Stabilizing effect of amino acids on protein and colloidal dispersions.

Amino acids (AAs) have a long history of being used as stabilizers for biological media. For example, they are important components in biomedical formulations. The effect of AAs on biological systems is also starting to be appreciated.

Structure and mechanism of the mitochondrial calcium transporter NCLX.

As a key mitochondrial Ca transporter, NCLX regulates intracellular Ca signalling and vital mitochondrial processes. The importance of NCLX in cardiac and nervous-system physiology is reflected by acute heart failure and neurodegenerative disorders caused by its malfunction. Despite substantial advances in the field, the transport mechanisms of NCLX remain unclear.

ABCA7 variants impact phosphatidylcholine and mitochondria in neurons.

Loss-of-function variants in the lipid transporter ABCA7 substantially increase the risk of Alzheimer's disease, yet how they impact cellular states to drive disease remains unclear. Here, using single-nucleus RNA-sequencing analysis of human brain samples, we identified widespread gene expression changes across multiple neural cell types associated with rare ABCA7 loss-of-function variants. Excitatory neurons, which expressed the highest levels of ABCA7, showed disrupted lipid metabolism, mitochondrial function, DNA repair and synaptic signalling pathways.

Fluctuating DNA methylation tracks cancer evolution at clinical scale.

Cancer development and response to treatment are evolutionary processes, but characterizing evolutionary dynamics at a clinically meaningful scale has remained challenging. Here we develop a new methodology called EVOFLUx, based on natural DNA methylation barcodes fluctuating over time, that quantitatively infers evolutionary dynamics using only a bulk tumour methylation profile as input. We apply EVOFLUx to 1,976 well-characterized lymphoid cancer samples spanning a broad spectrum of diseases and show that initial tumour growth rate, malignancy age and epimutation rates vary by orders of magnitude across disease types.

Acute kidney injury and subsequent risk of late-onset infection among extremely low gestational age newborns.

Objective: Determine whether acute kidney injury (AKI) is associated with subsequent late-onset infection (LOI) among extremely low gestational age newborns (ELGAN).

Study Design: Secondary analysis of participants in the Preterm Erythropoietin for Neuroprotection Trial. Infants surviving ≥7 days with sufficient serum creatinine data were included.

Nanotechnology for CAR T cells and tumour-infiltrating lymphocyte therapies.

Adoptive T-cell therapies, and particularly CAR T cells and tumour-infiltrating lymphocytes, have transformed cancer treatment by selectively targeting malignant cells. Despite their clinical success, these therapies face substantial challenges, including costly manufacturing processes and tumour-imposed barriers that limit efficacy. Advances in understanding the nanoscale mechanisms governing T-cell activation and the role of the tumour microenvironment in restricting T-cell responses have driven the development of nanotechnology-based strategies that integrate key chemical and physical cues.

Nanofibrous supramolecular peptide hydrogels for controlled release of small-molecule drugs and biologics.

Maintaining safe and potent drug levels in vivo is challenging. Multidomain peptides assemble into supramolecular hydrogels with a well-defined, highly porous nanostructure that makes them attractive for drug delivery. However, their ability to extend release is typically limited by rapid drug diffusion.

Longitudinal single-cell analysis reveals treatment-resistant stem and mast cells with potential treatments for pediatric AML.

Pediatric acute myeloid leukemia (pAML) is a heterogeneous malignancy driven by diverse cytogenetic mutations. While identification of cytogenetic lesions improved risk stratification, prognostication remains inadequate with 30% of standard-risk patients experiencing relapse within 5 years. To deeply characterize pAML heterogeneity and identify poor outcome-associated blast cell profiles, we performed an analysis on 708,285 cells from 164 bone marrow biopsies of 95 patients and 11 healthy controls.

GluN2A-NMDA receptor inhibition disinhibits the prefrontal cortex, reduces forced swim immobility, and impairs sensorimotor gating.

Recent investigations into the rapid antidepressant effects of ketamine, along with studies on schizophrenia-related susceptibility genes, have highlighted the GluN2A subunit as a critical regulator of both emotion and cognition. However, the specific impacts of acute pharmacological inhibition of GluN2A-containing NMDA receptors on brain microcircuits and the subsequent behavioral consequences remain poorly understood. In this study, we first examined the effects of MPX-004, a selective GluN2A NMDA receptor inhibitor, on behavior within the dorsomedial prefrontal cortex (dmPFC).

Dysregulated RNA splicing impairs regeneration in alcohol-associated liver disease.

Individuals with progressive liver failure risk dying without liver transplantation. However, our understanding of why regenerative responses are disrupted in failing livers is limited. Here, we perform multiomic profiling of healthy and diseased human livers using bulk and single-nucleus RNA- and ATAC-seq.

Metagenomic complexity of high, seasonal transmission of Plasmodium spp. in asymptomatic carriers in Northern Sahelian Ghana.

Background: Mixed-species, mixed-strain plasmodia infections are known to occur in humans in malaria endemic areas. It may be surprising that to date, the extent of this complexity has not been systematically explored in high-burden countries of sub-Saharan Africa, especially in the reservoir of asymptomatic infections in all ages, which sustains transmission.

Methods: Here we take a metagenomic lens to these infections by sampling variable blood volumes from 188 afebrile residents living in high, seasonal transmission in Northern Sahelian Ghana.

Digging into the evolutionary history of the fungus-growing-ant symbiont, Escovopsis (Hypocreaceae).

Symbiotic relationships shape the evolution of organisms. Fungi in the genus Escovopsis share an evolutionary history with the fungus-growing "attine" ant system and are only found in association with these social insects. Despite this close relationship, there are key aspects of Escovopsis evolution that remain poorly understood.

Modulating the PPARγ pathway upregulates NECTIN4 and enhances chimeric antigen receptor (CAR) T cell therapy in bladder cancer.

With the approval of the antibody-drug conjugate enfortumab vedotin (EV), NECTIN4 has emerged as a bona fide therapeutic target in urothelial carcinoma (UC). Here, we report the development of a NECTIN4-directed chimeric antigen receptor (CAR) T cell, which exhibits reactivity across cells expressing a range of endogenous NECTIN4, with enhanced activity in high expressors. We demonstrate that the PPARγ pathway, critical for luminal differentiation, transcriptionally controls NECTIN4, and that the PPARγ agonist rosiglitazone primes and augments NECTIN4 expression, thereby increasing sensitivity to NECTIN4-CAR T cell-mediated killing.

Proximity labeling of axonemal protein CFAP91 identifies EFCAB5 that regulates sperm motility.

Radial spokes (RSs) are conserved multimolecular structures attached to the axonemal microtubule doublets and are essential for the motility control of both cilia and sperm flagella. CFAP91, an RS3 protein, is implicated in human male infertility, yet its molecular function remains poorly understood. Here, we demonstrate that Cfap91 knockout (KO) mice exhibit impaired sperm flagellum formation and male infertility.

The Fuetsan Manhoben Curriculum: Effects on Risk Perceptions and Intentions Regarding Tobacco and Betel Nut Use Among Adolescents in Guam.

: While there are known high rates of tobacco and betel (areca) nut use in the U.S.-Affiliated Pacific Islands (USAPI), there have been limited efforts at preventing the initiation of tobacco and betel nut among those living in the region, particularly, adolescents.

Multiple human enhancer RNAs contain long translated open reading frames.

Enhancer RNAs (eRNAs) are transcribed by during enhancer activation but are typically rapidly degraded in the nucleus. During states of reduced RNA surveillance, however, eRNAs and other similar "noncoding" RNAs (including, e.g.

A critical affinity window for IgSF proteins DIP-α and Dpr10 is required for proper motor neuron arborization.

For neurons to establish the correct connections in animal nervous systems, interactions between cell adhesion molecules (CAMs), expressed presynaptically and postsynaptically, are thought to guide neurons to their targets. Here, we assess the role that affinity between two cognate CAMs-DIP-α and Dpr10-plays in establishing the leg neuromuscular system in If affinity decreases or, surprisingly, increases past certain thresholds, motor neuron (MN) terminal branches fail to be maintained. Live imaging during development shows that when affinities are aberrant, MN filopodia are unable to productively engage their muscle targets.

Prelude to the perfect storm: the many triggers of secondary hemophagocytic lymphohistiocytosis.

Hemophagocytic lymphohistiocytosis (HLH) is an increasingly recognized disorder of immune hyperactivity that often leads to multiorgan failure and death. In adults, HLH is usually triggered by infection, malignancy, or an autoimmune/autoinflammatory disorder that precipitates a destructive cytokine storm. Treatment aims to deescalate the hyperimmunity by treating the triggers while interfering with the immune pathways that cause the morbidity.

Comparing Two Approaches to Identify Individuals with Severe Asthma in United States Claims Data.

Purpose: Given the increased likelihood for individuals with severe asthma to experience comorbidities, disease complications, emergency room visits, and hospitalizations, the ability to stratify asthma populations on severity is often important. Although pharmacoepidemiologic studies using administrative healthcare databases sometimes categorize asthma severity, there is no consensus on an approach.

Methods: Individuals with asthma (≥ 2 ICD-10-CM diagnosis codes J45) aged ≥ 6 years were identified in Optum's de-identified Clinformatics Data Mart Database between January 2017 and November 2023.