Heterogeneity in glacier thinning and slowdown of ice movement in the Garhwal Himalaya, India.

Limited ground-based surveys and extensive remote sensing analyses have confirmed glacier thinning in the Garhwal Himalaya. More detailed studies on specific glaciers and the drivers of reported changes are essential to comprehend small-scale differences in the effects of climatic warming on Himalayan glaciers. We computed elevation changes and surface flow distribution for 205 (≥0.1 km2) glaciers in the Alaknanda, Bhagirathi, and Mandakini basins, all located in the Garhwal Himalaya, India. This study also investigates a detailed integrated analysis of elevation changes and surface flow velocities for 23 glaciers with varying characteristics to understand the impact of ice thickness loss on overall glacier dynamics. We observed significant heterogeneity in glacier thinning and surface flow velocity patterns using temporal DEMs and optical satellite images with ground-based verification. The average thinning rate was found to be 0.07 ± 0.09 m a-1 from 2000 to 2015, and it increased to 0.31 ± 0.19 m a-1 from 2015 to 2020, with pronounced differences between individual glaciers. Between 2000 and 2015, Gangotri Glacier thinned nearly twice as much as the neighbouring Chorabari and Companion glaciers, which have thicker supraglacial debris that protects the beneath ice from melting. The transitional zone between debris-covered and clean ice glaciers showed substantial flow during the observation period. However, the lower reaches of their debris-covered terminus areas are almost stagnant. These glaciers experienced a significant slowdown (~25 %) between 1993-1994 and 2020-2021, and only the Gangotri Glacier was active even in its terminus region during most observational periods. The decreasing surface gradient reduces the driving stress and causes slow-down surface flow velocities and an increase in stagnant ice. Surface lowering of these glaciers may have substantial long-term impacts on downstream communities and lowland populations, including more frequent cryospheric hazards, which may threaten future water and livelihood security.

Emission of greenhouse gases due to anthropogenic activities: an environmental assessment from paddy rice fields.

Paddy rice fields (PRFs) are a potent source of global atmospheric greenhouse gases (GHGs), particularly CH4 and CO2. Despite socio-environmental importance, the emission of GHGs has rarely been measured from Haryana agricultural fields. We have used new technology to track ambient concentration and soil flux of GHGs (CH4, CO2, and H2O) near Karnal's Kuchpura agricultural fields, India. The observations were conducted using a Trace Gas Analyzer (TGA) and Soil Flux Smart Chamber over various parts, i.e., disturbed and undisturbed zone of PRFs. The undisturbed zone usually accounts for a maximum ambient concentration of ~ 2434.95 ppb and 492.46 ppm of CH4 and CO2, respectively, higher than the average global concentration. Soil flux of CH4 and CO2 was highly varied, ranging from 0.18 to 11.73 nmol m-2 s-1 and 0.13-4.98 µmol m-2 s-1, respectively. An insignificant correlation was observed between ambient concentration and soil flux of GHGs from PRFs. Waterlogged (i.e., irrigated and rain-fed) soil contributed slightly lower CH4 flux to the atmosphere. Interestingly, such an agricultural field shows low CO2 and CH4 fluxes compared to the field affected by the backfilling of rice husk ash (RHA). This article suggests farmers not mix RHA to increase soil fertility because of their adverse environmental effects. Also, this study is relevant in understanding the GHGs' emissions from paddy rice fields to the atmosphere, their impacts, and mitigating measures for a healthy ecosystem.

Synthesis of Sulfide Perovskites by Sulfurization with Boron Sulfides.

Chalcogenide perovskites (CPs), with the general composition ABX3, where A and B are metals and X = S and Se, have recently emerged as promising materials for application in photovoltaics. However, the development of CPs and their applications has been hindered by the limitations of available preparation methods. Here we present a new approach for the synthesis of CPs, based on the sulfurization of ternary and binary oxides or carbonates with in situ formed boron sulfides. In contrast to the previously described approaches, the method presented here uses chemically stable starting materials and yields pure-phase crystalline CPs within several hours, under low hazard conditions. CP yields over 95% are obtained at temperatures as low as 600 °C. The generality of the approach is demonstrated by the preparation of CPs with compositions BaZrS3, ß-SrZrS3, BaHfS3, SrHfS3, and EuHfS3. Mechanistic insights about the formation of CPs are discussed.

Aquatic geochemistry of a major freshwater lake in the Kashmir Himalaya: solute acquisition and denudation process in the lacustrine system.

Lakes, the main entities of lacustrine environments, are a rich archive of environmental and geogenic changes in terms of compositional variation of water and sediment. Water and sediment samples (N = 173) were collected during 2013-2014 from the Wular Lake, one of the important fresh lakes within the Indian landmass. The study provides insights on the solutes acquisition mechanism and provenance of ionic constituents within the lake water and the sediments. Besides, the impact of catchment attributes on the lake system was in addition assessed. The hydrochemical results suggest that the chemical weathering of silicate and carbonates within the catchment shapes the lake water chemistry and characterizes the facies pattern into a hybrid type. The geochemical results of the lake sediments demonstrate that the improved abrasion rates and ensuant settling of detritus into the lake are closely linked with the prominent physical weathering over chemical weathering. The new finding of the present study is that sediments represent an unweathered basalt compositional trend, plausible provenance from mafic rocks, experiencing low to moderate degree of chemical weathering. The study found that increased encroachment within the lake catchment due to continued anthropogenic forcing is the primary source contributing the organic matter (OM) as well as the higher levels of Cl, NO3, SO4, and P to the lake. These findings corroborate with the land use-land cover changes (from the last 50 years) within the lake catchment in significantly deteriorating the lake system. The study recommends that the ongoing conversion of lake peripheral areas into urban settlement and agro-horticulture land by filling activities should be restricted.

Autophagy is required during high MUC2 mucin biosynthesis in colonic goblet cells to contend metabolic stress.

Goblet cells are specialized for the production and secretion of MUC2 glycoproteins that forms a thick layer covering the mucosal epithelium as a protective barrier against noxious substances and invading microbes. High MUC2 mucin biosynthesis induces endoplasmic reticulum (ER) stress and apoptosis in goblet cells during inflammatory and infectious diseases. Autophagy is an intracellular degradation process required for maintenance of intestinal homeostasis. In this study, we hypothesized that autophagy was triggered during high MUC2 mucin biosynthesis from colonic goblet cells to cope with metabolic stress. To interrogate this, we analyzed the autophagy process in high MUC2-producing human HT29-H and a clone HT29-L silenced for MUC2 expression by lentivirus-mediated shRNA, and WT and CRISPR/Cas9 MUC2 KO LS174T cells. Autophagy was constitutively increased in high MUC2-producing cells characterized by elevated pULK1S555 expression and increased numbers of autophagosomes as compared with MUC2 silenced or gene edited cells. Similarly, colonoids from Muc2+/+ but not Muc2-/- littermates differentiated into goblet cells showed increased autophagy. IL-22 treatment corrected misfolded MUC2 protein and alleviated the autophagy process in LS174T cells. This study highlights that autophagy plays an essential role in goblet cells to survive during high mucin biosynthesis by regulating cellular homeostasis.NEW & NOTEWORTHY It is unclear how colonic goblet cells survive by producing high output MUC2 mucin that triggers endoplasmic stress by misfolded MUC2 proteins. To cope with metabolic stress, we interrogated if autophagy played an essential role in regulating cellular homeostasis. Indeed, high MUC2 mucin biosynthesis dysregulated autophagy processes that was regulated by IL-22 to maintain gut barrier innate host defenses.

High-altitude meteorology of Indian Himalayan Region: complexities, effects, and resolutions.

The Himalaya, by virtue of its location and stupendous height, acts as a great climatic divide and regulates meteorological conditions in the subcontinent regions of South Asia. However, the associated complexities and their effects are yet to be resolved to understand the meteorology of the Indian Himalayan Region (IHR). In this review volume, we synthesize the results and inferences of several studies carried out in the IHR using in situ data, remotely sensed data, and model-based meteorological observations. Results provide insights into climate change, scientific gaps, and their causes in deciphering meteorological observations from the last century to recent decades and envisage impacts of climate change on water reservoirs in the future. Warming trend of air temperature, in contrast to global temperature, has been projected in recent decades (after 1990) with a greater warming rate in the maximum temperature than the minimum temperature. This drifting of air temperature from the beginning of last century accelerates the diurnal temperature range of the Himalayas. An elevation-dependent warming trend is mostly perceived in the northwest Himalayan region, implicating an increased warming rate in the Greater Himalaya as compared to the lower and Karakoram Himalaya. No definite trends of precipitation have been observed over different regions of the IHR, suggesting heterogeneous cryosphere-climate interaction between western and central Himalaya. In this review, we have tried to emphasize to the scientific community and policy-makers for enhancing the knowledge of physical and dynamical processes associated with meteorological parameters in the Himalayan terrain.

Evaluating CO2 flux and recharge source in geothermal springs, Garhwal Himalaya, India: stable isotope systematics and geochemical proxies.

Evaluation of geogenic carbon fluxes between solid Earth and its atmosphere is essential to understand the global geological carbon cycle. Some of the key geogenic CO2 suppliers are the magmatic mantle and metamorphic degassing from active and quiescent volcanoes, fault zones, geothermal systems and CO2 rich groundwater. Indian Himalayan geothermal field hosts about 340 geothermal springs in natural as well as artesian condition that eject hot waters and volatiles with varied temperature and chemical composition. These sites provide an opportunity to analyse tectonically driven gas emissions and their impact on regional and global climate. Here we adopt a method for direct measurement of Dissolved Inorganic Carbon (DIC ≈ HCO3) concentration in the geothermal springs to estimate geogenic CO2 flux from an active region based on water discharge and area of geothermal system between the tectonic boundaries of the Main Central Thrust (MCT) and Main Boundary Thrust (MBT) of the Garhwal (Northwest) Himalaya. In the study area, geothermal spring water contain high δ13CDIC ratio (- 8.5‰ to + 4.0‰ VPDB), and among the major ions, bicarbonate (HCO3-) varies by an order of magnitude from 1697 to 21,553 µEq/L; chloride and sodium vary from 90 to 19,171 µEq/L and 436 to 23181 µEq/L. The elevated concentration of Cl- and Na+ in geothermal spring waters suggests affinity towards their deeper origin. These geothermal springs cover a large area of nearly 10,000 km2 of the Garhwal region showing a significant discharge of CO2 rich water with an estimated carbon dioxide degassing flux of ~7.2 × 106 mol/year to the atmosphere. Considering widespread occurrences of geothermal springs in tectonically active areas worldwide, the proposed direct measurement of DIC may be used as a reliable tool to estimate CO2 fluxes in different active orogenic settings within the Earth system. Results of stable isotopes of δ18O (VSMOW) and δD (VSMOW) in these geothermal spring waters follow the Global Meteoric Water Line (GMWL), suggesting affinity of their recharge through the meteoric origin.

High MUC2 Mucin Biosynthesis in Goblet Cells Impedes Restitution and Wound Healing by Elevating Endoplasmic Reticulum Stress and Altered Production of Growth Factors.

Intestinal epithelial cell wound healing involves cell migration, proliferation, and differentiation. Although numerous studies have analyzed the migration of absorptive epithelial cells during wound healing, it remains unclear how goblet cells restitute and how MUC2 mucin production affects this process. In this study, we examined the role of high MUC2 production in goblet cell migration during wound healing and demonstrated that during high MUC2 output, goblet cells migrated slower because of impaired production of wound healing factors and endoplasmic reticulum (ER) stress. Two goblet cell lines, HT29-H and HT29-L, that produced high and low MUC2 mucin, respectively, were used. HT29-L healed wounds faster than HT29-H cells by producing significantly higher amounts of fibroblast growth factor (FGF) 1, FGF2, vascular endothelial growth factor-C, and matrix metallopeptidase 1. Predictably, treatment of HT29-H cells with recombinant FGF2 significantly enhanced migration and wound healing. High MUC2 biosynthesis in HT29-H cells induced ER stress and delayed migration that was abrogated by inhibiting ER stress with tauroursodeoxycholic acid and IL-22. FGF2- and IL-22-induced wound repair was dependent on STAT1 and STAT3 signaling. During wound healing after dextran sulfate sodium-induced colitis, restitution of Math1M1GFP+ goblet cells occurred earlier in the proximal colon, followed by the middle and then distal colon, where ulceration was severe. We conclude that high MUC2 output during colitis impairs goblet cell migration and wound healing by reducing production of growth factors critical in wound repair.

High MUC2 Mucin Expression and Misfolding Induce Cellular Stress, Reactive Oxygen Production, and Apoptosis in Goblet Cells.

MUC2 mucin is a large glycoprotein produced by goblet cells that forms the protective mucus blanket overlying the intestinal epithelium as the first line of innate host defense. High MUC2 production in inflammatory bowel disease and infectious colitis depletes goblet cells and the mucus layer by an unknown mechanism. Herein, we analyzed the effect of high MUC2 biosynthesis on endoplasmic reticulum (ER) stress and apoptosis in goblet cells using a high MUC2-producing human goblet cell line (HT29-H) and an HT29-H clone (HT29-L) silenced for MUC2 expression by lentivirus-mediated shRNA. Goblet cell ER stress and apoptosis were quantified during early onset of dextran sulfate sodium-induced colitis in C57BL/6 and Math1M1GFP mice. Compared with HT29-L and MUC2 nonproducing Caco-2 cells, high MUC2-producing HT29-H cells had significantly increased ER stress and apoptosis after treatment with ER stress-inducing agents. Apoptosis was driven by increased misfolded MUC2 that triggered elevated levels of reactive oxygen species. Correcting MUC2 folding and inhibiting reactive oxygen species alleviated ER stress and rescued cells from apoptosis. During early-onset colitis, mucus hypersecretion caused severe ER stress and apoptosis of goblet cells that preceded absorptive epithelial cell damage. Thus, in gastrointestinal inflammation, high MUC2 biosynthesis and goblet cell apoptosis lead to a dysfunctional epithelial barrier. Enhancing MUC2 folding may help alleviate goblet cell depletion and maintain mucosal integrity.

RD-1 encoded EspJ protein gets phosphorylated prior to affect the growth and intracellular survival of mycobacteria.

Mycobacterium tuberculosis (MTB) synchronizes a number of processes and controls a series of events to subvert host defense mechanisms for the sake of residing inside macrophages. Besides these, MTB also possesses a wide range of signal enzyme systems, including eleven serine threonine protein kinases (STPKs). The present study describes STPK modulated modification in one of the hypothetical proteins of the RD1 region; EspJ (ESX-1 secretion associated protein), which is predicted to be involved in virulence of MTB. We have employed knock-out MTB, and M. bovis BCG as a surrogate strain to elaborate the consequence of the phosphorylation of EspJ. The molecular and mass spectrometric analyses in this study, confirmed EspJ as one of the substrates of STPKs. The ectopic expression of phosphoablative mutants of espJ in M. bovis BCG also articulated the effect of phosphorylation on the growth and in survival of mycobacteria. Importantly, the level of phosphorylation of EspJ also differed between pathogenic H37 Rv (Rv) and non pathogenic H37 Ra (Ra) strains of MTB. This further suggested that to a certain extent, the STPKs mediated phosphorylation may be accountable, in determining the growth and in intra-cellular survival of mycobacteria.

Identification of Novel Inhibitors of Mycobacterium tuberculosis PknG Using Pharmacophore Based Virtual Screening, Docking, Molecular Dynamics Simulation, and Their Biological Evaluation.

PknG is a Ser/thr protein kinase that plays a crucial role in regulatory processes within the mycobacterial cell and signaling cascade of the infected host cell. The essentiality of PknG in mycobacterial virulence by blocking phagosome-lysosome fusion as well as its role in intrinsic antibiotic resistance makes it an attractive drug target. However, only very few compounds have been reported as Mycobacterium tuberculosis PknG (MtPknG) inhibitors so far. Therefore, in an effort to find potential inhibitors against MtPknG, we report here a sequential pharmacophore-based virtual screening workflow, 3-fold docking with different search algorithms, and molecular dynamic simulations for better insight into the predicted binding mode of identified hits. After detailed analysis of the results, six ligands were selected for in vitro analysis. Three of these molecules showed significant inhibitory activity against MtPknG. In addition, inhibitory studies of mycobacterial growth in infected THP-1 macrophages demonstrated considerable growth inhibition of M. bovis BCG induced through compound NRB04248 without any cytotoxic effect against host macrophages. Our results suggest that the compound NRB04248 can be explored for further design and optimization of MtPknG inhibitors.

DNA demethylases target promoter transposable elements to positively regulate stress responsive genes in Arabidopsis.

BACKGROUND: DNA demethylases regulate DNA methylation levels in eukaryotes. Arabidopsis encodes four DNA demethylases, DEMETER (DME), REPRESSOR OF SILENCING 1 (ROS1), DEMETER-LIKE 2 (DML2), and DML3. While DME is involved in maternal specific gene expression during seed development, the biological function of the remaining DNA demethylases remains unclear. RESULTS: We show that ROS1, DML2, and DML3 play a role in fungal disease resistance in Arabidopsis. A triple DNA demethylase mutant, rdd (ros1 dml2 dml3), shows increased susceptibility to the fungal pathogen Fusarium oxysporum. We identify 348 genes differentially expressed in rdd relative to wild type, and a significant proportion of these genes are downregulated in rdd and have functions in stress response, suggesting that DNA demethylases maintain or positively regulate the expression of stress response genes required for F. oxysporum resistance. The rdd-downregulated stress response genes are enriched for short transposable element sequences in their promoters. Many of these transposable elements and their surrounding sequences show localized DNA methylation changes in rdd, and a general reduction in CHH methylation, suggesting that RNA-directed DNA methylation (RdDM), responsible for CHH methylation, may participate in DNA demethylase-mediated regulation of stress response genes. Many of the rdd-downregulated stress response genes are downregulated in the RdDM mutants nrpd1 and nrpe1, and the RdDM mutants nrpe1 and ago4 show enhanced susceptibility to F. oxysporum infection. CONCLUSIONS: Our results suggest that a primary function of DNA demethylases in plants is to regulate the expression of stress response genes by targeting promoter transposable element sequences.

Phosphorylation of pyruvate kinase A by protein kinase J leads to the altered growth and differential rate of intracellular survival of mycobacteria.

PknJ (Rv2088) is a serine/threonine protein kinase of mycobacteria which is present in Mycobacterium tuberculosis (MTB), but its gene is absent in Mycobacterium smegmatis (MS); a fast grower and nonpathogenic species of mycobacteria. The heterologous expression of MTB-specific PknJ in MS altered the growth of recombinant mycobacteria highlighting one of the characteristics of this protein. This nature of the protein was further confirmed when Mycobacterium bovis BCG (BCG) containing antisense copy of pknJ resulted in the increased growth of BCG. The real-time RNA quantification analysis pointed out toward increased expression of this protein during infection of THP-1 macrophage cells which further emphasized that the protein is essential for the intracellular survival of mycobacteria. The differential in gel electrophoresis (DIGE) data followed by mass spectroscopy suggested that PknJ is involved in regulation of pyruvate kinase A (Rv1617). Since pyruvate kinase (PK) A is one of the key enzymes which controls glycolytic cycle in mycobacteria, we looked for its interaction with PknJ during extracellular and intracellular growth of mycobacteria. In order to identify the specific residue(s) involved in post-translational modification, the phospho-null mutants of PK were generated, and their substrate specificities in response to PknJ were assessed through kinase assay. The findings thus underlined that the PK activity is predominantly dependent on the threonine residue at the 94(th) position and further suggested that this site may be plausible in intracellular survival of mycobacteria upon phosphorylation with PknJ.

Putative roles of a proline-glutamic acid-rich protein (PE3) in intracellular survival and as a candidate for subunit vaccine against Mycobacterium tuberculosis.

The proline-glutamic acid (PE) protein family of Mycobacterium tuberculosis (Mtb) plays diverse roles in the pathogenesis and modulation of host immune responses. The uniqueness of conserved regions of PE proteins may be useful to test and validate their corresponding functions. Hence, the present study has been undertaken to demonstrate the role of PE3 (Rv0159c) for persistence, host immune response and immunoprophylaxis. We have expressed Mtb-specific PE3 gene in M. smegmatis (MS) and used the strain to infect J774A.1 macrophage cells and BALB/c mice. It was observed that during the infection, the MS expressing PE3 showed higher bacterial load when compared to infection with wild-type MS. In hypoxic condition, the expression level of PE3 gene was induced in Mtb, which further showed its relevance in the cell survival during hypoxia-induced persistence. The expression level of PE3 in Mtb was markedly induced during chronic stage of murine infection, which reiterated its importance in mycobacterial persistence in the host. The immunization of mice with recombinant PE3 protein stimulated the secretion of TNF, IL-6 and IL-2 cytokines and generated strong protective immunity against challenge with live mycobacteria, which was evidenced by decreased viable bacilli in the lungs, histopathological changes and increased survival of PE3 immunized mice. Conclusively, the results indicated that PE3 plays significant roles in mycobacterial persistence during infection, modulate host immune response and hence could be a prospective candidate for the development of subunit vaccine against tuberculosis.

Rv3080c regulates the rate of inhibition of mycobacteria by isoniazid through FabD.

The mycobacterial FASII multi-enzyme complex has been identified to be a target of Ser/Thr protein kinases (STPKs) of Mycobacterium tuberculosis (MTB), with substrates, including the malonyl-CoA:ACP transacylase (FabD) and the ß-ketoacyl-ACP synthases KasA and KasB. These proteins are phosphorylated by various kinases in vitro. The present study links the correlation of FASII pathway with serine threonine protein kinase of MTB. In the preliminary finding, we have shown that mycobacterial protein Rv3080c (PknK) phosphorylates FabD and the knockdown of PknK protein in mycobacteria down regulates FabD expression. This event leads to the differential inhibition of mycobacteria in the presence of isoniazid (INH), as the inhibition of growth of mycobacteria in the presence of INH is enhanced in PknK deficient mycobacteria.

Synthesis and evaluation of small libraries of triazolylmethoxy chalcones, flavanones and 2-aminopyrimidines as inhibitors of mycobacterial FAS-II and PknG.

A synthetic strategy to access small libraries of triazolylmethoxy chalcones 4{1-20}, triazolylmethoxy flavanones 5{1-10} and triazolylmethoxy aminopyrimidines 6{1-17} from a common substrate 4-propargyloxy-2-hydroxy acetophenone using a set of different reactions has been developed. The chalcones and flavanones were screened against mycobacterial FAS-II pathway using a recombinant mycobacterial strain, against which the most potent compound showed ∼88% inhibition in bacterial growth and substantially induction of reporter gene activity at 100 µM concentration. The triazolylmethoxy aminopyrimdines were screened against PknG of Mycobaceterium tuberculosis displaying moderate to good activity (23-53% inhibition at 100 µM), comparable to the action of a standard inhibitor.