BioDolphin as a comprehensive database of lipid-protein binding interactions.

Lipid-protein interactions are crucial for virtually all biological processes in living cells. However, existing structural databases focusing on these interactions are limited to integral membrane proteins. A systematic understanding of diverse lipid-protein interactions also encompassing lipid-anchored, peripheral membrane and soluble lipid binding proteins remains to be elucidated.

Multifaceted impact of HIV inhibitor dapivirine on triple negative breast cancer cells reveals potential entities as targets for novel therapy.

Breast cancer is the most common cancer in women worldwide. Many breast cancers originate from the cells lining the milk duct and some become invasive. Breast cancer lacking estrogen, progesterone receptors (ER-, PR-) and epidermal growth factor receptor 2 (HER2-) amplification, termed "Triple negative" (TNBC) is reported to frequently affect Black women and younger women.

Drink like a man? Modified Poisson analysis of adolescent binge drinking in the US, 1976-2022.

This study estimates temporal trajectories and sociodemographic disparities in underage adolescent binge drinking in the United States over the past four decades. By compiling 47 waves of national representative data from the Monitoring the Future (MTF) study between 1976 and 2022, we analyzed two types of adolescent binge drinking behaviors, past-two-week excessive drinking and drunkenness in the past 30 days, using the innovative modified Poisson (mixture) approach to grouped and right-censored counts (GRC). The overall decrease in incidence rates was attributable to substantial reductions in the risks of excessive drinking (45.

Evaluating coarse PM composition and sources based on bulk and molecular speciation of PM and PM in Nanjing, East China.

To understand the differences in the composition and sources of PM and PM caused by coarse particles, integrated PM and PM samples were synchronously collected in Nanjing, East China, in summer 2020 and winter 2020/2021. Bulk and molecular speciation and light absorption measurements of aerosol extracts were performed, followed by positive matrix factorization (PMF) based on the PM and PM data sets, respectively. The difference in average concentrations of total bulk species between PM and PM was mainly caused by the distribution of considerable NO, SO, Ca, and organic carbon (OC) in coarse particles.

Nanocarriers Made of Natural Fatty Acids: Modulation of Their Release Profiles through Photo-Crosslinking.

Natural fatty acids are attractive carrier materials for drug delivery, but their rapid dissolution and degradation in vivo calls for new strategies to enhance their stability. Here we report a simple and versatile method capable of photo-crosslinking carriers made of natural fatty acids for drug delivery under controlled release. By optimizing the crosslinking density, the nanoscale carriers show a high drug loading efficiency, together with a stable network structure for minimal degradation in a body fluid mimic.

The Role of p16Ink4a as an Early Predictor of Physiological Decline during Natural Aging.

Cellular senescence is a prominent accomplice of aging. The expression of gene p16ink4a has been established as a biomarker of cellular senescence in humans and animal models. However, it has not been extensively studied in clinical settings in the context of natural aging and the development of age-related diseases.

Experimental evolution at ecological scales allows linking of viral genotypes to specific host strains.

Viruses shape microbial community structure and activity through the control of population diversity and cell abundances. Identifying and monitoring the dynamics of specific virus-host pairs in nature is hampered by the limitations of culture-independent approaches such as metagenomics, which do not always provide strain-level resolution, and culture-based analyses, which eliminate the ecological background and in-situ interactions. Here, we have explored the interaction of a specific "autochthonous" host strain and its viruses within a natural community.

Microbial Metagenomes Across a Complete Phytoplankton Bloom Cycle: High-Resolution Sampling Every 4 Hours Over 22 Days.

In May and June of 2021, marine microbial samples were collected for DNA sequencing in East Sound, WA, USA every 4 hours for 22 days. This high temporal resolution sampling effort captured the last 3 days of a Rhizosolenia sp. bloom, the initiation and complete bloom cycle of Chaetoceros socialis (8 days), and the following bacterial bloom (2 days).

Challenging the Bayesian confidence hypothesis in perceptual decision-making.

The Bayesian confidence hypothesis (BCH), which postulates that confidence reflects the posterior probability that a decision is correct, is currently the most prominent theory of confidence. Although several recent studies have found evidence against it in the context of relatively complex tasks, BCH remains dominant for simpler tasks. The major alternative to BCH is the confidence in raw evidence space (CRES) hypothesis, according to which confidence is based directly on the raw sensory evidence without explicit probability computations.

Small-molecule disruption of androgen receptor-dependent chromatin clusters.

Sustained androgen receptor (AR) signaling during relapse is a central driver of metastatic castration-resistant prostate cancer (mCRPC). Current AR antagonists, such as enzalutamide, fail to provide long-term benefit for the mCRPC patients who have dramatic increases in AR expression. Here, we report AR antagonists with efficacy in AR-overexpressing models.

Optimized Clinical Feature Analysis for Improved Cardiovascular Disease Risk Screening.

To develop a clinical decision support tool that can predict cardiovascular disease (CVD) risk with high accuracy while requiring minimal clinical feature input, thus reducing the time and effort required by clinicians to manually enter data prior to obtaining patient risk assessment. In this study, we propose a robust feature selection approach that identifies five key features strongly associated with CVD risk, which have been found to be consistent across various models. The machine learning model developed using this optimized feature set achieved state-of-the-art results, with an AUROC of 91.

Antigen-specific T cell immunotherapy by in vivo mRNA delivery.

Immunotherapy has shown promise for treating patients with autoimmune diseases or cancer, yet treatment is associated with adverse effects associated with global activation or suppression of T cell immunity. Here, we developed antigen-presenting nanoparticles (APNs) to selectively engineer disease antigen (Ag)-specific T cells by mRNA delivery. APNs consist of a lipid nanoparticle core functionalized with peptide-major histocompatibility complexes (pMHCs), facilitating antigen-specific T cell transfection through cognate T cell receptor-mediated endocytosis.

Hippocampal area CA2 activity supports social investigation following an acute social stress.

Neuronal activity in the hippocampus is critical for many types of memory acquisition and retrieval and influences an animal's response to stress. Moreover, the molecularly distinct principal neurons of hippocampal area CA2 are required for social recognition memory and aggression in mice. To interrogate the effects of stress on CA2-dependent behaviors, we chemogenetically manipulated neuronal activity in vivo during an acute, socially derived stressor and tested whether memory for the defeat was influenced.

Mechanotransduction governs CD40 function and underlies X-linked hyper-IgM syndrome.

B cell maturation depends on cognate interactions between the T and B cells. Upon interaction with CD40 ligand (CD40L) on T cells, CD40 delivers costimulatory signals alongside B cell antigen receptor (BCR) signaling to regulate affinity maturation and antibody class switch. Mutations affecting CD40-CD40L interactions cause abnormal antibody responses in immunodeficiencies known as X-linked hyper-IgM syndrome (X-HIgM).

Adaptive wheel exercise for mouse models of Parkinson's Disease.

Background: Physical exercise has been extensively studied for its therapeutic properties in neurological disease, particularly Parkinson's Disease (PD). However, the established techniques for exercise in mice are not well suited to motor-deficient disease-model animals, rely on spontaneous activity or force exercise with aversive stimuli, and do not facilitate active measurement of neurophysiology with tethered assays. Motorized wheel exercise may overcome these limitations, but has not been shown to reliably induce running in mice.

Overcoming nucleotide bias in the nonenzymatic copying of RNA templates.

The RNA World hypothesis posits that RNA was the molecule of both heredity and function during the emergence of life. This hypothesis implies that RNA templates can be copied, and ultimately replicated, without the catalytic aid of evolved enzymes. A major problem with nonenzymatic template-directed polymerization has been the very poor copying of sequences containing rA and rU.

High throughput electronic detection of biomarkers using enzymatically amplified metallization on nanostructured surfaces.

Enzyme-linked immunosorbent assays are commonly used for clinical biomarker detection. However, they remain resource-intensive and difficult to scale globally. Here we present a miniaturized direct electronic biosensing modality which generates a simple and sensitive, quantitative, resistive readout of analyte binding in immunoassays.