Publications by authors named "Sukhwinder Singh"

84 Publications

Vaccination boosts protective responses and counters SARS-CoV-2-induced pathogenic memory B cells.

medRxiv 2021 Apr 14. Epub 2021 Apr 14.

Given the rapid spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the recent implementation of SARS-CoV-2 vaccination, we have much to learn about the duration of immune protection and the interface between the immune responses to infection and to vaccination. To address these questions, we monitored immune responses to SARS-CoV-2 infection in convalescent individuals over seven months and following mRNA vaccination. Spike Receptor-Binding-Domain (RBD)-specific circulating antibodies and plasma neutralizing activity generally decreased over time, whereas RBD-specific memory B cells persisted. Additionally, using antibody depletion techniques, we showed that the neutralizing activity of plasma specifically resides in the anti-RBD antibodies. More vigorous antibody and B cell responses to vaccination were observed in previously infected subjects relative to uninfected comparators, presumably due to immune priming by infection. SARS-CoV-2 infection also led to increased numbers of double negative B memory cells, which are described as a dysfunctional B cell subset. This effect was reversed by SARS-CoV-2 vaccination, providing a potential mechanistic explanation for the vaccination-induced reduction in symptoms in patients with "Long-COVID".
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http://dx.doi.org/10.1101/2021.04.11.21255153DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8057254PMC
April 2021

Genome-wide association analysis of Mexican bread wheat landraces for resistance to yellow and stem rust.

PLoS One 2021 29;16(1):e0246015. Epub 2021 Jan 29.

International Maize and Wheat Improvement Center (CIMMYT), El Batán, Texcoco, Mexico.

Deploying under-utilized landraces in wheat breeding has been advocated to accelerate genetic gains in current era of genomics assisted breeding. Mexican bread wheat landraces (Creole wheats) represent an important resource for the discovery of novel alleles including disease resistance. A core set of 1,098 Mexican landraces was subjected to multi-location testing for rust diseases in India, Mexico and Kenya. The landrace core set showed a continuous variation for yellow (YR) and stem rust (SR) disease severity. Principal component analysis differentiated Mexican landraces into three groups based on their respective collection sites. Linkage disequilibrium (LD) decay varied from 10 to 32 Mb across chromosomes with an averge of 23Mb across whole genome. Genome-wide association analysis revealed marker-trait associations for YR resistance in India and Mexico as well as for SR resistance in Kenya. In addition, significant additive-additive interaction effects were observed for both YR and SR resistance including genomic regions on chromosomes 1BL and 3BS, which co-locate with pleiotropic genes Yr29/Lr46/Sr58/Pm39/Ltn2 and Sr2/Yr30/Lr27, respectively. Study reports novel genomic associations for YR (chromosomes 1AL, 2BS, and 3BL) and SR (chromosomes 2AL, 4DS, and 5DS). The novel findings in Creole wheat landraces can be efficiently utilized for the wheat genetic improvement.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0246015PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7846011PMC
January 2021

A GWAS to identify the cereal cyst nematode (Heterodera filipjevi) resistance loci in diverse wheat prebreeding lines.

J Appl Genet 2021 Feb 6;62(1):93-98. Epub 2021 Jan 6.

Geneshifters, 222 Mary Jena Lane, Pullman, WA, 99163, USA.

Yield losses because of cereal cyst nematodes could be as high as 92%, causing a bottleneck for wheat production. An integrated approach (application of pesticides, crop rotation, and use of host resistance) is needed to manage this devastating pathogen where resistant cultivars are considered most effective. This necessitates the identification of nematode-resistant sources in the available germplasm. Here, we report on the genetic mapping of nematode resistance in 255 diverse prebreeding lines (PBLs) employing an association mapping strategy. Altogether, seven additive quantitative trait loci (QTL) were identified on chromosomes 1A, 2A, 2B, 2D, 3A, 6B, and 6D explaining a maximum of 9.42% phenotypic variation where at least five QTL (on chromosomes 2A, 2B, 2D, 6B, and 6D) are located on the same chromosomes that harbor the already known nematode resistance genes. Resistant PBLs carried Aegilops squarrosa (436) in their pedigree which could be the possible source of positive alleles. To add to it, better yield performance of the identified nematode-resistant lines under stress conditions indicates that the germplasm can provide both nematode resistance and high-yielding cultivars.
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http://dx.doi.org/10.1007/s13353-020-00607-yDOI Listing
February 2021

Diversity analysis of 80,000 wheat accessions reveals consequences and opportunities of selection footprints.

Nat Commun 2020 09 11;11(1):4572. Epub 2020 Sep 11.

Genetic Resources Program, International Maize and Wheat Improvement Center (CIMMYT), Carretera México-Veracruz Km. 45 El Batán, Texcoco, C.P., 56237, Mexico.

Undomesticated wild species, crop wild relatives, and landraces represent sources of variation for wheat improvement to address challenges from climate change and the growing human population. Here, we study 56,342 domesticated hexaploid, 18,946 domesticated tetraploid and 3,903 crop wild relatives in a massive-scale genotyping and diversity analysis. Using DArTseq technology, we identify more than 300,000 high-quality SNPs and SilicoDArT markers and align them to three reference maps: the IWGSC RefSeq v1.0 genome assembly, the durum wheat genome assembly (cv. Svevo), and the DArT genetic map. On average, 72% of the markers are uniquely placed on these maps and 50% are linked to genes. The analysis reveals landraces with unexplored diversity and genetic footprints defined by regions under selection. This provides fertile ground to develop wheat varieties of the future by exploring specific gene or chromosome regions and identifying germplasm conserving allelic diversity missing in current breeding programs.
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http://dx.doi.org/10.1038/s41467-020-18404-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7486412PMC
September 2020

Frontline Science: AMPK regulates metabolic reprogramming necessary for interferon production in human plasmacytoid dendritic cells.

J Leukoc Biol 2021 02 8;109(2):299-308. Epub 2020 Jul 8.

Department of Pathology, Immunology, and Laboratory Medicine, Rutgers New Jersey Medical School, Newark, New Jersey, USA.

Plasmacytoid dendritic cells (pDCs) play a crucial role in innate viral immunity as the most potent producers of type I interferons (IFN) in the human body. However, the metabolic regulation of IFN production in such vast quantity remains poorly understood. In this study, AMP-activated protein kinase (AMPK) is strongly implicated as a driver of metabolic reprogramming that the authors and others have observed in pDCs after activation via TLR7/9. Oxygen consumption and mitochondrial membrane potential (MMP) were elevated following stimulation of pDCs with influenza or herpes simplex virus. Blocking these changes using mitochondrial inhibitors abrogated IFN-α production. While it appears that multiple carbon sources can be used by pDCs, blocking pyruvate metabolism had the strongest effect on IFN-α production. Furthermore, we saw no evidence of aerobic glycolysis (AG) during pDC activation and blocking lactate dehydrogenase activity did not inhibit IFN-α. TLR7/9 ligation induces a posttranslational modification in Raptor that is catalyzed by AMPK, and blocking TLR7/9 before virus introduction prevents this change. Finally, it is demonstrated that Dorsomorphin, an AMPK inhibitor, inhibited both IFN-α production and MMP in a dose-dependent manner. Taken together, these data reveal a potential cellular mechanism for the metabolic reprogramming in TLR 7/9-activated pDCs that supports activation and IFN-α production.
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http://dx.doi.org/10.1002/JLB.3HI0220-130DOI Listing
February 2021

Triggering of the cGAS-STING Pathway in Human Plasmacytoid Dendritic Cells Inhibits TLR9-Mediated IFN Production.

J Immunol 2020 07 29;205(1):223-236. Epub 2020 May 29.

Rutgers School of Graduate Studies, Newark, NJ 07103;

Plasmacytoid dendritic cells (pDCs) are potent producers of type I and type III IFNs and play a major role in antiviral immunity and autoimmune disorders. The innate sensing of nucleic acids remains the major initiating factor for IFN production by pDCs. TLR-mediated sensing of nucleic acids via endosomal pathways has been studied and documented in detail, whereas the sensing of DNA in cytosolic compartment in human pDCs remains relatively unexplored. We now demonstrate the existence and functionality of the components of cytosolic DNA-sensing pathway comprising cyclic GMP-AMP (cGAMP) synthase (cGAS) and stimulator of IFN gene (STING) in human pDCs. cGAS was initially located in the cytosolic compartment of pDCs and time-dependently colocalized with non-CpG double-stranded immunostimulatory DNA (ISD). Following the colocalization of ISD with cGAS, the downstream pathway was triggered as STING disassociated from its location at the endoplasmic reticulum. Upon direct stimulation of pDCs by STING agonist 2'3' cGAMP or dsDNA, pDC-s produced type I, and type III IFN. Moreover, we documented that cGAS-STING-mediated IFN production is mediated by nuclear translocation of IRF3 whereas TLR9-mediated activation occurs through IRF7. Our data also indicate that pDC prestimulation of cGAS-STING dampened the TLR9-mediated IFN production. Furthermore, triggering of cGAS-STING induced expression of SOCS1 and SOCS3 in pDCs, indicating a possible autoinhibitory loop that impedes IFN production by pDCs. Thus, our study indicates that the cGAS-STING pathway exists in parallel to the TLR9-mediated DNA recognition in human pDCs with cross-talk between these two pathways.
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http://dx.doi.org/10.4049/jimmunol.1800933DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7460725PMC
July 2020

Epidemiology and Antifungal Susceptibility of Infections Caused by Species: An Emerging Non- and Non- Yeast Worldwide.

Indian J Med Microbiol 2019 Oct-Dec;37(4):536-541

Department of Dermatology, VMMC and Safdarjung Hospital, New Delhi, India.

Introduction: Over the past four decades, there has been an increase in the number of fatal opportunistic invasive trichosporonosis cases especially in immunocompromised hosts.

Objective: The objective of the study is to evaluate the epidemiological, clinical details and antifungal susceptibility pattern of the patients with Trichosporon infections.

Materials And Methods: Twenty-four clinical isolates of Trichosporon species isolated from blood, samples, pleural fluid and nail were included in this study, over a period of 12 years (2005-2016) in a tertiary hospital in North India. The isolates were characterised phenotypically and few representative isolates were sequenced also. The minimum inhibitory concentration (MIC) was determined as per Clinical and Laboratory Standards Institute, 2012.

Results: Trichosporon spp. from blood culture (57.78%), nail (37.5%) and pleural fluid (4.17%). On phenotypic tests, 79.16% of the isolates were Trichosporon asahii, followed by Trichosporon dermatis (8.33%), Trichosporon japonicum (4.17%), Trichosporon ovoides (4.17%) and Trichosporon mucoides (4.17%). The MIC range of Trichosporon species from invasive infections were fluconazole (0.06-256 μg/ml), amphotericin B (0.125-16 μg/ml), voriconazole (0.0616-8 μg/ml), posaconazole (0.0616-32 μg/ml) and caspofungin (8-32 μg/ml). The isolates from superficial infection were resistant to fluconazole (0.06-256 μg/ml) and itraconazole (0.125-32 μg/ml), all were susceptible to ketoconazole and while only two were resistant to voriconazole (0.25-4 μg/ml).

Conclusion: T. asahii was the most common isolate. Disseminated trichosporonosis is being increasingly reported worldwide including India and represents a challenge for both diagnosis and species identification. Prognosis is limited, and antifungal regimens containing triazoles appear to be the best therapeutic approach. In addition, accurate identification, removal of central venous lines and voriconazole-based treatment along with control of underlying conditions were associated with favourable outcomes.
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http://dx.doi.org/10.4103/ijmm.IJMM_19_146DOI Listing
July 2020

Molecular Markers Associated with Agro-Physiological Traits under Terminal Drought Conditions in Bread Wheat.

Int J Mol Sci 2020 Apr 30;21(9). Epub 2020 Apr 30.

International Maize and Wheat Improvement Centre (CIMMYT) km, 45, Carretera Mex-Veracruz, El-Batan, Texcoco CP 56237, Mexico.

Terminal drought stress poses a big challenge to sustain wheat grain production in rain-fed environments. This study aimed to utilize the genetically diverse pre-breeding lines for identification of genomic regions associated with agro-physiological traits at terminal stage drought stress in wheat. A total of 339 pre-breeding lines panel derived from three-way crosses of 'exotics × elite × elite' lines were evaluated in field conditions at Obregon, Mexico for two years under well irrigated as well as drought stress environments. Drought stress was imposed at flowering by skipping the irrigations at pre and post anthesis stage. Results revealed that drought significantly reduced grain yield (Y), spike length (SL), number of grains spikes (NGS) and thousand kernel weight (TKW), while kernel abortion (KA) was increased. Population structure analysis in this panel uncovered three sub-populations. Genome wide linkage disequilibrium (LD) decay was observed at 2.5 centimorgan (cM). The haplotypes-based genome wide association study (GWAS) identified significant associations of Y, SL, and TKW on three chromosomes; 4A (HB10.7), 2D (HB6.10) and 3B (HB8.12), respectively. Likewise, associations on chromosomes 6B (HB17.1) and 3A (HB7.11) were found for NGS while on chromosome 3A (HB7.12) for KA. The genomic analysis information generated in the study can be efficiently utilized to improve Y and/or related parameters under terminal stage drought stress through marker-assisted breeding.
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http://dx.doi.org/10.3390/ijms21093156DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7247584PMC
April 2020

Regional differences in agricultural and socioeconomic factors associated with farmer household dietary diversity in India.

PLoS One 2020 16;15(4):e0231107. Epub 2020 Apr 16.

School for Environmental and Sustainability (SEAS), University of Michigan, Ann Arbor, MI, United States of America.

This paper investigated whether there are any regional-level differences in factors associated with farmer household dietary diversity using the Food Consumption Score (FCS), in two states of India: Haryana and Gujarat. Our results suggest that the factors associated with farmer household dietary diversity were region-specific, with diverse drivers across districts. For example, in Vadodara (Gujarat), farmers who had greater crop diversity and planted more cash crops had higher dietary diversity while large landholders in Bhavnagar (Gujarat) had higher dietary diversity. In Karnal (Haryana), more educated farmer households and those who cultivated large landholdings had higher dietary diversity while farmers in Bhiwani (Haryana) who were more educated and sold more crops to market had higher dietary diversity. Thus, factors associated with FCS differed even within the same state. These results suggest that in some regions of India, higher crop diversity and better education could improve farmer household dietary diversity. On the other hand, in some other regions, dietary diversity is best improved through the income generation pathway, where households that earn increased income from selling more crops were able to purchase more diverse food from markets. Our study suggests that the drivers of household dietary diversity across rural India are complex and heterogeneous; thus, future policies and programs to improve farmer household nutrition should be tailored considering regional differences in the factors associated with household nutrition.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0231107PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7161949PMC
July 2020

GWAS revealed a novel resistance locus on chromosome 4D for the quarantine disease Karnal bunt in diverse wheat pre-breeding germplasm.

Sci Rep 2020 04 7;10(1):5999. Epub 2020 Apr 7.

International Maize and Wheat Improvement Center (CIMMYT), Carretera México-Veracruz Km. 45, El Batán, Texcoco, C.P. 56237, México.

This study was initiated to identify genomic regions conferring resistance to Karnal Bunt (KB) disease in wheat through a genome-wide association study (GWAS) on a set of 179 pre-breeding lines (PBLs). A GWAS of 6,382 high-quality DArTseq SNPs revealed 15 significant SNPs (P-value <10) on chromosomes 2D, 3B, 4D and 7B that were associated with KB resistance in individual years. In particular, two SNPs (chromosome 4D) had the maximum R values: SNP 1114200 | F | 0-63:T > C at 1.571 cM and R of 12.49% and SNP 1103052 | F | 0-61:C > A at 1.574 cM and R of 9.02%. These two SNPs displayed strong linkage disequilibrium (LD). An in silico analysis of SNPs on chromosome 4D identified two candidate gene hits, TraesCS4D02G352200 (TaNox8; an NADPH oxidase) and TraesCS4D02G350300 (a rhomboid-like protein belonging to family S54), with SNPs 1103052 | F | 0-61:C > A and 1101835 | F | 0-5:C > A, respectively, both of which function in biotic stress tolerance. The epistatic interaction analysis revealed significant interactions among 4D and 7B loci. A pedigree analysis of confirmed resistant PBLs revealed that Aegilops species is one of the parents and contributed the D genome in these resistant PBLs. These identified lines can be crossed with any elite cultivar across the globe to incorporate novel KB resistance identified on 4B.
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http://dx.doi.org/10.1038/s41598-020-62711-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7138846PMC
April 2020

Multi-Locus Genome Wide Association Mapping for Yield and Its Contributing Traits in Hexaploid Wheat under Different Water Regimes.

Sci Rep 2019 12 20;9(1):19486. Epub 2019 Dec 20.

Department of Genetics and Plant Breeding, Ch. Charan Singh University, Meerut, India.

Multi-locus genome wide association study was undertaken using a set of 320 diverse spring wheat accessions, which were each genotyped for 9,626 SNPs. The association panel was grown in replicated trials in four environments [two each in irrigated (IR) and rainfed (RF) environments], and phenotypic data were recorded for five traits including days to heading, days to maturity, plant height, thousand grain weight and grain yield. Forty-six significant marker-trait associations (MTAs) were identified for five traits. These included 20 MTAs in IR and 19 MTAs in RF environments; seven additional MTAs were common to both the environments. Five of these MTAs were co-localized with previously known QTL/MTAs and the remaining MTAs were novel and add to the existing knowledge. Three desirable haplotypes for agronomic traits, one for improvement in RF environment and two for improvement in IR environment were identified. Eighteen (18) promising candidate genes (CGs) involved in seven different biological activities were also identified. The expression profiles of four (Trehalose-6-Phosphate, APETALA2/Ethylene-responsive factor, DNA-binding One Zinc Finger and Gibberellin-dioxygenases) of the 18 genes showed that they were induced by drought stress in the wheat seedlings. The MTAs, haplotypes and CG-based markers may be used in marker-assisted breeding for drought tolerance in wheat.
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http://dx.doi.org/10.1038/s41598-019-55520-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6925107PMC
December 2019

Impact of Advocacy, Communication, Social Mobilization and Active Case Finding on TB Notification in Jharkhand, India.

J Epidemiol Glob Health 2019 12;9(4):233-242

Infectious Diseases, Foundation for Innovative New Diagnostics (FIND), New Delhi, India.

Community-level benefits of screening for active tuberculosis (TB) disease remain uncertain. Project Axshya (meaning free of TB) conducted advocacy, communication, social mobilization, and active case finding among vulnerable/marginalized populations of India. Among 15 districts of Jharkhand state, the project was initiated in 36 subdistrict level administrative units - tuberculosis units (TUs) in a staggered manner between April 2013 and September 2014, and continued till the end of 2015. Seven TUs did not implement the project. We assessed the relative change in the quarterly TB case finding indicators ( = 4) after inclusion of a TU within the project. By fitting four multilevel models (mixed-effects maximum likelihood regression using random intercept), we adjusted for secular (over previous five quarters) and seasonal trends, baseline differences within Axshya and non-Axshya TUs, and population size and clustering within districts and within TUs. After inclusion of a TU within the project, we found a significant increase [95% confidence interval (CI)] in TU-level presumptive TB sputum examination rate, new sputum-positive TB Case Notification Rate (CNR), sputum-positive TB CNR, and all forms TB CNR by 12 (5.5, 18.5), 1.1 (0.5, 1.7), 1.3 (0.6, 2.0), and 1.2 (0.1, 2.2) per 100,000 population per quarter, respectively. Overall, the project resulted in an increase (95% CI) in sputum examination and detection of new sputum-positive TB, sputum-positive TB and all forms of TB patients by 22,410 (10,203, 34,077), 2066 (923, 3210), 2380 (1162, 3616), and 2122 (203, 4059), respectively. This provides evidence for implementing project Axshya over and above the existing passive case finding.
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http://dx.doi.org/10.2991/jegh.k.190812.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7310791PMC
December 2019

GWAS to Identify Genetic Loci for Resistance to Yellow Rust in Wheat Pre-Breeding Lines Derived From Diverse Exotic Crosses.

Front Plant Sci 2019 30;10:1390. Epub 2019 Oct 30.

Department of Bioscience, Centro Internacional de Mejoramiento de Maíz y Trigo, Texcoco, Mexico.

Yellow rust (YR) or stripe rust, caused by f. sp Eriks (), is a major challenge to resistance breeding in wheat. A genome wide association study (GWAS) was performed using 22,415 single nucleotide polymorphism (SNP) markers and 591 haplotypes to identify genomic regions associated with resistance to YR in a subset panel of 419 pre-breeding lines (PBLs) developed at International Center for Maize and Wheat Improvement (CIMMYT). The 419 PBLs were derived from an initial set of 984 PBLs generated by a three-way crossing scheme (exotic/elite1//elite2) among 25 best elites and 244 exotics (synthetics, landraces) from CIMMYT's germplasm bank. For the study, 419 PBLs were characterized with 22,415 high-quality DArTseq-SNPs and phenotyped for severity of YR disease at five locations in Mexico. A population structure was evident in the panel with three distinct subpopulations, and a genome-wide linkage disequilibrium (LD) decay of 2.5 cM was obtained. Across all five locations, 14 SNPs and 7 haplotype blocks were significantly ( < 0.001) associated with the disease severity explaining 6.0 to 14.1% and 7.9 to 19.9% of variation, respectively. Based on average LD decay of 2.5 cM, identified 14 SNP-trait associations were delimited to seven quantitative trait loci in total. Seven SNPs were part of the two haplotype blocks on chromosome 2A identified in haplotypes-based GWAS. analysis of the identified SNPs showed hits with interesting candidate genes, which are related to pathogenic process or known to regulate induction of genes related to pathogenesis such as those coding for glunolactone oxidase, quinate O-hydroxycinnamoyl transferase, or two-component histidine kinase. The two-component histidine kinase, for example, acts as a sensor in the perception of phytohormones ethylene and cytokinin. Ethylene plays a very important role in regulation of multiple metabolic processes of plants, including induction of defense mechanisms mediated by jasmonate. The SNPs linked to the promising genes identified in the study can be used for marker-assisted selection.
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http://dx.doi.org/10.3389/fpls.2019.01390DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6831551PMC
October 2019

Characterization of QTLs for Seedling Resistance to Tan Spot and Septoria Nodorum Blotch in the PBW343/Kenya Nyangumi Wheat Recombinant Inbred Lines Population.

Int J Mol Sci 2019 Oct 31;20(21). Epub 2019 Oct 31.

International Maize and Wheat Improvement Center (CIMMYT), Apdo. Postal 6-641, México 06600, D.F., Mexico.

Tan spot (TS) and Septoria nodorum blotch (SNB) induced by and , respectively, cause significant yield losses and adversely affect grain quality. The objectives of this study were to decipher the genetics and map the resistance to TS and SNB in the PBW343/Kenya Nyangumi (KN) population comprising 204 F recombinant inbred lines (RILs). Disease screening was performed at the seedling stage under greenhouse conditions. TS was induced by isolate MexPtr1 while SNB by isolate MexSN1. Segregation pattern of the RILs indicated that resistance to TS and SNB in this population was quantitative. Diversity Array Technology (DArTs) and simple sequence repeats (SSRs) markers were used to identify the quantitative trait loci (QTL) for the diseases using inclusive composite interval mapping (ICIM). Seven significant additive QTLs for TS resistance explaining 2.98 to 23.32% of the phenotypic variation were identified on chromosomes 1A, 1B, 5B, 7B and 7D. For SNB, five QTLs were found on chromosomes 1A, 5A, and 5B, explaining 5.24 to 20.87% of the phenotypic variation. The TS QTL on 1B chromosome coincided with the pleiotropic adult plant resistance (APR) gene . This is the first report of the APR gene contributing to TS resistance.
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http://dx.doi.org/10.3390/ijms20215432DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6862150PMC
October 2019

Phase Space Reconstruction of EEG Signals for Classification of ADHD and Control Adults.

Clin EEG Neurosci 2020 Mar 19;51(2):102-113. Epub 2019 Sep 19.

Department of Psychiatry, Government Medical College and Hospital, Chandigarh, India.

Attention deficit hyperactivity disorder (ADHD) is a childhood behavioral disorder that can persist into adulthood. Electroencephalography (EEG) plays a significant role in assessing the neurophysiology of ADHD because of its ability to reveal complex brain activity. The present study proposes an EEG-based diagnosis system using the phase space reconstruction technique to classify ADHD and control adults. Electric activity is recorded for 47 ADHD and 50 control adults during the eyes-open, eyes-closed, and Continuous Performance Test (CPT) condition. Various statistical features are extracted from Euclidean distances based on phase space reconstruction of signals. The proposed system is evaluated with 2 feature selection methods (correlation-based feature selection and particle swarm optimization) and 5 machine learning methods (neural dynamic classifier, support vector machine, enhanced probabilistic neural network, k-nearest neighbor, and naive-Bayes classifier). Experimental results showed the highest testing accuracy of 93.3% under the eyes-open, 90% under the eyes-closed, and 100% under the CPT condition. This study focused on the utility of phase space reconstruction of brain signals to discriminate between ADHD and control adults.
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http://dx.doi.org/10.1177/1550059419876525DOI Listing
March 2020

Population-dependent reproducible deviation from natural bread wheat genome in synthetic hexaploid wheat.

Plant J 2019 11 3;100(4):801-812. Epub 2019 Sep 3.

Agriculture Victoria, AgriBio, Centre for AgriBiosciences, Bundoora, VIC, Australia.

Sequence elimination is one of the main mechanisms that increases the divergence among homoeologous chromosomes after allopolyploidization to enhance the stability of recently established lineages, but it can cause a loss of some economically important genes. Synthetic hexaploid wheat (SHW) is an important source of genetic variation to the natural hexaploid wheat (NHW) genepool that has low genetic diversity. Here, we investigated the change between SHW and NHW genomes by utilizing a large germplasm set of primary synthetics and synthetic derivatives. Reproducible segment elimination (RSE) was declared if a large chromosomal chunk (>5 cM) produced no aligned reads in more than five SHWs. RSE in five genomic regions was the major source of variation between SHW and NHW. One RSE eliminated almost the complete short arm of chromosome 1B, which contains major genes for flour quality, disease resistance and different enzymes. The occurrence of RSE was highly dependent on the choice of diploid and tetraploid parental lines, their ancestral subpopulation and admixture, e.g. SHWs derived from Triticum dicoccon or from one of two Aegilops tauschii subpopulations were almost free of RSE, while highly admixed parents had higher RSE rates. The rate of RSE in synthetic derivatives was almost double that in primary synthetics. Genome-wide association analysis detected four loci with minor effects on the occurrence of RSE, indicating that both parental lines and genetic factors were affecting the occurrence of RSE. Therefore, pre-pre-breeding strategies should be applied before introducing SHW into pre-breeding programs to ensure genomic stability and avoid undesirable gene loss.
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http://dx.doi.org/10.1111/tpj.14480DOI Listing
November 2019

X-Linked IRAK1 Polymorphism is Associated with Sex-Related Differences in Polymorphonuclear Granulocyte and Monocyte Activation and Response Variabilities.

Shock 2020 04;53(4):434-441

Department of Surgery, Rutgers New Jersey Medical School, Newark, New Jersey.

Common X-linked genetic polymorphisms are expected to alter cellular responses affecting males and females differently through sex-linked inheritance pattern as well as X chromosome (ChrX) mosaicism and associated ChrX skewing, which is unique to females. We tested this hypothesis in ex vivo lipopolysaccharide and phorbol ester-stimulated polymorphonuclear granulocytes (PMNs) and monocytes from healthy volunteers (n = 51). Observations were analyzed after stratification by sex alone or the presence of variant IRAK1 haplotype a common X-linked polymorphism with previously demonstrated major clinical impacts. Upon cell activation, CD11b, CD45, CD66b, CD63, and CD14 expression was markedly and similarly elevated in healthy males and females. By contrast, PMN and monocyte activation measured by CD11b, CD66b, and CD63 was increased in variant-IRAK1 subjects as compared with WT. Stratification by IRAK1 genotype and sex showed similar cell activation effect on variant-IRAK1 subjects and an intermediate degree of cell activation in heterozygous mosaic females. The increased membrane expression of these proteins in variant-IRAK1 subjects was associated with similar or increased intersubject but uniformly decreased intrasubject cell response variabilities as compared with WT. We also tested white blood cell ChrX skewing in the healthy cohort as well as in a sample of female trauma patients (n = 201). ChrX inactivation ratios were similar in IRAK1 WT, variant, and heterozygous healthy subjects. Trauma patients showed a trend of blunted ChrX skewing at admission in homozygous variant-IRAK1 and heterozygous mosaic-IRAK1 female subjects as compared with WT. Trauma-induced de novo ChrX skewing was also depressed in variant-IRAK1 and mosaic-IRAK1 female trauma patients as compared with WT. Our study indicates that augmented PMN and monocyte activation in variant-IRAK1 subjects is accompanied by decreased intrasubject cellular variability and blunted de novo ChrX skewing in response to trauma. A more pronounced cell activation of PMNs and monocytes accompanied by decreased response variabilities in variant-IRAK1 subjects may be a contributing mechanism affecting the course of sepsis and trauma and may also impact sex-based outcome differences due to its X-linked inheritance pattern and high prevalence.
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http://dx.doi.org/10.1097/SHK.0000000000001404DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6952590PMC
April 2020

Bacteremia by in a Patient with Lung Cancer: A Clinical and Microbiological Investigation.

Indian J Crit Care Med 2019 Mar;23(3):157-159

Department of Microbiology, Dharmshila Narayana Superspeciality Hospital, Delhi, India.

We present a case of bacteremia by an unsual, instrinsically multidrug resistant organism, in a 59 year old gentleman with squamous cell carcinoma of lung with multiple metastasis. Despite of treating as per sensitivity report after isolating, patient could not be survived. The pathogenicity and predictability of the organism towards antibiotics, both and needs further research.

How To Cite This Article: Bhagawati G, Bhardwaj A . Bacteremia by in a Patient with Lung Cancer: A Clinical and Microbiological Investigation. Indian J Crit Care Med 2019;23(3):157-159.
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http://dx.doi.org/10.5005/jp-journals-10071-23142DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6487623PMC
March 2019

Event-Related Potential Analysis of ADHD and Control Adults During a Sustained Attention Task.

Clin EEG Neurosci 2019 Nov 18;50(6):389-403. Epub 2019 Apr 18.

2 Department of Psychiatry, Government Medical College and Hospital, Chandigarh, India.

. Event-related potentials (ERPs) of attention deficit hyperactivity disorder (ADHD) population have been extensively studied using the time-domain representation of signals but time-frequency domain techniques are less explored. Although, adult ADHD is a proven disorder, most of the electrophysiological studies have focused only on children with ADHD. . ERP data of 35 university students with ADHD and 35 control adults were recorded during visual continuous performance task (CPT). Gray level co-occurrence matrix-based texture features were extracted from time-frequency () images of event-related EEG epochs. Different ERP components measures, that is, amplitudes and latencies corresponding to N1, N2, and P3 components were also computed relative to standard and target stimuli. . Texture analysis has shown that the mean value of contrast, dissimilarity, and difference entropy is significantly reduced in adults with ADHD than in control adults. The mean correlation and homogeneity in adults with ADHD were significantly increased as compared with control adults. ERP components analysis has reported that adults with ADHD have reduced N1 amplitude to target stimuli, reduced N2 and P3 amplitude to both standard and target stimuli than controls. . The differences in texture features obtained from images of ERPs point toward altered information processing in adults with ADHD during a cognitive task. Findings of reduction in N1, N2, and P3 components highlight deficits of early sensory processing, stimulus categorization, and attentional resources, respectively, in adults with ADHD.
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http://dx.doi.org/10.1177/1550059419842707DOI Listing
November 2019

Unravelling the Complex Genetics of Karnal Bunt () Resistance in Common Wheat () by Genetic Linkage and Genome-Wide Association Analyses.

G3 (Bethesda) 2019 05 7;9(5):1437-1447. Epub 2019 May 7.

Grains Research and Development Corporation, P.O. Box 5367, Kingston, ACT 2604, Australia.

Karnal bunt caused by Mitra [syn. (Mitra) Mundkur] is a significant biosecurity concern for wheat-exporting countries that are free of the disease. It is a seed-, soil-and air-borne disease with no effective chemical control measures. The current study used data from multi-year field experiments of two bi-parental populations and a genome-wide association (GWA) mapping panel to unravel the genetic basis for resistance in common wheat. Broad-sense heritability for Karnal bunt resistance in the populations varied from 0.52 in the WH542×HD29 population, to 0.61 in the WH542×W485 cross and 0.71 in a GWAS panel. Quantitative trait locus (QTL) analysis with seven years of phenotypic data identified a major locus on chromosome 3B (R = 27.8%) and a minor locus on chromosome 1A (R = 12.2%), in the WH542×HD29 population, with both parents contributing the high-value alleles. A major locus (R = 27.8%) and seven minor loci (R = 4.4-15.8%) were detected in the WH542×W485 population. GWA mapping validated QTL regions in the bi-parent populations, but also identified novel loci not previously associated with Karnal bunt resistance. Meta-QTL analysis aligned the results from this study with those reported in wheat over the last two decades. Two major clusters were detected, the first on chromosome 4B, which clustered with , , , and the second on chromosome 3B, which clustered with , and The results provide definitive chromosomal assignments for QTL/genes controlling Karnal bunt resistance in common wheat, and will be useful in pre-emptive breeding against the pathogen in wheat-producing areas that are free of the disease.
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http://dx.doi.org/10.1534/g3.119.400103DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6505162PMC
May 2019

Integrating genomic resources to present full gene and putative promoter capture probe sets for bread wheat.

Gigascience 2019 04;8(4)

Earlham Institute, Norwich Research Park, Norwich, NR4 7UZ, UK.

Background: Whole-genome shotgun resequencing of wheat is expensive because of its large, repetitive genome. Moreover, sequence data can fail to map uniquely to the reference genome, making it difficult to unambiguously assign variation. Resequencing using target capture enables sequencing of large numbers of individuals at high coverage to reliably identify variants associated with important agronomic traits. Previous studies have implemented complementary DNA/exon or gene-based probe sets in which the promoter and intron sequence is largely missing alongside newly characterized genes from the recent improved reference sequences.

Results: We present and validate 2 gold standard capture probe sets for hexaploid bread wheat, a gene and a putative promoter capture, which are designed using recently developed genome sequence and annotation resources. The captures can be combined or used independently. We demonstrate that the capture probe sets effectively enrich the high-confidence genes and putative promoter regions that were identified in the genome alongside a large proportion of the low-confidence genes and associated promoters. Finally, we demonstrate successful sample multiplexing that allows generation of adequate sequence coverage for single-nucleotide polymorphism calling while significantly reducing cost per sample for gene and putative promoter capture.

Conclusions: We show that a capture design employing an "island strategy" can enable analysis of the large gene/putative promoter space of wheat with only 2 × 160 Mbp probe sets. Furthermore, these assays extend the regions of the wheat genome that are amenable to analyses beyond its exome, providing tools for detailed characterization of these regulatory regions in large populations.
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http://dx.doi.org/10.1093/gigascience/giz018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6461119PMC
April 2019

Efficient curation of genebanks using next generation sequencing reveals substantial duplication of germplasm accessions.

Sci Rep 2019 01 24;9(1):650. Epub 2019 Jan 24.

Wheat Genetics Resource Center, Department of Plant Pathology, Kansas State University, Manhattan, KS, 66506, USA.

Genebanks are valuable resources for crop improvement through the acquisition, ex-situ conservation and sharing of unique germplasm among plant breeders and geneticists. With over seven million existing accessions and increasing storage demands and costs, genebanks need efficient characterization and curation to make them more accessible and usable and to reduce operating costs, so that the crop improvement community can most effectively leverage this vast resource of untapped novel genetic diversity. However, the sharing and inconsistent documentation of germplasm often results in unintentionally duplicated collections with poor characterization and many identical accessions that can be hard or impossible to identify without passport information and unmatched accession identifiers. Here we demonstrate the use of genotypic information from these accessions using a cost-effective next generation sequencing platform to find and remove duplications. We identify and characterize over 50% duplicated accessions both within and across genebank collections of Aegilops tauschii, an important wild relative of wheat and source of genetic diversity for wheat improvement. We present a pipeline to identify and remove identical accessions within and among genebanks and curate globally unique accessions. We also show how this approach can also be applied to future collection efforts to avoid the accumulation of identical material. When coordinated across global genebanks, this approach will ultimately allow for cost effective and efficient management of germplasm and better stewarding of these valuable resources.
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http://dx.doi.org/10.1038/s41598-018-37269-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6346010PMC
January 2019

Cytokine profile in prediction of acute lung injury in patients with acute pancreatitis.

Pancreatology 2018 Dec 18;18(8):878-884. Epub 2018 Oct 18.

Department of Gastroenterology, Postgraduate Institute of Medical Education and Research, Chandigarh, India. Electronic address:

Objectives: To study the role of cytokines in prediction of acute lung injury (ALI) in acute pancreatitis.

Methods: Levels of TNFα, IL-6, IL-10, IL-8 and IL-1β were measured in 107 patients at presentation and at 72 h in patients who developed acute lung injury. A model was devised to predict development of ALI using cytokine levels and SIRS score.

Results: The levels of TNF α (p < 0.0001), IL-6 (p < 0.0001), IL-8 (p < 0.0001) and IL-1β (p < 0.0001) were significantly higher in the ALI group. IL-10 levels were significantly lower in persistent ALI (p-ALI) than in transient ALI (t-ALI) patients (p < 0.038). p-ALI group had significant rise of TNFα (p = 0.019) and IL-1β (p = 0.001) while t-ALI group had significant rise of only IL-1β (p = 0.044) on day 3 vs day 1. Combined values of IL-6 and IL-8 above 251 pg/ml had sensitivity of 90.9% and a specificity of 100% to predict future development of ALI. Composite marker-I (IL6 ≥ 80 pg/ml + SIRS) yielded sensitivity and specificity of 73% and 98% whereas composite marker-II (IL8 ≥ 100 pg/ml + SIRS) yielded sensitivity and specificity of 73% and 95% to predict future ALI.

Conclusions: IL-6 and IL-8 can predict future development of ALI. When they are combined with SIRS, they can be used as comprehensive composite markers.
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http://dx.doi.org/10.1016/j.pan.2018.10.006DOI Listing
December 2018

Storage lipid studies in tuberculosis reveal that foam cell biogenesis is disease-specific.

PLoS Pathog 2018 08 30;14(8):e1007223. Epub 2018 Aug 30.

Public Health Research Institute, New Jersey Medical School, Rutgers, The State University of New Jersey, Newark, NJ, United States of America.

Foam cells are lipid-laden macrophages that contribute to the inflammation and tissue damage associated with many chronic inflammatory disorders. Although foam cell biogenesis has been extensively studied in atherosclerosis, how these cells form during a chronic infectious disease such as tuberculosis is unknown. Here we report that, unlike the cholesterol-laden cells of atherosclerosis, foam cells in tuberculous lung lesions accumulate triglycerides. Consequently, the biogenesis of foam cells varies with the underlying disease. In vitro mechanistic studies showed that triglyceride accumulation in human macrophages infected with Mycobacterium tuberculosis is mediated by TNF receptor signaling through downstream activation of the caspase cascade and the mammalian target of rapamycin complex 1 (mTORC1). These features are distinct from the known biogenesis of atherogenic foam cells and establish a new paradigm for non-atherogenic foam cell formation. Moreover, they reveal novel targets for disease-specific pharmacological interventions against maladaptive macrophage responses.
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http://dx.doi.org/10.1371/journal.ppat.1007223DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6117085PMC
August 2018

Harnessing genetic potential of wheat germplasm banks through impact-oriented-prebreeding for future food and nutritional security.

Sci Rep 2018 08 21;8(1):12527. Epub 2018 Aug 21.

ICAR-Indian Agricultural Research Institute, Regional Station, Shimla, 171004, India.

The value of exotic wheat genetic resources for accelerating grain yield gains is largely unproven and unrealized. We used next-generation sequencing, together with multi-environment phenotyping, to study the contribution of exotic genomes to 984 three-way-cross-derived (exotic/elite1//elite2) pre-breeding lines (PBLs). Genomic characterization of these lines with haplotype map-based and SNP marker approaches revealed exotic specific imprints of 16.1 to 25.1%, which compares to theoretical expectation of 25%. A rare and favorable haplotype (GT) with 0.4% frequency in gene bank identified on chromosome 6D minimized grain yield (GY) loss under heat stress without GY penalty under irrigated conditions. More specifically, the 'T' allele of the haplotype GT originated in Aegilops tauschii and was absent in all elite lines used in study. In silico analysis of the SNP showed hits with a candidate gene coding for isoflavone reductase IRL-like protein in Ae. tauschii. Rare haplotypes were also identified on chromosomes 1A, 6A and 2B effective against abiotic/biotic stresses. Results demonstrate positive contributions of exotic germplasm to PBLs derived from crosses of exotics with CIMMYT's best elite lines. This is a major impact-oriented pre-breeding effort at CIMMYT, resulting in large-scale development of PBLs for deployment in breeding programs addressing food security under climate change scenarios.
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http://dx.doi.org/10.1038/s41598-018-30667-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6104032PMC
August 2018

An informational view of accession rarity and allele specificity in germplasm banks for management and conservation.

PLoS One 2018 28;13(2):e0193346. Epub 2018 Feb 28.

International Maize and Wheat Improvement Center (CIMMYT), Mexico City, Mexico.

Germplasm banks are growing in their importance, number of accessions and amount of characterization data, with a large emphasis on molecular genetic markers. In this work, we offer an integrated view of accessions and marker data in an information theory framework. The basis of this development is the mutual information between accessions and allele frequencies for molecular marker loci, which can be decomposed in allele specificities, as well as in rarity and divergence of accessions. In this way, formulas are provided to calculate the specificity of the different marker alleles with reference to their distribution across accessions, accession rarity, defined as the weighted average of the specificity of its alleles, and divergence, defined by the Kullback-Leibler formula. Albeit being different measures, it is demonstrated that average rarity and divergence are equal for any collection. These parameters can contribute to the knowledge of the structure of a germplasm collection and to make decisions about the preservation of rare variants. The concepts herein developed served as the basis for a strategy for core subset selection called HCore, implemented in a publicly available R script. As a proof of concept, the mathematical view and tools developed in this research were applied to a large collection of Mexican wheat accessions, widely characterized by SNP markers. The most specific alleles were found to be private of a single accession, and the distribution of this parameter had its highest frequencies at low levels of specificity. Accession rarity and divergence had largely symmetrical distributions, and had a positive, albeit non-strictly linear relationship. Comparison of the HCore approach for core subset selection, with three state-of-the-art methods, showed it to be superior for average divergence and rarity, mean genetic distance and diversity. The proposed approach can be used for knowledge extraction and decision making in germplasm collections of diploid, inbred or outbred species.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0193346PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5831390PMC
May 2018

Decomposing Additive Genetic Variance Revealed Novel Insights into Trait Evolution in Synthetic Hexaploid Wheat.

Front Genet 2018 6;9:27. Epub 2018 Feb 6.

Grains Research and Development Corporation, Kingston, ACT, Australia.

Whole genome duplication (WGD) is an evolutionary phenomenon, which causes significant changes to genomic structure and trait architecture. In recent years, a number of studies decomposed the additive genetic variance explained by different sets of variants. However, they investigated diploid populations only and none of the studies examined any polyploid organism. In this research, we extended the application of this approach to polyploids, to differentiate the additive variance explained by the three subgenomes and seven sets of homoeologous chromosomes in synthetic allohexaploid wheat (SHW) to gain a better understanding of trait evolution after WGD. Our SHW population was generated by crossing improved durum parents ( 2n = 4x = 28, AABB subgenomes) with the progenitor species (syn ; 2n = 2x = 14, DD subgenome). The population was phenotyped for 10 fungal/nematode resistance traits as well as two abiotic stresses. We showed that the wild D subgenome dominated the additive effect and this dominance affected the A more than the B subgenome. We provide evidence that this dominance was not inflated by population structure, relatedness among individuals or by longer linkage disequilibrium blocks observed in the D subgenome within the population used for this study. The cumulative size of the three homoeologs of the seven chromosomal groups showed a weak but significant positive correlation with their cumulative explained additive variance. Furthermore, an average of 69% for each chromosomal group's cumulative additive variance came from one homoeolog that had the highest explained variance within the group across all 12 traits. We hypothesize that structural and functional changes during diploidization may explain chromosomal group relations as allopolyploids keep balanced dosage for many genes. Our results contribute to a better understanding of trait evolution mechanisms in polyploidy, which will facilitate the effective utilization of wheat wild relatives in breeding.
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http://dx.doi.org/10.3389/fgene.2018.00027DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5807918PMC
February 2018

B Cell-Intrinsic Role for IRF5 in TLR9/BCR-Induced Human B Cell Activation, Proliferation, and Plasmablast Differentiation.

Front Immunol 2017 10;8:1938. Epub 2018 Jan 10.

Center for Autoimmune Musculoskeletal and Hematopoietic Diseases, The Feinstein Institute for Medical Research, Manhasset, NY, United States.

Upon recognition of antigen, B cells undergo rapid proliferation followed by differentiation to specialized antibody secreting cells (ASCs). During this transition, B cells are reliant upon a multilayer transcription factor network to achieve a dramatic remodeling of the B cell transcriptional landscape. Increased levels of ASCs are often seen in autoimmune diseases and it is believed that altered expression of regulatory transcription factors play a role in this imbalance. The transcription factor interferon regulatory factor 5 (IRF5) is one such candidate as polymorphisms in associate with risk of numerous autoimmune diseases and correlate with elevated expression. genetic risk has been widely replicated in systemic lupus erythematosus (SLE), and loss of ameliorates disease in murine lupus models, in part, through the lack of pathogenic autoantibody secretion. It remains unclear, however, whether IRF5 is contributing to autoantibody production through a B cell-intrinsic function. To date, IRF5 function in healthy human B cells has not been characterized. Using human primary naive B cells, we define a critical intrinsic role for IRF5 in B cell activation, proliferation, and plasmablast differentiation. Targeted IRF5 knockdown resulted in significant immunoglobulin (Ig) D retention, reduced proliferation, plasmablast differentiation, and IgG secretion. The observed decreases were due to impaired B cell activation and clonal expansion. Distinct from murine studies, we identify and confirm new IRF5 target genes, , and , and pathways that mediate IRF5 B cell-intrinsic function. Together, these results identify IRF5 as an early regulator of human B cell activation and provide the first dataset in human primary B cells to map IRF5 dysfunction in SLE.
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http://dx.doi.org/10.3389/fimmu.2017.01938DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5768180PMC
January 2018

Inactivates Human Plasmacytoid Dendritic Cells by Functional Mimicry of IL-10.

J Immunol 2018 01 27;200(1):186-195. Epub 2017 Nov 27.

Department of Pathology and Laboratory Medicine, Rutgers New Jersey Medical School, Newark, NJ 07103;

Plasmacytoid dendritic cells (pDCs) are the major producers of IFN-α, an antiviral cytokine involved in immunomodulation and control of HIV type 1 replication, whereas is a life-threatening opportunistic infection in AIDS patients. During infection with HIV type 1, human pDCs decrease in circulation and remaining pDC produce lower amounts of IFN-α in response to viral stimulation. In this study, we investigated the impact of coinfection with on the innate virus-directed responses of human pDCs. Using intracellular flow cytometry and fluorescence microscopy, we determined that invaded but did not induce IFN-α or TNF-α in human pDC. However, inhibited IFN-α and TNF-α produced in response to HSV and HIV, thus functionally inactivating pDC. IFN-α production was inhibited only in cells infected by , which inhibited neither uptake of GFP-HSV nor localization of TLR9 in CD71 endosomes, directing us to investigate downstream events. Using imaging flow cytometry, we found that both and IL-10 inhibited virus-induced nuclear translocation, but not phosphorylation, of IFN response factor 7. Blockade of IFN response factor 7 nuclear translocation and inhibition of the IFN-α response was partially reversed by a deficiency in the -derived ROP16 kinase, known to directly phosphorylate STAT3, a critical mediator of IL-10's anti-inflammatory effects. Taken together, our results indicate that suppresses pDC activation by mimicking IL-10's regulatory effects through an ROP16 kinase-dependent mechanism. Our findings further imply a convergent mechanism of inhibition of TLR signaling by and IL-10 and suggest potential negative consequences of HIV/ coinfection.
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http://dx.doi.org/10.4049/jimmunol.1701045DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7441501PMC
January 2018

Genome-Wide Association Study Reveals Novel Genes Associated with Culm Cellulose Content in Bread Wheat (, L.).

Front Plant Sci 2017 6;8:1913. Epub 2017 Nov 6.

Department of Plant Science, McGill University, Sainte Anne de Bellevue, QC, Canada.

Plant cell wall formation is a complex, coordinated and developmentally regulated process. Cellulose is the most dominant constituent of plant cell walls. Because of its paracrystalline structure, cellulose is the main determinant of mechanical strength of plant tissues. As the most abundant polysaccharide on earth, it is also the focus of cellulosic biofuel industry. To reduce culm lodging in wheat and for improved ethanol production, delineation of the variation for stem cellulose content could prove useful. We present results on the analysis of the stem cellulose content of 288 diverse wheat accessions and its genome-wide association study (GWAS). Cellulose concentration ranged from 35 to 52% (w/w). Cellulose content was normally distributed in the accessions around a mean and median of 45% (w/w). Genome-wide marker-trait association study using 21,073 SNPs helped identify nine SNPs that were associated ( < 1E-05) with cellulose content. Four strongly associated ( < 8.17E-05) SNP markers were linked to wheat unigenes, which included β, and a putative transmembrane protein of unknown function. These genes may be directly or indirectly involved in the formation of cellulose in wheat culms. GWAS results from this study have the potential for genetic manipulation of cellulose content in bread wheat and other small grain cereals to enhance culm strength and improve biofuel production.
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http://dx.doi.org/10.3389/fpls.2017.01913DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5681534PMC
November 2017