.92 mg ml of (GlcNAc). Further derivation of optimum conditions through two-factor-9 run experiments resulted in to 1.5 and 1.3 fold increments in (GlcNAc) and (GlcNAc) production, respectively. 0.1 g of both (GlcNAc) and (GlcNAc) has been purified from the Trihexyltetradecylphosphonium bis(2,4,4-trimethylpentyl)phosphinate pretreated chitin (1 g) employing cation exchange chromatography. The present study will lay the foundation for development of a green sustainable solution for cost effective upcycling of coastal residual resources to chito-bioactives.
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http://dx.doi.org/10.1016/j.biortech.2021.125399DOI Listing
October 2021

CSN5A Subunit of COP9 Signalosome Is Required for Resetting Transcriptional Stress Memory after Recurrent Heat Stress in .

Biomolecules 2021 Apr 30;11(5). Epub 2021 Apr 30.

Jacob Blaustein Institutes for Desert Research, Ben-Gurion University of the Negev, Midreshet Ben-Gurion 8499000, Israel.

In nature, plants are exposed to several environmental stresses that can be continuous or recurring. Continuous stress can be lethal, but stress after priming can increase the tolerance of a plant to better prepare for future stresses. Reports have suggested that transcription factors are involved in stress memory after recurrent stress; however, less is known about the factors that regulate the resetting of stress memory. Here, we uncovered a role for Constitutive Photomorphogenesis 5A (CSN5A) in the regulation of stress memory for resetting transcriptional memory genes ( and ) and H3K4me3 following recurrent heat stress. Furthermore, CSN5A is also required for the deposition of H3K4me3 following recurrent heat stress. Thus, CSN5A plays an important role in the regulation of histone methylation and transcriptional stress memory after recurrent heat stress.
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http://dx.doi.org/10.3390/biom11050668DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8146153PMC
April 2021

Ferulic acid-mediated modulation of apoptotic signaling pathways in cancer.

Adv Protein Chem Struct Biol 2021 9;125:215-257. Epub 2021 Feb 9.

Lake Erie College of Osteopathic Medicine, Bradenton, FL, United States. Electronic address:

Ferulic acid (4-hydroxy-3-methoxycinnamic acid, FA), a hydroxycinnamic acid derived from various seeds, nuts, leaves, and fruits, exists in a free form as well as is covalently conjugated with polysaccharides, glycoproteins, polyamines, lignin, and hydroxy fatty acids of plant cell walls. It exhibits a variety of pharmacological effects, such as antioxidant, anti-inflammatory, vasodilatory, antithrombotic, antimicrobial, anti-allergic, antiviral, hepatoprotective, and anticancer activities. FA induces the expression of cell cycle-related proteins, such as p53 and p21, and reduces cyclin D1 and cyclin E levels. Moreover, FA triggers apoptosis and autophagic cell death depending on intracellular reactive oxygen species production in various cancer cell lines. The potential apoptotic action of FA is mediated by altered expression of procaspase-3, procaspase-8, procaspase-9, poly (ADP ribose) polymerase, Bcl-2, and Bax. It blocks the activation of both the canonical Smad and noncanonical extracellular-signal-regulated kinase/Akt (protein kinase B) pathways in various cancer cells. However, due to low solubility and permeability, its availability to biological systems is limited. Therefore, encapsulation of FA into chitosan tripolyphosphate nanoparticles may enhance its cytocompatibility, solubility, and anticancer potential. The nanohybrids of FA and double layered hydroxide exhibit cellular delivery properties of intercalated molecules on cancer cell lines. This chapter summarizes the anticancer efficacy of FA with an emphasis on the role of apoptosis, and underlying molecular mechanisms involving various signaling pathways in tumor cells.
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http://dx.doi.org/10.1016/bs.apcsb.2020.12.005DOI Listing
February 2021

Phialemonium obovatum Infection of the Renal Allograft: Case Report and Review of the Literature.

Exp Clin Transplant 2021 Apr 16. Epub 2021 Apr 16.

From the Department of Nephrology, Dr. Ram Manohar Lohia Institute of Medical Sciences, Lucknow, India.

In this case report, we describe the first case of Phialemonium obovatum infection involving the renal allograft in a recipient beyond 1 year after living renal transplant. The patient presented with a locally invasive mycetoma caused by this melanized fungus in the anterior abdominal wall, which extended during the hospital stay to involve the allograft. The fungus was identified by its characteristic micromorphological features present on potato dextrose agar and Sabourad dextrose agar and on subsequent slide cultures. The patient did not survive despite repeated surgical procedures, including partial allograft nephrectomy and broad-spectrum antifungal medications. Other cases of Phialemonium infections involving renal and stem cell transplant recipients are reviewed.
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http://dx.doi.org/10.6002/ect.2020.0313DOI Listing
April 2021

Neuroprotective Potential of Ellagic Acid: A Critical Review.

Adv Nutr 2021 Jul;12(4):1211-1238

Lake Erie College of Osteopathic Medicine, Bradenton, FL, USA.

Ellagic acid (EA) is a dietary polyphenol present in various fruits, vegetables, herbs, and nuts. It exists either independently or as part of complex structures, such as ellagitannins, which release EA and several other metabolites including urolithins following absorption. During the past few decades, EA has drawn considerable attention because of its vast range of biological activities as well as its numerous molecular targets. Several studies have reported that the oxidative stress-lowering potential of EA accounts for its broad-spectrum pharmacological attributes. At the biochemical level, several mechanisms have also been associated with its therapeutic action, including its efficacy in normalizing lipid metabolism and lipidemic profile, regulating proinflammatory mediators, such as IL-6, IL-1β, and TNF-α, upregulating nuclear factor erythroid 2-related factor 2 and inhibiting NF-κB action. EA exerts appreciable neuroprotective activity by its free radical-scavenging action, iron chelation, initiation of several cell signaling pathways, and alleviation of mitochondrial dysfunction. Numerous in vivo studies have also explored the neuroprotective attribute of EA against various neurotoxins in animal models. Despite the increasing number of publications with experimental evidence, a critical analysis of available literature to understand the full neuroprotective potential of EA has not been performed. The present review provides up-to-date, comprehensive, and critical information regarding the natural sources of EA, its bioavailability, metabolism, neuroprotective activities, and underlying mechanisms of action in order to encourage further studies to define the clinical usefulness of EA for the management of neurological disorders.
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http://dx.doi.org/10.1093/advances/nmab007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8321875PMC
July 2021

Sexually transmitted infections (STIs) and its changing scenario: A scoping review.

Comb Chem High Throughput Screen 2021 Feb 28. Epub 2021 Feb 28.

Department of lab medicine, Max Super speciality hospital, Saket Delhi -110017. India.

Sexually transmitted infections (STIs) and reproductive tract infections (RTIs) have existed worldwide since ancient time, causing significant morbidity and mortality. To maintain healthy sexual and reproductive life, it is highly essential to prevent STIs, RTIs and related illnesses. STIs are transmitted by swapping body fluids among people during sexual intercourse. The etiological agents for STIs are bacteria, virus and parasites for most cases, but proportions by different aetiology are changing. Various studies have shown that STIs are increasing, and its primary aetiology is changing worldwide. That should be considered seriously and needs necessary actions. Several factors related to hosts and disease-causing agents have identified to influence STIs' current strategies in the prevention and control program. The present assessment attempts to review the history, changing aetiology and antimicrobial resistance in STIs. This review has also highlighted the prevalence of STIs at the global level and their past and present trends in India, emphasising its future challenges and perspectives for making effective public health policies to prevent and control STIs.
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http://dx.doi.org/10.2174/1386207324666210301093001DOI Listing
February 2021

Stochastic filtering based transmissibility estimation of novel coronavirus.

Digit Signal Process 2021 May 15;112:103001. Epub 2021 Feb 15.

Central Research Laboratory, BEL, Ghaziabad, Uttar Pradesh, India.

In this study, the transmissibility estimation of novel coronavirus (COVID-19) has been presented using the generalized fractional-order calculus (FOC) based extended Kalman filter (EKF) and wavelet transform (WT) methods. Initially, the state-space representation for the bats-hosts-reservoir-people (BHRP) model is obtained using a set of fractional order differential equations for the susceptible-exposed-infectious-recovered (SEIR) model. Afterward, the EKF and Kronecker product based WT methods have been applied to the discrete vector representation of the BHRP model. The main advantage of using EKF in this system is that it considers both the process and the measurement noise, which gives better accuracy and probable states, which are the Markovian (processes). The importance of proposed models lies in the fact that these models can accommodate conventional EKF and WT methods as their special cases. Further, we have compared the estimated number of contagious people and recovered people with the actual number of infectious people and recovered people in India and China.
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http://dx.doi.org/10.1016/j.dsp.2021.103001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7883689PMC
May 2021

Physicochemical defect guided dewetting of ultrathin films to fabricate nanoscale patterns.

Nanotechnology 2021 May;32(19):195303

Department of Chemical Engineering, Indian Institute of Technology Guwahati, Assam 781039, India.

Pathways to fabricate self-organized nanostructures have been identified exploiting the instabilities of ultrathin (<100 nm) polystyrene (PS) film on the polydimethylsiloxane (PDMS) substrates loaded with discrete and closely packed gold nanoparticles (AuNPs). The AuNPs were deposited on the PDMS substrates by chemical treatment, and the size and periodicity of the AuNPs were varied before coating the PS films. The study unveils that the physicochemical heterogeneity created by the AuNPs on the PDMS surface could guide the hole-formation, influence the average spacing between the holes formed at the initial dewetting stage, and affects the spacing and periodicity of the droplets formed at the end of the dewetting phase. The size and spacing of the holes and the droplets could be tuned by varying the nanoparticle loading on the PDMS substrate. Interestingly, as compared to the dewetting of PS films on the homogeneous PDMS surfaces, the AuNP guided dewetted patterns show ten-fold miniaturization, leading to the formation of the micro-holes and nanodroplets. The spacing between the droplets could also see a ten-fold reduction resulting in high-density random patterns on the PDMS substrate. Further, the use of a physicochemical substrate with varying density of physicochemical heterogeneities could impose a long-range order to the dewetted patterns to develop a gradient surface. The reported results can be of significance in the fabrication of high-density nanostructures exploiting the self-organized instabilities of thin polymers films.
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http://dx.doi.org/10.1088/1361-6528/abe2c8DOI Listing
May 2021

Prevalence of prediabetes, and diabetes in Chandigarh and Panchkula region based on glycated haemoglobin and Indian diabetes risk score.

Endocrinol Diabetes Metab 2021 01 11;4(1):e00162. Epub 2020 Nov 11.

Swami Vivekananda Yoga Anusandhana Samsthana (S-VYASA) Bengaluru India.

There is a rapid increase in the prevalence of diabetes in India. We wanted to review the status of prediabetes and diabetes in the combined population of Chandigarh and Panchkula region based on both Indian Diabetes Risk Score (IDRS) and Glycated Haemoglobin (HbA1c). A total of 1215 subjects were recruited during the screening process, out of which 444 i subjects have been analysed for the current study on the basis of high risk for IDRS (≥60) and their known diabetes status. This study included 431 subjects having high risk for IDRS (≥60) and 13 known subjects with diabetes (IDRS < 60) which were further analysed for biochemical and anthropometric parameters. The prevalence of diabetes was found to be 12.67% and prediabetes 11.69% in the combined population of Chandigarh and Panchkula. There was an increased level of fasting blood glucose (183.12 ± 68.61), postprandial blood glucose (262.57 ± 96.92), triglyceride (193.84 ± 119.88), very low-density lipoprotein (VLDL) (34.87 ± 15.42) and High Density Lipoprotein(HDL) (4.61 ± 1.39) in the said diabetes population. Mean HDL was found to be decreased in subjects having diabetes. Glucose-induced lipid intolerance study revealed significant alteration in triglyceride, HDL and VLDL. The study has revealed that high prevalence of diabetes in the sampled population when compared with the national average of 8.8%.
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http://dx.doi.org/10.1002/edm2.162DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7831224PMC
January 2021

Giant Wharton's duct sialolithiasis causing sialo-oral fistula: a rare case report with literature review.

J Family Med Prim Care 2020 Nov 30;9(11):5793-5795. Epub 2020 Nov 30.

Department of Radiodiagnosis, Jawaharlal Nehru Medical College, Datta Meghe Institute of Medical Sciences (Deemed University) Sawangi (Meghe), Wardha, Maharashtra, India.

Giant submandibular sialolithiasis is uncommon and sialoliths causing sialo-oral fistula are rare. We report a case of giant Wharton's duct sialolithiasis causing sialo-oral fistula in a 40 years male who presented with pain and swelling over right side of floor of mouth for more than two years and visualisation of yellow coloured stone like structure at floor of mouth in the last two days. With diagnosis of Submandibular gland sialolithiasis with sialo-oral fistula, sialolithotomy and marsupialization of Wharton's duct was done under local anaesthesia.
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http://dx.doi.org/10.4103/jfmpc.jfmpc_1525_20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7842423PMC
November 2020

Interplay between miRNAs and Mycobacterium tuberculosis: diagnostic and therapeutic implications.

Drug Discov Today 2021 May 23;26(5):1245-1255. Epub 2021 Jan 23.

Immunology Division, ICMR-National JALMA Institute For Leprosy & Other Mycobacterial Diseases, M. Miyazaki Marg, Tajganj, Agra, India.

Increasing evidence suggests that mycobacteria change the host miRNA profile to their advantage. The active participation of miRNAs in controlling immune responses in TB has raised the possibility of utilizing miRNA-based therapy itself or canonically with a standard drug regimen for shortening the duration of treatment. The development of delivery systems for optimal delivery of oligonucleotides, including small interfering (si)RNA/miRNAs-based therapeutics has shown potential as a new therapeutic intervention. However, studies related to the exploitation of miRNAs as both biomarkers and as therapeutics in TB are scarce; thus, more in vitro and in vivo studies are required to fully determine the role of miRNAs as potential diagnostic biomarkers and to improve the pharmacological profile of this class of therapeutics.
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http://dx.doi.org/10.1016/j.drudis.2021.01.021DOI Listing
May 2021

Effects of Dietary Fiber on Nutrients Utilization and Gut Health of Poultry: A Review of Challenges and Opportunities.

Animals (Basel) 2021 Jan 14;11(1). Epub 2021 Jan 14.

Department of Poultry Science, University of Georgia, Athens, GA 30602, USA.

Many fibrous ingredients incorporated in poultry feed to reduce production costs have low digestibility and cause poor growth in poultry. However, all plant-based fibers are not equal, and thus exert variable physiological effects on the birds, including but not limited to, digestibility, growth performance, and microbial fermentation. Several types of fibers, especially oligosaccharides, when supplemented in poultry diets in isolated form, exhibit prebiotic effects by enhancing beneficial gut microbiota, modulating gut immunity, boosting intestinal mucosal health, and increasing the production of short-chain fatty acids (SCFA) in the gut. Recently, poultry producers are also facing the challenge of limiting the use of antibiotic growth promoters (AGP) in poultry feed. In addition to other alternatives in use, exogenous non-starch polysaccharides digesting enzymes (NSPase) and prebiotics are being used to provide substrates to support the gut microbiome. We also conducted a meta-analysis of different studies conducted in similar experimental conditions to evaluate the variability and conclusiveness in effects of NSPase on growth performance of broilers fed fibrous ingredients. This review presents a holistic approach in discussing the existing challenges of incorporating high-fiber ingredients in poultry feed, as well as strategies to fully utilize the potential of such ingredients in improving feed efficiency and gut health of poultry.
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http://dx.doi.org/10.3390/ani11010181DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7828824PMC
January 2021

Targeted Pulmonary Delivery of the Green Tea Polyphenol Epigallocatechin Gallate Controls the Growth of by Enhancing the Autophagy and Suppressing Bacterial Burden.

ACS Biomater Sci Eng 2020 07 25;6(7):4126-4140. Epub 2020 Jun 25.

Institute of Nano Science and Technology (INST), Phase-10, Sector-64, Mohali, Punjab-160062, India.

Growing rates of tuberculosis (TB) superbugs are alarming, which has hampered the progress made to-date to control this infectious disease, and new drug candidates are few. Epigallocatechin gallate (EGCG), a major polyphenolic compound from green tea extract, shows powerful efficacy against TB bacteria in studies. However, the therapeutic efficacy of the molecule is limited due to poor pharmacokinetics and low bioavailability following oral administration. Aiming to improve the treatment outcomes of EGCG therapy, we investigated whether encapsulation and pulmonary delivery of the molecule would allow the direct targeting of the site of infection without compromising the activity. Microencapsulation of EGCG was realized by scalable spray-freeze-drying (SFD) technology, forming free-flowing micrometer-sized microspheres (epigallocatechin-3-gallate-loaded trehalose microspheres, EGCG-t-MS) of trehalose sugar. These porous microspheres exhibited appropriate aerodynamic parameters and high encapsulation efficiencies. studies demonstrated that EGCG-t-MS exhibited dose- and time-dependent killing of TB bacteria inside mouse macrophages by cellular mechanisms of lysosome acidification and autophagy induction. In a preclinical study on TB-infected Balb/c mice model (4 weeks of infection), we demonstrate that the microencapsulated EGCG, administered 5 days/week for 6 weeks by pulmonary delivery, showed exceptional efficacy compared to oral treatment of free drug. This treatment approach exhibited therapeutic outcomes by resolution of inflammation in the infected lungs and significant reduction ( < 0.05) in bacterial burden (up to ∼2.54 Log CFU) compared to untreated control and orally treated mice groups. No pathological granulomas, lesions, and inflammation were observed in the histopathological investigation, compared to untreated controls. The encouraging results of the study may pave the avenues for future use of EGCG in TB therapeutics by targeted pulmonary delivery and lead to its translational success.
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http://dx.doi.org/10.1021/acsbiomaterials.0c00823DOI Listing
July 2020

Comparative RNA-Seq analysis unfolds a complex regulatory network imparting yellow mosaic disease resistance in mungbean [Vigna radiata (L.) R. Wilczek].

PLoS One 2021 12;16(1):e0244593. Epub 2021 Jan 12.

World Vegetable Center, South Asia, ICRISAT Campus Patancheru, Hyderabad, India.

Yellow Mosaic Disease (YMD) in mungbean [Vigna radiata (L.) R. Wilczek] is one of the most damaging diseases in Asia. In the northern part of India, the YMD is caused by Mungbean Yellow Mosaic India Virus (MYMIV), while in southern India this is caused by Mungbean Yellow Mosaic Virus (MYMV). The molecular mechanism of YMD resistance in mungbean remains largely unknown. In this study, RNA-seq analysis was conducted between a resistant (PMR-1) and a susceptible (Pusa Vishal) mungbean genotype under infected and control conditions to understand the regulatory network operating between mungbean-YMV. Overall, 76.8 million raw reads could be generated in different treatment combinations, while mapping rate per library to the reference genome varied from 86.78% to 93.35%. The resistance to MYMIV showed a very complicated gene network, which begins with the production of general PAMPs (pathogen-associated molecular patterns), then activation of various signaling cascades like kinases, jasmonic acid (JA) and brassinosteroid (BR), and finally the expression of specific genes (like PR-proteins, virus resistance and R-gene proteins) leading to resistance response. The function of WRKY, NAC and MYB transcription factors in imparting the resistance against MYMIV could be established. The string analysis also revealed the role of proteins involved in kinase, viral movement and phytoene synthase activity in imparting YMD resistance. A set of novel stress-related EST-SSRs are also identified from the RNA-Seq data which may be used to find the linked genes/QTLs with the YMD resistance. Also, 11 defence-related transcripts could be validated through quantitative real-time PCR analysis. The identified gene networks have led to an insight about the defence mechanism operating against MYMIV infection in mungbean which will be of immense use to manage the YMD resistance in mungbean.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0244593PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7802970PMC
May 2021

Crosstalk between phytohormones and secondary metabolites in the drought stress tolerance of crop plants: A review.

Physiol Plant 2021 Jun 21;172(2):1106-1132. Epub 2021 Jan 21.

Biomedical Engineering Department, Tufts University, Medford, Massachusetts, USA.

Drought stress negatively affects crop performance and weakens global food security. It triggers the activation of downstream pathways, mainly through phytohormones homeostasis and their signaling networks, which further initiate the biosynthesis of secondary metabolites (SMs). Roots sense drought stress, the signal travels to the above-ground tissues to induce systemic phytohormones signaling. The systemic signals further trigger the biosynthesis of SMs and stomatal closure to prevent water loss. SMs primarily scavenge reactive oxygen species (ROS) to protect plants from lipid peroxidation and also perform additional defense-related functions. Moreover, drought-induced volatile SMs can alert the plant tissues to perform drought stress mitigating functions in plants. Other phytohormone-induced stress responses include cell wall and cuticle thickening, root and leaf morphology alteration, and anatomical changes of roots, stems, and leaves, which in turn minimize the oxidative stress, water loss, and other adverse effects of drought. Exogenous applications of phytohormones and genetic engineering of phytohormones signaling and biosynthesis pathways mitigate the drought stress effects. Direct modulation of the SMs biosynthetic pathway genes or indirect via phytohormones' regulation provides drought tolerance. Thus, phytohormones and SMs play key roles in plant development under the drought stress environment in crop plants.
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http://dx.doi.org/10.1111/ppl.13328DOI Listing
June 2021

Antioxidant, anti-inflammatory and hepatoprotective activities of and its bioactive component ellagic acid against diclofenac induced oxidative stress and hepatotoxicity.

Toxicol Rep 2021 24;8:44-52. Epub 2020 Dec 24.

Department of Biochemistry, University of Allahabad, Allahabad, 211002, India.

Long term usage and overdose of diclofenac (DCF), an anti-inflammatory drug is known to cause oxidative stress and liver injury. The present study reports the antioxidant, anti-inflammatory and hepatoprotective activities of (Tb) fruit aqueous and ethyl acetate extracts and its bioactive compound ellagic acid (EA) against DCF-induced toxicity. antioxidant activities were measured by ABTS and FRAP assays while anti-inflammatory activity was assessed by the albumin denaturation method. The adverse effects of DCF and hepatoprotective potential of Tb extracts and EA were assessed in serum and liver tissue of rats after oral administration for 21 days. Silymarin was used as standard hepatoprptective agent for comparison. Hepatic markers analyzed in serum included ALP, GPT, GOT, LDH, γ-glutamyl transferase, total protein, creatinine, and uric acid while superoxide dismutase (SOD) and catalase (CAT) were analyzed in liver tissue. The EA exhibited superior ABTS radical scavenging, FRAP, and anti-inflammatory activities as compared to fruit extracts. DCF treatment led to rise in the levels of most of the serum hepatic markers with decline in total serum protein as well as SOD and CAT in liver tissue. The supplementation of extracts, EA and silymarin in DCF treated rats significantly reduced the adverse effects of DCF on serum and tissue markers. Histopathology of the liver indicated that extracts and EA significantly decreased the degree of liver fibrosis. The hepatoprotective ability of EA was comparable to the silymarin but activity of Tb fruit extracts was little lower. Among fruit extracts ethyl acetate extract exhibited better activity than aqueous extract. The results revealed that ellagic acid and fruit extracts have potential to mitigate oxidative stress and hepatotoxicity produced by long term use of diclofenac.
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http://dx.doi.org/10.1016/j.toxrep.2020.12.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7772792PMC
December 2020

Identification of QTLs/Defense Genes Effective at Seedling Stage Against Prevailing Races of Wheat Stripe Rust in India.

Front Genet 2020 27;11:572975. Epub 2020 Nov 27.

Indian Council of Agricultural Research-National Bureau of Plant Genetic Resources, New Delhi, India.

Resistance in modern wheat cultivars for stripe rust is not long lasting due to the narrow genetic base and periodical evolution of new pathogenic races. Though nearly 83 genes conferring resistance to stripe rust have been cataloged so far, few of them have been mapped and utilized in breeding programs. Characterization of wheat germplasm for novel sources of resistance and their incorporation into elite cultivars is required to achieve durable resistance and thus to minimize the yield losses. Here, a genome-wide association study (GWAS) was performed on a set of 391 germplasm lines with the aim to identify quantitative trait loci (QTL) using 35K Axiom® array. Phenotypic evaluation disease severity against four stripe rust pathotypes, i.e., 46S119, 110S119, 238S119, and 47S103 (T) at the seedling stage in a greenhouse providing optimal conditions was carried out consecutively for 2 years (2018 and 2019 winter season). We identified, a total of 17 promising QTl which passed FDR criteria. Moreover these 17 QTL identified in the current study were mapped at different genomic locations i.e. 1B, 2A, 2B, 2D, 3A, 3B, 3D, 4B, 5B and 6B. These 17 QTLs identified in the present study might play a key role in marker-assisted breeding for developing stripe rust resistant wheat cultivars.
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http://dx.doi.org/10.3389/fgene.2020.572975DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7728992PMC
November 2020

Recognition System Using Fusion Normalization Based on Morphological Features of Post-Exercise ECG for Intelligent Biometrics.

Sensors (Basel) 2020 Dec 12;20(24). Epub 2020 Dec 12.

IT Research Institute, Chosun University, Gwangju 61452, Korea.

Although biometrics systems using an electrocardiogram (ECG) have been actively researched, there is a characteristic that the morphological features of the ECG signal are measured differently depending on the measurement environment. In general, post-exercise ECG is not matched with the morphological features of the pre-exercise ECG because of the temporary tachycardia. This can degrade the user recognition performance. Although normalization studies have been conducted to match the post- and pre-exercise ECG, limitations related to the distortion of the P wave, QRS complexes, and T wave, which are morphological features, often arise. In this paper, we propose a method for matching pre- and post-exercise ECG cycles based on time and frequency fusion normalization in consideration of morphological features and classifying users with high performance by an optimized system. One cycle of post-exercise ECG is expanded by linear interpolation and filtered with an optimized frequency through the fusion normalization method. The fusion normalization method aims to match one post-exercise ECG cycle to one pre-exercise ECG cycle. The experimental results show that the average similarity between the pre- and post-exercise states improves by 25.6% after normalization, for 30 ECG cycles. Additionally, the normalization algorithm improves the maximum user recognition performance from 96.4 to 98%.
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http://dx.doi.org/10.3390/s20247130DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7763883PMC
December 2020

Quantification of Superficial Venous Reflux by Duplex Ultrasound - Role of Peak Reflux Velocity and Reflux Time in the Assessment of Varicose Vein.

J Nepal Health Res Counc 2020 Nov 14;18(3):442-447. Epub 2020 Nov 14.

Department of Surgery, Dhulikhel Hospital, Kathmandu University Hospital, Nepal.

Background: The study compared the peak reflux velocity and reflux time in cases of varicose veins and non-varicose veins with a focus on quantifying the reflux parameters.

Methods: This is a hospital based observational comparative study. The limbs with CEAP Clinical classification of C2 or more were taken as diseased limbs and contra-lateral limbs with no symptoms or disease were taken as control limbs.

Results: Altogether 792 limbs (452 diseased limbs and 340 control limbs) were evaluated with color duplex. Mean Great Saphenous Vein diameter was 5.68 ± 2.07 mm and 4.00 ± 1.34mmin diseased limbs and control limbs respectively (p=0.0001). Mean sapheno-femoral junction diameter was 8.23 ± 2.64 mm and 6.16 ± 1.93 mm in diseased limbs and control limbs respectively (p=0.0001). Mean peak reflux velocity in diseased limbs was significantly higher than control limbs (77.38 cm/sec vs 7.95 cm/sec; p=0.0001).  Similarly mean reflux time was significantly longer in diseased limbs than non-diseased limb (406.58ms and 67.28 ms respectively; p=0.0001). An optimal cut-off point of 27.4 cm/s for peak reflux velocity and 250 ms for the reflux time at Sapheno-Femoral junction had a discriminatory power between the two groups.

Conclusion: The quantification of peak reflux velocity seems to be more consistent than reflux time in determining the superficial venous reflux. An optimal peak reflux velocity cut off point of 27.4 cm/sec has the discriminatory power between diseased and non-diseased limb.
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http://dx.doi.org/10.33314/jnhrc.v18i3.2558DOI Listing
November 2020

A comprehensive review on promising anti-viral therapeutic candidates identified against main protease from SARS-CoV-2 through various computational methods.

J Genet Eng Biotechnol 2020 Nov 3;18(1):69. Epub 2020 Nov 3.

Department of Biotechnology, School of Engineering and Technology, Sharda University, Greater Noida, U.P, P.C. 201310, India.

Background: The COVID-19 pandemic caused by SARS-CoV-2 has shown an exponential trend of infected people across the planet. Crediting its virulent nature, it becomes imperative to identify potential therapeutic agents against the deadly virus. The 3-chymotrypsin-like protease (3CLpro) is a cysteine protease which causes the proteolysis of the replicase polyproteins to generate functional proteins, which is a crucial step for viral replication and infection. Computational methods have been applied in recent studies to identify promising inhibitors against 3CLpro to inhibit the viral activity. This review provides an overview of promising drug/lead candidates identified so far against 3CLpro through various in silico approaches such as structure-based virtual screening (SBVS), ligand-based virtual screening (LBVS) and drug-repurposing/drug-reprofiling/drug-retasking. Further, the drugs have been classified according to their chemical structures or biological activity into flavonoids, peptides, terpenes, quinolines, nucleoside and nucleotide analogues, protease inhibitors, phenalene and antibiotic derivatives. These are then individually discussed based on the various structural parameters namely estimated free energy of binding (ΔG), key interacting residues, types of intermolecular interactions and structural stability of 3CLpro-ligand complexes obtained from the results of molecular dynamics (MD) simulations.

Conclusion: The review provides comprehensive information of potential inhibitors identified through several computational methods thus far against 3CLpro from SARS-CoV-2 and provides a better understanding of their interaction patterns and dynamic states of free and ligand-bound 3CLpro structures.
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http://dx.doi.org/10.1186/s43141-020-00085-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7607901PMC
November 2020

Influence of pre and postpartum alpha-tocopherol supplementation on milk yield, milk quality, and udder health of Jersey crossbred cows at tropical lower Gangetic region.

Vet World 2020 Sep 26;13(9):2006-2011. Epub 2020 Sep 26.

Animal Nutrition Section, ICAR-National Dairy Research Institute, Eastern Regional Station, Kalyani, West Bengal, India.

Background And Aim: Alpha-tocopherol supplementation influences milk yield, milk quality, and udder health of dairy cows, which needs to be investigated for Jersey crossbred cows at hot-humid climate. Therefore, the present study was framed with an objective to study the effect of pre and postpartum Alpha-tocopherol supplementation on milk yield, milk quality, and udder health status of Jersey crossbred cows at tropical climate.

Materials And Methods: For this study, 19 similar parity, body condition score, and production level dairy animals were separated randomly into three groups, namely, Control, T1 and T2. Control group (no supplementation) was compared with two treatment groups, namely, T1 and T2. Supplementation of Alpha-tocopherol was done in concentrate fed to the animals (at 1 g/cow/day) 30 days prepartum to 30 days postpartum in T1 and 30 days prepartum to 60 days postpartum in T2 groups. Observations were taken for different parameters up to 5 months of lactation.

Results: Statistically analyzed data revealed that overall significantly (p<0.01) more milk production was found in T2, followed by T1 than the control group. Overall significantly (p<0.01) lower somatic cell counts and modified California mastitis tests were recorded in T2, followed by T1 than the control group. Overall significantly (p<0.01), better milk quality in terms of methylene blue reduction test was found in T2, followed by T1 than control groups. Differences in the milk composition of all three groups were non-significant (p>0.05).

Conclusion: Supplementation of Alpha-tocopherol during prepartum to initial lactation period may enhance milk yield, milk quality, and udder health status of Jersey crossbred cows at the tropical lower Gangetic region.
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http://dx.doi.org/10.14202/vetworld.2020.2006-2011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7566249PMC
September 2020

A study on diabetic foot ulcers in Central rural India to formulate empiric antimicrobial therapy.

J Family Med Prim Care 2020 Aug 25;9(8):4216-4222. Epub 2020 Aug 25.

Department of Microbiology, Jawaharlal Nehru Medical College, Datta Meghe Institute of Medical Sciences (Deemed University) Sawangi (Meghe), Wardha, Maharashtra, India.

Aim: This study was carried out on patients with diabetic foot ulcer (DFU) to assess the clinical characteristics, spectrum of microbial flora, antibiotic sensitivity, and devise an empiric antimicrobial therapy.

Material Methods: Clinical data and tissue samples were collected from 105 diabetic foot ulcer patients between December 2018 and November 2019. The collected samples were processed as per Clinical and Laboratory Standards Institute guidelines and clinical and microbiological data was analyzed.

Results: In this study of 105 patients, DFU was most common in males in 5 and 6 decade of life. Majority of patients had poor glycemic control and neuropathy. Of 110 bacterial isolates obtained from 97 samples, 73.7% were Gram-negative bacteria, and 27.3% were Gram-positive. Most of samples (48.6%) showed growth of single bacteria, growth of two bacteria and polymicrobial growth was seen in 28.6% and 15.2% of tissue samples respectively of which. was predominant isolate (27.3%) sensitive to imipenem (90%), amikacin (86.6%), gentamicin (83.3%), and cefotaxime (80%) followed by (19.1%) sensitive to amikacin and gentamicin (100%), and ofloxacin (90%). and were highly resistant to ampicillin and amoxicillin-clavulanic acid.

Conclusion: This study showed DFU are common in 5 and 6 decades of life. Gram-negative bacteria are predominant infective organism. Most of both Gram-negative and Gram-positive bacteria are resistant to variable degrees to commonly used antibiotics and sensitive to aminoglycosides. Amikacin and gentamicin can be used as empiric antibiotics for treatment of DFU infections.
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http://dx.doi.org/10.4103/jfmpc.jfmpc_700_20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7586547PMC
August 2020

Identification of promising molecules against MurD ligase from Acinetobacter baumannii: insights from comparative protein modelling, virtual screening, molecular dynamics simulations and MM/PBSA analysis.

J Mol Model 2020 Oct 17;26(11):304. Epub 2020 Oct 17.

Department of Biotechnology, School of Engineering and Technology, Sharda University, Greater Noida, U.P., P.C. 201310, India.

Acinetobacter baumannii, an opportunistic bacterium of the multidrug-resistant (MDR) ESKAPE family of pathogens, is responsible for 2-10% infections associated with all gram-negative bacteria. The hospital-acquired nosocomial infections caused by A.baumannii include deadly diseases like ventilator-associated pneumonia, bacteremia, septicemia and urinary tract infections (UTI). Over the last 3 years, it has evolved into multiple strains demonstrating high antibiotic resistance against a wide array of antibiotics. Hence, it becomes imperative to identify novel drug-like molecules to treat such infections effectively. UDP-N-acetylmuramoyl-L-alanine-D-glutamate ligase (MurD) is an essential enzyme of the Mur family which is responsible for peptidoglycan biosynthesis, making it a unique and ideal drug target. Initially, a homology modelling approach was employed to predict the three-dimensional model of MurD from A. baumannii using MurD from Escherichia coli (PDB ID: 4UAG) as a suitable structural template. Subsequently, an optimised model of MurD was subjected to virtual high-throughput screening (vHTS) against a ZINC library of ~ 642,759 commercially available molecules to identify promising lead compounds demonstrating high binding affinities towards it. From the screening process, four promising molecules were identified based on the estimated binding affinities (ΔG), estimated inhibition constants (Ki), catalytic residue interactions and drug-like properties, which were then subjected to molecular dynamics (MD) simulation studies to reflect the physiological state of protein molecules in vivo equivalently. The binding free energies of the selected MurD-ligand complexes were also calculated using MM/PBSA (molecular mechanics with Poisson-Boltzmann and surface area solvation) approach. Finally, the global dynamics along with binding free energy analysis suggested that ZINC19221101 (ΔG = - 62.6 ± 5.6 kcal/mol) and ZINC12454357 (ΔG = - 46.1 ± 2.6 kcal/mol) could act as most promising candidates for inhibiting the function of MurD ligase and aid in drug discovery and development against A.baumannii. Graphical abstract.
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http://dx.doi.org/10.1007/s00894-020-04557-4DOI Listing
October 2020

Genome-Wide Association Study Reveals Genomic Regions Associated With Ten Agronomical Traits in Wheat Under Late-Sown Conditions.

Front Plant Sci 2020 17;11:549743. Epub 2020 Sep 17.

ICAR-Indian Institute of Wheat and Barley Research, Karnal, India.

Poor understanding of the genetic and molecular basis of heat tolerance component traits is a major bottleneck in designing heat tolerant wheat cultivars. The impact of terminal heat stress is generally reported in the case of late sown wheat. In this study, our aim was to identify genomic regions for various agronomic traits under late sown conditions by using genome-wide association approach. An association mapping panel of 205 wheat accessions was evaluated under late sown conditions at three different locations in India. Genotyping of the association panel revealed 15,886 SNPs, out of which 11,911 SNPs with exact physical locations on the wheat reference genome were used in association analysis. A total of 69 QTLs (10 significantly associated and 59 suggestive) were identified for ten different traits including productive tiller number (17), grain yield (14), plant height (12), grain filling rate (6), grain filling duration (5), days to physiological maturity (4), grain number (3), thousand grain weight (3), harvest index (3), and biomass (2). Out of these associated QTLs, 17 were novel for traits, namely PTL (3), GY (2), GFR (6), HI (3) and GNM (3). Moreover, five consistent QTLs across environments were identified for GY (4) and TGW (1). Also, 11 multi-trait SNPs and three hot spot regions on Chr1Ds, Chr2BS, Chr2DS harboring many QTLs for many traits were identified. In addition, identification of heat tolerant germplasm lines based on favorable alleles HD2888, IC611071, IC611273, IC75240, IC321906, IC416188, and J31-170 would facilitate their targeted introgression into popular wheat cultivars. The significantly associated QTLs identified in the present study can be further validated to identify robust markers for utilization in marker-assisted selection (MAS) for development of heat tolerant wheat cultivars.
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http://dx.doi.org/10.3389/fpls.2020.549743DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7527491PMC
September 2020

Generation and molecular marker and cytological characterization of wheat - subsp derivatives.

Genome 2021 Jan 1;64(1):29-38. Epub 2020 Oct 1.

Plant Breeding Institute, School of Life and Environmental Sciences, The University of Sydney, NSW, Australia.

Cereal rye and its wild forms are important sources of genetic diversity for wheat breeding due to their resistances to biotic and abiotic stresses. subsp. (Boiss.) K. Hammer (SSA) is a weedy relative of cultivated rye, . Meiotic chromosome pairing in F hybrids of SSA and reveals strong genomic affinity between the two genomes. A study of the transferability of sequence-based markers to SSA and hexaploid triticale demonstrated their applicability for tracing SSA chromatin in wheat. The transferability of the markers was over 80% from homoeologous groups 1, 2, and 3, and greater than 70% from groups 4 to 7. This study focused on the generation and molecular and cytogenetic characterization of wheat-SSA alien derivatives. Twelve were identified using combinations of non-denaturing fluorescence in situ hybridization (ND-FISH), genomic in situ hybridization (GISH), and molecular marker analysis. All SSA chromosomes, except 3R and 6R, were transferred to wheat either in the form of monosomic additions (MA), mono-telosomic additions (MtA), double-mono-telosomic additions (dMtA), or double-monosomic additions (dMA). The germplasm developed in this study will help to enhance the genetic base of wheat and facilitate molecular breeding of wheat and triticale.
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http://dx.doi.org/10.1139/gen-2020-0060DOI Listing
January 2021
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