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While specificity of biomolecular interactions is typically understood to require interactions involving ordered structures, several biomolecular condensates exhibit specificity in the absence of apparent structural order. We have previously shown that condensates composed of the disordered region of MED1 partition specific proteins, mediated by sequence patterns of charged amino acids on the disordered regions of both MED1 and the interacting partner. Whether this specificity is due to an...

The environmental risks of PAHs are well-documented, yet far less is known about their more toxic and persistent derivatives, MePAHs and NPAH, especially in the unique context of seasonally frozen wetlands. This study provides the first evidence of MePAHs and NPAHs enrichment in ice within a temperate wetland, based on their distribution behavior, migration behavior, and associated environmental risks in the Songhua River. Using GC-MS/MS quantification combined with ice enrichment factors (IEFs)...

The goal of the Human Liver Cell Atlas (HLiCA) is to create a comprehensive map that defines the normal functions of diverse liver cell types and their spatial relationships over the human lifespan. This project fits within the goals of the Human Cell Atlas to create comprehensive reference maps of all human cells as a basis for both understanding human health and diagnosing, monitoring and treating disease. Through collection of samples from diverse individuals, data integration across...

Decreased gut microbial diversity is associated with greater depression symptoms in adults. Findings on the relationship between the gut microbiome and depression or anxiety in children and adolescents are mixed, and evidence syntheses are needed. Seven databases were searched for peer-reviewed studies on the gut microbiome and internalizing symptoms, depression, or anxiety, in children and adolescents (<19 years). Random-effects meta-analyses of alpha diversity indices were performed. Youth...

The functions of most long non-coding RNAs (lncRNAs) are not known. Here, we define a group of "tRNA-overlapping lncRNA" (tROL) genes that are upregulated during in vitro cartilage development. Deletions of tROLs result in changes in the expression of codon-biased genes, where downregulated genes are enriched in codons corresponding to tRNAs overlapping disrupted tROLs. tROL loci are located in gene-dense regions and interact extensively between chromosomes, and tROL whole-gene deletions result...

As the consequences of climate change have become increasingly evident and the environmental impact of cancer care continues to grow, there is a clear need for practice guidelines that integrate sustainability into the radiologic assessment and management of cancer. The use of imaging and image-guided procedures in cancer care has expanded substantially, contributing to improved patient outcomes, but also increased emissions and waste. This review examines the current environmental impact of...

Perioperative low cardiac output syndrome (LCOS) remains a significant complication in adult cardiac surgery, contributing to substantial morbidity, prolonged intensive care, and increased mortality. Its incidence is expected to rise further due to the evolving complexity of referred surgical patients, often characterised by advanced age, multiple comorbidities, challenging anatomy, and impaired haemodynamics. Despite advances in pharmacological and perioperative care, outcomes for high-risk...

Mitochondrial dynamics relies on the function of dynamin family GTPase proteins including mitofusin 1 (MFN1), mitofusin 2 (MFN2), and dynamin-related protein 1 (DRP1). The mitochondrial phosphatase phosphoglycerate mutase 5 (PGAM5) protein can regulate the phosphorylation levels and the function of both MFN2 and DRP1, however, the precise regulation of PGAM5 activity is unknown. We show that PGAM5 oligomerization and localization controls its function. Under depolarization and/or metabolic...

CONCLUSIONS: RHIs may lead to acute disbalance of tau and phosphorylated tau in plasma, and are associated with short-term decline in cognitive performance and neuroprotective pathways in elite female soccer players. The sexual dimorphism in response to RHI may reflect biological risk factors potentially relevant to the different degree of susceptibility to neurological disorders in females and males in later life.

CONCLUSION: Taken together, our healthy pediatric liver atlas reveals distinct age-related signatures and provides a background against which to interpret pediatric liver disease data.

OBJECTIVE: Autophagy is a fundamental biological pathway with vital roles in intracellular homeostasis. During autophagy, defective cargoes including mitochondria are targeted to lysosomes for clearance and recycling. Recessive truncating variants in the autophagy gene EPG5 have been associated with Vici syndrome, a severe early-onset neurodevelopmental disorder with extensive multisystem involvement. Here, we aimed to delineate the extended, age-dependent EPG5-related disease spectrum.

Machine learning (ML) is increasingly used in DNA-encoded library (DEL) screening for ligand discovery, but its success depends on access to suitable data sets, which are often proprietary and costly. To overcome this, we present the first fully open, automated DEL-ML framework using public DEL data sets and chemical fingerprints to enable reproducible, accessible drug discovery. Our workflow─from model training to virtual screening and compound selection─requires no human intervention. As a...

Prostate cancer (PCa) germline testing, while gaining momentum, is ancestry restrictive and African exclusive. Through whole genome sequencing for 217 African ancestral cases (186 southern African, 31 Pan representative), we identify 172 potentially pathogenic variants in 78 DNA damage repair or PCa related genes. Prevalence for reported (13/217, 5.99%) and cumulative predicted (24/217, 11.06%) variants of significance (11 genes) falls below that reported for non-Africans. Conversely, BRCA1,...

Huntington's disease (HD) is a fatal neurodegenerative disorder caused by a CAG repeat expansion in the Huntingtin (HTT) gene, with no disease-modifying therapies currently available. The precise molecular function of the HTT protein is unclear, and the lack of selective chemical tools has limited functional studies. We have identified and characterized macrocyclic peptide binders targeting HTT. These binders exhibit low-nanomolar affinity in vitro and engage distinct HTT and HTT-HAP40...

Quantifying biomass is essential for studying biofilms in biomanufacturing, yet widely used assays such as crystal violet (CV) often yield results that are difficult to compare across laboratories due to its reliance on absorbance as a subjective proxy for biomass. To address this, we present a standardized method that calibrates CV absorbance against cellular optical density (OD) and dry cell weight (DCW) using centrifuged planktonic cultures. By establishing a three-way correlation among OD,...

Diverse regulatory mechanisms enable precise spatio-temporal control of gene expression across developmental stages, tissues, and sexes, contributing to the proper development of the organism. Evolutionary divergence leads to species-specific gene expression patterns, even in preserved developmental structures, due to regulatory changes that can disproportionately influence subsets of developmental genetic networks. Here, we quantify the evolution of sex-biased and tissue-biased transcriptomes...

Gene expression patterns are determined to a large extent by transcription factor binding to non-coding regulatory regions in the genome. However, gene expression cannot yet be systematically predicted from genome sequences, in part because non-functional matches to the sequence patterns (motifs) recognized by transcription factors (TFs) occur frequently throughout the genome. Large-scale functional genomics data for many TFs has enabled characterization of regulatory networks in experimentally...

Long-read sequencing (LRS) technologies have enhanced the ability to resolve complex genomic architecture and determine the 'phase' relationships of genetic variants over long distances. Although genome-wide association studies (GWAS) identify individual variants associated with complex traits, they do not typically account for whether multiple associated signals at a locus may act in cis or trans, or whether they reflect allelic heterogeneity. As a result, effects that arise specifically from...

Metabolic engineering enables sustainable chemical production but often imposes metabolic burdens that reduce cellular viability and productivity. Dynamic control strategies, such as quorum sensing (QS)-based circuits, can mitigate these effects by autonomously regulating gene expression in response to cell density. In this study, we investigated a QS-regulated CRISPR interference (qCRISPRi) circuit for the dynamic control of metabolic pathways, focusing on the role of leaky expression and...

Dolichol-linked oligosaccharide (DLO) is the precursor for asparagine (N)-linked protein glycosylation. DLO synthesis can be impaired by genetic and environmental factors, leading to the accumulation of various immature DLO intermediates that are subsequently cleaved into phosphorylated oligosaccharides (POSs). Despite the fact that its activity has been known since the 1970s, the identity of the enzyme has not been clarified. Here, we identified a Saccharomyces cerevisiae gene encoding a...