Structure of E6AP in complex with HPV16-E6 and p53 reveals a novel ordered domain important for E3 ligase activation.

High-risk human papillomavirus E6 oncoprotein is a model system for the recognition and degradation of cellular p53 tumor suppressor protein. There remains a gap in the understanding of the ubiquitin transfer reaction, including placement of the E6AP catalytic HECT domain of the ligase concerning the p53 substrate and how E6 itself is protected from ubiquitination. We determined the cryoelectron microscopy (cryo-EM) structure of the E6AP/E6/p53 complex, related the structure to in vivo modeling of the tri-molecular complex, and identified structural interactions associated with activation of the ubiquitin ligase function.

Cervicovaginal microbiome and natural history of Chlamydia trachomatis in adolescents and young women.

This study investigated the cervicovaginal microbiome's (CVM's) impact on Chlamydia trachomatis (CT) infection among Black and Hispanic adolescent and young adult women. A total of 187 women with incident CT were matched to 373 controls, and the CVM was characterized before, during, and after CT infection. The findings highlight that a specific subtype of bacterial vaginosis (BV), identified from 16S rRNA gene reads using the molBV algorithm and community state type (CST) clustering, is a significant risk factor for CT acquisition.

The regulatory landscape of 5' UTRs in translational control during zebrafish embryogenesis.

The 5' UTRs of mRNAs are critical for translation regulation during development, but their in vivo regulatory features are poorly characterized. Here, we report the regulatory landscape of 5' UTRs during early zebrafish embryogenesis using a massively parallel reporter assay of 18,154 sequences coupled to polysome profiling. We found that the 5' UTR suffices to confer temporal dynamics to translation initiation and identified 86 motifs enriched in 5' UTRs with distinct ribosome recruitment capabilities.

Decoding the blueprint of receptor binding by filoviruses through large-scale binding assays and machine learning.

Evidence suggests that bats are important hosts of filoviruses, yet the specific species involved remain largely unidentified. Niemann-Pick C1 (NPC1) is an essential entry receptor, with amino acid variations influencing viral susceptibility and species-specific tropism. Herein, we conducted combinatorial binding studies with seven filovirus glycoproteins (GPs) and NPC1 orthologs from 81 bat species.

Longitudinal single-cell profiles of lung regeneration after viral infection reveal persistent injury-associated cell states.

Functional regeneration of the lung's gas exchange surface following injury requires the coordination of a complex series of cell behaviors within the alveolar niche. Using single-cell transcriptomics combined with lineage tracing of proliferating progenitors, we examined mouse lung regeneration after influenza injury, demonstrating an asynchronously phased response across different cellular compartments. This longitudinal atlas of injury responses has produced a catalog of transient and persistent transcriptional alterations in cells as they transit across axes of differentiation.

Modeling non-genetic adaptation in tumor cells.

Treatment resistance poses a significant challenge in the care of cancer patients. Hirsch et al. applied computational and genomic approaches, examining gene expression dynamics from a mouse model of melanoma at single-cell resolution to reveal that semi-heritable non-genetic alterations in tumor cell populations confer adaptive resistance to treatment.

CDK2 activity crosstalk on the ERK kinase translocation reporter can be resolved computationally.

The mitogen-activated protein kinase (MAPK) pathway integrates growth factor signaling through extracellular signal-regulated kinase (ERK) to control cell proliferation. To study ERK dynamics, many researchers use an ERK activity kinase translocation reporter (KTR). Our study reveals that this ERK KTR also partially senses cyclin-dependent kinase 2 (CDK2) activity, making it appear as if ERK activity rises as cells progress through the cell cycle.

Vitamin A deficiency and male-specific effects on heart function in mice.

Hepatic stores of Vitamin A (retinol) are mobilized and metabolized in the heart following myocardial infarction. The physiological consequences of this mobilization are poorly understood. Here we used dietary depletion in a lecithin retinol acyltransferase mutant mouse line to induce Vitamin A deficiency and investigate the effects on cardiac function and recovery from myocardial infarction.

Establishing quality assurance for COVID-19 antigen tests in the Indo Pacific Region: A multi-site implementation study.

Background: Quality assurance programs (QAPs) are used to evaluate the analytical quality of a diagnostic test and provide feedback to improve quality processes in testing. Rapid diagnostic tests were used in both laboratory and non-laboratory settings to diagnose COVID-19, although varied in reported performance. We aimed to design and implement a QAP for antigen rapid diagnostic tests (Ag-RDTs) for COVID-19 in Cambodia, Lao PDR, and Papua New Guinea.

The role of the hippocampus in working memory and word reading: Novel neural correlates of reading among youth living in the context of economic disadvantage.

A left-lateralized cortical reading circuit underlies successful reading and fails to engage in individuals with reading problems. Studies identifying this circuit included youth from economically advantaged backgrounds and focused on cortical, not subcortical, structures. However, among youth with low scores on reading tests who are living in the context of economic disadvantage, this brain network is actively engaged during reading, despite persistent reading problems.

Healthcare Costs and Early Complications in Liver-Transplanted Patients With Portal Vein Thrombosis: Experience From a Colombian Reference Center.

Objectives: This study aimed to analyze the direct healthcare costs and early complications associated with pretransplant portal vein thrombosis (PVT) in cirrhotic patients undergoing their first orthotopic liver transplant (LT) at a hospital in Colombia from 2013 to 2021.

Methods: A registry-based retrospective follow-up study was conducted on cirrhotic patients aged 14 years or older who underwent their first LT at the San Vicente Fundación Rionegro Hospital between January 2013 and April 2021. The primary outcomes were early (30-day) vascular and biliary complications and direct healthcare costs.

Advances in our understanding of the estrous cycle and applications for improving targeted reproductive management in livestock.

The scientific discipline of endocrinology has been invaluable to our understanding of the estrous cycle. In the second half of the twentieth century the development of immunoassay technologies provided a rapid and sensitive method to quantify circulating concentrations of reproductive hormones and relate them to stage of the estrous cycle and physiological status of the animal. Ovarian ultrasonography provided the ability to track the growth and regression of ovarian structures within the same animal across the estrous cycle in real time and, in combination with hormonal profiling, accurately identify mechanisms regulating the estrous cycle and early pregnancy.

Occurrence, seasonal distribution and probabilistic source-specific health risk assessment of dissolved trace metals in southwestern rivers, Nigeria.

The presence of trace metals (TMs) in river systems at certain levels can cause toxicity and pose significant risks to human health. In this study, nine TMs (Ba, Cd, Cr, Cu, Fe, Mn, Ni, Pb, and Zn) were determined by inductively coupled plasma optical emission spectrometry (ICP-OES) in water samples collected from six major rivers from southwestern Nigeria during both dry and wet seasons. Across both seasons, the mean concentrations (mg/L) ranged from 0.

Environmental contaminants assessment for frequently harvested migratory waterfowl in the Northeast Atlantic flyway.

Waterfowl serve as indicators of ecosystem health and represent a pathway of contaminant exposure for hunters who consume them. In the northeast Atlantic Flyway, data on baseline contaminant loads in waterfowl are lacking. We assessed five species of commonly harvested (and consumed) waterfowl for mercury, polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans, polychlorinated biphenyls (PCBs), organochlorine pesticides (OCPs), and per- and polyfluoroalkyl substances (PFAS).

Effects of warning information at medication initiation on deprescribing intentions in older adults: A hypothetical vignette.

Objectives: To explore to what degree providing patients warning information about the long-term risks of a medication would affect their subsequent desire to discontinue it.

Methods: We conducted a vignette-based online experiment in which participants aged ≥ 65 years from the United States were asked to imagine starting and subsequently stopping omeprazole. Participants were randomized to one of four vignettes about starting omeprazole (potential long-term harms or no harm information; OTC vs.

Opening the black box: Think Aloud as a method to study the spontaneous stream of consciousness.

Asking participants to Think Aloud is a common method for studying conscious experience, but it remains unclear whether this approach alters thought qualities-such as meta-awareness, rate of topic shifts, or the content of thoughts in task-absent conditions. To investigate this, we conducted two studies comparing thinking aloud to thinking silently. In Study 1, 111 participants alternated between 15-minute intervals of verbalizing and silently reflecting on their stream of consciousness in a counterbalanced design.

d-Limonene inhibits cytokines and chemokines expression by regulating NF-kappaB and STAT in HaCat cells and DNCB-induced atopic dermatitis in BALB/c mice.

Background: Atopic dermatitis (AD) is a chronic inflammatory skin disorder characterized by itching and redness, affecting individuals of all ages and significantly impairing their quality of life. The prevalence of AD is rising, posing serious health concern. Relief of itching is a primary treatment objective; however, steroid treatments can lead to adverse effects, including skin barrier thinning.

Can ecosystem services supply match local residents' perception: Linking macro-ESs and micro-individual perceptions in the Yellow River Basin.

Residents' satisfaction perceptions of ecosystem services (ESs) are essential for the ecological protection and high-quality development of the Yellow River Basin (YRB). Existing studies lacks large-scale survey of local residents' satisfaction perception at urban scale within river basins, and has not effectively explored the matching relationship between the ESs supply and the perceptions of local residents. To address this gap, this study develops a database on nine ESs supply and individual perceptions of the YRB, constructs a comprehensive framework to quantify the matching of ESs supply and local residents' satisfaction perceptions, and proposes targeted strategy.

Mangrove-based carbon market projects: What stakeholders need to address during pre-feasibility assessment.

Mangrove-based carbon market projects (MbCMP) aim to conserve, protect and restore mangrove habitats in order to generate high quality blue carbon credits via a crediting program, as a contribution to climate change mitigation/adaptation, biodiversity conservation, ecosystem services provision and local socio-economic development. The blue carbon credits generated are transferable, verifiable and sold through carbon markets to earn additional income for governments and local communities. The main aim of the paper is to provide important considerations for pre-field planning, that is, how challenges associated with fieldwork, project implementation, and monitoring reporting and verification (MRV) can be addressed with proper pre-field planning.

Genome assembly and multiomic analyses reveal insights into flower and bark colors of Lagerstroemia excelsa.

Lagerstroemia excelsa is a unique plant species from China, holds a significant aesthetic and economic value, and plays a crucial role in landscape architecture and horticulture. Thus far, there is little genetic and genomic information available about this species, which limits its use in development of new cultivars. In this study, a high-quality genome map of L.

Long-term suppression of Microcystis aeruginosa by tannic acid: Risks of microcystin pollution and proteomic mechanisms.

Harmful algal blooms are a critical eco-environmental issue with severe impacts on aquatic ecosystems and human health. Tannic acid (TA) has been suggested as an effective algal bloom control, but the molecular mechanisms of its interaction with algae cells and its effects on algal toxin release remain unclear. This study tracked toxin production and release in the toxigenic species Microcystis aeruginosa (M.

Impact of luteal blood perfusion and expression of estrus on pregnancy rates of Bos taurus embryo recipients exposed to fixed-time embryo transfer.

This study evaluated the impact of luteal blood perfusion (BP) and expression of estrus on pregnancy rates of Bos taurus embryo recipients exposed to fixed-timed embryo transfer (FTET) using a gonadotropin-releasing hormone (GnRH)- and progesterone-based ovulation synchronization protocol. Postpartum beef cows (n = 746) were exposed to a GnRH/progesterone-based ovulation synchronization protocol. Luteal morphometry and BP were assessed using color Doppler ultrasonography 9 days after CIDR removal concurrently with FTET.

Spatially constrained hyperpolarized 13C MRI pharmacokinetic rate constant map estimation using a digital brain phantom and a U-Net.

Fitting rate constants to Hyperpolarized [1-C]Pyruvate (HP C13) MRI data is a promising approach for quantifying metabolism in vivo. Current methods typically fit each voxel of the dataset using a least-squares objective. With these methods, each voxel is considered independently, and the spatial relationships are not considered during fitting.

Measurement of biomechanical properties of transversely isotropic biological tissue using traveling wave expansion.

The anisotropic mechanical properties of fiber-embedded biological tissues are essential for understanding their development, aging, disease progression, and response to therapy. However, accurate and fast assessment of mechanical anisotropy in vivo using elastography remains challenging. To address the dilemma of achieving both accuracy and efficiency in this inverse problem involving complex wave equations, we propose a computational framework that utilizes the traveling wave expansion model.