Background And Hypothesis: In accordance with the Cognitive Model of Negative Symptoms, defeatist performance beliefs (DPBs) are an important psychosocial mechanism of negative symptoms in schizophrenia-spectrum groups. DPBs are also mediators of negative symptom improvement in clinical trials. Despite the clinical significance of DPBs and their inclusion as a mechanism of change measure in clinical trials, the psychometric properties of the DPB scale have not been examined in any schizophrenia-spectrum group.
View Article and Find Full Text PDFAdvancements in genomic and proteomic technologies have powered the creation of large gene and protein networks ("interactomes") for understanding biological systems. However, the proliferation of interactomes complicates the selection of networks for specific applications. Here, we present a comprehensive evaluation of 45 current human interactomes, encompassing protein-protein interactions as well as gene regulatory, signaling, colocalization, and genetic interaction networks.
View Article and Find Full Text PDFBackground: Viral hemorrhagic fevers (VHFs) belong to a group of viral infectious diseases that interfere with the blood's clotting mechanism. VHF has a wide host range, including bats, rodents, or arthropods such as mosquitoes and ticks. Most VHFs emerge suddenly as outbreaks, making it difficult to predict occurrence.
View Article and Find Full Text PDFGene set enrichment is a mainstay of functional genomics, but it relies on gene function databases that are incomplete. Here we evaluate five large language models (LLMs) for their ability to discover the common functions represented by a gene set, supported by molecular rationale and a self-confidence assessment. For curated gene sets from Gene Ontology, GPT-4 suggests functions similar to the curated name in 73% of cases, with higher self-confidence predicting higher similarity.
View Article and Find Full Text PDFMechanistic studies of thiol reactivity can be challenging because electrophilic reaction intermediates, such as sulfenic acids (RSOH) and sulfenyl chlorides (RSCl), are generally too reactive to be observed directly. Herein we report the design and synthesis of a sterically-encumbered fluorinated triptycene thiol which enables direct observation of reaction intermediates in aqueous buffer by F NMR, as demonstrated in reactions with hydrogen peroxide and hypochlorous acid. Reactions with HO resulted in the formation of a persistent RSOH species, which was subsequently converted to a sulfinic acid (RSOH) and then a sulfonic acid (RSOH), while RSCl was found to be the intermediate in reactions with HOCl.
View Article and Find Full Text PDFFerroptosis is a regulated and non-apoptotic form of cell death mediated by iron-dependent peroxidation of polyunsaturated fatty acyl tails in phospholipids. Research of the past years has shed light on the occurrence of ferroptosis in organ injury and degenerative diseases of the brain, kidney, heart, and other tissues. Hence, ferroptosis inhibition may prove therapeutically beneficial to treat distinct diseases.
View Article and Find Full Text PDFCuATSM, a copper(II) complex of a bis(thiosemicarbazone) of diacetyl, prevents oxidative cell death and acts as a neuroprotectant , prompting its evaluation to treat amyotrophic lateral sclerosis and other neurodegenerative conditions in the clinic. We recently demonstrated that CuATSM functions as a potent radical-trapping antioxidant (RTA), inhibiting lipid peroxidation and associated ferroptotic cell death by a noncanonical mechanism based on radical addition to the ligand backbone. Herein we report our investigations of the generality of this reactivity, which include studies of corresponding complexes of various other metals, including Co, Ru, Ni, Pd, Pt, and Au.
View Article and Find Full Text PDFBackground: Primary sclerosing cholangitis (PSC) is a chronic liver disease characterized by inflammation and progressive fibrosis of the biliary tree. The pathogenesis of PSC remains poorly understood, and there are no effective therapeutic options. Previous studies have observed associations between changes in the colonic and biliary microbiome and PSC.
View Article and Find Full Text PDFThe impact of saltwater intrusion on coastal forests and farmland is typically understood as sea-level-driven inundation of a static terrestrial landscape, where ecosystems neither adapt to nor influence saltwater intrusion. Yet recent observations of tree mortality and reduced crop yields have inspired new process-based research into the hydrologic, geomorphic, biotic, and anthropogenic mechanisms involved. We review several negative feedbacks that help stabilize ecosystems in the early stages of salinity stress (e.
View Article and Find Full Text PDFFlooding and salinization triggered by storm surges threaten the survival of coastal forests. The forest root zone (top 40 cm of soil) is the most affected by surge flooding. Determining the effect of a storm surge on edaphic conditions is essential to estimate vegetation response.
View Article and Find Full Text PDFThis editorial provides an overview of the challenges and benefits of working as and supervising trial therapists from the perspective of investigators and trial therapists. Key differences between trial therapy and standard care are considered, with recommendations for best practice.
View Article and Find Full Text PDFDefining the subset of cellular factors governing SARS-CoV-2 replication can provide critical insights into viral pathogenesis and identify targets for host-directed antiviral therapies. While a number of genetic screens have previously reported SARS-CoV-2 host dependency factors, these approaches relied on utilizing pooled genome-scale CRISPR libraries, which are biased towards the discovery of host proteins impacting early stages of viral replication. To identify host factors involved throughout the SARS-CoV-2 infectious cycle, we conducted an arrayed genome-scale siRNA screen.
View Article and Find Full Text PDFThe link between imprisonment and adverse mental health is well established and linked to both recidivism and prison misconduct, with negative consequences for prisoners, the prison system and society. To help minimise these impacts, appropriate mental health interventions are required. However, owing to finite resources to deliver healthcare in prisons, interventions must be both clinically and cost-effective.
View Article and Find Full Text PDFCurr Opin Chem Biol
August 2024
The accumulation of lipid hydroperoxides (LOOHs) has long been associated with numerous pathologies and has more recently been shown to drive a specific type of cell death known as ferroptosis. In competition with their detoxification by glutathione peroxidases, LOOHs can react with both one-electron reductants and one-electron oxidants to afford radicals that initiate lipid peroxidation (LPO) chain reactions leading to more LOOH. These radicals can alternatively undergo a variety of (primarily unimolecular) reactions leading to electrophilic species that destabilize the membrane and/or react with cellular nucleophiles.
View Article and Find Full Text PDFThis article describes the Cell Maps for Artificial Intelligence (CM4AI) project and its goals, methods, standards, current datasets, software tools , status, and future directions. CM4AI is the in the U.S.
View Article and Find Full Text PDFBackground & Aims: Recurrent primary biliary cholangitis (rPBC) develops in approximately 30% of patients and negatively impacts graft and overall patient survival after liver transplantation (LT). There is a lack of data regarding the response rate to ursodeoxycholic acid (UDCA) in rPBC. We evaluated a large, international, multi-center cohort to assess the performance of PBC scores in predicting the risk of graft and overall survival after LT in patients with rPBC.
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