Assembly Graph as the Rosetta Stone of Ecological Assembly.

Ecological assembly-the process of ecological community formation through species introductions-has recently seen exciting theoretical advancements across dynamical, informational, and probabilistic approaches. However, these theories often remain inaccessible to non-theoreticians, and they lack a unifying lens. Here, I introduce the assembly graph as an integrative tool to connect these emerging theories.

Fragmenstein: predicting protein-ligand structures of compounds derived from known crystallographic fragment hits using a strict conserved-binding-based methodology.

Current strategies centred on either merging or linking initial hits from fragment-based drug design (FBDD) crystallographic screens generally do not fully leaverage 3D structural information. We show that an algorithmic approach (Fragmenstein) that 'stitches' the ligand atoms from this structural information together can provide more accurate and reliable predictions for protein-ligand complex conformation than general methods such as pharmacophore-constrained docking. This approach works under the assumption of conserved binding: when a larger molecule is designed containing the initial fragment hit, the common substructure between the two will adopt the same binding mode.

Pathogen delivery route impacts disease severity in experimental Mycoplasma ovipneumoniae infection of domestic lambs.

M. ovipneumoniae is a respiratory pathogen that can cause mild to moderate pneumonia and reduced productivity in domestic lambs. However, studies on both natural and experimental M.

An exploratory analysis of differences in serum protein expression by sex in patients with systemic sclerosis associated interstitial lung disease.

Background: Systemic sclerosis (SSc) is a rare connective tissue disease, frequently affecting the skin, lungs, and pulmonary vasculature. Approximately 30-50% of SSc patients develop interstitial lung disease (SSc-ILD), with 30-35% of related deaths attributed to it. Even though men are less likely to develop systemic sclerosis, they have a higher incidence of SSc-ILD than women, and they tend to develop it at a younger age with a higher mortality rate.

Solu: a cloud platform for real-time genomic pathogen surveillance.

Background: Genomic surveillance is extensively used for tracking public health outbreaks and healthcare-associated pathogens. Despite advancements in bioinformatics pipelines, there are still significant challenges in terms of infrastructure, expertise, and security when it comes to continuous surveillance. The existing pipelines often require the user to set up and manage their own infrastructure and are not designed for continuous surveillance that demands integration of new and regularly generated sequencing data with previous analyses.

Predictive equation derived from 6,497 doubly labelled water measurements enables the detection of erroneous self-reported energy intake.

Nutritional epidemiology aims to link dietary exposures to chronic disease, but the instruments for evaluating dietary intake are inaccurate. One way to identify unreliable data and the sources of errors is to compare estimated intakes with the total energy expenditure (TEE). In this study, we used the International Atomic Energy Agency Doubly Labeled Water Database to derive a predictive equation for TEE using 6,497 measures of TEE in individuals aged 4 to 96 years.

Sexual Networks and Behavioral Characteristics of HIV-Positive Male Military Members, Female Sex Workers, and Male Civilians.

Military members and female sex workers (FSWs) may be more likely to acquire or transmit HIV. Mapping HIV transmission across these high-risk populations and identifying behaviors associated with sexual network clustering are needed for effective HIV prevention approaches. A cross-sectional study recruited participants newly diagnosed with HIV among militaries, civilians, and FSWs in Zambia, Senegal, and Democratic Republic of the Congo (DRC).

Society of American Gastrointestinal and Endoscopic Surgeons guidelines development: Clinical Practice Guideline Update Standard Operating Procedure.

Introduction: The SAGES Guidelines Committee creates evidence-based clinical practice guidelines (CPGs). Updates which incorporate new evidence into the guidelines are necessary to maintain relevance for clinical use. A description of our standard operating procedure for this process is described here, which contributes to SAGES' commitment to producing high-quality clinical recommendations.

Rice transcription factor bHLH25 confers resistance to multiple diseases by sensing HO.

Hydrogen peroxide (HO) is a ubiquitous signal regulating many biological processes, including innate immunity, in all eukaryotes. However, it remains largely unknown that how transcription factors directly sense HO in eukaryotes. Here, we report that rice basic/helix-loop-helix transcription factor bHLH25 directly senses HO to confer resistance to multiple diseases caused by fungi or bacteria.

Soluble Fms-like tyrosine kinase-1 polymorphisms associated with severe-spectrum hypertensive disorders of pregnancy.

Background: sFLT-1 has been implicated in the pathogenesis of HDP. We aimed to examine the role of maternal and fetal polymorphisms in risk of HDP and severe-spectrum disease.

Methods: Cases of HDP (143) and controls (169) from mother-baby dyads were recruited at the Los Angeles County Women's and Children's Hospital (WCH).

Lifetime risk and projected burden of dementia.

Understanding the lifetime risk of dementia can inform public health planning and improve patient engagement in prevention. Using data from a community-based, prospective cohort study (n = 15,043; 26.9% Black race, 55.

Transforming an ATP-dependent enzyme into a dissipative, self-assembling system.

Nucleoside triphosphate (NTP)-dependent protein assemblies such as microtubules and actin filaments have inspired the development of diverse chemically fueled molecular machines and active materials but their functional sophistication has yet to be matched by design. Given this challenge, we asked whether it is possible to transform a natural adenosine 5'-triphosphate (ATP)-dependent enzyme into a dissipative self-assembling system, thereby altering the structural and functional mode in which chemical energy is used. Here we report that FtsH (filamentous temperature-sensitive protease H), a hexameric ATPase involved in membrane protein degradation, can be readily engineered to form one-dimensional helical nanotubes.

Epigenetic ageing clocks: statistical methods and emerging computational challenges.

Over the past decade, epigenetic clocks have emerged as powerful machine learning tools, not only to estimate chronological and biological age but also to assess the efficacy of anti-ageing, cellular rejuvenation and disease-preventive interventions. However, many computational and statistical challenges remain that limit our understanding, interpretation and application of epigenetic clocks. Here, we review these computational challenges, focusing on interpretation, cell-type heterogeneity and emerging single-cell methods, aiming to provide guidelines for the rigorous construction of interpretable epigenetic clocks at cell-type and single-cell resolution.

Somatic mutation as an explanation for epigenetic aging.

DNA methylation marks have recently been used to build models known as epigenetic clocks, which predict calendar age. As methylation of cytosine promotes C-to-T mutations, we hypothesized that the methylation changes observed with age should reflect the accrual of somatic mutations, and the two should yield analogous aging estimates. In an analysis of multimodal data from 9,331 human individuals, we found that CpG mutations indeed coincide with changes in methylation, not only at the mutated site but with pervasive remodeling of the methylome out to ±10 kilobases.

Accuracy of pathogen diagnostic codes for acute hematogenous musculoskeletal infections in children.

Administrative databases are powerful tools for pediatric research but lack patient-level microbiology results. This study aimed to determine the accuracy of pathogen discharge diagnosis codes for children hospitalized with acute hematogenous musculoskeletal infections (MSKIs). Medical records for 244 children hospitalized with acute hematogenous MSKIs were manually reviewed to determine which bacterial pathogen, if any, was identified for each MSKI based on microbiology results obtained during the hospitalization.

Staudinger Reaction-Responsive Coacervates for Cytosolic Antibody Delivery and TRIM21-Mediated Protein Degradation.

A low-molecular-weight compound whose structure strikes a fine balance between hydrophobicity and hydrophilicity may form coacervates via liquid-liquid phase separation in an aqueous solution. These coacervates may encapsulate and convoy proteins across the plasma membrane into the cell. However, releasing the cargo from the vehicle to the cytosol is challenging.

Two rodent suborders have evolved missing amino acids in the lipid-binding region of apolipoprotein E.

The order Rodentia comprises nearly 45% of all extant taxa, currently organized into 31 living families, some 450 genera, and roughly 2010 species (Kelt & Patton, 2020). Considering that rodents began evolving at least 66 million years ago, it is not surprising that they have diversified into five distinct suborders. With the advent of molecular biology, this difference can often be seen at the molecular level as well.

Evaluation of an AI-Based Voice Biomarker Tool to Detect Signals Consistent With Moderate to Severe Depression.

Purpose: Mental health screening is recommended by the US Preventive Services Task Force for all patients in areas where treatment options are available. Still, it is estimated that only 4% of primary care patients are screened for depression. The goal of this study was to evaluate the efficacy of machine learning technology (Kintsugi Voice, v1, Kintsugi Mindful Wellness, Inc) to detect and analyze voice biomarkers consistent with moderate to severe depression, potentially allowing for greater compliance with this critical primary care public health need.

Gender Differences in the Socioecological Contexts of Veterans Seeking Mental Health Services Following Military Sexual Trauma.

Military sexual trauma (MST) refers to sexual assault or harassment experienced during military service. Given the high prevalence of MST and negative mental and physical health outcomes that result from MST, Veterans Health Administration has identified a national priority for screening and treatment. An understanding of socioecological contexts of Veterans who seek mental health treatment to address difficulties following MST will support a holistic approach to care.