Understanding water dynamics in Dal Lake: a comprehensive analysis of physiological parameters and seasonal variations.

Maintaining the standard of water quality in an aquatic habitat necessitates continual assessment of its physicochemical properties. The purpose of this study was to evaluate physicochemical properties and to discuss the causes of spatiotemporal variability in key physicochemical parameters at five different locations of Dal Lake. Water samples were collected in four seasons for 3 years (i.e., January 2019-December 2021) to evaluate various physicochemical properties using standard methods. The analysis shows that the macrophytic development has increased due to organic and inorganic load, leading to the Lake's deterioration. The analysis indicates positive and negative correlations among various parameters across five sampling sites. Principal component analysis shows that two components (PC1 and PC2) explain 47.35, 47.54, and 48.11% of the variability in the years 2019, 2020, and 2021, respectively. From 2019 to 2021, the continuous decrease in dissolved oxygen and increased levels of magnesium, conductivity, alkalinity, total hardness, calcium hardness, total phosphorus, and nitrate-nitrogen suggest a trend toward eutrophication in the lake.

Recent advances in availability and synthesis of the economic costs of biological invasions.

Biological invasions are a global challenge that has received insufficient attention. Recently available cost syntheses have provided policy- and decision makers with reliable and up-to-date information on the economic impacts of biological invasions, aiming to motivate effective management. The resultant InvaCost database is now publicly and freely accessible and enables rapid extraction of monetary cost information. This has facilitated knowledge sharing, developed a more integrated and multidisciplinary network of researchers, and forged multidisciplinary collaborations among diverse organizations and stakeholders. Over 50 scientific publications so far have used the database and have provided detailed assessments of invasion costs across geographic, taxonomic, and spatiotemporal scales. These studies have provided important information that can guide future policy and legislative decisions on the management of biological invasions while simultaneously attracting public and media attention. We provide an overview of the improved availability, reliability, standardization, and defragmentation of monetary costs; discuss how this has enhanced invasion science as a discipline; and outline directions for future development.

Plant phenology shifts under climate warming: a systematic review of recent scientific literature.

Climate warming-driven temporal shifts in phenology are widely recognised as the foremost footprint of global environmental change. In this regard, concerted research efforts are being made worldwide to monitor and assess the plant phenological responses to climate warming across species, ecosystems and seasons. Here, we present a global synthesis of the recent scientific literature to assess the progress made in this area of research. To achieve this, we conducted a systematic review by following PRISMA protocol, which involved rigorous screening of 9476 studies on the topic and finally selected 215 studies for data extraction. The results revealed that woody species, natural ecosystems and plant phenological responses in spring season have been predominantly studied, with the herbaceous species, agricultural ecosystems and other seasons grossly understudied. Majority of the studies reported phenological advancement (i.e., preponement) in spring, followed by also advancement in summer but delay in autumn. Methodology-wise, nearly two -third of the studies have employed direct observational approach, followed by herbarium-based and experimental approaches, with the latter covering least temporal depth. We found a steady increase in research on the topic over the last decade with a sharp increase since 2014. The global country-wide scientific output map highlights the huge geographical gaps in this area of research, particularly in the biodiversity-rich tropical regions of the developing world. Based on the findings of this global synthesis, we identify the current knowledge gaps and suggest future directions for this emerging area of research in an increasingly warming world.

DNA marker based diversity across rice genotypes and advanced breeding lines bred for temperate regions of North-West India.

BACKGROUND: Characterization and evaluation of plant genetic resources play an important role for their utilization in the crop improvement programmes. METHODS AND RESULTS: This study involves the agro-morphological and cooking quality besides, molecular characterization of 51 genotypes/advance breeding lines of rice from Kashmir Himalayas. Significant variability was observed for all agro-morphological and cooking quality traits among all the studied genotypes. Cluster analysis using UPGMA method divided the genotypes into two major clusters having 15 and 36 genotypes. Thirty eight genotypes screened using 24 SSR markers detected 48 alleles with 2.0 alleles for each locus with average polymorphism information content (PIC) of 0.37. High polymorphism information content (PIC) values was observed for the primers RM263 (0.67), RM159 (0.59) and RM333 (0.50). Furthermore, out of 38 SSR markers screened on 192 temperate rice germpalsm lines, R4M17 accurately differentiated indica and temperate japonica genotypes amplifying 220 bp and 169 bp, respectively. Accordingly, 15 genotypes were reported as indica and 28 temperate japonica in addition to 149 genotypes as intermediate types. CONCLUSION: The information on marker-based diversity and performance based on cooking quality and agronomic traits helped to select the most divergent lines for crossing. Also the analysis was useful to classify the temperate germplasm into indica and temperate japonica. The classification could be helpful to devise a strategy for inter-sub species hybridization to breed for improved rice varieties.

Attitudinal behaviour of agriculturalists towards pesticide use in Pir Panjal Range of Kashmir Himalayas.

BACKGROUND: Attainment of safety during pesticide spraying relies on the farmer's knowledge of pesticide use, attitude and sense of safety. However, such investigations are insufficient in the current study area. METHODS: The study is based on a primary survey of 384 orchardists about the myriad of aspects affecting the use of pesticides and their subsequent effects. RESULTS: The study revealed that knowledge, attitude, and perception had a weighted average index (WAI) and a standard deviation (SD) of 2.85 ± 1.17, 3.55 ± 1.34, and 3.81 ± 0.98 correspondingly. The findings reflect the farmers have a low to moderate level of knowledge, a moderate attitude toward pesticides, and a favourable perception on their utilization. Thus, for farmer personal protective equipment (PPE) use, it scored 2.77 ± 0.90 on the WAI scale, indicating that most farmers use PPEs 'rarely to occasionally' and that none use full protective gear. Furthermore, attitude and PPE usage exhibited a negative relationship with age, as younger people use PPE more than older ones. The findings were consistent for both farming experience and PPE usage. Moreover, there exists a positive association between age with perception and farming experience, knowledge with perception and PPE use, and attitude with perception. CONCLUSIONS: The coefficient of determination (R2) shows that 67.2% of the variability in farmers' PPE use was attributed to factors including knowledge, attitude, perception, and education. A favorable behavioral shift in pesticide usage may be achieved by enhancing farmers' knowledge, attitudes and perceptions, and adequate PPE usage.

Climate warming-driven phenological shifts are species-specific in woody plants: evidence from twig experiment in Kashmir Himalaya.

Experimental evidences in support of climate warming-driven phenological shifts are still scarce, particularly from the developing world. Here, we investigated the effect of experimental warming on flowering phenology of selected woody plants in Kashmir Himalaya. We selected the twigs of four congeneric pairs of temperate woody species (Prunus, Populus, Ulmus, Viburnum)-typical spring-flowering plants in the region. Using randomised block design, we monitored these winter dormant twigs in controlled growth chambers to study the effect of different temperature regimes (9, 17, 20 and 23 °C) and species identity on the patterns of phenological shifts. We observed a significant phenological shift in all the species showing preponement in the first flower out and senescence phases ranging from 0.56 to 3.0 and 0.77 to 4.04 days per degree increase in temperature, respectively. The duration of flowering phase in all the species showed a corresponding decrease along the gradient of increasing temperature, which was more driven by preponement of the flower senescence than the start of flowering. The patterns of phenological shifts were highly species-specific, and the magnitude of these shifts significantly varied in all the four pairs of congeneric species despite their phylogenetic similarity. Our study provides experimental support to the previous long-term observation and herbarium-based studies showing that the patterns of phenological shifts in response to global climate warming are likely to vary between species, even those belonging to same evolutionary stock. Our findings highlight that a one-size-fits-all strategy to manage the likely impacts of climate warming-induced phenological shifts will seldom succeed, and should instead be designed for the specific phenological responses of species and regions.

Promoter CpG island hypermethylation and down regulation of XRCC1 gene can augment in the gastric carcinogenesis events.

Gastric cancer (GC) is a multistep process characterized by a gradual accumulation of genetic and epigenetic alterations in genes at various stages of progression. Epigenetic alterations like DNA methylation play an important role in cancer and may serve as a biomarker for cancer. The present study was aimed to investigate the promoter hypermethylation, expression profile, and Arg399Gln gene polymorphism of DNA repair gene XRCC1 (X-ray repair cross complimentary group I) in GC patients. A total of 60 histopathologically confirmed GC subjects were recruited in the study. Information on various dietary, lifestyle and environmental factors was obtained in face-to-face interviews using a structured questionnaire from each subject. Tissue samples were taken along with adjacent non-cancerous tissues for analysis. Promoter methylation status and expression of XRCC1 gene was evaluated using MS-PCR and western blotting respectively; while as Arg399Gln polymorphism was analyzed by PCR-RFLP. We found that the XRCC1 gene promoter of 38.3% cancerous tissues were methylated compared to 13.3% of adjacent normal tissues. The promoter hypermethylation status of the gene was found to be significantly associated with the loss of protein expression (P < 0.0001, OR = 14.63; 95% CI 4.01-53.43). However, we did not find any significant association of polymorphism of XRCC1 Arg399Gln with promoter methylation or protein expression. Further, comparison of methylation status and protein expression with clinical parameters like age, smoking status, etc. was also not significant (P > 0.05). The present study indicates that XRCC1 undergoes aberrant promoter hypermethylation with subsequent loss of protein expression in gastric cancer.

Gender focused training and knowledge enhances the adoption of climate resilient seeds.

Adoption of any agricultural technology depends upon the way in which farmers are being informed about its benefits. Educational status, caste, gender and other social issues also play a significant role in the adoption process. To evaluate the impact of trainings on quality seed production, access to the climate resilient rice seeds, availability of information about seed sources and use of IRRI super bags, a randomized experimental research was carried out over a period of two years across five different states of India. The baseline and a follow-up survey was conducted to capture the farming practices followed by during wet seasons of 2016 and 2017, respectively. The impact of trainings, seed use, information given and agro-based goods was evaluated by comparing the adoption behaviour of treatment and control farmers. There was an increase (28.8%) in the practice of using salt solution to clean seeds primarily due to the impact of quality seed production (QSP) trainings. Female farmers responded more than the male farmers as number of women adopting the practice was higher than men. The impact of the trainings on farmers' knowledge and adoption of climate resilient/stress tolerant rice varieties (STRV) was also more pronounced on females than on male farmers. Farmers' access to seeds substantially enhanced the adoption and reusability irrespective of the gender. Similarly, the information delivered to the farmers was quite economical in enhancing the awareness and adoption of climate resilient rice, but the effect was predominantly driven by female farmers. Female farmers performed relatively better with respect to the storing the new seeds in IRRI super bags. Thus, incentivising farmers in general and female farmers in particular can serve as a potential means to adopt agricultural technologies that have potential to boost rural economy and enhance the food security. The results are being supported by a rigorous empirical analysis.

Provision of Pre- and Postnatal Nutritional Supplements Generally Did Not Increase or Decrease Common Childhood Illnesses in Bangladesh: A Cluster-Randomized Effectiveness Trial.

BACKGROUND: Nutritional interventions may affect child morbidity. OBJECTIVE: The aim of this study was to examine whether providing lipid-based nutrient supplements (LNSs) to pregnant and lactating women or LNS or micronutrient powder (MNP) to their infants influences child morbidity. METHODS: In a 4-arm cluster-randomized effectiveness trial, participants enrolled at ≤20 weeks of gestation (n = 4011) received: 1) maternal LNSs until 6 mo postpartum and child LNSs from 6-24 mo of age (LNS-LNS); 2) iron and folic acid (IFA) until 3 mo postpartum and child LNSs at 6-24 mo (IFA-LNS); 3) IFA (as above) and child MNP at 6-24 mo (IFA-MNP); or 4) IFA and no child supplement (IFA-Control). At 6, 12, 18, and 24 mo of age, we collected information on acute lower and upper respiratory infection (ALRI/AURI), diarrhea, and fever in the previous 14 d, and on episodes of illness in the previous 6 mo. RESULTS: At 6 mo, prevalence of ALRI, fever, or diarrhea in the previous 14 d (17.6%, 18.9% and 6.8%, respectively) did not differ between infants of women who received LNS and infants of women who received IFA, but prevalence of AURI was lower in the LNS-LNS group than in all other groups combined (27.7% compared with 31.7%; OR: 0.83; 95% CI: 0.70, 0.99). At 12, 18, and 24 mo, the 4 arms did not differ in prevalence of fever (∼18.3%) or ALRI (≤15%) in the previous 14 d, but prevalence of AURI at 12 mo was lower in IFA-LNS than in IFA-Control infants (27.6% compared with 33.9%, OR: 0.74; 95% CI: 0.56, 0.99). The mean ± SD number of diarrhea episodes in the previous 6 mo was significantly higher among IFA-LNS than among IFA-Control infants at 6-12 (0.46 ± 0.04 compared with 0.33 ± 0.03) and 12-18 (0.45 ± 0.03 compared with 0.33 ± 0.02) mo. No other pairwise group differences were significant. CONCLUSION: Providing LNSs to women or LNSs or MNP to children generally did not increase or decrease childhood illnesses. This trial was registered at clinicaltrials.gov as NCT01715038.

Direct physical interaction of active Ras with mSIN1 regulates mTORC2 signaling.

BACKGROUND: The mechanistic (or mammalian) target of rapamycin (mTOR), a Ser/Thr kinase, associates with different subunits forming two functionally distinct complexes, mTORC1 and mTORC2, regulating a diverse set of cellular functions in response to growth factors, cellular energy levels, and nutrients. The mechanisms regulating mTORC1 activity are well characterized; regulation of mTORC2 activity, however, remains obscure. While studies conducted in Dictyostelium suggest a possible role of Ras protein as a potential upstream regulator of mTORC2, definitive studies delineating the underlying molecular mechanisms, particularly in mammalian cells, are still lacking. METHODS: Protein levels were measured by Western blotting and kinase activity of mTORC2 was analyzed by in vitro kinase assay. In situ Proximity ligation assay (PLA) and co-immunoprecipitation assay was performed to detect protein-protein interaction. Protein localization was investigated by immunofluorescence and subcellular fractionation while cellular function of mTORC2 was assessed by assaying extent of cell migration and invasion. RESULTS: Here, we present experimental evidence in support of the role of Ras activation as an upstream regulatory switch governing mTORC2 signaling in mammalian cancer cells. We report that active Ras through its interaction with mSIN1 accounts for mTORC2 activation, while disruption of this interaction by genetic means or via peptide-based competitive hindrance, impedes mTORC2 signaling. CONCLUSIONS: Our study defines the regulatory role played by Ras during mTORC2 signaling in mammalian cells and highlights the importance of Ras-mSIN1 interaction in the assembly of functionally intact mTORC2.

Safety and efficacy of switching from unfractionated heparin to bivalirudin during primary percutaneous coronary intervention.

OBJECTIVES: To evaluate the safety and efficacy of switching to bivalirudin during primary percutaneous coronary intervention (PCI) for patients who received preprocedure unfractionated heparin (UFH). BACKGROUND: Current guidelines favor bivalirudin for primary PCI in patients at high risk of bleeding, particularly when femoral access is used. However, patients with ST-segment elevation myocardial infarction frequently receive UFH before arrival in the catheterization laboratory. METHODS: Scientific databases and websites were searched for randomized controlled trials. Patients were divided into those who received heparin with or without glycoprotein IIb/IIIa inhibitors (heparin group); those switched to bivalirudin during primary PCI from preprocedure UFH (switch group); and those who received bivalirudin without preprocedure UFH (Biv-alone group). Both traditional pairwise meta-analyses using moderator analyses and network meta-analyses using mixed-treatment comparison models were performed. RESULTS: Data from five trials including13,547 patients were analyzed. In mixed-comparison models, switching to bivalirudin during primary PCI was associated with lower rates for all-cause mortality and major adverse cardiovascular events (MACEs) compared to the other strategies. Rates for all-cause mortality, MACEs, and net adverse clinical events (NACEs) were similar for the heparin and Biv-alone groups. Switching strategies was also associated with lower major bleeding rates compared to heparin alone. Similarly, in a standard pairwise model, both the switch and Biv-alone groups were associated with decreased bleeding risk compared to the heparin group. However, only the switch strategy was associated with decreased all-cause mortality (RR, 0.47; 95% CI, 0.30-0.75; P = 0.001), MACE (RR, 0.67; 95% CI, 0.49-0.91; P = 0.012), and NACE (RR, 0.61; 95% CI, 0.41-0.92; P = 0.019) compared with heparin alone. CONCLUSIONS: During primary PCI, use of bivalirudin for those receiving preprocedure UFH was associated decreased rates for major bleeding, NACEs, MACEs, and all-cause mortality compared to heparin +/- GPI. This strategy was also associated with decreased rates for MACEs and all-cause mortality compared to bivalirudin alone without preprocedure UFH.

Factors associated with diarrhea and acute respiratory infection in children under two years of age in rural Bangladesh.

BACKGROUND: Diarrhea and acute respiratory infection (ARI) are major causes of child mortality. We aimed to identify risk factors associated with diarrhea and ARI among children under 2 years of age in rural northern Bangladesh. METHOD: We collected information on diarrhea and ARI in the previous 14 days and the previous 6 months at 6, 12, 18 and 24 months of age as part of a longitudinal, cluster randomized effectiveness trial, the Rang-Din Nutrition Study which enrolled 4011 pregnant women at ≤20 gestational weeks. Women and their children were followed up until 2 years postpartum. Information on household socioeconomic status, type of toilet, garbage disposal system, food insecurity, number of under-five children in the household, type of family, maternal characteristics and child characteristics was collected at baseline and/or at 6, 12, 18 and 24 months postpartum. Data on newborn health and feeding behaviors were collected within 72 h of delivery. Associations between potential risk factors and morbidity prevalence outcomes were assessed using logistic regression controlling for potential confounders. RESULTS: Out of 3664 live born children, we collected information from ~ 3350 children at 6, 12, 18 and 24 months of age. Diarrhea in the previous 14 days, and in the previous 6 months, was associated with maternal depression score and food insecurity; diarrhea in the previous 6 months was also associated with family type (nuclear vs. joint). ARI in the previous 14 days was associated with maternal depression score, type of toilet and garbage disposal, household food insecurity and sex. Cough or nasal discharge in the past 6 months was associated with maternal depression score, type of toilet and garbage disposal, household food insecurity, sex and perceived overall physical condition of the infant after birth. CONCLUSION: Maternal depression and food insecurity appear to be important risk factors for diarrhea and respiratory infection among children under 2 years of age in this setting. These findings suggest that policies and programs that include strategies to address maternal mental health and household food insecurity may contribute to improved child health. TRIAL REGISTRATION: The trial was registered with the US National Institutes of Health at ClinicalTrials.gov, # NCT01715038 , with registration completed October 26, 2012.

Newborn physical condition and breastfeeding behaviours: Secondary outcomes of a cluster-randomized trial of prenatal lipid-based nutrient supplements in Bangladesh.

Prenatal nutritional supplements may improve birth outcomes. This study aims to examine the effect of prenatal lipid-based nutrient supplements (LNS), compared with iron and folic acid (IFA), on general newborn physical condition and feeding behaviours. We conducted a cluster-randomized effectiveness trial that enrolled 4,011 pregnant women at ≤20 gestational weeks. LNS and IFA were provided to women in 48 and 16 clusters, respectively, for daily consumption until delivery. We collected data on household socio-economic, food insecurity, and maternal characteristics during early pregnancy and on newborn condition and feeding within 72 hr of delivery. We analysed intervention effects on these secondary outcomes using mixed models with analysis of covariance for continuous outcomes and logistic regression for dichotomous outcomes. Among 3,664 live births, intervention groups did not differ in newborn response, mother's rating of the general condition of her newborn, early initiation of breastfeeding (EIBF), suckling ability, or frequency and exclusivity of breastfeeding in the first 24 hr. If the mother perceived her infant to be healthy, EIBF was more likely (OR [95% CI]: 2.08 [1.46, 2.97]) and frequency of breastfeeding in the first 24 hr was greater (mean difference [95% CI]: 3.0 [1.91, 4.01]), but there was no difference in exclusive breastfeeding in the first 24 hr. Newborn condition and early breastfeeding practices were not affected by giving mothers prenatal LNS versus IFA. However, early breastfeeding practices were related to maternal perception of her newborn's condition. Thus, interventions to improve breastfeeding practices for newborns with poorer perceived health status may be useful.

Prenatal and Postnatal Supplementation with Lipid-Based Nutrient Supplements Reduces Anemia and Iron Deficiency in 18-Month-Old Bangladeshi Children: A Cluster-Randomized Effectiveness Trial.

Background: Anemia, iron deficiency (ID), and iron deficiency anemia (IDA) among young children are public health concerns in developing countries. Objective: We evaluated the effects of small-quantity lipid-based nutrient supplements (LNSs) and micronutrient powder (MNP) on anemia, ID, and IDA in 18-mo-old Bangladeshi children. Methods: We enrolled 4011 pregnant women in a cluster-randomized effectiveness trial with 4 arms-1) LNS-LNS: LNSs (including 20 mg Fe) for women daily during pregnancy and 6 mo postpartum and LNSs (including 9 mg Fe) for children daily from 6 to 24 mo of age (LNS-C); 2) IFA-LNS: iron (60 mg) and folic acid (IFA) for women daily during pregnancy and every other day for 3 mo postpartum and LNS-C for children; 3) IFA-MNP: IFA for women, and MNP (including 10 mg Fe) for children daily from 6 to 24 mo; and 4) IFA-Control: IFA for women and no child supplement. Hemoglobin, serum ferritin, and soluble transferrin receptor (sTfR) were assessed in a subsample of children (n = 1121) at 18 mo to identify anemia (hemoglobin <110g/L), ID (ferritin <12 µg/L or sTfR >8.3 mg/L), and IDA. Data were analyzed with the use of mixed-effects modeling. Results: Compared with the IFA-Control arm, hemoglobin was higher in the LNS-LNS and IFA-LNS arms and ferritin was higher and sTfR was lower in the LNS-LNS, IFA-LNS, and IFA-MNP arms; LNS-LNS children had reduced odds of anemia (OR: 0.46; 95% CI: 0.25, 0.84), high sTfR (OR: 0.47; 95% CI: 0.29, 0.73), and ID (OR: 0.45; 95% CI: 0.28, 0.71); and all 3 groups had lower odds of low ferritin [corrected for inflammation; OR (95% CI)-LNS-LNS: 0.29 (0.13, 0.63); IFA-LNS: 0.25 (0.11, 0.59); and IFA-MNP: 0.37 (0.18, 0.76)] and IDA [LNS-LNS: 0.35 (0.18, 0.67); IFA-LNS: 0.45 (0.24,0.85); and IFA-MNP: 0.47 (0.26, 0.87)]. Conclusions: Home fortification using LNSs or MNP reduced IDA in 18-mo-old Bangladeshi children. The provision of LNSs in both pregnancy and childhood also reduced child anemia and ID. These findings are relevant to programs targeting similar populations. This trial was registered at www.clinicaltrials.gov as NCT01715038.

Amelioration of hyperglycaemia and modulation of antioxidant status by Alcea rosea seeds in alloxan-induced diabetic rats.

CONTEXT: Alcea rosea L. (Malvaceae) has various medicinal uses including anticancer, anti-inflammatory and analgesic properties. However, there is no report on its antidiabetic activity. OBJECTIVE: Alcea rosea seed extracts were evaluated for antihyperglycaemic and antioxidative potential in diabetic rats. MATERIALS AND METHODS: Single intra-peritoneal injection of alloxan (130 mg/kg b.w.) was used for induction of diabetes in Albino Wistar rats. Antihyperglycaemic and antioxidant activities of methanol and aqueous extracts of Alcea rosea seed (100 and 300 mg/kg b.w.), administered orally on daily basis for 15 days, were assessed in vivo for fasting blood glucose level and antioxidant status of liver and pancreas. Metformin was used as a positive control. RESULTS: Aqueous and methanol extracts (300 mg/kg b.w.) decreased blood glucose level in diabetic rats by 24% and 46%, respectively. Administration of aqueous and methanol extracts at 300 mg/kg b.w. significantly (p < 0.01) modulated the antioxidant status of liver in diabetic rats by increasing levels of GR (22.5 ± 1.0, 24.4 ± 1.02 µg GSSG utilized/min/mg of protein), GPx (20.7 ± 1.2, 23.6 ± 2.04 µg GSH utilized/min/mg of protein), SOD (36.1 ± 1.7, 39.05 ± 1.5 units/mg of protein) and CAT (1744.5 ± 132.5, 1956.6 ± 125.2 nmol H2O2 decomposed/min/mg of protein), respectively. Similar results were observed for pancreas. DISCUSSION AND CONCLUSIONS: Antihyperglycaemic and antioxidative potentials of Alcea rosea seeds suggest its usefulness in management of diabetes and its complications. This is the first report on antidiabetic activity of this plant.

Full-length direct RNA sequencing uncovers stress-granule dependent RNA decay upon cellular stress.

Cells react to stress by triggering response pathways, leading to extensive alterations in the transcriptome to restore cellular homeostasis. The role of RNA metabolism in shaping the cellular response to stress is vital, yet the global changes in RNA stability under these conditions remain unclear. In this work, we employ direct RNA sequencing with nanopores, enhanced by 5' end adaptor ligation, to comprehensively interrogate the human transcriptome at single-molecule and nucleotide resolution. By developing a statistical framework to identify robust RNA length variations in nanopore data, we find that cellular stress induces prevalent 5' end RNA decay that is coupled to translation and ribosome occupancy. Unlike typical RNA decay models in normal conditions, we show that stress-induced RNA decay is dependent on XRN1 but does not depend on removal of the poly(A) tail. We observed that RNAs undergoing decay are predominantly enriched in the stress granule transcriptome. Inhibition of stress granule formation via genetic ablation of G3BP1 and G3BP2 fully rescues RNA length and suppresses stress-induced decay. Our findings reveal RNA decay as a key determinant of RNA metabolism upon cellular stress and dependent on stress-granule formation.

Clinical profile, treatment patterns and one-year outcome of heart failure patients admitted in tertiary care hospital of North India.

Introduction: Because of wide heterogeneity in the epidemiology of heart failure among different populations, it is imperative to establish population-specific databases. Aims and Objectives: To describe the clinical profile, treatment patterns, and outcomes of heart failure patients admitted to our tertiary care hospital. Material and Methods: The study was a prospective observational study conducted over two years at our tertiary care hospital. It included patients admitted with acute and acute-on-chronic heart failure. Results: We recruited 264 patients. Mean age of the study population was 57.8 ± 15.14 years. Males were 157 (59.5%). Dilated cardiomyopathy was the most common cause followed by ischemic heart disease. Most common risk factors were hypertension, tobacco use, anemia, and diabetes. Heart failure with reduced ejection fraction was present in 154 (62%) patients. Acute de novo heart failure was present in 91 (34.5%) patients. The most common precipitant for heart failure exacerbation was infection, followed by ischemic causes and non-adherence to drugs. The mean duration of hospital stay was 7.5 ± 3.1 days. The in-hospital mortality was 8.7%, and cumulative six-month and one-year mortality was 23% and 28%, respectively. In multivariate analysis, renal failure, readmission, and not being on guideline-directed medical treatment were significant predictors of mortality. Conclusion: Our patients were younger, predominantly males, with dilated and ischemic cardiomyopathy as commonest etiology. Hypertension and tobacco smoking were most common risk factors, with infections as most common precipitants. Only one-third of patients were on guideline-directed medical therapy. The one-year mortality was 28% and was higher in those without guideline-directed medical therapy.

Socioeconomic status and esophageal squamous cell carcinoma risk in Kashmir, India.

Studies have persistently associated esophageal squamous cell carcinoma (ESCC) risk with low socioeconomic status (SES), but this association is unexplored in Kashmir, an area with a high incidence of ESCC in the northernmost part of India. We carried out a case-control study to assess the association of multiple indicators of SES and ESCC risk in the Kashmir valley. A total number of 703 histologically confirmed ESCC cases and 1664 controls matched to the cases for age, sex, and district of residence were recruited from October 2008 to January 2012. Conditional logistic regression models were used to calculate unadjusted and adjusted odds ratios and 95% confidence intervals. Composite wealth scores were constructed based on the ownership of several appliances using multiple correspondence analyses. Higher education, living in a kiln brick or concrete house, use of liquefied petroleum gas and electricity for cooking, and higher wealth scores all showed an inverse association with ESCC risk. Compared to farmers, individuals who had government jobs or worked in the business sector were at lower risk of ESCC, but this association disappeared in fully adjusted models. Occupational strenuous physical activity was strongly associated with ESCC risk. In summary, we found a strong relationship of low SES and ESCC in Kashmir. The findings need to be studied further to understand the mechanisms through which such SES parameters increase ESCC risk.

Lewis-Acid-Catalyzed Reductive Hydroalkoxylation of Propargylic N-Hydroxylamines Gives Stereoselective Access to Isoxazolidines.

Lewis-acid-catalyzed 5-endo-dig reductive hydroalkoxylation cascade on propargylic N-hydroxylamine gave expedient, stereoselective access to isoxazolidine derivatives. The developed method provides a new approach toward the synthesis of isoxazolidine, a biologically privileged scaffold. The synthetic potential of the developed methodology was demonstrated by synthesizing 1,3-aminoalcohol, 4-aminotetrahydropyran, and sedamine natural products.