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The study was carried out for investigation and analysis of long-term (45 years) monthly rainfall data of Rajshahi from 1975 to 2019 for better selection of crops and agricultural technology in this region of Bangladesh. The rainfall trend was determined using parametric and non-parametric method. Probability analysis of rainfall was performed for estimation of dry, wet, and average year rainfall. The results revealed negative trend of yearly rainfall, but it is statistically insignificant. By non-parametric method, ‘no trend’ was observed for yearly rainfall. Increasing trend of monthly rainfall during March and May and decreasing trend in other months were observed. The rainfall deficit period continued from November to March, and in some instant up to April (rainfall

The study was conducted for assessing water quality for drinking and irrigation purposes of groundwater sources. Total 50 water samples were collected from different locations of Nachol and Niamatpurupazilla of Chapainawabgonj and Naogaon district in January 2019 and January 2020. Water quality parameters like pH, electrical conductivity (Ec), iron (Fe), manganese (Mn), calcium (Ca), magnesium (Mg), zinc (Zn), copper (Cu), sodium (Na), potassium (K), total hardness (TH), alkalinity, sulphate (SO4), nitrate (NO3), nitrite (NO2), ammonia (NH4), phosphate (PO4), chloride (Cl), dissolved oxygen (DO), and total dissolved solids (TDS) were analyzed in the laboratory. All the analyzed parameters were compared with national and international drinking and irrigation water quality standards to understand the overall groundwater quality status of the study area. The study showed that the water samples of almost all the locations were suitable for consumption and irrigation.

Recently released zinc enriched, high yielding, medium slender grain containing rice variety BRRI dhan100, appropriate for irrigated ecosystem of Bangladesh is an improvement over existing zinc enriched rice varieties for Bangladesh. The variety has satisfactorily passed the Proposed Variety Trial (PVT) conducted in the farmers’ field in Boro 2019-20 season. As a result National Seed Board (NSB) approved this variety for commercial cultivation in the Boro season (dry season) in 2021. It has modern plant type with 101 cm plant height and matures by 148 days. The proposed variety showed 1.20 t/ha higher yield than check variety BRRI dhan84. Identifying characters of this variety are green leaf, intermediate plant height, erect flag leaf, medium slender grain, intermediate leaf senescence grain. It can produce 7.7 - 8.8 t/ha grain yield. Thousand grain weight of the variety is 16.7 gm and head rice yield is 64%. The rice has zinc content 25.7 mg/kg, 26.8% amylose content with 7.8% protein content. The zinc enriched BRRI dhan100 is a superb variety for cultivating in the Boro season (dry) and farmers can be economically benefited and the country will be nutritionally benefited by the cultivation of BRRI dhan100.

Molecular mapping and application of quantitative trait loci (QTL) associated with a higher level of grain Zinc is a viable option to enhance zinc content in rice through breeding. An F2 population derived from a cross between a high yielding variety, BRRI dhan28, and a locally adapted Zn enriched cultivar, Kalobokri was used to map QTLs associated with higher levels of Zn in rice grain. The F2:3 progenies varied significantly (P ＜ 0.0001) in Zinc contents with a mean value remarkably higher than those in the superior parent. Through marker by trait analysis using IciMapping, we detected a large-effect QTL, qGZn3 on chromosome 3 between RM5419 and RM1164 spanning 1.83 Mb interval at the 0.05 level of significance with a threshold LOD of 10.61. This QTL showed a21.1% (R2 value) contribution to the total phenotypic variation for zinc content in the unpolished rice grains with 4.68 μg/g additive effect of Kalobokri alleles. We also detected 11 metal homeostasis related genes within the interval of qGZn3. In-silico analysis showed that four expressed sequence tags of one candidate gene (LOC_Os03g22810) encoding Cu/Zn superoxide dismutase, a metal-binding protein, are highly active in the endosperm as well as in the embryonic tissue of rice grain. Taken together, our results suggest that qGZn3 is a major QTL associated with high grain Zn content in the F2 progenies of rice. Our findings offer valuable genetic resources to facilitate breeding for high yielding and Zinc-enriched rice variety.

IL-17 contributes to the pathogenesis of certain autoimmune diseases, but conversely is essential for host defense against fungi. Antibody-based biologic drugs that neutralize IL-17 are effective in autoimmunity but can be accompanied by adverse side effects. Candida albicans is a commensal fungus that is the primary causative agent of oropharyngeal and disseminated candidiasis. Defects in IL-17 signaling cause susceptibility to candidiasis in mice and humans. A key facet of IL-17 receptor signaling involves RNA binding proteins (RBP), which orchestrate the fate of target mRNA transcripts. In tissue culture models we showed that the RBP AT-rich interacting protein 5a (Arid5a) promotes the stability and/or translation of multiple IL-17-dependent mRNAs. Moreover, during OPC, Arid5a is elevated within the oral mucosa in an IL-17-dependent manner. However, the contribution of Arid5a to IL-17-driven events in vivo is poorly defined. Here, we used CRISPR/Cas9 to generate mice lacking Arid5a. Arid5a-/- mice were fully resistant to experimental autoimmune encephalomyelitis (EAE), an autoimmune setting in which IL-17 signaling drives pathology. Surprisingly, Arid5a-/- mice were resistant to OPC and systemic candidiasis, similar to immunocompetent WT mice and contrasting with mice defective in IL-17 signaling. Therefore, Arid5a-dependent signals mediate pathology in autoimmunity yet are not required for immunity to candidiasis, indicating that selective targeting of IL-17 signaling pathway components may be a viable strategy for development of therapeutics that spare IL-17-driven host defense.

A newly released zinc enriched, high yielding, slender and red pericarp grain containing rice variety BRRI dhan84, suitable for dry ecosystem (Boro season) of Bangladesh is an improvement over existing zinc enriched rice varieties for Bangladesh. The main objective of this research was to develop the of high yielding rice varieties with improved nutritional quality in term of high zinc (Zn≥24 mg/kg) in polished grain. The study was taken in 2004 by crossing between BRRIdhan29/IR68144//BRRI dhan28///BR11 and it takes near about 13 years to develop the targeted variety. After selection of one homozygous advanced line (BR7831-59-1-1-4-5-1-9-P1) the Regional Yield Trial (RYT) was conducted in Boro 2014-15 saeson and the Advanced Line Adaptive Research Trial (ALART) was evaluated at different farmers’ field in Boro 2015-16 season and different yield trials were conducted using Randomized Complete Block Desing (RCBD). The variety has satisfactorily passed the Proposed Variety Trial (PVT) conducted in the farmers’ field in Boro 2016-17 season. As a result National Seed Board (NSB) approved this variety for commercial cultivation in the dry season (Boro season) in 2017. It has modern plant type with 96 cm plant height and matures by 140 days. The salient feature of this variety is the red colored grain, earlier than check variety, the proposed variety showed higher yield than check variety BRRI dhan28. Identifying characters of this variety are dark green leaf, semi erect flag leaf, long slender and red colored grain. It can produce 6.0-6.5 t/ha grain yield. Thousand grain weight of the variety is 22.8 g and it has colored grain tip. The rice has zinc content 27.6 mg/kg, 25.9% amylose content with 9.7% protein content. BRRI dhan84 was released as a high yielding, zinc enriched rice variety to meet the nutritional (zinc) demand of the country. The zinc enriched BRRI dhan84 is a superb variety for cultivating in the dry (Boro) season and farmers can be economically benefited and the country will be nutritionally benefited by the cultivation of BRRI dhan84.

Drought stress is a major constraint to the sustainable production of of crops. Rice (Oryza sativa L.) is considered as a drought-sensitive crop species. The experiment was carried out to investigate the response of two rice mutants to drought condition and to develop appropriate irrigation management. Experiment was conducted at mini-lysimeter (1.5 m x 1.0 m x 0.28 m, having drainage outlet and rain-shed) at BINA, Mymensingh in Aman season (August to October, 2017) and Aus season (March to June, 2018) consecutively. The mutants used were N4/250/P-1(2) and N4/250/P-2(6)-26. The mutants were tested against four levels of drought stress. The imposed treatments were: Normal irrigation (3 days AWD), supplemental irrigation (ASM drops below 85%, throughout the growing season), irrigation at 0.85 ASM (up to booting stage) then irrigation at 0.60 PASM, irrigation at 0.85 ASM (throughout the growing season). Treatments were imposed after 3 weeks from transplanting. Experiment was laid out according to random complete block design (RCBD) with split-plot arrangements and three replications. The results showed that the mutants produced reasonable yield under stress condition compared to normal irrigation condition, which indicates their tolerance capacity under drought condition. Rice drought tolerance could help the country deal with the shortages in water that are facing Bangladesh farmers already.

Rice plants are sensitive to cold stress at various growth stages starting from germination to maturity. Exploitation of cold tolerance for the development of cold tolerant varieties may help in saving crop loss or cost of production in the cold prone environment. Introgression of quantitative trait loci (QTLs) conferring cold tolerance in the elite variety may be the most effective and sustainable approach to address this issue. A F2:3 mapping population of a cross between a cold susceptible variety (BR1) and a cold tolerant variety (BR18) was used to map QTLs for cold tolerance at seedling stage. Three significant QTLs on chromosomes 1, 3 and 12 associated with cold tolerance were mapped between the markers intervals of RM220-RM10829, RM546-RM7 and RM27877-RM463, respectively at a threshold LOD of 4.3 through composite interval mapping. Phenotypic contributions of these QTLs were 50.7, 39 and 52.7%, respectively. Marker information of such a large effect QTL could be used in the breeding program after necessary validation to develop cold tolerant high yielding rice varieties.

Excessive inflammatory responses can cause collateral tissue damage or autoimmune inflammation, sometimes with severe morbidity or mortality. During host defense responses, numerous negative feedback mechanisms are established to prevent excessive unchecked inflammation. However, this restraint can sometimes come at the cost of suboptimal infection control, and we do not fully understand how this balance is maintained during different infection settings. The endoribonuclease Regnase-1 (Reg1, Zc3h12a, MCPIP1) is an RNA binding protein (RBP) that binds and degrades many target mRNA transcripts. Reg1 is a potent feedback regulator of IL-17 and LPS signal transduction, among other stimuli. Consequently, Reg1 deficiency exacerbates autoimmune inflammation in multiple mouse models, but on the other hand, reduced Reg1 improves immunity to fungal infection. To date, the role of Reg1 in bacterial immunity is poorly defined. Here, we show that mice deficient in Reg1 are more resistant to pulmonary Klebsiella pneumoniae (KP) infection. Unexpectedly, effects of Reg1 deficiency were not due to accelerated eradication of bacteria or increased pro-inflammatory cytokine expression. Rather, alveolar macrophages from Reg1-deficient mice showed enrichment of Type I IFN-related genes upon KP infection, accompanied by increased Ifnb1 expression. Surprisingly, the stability of Ifnb1 mRNA was not altered by Reg1-deficiency; rather, mRNA encoding its upstream regulator IRF7 appeared to be a more prominent target. Blockade of IFNR during KP infection reversed disease improvement. Thus, impaired Reg1 induces Type I IFN and enhances resistance to KP, raising the possibility that Reg1 could be a potential clinical target in acute bacterial infections.Graphical abstract

Breast cancer (BC) is the most common type of cancer in both men and women alike, but it is more prevalent in women. Natural compounds that can modulate the oncogenic process can be considered a significant anti-cancer agent for treating BC. These natural compounds are more effective than synthetic drugs, which have profound side effects on the normal cell and resistance to cancer cells. Genistein is a type of dietary phytoestrogen included in the flavonoid group with a similar structure of estrogen that might provide a strong alternative and complementary medicine to existing chemotherapeutics drugs. Several research studies demonstrated that it can target the estrogen receptor (ER), Human epidermal growth factor receptor-2 (HER2), and Breast cancer gene-1 (BRCA-1) in multiple BC cell lines, as well as sensitize cancer cell lines to this compound when used at an optimal inhibitory concentration. Genistein effectively showed anti-cancer activities through apoptosis induction, arresting cell cycle, inhibiting angiogenesis with metastasis, reducing inflammation, mammosphere formation, tumor growth, up-regulating tumor suppressor gene, and downregulating oncogene in suppressing cancer progression in vitro and animal model study. In addition, research studies have also suggested that these phytochemicals synergistically reverse the resistance mechanism of chemotherapeutic drugs, increasing the efficacy of some chemoinformatics drugs. Our review article aims to unbox and validate the molecular pharmacology in breast tissue, cell-specific anti-cancer mechanism with synergistic activity, and possible pharmacokinetic parameters of Genistein as a potential alternative therapeutic option for the treatment of BC.

Excessive cytokine activity underlies many autoimmune conditions, particularly through the interleukin-17 (IL-17) and tumor necrosis factor-α (TNFα) signaling axis. Both cytokines activate nuclear factor κB, but appropriate induction of downstream effector genes requires coordinated activation of other transcription factors, notably, CCAAT/enhancer binding proteins (C/EBPs). Here, we demonstrate the unexpected involvement of a posttranscriptional "epitranscriptomic" mRNA modification [N6-methyladenosine (m6A)] in regulating C/EBPβ and C/EBPδ in response to IL-17A, as well as IL-17F and TNFα. Prompted by the observation that C/EBPβ/δ-encoding transcripts contain m6A consensus sites, we show that Cebpd and Cebpb mRNAs are subject to m6A modification. Induction of C/EBPs is enhanced by an m6A methylase "writer" and suppressed by a demethylase "eraser." The only m6A "reader" found to be involved in this pathway was IGF2BP2 (IMP2), and IMP2 occupancy of Cebpd and Cebpb mRNA was enhanced by m6A modification. IMP2 facilitated IL-17-mediated Cebpd mRNA stabilization and promoted translation of C/EBPβ/δ in response to IL-17A, IL-17F, and TNFα. RNA sequencing revealed transcriptome-wide IL-17-induced transcripts that are IMP2 influenced, and RNA immunoprecipitation sequencing identified the subset of mRNAs that are directly occupied by IMP2, which included Cebpb and Cebpd Lipocalin-2 (Lcn2), a hallmark of autoimmune kidney injury, was strongly dependent on IL-17, IMP2, and C/EBPβ/δ. Imp2-/- mice were resistant to autoantibody-induced glomerulonephritis (AGN), showing impaired renal expression of C/EBPs and Lcn2 Moreover, IMP2 deletion initiated only after AGN onset ameliorated disease. Thus, posttranscriptional regulation of C/EBPs through m6A/IMP2 represents a previously unidentified paradigm of cytokine-driven autoimmune inflammation.

Medicinal plants possess a surplus of novel and biologically active secondary metabolites that are responsible for counteracting diseases. Traditionally, Gomphandra tetrandra (Wall.) Sleumer is used to treat mental disorders. The present research was designed to explore phytochemicals from the ethanol leaf extract of Gomphandra tetrandra (Wall.) Sleumer to identify the potential pharmacophore(s) in the treatment of neurological disorders. The chemical compounds of the experimental plant were identified through GC-MS analysis. Besides, in-vitro antioxidant activity was assessed using different methods. Furthermore, in-vivo neurological activity was assessed in Swiss-albino mice. Computer aided analysis was appraised to determine the best-fit phytoconstituent of a total of fifteen identified compounds in the experimental plant extract against beta-amyloid precursor protein. The experimental extract revealed fifteen compounds in GC-MS analysis and the highest content was 9, 12, 15-octadecatrienoic acid (Z, Z, Z). Also, the extract showed potent anti-oxidant activity in in-vitro assays. Furthermore, in in-vivo neurological assays, the extract disclosed significant (p

Antibody-mediated glomerulonephritis (AGN) is a clinical manifestation of many autoimmune kidney diseases for which few effective treatments exist. Chronic inflammatory circuits in renal glomerular and tubular cells lead to tissue damage in AGN. These cells are targeted by the cytokine IL-17, which has recently been shown to be a central driver of the pathogenesis of AGN. However, surprisingly little is known about the regulation of pathogenic IL-17 signaling in the kidney. Here, using a well-characterized mouse model of AGN, we show that IL-17 signaling in renal tubular epithelial cells (RTECs) is necessary for AGN development. We also show that Regnase-1, an RNA binding protein with endoribonuclease activity, is a negative regulator of IL-17 signaling in RTECs. Accordingly, mice with a selective Regnase-1 deficiency in RTECs exhibited exacerbated kidney dysfunction in AGN. Mechanistically, Regnase-1 inhibits IL-17-driven expression of the transcription factor IκBξ and, consequently, its downstream gene targets, including Il6 and Lcn2. Moreover, deletion of Regnase-1 in human RTECs reduced inflammatory gene expression in a IκBξ-dependent manner. Overall, these data identify an IL-17-driven inflammatory circuit in RTECs during AGN that is constrained by Regnase-1.

Signaling via G protein-coupled receptors (GPCRs) can modulate levels of cyclic adenosine monophosphate (cAMP) and shape the functions of fibroblasts in idiopathic pulmonary fibrosis (IPF). We have identified Chemokine (C-X-C) Motif Ligand 6 (CXCL6) as a potential pro-fibrotic GPCR ligand. We tested the function of CXCL6 in ex vivo human donor and fibrotic lung fibroblasts and in an animal model of pulmonary fibrosis. We also measured levels of CXCL6 in the blood and bronchoalveolar lavage (BAL) of patients with IPF. CXCL6 decreased cAMP levels in a dose-dependent manner in Donor and IPF Fibroblasts. CXCL6 mRNA and protein were localized to epithelial cells. Administration of mCXCL5 (LIX, murine CXCL6 homologue) to mice increased collagen synthesis with and without bleomycin. CXCL6 increased Collagen I and α-SMA levels in Donor and IPF Fibroblasts. Silencing of CXCR1/2 as well as Reparixin, a CXCR1/2 inhibitor, blocked effects of CXCL6. Treprostinil blocked effects of CXCL6 only on levels of α-SMA but not on Collagen I. CXCL6 levels in the BAL of two separate cohorts of patients with IPF was associated with poor survival. We conclude that high CXCL6 drives fibroblast function and correlates with poor outcomes in IPF.

The mechanisms involved in immune responses to cancer have been extensively studied for several decades and, considerable attention has been paid to harnessing the immune system's therapeutic potential. Cancer immunotherapy has established itself as a promising new treatment option for a variety of cancer types. Various strategies including cancer vaccines, monoclonal antibodies (mAbs), adoptive T-cell-cancer therapy and immune test therapy have gained prominence through immunotherapy. However, it remains to be accomplished the full potential of cancer immunotherapy. In spite of having startling aspects, the cancer immunotherapies have some difficulties including the inability to effectively targeting the cancer antigens and the abnormalities in patient response. With the advancement of technology, this system has changed the genome-based immunotherapy process in the human body including generation of engineered T cells. Due to its high specificity, CRISPR-Cas9 has become a simple and flexible genome-editing tool to target nearly any genomic locus. Recently, the CD19-mediated CAR-T cell (chimeric antigen receptor T cell) therapy has opened a new avenue for the treatment of human cancer, though low efficiency is a major drawback of this process. Thus, increasing the efficiency of the CAR-T cell (engineered T cells that induce the chimeric antigen receptor) by using CRISPR-Cas9 technology could be a better weapon to fight against the cancer. In this review, we have broadly focused on the use of CRISPR-Cas9 technology for the modification of the T-cell, which can specifically recognize cancer cells and be used as immune therapeutics against cancer. We have also demonstrated the other potential strategies for the treatment of cancer.

Summary The kidney local microenvironment (KLM) plays a critical role in the pathogenesis of kidney fibrosis. However, the composition and regulation of a fibrotic KLM remain unclear. Through a multidisciplinary approach, we investigated the roles of the hepatocyte growth factor/c-met signaling pathway in regulating KLM formation in various chronic kidney disease (CKD) models. We performed a retrospective analysis of single-cell RNA sequencing data and determined that tubular epithelial cells and macrophages are two major cell populations in a fibrotic kidney. We then created a mathematical model that predicted loss of c-met in tubular cells would cause greater responses to injury than loss of c-met in macrophages. By generating c-met conditional knockout mice, we validated that loss of c-met influences epithelial plasticity, myofibroblast activation, and extracellular matrix synthesis/degradation, which ultimately determined the characteristics of the fibrotic KLM. Our findings open the possibility of designing effective therapeutic strategies to retard CKD., Graphical abstract, Highlights • A fibrotic kidney local microenvironment (KLM) is focal and segmental • C-met is more enriched in the distal tubule and collecting duct than in macrophages • Loss of c-met in tubular cells causes superior quick responses to simulated injury • HGF/c-met pathway determines the characteristics of a formed fibrotic KLM

Flowering time (heading date) of the rice plant is considered an important agronomic trait for environmental adaptation and grain yield. It is controlled by multiple genes and is regulated by different environmental factors, such as day length, temperature, soil moisture, etc. So far, approximately 125 genes regulating flowering process and floral organ identity or development directly or indirectly have been reported in rice. Among these genes, Heading date 3a (Hd3a), RICE FLOWERING LOCUS T1 (RFT1), Heading date 5 (Hd5), MORF-RELATED GENE702 (MRG702), Casein kinases, CKI and CK2α, Pseudo-Response Regulator 37 (PRR37), Hd gene family have been reported as the key genes regulating flowering time in rice; however, their functions are mostly inter-related. Hd3a and RFT1 that encode florigens, are known as the floral transition genes in rice. In rice, florigen immediately induces downstream genes in the shoot apical meristem (SAM) to start the transition from vegetative to reproductive phase. RFT1 gene regulates flowering time with pivotal action while Hd3a, regulates under long day conditions. The Hd5 gene regulates flowering time in variation of early heading for adaptation depending on environmental signals. MRG702, a reader protein, promotes flowering. Casein kinases, CKI and CK2α directly influence the function of the early heading regulator PRR37. Hd16/CKI hinders flowering time in the Ehd1-concerned pathway through phosphorylation of Ghd7 and PRR37. Natural variants of Hd1, PRR37, Ghd7, DTH8, Hd6, and Hd16 were found in the rice varieties that are cultivated presently in Asia and Europe, and their variants play significant roles in the down streaming of Ehd1 expression to delay flowering time in natural long day (LD) conditions.

Fibrosis affects all vital organs accounting for a staggering 45% of deaths worldwide and no effective therapies are currently available. Unresolved inflammation triggers downstream signaling events that lead to organ fibrosis. In recent years, proinflammatory cytokine Interleukin-17 (IL-17) has been implicated in several chronic inflammatory diseases that often culminate in organ damage followed by impaired wound healing and fibrosis. In this review, we outline the contribution of the IL-17 in mediating fibrotic diseases in various organs. A comprehensive understanding of the inflammatory events, and particularly the details of IL-17 signaling in vivo, could be beneficial in designing new therapeutic or preventive approaches to treat fibrosis. Additionally, understanding organ-specific differences in IL-17 activity could lead to targeted therapies and help spare other organs from unwanted side effects.

Cultivation with Arsenic (As) contaminated water severely affects growth of rice plants that results into reduced grain yield. This study was carried out to develop a rapid and effective method of screening rice varieties and/or segregating population against arsenic phyto-toxicity tolerance. Sodium arsenate was used as arsenic source. Ten pre-germinated seeds of each variety were grown on styro-foam placed on a tray filled with either phosphate-free nutrient solution (control) or the same nutrient solution supplemented with di-sodium hydrogen arsenate (treatment). The trays were kept at controlled environmental condition in a growth chamber at 26±1℃ with 70% humidity and 3500 lux. After 7 days of growth, standard growth parameters such as shoot length, root length, root-shoot biomass were recorded and percentages reduction for shoot length, root length and root shoot biomass compared to those of control were calculated. Arsenic stress reduced the phenotypic expression of all three seedling traits but the effect of arsenic was more prominent on root length compared to the shoot length and root-shoot biomass. The dose response experiment showed that the 0.75-1.25 mgL-1 Arsenic concentrations had much promise to discriminate rice genotypes for arsenic phyto-toxicity tolerance at early growth stage. The validation experiment with the 0.75-1.25 mgL-1 Arsenic doses on a set of 20 genotypes identified 1.25 mgL-1 Arsenic could effectively and efficiently differentiate rice genotypes, particularly for tolerance in shoot length and root-shoot biomass reduction, where 1.0 mgL-1 Arsenic was found sufficient for discriminating varieties for tolerance in root length reduction. The rice variety BRRI dhan47 showed more tolerance against Arsenic contaminated water.

Lymph-node (LN) stromal cell populations expand during the inflammation that accompanies T cell activation. Interleukin-17 (IL-17)-producing helper T cells (TH17 cells) promote inflammation through the induction of cytokines and chemokines in peripheral tissues. We demonstrate a critical requirement for IL-17 in the proliferation of LN and splenic stromal cells, particularly fibroblastic reticular cells (FRCs), during experimental autoimmune encephalomyelitis and colitis. Without signaling via the IL-17 receptor, activated FRCs underwent cell cycle arrest and apoptosis, accompanied by signs of nutrient stress in vivo. IL-17 signaling in FRCs was not required for the development of TH17 cells, but failed FRC proliferation impaired germinal center formation and antigen-specific antibody production. Induction of the transcriptional co-activator IκBζ via IL-17 signaling mediated increased glucose uptake and expression of the gene Cpt1a, encoding CPT1A, a rate-limiting enzyme of mitochondrial fatty acid oxidation. Hence, IL-17 produced by locally differentiating TH17 cells is an important driver of the activation of inflamed LN stromal cells, through metabolic reprogramming required to support proliferation and survival. Fibroblastic reticular cells support lymph-node function and adaptive immunity. McGeachy and colleagues show that the cytokine IL-17 is needed to trigger metabolic changes required for the proliferation and survival of these cells in reactive lymph nodes.

Background and aims The patients in the intensive care unit (ICU) are often infected with multidrug resistant (MDR) organisms. When they are transferred to other ICUs, they can expand the reservoir of MDR organisms and pose a threat to the infection control program. The present observational study was undertaken to describe the epidemiology and compare the outcome of MDR and non-MDR infections after inter ICU patient transfer. Materials and methods A retrospective study was conducted in a cohort of 134 consecutive admitted patients in a tertiary care ICU from other ICUs. The primary objective was to measure the prevalence of MDR and non-MDR infections. The secondary objective was to compare the outcome between MDR and non-MDR group and identify the factors independently associated with mortality for each group. Results Among 134 patients, 89 had infections (66.4%) and in 29 (21.6%) were due to MDR organisms. The most common organism was Klebsiella in the MDR and E. coli in the non-MDR group. There was no difference between the groups in mortality, duration of mechanical ventilation and length of ICU stay. The duration of mechanical ventilation and ICU stay >7 days was independently associated with mortality in the MDR group. No association was found in the non-MDR group. Conclusion The study demonstrates a high prevalence of MDR infections after inter ICU transfer. There is no difference in outcome between the groups, but the mortality in the MDR group is independently associated with a longer duration of mechanical ventilation and ICU stay. How to cite this article Choudhuri AH, Ahuja B, Biswas PS, Uppal R. Epidemiology of Multidrug Resistant Infections after Inter-ICU Transfer in India. Indian Journal of Critical Care Medicine, January 2019;23(1):1-6.

Golden Rice with β-carotene in the grain helps to address the problem of vitamin A deficiency. Prior to commercialize Golden Rice, several performance and regulatory checkpoints must be achieved. We report results of marker assisted backcross breeding of the GR2E trait into three popular rice varieties followed by a series of confined field tests of event GR2E introgression lines to assess their agronomic performance and carotenoid expression. Results from confined tests in the Philippines and Bangladesh have shown that GR2E introgression lines matched the performance of the recurrent parents for agronomic and yield performance, and the key components of grain quality. Moreover, no differences were observed in terms of pest and disease reaction. The best performing lines identified in each genetic background had significant amounts of carotenoids in the milled grains. These lines can supply 30–50% of the estimated average requirements of vitamin A.

Antibody-mediated glomerulonephritis (AGN) is a clinical manifestation of many autoimmune kidney diseases for which few effective treatments exist. Chronic inflammatory circuits in renal glomerular and tubular cells lead to tissue damage in AGN. These cells are targeted by the cytokine IL-17, which has recently been shown to be a central driver of the pathogenesis of AGN. However, surprisingly little is known about the regulation of pathogenic IL-17 signaling in the kidney. Here, using a well characterized mouse model of AGN, we show that IL-17 signaling in renal tubular epithelial cells (RTECs) is necessary for AGN development. We also show that Regnase-1, an RNA binding protein with endoribonuclease activity, is a negative regulator of IL-17 signaling in RTECs. Accordingly, mice with a selective Regnase-1 deficiency in RTECs exhibited exacerbated kidney dysfunction in AGN. Mechanistically, Regnase-1 inhibits IL-17-driven expression of the transcription factor IκBξ and consequently its downstream gene targets including Il6 and Lcn2. Moreover, deletion of Regnase-1 in human RTECs reduced inflammatory gene expression in an IκBξ-dependent manner. Overall, these data identify an IL-17-driven inflammatory circuit in RTECs during AGN that is constrained by Regnase-1.

The lack of dietary diversity among poor communities has led to nutritional consequences, particularly zinc deficiency. An adequate intake of mineral- and vitamin-rich food is necessary for achieving and maintaining good health. Zinc is one of the micronutrients considered essential to improve human health and decrease the risk of malnutrition. Biofortification of rice through breeding is a cost-effective and sustainable strategy to solve micronutrient malnutrition. The Biofortification Priority Index prepared by HarvestPlus clearly identified several countries in Asia with an immediate need for Zn biofortification. The International Rice Research Institute (IRRI) and its national partners in target countries are making efforts to develop Zn-biofortified rice varieties. The first set of high-Zn rice varieties has been released for commercial cultivation in Bangladesh, India, the Philippines, and Indonesia. Efforts have begun to mainstream grain Zn to ensure that the Zn trait becomes an integral part of future varieties. Huge scope exists to apply advanced genomics technologies such as genomic selection and genome editing to speed up high-Zn varietal development. An efficient rice value chain for Zn-biofortified varieties, quality control, and promotion are essential for successful adoption and consumption. The development of next-generation high-Zn rice varieties with higher grain-Zn content, stacking of multiple nutrients, along with good grain quality and acceptable agronomic traits has to be fast-tracked. Healthier rice has a large demand from all stakeholders, so we need to keep up the pace of developing nutritious rice to meet the demand and to achieve nutritional security.

INTRODUCTION: The treatment of SARS CoV2 (Severe Acute Respiratory Syndrome corona virus 2) also known as COVID-19 (corona virus disease 2019) continues to remain an enigma even after six months of the pandemic. Hydroxychloroquine (HCQ) has been one of the most widely tested drugs for SARS CoV2 on account of its antiviral properties. However the results so far have been far from categorical. The meta-analyses conducted till date are also lacking in precision and appropriateness. This systematic review and meta-analysis addresses the efficacy and safety of HCQ in SARS CoV2 by overcoming the limitations of earlier meta-analysis. METHODS: A total of 5 prominent medical databases were searched and fourteen studies (n = 12455) were included in the systematic review and meta-analyses. The data on survival, alleviation of symptoms, conversion of RT PCR positivity to negativity, use and efficacy in presence of co-morbidities (Hypertension, diabetes and heart disease) and cardiac and gastrointestinal side effects were extracted. Meta-analysis was applied to calculate the pooled estimates. Fixed-effects model results were chosen since I2 was

Disseminated candidiasis caused by the fungus Candida albicans is a major clinical problem in individuals with kidney disease and accompanying uremia; disseminated candidiasis fatality is twice as common in patients with uremia as those with normal kidney function. Many antifungal drugs are nephrotoxic, making treatment of these patients particularly challenging. The underlying basis for this impaired capacity to control infections in uremic individuals is poorly understood. Here, we show in multiple models that uremic mice exhibit an increased susceptibility to systemic fungal infection. Uremia inhibits Glut1-mediated uptake of glucose in neutrophils by causing aberrant activation of GSK3β, resulting in reduced ROS generation and hence impaired killing of C. albicans in mice. Consequently, pharmacological inhibition of GSK3β restored glucose uptake and rescued ROS production and candidacidal function of neutrophils in uremic mice. Similarly, neutrophils isolated from patients with kidney disease and undergoing hemodialysis showed similar defect in the fungal killing activity, a phenotype rescued in the presence of a GSK3β inhibitor. These findings reveal a mechanism of neutrophil dysfunction during uremia and suggest a potentially translatable therapeutic avenue for treatment of disseminated candidiasis.

Excessive cytokine activity underlies many autoimmune conditions, particularly through the IL-17 and TNFα signaling axes. Both cytokines activate NF-κB, but appropriate induction of downstream effector genes requires coordinated activation of other transcription factors, notably CCAAT/Enhancer Binding Proteins (C/EBPs). Here we demonstrate the unexpected involvement of a post-transcriptional ‘epitranscriptomic’ mRNA modification (N6-methyladenosine, m(6)A) in regulating C/EBPβ and C/EBPδ in response to IL-17A, as well as IL-17F and TNFα. Prompted by the observation that C/EBPβ/δ-encoding transcripts contain m(6)A consensus sites, we show that Cebpd and Cebpb mRNAs are subject to m(6)A modification. Induction of C/EBPs is enhanced by an m(6)A methylase ‘writer’ and suppressed by a demethylase ‘eraser.’ The only m(6)A ‘reader’ found to be involved in this pathway was IGF2BP2 (IMP2), and IMP2 occupancy of Cebpd and Cebpb mRNA was enhanced by m(6)A modification. IMP2 facilitated IL-17-mediated Cebpd mRNA stabilization and promoted translation of C/EBPβ/δ in response to IL-17A, IL-17F and TNFα. RNASeq revealed transcriptome-wide IL-17-induced transcripts that are IMP2-influenced, and RIPSeq identified the subset of mRNAs that are directly occupied by IMP2, which included Cebpb and Cebpd. Lipocalin-2 (Lcn2), a hallmark of autoimmune kidney injury, was strongly dependent on IL-17, IMP2 and C/EBPβ/δ. Indeed, Imp2(−/−) mice were resistant to autoantibody-induced glomerulonephritis (AGN), showing impaired renal expression of C/EBPs and Lcn2. Moreover, IMP2 deletion initiated only after AGN onset ameliorated disease. Thus, post-transcriptional regulation of C/EBPs through m(6)A/IMP2 represents a new paradigm of cytokine-driven autoimmune inflammation.

Background and Aims: The implementation of safety measures during airway management is a major concern to prevent COVID-19 transmission during pandemic. Various guidelines and advisories are in vogue to ensure safe practices. However, their success depends on the caregivers' knowledge and understanding. This survey was conducted to assess the knowledge and safety concerns amongst physicians towards airway management in the background of COVID-19 pandemic. Material and Methods: A survey instrument of thirty questions covering three timelines of airway management viz. 'before', 'during' and 'after' airway intervention was created. The questionnaire was electronically mailed to the eligible physicians over a period of one month via a web-based platform and the responses were analyzed. The responses were depicted numerically as percentage. A multiple discriminant analysis was used to test the accuracy of responses after adjusting for common variables. Results: Out of 407 responses, 300 were eligible for analysis. The respondents with correct answers to questions with single correct response were 46%, 69% and 57.3%, along the three timelines and the respondents with more than 75% correct responses in questions with multiple correct responses were 49%, 58% and 31% along the same timelines. About 75% of the participants became aware of transmission through aerosols aftermath pandemic. About two-third of the participants had knowledge about the safety guidelines and recommendations. Majority of the respondents were aware of the safety measures 'during airway intervention'. Conclusion: Our study found satisfactory knowledge and appreciable concern among the practicing physicians regarding airway safety measures in the wake of COVID-19 pandemic. However, more physicians were aware about the measures required to be adopted 'during' airway intervention. The survey highlights the need for a more focused training of the caregivers about safety measures 'before' and 'after' airway intervention.

Consumable herbs play a basic part in sustenance and human health. Traditionally, Colocasia gigantea Hook (Araceae) is used to treat fever, infection, wounds healing, drowsiness, tuberculosis, stomach problems etc. AIM OF THE STUDY: The study aspired to identify bioactive compounds, to evaluate anti-inflammatory and analgesic potentials of edible herb C. gigantea, and to molecular docking study against anti-inflammatory enzyme Cyclooxygenase-2 (COX-2).Chemical components of C. gigantea were discerned by HPLC and GCMS assays. In vitro anti-inflammatory activity was appraised by heat-induced, hypotonicity, and hydrogen peroxide-induced hemolysis assays and in vivo by formalin-induced paw edema assay. In vivo analgesic activity was evaluated by acetic acid-induced pain modulation assay. Also, molecular docking of the identified compounds was explored against the anti-inflammatory enzyme cyclooxygenase-2.HPLC-DAD analysis divulged the presence of trans-cinnamic acid along with (-)-epicatechin as a prime component. Also, 9, 12-Octadecadienoic acid (37.86%) and n-Hexadecanoic acid (25.89%) as the major as well as 24 other compounds were confirmed through GCMS in the extract. In in vitro anti-inflammatory study, C. gigantea extract indicated prominent erythrocyte membrane stabilization activity with good percentage aegis in all experimental assays. In addition to, formalin-induced in vivo anti-inflammatory assay revealed the maximum (42.37% and 48.72%) suppression of edema at the fourth hour at 250 and 500 mg/kg body weight, respectively. Moreover, an in-vivo pain modulation assay exposed significant (p 0.05) activity at experimental doses. Furthermore, in the docking study, (-)-epicatechin was more active rather than other identified compounds with strong binding affinity to COX-2 protein.The extract evinced remarkable anti-inflammatory and analgesic activities. Identified bioactive components along with other components of the extract might play a pivotal role in the observed bioactivity and the results vindicate the use of edible herb C. gigantea in ancestral medicine.

Medicinal plants possess a surplus of novel and biologically active secondary metabolites that are responsible for counteracting diseases. Traditionally, Gomphandra tetrandra (Wall.) Sleumer is used to treat mental disorders. The present research was designed to explore phytochemicals from the ethanol leaf extract of Gomphandra tetrandra (Wall.) Sleumer to identify the potential pharmacophore(s) in the treatment of neurological disorders. The chemical compounds of the experimental plant were identified through GC-MS analysis. In-vitro antioxidant activity was assessed using different methods. Furthermore, in-vivo neurological activity was assessed in Swiss-albino mice. Computer-aided analysis was appraised to determine the best-fit phytoconstituent of a total of fifteen identified compounds in the experimental plant extract against beta-amyloid precursor protein. The experimental extract revealed fifteen compounds in GC-MS analysis and the highest content was 9, 12, 15-octadecatrienoic acid (z,z,z). The extract showed potent antioxidant activity in in-vitro assays. Furthermore, in in-vivo neurological assays, the extract disclosed significant (p &lt, 0.05) neurological activity. The most favorable phytochemicals as neurological agents were selected via ADMET profiling, and molecular docking was studied with beta-amyloid precursor protein. In the computer-aided study, 1, 5-diphenyl-2h-1, 2, 4-triazoline-3-thione (Pub Chem CID: 2802516) was more active than other identified compounds with strong binding affinity to beta-amyloid precursor protein. The present in vivo and in silico studies revealed neuropharmacological features of G. tetrandra leaf extract as a natural agent against neurological disorders, especially Alzheimer’s disease.

Oropharyngeal candidiasis (OPC) is an opportunistic infection of the oral mucosa caused by the commensal fungus Candida albicans. IL-17 and IL-22 both mediate antifungal immunity yet activate distinct downstream signaling pathways. While much is known about IL-17-dependent immunity in OPC, the activities of IL-22 are less well delineated. We show that induction of Il22 is independent of Dectin-1, CARD9 and aryl hydrocarbon receptor (AhR) and is driven by IL-23 and the C. albicans pore forming peptide candidalysin. Despite similar induction requirements and cellular sources, IL-22 and IL-17 function non-redundantly during OPC and exert opposing roles in neutrophil recruitment. The IL-22 and IL-17 receptors are required in anatomically distinct locations; loss of IL-22RA1 in the oral basal epithelial layer (BEL) but not the suprabasal epithelial layer (SEL) causes susceptibility to OPC, whereas IL-17RA is needed in the SEL. Our data reveal that IL-22 is a major activator of STAT3 in the BEL during OPC. Moreover, loss of STAT3 in the BEL but not the SEL renders mice susceptible to OPC. Transcriptional profiling of RNASeq data linked IL-22/STAT3 to oral epithelial cell proliferation and survival, but also, unexpectedly, to driving an IL-17 gene signature. We show that IL-22 acts on the BEL to replenish the IL-17RA-expressing SEL, thereby restoring the ability of the oral epithelium to respond to IL-17. Consequently, IL-22 signaling in BEL ‘licenses’ IL-17R signaling in the oral epithelium, revealing spatially distinct yet cooperative activities of IL-22 and IL-17 in oral candidiasis. This work also suggests that oral thrush in Jobs’ syndrome patients may be caused by STAT3 impairments in the oral epithelium, not just Th17 cells.

Dysregulated activity of IL-17 underlies many autoimmune conditions, but the molecular mechanisms by which IL-17 mediates pathogenic inflammation remain poorly understood. IL-17 regulates pathogenic inflammatory genes by two key transcription factor classes, NF-κB and CCAAT/Enhancer Binding (C/EBP) proteins. Surprisingly little is known about mechanisms that activate C/EBPs. In seeking to understand how IL-17 upregulates C/EBPs, we found that IL-17 signaling enhanced Cebpd mRNA stability, concomitant with increased levels of C/EBPδ translation. In contrast, IL-17 had only a marginal inductive effect on Cebpb mRNA, yet C/EBPβ protein was strongly upregulated. Examination of Cebpb and Cebpd noncoding sequences identified consensus sites for N6-methyladenosine (m6A) modification, an epitranscriptomic mark that influences mRNA fate. knockdown of the m6A ‘writer’ METTL3 decreased C/EBP expression, which was reversed by the ‘eraser’ FTO. Moreover, we found that loss of an unusual m6A ‘reader’ IGF2BP2 (IMP2), an RNA binding protein known to control mRNA stability, impaired IL-17 induction of C/EBPs. IMP2 bound directly to Cebps transcripts, leading to enhanced Cebpd half-life and enhanced translation of both C/EBPs. Transcriptomic analysis revealed that IMP2 regulates C/EBP-dependent genes, including IL-6 and Lcn2. Lcn2 is a biomarker of autoantibody-induced glomerulonephritis (AGN), a setting of IL-17-driven inflammatory nephritis. Imp2−/− mice were resistant to AGN, which was linked to impaired upregulation of C/EPBs and Lcn2 in kidney. Thus, IL-17-induced autoimmunity is mediated through m6A-dependent post-transcriptional regulation of C/EBP transcription factors.

Idiopathic pulmonary fibrosis (IPF) is a disease characterized by the accumulation of apoptosis-resistant fibroblasts in the lung. We have previously shown that high expression of the transcription factor Twist1 may explain this prosurvival phenotype in vitro. However, this observation has never been tested in vivo. We found that loss of Twist1 in COL1A2+ cells led to increased fibrosis characterized by very significant accumulation of T cells and bone marrow–derived matrix-producing cells. We found that Twist1-null cells expressed high levels of the T cell chemoattractant CXCL12. In vitro, we found that the loss of Twist1 in IPF lung fibroblasts increased expression of CXCL12 downstream of increased expression of the noncanonical NF-κB transcription factor RelB. Finally, blockade of CXCL12 with AMD3100 attenuated the exaggerated fibrosis observed in Twist1-null mice. Transcriptomic analysis of 134 IPF patients revealed that low expression of Twist1 was characterized by enrichment of T cell pathways. In conclusion, loss of Twist1 in collagen-producing cells led to increased bleomycin-induced pulmonary fibrosis, which is mediated by increased expression of CXCL12. Twist1 expression is associated with dysregulation of T cells in IPF patients. Twist1 may shape the IPF phenotype and regulate inflammation in fibrotic lung injury.

A set of 100 IRRI bred advanced breeding lines were tested at Gazipur (as moderate productive control site) and at Habiganj (as high productive site) following row-column design with 2 replications. The breeding lines were highly variable in days to maturity and plant height but not in grain yield. However the interaction effects between genotype and environment (GXE) were significant for all three traits. At Gazipur, the breeding lines yielded with range between 3.3 to 7.3 t/ha with a growth duration range of 138-154 days, while at Habiganj they yielded 5.1-7.9 t/ha with growth duration of 139-159 days. The highest yielding genotype was IR99092-B-B-78 followed by IR13A390, IR99061-B-B-7, IR14D111, etc at Gazipur, while IR13A390 followed by IR100008-91-B yielded the highest at Habiganj site. Based on yield and growth duration, 22 breeding lines showing better performance at Gazipur, 9 lines at Habiganj and 2 lines for both locations were selected for further evaluation.

Relaxin is a hormone that has been considered as a potential therapy for patients with fibrotic diseases.To gauge the potential efficacy of relaxin-based therapies in idiopathic pulmonary fibrosis (IPF), we studied gene expression for relaxin/insulin-like family peptide receptor 1 (RXFP1) in IPF lungs and controls.We analyzed gene expression data obtained from the Lung Tissue Research Consortium and correlated RXFP1 gene expression data with cross-sectional clinical and demographic data. We also employed ex vivo donor and IPF lung fibroblasts to test RXFP1 expression in vitro. We tested CGEN25009, a relaxin-like peptide, in lung fibroblasts and in bleomycin injury.We found that RXFP1 is significantly decreased in IPF. In patients with IPF, the magnitude of RXFP1 gene expression correlated directly with diffusing capacity of the lung for carbon monoxide (P 0.0001). Significantly less RXFP1 was detected in vitro in IPF fibroblasts than in donor controls. Transforming growth factor-β decreased RXFP1 in both donor and IPF lung fibroblasts. CGEN25009 was effective at decreasing bleomycin-induced, acid-soluble collagen deposition in vivo. The relaxin-like actions of CGEN25009 were abrogated by RXFP1 silencing in vitro, and, in comparison with donor lung fibroblasts, IPF lung fibroblasts exhibited decreased sensitivity to the relaxin-like effects of CGEN25009.IPF is characterized by the loss of RXFP1 expression. RXFP1 expression is directly associated with pulmonary function in patients with IPF. The relaxin-like effects of CGEN25009 in vitro are dependent on expression of RXFP1. Our data suggest that patients with IPF with the highest RXFP1 expression would be predicted to be most sensitive to relaxin-based therapies.

Rice crops are substantially affected by low-temperature or cold stress across the world ranging from floodplains to high altitudes. Rice is affected at various growth stages starting from germination to the reproductive stages depending on the intensity of low-temperature and duration of exposure. The primary symptoms of cold injury at the vegetative stage are, low germination, stunted growth, yellowing, seedling death and delayed heading, and during the reproductive stage these manifest as reduced stem elongation, incomplete panicle exertion, panicle degeneration, and spikelet sterility. All these ultimately result in a low yield of rice. There are different crop management practices to reduce cold injury but the genetic improvement of rice for cold tolerance is the most sustainable one. However, genetic improvement is largely limited by the polygenic control of cold-tolerant genes/quantitative trait loci (QTLs), which are mostly confined in japonica background, although indica rice contributes more than 80% of the global rice production. The advent of molecular marker technology has shown much promise in exploiting genetic variations of japonica germplasm for cold tolerance and using it in the breeding program for both indica and japonica rice. So far more than 270 QTLs have been mapped and reported for the seedling and reproductive stages but due to their polygenic and epistatic nature, no noteworthy progress has been reported so far. Genomic selection, high throughput SNP genotyping and repeatable phenotyping, and the use of functional markers in forward breeding can enhance favorable alleles in the breeding population and, thereby, rice segregants can be developed with repeatable variance for cold tolerance in order to withstand and yield higher in cold prone environments.

Disseminated candidiasis (DC) caused by the fungus Candida albicans is a major clinical problem in individuals with kidney disease and accompanying uremia. DC fatality is twice as common in patients with uremia as those without renal impairments. Many antifungal drugs are nephrotoxic, making treatment of these patients challenging. The underlying basis for this impaired capacity to control infections in uremic individuals is poorly understood. Here we show that uremic mice show an increased susceptibility to DC. Uremia inhibits Glut1-mediated uptake of glucose in neutrophils by causing aberrant activation of GSK3beta, resulting in reduced ROS generation and hence impaired killing of C. albicans in both mice and human cells. Consequently, pharmacological inhibition of GSK3beta ‘de-programed’ glucose metabolism and rescued ROS production and candidacidal function of neutrophils in uremic mice. These findings reveal a central mechanism of neutrophil dysfunction during uremia and suggest a potentially translatable therapeutic avenue for treatment of DC.

Autophagy is a vacuolar, lysosomal degradation pathway for injured and damaged protein molecules and organelles in eukaryotic cells, which is controlled by nutrients and stress responses. Dysregulation of cellular autophagy may lead to various diseases such as neurodegenerative disease, obesity, cardiovascular disease, diabetes, and malignancies. Recently, natural compounds have come to attention for being able to modulate the autophagy pathway in cancer prevention, although the prospective role of autophagy in cancer treatment is very complex and not yet clearly elucidated. Numerous synthetic chemicals have been identified that modulate autophagy and are favorable candidates for cancer treatment, but they have adverse side effects. Therefore, different phytochemicals, which include natural compounds and their derivatives, have attracted significant attention for use as autophagy modulators in cancer treatment with minimal side effects. In the current review, we discuss the promising role of natural compounds in modulating the autophagy pathway to control and prevent cancer, and provide possible therapeutic options.

Arsenic phyto-toxicity is a limiting factor affecting rice production in the Indo-Gangetic flood plain. In this study, 98 microsatellite markers were used to map quantitative trait loci (QTL) conferring arsenic phyto-toxicity tolerance (AsT) at seedling stage from a F2 population derived from a cross between an arsenic sensitive indica rice cultivar (BRRI dhan45) and an arsenic tolerant indica rice cultivar (BRRI dhan47) using selective genotyping technique. Arsenic phyto-toxicity tolerance of F2:3 population was assessed with an arsenic stress of 1.25 mg L−1 under hydroponic culture in a climate chamber. AsT indices for shoot length, root length and root-shoot biomass were estimated in terms of comparative growth in treated plants compared to that in control plants. A total of four main effect QTLs with significant LOD comprising two for relative growth in shoot length, one for each of root length and root-shoot biomass under arsenic stress were identified on chromosomes 8 and 12 using composite interval mapping approach. A large effect QTL for arsenic phyto-toxicity tolerance in root length contributing 24.9 % phenotypic variation was identified on chromosome 8 with plausible pleiotropic effect on shoot length and root-shoot biomass.

Crescentic glomerulonephritis (cGN) is a severe clinical manifestation in a subset of patients with Systemic lupus erythematosus. Lack of understanding of the pathogenesis of cGN act as a major constraint in treating these patients. Emerging evidence suggest a critical role of IL-17 in the pathogenesis of membranoproliferative glomerulonephritis in lupus. However, the role of IL-17 receptor (IL-17RA) signaling in cGN is unknown. Here, we developed a model of poly I:C-induced Type I Interferon (IFN-I)-dependent cGN in B6.MRL-Faslpr/J (B6.lpr) mice. B6.lpr mice deficient in IL-17RA were protected from IFN-I-dependent cGN. While systemic response was unabated, renal infiltration of alternatively activated macrophages was severely impaired in IL-17RA(-/-) mice. Finally, we show that IL-17 differentially regulates the expression of macrophage chemo-attractant genes in renal tubular epithelial cells and macrophages in association with IFN-I. These results suggest that neutralization IL-17 may confer better protection in SLE patients with high IFN-I gene signature and cGN.

Oropharyngeal candidiasis (OPC) is an opportunistic infection of the oral mucosa caused by the commensal fungus Candida albicans. IL-17 and IL-22 both mediate antifungal immunity yet activate distinct downstream signaling pathways. While much is known about IL-17-dependent immunity in OPC, the activities of IL-22 are less well delineated. We show that induction of Il22 is independent of Dectin-1, CARD9 and aryl hydrocarbon receptor (AhR) and is driven by IL-23 and the C. albicans pore forming peptide candidalysin. Despite similar induction requirements and cellular sources, IL-22 and IL-17 function non-redundantly during OPC and exert opposing roles in neutrophil recruitment. The IL-22 and IL-17 receptors are required in anatomically distinct locations; loss of IL-22RA1 in the oral basal epithelial layer (BEL) but not the suprabasal epithelial layer (SEL) causes susceptibility to OPC, whereas IL-17RA is needed in the SEL. Our data reveal that IL-22 is a major activator of STAT3 in the BEL during OPC. Moreover, loss of STAT3 in the BEL but not the SEL renders mice susceptible to OPC. Transcriptional profiling of RNASeq data linked IL-22/STAT3 to oral epithelial cell proliferation and survival, but also, unexpectedly, to driving an IL-17 gene signature. We show that IL-22 acts on the BEL to replenish the IL-17RA-expressing SEL, thereby restoring the ability of the oral epithelium to respond to IL-17. Consequently, IL-22 signaling in BEL ‘licenses’ IL-17R signaling in the oral epithelium, revealing spatially distinct yet cooperative activities of IL-22 and IL-17 in oral candidiasis. This work also suggests that oral thrush in Jobs’ syndrome patients may be caused by STAT3 impairments in the oral epithelium, not just Th17 cells.

The kidney is an organ particularly susceptible to damage caused by infections and autoimmune conditions. Renal inflammation confers protection against microbial infections. However, if unchecked, unresolved inflammation may lead to kidney damage. Although proinflammatory cytokine IL-17 is required for immunity against extracellular pathogens, dysregulated IL-17 response is also linked to autoimmunity. In this review, we will discuss the current knowledge of IL-17 activity in the kidney in context to renal immunity and autoimmunity and raise the intriguing question to what extent neutralization of IL-17 is beneficial or harmful to renal inflammation.

Lymph-node (LN) stromal cell populations expand during the inflammation that accompanies T cell activation. Interleukin-17 (IL-17)-producing helper T cells (T

Candida albicans is a dimorphic commensal fungus that causes severe oral infections in immunodeficient patients. Invasion of C. albicans hyphae into oral epithelium is an essential virulence trait. Interleukin-17 (IL-17) signaling is required for both innate and adaptive immunity to C. albicans. During the innate response, IL-17 is produced by γδ T cells and a poorly understood population of innate-acting CD4+ αβ T cell receptor (TCRαβ)+ cells, but only the TCRαβ+ cells expand during acute infection. Confirming the innate nature of these cells, the TCR was not detectably activated during the primary response, as evidenced by Nur77eGFP mice that report antigen-specific signaling through the TCR. Rather, the expansion of innate TCRαβ+ cells was driven by both intrinsic and extrinsic IL-1R signaling. Unexpectedly, there was no requirement for CCR6/CCL20-dependent recruitment or prototypical fungal pattern recognition receptors. However, C. albicans mutants that cannot switch from yeast to hyphae showed impaired TCRαβ+ cell proliferation and Il17a expression. This prompted us to assess the role of candidalysin, a hyphal-associated peptide that damages oral epithelial cells and triggers production of inflammatory cytokines including IL-1. Candidalysin-deficient strains failed to up-regulate Il17a or drive the proliferation of innate TCRαβ+ cells. Moreover, candidalysin signaled synergistically with IL-17, which further augmented the expression of IL-1α/β and other cytokines. Thus, IL-17 and C. albicans, via secreted candidalysin, amplify inflammation in a self-reinforcing feed-forward loop. These findings challenge the paradigm that hyphal formation per se is required for the oral innate response and demonstrate that establishment of IL-1– and IL-17–dependent innate immunity is induced by tissue-damaging hyphae.