The Historical Evolution and Significance of Multiple Sequence Alignment in Molecular Structure and Function Prediction.

Multiple sequence alignment (MSA) has evolved into a fundamental tool in the biological sciences, playing a pivotal role in predicting molecular structures and functions. With broad applications in protein and nucleic acid modeling, MSAs continue to underpin advancements across a range of disciplines. MSAs are not only foundational for traditional sequence comparison techniques but also increasingly important in the context of artificial intelligence (AI)-driven advancements.

Oxidative Stress in Kidney Injury and Hypertension.

Hypertension (HTN) is a major contributor to kidney damage, leading to conditions such as nephrosclerosis and hypertensive nephropathy, significant causes of chronic kidney disease (CKD) and end-stage renal disease (ESRD). HTN is also a risk factor for stroke and coronary heart disease. Oxidative stress, inflammation, and activation of the renin-angiotensin-aldosterone system (RAAS) play critical roles in causing kidney injury in HTN.

Healthier Lipid Profiles of Japanese Adults, Especially in Women with Elevated High-Density Lipoprotein Cholesterol (HDL-C), Are Associated with Low HDL-C Peroxide Content.

Japanese adults typically have healthier lipid profiles than American and European adults and a lower prevalence and later onset of atherosclerotic cardiovascular disease (ASCVD). Many Japanese also have uniquely elevated levels of high-density lipoprotein cholesterol (HDL-C). The following analysis examined the relationship between HDL-C level and HDL-C peroxide content, a bioindicator of unhealthy lipid metabolism in Japanese adults.

Virus-induced vesicular acidification enhances HIV immune evasion.

To inhibit endocytic entry of some viruses, cells promote acidification of endosomes by expressing the short isoform of human nuclear receptor 7 (NCOA7) which increases activity of vacuolar ATPase (V-ATPase). While we found that HIV-1 infection of primary T cells led to acidification of endosomes, NCOA7 levels were only marginally affected. Contrastingly, levels of the 50 kDa form of the sodium/hydrogen exchanger 6 (NHE6) were greatly reduced.

Cellular cartography reveals mouse prostate organization and determinants of castration resistance.

Inadequate response to androgen deprivation therapy (ADT) frequently arises in prostate cancer, driven by cellular mechanisms that remain poorly understood. Here, we integrated single-cell RNA sequencing, single-cell multiomics, and spatial transcriptomics to define the transcriptional, epigenetic, and spatial basis of cell identity and castration response in the mouse prostate. Leveraging these data along with a meta-analysis of human prostates and prostate cancer, we identified cellular orthologs and key determinants of ADT response and resistance.

Genetically Labeled Premyelinating Oligodendrocytes: Bridging Oligodendrogenesis and Neuronal Activity.

To myelinate axons, oligodendrocyte precursor cells (OPCs) must stop dividing and differentiate into premyelinating oligodendrocytes (preOLs). PreOLs are thought to survey and begin ensheathing nearby axons, and their maturation is often stalled at human demyelinating lesions. Lack of genetic tools to visualize and manipulate preOLs has left this critical differentiation stage woefully understudied.

Mechanistic origins of temperature scaling in the early embryonic cell cycle.

Temperature profoundly impacts organismal physiology and ecological dynamics, particularly affecting ectothermic species and making them especially vulnerable to climate changes. Although complex physiological processes usually involve dozens of enzymes, empirically it is found that the rates of these processes often obey the Arrhenius equation, which was originally derived for single-enzyme-catalyzed reactions. Here we have examined the temperature scaling of the early embryonic cell cycle, with the goal of understanding why the Arrhenius equation approximately holds and why it breaks down at temperature extremes.

Clinically meaningful classes of financial toxicity for patients with diabetes.

Aims: This study aims to improve the interpretability and clinical utility of the COmprehensive Score for financial Toxicity-Functional Assessment of Chronic Illness Therapy (COST-FACIT) by identifying distinct financial toxicity classes in adults with diabetes.

Methods: Data included a sample of 600 adults with Type 1 or Type 2 diabetes and high A1c. Latent Class Analysis was used to identify subgroups of patients based on COST-FACIT score patterns.

Exploring novel determinants of exercise behavior: a lagged exposure-wide approach.

Unlabelled: Many middle-aged to older adults do not engage in regular exercise at all, despite its importance for healthy aging. Extensive research grounded in behavioral and social science theories has identified numerous determinants of exercise. However, few studies used an exposure-wide approach, a data-driven exploratory method particularly useful for identifying novel determinants.

The impact of race, ethnicity, and socioeconomic status on early adolescent sleep disturbances for youth exposed to adverse childhood experiences.

Background: Adverse childhood experiences (ACEs) may increase the risk for adolescent sleep disturbances, though the impact of race, ethnicity, and socioeconomic status (SES) remains unclear.

Objective: We sought to determine the direct and moderating impact of race, ethnicity, family SES, and community SES on sleep disturbances across early adolescence for ACE-exposed youth.

Participants And Setting: This secondary analysis used longitudinal Adolescent Brain Cognitive Development Study® data (2016-2022) from youth who experienced ≥1 ACE by age 9-10 years.

NEK7 phosphorylation amplifies NLRP3 inflammasome activation downstream of potassium efflux and gasdermin D.

The NLRP3 inflammasome plays a critical role in innate immunity and inflammatory diseases. NIMA-related kinase 7 (NEK7) is essential for inflammasome activation, and its interaction with NLRP3 is enhanced by K efflux. However, the mechanism by which K efflux promotes this interaction remains unknown.

Deciphering neutrophil dynamics: Enhanced phagocytosis of elastic particles and impact on vascular-targeted carrier performance.

Particle elasticity has widely been established to substantially influence immune cell clearance and circulation time of vascular-targeted carriers (VTCs). However, prior studies have primarily investigated interactions with macrophages, monocytic cell lines, and in vivo murine models. Interactions between particles and human neutrophils remain largely unexplored, although they represent a critical aspect of VTC performance.

Development of an implementation intervention to promote adoption of the COMFORT clinical practice guideline for peripartum pain management: a qualitative study.

Background: Pain management after childbirth is widely variable, increasing risk of untreated pain, opioid harms, and inequitable experiences of care. The Creating Optimal Pain Management FOR Tailoring Care (COMFORT) clinical practice guideline (CPG) seeks to promote evidence-based, equitable acute peripartum pain management in the United States. We aimed to identify contextual conditions (i.

Empathy is associated with older adults' social behaviors and verbal emotional expressions throughout the day.

Empathy plays a crucial role in promoting older adults' interpersonal experiences, but it remains unclear how these benefits of empathy occur. To address this gap, we examined associations between empathy and how older adults behave and express emotions during their daily interpersonal encounters. Participants included 268 adults aged 65+ (46% men, n = 124) from the Daily Experiences and Well-being Study.

Identification of a selective pyruvate dehydrogenase kinase 1 (PDHK1) chemical probe by virtual screening.

PDHK1 is a non-canonical Ser/Thr kinase that negatively regulates the pyruvate dehydrogenase complex (PDC), restricting entry of acetyl-CoA into the tricarboxylic acid (TCA) cycle and downregulating oxidative phosphorylation. In many glycolytic tumors, PDHK1 is overexpressed to suppress activity of the PDC and cause a shift in metabolism toward an increased reliance on glycolysis (the Warburg effect). Genetic studies have shown that knockdown or knockout of PDHK1 reverts this phenotype and inhibits tumor growth in vitro and in vivo, but chemical tools to pharmacologically validate and build upon these data are lacking.

Sub-terahertz transmissive reconfigurable intelligent surface for integrated beam steering and self-OOK-modulation.

Boasting superior flexibility in beam manipulation and a simpler framework than traditional phased arrays, terahertz metasurface-based phased arrays show great promise for 5G-A/6G communication networks. Compared with the reflective reconfigurable intelligent surface (reflective RIS), the transmissive RIS (TRIS) offers more feasibility for transceiver multiplexing systems to meet the growing demand for high-performance beam tracking in terahertz communication and radar systems. However, the terahertz TRIS encounters greater challenges in phase shift, beam efficiency, and complex circuitry.

Promoter analysis reveals conserved 30-base-pair core sequences controlling the nonhair-cell preferential expression of WEREWOLF in Arabidopsis.

The root epidermis of Arabidopsis (Arabidopsis thaliana) consists of two distinct cell types: hair (H) cells and non-hair (N) cells, whose patterning is regulated by a network of genes. Among these, the WEREWOLF (WER) gene, encoding an R2R3 MYB transcription factor, acts as a master regulator by promoting the expression of key downstream genes, such as GLABRA2 and CAPRICE. However, the mechanisms controlling WER expression have remained largely unexplored.

Associations of prenatal urinary melamine, melamine analogues, and aromatic amines with gestational duration and fetal growth in the ECHO Cohort.

Melamine, its analogues, and aromatic amines (AAs) were commonly detected in a previous study of pregnant women in the Environmental influences on Child Health Outcomes (ECHO) Cohort. While these chemicals have identified toxicities, little is known about their influences on fetal development. We measured these chemicals in gestational urine samples in 3 ECHO cohort sites to assess associations with birth outcomes (n = 1,231).

Evolution takes multiple paths to evolvability when facing environmental change.

Life at all scales is surprisingly effective at exploiting new opportunities, as demonstrated by the rapid emergence of antimicrobial resistance and novel pathogens. How populations acquire this level of evolvability and the various ways it aids survival are major open questions with direct implications for human health. Here, we use digital evolution to show that changing environments facilitate the simultaneous evolution of high mutation rates and a distribution of mutational effects skewed toward beneficial phenotypes.

mRNA decay pre-complex assembly drives timely cell-state transitions during differentiation.

Complexes that control mRNA stability and translation promote timely cell-state transitions during differentiation by ensuring appropriate expression patterns of key developmental regulators. The Drosophila RNA-binding protein brain tumor (Brat) promotes the degradation of target transcripts during the maternal-to-zygotic transition in syncytial embryos and uncommitted intermediate neural progenitors (immature INPs). We identify ubiquitin-specific protease 5 (Usp5) as a candidate Brat interactor essential for the degradation of Brat target mRNAs.

Competition increases the magnitude of dishonest reporting even when controlling for reward uncertainty.

Does competition increase cheating? This question has been investigated by both psychologists and economists in the past and received conflicting answers. Notably, prior experimental work compared how people behaved under competitive and non-competitive tasks that were associated with different levels of uncertainty about the reward that people would receive. We aim to experimentally disentangle the effect of competition from the effects of uncertain rewards.

Automated chest CT three-dimensional quantification of body composition: adipose tissue and paravertebral muscle.

This retrospective study developed an automated algorithm for 3D segmentation of adipose tissue and paravertebral muscle on chest CT using artificial intelligence (AI) and assessed its feasibility. The study included patients from the Boston Lung Cancer Study (2000-2011). For adipose tissue quantification, 77 patients were included, while 245 were used for muscle quantification.

Functional anatomy of zinc finger antiviral protein complexes.

ZAP is an antiviral protein that binds to and depletes viral RNA, which is often distinguished from vertebrate host RNA by its elevated CpG content. Two ZAP cofactors, TRIM25 and KHNYN, have activities that are poorly understood. Here, we show that functional interactions between ZAP, TRIM25 and KHNYN involve multiple domains of each protein, and that the ability of TRIM25 to multimerize via its RING domain augments ZAP activity and specificity.

From evidence to advice in France, Germany, and the UK: transparency, accountability, and participation in pandemic science advice.

Politicians often claim to be "following science" but their claims are, reasonably, disputed. To claim to be following the science can mean that scientific evidence affects or legitimates decisions. The evidence that politicians are following science often comes from formal systems of advice that translate science into advice.