Estrobolome dysregulation is associated with altered immunometabolism in a mouse model of endometriosis.

Introduction: Endometriosis is a painful disease that affects around 5% of women of reproductive age. In endometriosis, ectopic endometrial cells or seeded endometrial debris grow in abnormal locations including the peritoneal cavity. Common manifestations of endometriosis include dyspareunia, dysmenorrhea, chronic pelvic pain and often infertility and symptomatic relief or surgical removal are mainstays of treatment. Endometriosis both promotes and responds to estrogen imbalance, leading to intestinal bacterial estrobolome dysregulation and a subsequent induction of inflammation. Methods: In the current study, we investigated the linkage between gut dysbiosis and immune metabolic response in endometriotic mice. Ovariectomized BALB/c mice received intraperitoneal transplantation of endometrial tissue from OVX donors (OVX+END). Control groups included naïve mice (Naïve), naïve mice that received endometrial transplants (Naive+END) and OVX mice that received the vehicle (OVX+VEH). Colonic content was collected 2 weeks post-transplantation for 16s rRNA pyrosequencing and peritoneal fluid was collected to determine the phenotype of inflammatory cells by flow cytometry. Results: We noted a significant increase in the number of peritoneal fluid cells, specifically, T cells, natural killer (NK) cells, and NKT cells in OVX+END mice. Phylogenetic taxonomy analysis showed significant dysbiosis in OVX+END mice, with an increase in abundance of Phylum Tenericutes, Class Mollicutes, Order Aneroplasmatales, and Genus Aneroplasma, and a decrease in Order Clostridiales, and Genus Dehalobacterium, when compared to OVX+VEH controls. The metabolomic profile showed an increase in some tricarboxylic acid cycle (TCA)-related metabolites accompanied by a reduction in short-chain fatty acids (SCFA) such as butyric acid in OVX+END mice. Additionally, the mitochondrial and ATP production of immune cells was enforced to a maximal rate in OVX+END mice when compared to OVX+VEH mice. Conclusion: The current study demonstrates that endometriosis alters the gut microbiota and associated immune metabolism.

Corrigendum: Resveratrol attenuates allergic asthma and associated inflammation in the lungs through regulation of miRNA-34a that targets FoxP3 in mice.

[This corrects the article DOI: 10.3389/fimmu.2018.02992.].

2,3,7,8-Tetrachlorodibenzo-p-dioxin induces multigenerational alterations in the expression of microRNA in the thymus through epigenetic modifications.

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD), a potent AhR ligand, is an environmental contaminant that is known for mediating toxicity across generations. However, whether TCDD can induce multigenerational changes in the expression of microRNAs (miRs) has not been previously studied. In the current study, we investigated the effect of administration of TCDD in pregnant mice (F0) on gestational day 14, on the expression of miRs in the thymus of F0 and subsequent generations (F1 and F2). Of the 3200 miRs screened, 160 miRs were dysregulated similarly in F0, F1, and F2 generations, while 46 miRs were differentially altered in F0 to F2 generations. Pathway analysis revealed that the changes in miR signature profile mediated by TCDD affected the genes that regulate cell signaling, apoptosis, thymic atrophy, cancer, immunosuppression, and other physiological pathways. A significant number of miRs that showed altered expression exhibited dioxin response elements (DRE) on their promoters. Focusing on one such miR, namely miR-203 that expressed DREs and was induced across F0 to F2 by TCDD, promoter analysis showed that one of the DREs expressed by miR-203 was functional to TCDD-mediated upregulation. Also, the histone methylation status of H3K4me3 in the miR-203 promoter was significantly increased near the transcriptional start site in TCDD-treated thymocytes across F0 to F2 generations. Genome-wide chromatin immunoprecipitation sequencing study suggested that TCDD may cause alterations in histone methylation in certain genes across the three generations. Together, the current study demonstrates that gestational exposure to TCDD can alter the expression of miRs in F0 through direct activation of DREs as well as across F0, F1, and F2 generations through epigenetic pathways.

Development and implementation of a sustainable COVID-19 training package for healthcare workers: Experience from a teaching hospital of North India.

Background: With the impending threat of future COVID-19 waves, it is imperative that teaching hospitals develop, implement, and evaluate a systematic training program to render HCW elastic in delivering COVID-19 related services. We present our experience in developing, implementing, and evaluating a sustainable and scalable COVID-19 patient management training package for healthcare workers. Materials and Methods: A mixed-methods study design was used. Rapid assessment to understand the need of the trainees and identify the available resources was done followed by planning of the training module and its implementation. The program was evaluated for effectiveness and sustainability. Data analysis was done using descriptive statistics and qualitative data generated from open-ended questions in the feedback forms and the discussions were analyzed using rapid content analysis. Results: A total of 66.8% of the doctors and 18.9% of the nurses were trained by online synchronous mode while 55.0% of the nursing officers and 47.1% of the nursing orderlies and paramedical staff were trained in onsite skill development sessions. Need assessment identified that healthcare workers were ill-prepared to use medical devices such as Bipap machines, ventilators, and oxygen delivery devices. The participants mentioned that the multidisciplinary approach and video-based demonstrations facilitated their online learning while the incremental learning approach, easy-to-understand terminology and hands-on experience facilitated their onsite skill development sessions. Conclusion: The COVID-19 training package developed was multidisciplinary, effective, sustainable, and scalable in a resource-limited setting. We suggest that this model can be adapted by healthcare organizations to develop and implement such training packages for their healthcare workers.

Characterizing plant trait(s) for improved heat tolerance in field pea (Pisum sativum L.) under subtropical climate.

Field pea is highly sensitive to climatic vagaries, particularly high-temperature stress. The crop often experiences terminal heat stress in tropical climates indicating the need for the development of heat-tolerant cultivars. Characterization and identification of stress-adaptive plant traits are pre-requisites for breeding stress-tolerant/adaptive cultivar(s). In the study, a panel of 150 diverse field pea genotypes was tested under three different temperature environments (i.e., normal sowing time or non-heat stress environment (NSTE), 15 days after normal sowing time or heat stress environment-I (LSHTE-I), and 30 days after normal sowing time or heat stress environment-II (LSHTE-II)) to verify the effect of high-temperature environment, genotype, and genotype × environment interaction on different plant traits and to elucidate their significance in heat stress adaptation/tolerance. The delayed sowing had exposed field pea crops to high temperatures during flowering stage by + 3.5 °C and + 8.1 °C in the LSHTE-I and LSHTE-II, respectively. Likewise, the maximum ambient temperature during the grain-filling period was + 3.3 °C and + 6.1 °C higher in the LSHTE-I and LSHTE-II over the NSTE. The grain yield loss with heat stress was 25.8 ± 2.2% in LSHTE-I, and 59.3 ± 1.5% in LSHTE-II compared to the NSTE. Exposure of crops to a high-temperature environment during the flowering stage had a higher impact on grain yield than the heat stress at the grain filling period. Results suggested that the reduced sink capacity (pod set (pod plant-1), seed set (seed pod-1)) was the primary cause of yield loss under the heat stress environments, while, under the NSTE, yield potential was mostly attributed to the source capacity (plant biomass). The high-temperature stress resulted in forced maturity as revealed by shrinkage in crop period (5-11%) and reproductive period (15-36%), prominently in long-duration genotypes. The failure of pod set in the upper nodes and higher ovule abortion (7-16%) was noticed under the high-temperature environments, particularly in the LSHTE-II. Multivariate analysis results revealed seed set, pods plant-1, last pod bearing node, and plant biomass as a critical yield determinant under the heat stress. The GGE biplot suggested that the genotypes G-112, G-114, and G-33 had higher potential to sustain yield coupled with higher stability across the environments and, thus, could serve as a source for breeding heat-tolerant high yielding cultivars.

Microbiological profile and their antibiogram of bloodstream infections amongst first and second surge of the COVID-19 patients in a tertiary care hospital.

Introduction: The world is experiencing a pandemic of coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2. The prescription of a superfluity of unnecessary antibiotics without regard for the potential for increased antimicrobial resistances is extensive and unimpeded during the COVID-19 pandemic. Aims: To compare the microorganisms and the pattern of antimicrobial resistance of bacteremia during the first and second waves of the COVID-19 pandemic in a tertiary care hospital. Methods and Material: This retrospective observational study, to compared the blood culture of the COVID-19 pandemic during the first wave (April 2020 to September 2020) and the second wave (April 2021 to September 2021). All the blood culture isolates were identified and the antimicrobial susceptibility testing was done according to standard guidelines. Results: Out of 1470 blood culture samples, 259 (17.6%) blood bacterial isolates were grown in the first wave and, out of 4200 blood culture samples, 711 (16.9%) bacterial isolated during the second wave of the COVID-19 pandemic. Coagulase-negative staphylococcus (CONS) was 32.8% followed by Staphylococcus aureus 29.7% in COVID first wave and staphylococcus aureus (48.9%) followed by Klebsiella pneumoniae (11.6%) during COVID second wave were the most prevalent isolates. Conclusions: This study shows that coagulase-negative staphylococcus aureus and multidrug-resistant Klebsiella spp. are the leading causes of bloodstream coagulase-negative infections during both the first and second wave in the bloodstream COVID-19 pandemic.

Translational Chickpea Genomics Consortium to Accelerate Genetic Gains in Chickpea (Cicer arietinum L.).

The Translational Chickpea Genomics Consortium (TCGC) was set up to increase the production and productivity of chickpea (Cicer arietinum L.). It represents research institutes from six major chickpea growing states (Madhya Pradesh, Maharashtra, Andhra Pradesh, Telangana, Karnataka and Uttar Pradesh) of India. The TCGC team has been engaged in deploying modern genomics approaches in breeding and popularizing improved varieties in farmers' fields across the states. Using marker-assisted backcrossing, introgression lines with enhanced drought tolerance and fusarium wilt resistance have been developed in the genetic background of 10 elite varieties of chickpea. Multi-location evaluation of 100 improved lines (70 desi and 30 kabuli) during 2016-2017 and 2018-2019 enabled the identification of top performing desi and kabuli lines. In total, 909 Farmer Participatory Varietal Selection trials were conducted in 158 villages in 16 districts of the five states, during 2017-2018, 2018-2019, and 2019-2020, involving 16 improved varieties. New molecular breeding lines developed in different genetic backgrounds are potential candidates for national trials under the ICAR-All India Coordinated Research Project on Chickpea. The comprehensive efforts of TCGC resulted in the development and adoption of high-yielding varieties that will increase chickpea productivity and the profitability of chickpea growing farmers.

A chickpea genetic variation map based on the sequencing of 3,366 genomes.

Zero hunger and good health could be realized by 2030 through effective conservation, characterization and utilization of germplasm resources1. So far, few chickpea (Cicer arietinum) germplasm accessions have been characterized at the genome sequence level2. Here we present a detailed map of variation in 3,171 cultivated and 195 wild accessions to provide publicly available resources for chickpea genomics research and breeding. We constructed a chickpea pan-genome to describe genomic diversity across cultivated chickpea and its wild progenitor accessions. A divergence tree using genes present in around 80% of individuals in one species allowed us to estimate the divergence of Cicer over the last 21 million years. Our analysis found chromosomal segments and genes that show signatures of selection during domestication, migration and improvement. The chromosomal locations of deleterious mutations responsible for limited genetic diversity and decreased fitness were identified in elite germplasm. We identified superior haplotypes for improvement-related traits in landraces that can be introgressed into elite breeding lines through haplotype-based breeding, and found targets for purging deleterious alleles through genomics-assisted breeding and/or gene editing. Finally, we propose three crop breeding strategies based on genomic prediction to enhance crop productivity for 16 traits while avoiding the erosion of genetic diversity through optimal contribution selection (OCS)-based pre-breeding. The predicted performance for 100-seed weight, an important yield-related trait, increased by up to 23% and 12% with OCS- and haplotype-based genomic approaches, respectively.

Gene regulation: Context is everything.

How transcription factors regulate a distinct set of target genes in different cell types is a fundamental question. A new study demonstrates how Ultrabithorax, a Hox transcription factor, acts as both a repressor and an activator in a cell type-specific manner to alter chromatin accessibility and gene regulation.

Global gene expression analysis of pigeonpea with male sterility conditioned by A2 cytoplasm.

Cytoplasmic male sterility(CMS), a maternally inherited trait, provides a promising means to harness yield gains associated with hybrid vigor. In pigeonpea [Cajanus cajan (L.) Huth], nine types of sterility-inducing cytoplasm have been reported, of which A2 and A4 have been successfully deployed in hybrid breeding. Unfortunately, molecular mechanism of the CMS trait is poorly understood because of limited research invested. More recently, an association between a mitochondrial gene (nad7) and A4 -CMS has been demonstrated in pigeonpea; however, the mechanism underlying A2 -CMS still remains obscure. The current investigation aimed to analyze the differences in A2 -CMS line (ICPL 88039A) and its isogenic maintainer line (ICPL 88039B) at transcriptome level using next-generation sequencing. Gene expression profiling uncovered a set of 505 genes that showed altered expression in response to CMS, of which, 412 genes were upregulated while 93 were downregulated in the fertile maintainer line vs. the CMS line. Further, gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and protein-protein interaction (PPI) network analyses revealed association of CMS in pigeonpea with four major pathways: glucose and lipid metabolism, ATP production, pollen development and pollen tube growth, and reactive oxygen species (ROS) scavenging. Patterns of digital gene expression were confirmed by quantitative real-time polymerase chain reaction (qRT-PCR) of six candidate genes. This study elucidates candidate genes and metabolic pathways having potential associations with pollen development and male sterility in pigeonpea A2 -CMS. New insights on molecular mechanism of CMS trait in pigeonpea will be helpful to accelerate heterosis utilization for enhancing productivity gains in pigeonpea.

Major QTLs and Potential Candidate Genes for Heat Stress Tolerance Identified in Chickpea (Cicer arietinum L.).

In the context of climate change, heat stress during the reproductive stages of chickpea (Cicer arietinum L.) leads to significant yield losses. In order to identify the genomic regions responsible for heat stress tolerance, a recombinant inbred line population derived from DCP 92-3 (heat sensitive) and ICCV 92944 (heat tolerant) was genotyped using the genotyping-by-sequencing approach and evaluated for two consecutive years (2017 and 2018) under normal and late sown or heat stress environments. A high-density genetic map comprising 788 single-nucleotide polymorphism markers spanning 1,125 cM was constructed. Using composite interval mapping, a total of 77 QTLs (37 major and 40 minor) were identified for 12 of 13 traits. A genomic region on CaLG07 harbors quantitative trait loci (QTLs) explaining >30% phenotypic variation for days to pod initiation, 100 seed weight, and for nitrogen balance index explaining >10% PVE. In addition, we also reported for the first time major QTLs for proxy traits (physiological traits such as chlorophyll content, nitrogen balance index, normalized difference vegetative index, and cell membrane stability). Furthermore, 32 candidate genes in the QTL regions that encode the heat shock protein genes, heat shock transcription factors, are involved in flowering time regulation as well as pollen-specific genes. The major QTLs reported in this study, after validation, may be useful in molecular breeding for developing heat-tolerant superior lines or varieties.

Untangling the Influence of Heat Stress on Crop Phenology, Seed Set, Seed Weight, and Germination in Field Pea (Pisum sativum L.).

The apparent climatic extremes affect the growth and developmental process of cool-season grain legumes, especially the high-temperature stress. The present study aimed to investigate the impacts of high-temperature stress on crop phenology, seed set, and seed quality parameters, which are still uncertain in tropical environments. Therefore, a panel of 150 field pea genotypes, grouped as early (n = 88) and late (n = 62) maturing, were exposed to high-temperature environments following staggered sowing [normal sowing time or non-heat stress environment (NHSE); moderately late sowing (15 days after normal sowing) or heat stress environment-I (HSE-I); and very-late sowing (30 days after normal sowing) or HSE-II]. The average maximum temperature during flowering was about 22.5 ± 0.17°C for NHSE and increased to 25.9 ± 0.11°C and 30.6 ± 0.19°C in HSE-I and HSE-II, respectively. The average maximum temperature during the reproductive period (RP) (flowering to maturity) was in the order HSE-II (33.3 ± 0.03°C) > HSE-I (30.5 ± 0.10°C) > NHSE (27.3 ± 0.10°C). The high-temperature stress reduced the seed yield (24-60%) and seed germination (4-8%) with a prominent effect on long-duration genotypes. The maximum reduction in seed germination (>15%) was observed in HSE-II for genotypes with >115 days maturity duration, which was primarily attributed to higher ambient maximum temperature during the RP. Under HSEs, the reduction in the RP in early- and late-maturing genotypes was 13-23 and 18-33%, suggesting forced maturity for long-duration genotypes under late-sown conditions. The cumulative growing degree days at different crop stages had significant associations (p < 0.001) with seed germination in both early- and late-maturing genotypes; and the results further demonstrate that an extended vegetative period could enhance the 100-seed weight and seed germination. Reduction in seed set (7-14%) and 100-seed weight (6-16%) was observed under HSEs, particularly in HSE-II. The positive associations of 100-seed weight were observed with seed germination and germination rate in the late-maturing genotypes, whereas in early-maturing genotypes, a negative association was observed for 100-seed weight and germination rate. The GGE biplot analysis identified IPFD 11-5, Pant P-72, P-1544-1, and HUDP 11 as superior genotypes, as they possess an ability to produce more viable seeds under heat stress conditions. Such genotypes will be useful in developing field pea varieties for quality seed production under the high-temperature environments.

Genome-wide comparative transcriptome analysis of the A4-CMS line ICPA 2043 and its maintainer ICPB 2043 during the floral bud development of pigeonpea.

Cytoplasmic male sterility (CMS) offers a unique system to understand cytoplasmic nuclear crosstalk, and is also employed for exploitation of hybrid vigor in various crops. Pigeonpea A4-CMS, a predominant source of male sterility, is being used for efficient hybrid seed production. The molecular mechanisms of CMS trait remain poorly studied in pigeonpea. We performed genome-wide transcriptome profiling of A4-CMS line ICPA 2043 and its isogenic maintainer ICPB 2043 at two different stages of floral bud development (stage S1 and stage S2). Consistent with the evidences from some other crops, we also observed significant difference in the expression levels of genes in the later stage, i.e., stage S2. Differential expression was observed for 143 and 55 genes within the two stages of ICPA 2043 and ICPB 2043, respectively. We obtained only 10 differentially expressed genes (DEGs) between the stage S1 of the two genotypes, whereas expression change was significant for 582 genes in the case of stage S2. The qRT-PCR assay of randomly selected six genes supported the differential expression of genes between ICPA 2043 and ICPB 2043. Further, GO and KEGG pathway mapping suggested a possible compromise in key bioprocesses during flower and pollen development. Besides providing novel insights into the functional genomics of CMS trait, our results were in strong agreement with the gene expression atlas of pigeonpea that implicated various candidate genes like sucrose-proton symporter 2 and an uncharacterized protein along with pectate lyase, pectinesterase inhibitors, L-ascorbate oxidase homolog, ATPase, ß-galactosidase, polygalacturonase, and aldose 1-epimerase for pollen development of pigeonpea. The dataset presented here provides a rich genomic resource to improve understanding of CMS trait and its deployment in heterosis breeding in pigeonpea.

Identification of microRNAs and their gene targets in cytoplasmic male sterile and fertile maintainer lines of pigeonpea.

MAIN CONCLUSION: Comparative analysis of genome-wide miRNAs and their gene targets between cytoplasmic male sterile (CMS) and fertile lines of pigeonpea suggests a possible role of miRNA-regulated pathways in reproductive development. Exploitation of hybrid vigor using CMS technology has delivered nearly 50% yield gain in pigeonpea. Among various sterility-inducing cytoplasms (A1-A9) reported so far in pigeonpea, A2 and A4 are the two major sources that facilitate hybrid seed production. Recent evidence suggests involvement of micro RNA in vast array of biological processes including plant reproductive development. In pigeonpea, information about the miRNAs is insufficient. In view of this, we sequenced six small RNA libraries of CMS line UPAS 120A and isogenic fertile line UPAS 120B using Illumina technology. Results revealed 316 miRNAs including 248 known and 68 novel types. A total of 637 gene targets were predicted for known miRNAs, while 324 genes were associated with novel miRNAs. Degradome analysis revealed 77 gene targets of predicted miRNAs, which included a variety of transcription factors playing key roles in plant reproduction such as F-box family proteins, apetala 2, auxin response factors, ethylene-responsive factors, homeodomain-leucine zipper proteins etc. Differential expression of both known and novel miRNAs implied roles for both conserved as well as species-specific players. We also obtained several miRNA families such as miR156, miR159, miR167 that are known to influence crucial aspects of plant fertility. Gene ontology and pathway level analyses of the target genes showed their possible implications for crucial events during male reproductive development such as tapetal degeneration, pollen wall formation, retrograde signaling etc. To the best of our knowledge, present study is first to combine deep sequencing of small RNA and degradome for elucidating the role of miRNAs in flower and male reproductive development in pigeonpea.

Introgression of "QTL-hotspot" region enhances drought tolerance and grain yield in three elite chickpea cultivars.

With an aim of enhancing drought tolerance using a marker-assisted backcrossing (MABC) approach, we introgressed the "QTL-hotspot" region from ICC 4958 accession that harbors quantitative trait loci (QTLs) for several drought-tolerance related traits into three elite Indian chickpea (Cicer arietinum L.) cultivars: Pusa 372, Pusa 362, and DCP 92-3. Of eight simple sequence repeat (SSR) markers in the QTL-hotspot region, two to three polymorphic markers were used for foreground selection with respective cross-combinations. A total of 47, 53, and 46 SSRs were used for background selection in case of introgression lines (ILs) developed in genetic backgrounds of Pusa 372, Pusa 362, and DCP 92-3, respectively. In total, 61 ILs (20 BC3 F3 in Pusa 372; 20 BC2 F3 in Pusa 362, and 21 BC3 F3 in DCP 92-3), with >90% recurrent parent genome recovery were developed. Six improved lines in different genetic backgrounds (e.g. BGM 10216 in Pusa 372; BG 3097 and BG 4005 in Pusa 362; IPC(L4-14), IPC(L4-16), and IPC(L19-1) in DCP 92-3) showed better performance than their respective recurrent parents. BGM 10216, with 16% yield gain over Pusa 372, has been released as Pusa Chickpea 10216 by the Central Sub-Committees on Crop Standards, Notification and Release of Varieties of Agricultural Crops, Ministry of Agriculture and Farmers Welfare, Government of India, for commercial cultivation in India. In summary, this study reports introgression of the QTL-hotspot for enhancing yield under rainfed conditions, development of several introgression lines, and release of Pusa Chickpea 10216 developed through molecular breeding in India.

Mapping QTL for important seed traits in an interspecific F2 population of pigeonpea.

Seed traits present important breeding targets for enhancing grain yield and quality in various grain legume crops including pigeonpea. The present study reports significant genetic variation for six seed traits including seed length (SL), seed width (SW), seed thickness (ST), seed weight (SWT), electrical conductivity (EC) and water uptake (WU) among Cajanus cajan (L.) Millspaugh acc. ICPL 20340 and Cajanus scarabaeoides (L.) Thouars acc. ICP 15739 and an F2 population derived from this interspecific cross. Maximum phenotypic values recorded for the F2 population were higher than observed in the parent ICPL 20340 [F2 max vs ICPL 20340: SW (7.05 vs 5.38), ST (4.63 vs 4.51), EC (65.17 vs 9.72), WU (213.17 vs 109.5)], which suggested contribution of positive alleles from the wild parent, ICP 15739. Concurrently, to identify the QTL controlling these seed traits, we assayed two parents and 94 F2 individuals with 113 polymorphic simple sequence repeat (SSR) markers. In the F2 population, 98 of the 113 SSRs showed Mendelian segregation ratio 1:2:1, whereas significant deviations were observed for 15 SSRs with their χ 2 values ranging between 6.26 and 20.62. A partial genetic linkage map comprising 83 SSR loci was constructed. QTL analysis identified 15 marker-trait associations (MTAs) for seed traits on four linkage groups i.e. LG01, LG02, LG04 and LG05. Phenotypic variations (PVs) explained by these QTL ranged from 4.4 (WU) to 19.91% (EC). These genomic regions contributing significantly towards observed variability of seed traits would serve as potential candidates for future research that aims to improve seed traits in pigeonpea.

Administration of Δ9-Tetrahydrocannabinol (THC) Post-Staphylococcal Enterotoxin B Exposure Protects Mice From Acute Respiratory Distress Syndrome and Toxicity.

Acute Respiratory Distress Syndrome (ARDS) is a life-threatening complication that can ensue following Staphylococcus aureus infection. The enterotoxin produced by these bacteria (SEB) acts as a superantigen thereby activating a large proportion of T cells leading to cytokine storm and severe lung injury. Δ9Tetrahydrocannabinol (THC), a psychoactive ingredient found in Cannabis sativa, has been shown to act as a potent anti-inflammatory agent. In the current study, we investigated the effect of THC treatment on SEB-induced ARDS in mice. While exposure to SEB resulted in acute mortality, treatment with THC led to 100% survival of mice. THC treatment significantly suppressed the inflammatory cytokines, IFN-γ and TNF-α. Additionally, THC elevated the induction of regulatory T cells (Tregs) and their associated cytokines, IL-10 and TGF-ß. Moreover, THC caused induction of Myeloid-Derived Suppressor Cells (MDSCs). THC acted through CB2 receptor as pharmacological inhibitor of CB2 receptors blocked the anti-inflammatory effects. THC-treated mice showed significant alterations in the expression of miRNA (miRs) in the lung-infiltrated mononuclear cells (MNCs). Specifically, THC caused downregulation of let7a-5p which targeted SOCS1 and downregulation of miR-34-5p which caused increased expression of FoxP3, NOS1, and CSF1R. Together, these data suggested that THC-mediated alterations in miR expression in the lungs may play a critical role in the induction of immunosuppressive Tregs and MDSCs as well as suppression of cytokine storm leading to attenuation of SEB-mediated lung injury.

Integrating genomics for chickpea improvement: achievements and opportunities.

KEY MESSAGE: Integration of genomic technologies with breeding efforts have been used in recent years for chickpea improvement. Modern breeding along with low cost genotyping platforms have potential to further accelerate chickpea improvement efforts. The implementation of novel breeding technologies is expected to contribute substantial improvements in crop productivity. While conventional breeding methods have led to development of more than 200 improved chickpea varieties in the past, still there is ample scope to increase productivity. It is predicted that integration of modern genomic resources with conventional breeding efforts will help in the delivery of climate-resilient chickpea varieties in comparatively less time. Recent advances in genomics tools and technologies have facilitated the generation of large-scale sequencing and genotyping data sets in chickpea. Combined analysis of high-resolution phenotypic and genetic data is paving the way for identifying genes and biological pathways associated with breeding-related traits. Genomics technologies have been used to develop diagnostic markers for use in marker-assisted backcrossing programmes, which have yielded several molecular breeding products in chickpea. We anticipate that a sequence-based holistic breeding approach, including the integration of functional omics, parental selection, forward breeding and genome-wide selection, will bring a paradigm shift in development of superior chickpea varieties. There is a need to integrate the knowledge generated by modern genomics technologies with molecular breeding efforts to bridge the genome-to-phenome gap. Here, we review recent advances that have led to new possibilities for developing and screening breeding populations, and provide strategies for enhancing the selection efficiency and accelerating the rate of genetic gain in chickpea.