CSF immune cell alterations in women with neuropsychiatric Long COVID.

Background: Women are disproportionately affected by neuropsychiatric symptoms following recovery from acute COVID-19. However, whether there are central nervous system-specific changes in gene expression in women with neuropsychiatric Long COVID (NP-Long COVID) remains unknown.

Methods: Twenty-two women with and ten women without NP-Long COVID were enrolled from New Haven, CT, and the surrounding region and consented to a blood draw and large volume lumbar puncture.

KGG: Knowledge-Guided Graph Self-Supervised Learning to Enhance Molecular Property Predictions.

Molecular property prediction has become essential in accelerating advancements in drug discovery and materials science. Graph Neural Networks have recently demonstrated remarkable success in molecular representation learning; however, their broader adoption is impeded by two significant challenges: (1) data scarcity and constrained model generalization due to the expensive and time-consuming task of acquiring labeled data and (2) inadequate initial node and edge features that fail to incorporate comprehensive chemical domain knowledge, notably orbital information. To address these limitations, we introduce a Knowledge-Guided Graph (KGG) framework employing self-supervised learning to pretrain models using orbital-level features in order to mitigate reliance on extensive labeled data sets.

AXL and MERTK facilitate tissue repair in severe acute pancreatitis via a CCR5-dependent neutrophil and macrophage crosstalk.

Severe acute pancreatitis (SAP) is a potentially life-threatening inflammatory disorder of the exocrine pancreas, characterized by massive cell death, which drives the progression and resolution of the disease. However, little is known about the key regulators in the tissue microenvironment that mediate tissue damage and repair. In this study, we discovered that AXL and MERTK in macrophages are responsible for tissue repair and pancreatic inflammation following SAP.

EZH2-TTP-mTORC1 Axis Drives Phenotypic Plasticity and Therapeutic Vulnerability in Lethal Prostate Cancer.

Phenotypic plasticity is a recognized mechanism of therapeutic resistance in prostate cancer (PCa), however current knowledge of driver mechanisms and therapeutic interventions are limited. Using genetically engineered mouse models (GEMMs) devoid of Pten and Rb1, we previously demonstrated the chromatin reprogramming factor enhancer of zeste homolog 2 (EZH2) as an important regulator of alternative transcription programs promoting phenotypic plasticity. Here, using a multi-omics approach we demonstrate that EZH2 regulates multilineage cell states dependent on the RNA binding protein Tristetraprolin (TTP) that mediates RNA stability and activation of translation.

Prediction of Circular RNA Secondary Structures and Their Targets.

At the level of secondary structure, circular RNAs (circRNAs) can be understood in terms of base pairing, base-pair stacking, and entropic loop contribution in the same way as linear RNAs and intermolecular RNA-RNA interactions. The folding problem of circular RNAs can thus be solved by dynamic programming algorithms in essentially the same manner. In this chapter, we review the similarities and differences between circular and linear RNAs with a focus on the software tools provided by the ViennaRNA package.

Deciphering the Diagnostic Potential of Small Non-Coding RNAs for the Detection of Pancreatic Ductal Adenocarcinoma Through Liquid Biopsies.

Pancreatic Ductal Adenocarcinoma (PDAC) is one of the most lethal cancers, accounting for a significant proportion of cancer-related deaths globally. Despite advancements in medical science, treatment options for PDAC remain limited, and the prognosis is often poor. Early detection is a critical factor in improving patient outcomes, but current diagnostic methods often fail to detect PDAC until it has advanced to a late stage.

Molecular Fingerprint of Cold Adaptation in Antarctic Icefish PepT1 (): A Comparative Molecular Dynamics Study.

Cold environments challenge the structural and functional integrity of membrane proteins, requiring specialized adaptations to maintain activity under low thermal energy. Here, we investigate the molecular basis of cold tolerance in the peptide transporter PepT1 from the Antarctic icefish (, ChPepT1) using molecular dynamics simulations, binding free energy calculations (MM/GBSA), and dynamic network analysis. We compare ChPepT1 to its human ortholog (hPepT1), a non-cold-adapted variant, to reveal key features enabling psychrophilic function.

DECIPHER for learning disentangled cellular embeddings in large-scale heterogeneous spatial omics data.

The functional role of a cell, shaped by the sophisticated interplay between its molecular identity and spatial context, is often obscured in current spatial modeling. In efforts to model large-scale heterogeneous spatial data in silico effectively and efficiently, we introduce DECIPHER, which disentangles cells' intra-cellular and extra-cellular representation through a novel cross-scale contrast learning strategy. In addition to superior performance over state-of-arts, systematic benchmarks and various real-world case studies showed that the disentangled embeddings produced by DECIPHER enable delineating cell-environment interaction across multiple scales.

Microbial and Geochemical Diversity of Laguna Timone, an Extreme Hypersaline Crater Lake in Patagonia (52° S).

Extreme environments, such as hypersaline habitats, hot springs, deep-sea hydrothermal vents, glaciers, and permafrost, provide diverse ecological niches for studying microbial evolution. However, knowledge of microbial communities in extreme environments at high southern latitudes remains limited, aside from Antarctica. Laguna Timone is a hypersaline crater lake located in a Pleistocene maar of the Pali Aike Volcanic Field, southern Patagonia; the lake was formed during basaltic eruptions in a periglacial setting.

Inhibitor-induced dimerization mediates lufotrelvir resistance in mutants of SARS-CoV-2 3C-like protease.

The emergence of SARS-CoV-2 and other lethal coronaviruses has prompted extensive research into targeted antiviral treatments, particularly focusing on the viral 3C-like protease (3CL) due to its essential role for viral replication. However, the rise of drug resistance mutations poses threats to public health and underscores the need to predict resistance mutations and understand the mechanism of how these mutations confer resistance. The binding of inhibitor to 3CL drives it from the monomeric to the active dimeric form, which can counterintuitively lead to enzyme activation rather than inhibition.

Molecular insights into PARP1 activation: structural dynamics of DNA, NAD+, and zinc‑mediated allosteric regulation.

PARP1 serves as a crucial protein for preserving genomic stability, especially in BRCA1/2-mutant cancers that lack homologous recombination repair. In response to DNA breaks, PARP1 triggers an allosteric response that communicates to its catalytic domain, initiating the synthesis of poly (ADP-ribose) from NAD+. In this study, we used RMSF, hydrogen bond, hydrophobic, and MMPBSA analyses to construct an interface-specific map of PARP1 activation, revealing how DNA, Zn ions, and NAD+ act at each domain interface to drive activation.

A global perspective on the genomics of .

is an opportunistic pathogen of the human respiratory tract, primarily associated with otitis media in children and exacerbations of chronic obstructive pulmonary disease in adults. Despite its clinical importance, the genomic diversity and functional specialization of remain insufficiently characterized. This study aimed to analyse the global genetic diversity of using whole-genome sequencing to identify phylogenetic lineages, antimicrobial resistance patterns and key virulence factors.

Functional Genomics and Probiotic Traits of Lactiplantibacillus plantarum MB685 from Fermented Broccoli: Gut Health and Metabolic Insights.

The current study aimed to isolate and characterize probiotic bacteria with potential health benefits from fermented broccoli. Sixteen bacterial strains were isolated, and two strains (MB685 and MB686) were selected based on their probiotic potential. The isolated strains showed tolerance to pH and temperature variations, and survived well in bile salt concentrations of 0.

Perspective on integrated multi-omics approaches and constraint-based modeling to explore metabolic functionality on the evolution of bacterial antibiotic resistance.

Antimicrobial resistance (AMR) is one of the greatest threats to humanity globally as it has been escalated by the over-prescription and usage of antibiotics for both humans and animals. AMR occurs when the bacteria develop a way of resisting the antimicrobial compounds, thus leading to increased mortality rates, health expenses, and issues of handling infections. The development of AMR occurs through mutations of bacterial genes or through horizontal gene transfer that results in increased minimum inhibitory concentration and bacterial tolerance.

Exploring a peripheral PIP2-binding site and its role in the alternative regulation of the TRP channel superfamily.

Phosphatidylinositol 4,5-bisphosphate (PIP2) is recognized as an essential modulator of transient receptor potential (TRP) channels. Specifically, it influences the vanilloid receptor I (TRPV1), a pain receptor activated by a wide range of stimuli, including the binding of phospholipids, such as PIP2. The primary PIP2-binding site in TRPV1 has been identified through advanced techniques, revealing that the PIP2 binds to a specific pocket composed of positively charged residues located predominantly within the proximal C-terminus region.

Adenosine kinase and ADAL coordinate detoxification of modified adenosines to safeguard metabolism.

RNA contains diverse post-transcriptional modifications, and its catabolic breakdown yields numerous modified nucleosides requiring correct processing, but the mechanisms remain unknown. Here, we demonstrate that three RNA-derived modified adenosines, N-methyladenosine (mA), N,N-dimethyladenosine (mA), and N-isopentenyladenosine (iA), are sequentially metabolized into inosine monophosphate (IMP) to mitigate their intrinsic cytotoxicity. After phosphorylation by adenosine kinase (ADK), they undergo deamination by adenosine deaminase-like (ADAL).

EZH2-TTP-mTORC1 Axis Drives Phenotypic Plasticity and Therapeutic Vulnerability in Lethal Prostate Cancer.

Phenotypic plasticity is a recognized mechanism of therapeutic resistance in prostate cancer (PCa), however current knowledge of driver mechanisms and therapeutic interventions are limited. Using genetically engineered mouse models (GEMMs) devoid of Pten and Rb1, we previously demonstrated the chromatin reprogramming factor enhancer of zeste homolog 2 (EZH2) as an important regulator of alternative transcription programs promoting phenotypic plasticity. Here, using a multi-omics approach we demonstrate that EZH2 regulates multilineage cell states dependent on the RNA binding protein Tristetraprolin (TTP) that mediates RNA stability and activation of translation.

ChEA-KG: Human Transcription Factor Regulatory Network with a Knowledge Graph Interactive User Interface.

Background: Gene expression is controlled by transcription factors (TFs) that selectively bind and unbind to DNA to regulate mRNA expression of all human genes. TFs control the expression of other TFs, forming a complex gene regulatory network (GRN) with switches, feedback loops, and other regulatory motifs. Many experimental and computational methods have been developed to reconstruct the human intracellular GRN.

The path-label reconciliation (PLR) dissimilarity measure for gene trees.

Background: In this study, we investigate the problem of comparing gene trees reconciled with the same species tree using a novel semi-metric, called the Path-Label Reconciliation (PLR) dissimilarity measure. This approach not only quantifies differences in the topology of reconciled gene trees, but also considers discrepancies in predicted ancestral gene-species maps and speciation/duplication events, offering a refinement of existing metrics such as Robinson-Foulds (RF) and their labeled extensions LRF and ELRF. A tunable parameter also allows users to adjust the balance between its species map and event labeling components.

Integrative proteogenomic characterization of Wilms tumor.

Wilms tumor (WT), the most common pediatric renal malignancy, exhibits a relatively low mutational burden compared to adult cancers, which hinders the development of targeted therapies. To elucidate the molecular landscape of WT, we perform integrative proteomic, phosphoproteomic, transcriptomic, and whole-exome sequencing analyses of WT and normal kidney tissue adjacent to tumor. Our multi-omics approach uncovers prognostic genetic alterations, distinct molecular subgroups, immune microenvironment features, and potential biomarkers and therapeutic targets.

Reg2ST: recognizing potential patterns from gene expression for spatial transcriptomics prediction.

Spatial transcriptomics is able to acquire cellular gene expression while retaining spatial location. It is often accompanied by matched hematoxylin and eosin-stained histology whole-slide images. This retention of spatial information is critical for studying key issues in cell biology, developmental biology, neurobiology, and tumor biology.

Latent Growth Models of Longitudinal Changes in Functional Connectivity during Early Stage Psychosis.

Resting state functional magnetic resonance imaging (fMRI) is a useful technique to characterize functional connectivity patterns between regions of the brain, based on the Fisher-transformed Pearson correlations in the BOLD signal. Pinpointing how connectivity patterns change in neuropathies like early-stage psychosis (ESP) can help understand the disorders and track progression. Using study data from 21 ESP subjects with complete data for three consecutive scans, we examined connectivity changes throughout the whole brain with a region of interest (ROI) to ROI-based approach for ROI defined by the Harvard-Oxford cortical and subcortical atlases, supplemented by the AAL atlas for the cerebellum, and by networks defined by the CONN toolbox independent component analysis of the Human Connectome Project.

Environmental justice index and prevalence of asthma and COPD in US neighborhoods- a population-based study.

Background: The independent effects of social and environmental factors on asthma and chronic obstructive pulmonary disease (COPD) are well-documented, but less is known about their combined impact across US neighborhoods. This study aimed to determine the combined and individual associations of neighborhood-level social vulnerability and environmental burden with the prevalence of asthma and COPD.

Methods: This cross-sectional study analyzed 71,677 US census tracts, linking the 2022 CDC Environmental Justice Index (EJI) rankings and its subcomponents (environmental burden module [EBM] and social vulnerability module [SVM]) to the 2023 CDC PLACES dataset.

Trophectoderm-like cells from EPS cells enable generating EPS cell-derived post-implantation embryoids that complete gastrulation.

Mouse extended pluripotent stem (EPS) cells have demonstrated significant potential for generating embryo models in vitro. However, their limited capacity for extraembryonic trophoblast development has hindered their use in constructing whole embryo models, particularly post-implantation embryoids. Here, we establish a stepwise induction protocol to generate trophectoderm-like cells from mouse EPS cells.