Benchmarking protein language models for protein crystallization.

The problem of protein structure determination is usually solved by X-ray crystallography. Several in silico deep learning methods have been developed to overcome the high attrition rate, cost of experiments and extensive trial-and-error settings, for predicting the crystallization propensities of proteins based on their sequences. In this work, we benchmark the power of open protein language models (PLMs) through the TRILL platform, a be-spoke framework democratizing the usage of PLMs for the task of predicting crystallization propensities of proteins.

Ambient air pollution and daily mortality in ten cities of India: a causal modelling study.

Background: The evidence for acute effects of air pollution on mortality in India is scarce, despite the extreme concentrations of air pollution observed. This is the first multi-city study in India that examines the association between short-term exposure to PM and daily mortality using causal methods that highlight the importance of locally generated air pollution.

Methods: We applied a time-series analysis to ten cities in India between 2008 and 2019.

NLRC5 senses NAD depletion, forming a PANoptosome and driving PANoptosis and inflammation.

NLRs constitute a large, highly conserved family of cytosolic pattern recognition receptors that are central to health and disease, making them key therapeutic targets. NLRC5 is an enigmatic NLR with mutations associated with inflammatory and infectious diseases, but little is known about its function as an innate immune sensor and cell death regulator. Therefore, we screened for NLRC5's role in response to infections, PAMPs, DAMPs, and cytokines.

VISH-Pred: an ensemble of fine-tuned ESM models for protein toxicity prediction.

Peptide- and protein-based therapeutics are becoming a promising treatment regimen for myriad diseases. Toxicity of proteins is the primary hurdle for protein-based therapies. Thus, there is an urgent need for accurate in silico methods for determining toxic proteins to filter the pool of potential candidates.

The protein phosphatase PP6 promotes RIPK1-dependent PANoptosis.

Background: The innate immune system serves as the first line of host defense. Transforming growth factor-β-activated kinase 1 (TAK1) is a key regulator of innate immunity, cell survival, and cellular homeostasis. Because of its importance in immunity, several pathogens have evolved to carry TAK1 inhibitors.

Modulation of Nuclear Receptor 4A1 Expression Improves Insulin Secretion in a Mouse Model of Chronic Pancreatitis.

Objectives: Diabetes secondary to chronic pancreatitis (CP) presents clinical challenges due to lack of understanding on factor(s) triggering insulin secretory defects. Therefore, we aimed to delineate the molecular mechanism of β-cell dysfunction in CP.

Materials And Methods: Transcriptomic analysis was conducted to identify endocrine-specific receptor expression in mice and human CP on microarray.

NINJ1 mediates inflammatory cell death, PANoptosis, and lethality during infection conditions and heat stress.

Innate immunity provides the first line of defense through multiple mechanisms, including pyrogen production and cell death. While elevated body temperature during infection is beneficial to clear pathogens, heat stress (HS) can lead to inflammation and pathology. Links between pathogen exposure, HS, cytokine release, and inflammation have been observed, but fundamental innate immune mechanisms driving pathology during pathogen exposure and HS remain unclear.

Excess Mortality Risk Due to Heat Stress in Different Climatic Zones of India.

India is at a high risk of heat stress-induced health impacts and economic losses owing to its tropical climate, high population density, and inadequate adaptive planning. The health impacts of heat stress across climate zones in India have not been adequately explored. Here, we examine and report the vulnerability to heat stress in India using 42 years (1979-2020) of meteorological data from ERA-5 and developed climate-zone-specific percentile-based human comfort class thresholds.

Frequency dominates intensity of future heat waves over India.

Future changes in heat wave characteristics over India have been analyzed using Coordinated Regional Climate Downscaling Experiments (CORDEX) for South Asia (SA) regional climate model simulations for mid-term (2041-2060) and long-term (2081-2099) future under the representative concentration pathway (RCP) 4.5 and RCP 8.5 emission scenarios, respectively.

Comparative analysis identifies genetic and molecular factors associated with prognostic clusters of PANoptosis in glioma, kidney and melanoma cancer.

The importance of inflammatory cell death, PANoptosis, in cancer is increasingly being recognized. PANoptosis can promote or inhibit tumorigenesis in context-dependent manners, and a computational approach leveraging transcriptomic profiling of genes involved in PANoptosis has shown that patients can be stratified into PANoptosis High and PANoptosis Low clusters that have significant differences in overall survival for low grade glioma (LGG), kidney renal cell carcinoma (KIRC) and skin cutaneous melanoma (SKCM). However, the molecular mechanisms that contribute to differential prognosis between PANoptosis clusters require further elucidation.

Inflammatory cell death, PANoptosis, screen identifies host factors in coronavirus innate immune response as therapeutic targets.

The COVID-19 pandemic, caused by the β-coronavirus (β-CoV) severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), continues to cause significant global morbidity and mortality. While vaccines have reduced the overall number of severe infections, there remains an incomplete understanding of viral entry and innate immune activation, which can drive pathology. Innate immune responses characterized by positive feedback between cell death and cytokine release can amplify the inflammatory cytokine storm during β-CoV-mediated infection to drive pathology.

Pancancer network analysis reveals key master regulators for cancer invasiveness.

Background: Tumor invasiveness reflects numerous biological changes, including tumorigenesis, progression, and metastasis. To decipher the role of transcriptional regulators (TR) involved in tumor invasiveness, we performed a systematic network-based pan-cancer assessment of master regulators of cancer invasiveness.

Materials And Methods: We stratified patients in The Cancer Genome Atlas (TCGA) into invasiveness high (INV-H) and low (INV-L) groups using consensus clustering based on an established robust 24-gene signature to determine the prognostic association of invasiveness with overall survival (OS) across 32 different cancers.

Whole-genome CRISPR screen identifies RAVER1 as a key regulator of RIPK1-mediated inflammatory cell death, PANoptosis.

Transforming growth factor-β-activated kinase 1 (TAK1) is a central regulator of innate immunity, cell death, inflammation, and cellular homeostasis. Therefore, many pathogens carry TAK1 inhibitors (TAK1i). As a host strategy to counteract this, inhibition or deletion of TAK1 induces spontaneous inflammatory cell death, PANoptosis, through the RIPK1-PANoptosome complex, containing the NLRP3 inflammasome and caspase-8/FADD/RIPK3 as integral components; however, PANoptosis also promotes pathological inflammation.

NLRP12-PANoptosome activates PANoptosis and pathology in response to heme and PAMPs.

Cytosolic innate immune sensors are critical for host defense and form complexes, such as inflammasomes and PANoptosomes, that induce inflammatory cell death. The sensor NLRP12 is associated with infectious and inflammatory diseases, but its activating triggers and roles in cell death and inflammation remain unclear. Here, we discovered that NLRP12 drives inflammasome and PANoptosome activation, cell death, and inflammation in response to heme plus PAMPs or TNF.

An integrated tumor, immune and microbiome atlas of colon cancer.

The lack of multi-omics cancer datasets with extensive follow-up information hinders the identification of accurate biomarkers of clinical outcome. In this cohort study, we performed comprehensive genomic analyses on fresh-frozen samples from 348 patients affected by primary colon cancer, encompassing RNA, whole-exome, deep T cell receptor and 16S bacterial rRNA gene sequencing on tumor and matched healthy colon tissue, complemented with tumor whole-genome sequencing for further microbiome characterization. A type 1 helper T cell, cytotoxic, gene expression signature, called Immunologic Constant of Rejection, captured the presence of clonally expanded, tumor-enriched T cell clones and outperformed conventional prognostic molecular biomarkers, such as the consensus molecular subtype and the microsatellite instability classifications.

An integrated multi-omic approach demonstrates distinct molecular signatures between human obesity with and without metabolic complications: a case-control study.

Objectives: To examine the hypothesis that obesity complicated by the metabolic syndrome, compared to uncomplicated obesity, has distinct molecular signatures and metabolic pathways.

Methods: We analyzed a cohort of 39 participants with obesity that included 21 with metabolic syndrome, age-matched to 18 without metabolic complications. We measured in whole blood samples 754 human microRNAs (miRNAs), 704 metabolites using unbiased mass spectrometry metabolomics, and 25,682 transcripts, which include both protein coding genes (PCGs) as well as non-coding transcripts.

AI-driven drug repurposing and binding pose meta dynamics identifies novel targets for monkeypox virus.

Monkeypox virus (MPXV) was confirmed in May 2022 and designated a global health emergency by WHO in July 2022. MPX virions are big, enclosed, brick-shaped, and contain a linear, double-stranded DNA genome as well as enzymes. MPXV particles bind to the host cell membrane via a variety of viral-host protein interactions.

Hydrogeochemical characterization and geochemical modeling for the evaluation of groundwater quality and health risk assessment in the Varuna River basin, India.

This study focuses on determining significant controlling factors of chemical consequences, inverse geochemical modeling, water quality, and human health risk in the Varuna River basin of India. The study interprets that according to pH, total dissolved solids, and total hardness, the maximum number of groundwater samples are alkaline, fresh, and have substantial hardness. The abundance of major ions follows a pattern: Na > Ca > Mg > K, and HCO > Cl > SO > NO > F.

Double transplantation as a climate resilient and sustainable resource management strategy for rice production in eastern Uttar Pradesh, north India.

-Enhancing the productivity of rainfed crops, especially rice, while coping with climate adversities and saving critical natural resources is essential for ensuring the food and nutrition security of a growing population. With this context, the present study was undertaken to validate promising farm innovation and adaptation practices used by small-medium landholding farmers for rice cultivation in eastern Uttar Pradesh (UP), north India, as well as to examine the sustainability of innovative practices for large-scale adoption. For this, a 3-year study comprising extensive field surveys and experiments was undertaken to compare single transplantation (ST) and double transplantation (DT) in rice along with organic addition (farm-yard manure, FYM) on crop growth, yield, climate resilience, soil quality, and overall sustainability i.

Pancancer transcriptomic profiling identifies key PANoptosis markers as therapeutic targets for oncology.

Resistance to programmed cell death (PCD) is a hallmark of cancer. While some PCD components are prognostic in cancer, the roles of many molecules can be masked by redundancies and crosstalks between PCD pathways, impeding the development of targeted therapeutics. Recent studies characterizing these redundancies have identified PANoptosis, a unique innate immune-mediated inflammatory PCD pathway that integrates components from other PCD pathways.

Investigation of the Effect of Exendin-4 on Oleic Acid-Induced Steatosis in HepG2 Cells Using Fourier Transform Infrared Spectroscopy.

Non-alcoholic fatty liver disease (NAFLD) is a common liver lesion that is untreatable with medications. Glucagon-like peptide-1 receptor (GLP-1R) agonists have recently emerged as a potential NAFLD pharmacotherapy. However, the molecular mechanisms underlying these drugs' beneficial effects are not fully understood.