Publications by authors named "Jyoti Kumari"

50 Publications

Growth and Antioxidant Responses in Iron-Biofortified Lentil under Cadmium Stress.

Toxics 2021 Jul 31;9(8). Epub 2021 Jul 31.

The UWA Institute of Agriculture, The University of Western Australia, Perth, WA 6001, Australia.

Cadmium (Cd) is a hazardous heavy metal, toxic to our ecosystem even at low concentrations. Cd stress negatively affects plant growth and development by triggering oxidative stress. Limited information is available on the role of iron (Fe) in ameliorating Cd stress tolerance in legumes. This study assessed the effect of Cd stress in two lentil ( Medik.) varieties differing in seed Fe concentration (L4717 (Fe-biofortified) and JL3) under controlled conditions. Six biochemical traits, five growth parameters, and Cd uptake were recorded at the seedling stage (21 days after sowing) in the studied genotypes grown under controlled conditions at two levels (100 μM and 200 μM) of cadmium chloride (CdCl). The studied traits revealed significant genotype, treatment, and genotype × treatment interactions. Cd-induced oxidative damage led to the accumulation of hydrogen peroxide (HO) and malondialdehyde in both genotypes. JL3 accumulated 77.1% more HO and 75% more lipid peroxidation products than L4717 at the high Cd level. Antioxidant enzyme activities increased in response to Cd stress, with significant genotype, treatment, and genotype × treatment interactions ( < 0.01). L4717 had remarkably higher catalase (40.5%), peroxidase (43.9%), superoxide dismutase (31.7%), and glutathione reductase (47.3%) activities than JL3 under high Cd conditions. In addition, L4717 sustained better growth in terms of fresh weight and dry weight than JL3 under stress. JL3 exhibited high Cd uptake (14.87 mg g fresh weight) compared to L4717 (7.32 mg g fresh weight). The study concluded that the Fe-biofortified lentil genotype L4717 exhibited Cd tolerance by inciting an efficient antioxidative response to Cd toxicity. Further studies are required to elucidate the possibility of seed Fe content as a surrogacy trait for Cd tolerance.
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http://dx.doi.org/10.3390/toxics9080182DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8402566PMC
July 2021

Magnetic Stiffening in 3D Cell Culture Matrices.

Nano Lett 2021 08 13;21(16):6740-6747. Epub 2021 Aug 13.

Radboud University, Institute for Molecules and Materials, Heyendaalseweg 135, 6525 AJ Nijmegen, The Netherlands.

The mechanical environment of a cell is not constant. This dynamic behavior is exceedingly difficult to capture in (synthetic) matrices. This paper describes a novel, highly adaptive hybrid hydrogel composed of magnetically sensitive magnetite nanorods and a stress-responsive synthetic matrix. Nanorod rearrangement after application of (small) magnetic fields induces strain in the network, which results in a strong (over 10-fold) stiffening even at minimal (2.5 wt %) nanorod concentrations. Moreover, the stiffening mechanism yields a fast and fully reversible response. In the manuscript, we quantitatively analyze that forces generated by the particles are comparable to cellular forces. We demonstrate the value of magnetic stiffening in a 3D MCF10A epithelial cell experiment, where simply culturing on top of a permanent magnet gives rise to changes in the cell morphology. This work shows that our hydrogels are uniquely suited as 3D cell culture systems with on-demand adaptive mechanical properties.
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http://dx.doi.org/10.1021/acs.nanolett.1c00371DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8392345PMC
August 2021

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

Genomics 2021 Sep 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
September 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

Foreign Institutional Investors: Fair-Weather Friends or Smart Traders?

J Quant Econ 2021 Apr 3:1-26. Epub 2021 Apr 3.

Department of Economics & International Business, University of Petroleum and Energy Studies, Dehradun, India.

We examine a theoretically robust but previously undocumented issue of what drives foreign portfolio investments into emerging markets. Foreign institutional investors (FIIs) are often blamed as fair-weather friends who pull out their investment at the first sign of trouble. Using a bottom-up approach, we explore this possibility. We demonstrate the influence of the firm-specific factors such as size, book to market ratio, the riskiness of the stocks, stock prices, dividend yield, liquidity, leverage, and earnings on the FII ownership. We find no evidence to show foreign investors as fair-weather friends. Instead, they are smart traders who follow a diligent investment strategy. We suggest reforms in corporate governance and improvement in financial fundamentals of the companies to attract FII ownership.

Supplementary Information: The online version contains supplementary material available at 10.1007/s40953-021-00233-3.
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http://dx.doi.org/10.1007/s40953-021-00233-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8019337PMC
April 2021

Recent advances in bioprinting technologies for engineering hepatic tissue.

Mater Sci Eng C Mater Biol Appl 2021 Apr 5;123:112013. Epub 2021 Mar 5.

Department of Engineering Science and Mechanics Department, Penn State University, University Park, PA 16802, USA; The Huck Institutes of the Life Sciences, Penn State University, University Park, PA 16802, USA; Biomedical Engineering Department, Penn State University, University Park, PA 16802, USA; Materials Research Institute, Penn State University, University Park, PA 16802, USA; Department of Neurosurgery, Penn State College of Medicine, Hershey, PA 17033, USA. Electronic address:

In the sphere of liver tissue engineering (LTE), 3D bioprinting has emerged as an effective technology to mimic the complex in vivo hepatic microenvironment, enabling the development of functional 3D constructs with potential application in the healthcare and diagnostic sector. This review gears off with a note on the liver's microscopic 3D architecture and pathologies linked to liver injury. The write-up is then directed towards unmasking recent advancements and prospects of bioprinting for recapitulating 3D hepatic structure and function. The article further introduces available stem cell opportunities and different strategies for their directed differentiation towards various hepatic stem cell types, including hepatocytes, hepatic sinusoidal endothelial cells, stellate cells, and Kupffer cells. Another thrust of the article is on understanding the dynamic interplay of different hepatic cells with various microenvironmental cues, which is crucial for controlling differentiation, maturation, and maintenance of functional hepatic cell phenotype. On a concluding note, various critical issues and future research direction towards clinical translation of bioprinted hepatic constructs are discussed.
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http://dx.doi.org/10.1016/j.msec.2021.112013DOI Listing
April 2021

Role of Telemedicine in Follow-up Care of Children with Respiratory Illnesses at a Tertiary Care Hospital - An Ambispective Observational Study.

Indian J Pediatr 2021 10 4;88(10):974-978. Epub 2021 Jan 4.

Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, 110029, India.

Objective: To assess if telemedicine can be used successfully for follow-up care of children with respiratory illnesses. The authors also assessed problems faced by the doctors and satisfaction of caregivers of these patients with telemedicine.

Methods: The authors conducted an ambispective observational study. Data related to demographic details and diagnoses of patients who had telemedicine consultation (teleconsultation) appointments between 2nd April 2020 to 15th May 2020 were reviewed retrospectively. They noted proportion of patients having successful prescription. To assess problems faced by doctors and satisfaction of caregiver of patients with teleconsultation, a prospective questionnaire was sent via Google Forms 6-10 wk after the initial appointment date. Those who did not respond to Google Forms were called by phone to assess the same.

Results: A total of 188 patients received teleconsultation during the study period. Team was able to prescribe treatment in 181 (96.3%) patients via teleconsultation and other seven (3.7%) required physical evaluation. Mean (SD) age of patients was 9.7 (4.9) y, range 3 mo to 18 y. There were 117 (62.2%) boys and 71 (37.8%) girls. Majority (58%) of the patients were asthmatics. The team advised refill prescription in 83% patients as symptoms were controlled. Three out of five residents faced minor problems while providing teleconsultation. In satisfaction assessment, 78% of caregivers rated teleconsultation 8 or more, out of 10 points, suggesting that most of them were satisfied with telemedicine.

Conclusion: In majority of children with respiratory illnesses, successful follow-up care can be provided by telemedicine.
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http://dx.doi.org/10.1007/s12098-020-03590-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7780214PMC
October 2021

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

Drought tolerance in L. genotypes associated with enhanced antioxidative protection and declined lipid peroxidation.

3 Biotech 2020 Jun 2;10(6):281. Epub 2020 Jun 2.

ICAR-National Bureau of Plant Genetic Resources, Pusa Campus, New Delhi, 110 012 India.

Drought is one of the major constraints in wheat production and causes a huge loss at grain-filling stage. In this study we highlighted the response of different wheat genotypes under drought stress at the grain-filling stage. Field experiments were conducted to evaluate 72 wheat ( L.) genotypes under two water regimes: irrigated and drought condition. Four wheat genotypes, two each of drought tolerant (IC36761A, IC128335) and drought-susceptible category (IC335732 and IC138852) were selected on the basis of agronomic traits and drought susceptibility index (DSI), to understand their morphological, biochemical and molecular basis of drought stress tolerance. Among agronomic traits, productive tillers followed by biomass had high percent reduction under drought stress, thus drought stress had a great impact. Antioxidant activity (AO), total phenolic and proline content were found to be significantly higher in IC128335 genotype. Differential expression pattern of transcription factors of ten genes revealed that transcription factor qTaWRKY2 followed by qTaDREB, qTaEXPB23 and qTaAPEX might be utilized for developing wheat varieties resistant to drought stress. Understanding the role of TFs would be helpful to decipher the molecular mechanism involved in drought stress. Identified genotypes (IC128335 and IC36761A) may be useful as parental material for future breeding program to generate new drought-tolerant varieties.
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http://dx.doi.org/10.1007/s13205-020-02264-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7266904PMC
June 2020

Na/K-ATPase a Primary Membrane Transporter: An Overview and Recent Advances with Special Reference to Algae.

J Membr Biol 2020 06 19;253(3):191-204. Epub 2020 May 19.

Applied Phycology and Biotechnology Division, CSIR-Central Salt and Marine Chemicals Research Institute (CSIR-CSMCRI), Council of Scientific and Industrial Research (CSIR), G.B. Marg, Bhavnagar, Gujarat, 364001, India.

The maintenance of ionic homeostasis in the cytoplasm is an essential and crucial physiological process for all living beings. At cellular level, Na concentrations are maintained by specialized Na transporting molecular machines, which operate in the cell or plasma membrane. In eukaryotes Na transporting P-type ATPase play an important role in Na homeostasis that is known as Na/K-ATPase in animal cells in which K acts as a counter ion for the exchange of sodium. Na/K-ATPase is not found in plants. In plants and fungi, proton gradients are maintained by plasma membrane H-ATPase while in animal cells Na and K gradient is maintained by Na/K-ATPase. However, in case of algae, a few reports of Na/K-ATPase are available, that maintains optimum concentration gradients in the cytoplasm and is used by Na/H antiporter to exchange of Na and H ions. The membrane potential derived as a result of ion gradients across the membrane is base for a variety of cellular processes. An active Na dependent cycle (P-type ATPase) is scarcely reported in algae as compared to marine bacteria/cyanobacteria and animals. The characterization of these transporter gene-encoding membrane transports in seaweed would contribute to the understanding of abiotic stress tolerance in these organisms. This review highlights the detailed account of algal along with animal type Na-ATPase i.e. occurrence, properties, significance and their recent progress.
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http://dx.doi.org/10.1007/s00232-020-00119-0DOI Listing
June 2020

Structural dynamics of the GluK3-kainate receptor neurotransmitter binding domains revealed by cryo-EM.

Int J Biol Macromol 2020 Apr 30;149:1051-1058. Epub 2020 Jan 30.

Laboratory of Membrane Protein Biology, National Centre for Cell Science, NCCS Complex, S. P. Pune University, Pune, Maharashtra 411007, India. Electronic address:

Kainate receptors belong to the ionotropic glutamate receptor family and play critical roles in the regulation of synaptic networks. The kainate receptor subunit GluK3 has unique functional properties and contributes to presynaptic facilitation at the hippocampal mossy fiber synapses along with roles at the post-synapses. To gain structural insights into the unique functional properties and dynamics of GluK3 receptor, we imaged them via electron microscopy in the apo-state and in complex with either agonist kainate or antagonist UBP301. Our analysis of all the GluK3 full-length structures not only provides insights into the receptor transitions between desensitized and closed states but also reveals a "non-classical" conformation of neurotransmitter binding domain in the closed-state distinct from that observed in AMPA and other kainate receptor structures. We show by molecular dynamics simulations that Asp759 influences the stability of the LBD dimers and hence could be responsible for the observed conformational variability and dynamics of the GluK3 via electron microscopy. Lower dimer stability could explain faster desensitization and low agonist sensitivity of GluK3. In overview, our work helps to associate biochemistry and physiology of GluK3 receptors with their structural biology and offers structural insights into the unique functional properties of these atypical receptors.
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http://dx.doi.org/10.1016/j.ijbiomac.2020.01.282DOI Listing
April 2020

Identification and evolutionary analysis of polycistronic miRNA clusters in domesticated and wild wheat.

Genomics 2020 05 8;112(3):2334-2348. Epub 2020 Jan 8.

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

MicroRNAs are ~22 nucleotide long non-coding RNAs that regulate gene expression at posttranscriptional level. Genome-wide analysis was performed to identify polycistronic miRNAs from wheat. Total 89 polycistronic miRNAs were identified in bread wheat which were distributed on three component sub-genomes (A = 26, B = 33 and D = 30). Except some, most of the identified polycistronic miRNAs were also present in other cultivated and wild wheat species. Expression of 11 identified polycistronic miRNAs could be validated using previously assembled transcriptomes, RNA-seq/s-RNA seq data of cultivated and wild wheats and RT-PCR. Polycistronic miRNAs orthologs were also localized on rice and Brachypodium genomes. As a case study, we also analyzed molecular evolution of miR395 family polycistrons in wheat. Both tandem and segmental duplications contributed to expansion of miR395 family polycistrons. Our findings provide a comprehensive view on wheat polycitronic miRNAs that will enable their in-depth functional analysis in the future.
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http://dx.doi.org/10.1016/j.ygeno.2020.01.005DOI Listing
May 2020

Development of novel carbazole derivatives with effective multifunctional action against Alzheimer's diseases: Design, synthesis, in silico, in vitro and in vivo investigation.

Bioorg Chem 2020 01 28;95:103524. Epub 2019 Dec 28.

Dr. B. R. Ambedkar Centre for Biomedical Research, University of Delhi, New Delhi 110007, India. Electronic address:

Carbazole based novel multifunctional agents has been rationally designed and synthesized as potential anti-Alzheimer agents. Multi-functional activity of these derivatives have been assessed by performing various in-vitro assays and these compounds appeared to be potent AChE inhibitors, Aβ aggregation inhibitors, anti-oxidant and neuroprotective agents. Among the entire series, MT-1 and MT-6 were most potent multifunctional agents which displayed effective and selective AChE inhibition, Aβ disaggregation, anti-oxidant and metal chelation action. Neuroprotective activity of MT-6 has been examined against HO induced toxicity in SHSY-5Y cells and they have shown effective neuroprotection. Additionally, MT-6 did not display any significant toxicity in SHSY-5Y cells, indicating its non-toxic nature. Molecular docking and MD simulation studies have been also performed to explore molecular level interaction with AChE and Aβ. Finally, MT-6 was evaluated against scopolamine induced dementia model of mice and this compound actively improved memory deficit and cognition impairment in scopolamine treated mice. Thus, novel carbazole derivative MT-6 has been explored as an effective and safe multifunctional agent against AD and this molecule may be used as a suitable lead for development of effective anti-Alzheimer agents in future.
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http://dx.doi.org/10.1016/j.bioorg.2019.103524DOI Listing
January 2020

Prevalence and Risk Factors of Allergic Bronchopulmonary Aspergillosis and Aspergillus Sensitization in Children with Poorly Controlled Asthma.

J Trop Pediatr 2020 06;66(3):275-283

Department of Pediatrics, All India Institute of Medical Sciences, 110029 New Delhi, India.

Background: Allergic bronchopulmonary aspergillosis (ABPA) may be a risk factor for poorly controlled asthma in children. The studies regarding prevalence and risk factors of ABPA in children with poorly controlled asthma are limited in number.

Objectives: To determine prevalence and risk factors of ABPA and aspergillus sensitization (AS) in children with poorly controlled asthma.

Methods: In this prospective cross-sectional study from a tertiary care center in India, we enrolled asthmatic children 5-15 years of age with poorly controlled asthma. We did the following investigations: spirometry, skin prick test, serum total immunoglobulin E (IgE), aspergillus-specific IgE and immunoglobulin G, serum precipitin for Aspergillus, absolute eosinophil count, chest X-ray and high-resolution computed tomography of the chest. ABPA and AS were diagnosed as per the recently proposed criteria.

Results: We enrolled 106 children [boys 72 (67.9%); mean age of 10.2 ± 2.6 years] with poorly controlled asthma. The prevalence of ABPA and AS were 11.3% (95% CI, 5.2-17.5%) and 61.3% (95% CI, 52.0-70.7%), respectively. The presence of brownish sputum was significantly more in ABPA compared with non-ABPA patients (33.3 vs. 4.2%, p = 0.002). The age, gender, allergic rhinitis and gastroesophageal reflux were not significantly different in ABPA compared with non-ABPA patients.

Conclusion: The prevalence of ABPA and AS was 11.3 and 61.3%, respectively in children with poorly controlled asthma. We could not find any risk factors for ABPA except that the presence of brownish sputum was more in children with ABPA. Spirometry parameters were not significantly different in ABPA compared with non-ABPA patients.
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http://dx.doi.org/10.1093/tropej/fmz066DOI Listing
June 2020

A small bioactive glycoside inhibits epsilon toxin and prevents cell death.

Dis Model Mech 2019 10 10;12(10). Epub 2019 Oct 10.

Special Centre for Molecular Medicine, Jawaharlal Nehru University, New Delhi 110067, India

epsilon toxin (Etx) is categorized as the third most lethal bioterrorism agent by the Centers for Disease Control and Prevention (CDC), with no therapeutic counter measures available for humans. Here, we have developed a high-affinity inhibitory compound by synthesizing and evaluating the structure activity relationship (SAR) of a library of diverse glycosides (numbered 1-12). SAR of glycoside-Etx heptamers revealed exceptionally strong H-bond interactions of glycoside-4 with a druggable pocket in the oligomerization and β-hairpin region of Etx. Analysis of its structure suggested that glycoside-4 might self-aggregate to form a robust micelle-like supra-molecular complex due to its linear side-chain architecture, which was authenticated by fluorescence spectroscopy. Further, this micelle hinders the Etx monomer-monomer interaction required for oligomerization, validated by both surface plasmon resonance (SPR) and immunoblotting. This phenomenon in turn leads to blockage of pore formation. Downstream evaluation revealed that glycoside-4 effectively blocked cell death of Etx-treated cultured primary cells and maintained cellular homeostasis via disrupting oligomerization, blocking pore formation, restoring calcium homeostasis, stabilizing the mitochondrial membrane and impairing high mobility group box 1 (HMGB1) translocation from nucleus to cytoplasm. Furthermore, a single dosage of glycoside-4 protected the Etx-challenged mice and restored normal function to multiple organs. This work reports for the first time a potent, nontoxic glycoside with strong ability to occlude toxin lethality, representing it as a bio-arm therapeutic against Etx-based biological threat.
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http://dx.doi.org/10.1242/dmm.040410DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6826021PMC
October 2019

A minimally-invasive cryogel based approach for the development of human ectopic liver in a mouse model.

J Biomed Mater Res B Appl Biomater 2020 04 9;108(3):1022-1032. Epub 2019 Aug 9.

Department of Biological Sciences and Bioengineering, Indian Institute of Technology Kanpur, Kanpur, UP, India.

Human liver tissue is preferable over nonhuman liver tissue for preclinical drug screening, as the former can better predict side effects specific to humans. However, due to limited supply and ethical issues with human liver tissue, it is desirable to develop an animal model having functional human liver tissue. In this study, we have established an ectopic functional human liver tissue in a mouse model, using a minimally-invasive method. Firstly, a human liver tissue mass using HepG2 cells and poly(N-isopropylacrylamide) (PNIPAAm) incorporated poly(ethylene glycol)-alginate-gelatin (PAG) cryogel matrix was developed in vitro. It was later implanted in mouse peritoneal cavity using a 16 G needle. Viscoelastic nature along with low Young's modulus provided injectable properties to the cryogel. We confirmed minimal cell loss/death while injecting. Further, by in vivo study efficacy of both injectable and surgical implantation approaches were compared. No significant difference in terms of cell infiltration, human serum albumin (HSA) secretion and enzyme activity confirmed efficacy. This model developed using a minimally-invasive approach can overcome the limitations of surgical implantation due to its cost effective and user friendly nature.
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http://dx.doi.org/10.1002/jbm.b.34454DOI Listing
April 2020

Structural and Functional Insights into GluK3-kainate Receptor Desensitization and Recovery.

Sci Rep 2019 07 16;9(1):10254. Epub 2019 Jul 16.

Laboratory of Membrane Protein Biology, National Centre for Cell Science, NCCS Complex, S. P. Pune University, Maharashtra, Pune, 411007, India.

GluK3-kainate receptors are atypical members of the iGluR family that reside at both the pre- and postsynapse and play a vital role in the regulation of synaptic transmission. For a better understanding of structural changes that underlie receptor functions, GluK3 receptors were trapped in desensitized and resting/closed states and structures analyzed using single particle cryo-electron microscopy. While the desensitized GluK3 has domain organization as seen earlier for another kainate receptor-GluK2, antagonist bound GluK3 trapped a resting state with only two LBD domains in dimeric arrangement necessary for receptor activation. Using structures as a guide, we show that the N-linked glycans at the interface of GluK3 ATD and LBD likely mediate inter-domain interactions and attune receptor-gating properties. The mutational analysis also identified putative N-glycan interacting residues. Our results provide a molecular framework for understanding gating properties unique to GluK3 and exploring the role of N-linked glycosylation in their modulation.
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http://dx.doi.org/10.1038/s41598-019-46770-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6635489PMC
July 2019

Mining of Indian wheat germplasm collection for adult plant resistance to leaf rust.

PLoS One 2019 28;14(3):e0213468. Epub 2019 Mar 28.

Sardarkrushinagar Dantiwada Agricultural University, Vijapur, Gujarat, India.

Leaf rust (Puccinia triticina Eriks.) is a fungal disease of wheat (Triticum spp.), which causes considerable yield loss. Adult plant resistance (APR) is one of the most sustainable approaches to control leaf rust. In this study, field-testing was carried out across ten different locations, followed by molecular screening, to detect the presence of APR genes, Lr34+, Lr46+, Lr67+ and Lr68 in Indian wheat germplasm. In field screening, 190 wheat accessions were selected from 6,319 accessions based on leaf tip necrosis (LTN), disease severity and the average coefficient of infection. Molecular screening revealed that 73% of the accessions possessed known APR genes either as single or as a combination of two or three genes. The occurrence of increased LTN intensity, decreased leaf rust severity and greater expression of APR genes were more in relatively cooler locations. In 52 lines, although the presence of the APR genes was not detected, it still displayed high levels of resistance. Furthermore, 49 accessions possessing either two or three APR genes were evaluated for stability across locations for grain yield. It emerged that eight accessions had wider adaptability. Resistance based on APR genes, in the background of high yielding cultivars, is expected to provide a high level of race non-specific resistance, which is durable.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0213468PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6438482PMC
December 2019

Identification, analysis and development of salt responsive candidate gene based SSR markers in wheat.

BMC Plant Biol 2018 Oct 20;18(1):249. Epub 2018 Oct 20.

Division of Germplasm Conservation, ICAR-National Bureau of Plant Genetic Resources, Pusa, New Delhi, 110012, India.

Background: Salinity severely limits wheat production in many parts of the world. Development of salt tolerant varieties represents the most practical option for enhancing wheat production from these areas. Application of marker assisted selection may assist in fast tracking development of salt tolerant wheat varieties. However, SSR markers available in the public domain are not specifically targeted to functional regions of wheat genome, therefore large numbers of these need to be analysed for identification of markers associated with traits of interest. With the availability of a fully annotated wheat genome assembly, it is possible to develop SSR markers specifically targeted to genic regions. We performed extensive analysis to identify candidate gene based SSRs and assessed their utility in characterizing molecular diversity in a panel of wheat genotypes.

Results: Our analysis revealed, 161 SSR motifs in 94 salt tolerance candidate genes of wheat. These SSR motifs were nearly equally distributed on the three wheat sub-genomes; 29.8% in A, 35.7% in B and 34.4% in D sub-genome. The maximum number of SSR motifs was present in exons (31.1%) followed by promoters (29.8%), 5'UTRs (21.1%), introns (14.3%) and 3'UTRs (3.7%). Out of the 65 candidate gene based SSR markers selected for validation, 30 were found polymorphic based on initial screening and employed for characterizing genetic diversity in a panel of wheat genotypes including salt tolerant and susceptible lines. These markers generated an average of 2.83 alleles/locus. Phylogenetic analysis revealed four clusters. Salt susceptible genotypes were mainly represented in clusters I and III, whereas high and moderate salt tolerant genotypes were distributed in the remaining two clusters. Population structure analysis revealed two sub-populations, sub-population 1 contained the majority of salt tolerant whereas sub-population 2 contained majority of susceptible genotypes. Moreover, we observed reasonably higher transferability of SSR markers to related wheat species.

Conclusion: We have developed salt responsive gene based SSRs in wheat for the first time. These were highly useful in unravelling functional diversity among wheat genotypes with varying responses to salt stress. The identified gene based SSR markers will be valuable genomic resources for genetic/association mapping of salinity tolerance in wheat.
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http://dx.doi.org/10.1186/s12870-018-1476-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6195990PMC
October 2018

Diversity in protein profiling, pasting, empirical and dynamic dough rheological properties of meal from different durum wheat accessions.

J Food Sci Technol 2018 Apr 15;55(4):1256-1269. Epub 2018 Jan 15.

2National Bureau of Plant Genetic Resources Regional Station, Phagli, Shimla, 171004 India.

The particle size distribution, protein profile, pasting and dough rheological properties of meal from forty-two Indian durum wheat accessions were evaluated. Meal from accessions with higher grain hardness index (GHI) showed a high proportion of large size particles with higher protein content and lower paste viscosities. Elastic and viscous modulii (' and ″) of dough were negatively correlated with paste viscosities, which was associated with the presence/absence of LMW-GS and HMW-GS. Wheat accessions with allelic combinations of (13 + 16) with 97 + 91 kDa polypeptides (PPs) had higher ' and ″. The accession with 35 kDa PP showed higher while those with 35 and 62 kDa PPs showed lower paste viscosity. Among all accessions, 25 accessions possess 7 + 8 (97 and 88 kDa) type HMW-GS allelic combination. Durum accessions with diverse GHI, particle size distribution, protein profile, paste and dough rheology indicates their variation in milling and processing behaviour.
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http://dx.doi.org/10.1007/s13197-018-3036-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5876193PMC
April 2018

Isoniazid induced early-onset of motor dominant neuropathy and treatment with high dose of pyridoxine.

Indian J Tuberc 2018 Apr 3;65(2):175-176. Epub 2017 May 3.

Post Graduate Student (Pulmonary Medicine), Kamla Nehru Chest Hospital, Dr. S.N. Medical College, Jodhpur, Rajasthan, India.

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http://dx.doi.org/10.1016/j.ijtb.2017.04.004DOI Listing
April 2018

Comparison of Diagnostic Potential of Narrow Band Imaging Bronchoscopy Over White Light Bronchoscopy in Lung Cancer.

J Bronchology Interv Pulmonol 2018 Apr;25(2):132-136

Kamla Nehru Chest Hospital, Dr S.N. Medical College.

Background: Worldwide, lung cancer is the largest contributor to new cancer diagnoses and to death from cancer. Narrow band imaging (NBI) is a novel bronchoscopic technique which enables detailed examination of submucosal microcapillary grid and showed great potential in early detection of malignant lesions of the bronchial mucosa. The aim of this study was to compare diagnostic potential of NBI bronchoscopy over white light (WL) bronchoscopy in lung cancer.

Methods: We enrolled 187 patients having clinical and radiologic findings highly suspicious of lung cancer. Patients were further divided into 2 groups: NBI group (n=102), and control WL group (n=85). Bronchoscopy examination was performed with respective visualization modes and all pathologic lesions were biopsied and histologically confirmed.

Results: On NBI bronchoscopy, malignancy was suspected in 69 patients, of whom 62 had malignancy, and 33 patients were suspected of inflammation, of whom 32 had inflammation and only 1 patient had malignancy. Under WL bronchoscopy, 54 patients were suspected of malignancy, of whom 36 had malignancy, and 31 patients were suspected of inflammation, of whom 23 had inflammatory disease and 8 had malignancy. NBI bronchoscopy had sensitivity 98.1%, specificity 82.05%, positive predictive value 89.86% and negative predictive value 96.97% in comparison to standard WL bronchoscopy which had sensitivity 81.82%, specificity 56.10%, positive predictive value 66.67% and negative predictive value 74.19%.

Conclusion: NBI bronchoscopy demonstrated better results in comparison to WL bronchoscopy. The presence of pathologic vascularization of the tumor helps to better identify the malignant process. Inflammatory changes in the mucosa can be easily differentiated from malignant changes by the appearance of vessels.
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http://dx.doi.org/10.1097/LBR.0000000000000469DOI Listing
April 2018

Enhanced Hepatic Functions of Genetically Modified Mouse Hepatoma Cells by Spheroid Culture for Drug Toxicity Screening.

Biotechnol J 2017 Oct 6;12(10). Epub 2017 Sep 6.

Department of Biological Sciences and Bioengineering & Centre for Environmental Sciences and Engineering, Indian Institute of Technology Kanpur, Kanpur 208016, India.

While hepatic cell lines are mainly used for in vitro drug induced toxicity studies, they exhibit limited functionalities. To overcome this, the authors have employed genetically engineered mouse hepatoma cells, Hepa/8F5, wherein expression of liver enriched transcription factors is induced by doxycycline leading to increased functionality. Further enhancement in functionality is achieved by spheroid culture in a previously developed 3D cell culture platform. Cells are seeded in presence of temperature-responsive poly(N-isopropylacrylamide) on poly(N-isopropylacrylamide--co-gelatin) cryogel scaffold based high throughput platform. Cells seeded in presence of poly(N-isopropylacrylamide) and induced with doxycycline exhibited highest functionalities. There is an increase of ≈26, 36, and 39% in albumin secretion, ammonia removal, and CYP3A4 activity, respectively. Morphological analysis showed arrest in cell proliferation and enlarged nucleus in presence of doxycyline and spheroid formation in presence of poly(N-isopropylacrylamide). Drug induced liver toxicity studies revealed that cells induced with doxycycline are resistive to tamoxifen but sensitive to acetaminophen whereas, cultures initiated in presence of poly(N-isopropylacrylamide) are resistive to both the drugs which is indicative of diffusional barrier of the spheroids. The authors conclude that Hepa/8F5 cells show enhanced functionality in cryogel based spheroid culture platform which can be successfully used for high throughput screening of hepatic toxicity in vitro.
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http://dx.doi.org/10.1002/biot.201700274DOI Listing
October 2017

Overexpression of SbSI-1, A Nuclear Protein from Confers Drought and Salt Stress Tolerance and Maintains Photosynthetic Efficiency in Transgenic Tobacco.

Front Plant Sci 2017 13;8:1215. Epub 2017 Jul 13.

Marine Biotechnology and Ecology Division, CSIR-Central Salt and Marine Chemicals Research Institute, Council of Scientific and Industrial ResearchBhavnagar, India.

A novel S b Salt Inducible (-1) gene was isolated and overexpressed in tobacco for functional validation subjected to drought and salt stress. -1 is a nuclear protein. The transgenic tobacco overexpressing -1 gene exhibited better seed germination, growth performances, pigment contents, cell viability, starch accumulation, and tolerance index under drought and salt stress. Overexpression of -1 gene alleviated the build-up of reactive oxygen species (ROS) and curtailed the ROS-induced oxidative damages thus improved the physiological health of transgenic tobacco under stressed conditions. The higher activities of antioxidant enzymes, lower accumulation of ROS, higher membrane stability, relative water content, and polyphenol contents indicated the better survival of the transgenic tobacco than wild-type (WT) tobacco under stressed conditions. Transgenic tobacco had a higher net photosynthetic rate, PSII operating efficiency, and performance index under drought and salt stress. Higher accumulation of compatible solutes and K/Na ratio in transgenic tobacco than WT showed the better osmotic and redox homeostasis under stressed conditions. The up-regulation of genes encoding antioxidant enzymes (, and ) and transcription factors ( and ) in transgenic tobacco under stressed conditions showed the role of -1 in ROS alleviation and involvement of this gene in abiotic stress tolerance. Multivariate data analysis exhibited statistical distinction among growth responses, physiological health, osmotic adjustment, and photosynthetic responses of WT and transgenic tobacco under stressed conditions. The overexpression of -1 gene curtailed the ROS-induced oxidative damages and maintained the osmotic homeostasis under stress conditions thus improved physiological health and photosynthetic efficiencies of the transgenic tobacco overexpressing -1 gene.
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http://dx.doi.org/10.3389/fpls.2017.01215DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5508026PMC
July 2017

Biosynthesis, characterization and antibacterial activity of silver nanoparticles using an endophytic fungal supernatant of .

J Genet Eng Biotechnol 2017 Jun 22;15(1):31-39. Epub 2017 Apr 22.

Department of Applied Sciences, Manav Bharti University, Solan 173229, India.

In this study, biological synthesis of silver nanoparticles (AgNPs) from supernatant of endophytic fungus sp. isolated from the healthy leaves of is studied. The synthesized AgNPs are characterized using UV-vis spectroscopy and Fourier transform-infrared spectroscopy (FTIR). The structural analysis is done by powder X-ray diffraction (XRD) method. The stability of AgNPs is studied by dynamic light scattering (DLS) method. The size and shape of AgNPs are observed by transmission electron microscopy (TEM) and atomic force microscopy (AFM) and found to be spherical with an average particles size of 4-30 nm. Further, these AgNPs have been found to be highly toxic against human pathogenic bacteria, suggesting the possibility of using AgNPs as efficient antibacterial agents.
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http://dx.doi.org/10.1016/j.jgeb.2017.04.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6296651PMC
June 2017

Development of polymer based cryogel matrix for transportation and storage of mammalian cells.

Sci Rep 2017 01 31;7:41551. Epub 2017 Jan 31.

Department of Biological Sciences and Bioengineering, Indian Institute of Technology Kanpur, Kanpur- 208016, UP, India.

We studied the potential of polymeric cryogel matrices such as 2-hydroxyethyl methacrylate (HEMA)-agarose (HA) and gelatin matrix as a transporting and storage material for mammalian cells. Both the HA and gelatin matrices were found to possess a homogenous distribution of pores as shown by scanning electron microscopic (SEM) images and flow rate of 8 and 5 mL/min, respectively. In the case of HA cryogel, after 5 days of simulated transportation, C2C12 cells kept in cryogel matrix showed higher percentage viability (89%) as compared to 64.5% viability of cells kept in suspension culture. The cells recovered from the HA cryogel were able to proliferate as revealed by the microscopic analysis. In the case of gelatin cryogel, it was shown that C2C12 cells seeded on the cryogel under simulated transportation condition were found to proliferate over the period of 5 days. It was also observed that the cells after simulation can be cryopreserved and the duration of cryopreservation does not affect their viability. Furthermore, gelatin cryogel was used for cryopreservation of HepG2 and HUVEC cells to extend the system for other cell types. These results show the potential of cryogels as efficient, low-cost transporting matrix at room temperature and in cryo-conditions.
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http://dx.doi.org/10.1038/srep41551DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5282502PMC
January 2017

Evaluation of 19,460 Wheat Accessions Conserved in the Indian National Genebank to Identify New Sources of Resistance to Rust and Spot Blotch Diseases.

PLoS One 2016 12;11(12):e0167702. Epub 2016 Dec 12.

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

A comprehensive germplasm evaluation study of wheat accessions conserved in the Indian National Genebank was conducted to identify sources of rust and spot blotch resistance. Genebank accessions comprising three species of wheat-Triticum aestivum, T. durum and T. dicoccum were screened sequentially at multiple disease hotspots, during the 2011-14 crop seasons, carrying only resistant accessions to the next step of evaluation. Wheat accessions which were found to be resistant in the field were then assayed for seedling resistance and profiled using molecular markers. In the primary evaluation, 19,460 accessions were screened at Wellington (Tamil Nadu), a hotspot for wheat rusts. We identified 4925 accessions to be resistant and these were further evaluated at Gurdaspur (Punjab), a hotspot for stripe rust and at Cooch Behar (West Bengal), a hotspot for spot blotch. The second round evaluation identified 498 accessions potentially resistant to multiple rusts and 868 accessions potentially resistant to spot blotch. Evaluation of rust resistant accessions for seedling resistance against seven virulent pathotypes of three rusts under artificial epiphytotic conditions identified 137 accessions potentially resistant to multiple rusts. Molecular analysis to identify different combinations of genetic loci imparting resistance to leaf rust, stem rust, stripe rust and spot blotch using linked molecular markers, identified 45 wheat accessions containing known resistance genes against all three rusts as well as a QTL for spot blotch resistance. The resistant germplasm accessions, particularly against stripe rust, identified in this study can be excellent potential candidates to be employed for breeding resistance into the background of high yielding wheat cultivars through conventional or molecular breeding approaches, and are expected to contribute toward food security at national and global levels.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0167702PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5153299PMC
June 2017

Green synthesis of nanostructured silver particles and their catalytic application in dye degradation.

J Genet Eng Biotechnol 2016 Dec 11;14(2):311-317. Epub 2016 Oct 11.

Department of Biotechnology, Govind Ballabh Pant Engineering College, Pauri Garhwal, Uttarakhand 246194, India.

Today, discharge of hazardous dyes from textile industries in water bodies like lakes, rivers and groundwater has become a serious problem, which contributes to increase their pollution levels significantly. These pollutants are difficult to remove by traditional water treatment procedures. Thus, there is a need to develop more suitable methods of effluent treatment. Here, we describe use of green-synthesized nanostructured silver particles in degradation of hazardous dyes like Safranine O, Methyl red, Methyl orange and Methylene blue etc. The silver nanoparticles (AgNPs) used as nanocatalysts were synthesized using leaves. The reduction of silver ions and the formation of AgNPs have been assessed by UV-Vis spectroscopy. DLS, SEM-EDX, TEM, SAED and XRD studies revealed that the AgNPs were crystalline in nature with size range from 15 to 50 nm. The report emphasizes that the AgNPs are observed to be an excellent catalyst on reduction of hazardous dyes, which is confirmed by a decrease in absorbance maximum values.
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http://dx.doi.org/10.1016/j.jgeb.2016.09.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6299851PMC
December 2016

Evaluation of antibacterial activity from phytosynthesized silver nanoparticles against medical devices infected with spp.

J Taibah Univ Med Sci 2017 Feb 27;12(1):47-54. Epub 2016 Sep 27.

Department of Biotechnology, Govind Ballabh Pant Engineering College, Pauri Garhwal, India.

Objectives: Biofilm formation on the surface of medical devices, such as artificial prosthetics and catheters, are serious challenges to biomedical science. Most conventional methods, such as antibiotic therapy and medical device replacement, have failed because of low efficiency in medical environments. In the present study, we aimed to prevent infection by human pathogens (35984) and (740), which are resistant to antibiotic therapy. To prevent these infections, phytosynthesized silver nanoparticles (AgNPs) coating was tested.

Methods: The AgNPs were synthesized using aqueous extract of leaves and were characterized by UV-vis spectroscopy, X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), atomic force microscopy (AFM), energy dispersive spectroscopy (EDS), transmission electron microscopy (TEM), and selected area electron diffraction (SAED). The viable cells of bacteria were counted using a digital colony counter.

Results: AgNPs were 15 nm-35 nm in size and crystallized in a face-centred-cubic structure. Furthermore, the AgNPs coating on glass surfaces were bactericidal.

Conclusions: This study suggested that phytosynthesized AgNPs capped with various biomolecules present in leaf extracts of coated on glass surface prevent  and associated infections of medical devices. Thus, coating of phytosynthesized AgNPs on glass surfaces may provide efficient antibacterial treatment of infected medical devices.
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http://dx.doi.org/10.1016/j.jtumed.2016.08.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6694894PMC
February 2017
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