Recent ucr_som items

Contributions of Gray Matter Microstructure to Differences in Fluid Cognition and Episodic Memory Across the Healthy Adult Lifespan

Thu, 11 Jun 2026 00:00:00 +0000

Cognitive decline, in healthy older adults without cognitive impairment or dementia, has been associated with numerous microstructural alterations in brain tissue using magnetic resonance imaging (MRI). Prior studies have primarily linked age-related cognitive decline to alterations in white matter tissue, but methodological advances in diffusion-weighted imaging (dMRI) data acquisition and modeling now allow for these analyses to be extended to gray matter tissue. Here, using a sample of 152 healthy adults (18-88 years of age), we used a multicompartment dMRI model to assess (1) age-related differences in gray matter microstructure of functionally defined networks and (2) whether microstructural alterations accounted for age-related differences in episodic memory and speed-dependent fluid cognition. We observed significant age-related alterations in gray matter tissue in the form of nonlinear, age-related increases and decreases in intracellular and dispersed diffusion, respectively,...

The QuadMax Task: Parametrically Manipulating Associative Memory Load across the Adult Lifespan

Thu, 11 Jun 2026 00:00:00 +0000

Adults of all ages are worse at recognizing pairs of items that were previously seen together relative to the individual items, and this paired-associative memory deficit is exacerbated in aging. Less is known about memory for higher associative loads, which place greater demands on binding processes that link items into a cohesive memory trace, among other processes (e.g., working memory, recollection). In this study, adults across the lifespan (n = 250, 18-78 years) completed a novel recognition task in which they studied word pairs, triplets, and quadruplets and were tested on their memory for repeated, recombined, and novel word sets. Associative memory deficits were seen in adults of all ages as fewer correct responses to repeated sets (hits), more incorrect responses to recombined sets (recombined false alarm, FA), and larger differences between these measures (associative memory) at higher set sizes. In addition, older adults had worse associative memory...

The QuadMax Task: A Novel Parametric Manipulation of Associative Memory Load in Adults Across the Lifespan

Thu, 11 Jun 2026 00:00:00 +0000

Adults of all ages are worse at remembering which pairs of items were previously seen together relative to memory for the individual items, and this paired-associative memory deficit is exacerbated in aging. Less is known about memory for higher-order associations, including whether they place greater demands on the binding processes that link information into a cohesive memory trace. In this study, adults across the lifespan (Experiment 1: n = 250, 18-78 years) and in extreme age groups (Experiment 2: n = 64, 18-25 and 64-78 years) completed a novel recognition task in which they studied word pairs, triplets, and quadruplets and were later tested on their memory for repeated, recombined, and novel word sets. Associative memory deficits were seen in both experiments as the difference between correct responses to repeated (hits) and incorrect responses to recombined (recombined false alarm, FA) sets that decreased from pairs to quadruplets. In addition, older age groups had...

Connectome-based predictive modeling of grip strength: a marker of physical frailty

Thu, 11 Jun 2026 00:00:00 +0000

Introduction: Frailty is characterized by a persistent and progressive decline in functional capacity, leading to increased vulnerability to stressors and a heightened risk of adverse health outcomes, both physically and mentally. Despite frailty's prevalence in older adults, there is limited research on its neural substrates. Methods: In this study, we used connectome-based predictive modeling (CPM) to find a linear relationship between task-based connectomes taken from tasks that involved similar handgrip manipulations and a separate measure of physical frailty: the maximum grip strength in older adults. Results: We observed that the task-based connectomes were able to explain individual differences in grip strength, with the Subcortical and Cerebellum network, particularly the caudate nucleus functional connectivity, being the strongest predictor. Discussion: These findings demonstrate that task-based functional connectomes can serve as personalized markers for predicting individual...

Examining iron‐related off‐target binding effects of 18F‐AV1451 PET in the cortex of Aβ+ individuals

Thu, 11 Jun 2026 00:00:00 +0000

The presence of neurofibrillary tangles containing hyper-phosphorylated tau is a characteristic of Alzheimer's disease (AD) pathology. The positron emission tomography (PET) radioligand sensitive to tau neurofibrillary tangles (¹⁸F-AV1451) also binds with iron. This off-target binding effect may be enhanced in older adults on the AD spectrum, particularly those with amyloid-positive biomarkers. Here, we examined group differences in ¹⁸F-AV1451 PET after controlling for iron-sensitive measures from magnetic resonance imaging (MRI) and its relationships to tissue microstructure and cognition in 40 amyloid beta positive (Aβ+) individuals, 20 amyloid beta negative (Aβ-) with MCI and 31 Aβ- control participants. After controlling for iron, increased ¹⁸F-AV1451 PET uptake was found in the temporal lobe and hippocampus of Aβ+ participants compared to Aβ- MCI and control participants. Within the Aβ+ group, significant correlations were seen between ¹⁸F-AV1451...

Locus Coeruleus Engagement Drives Network Connectivity Dynamics In Humans And Rats

Thu, 11 Jun 2026 00:00:00 +0000

Locus Coeruleus Engagement Drives Network Connectivity Dynamics In Humans And Rats

Neuroimaging Measures of Iron and Gliosis Explain Memory Performance in Aging

Thu, 11 Jun 2026 00:00:00 +0000

Abstract Evidence from animal and histological studies have indicated that accumulation of iron in the brain results in reactive gliosis that contributes to cognitive deficits. The current study extends these findings to human cognitive aging and suggests that magnetic resonance imaging (MRI) techniques like quantitative relaxometry can be used to study iron and its effects in vivo . The effects of iron on microstructure and memory performance were examined using a combination of quantitative relaxometry and multi-compartment diffusion imaging in 35 young (21.06 ± 2.18 years) and 28 older (72.58 ± 6.47 years) adults, who also completed a memory task. Replicating past work, results revealed age-related increases in iron content (R 2 *) and diffusion, and decreases in memory performance. Independent of age group, iron content was significantly related to restricted (intracellular) diffusion in regions with low-moderate iron (hippocampus, caudate) and to all diffusion metrics in...

Aging of gray matter microstructure: A brain-wide characterization of, age group differences using NODDI

Thu, 11 Jun 2026 00:00:00 +0000

This study aimed to provide a complete characterization of age group differences in cortical lobar, hippocampal, and subcortical gray matter microstructure using a multi-compartment diffusion-weighted MRI (DWI) approach with parameters optimized for gray matter (Neurite Orientation Dispersion and Density Imaging, NODDI). 76 younger (undergraduate students) and 64 older (surrounding communities) adults underwent diffusion-, T1-, and susceptibility-weighted MRI. Results revealed eight unique patterns across the 12 regions of interest in the relative direction and magnitude of age effects across NODDI metrics, which were grouped into three prominent patterns: cortical gray matter had predominantly higher free diffusion in older than younger adults, the hippocampus and amygdala had predominantly higher dispersion of diffusion and intracellular diffusion in older than younger adults, and the putamen and globus pallidus had lower dispersion of diffusion in older than younger adults....

Age group differences in learning-related activity reflect task stage, not learning stage

Thu, 11 Jun 2026 00:00:00 +0000

Healthy aging is accompanied by declines in the ability to learn associations between events, even when their relationship cannot be described. Previous functional magnetic resonance imaging (fMRI) studies have attributed these implicit associative learning (IAL) deficits to differential engagement of the hippocampus and basal ganglia in older relative to younger adults in early and late stages of the task, respectively. However, these task stages have been confounded with age group differences in learning performance that emerge later and to a lesser degree in older adults. To disentangle the effects of task stage from learning stage (i.e., when there is significant evidence of learning) on age group differences in the neural substrates of IAL, we acquired fMRI data while 28 younger (20.8 ± 2.3 years) and 22 older (73.6 ± 6.8 years) healthy adults completed the Triplets Learning Task, in which the location of two cues predicted the location of a target with high (HF) or low...

Associations between iron and mean kurtosis in iron-rich grey matter nuclei in aging.

Thu, 11 Jun 2026 00:00:00 +0000

OBJECTIVE: Elevated kurtosis values have been observed in subcortical grey matter structures of patients with neurodegenerative diseases. Here, we examined relationships between iron measures and kurtosis in iron-rich subcortical grey matter structures.Please check and confirm the affiliation 4 for the author "Xiaoping P. Hu".Affiliation 4 for Xiaoping P. Hu was incorrect since he is not associated with that department. We have removed this affiliation. Thanks! MATERIALS AND METHODS: Multi-shell diffusion and multi-echo gradient echo acquisitions were used to derive mean kurtosis and iron measures (R₂* and magnetic susceptibility), respectively, in subcortical grey matter nuclei and white matter tracts in a discovery cohort (110 healthy older and 63 younger adults) and replication cohort (72 healthy older adults).Please confirm if the author names are presented accurately and in the correct sequence (Ilana J. Bennett and Xiaoping P. Hu). Also, kindly confirm the...

Handgrip strength relates to corticospinal tract microstructure in older adults

Thu, 11 Jun 2026 00:00:00 +0000

Handgrip strength relates to corticospinal tract microstructure in older adults

Iron content affects age group differences in associative learning-related fMRI activity

Thu, 11 Jun 2026 00:00:00 +0000

Brain regions accumulate different amounts of iron with age, with older adults having higher iron in the basal ganglia (globus pallidus, putamen, caudate) relative to the hippocampus. This has important implications for functional magnetic resonance imaging (fMRI) studies in aging as the presence of iron may influence both neuronal functioning as well as the measured fMRI (BOLD) signal, and these effects will vary across age groups and brain regions. To test this hypothesis, the current study examined the effect of iron on age group differences in task-related activity within each basal nuclei and the hippocampus. Twenty-eight younger and 22 older adults completed an associative learning task during fMRI acquisition. Iron content (QSM, R₂*) was estimated from a multi-echo gradient echo sequence. As previously reported, older adults learned significantly less than younger adults and age group differences in iron content were largest in the basal ganglia (putamen, caudate)....

TGFβ signaling is required during human and chick Neural Crest formation

Sun, 7 Jun 2026 00:00:00 +0000

Neural crest (NC) cells are multipotent cells unique to vertebrates that arise early in development, at the edge of the neural plate, and subsequently undergo an epithelial to mesenchymal transition, migrate throughout the body, and differentiate into many different derivatives, contributing to the formation of many organs and systems. NC induction research from multiple modeling organisms has identified critical roles for a few signaling pathways, including Wnt, BMP, FGF, Notch/ Delta, Indian Hedgehog, and Endothelin signaling (Prasad et al., 2019). Given the limitations of human embryo studies, pluripotent stem cell models of human NC formation have provided a resourceful alternative (Lee et al., 2007). Intriguingly, while TGFβ inhibition had not been identified as a signaling requirement for NC formation in any in vivo model organism, several pluripotent stem cell (PSC) models of human NC induction rely on TGFβ inhibition (Chambers et al., 2009). To address this issue, we evaluate...

Author Correction: A roadmap for equitable reuse of public microbiome data

Fri, 5 Jun 2026 00:00:00 +0000

Correction to: Nature Microbiologyhttps://doi.org/10.1038/s41564-025-02116-2, published online 26 September 2025. In the version of this article initially published, in the first paragraph of the “Survey on data reuse” section, a note on participant consent, confidentiality and institutional review was missing and has now been inserted in the HTML and PDF versions of the article.

Multifocal Renal Infarction and Diabetic Ketoacidosis: Diagnostic Challenges and Anticoagulation Management in a Complex Case.

Fri, 5 Jun 2026 00:00:00 +0000

BACKGROUND Incidental findings of renal infarct secondary to thrombosis in acutely ill patients present a unique challenge in diagnosis. We present a case of idiopathic renal infarct to highlight its workup and management and encourage further investigation of renal infarctions. CASE REPORT A 68-year-old woman with a past medical history of diet-controlled diabetes, hypertension, and hyperlipidemia presented to the Emergency Department (ED) for abdominal pain. She was found to be in diabetic ketoacidosis with pyelonephritis, so she was admitted to the Intensive Care Unit (ICU) for insulin and dextrose drip. Due to her abdominal pain, she underwent computed tomography (CT) of her abdomen and pelvis with contrast. This revealed multifocal infarcts of her right kidney with noncalcified thrombus at the proximal right renal artery. Subsequent CT angiography confirmed a right renal artery thrombus. She was started on subcutaneous enoxaparin and downgraded to basic level of care. Her...

Chemosis as an Initial Presentation of Systemic Lupus Erythematosus.

Fri, 5 Jun 2026 00:00:00 +0000

Systemic lupus erythematosus (SLE) can present in a multitude of ways, which can be confounding and misleading for a clinician. Chemosis as an initial presentation is rare and has only been documented on a few case reports. However, when present, simultaneous involvement of other organs is likely. We present a previously healthy 29-year-old male who presented with severe bilateral chemosis and was subsequently diagnosed with SLE and antiphospholipid syndrome. Complications included multiple acute cerebral infarcts, lupus psychosis, lupus pleuritis, and lupus nephritis. The patient recovered well with appropriate treatment and chemosis ultimately resolved. Recognizing chemosis as an initial presentation of SLE is vital for appropriate evaluation and timely treatment to prevent disease progression.

Decoding the origins of cellular self-organization for engineered biology

Thu, 4 Jun 2026 00:00:00 +0000

Decoding the origins of cellular self-organization for engineered biology

Visual Impairment and the Incidence of Concussions Among Youth Football Athletes

Thu, 4 Jun 2026 00:00:00 +0000

Background

Concussions are a prevalent concern in contact sports, particularly among youth American football players. While extensive research has examined concussion mechanics, the relationship between visual impairment and concussion risk remains understudied.

Purpose

To investigate the incidence of concussions among visually impaired versus non-visually impaired youth football players to inform clinical practice and preventive measures.

Study design

Cohort study; Level of evidence, 3.

Methods

A retrospective cohort study was performed using the TriNetX US Collaborative Network. Pediatric athletes aged 5 to 17 years with documented football participation were identified using International Classification of Diseases, Tenth Revision, codes. Visual impairment (H46-H47, H52-H54) was required to precede the index football encounter by ≥1 month. Concussions (S06.0) and concussion with loss of consciousness (LOC) (S06.0X1-S06.0X9) were assessed within...

Screening for Toxic Stress Response and Buffering Factors: A Case-Based, Trauma-Informed Approach to Health Equity

Thu, 4 Jun 2026 00:00:00 +0000

Introduction: Exposure to adverse childhood experiences (ACEs) can lead to a toxic stress response with impacts on health that affect health equity. As part of our Health Equity, Social Justice, and Anti-racism curriculum, our aim was to introduce second-year medical students to a case-based method using a template-based screening and application of toxic stress, buffering factors, and resiliency-fostering tools to address health disparities and inequities with a trauma-informed care approach. Methods: We developed an asynchronous e-learning module that demonstrated the impact of ACEs by introducing students to screening for toxic stress response and buffering factors on health, their role as health equity determinants, and the use of brief in-clinic resilience-fostering tools in patient care. This was followed by a synchronous, facilitated, small-group, virtual discussion of a clinical case. Pre- and postworkshop surveys assessed changes in knowledge, skills, and attitudes. A...

Effects of environmental setting and diet on the gut microbial ecology of eastern hellbenders (Cryptobranchus alleganiensis alleganiensis)

Mon, 25 May 2026 00:00:00 +0000

BackgroundEastern hellbenders (Cryptobranchus alleganiensis alleganiensis) have undergone substantial population declines throughout their range, leading them to become the focus of increased conservation efforts, including care in zoo and university settings. However, effective implementation of such conservation strategies often relies on a comprehensive understanding of host health, which can be directly influenced by the gut microbiome, yet characterization of gut microbiota often remains overlooked in ex situ conservation facilities. Additionally, effects on the gut microbiome associated with releasing zoo-reared animals into the wild are poorly understood. Therefore, these circumstances make hellbenders an ideal species to examine the relationship between zoo management strategies and gut microbial dynamics.Methods16S rRNA sequencing was used to investigate dissimilarities between the gut microbiome of hellbenders in zoo and wild settings and to evaluate the impact of implementing...

ThIEF: Finding Genome-wide Trajectories of Epigenetics Marks

Thu, 21 May 2026 00:00:00 +0000

We address the problem of comparing multiple genome-wide maps representing nucleosome positions or specific histone marks. These maps can originate from the comparative analysis of ChIP-Seq/MNase-Seq/FAIRE-Seq data for different cell types/tissues or multiple time points. The input to the problem is a set of maps, each of which is a list of genomics locations for nucleosomes or histone marks. The output is an alignment of nucleosomes/histone marks across time points (that we call trajectories), allowing small movements and gaps in some of the maps. We present a tool called ThIEF (TrackIng of Epigenetic Features) that can efficiently compute these trajectories. ThIEF comes into two "flavors": ThIEF:Iterative finds the trajectories progressively using bipartite matching, while ThIEF:LP solves a k-partite matching problem on a hyper graph using linear programming. ThIEF:LP is guaranteed to find the optimal solution, but it is slower than ThIEF:Iterative. We demonstrate the utility...

COVID-19 associated rhabdomyolysis leading to major amputation in the absence of macrovascular thrombosis.

Thu, 21 May 2026 00:00:00 +0000

A 50 year old patient presented with bilateral lower extremity weakness, lethargy, and dyspnea. Nasopharyngeal swab was positive for SARS-CoV-2. She progressed to acute hypoxemic respiratory failure and hemodynamic instability requiring intubation, pressor support, and hemodialysis. Maculopapular rashes developed on bilateral lower extremities with progressively worsening rhabdomyolysis. Bilateral lower extremity fasciotomies were performed with subsequent serial operative debridements to remove necrotic muscle. One month later, she required a right above knee amputation. There was no evidence of macrovascular thrombosis. A high clinical suspicion of rhabdomyolysis in COVID-19 patients is necessary to avoid major limb loss.

OMGS: Optical Map-Based Genome Scaffolding

Thu, 21 May 2026 00:00:00 +0000

Due to the current limitations of sequencing technologies, de novo genome assembly is typically carried out in two stages, namely contig (sequence) assembly and scaffolding. While scaffolding is computationally easier than sequence assembly, the scaffolding problem can be challenging due to the high repetitive content of eukaryotic genomes, possible mis-joins in assembled contigs and inaccuracies in the linkage information. Genome scaffolding tools either use paired-end/mate-pair/linked/Hi-C reads or genome-wide maps (optical, physical or genetic) as linkage information. Optical maps (in particular Bionano Genomics maps) have been extensively used in many recent large-scale genome assembly projects (e.g., goat, apple, barley, maize, quinoa, sea bass, among others). However, the most commonly used scaffolding tools have a serious limitation: they can only deal with one optical map at a time, forcing users to alternate or iterate over multiple maps. In this paper, we introduce a...

Selfish: discovery of differential chromatin interactions via a self-similarity measure

Thu, 21 May 2026 00:00:00 +0000

MOTIVATION: High-throughput conformation capture experiments, such as Hi-C provide genome-wide maps of chromatin interactions, enabling life scientists to investigate the role of the three-dimensional structure of genomes in gene regulation and other essential cellular functions. A fundamental problem in the analysis of Hi-C data is how to compare two contact maps derived from Hi-C experiments. Detecting similarities and differences between contact maps are critical in evaluating the reproducibility of replicate experiments and for identifying differential genomic regions with biological significance. Due to the complexity of chromatin conformations and the presence of technology-driven and sequence-specific biases, the comparative analysis of Hi-C data is analytically and computationally challenging. RESULTS: We present a novel method called Selfish for the comparative analysis of Hi-C data that takes advantage of the structural self-similarity in contact maps. We define a novel...

Evaluating Imatinib's Affinities and Specificities for Tyrosine Kinases Using Molecular Dynamics Simulations

Thu, 21 May 2026 00:00:00 +0000

Computational chemistry lets us model intermolecular interactions in ways assays cannot. My project focuses on the multi-kinase interactions of the cancer drug, imatinib. Most cancer drugs target one kinase, but some affect multiple kinases. Imatinib treats chronic myeloid leukemia by targeting ABL kinase. Proteomics data reveals it can interact with other kinases, such as KIT to treat gastrointestinal stromal tumors, but the mechanisms are unknown. Imatinib has different affinities for similar kinases, such as a 3000x difference between ABL and SRC, despite sharing 50% structural homology. Here, I investigate the conformational differences between free and imatinib-bound ABL, KIT, and SRC using Molecular Dynamics simulations to understand the key imatinib-kinase interactions. The alignment analysis shows the docked conformations are similar to co-crystal structures in the Protein Data Bank. Root-mean-square-deviation and fluctuation (RMSD and RMSF) analysis show that all simulations...

Bisulfite‐Conversion‐Based Methods for DNA Methylation Sequencing Data Analysis

Thu, 21 May 2026 00:00:00 +0000

Various techniques are available to profile DNA methylation, either genome‐wide or targeted at specific regions, such as CpG islands and gene promoters. In general, these techniques are divided into two categories: enrichment based and bisulfite conversion based methods. DNA methylation has been associated with gene expression, imprinting, transposon silencing, X‐chromosome inactivation, embryonic development, and cancer. Bisulfite‐conversion‐based methods involve the following three steps: chemical conversion of non‐methylated cytosines to uracils by treating DNA with sodium bisulfite; PCR amplification, and sequencing size‐selected DNA fragments. Sequencing errors, adapter contamination, end‐repair, and single‐nucleotide polymorphisms (SNPs) may affect erroneous methylation calls. Two common major performance measurements of an aligner for BS‐reads are mapping accuracy and methylation call accuracy. Both local alignment and alignment with indels are needed in order to map the...

Efficient and Accurate Detection of Topologically Associating Domains from Contact Maps

Thu, 21 May 2026 00:00:00 +0000

Continuous improvements to high-throughput conformation capture (Hi-C) are revealing richer information about the spatial organization of the chromatin and its role in cellular functions. Several studies have confirmed the existence of structural features of the genome 3D organization that are stable across cell types and conserved across species, called topological associating domains (TADs). The detection of TADs has become a critical step in the analysis of Hi-C data, e.g., to identify enhancer-promoter associations. Here we present East, a novel TAD identification algorithm based on fast 2D convolution of Haar-like features, that is as accurate as the state-of-the-art method based on the directionality index, but 75-80× faster. East is available in the public domain at https://github.com/ucrbioinfo/EAST.

Heterogeneous CPU+GPU-Enabled Simulations for DFTB Molecular Dynamics of Large Chemical and Biological Systems

Thu, 21 May 2026 00:00:00 +0000

We introduce a new heterogeneous CPU+GPU-enhanced DFTB approach for the routine and efficient simulation of large chemical and biological systems. Compared to homogenous computing with conventional CPUs, heterogeneous computing approaches exhibit substantial performance with only a modest increase in power consumption, both of which are essential to upcoming exascale computing initiatives. We show that DFTB-based molecular dynamics is a natural candidate for heterogeneous computing since the computational bottleneck in these simulations is the diagonalization of the Hamiltonian matrix, which is performed several times during a single molecular dynamics trajectory. To thoroughly test and understand the performance of our heterogeneous CPU+GPU approach, we examine a variety of algorithmic implementations, benchmarks of different hardware configurations, and applications of this methodology on several large chemical and biological systems. Finally, to demonstrate the capability of...

RAmbler: de novo genome assembly of complex repetitive regions

Thu, 21 May 2026 00:00:00 +0000

Complex repetitive regions (also known as segmental duplications) in eukaryotic genomes often contain essential functional and regulatory information. Despite remarkable algorithmic progress in genome assembly in the last twenty years, modern de novo assemblers still struggle to accurately reconstruct these highly repetitive regions. When sequenced reads will be long enough to span all repetitive regions, the problem will be solved trivially. However, even the third generation of sequencing technologies on the market cannot yet produce reads that are sufficiently long (and accurate) to span every repetitive region in large eukaryotic genomes. In this work, we introduce a novel algorithm called RAmbler to resolve complex repetitive regions based on high-quality long reads (i.e., PacBio HiFi). We first identify potentially repetitive regions by mapping the HiFi reads to the draft genome assembly. Regions with sequencing coverage much higher then the average indicate a collapsed...

Higher Classification Accuracy of Short Metagenomic Reads by Discriminative Spaced k-mers

Thu, 21 May 2026 00:00:00 +0000

The growing number of metagenomic studies in medicine and environmental sciences is creating new computational demands in the analysis of these very large datasets. We have recently proposed a time-efficient algorithm called Clark that can accurately classify metagenomic sequences against a set of reference genomes. The competitive advantage of Clark depends on the use of discriminative contiguousk-mers. In default mode, Clark’s speed is currently unmatched and its precision is comparable to the state-of-the-art, however, its sensitivity still does not match the level of the most sensitive (but slowest) metagenomic classifier. In this paper, we introduce an algorithmic improvement that allows Clark’s classification sensitivity to match the best metagenomic classifier, without a significant loss of speed or precision compared to the original version. Finally, on real metagenomes, Clark can assign with high accuracy a much higher proportion of short reads than its closest competitor....

Comparative structural analysis of protein complexes with SPICE.

Thu, 21 May 2026 00:00:00 +0000

Computational tools for studying the structure of protein complexes are essential for providing mechanistic insights into protein-protein interactions and therapeutic drug design. Here, we present SPICE (Structural Protein Interaction Complex Evaluator), a web-based platform that allows structural biologists to perform rapid, modular analyses of protein complexes directly from Protein Data Bank (PDB) structures. SPICE allows users to define and execute analysis workflows via an intuitive web interface, reducing analysis times from minutes to seconds. The platform offers a broad range of analytical capabilities, including (i) detection of hydrogen bonds, salt bridges, and disulfide bonds; (ii) protein-protein interface mapping; and (iii) computation of solvent accessibility, van der Waals energetics, and other key geometric descriptors. SPICE further provides interactive 3D visualization and supports comparative analyses across multiple complexes, enabling the study of mutational...

mClass: Cancer Type Classification with Somatic Point Mutation Data

Thu, 21 May 2026 00:00:00 +0000

Cancer is a complex disease associated with abnormal DNA mutations. Not all tumors are cancerous and not all cancers are the same. Correct cancer type diagnosis can indicate the most effective drug therapy and increase survival rate. At the molecular level, it has been shown that cancer type classification can be carried out from the analysis of somatic point mutation. However, the high dimensionality and sparsity of genomic mutation data, coupled with its small sample size has been a hindrance in accurate classification of cancer. We address these problems by introducing a novel classification method called mClass that accounts for the sparsity of the data. mClass is a feature selection method that ranks genes based on their similarity across samples and employs their normalized mutual information to determine the set of genes that provide optimal classification accuracy. Experimental results on TCGA datasets show that mClass significantly improves testing accuracy compared to...

Associations between iron and mean kurtosis in iron-rich grey matter nuclei in aging

Mon, 18 May 2026 00:00:00 +0000

ObjectiveElevated kurtosis values have been observed in subcortical grey matter structures of patients with neurodegenerative diseases. Here, we examined relationships between iron measures and kurtosis in iron-rich subcortical grey matter structures.Please check and confirm the affiliation 4 for the author "Xiaoping P. Hu".Affiliation 4 for Xiaoping P. Hu was incorrect since he is not associated with that department. We have removed this affiliation. Thanks! Materials and methodsMulti-shell diffusion and multi-echo gradient echo acquisitions were used to derive mean kurtosis and iron measures (R2* and magnetic susceptibility), respectively, in subcortical grey matter nuclei and white matter tracts in a discovery cohort (110 healthy older and 63 younger adults) and replication cohort (72 healthy older adults).Please confirm if the author names are presented accurately and in the correct sequence (Ilana J. Bennett and Xiaoping P. Hu). Also, kindly confirm the details in the...

FamilyBloom: Examining Ecologies of Collaboration in Family-Centered Health Tracking

Wed, 6 May 2026 00:00:00 +0000

Family health informatics tools can help support well-being with shared data tracking. Prior work typically focused on shared data review, but often in specific moments, like bedtime, or centered on caregiving of children or elderly members. To investigate how tracking can support mutual health collaboration between family members pervasively across daily contexts, we designed and deployed FamilyBloom, a glanceable smartwatch and home display system for mood and goal tracking. Twelve families with both neurotypical and ADHD members used FamilyBloom for three months on average. Our findings reveal how family-centered tracking created collaboration opportunities and tensions across multiple ecological systems: individual self-regulation, collaborations within family dynamics, involvement of care networks with varying trust levels, institutional school constraints and cultural stigma, and temporality of regular routines and crisis periods. We discuss an ecosystem-aware approach to...

Developing health care provider knowledge, confidence, and cultural sensitivity through resident transgender training: a controlled educational study

Wed, 6 May 2026 00:00:00 +0000

BackgroundTransgender and gender-diverse (TGD) individuals face substantial health disparities as a result of discrimination and poor provider competence in understanding their health needs. Relatively little work has been done studying educational interventions targeted toward increasing residents’ knowledge and ability to treat TGD individuals with sensitivity. We studied the effectiveness of implementing a lecture series on transgender health in preparing internal medicine residents to care for the TGD population.MethodsBoth study and control participants were recruited through their affiliated internal medicine residency programs. The study design was a pre-post controlled educational study. A lecture series was developed at Riverside University Health System as the educational intervention. We used a Transgender Assessment survey developed for the study to determine changes in the residents’ knowledge, self-confidence, and knowledge of barriers to care during the study period...

A roadmap for equitable reuse of public microbiome data

Mon, 27 Apr 2026 00:00:00 +0000

Science benefits from rapid open data sharing, but current guidelines for data reuse were established two decades ago, when databases were several million times smaller than they are today. These guidelines are largely unfamiliar to the scientific community, and, owing to the rapid increase in biological data generated in the past decade, they are also outdated. As a result, there is a lack of community standards suited to the current landscape and inconsistent implementation of data sharing policies across institutions. Here we discuss current sequence data sharing policies and their benefits and drawbacks, and present a roadmap to establish guidelines for equitable sequence data reuse, developed in consultation with a data consortium of 167 microbiome scientists. We propose the use of a Data Reuse Information (DRI) tag for public sequence data, which will be associated with at least one Open Researcher and Contributor ID (ORCID) account. The machine-readable DRI tag indicates...

TEACHING AND ADVANCING SUBSTANCE USE CARE FOR ADOLESCENTS AND YOUNG ADULTS

Thu, 23 Apr 2026 00:00:00 +0000

TEACHING AND ADVANCING SUBSTANCE USE CARE FOR ADOLESCENTS AND YOUNG ADULTS

Inferring fungal cis-regulatory networks from genome sequences via unsupervised and interpretable representation learning

Thu, 23 Apr 2026 00:00:00 +0000

Gene expression patterns are determined to a large extent by transcription factor (TF) binding to noncoding regulatory regions in the genome. However, gene expression cannot yet be systematically predicted from genome sequences, in part because nonfunctional matches to the sequence patterns (motifs) recognized by TFs occur frequently throughout the genome. Large-scale functional genomics data for many TFs has enabled characterization of regulatory networks in experimentally accessible cells such as budding yeast. Beyond yeast, fungi are important industrial organisms and pathogens, but large-scale functional data is only sporadically available. Uncharacterized regulatory networks control key pathways and gene expression programs associated with fungal phenotypes. Here, we explore a sequence-only approach to inferring regulatory networks by leveraging the 100s of genomes now available for many clades of fungi. We use gene orthology as the learning signal to infer interpretable,...

University of California, Riverside School of Medicine.

Thu, 23 Apr 2026 00:00:00 +0000

University of California, Riverside School of Medicine.

The hidden taxonomic novelty of anamorphic basidiomycetous yeasts in the phyllosphere and tidal flats in China

Thu, 23 Apr 2026 00:00:00 +0000

Basidiomycetous yeasts are taxonomically and ecologically diverse. While the phyllosphere of plants in China has been the subject of extensive research on yeast biodiversity, many unique and remote habitats remain significantly underexplored for their yeast species. The objective of this study was to investigate the hidden taxonomic novelty of basidiomycetous yeasts in these distinctive niches to comprehensively refine the current phylogenetic understanding. During intensive investigations, 164 yeast strains were identified from various samples collected from the phyllosphere and tidal flats in China. These isolates underwent detailed multi-gene phylogenetic analyses combined with phenotypic characterization for taxonomic placement. The analyses revealed a remarkable level of hidden diversity. These 164 isolates represent one new order (Sterigmoblongales), two new families (Sterigmoblongaceae and Turchettiaceae), five new genera (Nakasea, Sterigmoblongus, Buzzinia, Gracilitas,...

Effects of environmental setting and diet on the gut microbial ecology of eastern hellbenders (Cryptobranchus alleganiensis alleganiensis)

Thu, 23 Apr 2026 00:00:00 +0000

ABSTRACT Background Eastern hellbenders ( Cryptobranchus alleganiensis alleganiensis ) have undergone substantial population declines throughout their range, leading them to become the focus of increased conservation efforts, including care in zoo and university settings. However, effective implementation of such conservation strategies often relies on a comprehensive understanding of host health, which can be directly influenced by the gut microbiome, yet characterization of gut microbiota often remains overlooked in ex situ conservation facilities. Additionally, effects on the gut microbiome associated with releasing zoo-reared animals into the wild are poorly understood. Therefore, these circumstances make hellbenders an ideal species to examine the relationship between zoo management strategies and gut microbial dynamics. Methods 16S rRNA sequencing was used to investigate dissimilarities between the gut microbiome of hellbenders in zoo and wild settings and to evaluate...

Phyling: phylogenetic inference from annotated genomes

Thu, 23 Apr 2026 00:00:00 +0000

Phyling is a fast, scalable, and user-friendly tool supporting phylogenomic reconstruction of species phylogenies directly from protein-encoded genomic data. It identifies orthologous genes by searching protein sequences against a curated set of Hidden Markov Models profiles, consisting of single-copy orthologs derived from the BUSCO database. To optimize the speed of the final inference, Phyling includes a module to filter aligned orthologs based on their phylogenetic informativeness. Finally, Phyling provides a companion wrapper for automated species tree construction using either consensus or concatenation strategies. Phyling efficiently resolves large phylogenies by optimizing memory usage and data processing. Its checkpoint system enables users to incrementally add or remove samples without repeating the entire search process. For analyses involving closely related taxa, Phyling supports the use of nucleotide coding sequences, which may capture phylogenetic signals missed...

Genomic and Ecological Flexibility Shape the Global Distribution of a Black Fungus

Thu, 23 Apr 2026 00:00:00 +0000

Black fungi are among the most stress-resistant organisms known, yet the genetic and ecological foundations of their extraordinary resilience remain poorly understood. This study explores the adaptation strategies of the melanised fungus Elasticomyces elasticus by integrating genomic and ecological data. To uncover the mechanisms of adaptation, we combined whole-genome sequencing, functional annotation, environmental metadata, and large-scale soil metabarcoding analyses. Phylogenomic approaches were employed to delineate evolutionary lineages and assess ploidy levels. The results revealed that the global distribution of Elasticomyces phylotypes is primarily influenced by temperature, UV radiation, and soil organic carbon, suggesting that different phylotypes have evolved heterogeneous strategies for stress resistance. Comparative genomic analyses identified a set of 'sentinel pathways,' notably glutathione metabolism and nucleotide biosynthesis, which were enriched in strains...

Defining Immersive Learning

Thu, 23 Apr 2026 00:00:00 +0000

Immersive learning practices (ILPs) in higher education are multidisciplinary in nature and varied in levels of integration into the student learning process. They appear in a variety of higher education programs such as teacher education, social work, law, and health sciences, and in practices such as service-learning, study away, internships, and foreign-language instruction. Based on observations of teaching and data from an open-ended survey and semi-structured interviews with post-secondary educators from three different countries, this study theorizes that immersive learning practices are composed of six distinct underlying theoretical components that work in combination. These six components can be used to describe, define, compare, and design different types of structured ILPs. This study suggests that ILPs are pedagogically distinct from other forms of engaged and experiential learning.

systemPipeR: a multipurpose workflow management system for reproducible data analysis

Tue, 21 Apr 2026 00:00:00 +0000

Workflow management systems (WMS) are essential for creating and automating multi-step data analyses and ensuring the reproducibility of biological insights. Although numerous WMS solutions exist, few provide deep integration of command-line software with the R and Bioconductor ecosystems, where a substantial portion of statistical modeling and downstream scientific analysis is performed by a large user base. systemPipeR addresses this gap by offering a unified environment that links R-based analytical steps with command-line tools through a standardized workflow specification. It enables the design and execution of reproducible workflows on both local and high-performance computing systems, while allowing users to select the most appropriate R or command-line tool for each analysis step. The latest version introduces a fully redesigned architecture that streamlines workflow construction, execution, monitoring, and reporting. Key enhancements include a flexible workflow management...

Supporting Basic Psychological Needs in Medical Education: A Patient Best Practice.

Fri, 17 Apr 2026 00:00:00 +0000

Physician burnout remains a pervasive challenge in medical education, with significant implications for both physician well-being and the quality and safety of patient care. Despite growing awareness and interventions, medical educators often lack a cohesive theoretical framework that explains how learning environments can contribute to both burnout and clinical performance. This article highlights Self-Determination Theory (SDT) as a robust, evidence-based lens through which to understand and address these challenges by emphasizing the fulfillment of three basic psychological needs: autonomy, competence, and relatedness. Drawing on foundational and contemporary research across health professions education and healthcare, the authors argue that supporting these needs within clinical learning environments not only enhances learner motivation, engagement, and resilience, but also reduces burnout and its downstream effects on empathy, decision-making, teamwork, and patient outcomes....

Endothelial Adgrl2 expression and alternative splicing controls the cerebrovasculature.

Thu, 9 Apr 2026 00:00:00 +0000

Central nervous system development requires parallel but interrelated processes of neural circuit assembly and vascularization. Intersecting between these two processes is the cell-adhesion G-protein coupled receptor Adgrl2. In select neuronal populations, Adgrl2 is localized and control the assembly of specific synaptic sites. In non-neuronal brain cells, Adgrl2 is restricted in expression to endothelial cells. Testing for Adgrl2 function in these cells in mice (of either sex), here we find that endothelial cell specific Adgrl2 deletion results in an impairment in cerebrovascular integrity. To understand how it might be possible for Adgrl2 to function independently in neuronal and endothelial contexts, we surveyed Adgrl2 transcripts within these cell classes. By analyzing single-cell RNA sequencing datasets, we find that Adgrl2 mRNA is subject to robust cell type-specific alternative splicing that results in distinct isoforms...

PATIENT OUTCOMES AFTER BEING TREATED WITH BETA-BLOCKERS FOR HEART RATE CONTROL IN SEPTIC SHOCK

Thu, 9 Apr 2026 00:00:00 +0000

PATIENT OUTCOMES AFTER BEING TREATED WITH BETA-BLOCKERS FOR HEART RATE CONTROL IN SEPTIC SHOCK

Connectome-based predictive modelling predicts frailty levels in older adults

Thu, 26 Mar 2026 00:00:00 +0000

Frailty is characterized by a persistent and progressive decline in physiological reserves, leading to increased vulnerability to stressors and a heightened risk of adverse health outcomes, both physically and mentally. Despite frailty's prevalence in older adults, there is limited research on its neural substrates, especially using task-based brain functional connectivity. In this study, we used connectome-based predictive modelling (CPM) to find a linear relationship between task-based connectomes - taken from tasks that involved similar handgrip manipulations - and a separate measure of frailty: the maximum grip strength in older adults. We observed that the task-based connectomes were able to explain individual differences in grip strength, with the Subcortical and Cerebellum network, particularly the caudate nucleus, functional connectivity being the strongest predictor. These findings demonstrate that task-based functional connectomes can serve as personalized markers that...

Alzheimer's disease in patients prescribed statins: A real-world data analysis of U.S. patient health records.

Thu, 12 Mar 2026 00:00:00 +0000

BackgroundEvidence from observational studies and randomized controlled trials (RCTs) remains discordant on the impact of statin therapy on long-term outcomes related to Alzheimer's disease. Observational studies find relatively large effect sizes; RCTs fail to demonstrate cognitive benefits. Methodological limitations in both approaches may explain the disconnect.ObjectiveTo bridge the gap between observational and RCT studies, this study uses Real World Data (RWD) to evaluate the association between statin use and incident AD risk, and contributes additional detailed stratification by statin type and dosage.MethodsThis observational analysis of EHR data from over 125 million U.S. patients through the TriNetX platform compared statin exposure in adults over 45 years old with a diagnosis of dyslipidemia, and no prior AD diagnosis, controlling for demographics, a range of known comorbidities, laboratory values, and medications. Primary outcomes were incident AD, other degenerative...

Towards optimal selection of ultra-deep sequencing reads for de novo genome assembly

Thu, 12 Mar 2026 00:00:00 +0000

When sequencing a new genome, it is common practice to expect that 30-50× sequencing depth will be sufficient for a complete and highly contiguous assembly. With the rapid decrease in the cost of sequencing DNA, on small genomes it is not uncommon to have excessive sequencing data, sometimes exceeding 1000× sequencing depth (which we call ultra-deep). Because ultra-deep sequencing data significantly degrades the quality of the final assembly (for reasons not entirely clear to us), one faces the problem of how to select a subsample of the data for optimal assembly. The optimal read selection problem for genome assembly is largely unexplored. Here we first show that this problem is related to the minimum tiling path (MTP) problem which is known to be NP-hard. Then, we propose a heuristic (called AWinK) based on single-copy k-mer to select a subset of ultra-deep sequencing reads that maximizes the genomic coverage. Our experiments on both synthetic and real ultra-deep sequencing...

New persistent plant RNA virus carries mutations to weaken viral suppression of antiviral RNA interference

Thu, 12 Mar 2026 00:00:00 +0000

Persistent plant viruses are widespread in natural ecosystems. However, little is known about why persistent infection with these viruses may cause little or no harm to their host. Here, we discovered a new polerovirus that persistently infected wild rice plants by deep sequencing and assembly of virus-derived small-interfering RNAs (siRNAs). The new virus was named Rice tiller inhibition virus 2 (RTIV2) based on the symptoms developed in cultivated rice varieties following Agrobacterium-mediated inoculation with an infectious RTIV2 clone. We showed that RTIV2 infection induced antiviral RNA interference (RNAi) in both the wild and cultivated rice plants as well as Nicotiana benthamiana. It is known that virulent virus infection in plants depends on effective suppression of antiviral RNAi by viral suppressors of RNAi (VSRs). Notably, the P0 protein of RTIV2 exhibited weak VSR activity and carries alanine substitutions of two amino acids broadly conserved among diverse poleroviruses....

Prediction of DNA Methylation With Long-Range State-Space Models

Thu, 12 Mar 2026 00:00:00 +0000

The prediction of DNA methylation from the primary DNA sequence allows one to impute the methylation status of cytosines with insufficient sequencing coverage. Various deep learning models have been proposed in the literature, including transformer-based models and convolutional neural networks. In this study, we investigate the performance of long-range state-space models based on the Hyena architecture on the task of DNA methylation prediction on six plant species. First, we train the HyenaDNA framework to obtain a genome-wide foundation model for each species. Then, we fine-tune these foundation models using the sequence data surrounding the methylated or unmethylated cytosines. Extensive experimental results show that our model predicts DNA methylation with higher accuracy than state-of-the-art methods in the literature.

Exogenous Sex Hormones and Postoperative Nausea and Vomiting Risk in Transgender Patients

Thu, 12 Mar 2026 00:00:00 +0000

BACKGROUND: Postoperative nausea and vomiting (PONV) remain a significant consideration in perioperative care; however, the incidence and risk factors of PONV in transgender patients are poorly understood. This study investigated the rates of PONV in transgender patients receiving gender-affirming hormone therapy (GAHT) compared to cisgender patients. We postulate that exogenous testosterone GAHT reduces the risk of PONV while exogenous estrogen GAHT increases the risk of PONV. METHODS: This retrospective cohort study was conducted using the TriNetX database. Patients were divided into 2 groups: transgender and cisgender. Separate analyses were performed for hysterectomies (transgender male [assigned female at birth, AFAB] versus cisgender female), orchiectomies (transgender female [assigned male at birth, AMAB] versus cisgender male), and augmentation mammoplasties (transgender female [AMAB] versus cisgender female). Propensity score matching was performed for age, race, and...

Babesia hegotelforum sp. nov., a zoonotic Babesia species previously referred to as Babesia sp. MO1.

Thu, 12 Mar 2026 00:00:00 +0000

A zoonotic Babesia species previously referred to as Babesia sp. MO1 is formally described and named here as Babesia hegotelforum sp. nov. This taxon is distinct from Babesia divergens based on genome-wide sequence divergence, phylogenetic placement, host associations, and clinical presentation. The parasite infects erythrocytes of humans, and eastern cottontail rabbits (Sylvilagus floridanus), and is transmitted by Ixodes dentatus. The holotype consists of a Giemsa-stained thin blood smear and cryopreserved infected erythrocytes from the cloned isolate BML-Bh-B12 at ≤10 passages in continuous in vitro culture. Paratype material includes five additional clones (BML-Bh-H1, BML-Bh-F12, BML-Bh-H6, BML-Bh-A3, and BML-Bh-F1) derived from BEI Resources strain NR-50441, along with the original mixed isolate NR-50441. This species description meets the requirements of the International Code of Zoological...

Editing strigolactone hormone receptor for robust antiviral silencing in rice

Thu, 12 Mar 2026 00:00:00 +0000

The small interfering RNA (siRNA) pathway directs broad-spectrum antiviral defense through RNA silencing so that virulent infection requires efficient suppression of the defense mechanism. Here, we show that strigolactone (SL) hormone signaling promotes antiviral silencing in rice plants by transcriptional activation of RNA-dependent RNA polymerase 1 (RDR1) and RDR6. We demonstrate that protein P3 of the rice grassy stunt virus (RGSV) blocks SL signaling by directly sequestering the receptor DWARF14 from DWARF3. Structural and functional analyses of the P3-DWARF14 complex reveal that the aspartic acid at position 102 (D102) of DWARF14 is essential for the P3 interaction but not for SL perception. Notably, a single D102N substitution of DWARF14, introduced into two rice cultivars by cytosine base editing (CBE) confers resistance against RGSV by blocking viral suppression of SL signaling-dependent antiviral silencing. Our findings establish a transgene-free strategy for engineering...

Proposed Key Characteristics of Neurotoxic Chemicals

Wed, 11 Mar 2026 00:00:00 +0000

A critical component of evaluating whether a chemical can cause human neurotoxicity is hazard identification, which typically involves a comprehensive literature search to identify and synthesize epidemiological, animal, and mechanistic data for the chemical of interest. The key characteristics (KCs) concept has proven to be a useful tool for searching, organizing, and evaluating mechanistic data for hazard identification. KCs are the established chemical and biological properties of known human neurotoxic agents based on understanding of their mechanisms of neurotoxicity. KCs were originally developed for carcinogens but have now also been published for endocrine- and metabolism-disruptors and various organ-selective toxic chemicals. To identify KCs associated with neurotoxic chemicals, an expert committee was convened to consider current mechanistic understanding of chemicals known to be neurotoxic in humans with the goal of identifying established molecular and cellular actions...

Fuel-driven filamentous phage nanomotors

Thu, 26 Feb 2026 00:00:00 +0000

Virus-based nanocarriers have shown great potential for noninvasive delivery of drugs, diagnostics, and imaging agents to hard-to-reach anatomical locations. Yet, they largely depend on diffusion for transport, often lacking the force to actively penetrate biological barriers, and navigation to guide therapeutic agents. In these studies, the M13 bacteriophage, a linearly shaped virus, was converted from passive nanocarrier to actively propelled, fuel-driven nanomotor. Using the distinctive low symmetry of its capsid, a single Pt nanoparticle was added to one end of the M13 virus to form a tadpole-like structure. The Pt/M13 head/tail nanomotors exhibited notably enhanced diffusion in the presence of hydrogen peroxide fuel, and significantly improved uptake by SVOK3 ovarian cancer cells in vitro. Given the successes of the M13 bacteriophage as a nanocarrier, the demonstration of this simple, but comparatively mobile M13-based nanomotor platform represents an important step...

Progression of two Progressive Supranuclear Palsy phenotypes with comparable initial disability

Tue, 24 Feb 2026 00:00:00 +0000

INTRODUCTION: To avoid bias and optimize statistical power of disease-modifying therapeutic trials, it is critical to include homogeneous populations with similar rate of progression over time. Patients with Progressive Supranuclear Palsy (PSP)-Parkinsonism phenotype have overall slower disease progression than those with PSP-Richardson syndrome phenotype. However, it is unclear if the progression rate of PSP-Parkinsonism is the same when the PSP-Parkinsonism converts to PSP Richardson syndrome. We aimed to determine and compare disease progression rate of patients with the two most common PSP phenotypes: PSP-Parkinsonism and PSP Richardson syndrome, participating in the TAUROS trial. METHODS: 138 patients, 56 with PSP-Parkinsonism and 82 with PSP-Richardson syndrome, with similar clinical severity at baseline, were followed up to 60 weeks. PSP-Parkinsonism allocation was based on experts' judgement and PSP-Richardson on probable NINDS-PSP criteria. Global disease progression...

Poster 296 AbobotulinumtoxinA Injection Patterns in Patients with Cervical Dystonia from the ANCHOR‐CD Registry Study

Tue, 24 Feb 2026 00:00:00 +0000

Poster 296 AbobotulinumtoxinA Injection Patterns in Patients with Cervical Dystonia from the ANCHOR‐CD Registry Study

Nucleotide salvage, genome instability, and potential therapeutic applications.

Tue, 17 Feb 2026 00:00:00 +0000

Nucleotide salvage is crucial for maintaining DNA replication when de novo nucleotide synthesis is limited, but this metabolic flexibility poses potential threats to genome stability. Salvage kinases phosphorylate nucleosides broadly, allowing for oxidized and alkylated 2-deoxynucleosides as well as posttranscriptionally modified ribonucleosides to enter the 2-deoxynucleoside triphosphate (dNTP) pool. The ensuing contamination of the dNTP pool and the subsequent incorporation of modified nucleotides into genomic DNA promote mutagenesis, induce replication stress, elicit double-strand breaks, and disrupt epigenetic signaling. Although only a small subset of modified nucleosides have been assessed for salvage and genomic incorporation, the scope of salvageable substrates is probably much wider, with significant implications in mutational burden, chromatin instability, and epigenetic regulation. This overlooked aspect of genome instability is especially relevant in biological contexts...

Two cytochrome P450 epoxidases mediate juvenile hormone biosynthesis in Drosophila melanogaster

Thu, 29 Jan 2026 00:00:00 +0000

Juvenile hormones (JHs) mediate various biological processes such as development and reproduction in insects. Although pleiotropic functions of JHs are well investigated in the fruit fly Drosophila melanogaster, their biosynthetic mechanisms are less well understood, partly because many JH biosynthetic enzymes still remain unidentified in this important model species. Here we report that two cytochrome P450 (CYP) epoxidases mediate JH biosynthesis in D. melanogaster. In addition to previously reported Cyp6g2, a second epoxidase, Cyp6a13, also functions in the corpus allatum, the major JH biosynthetic endocrine gland. Combined mutations of the genes encoding these enzymes cause developmental and reproductive defects, which can be rescued by JH application. JH biosynthetic functions of these genes were further confirmed by using a heterologous expression system and ex vivo tissue culture. Collectively, our results indicate that these two CYP epoxidases function cooperatively to...

Entorhinal cortex layer III Adgrl2 expression controls topographical circuit connectivity required for sequence learning

Thu, 29 Jan 2026 00:00:00 +0000

The entorhinal cortex and hippocampus are interconnected brain regions required for episodic learning and memory. For this functional encoding, correct assembly of specific synaptic connections across this circuit is critical during development. To guide the connection specificity between neurons, a multitude of circuit building molecular components are required, including the latrophilin family of adhesion G protein-coupled receptors (Lphn1-3; gene symbols Adgrl1-3). Within this genetic family, Adgrl2 exhibits a unique topographical and cell-type specific expression patterning in the entorhinal cortex and hippocampus that mirrors connectivity. To investigate the role of Adgrl2 in a cell-type specific fashion for this circuit, we here created a transgenic mouse (Adgrl2fl/fl;pOxr1-Cre) with targeted and selective Adgrl2 deletion in medial entorhinal cortex layer III neurons (MECIII). Using these mice, we find two major input/output circuitry pathways to be topographically shifted...

Adhesion G protein-coupled receptors

Thu, 29 Jan 2026 00:00:00 +0000

Adhesion G protein-coupled receptors (aGPCRs) constitute a structurally and functionally distinct group within the superfamily of GPCRs. In 2015, the International Union of Pharmacology invited the Adhesion GPCR Consortium to publish a comprehensive review about aGPCRs and to establish a unified nomenclature. Since then, substantial progress has been made in delineating the biological roles, molecular architecture, biochemical properties, expression profiles, ligand repertoire, and activation and signaling strategies of aGPCRs. Commensurate with these advances, their relevance to human pathophysiology has become increasingly evident. In a coordinated effort, the Adhesion GPCR Consortium has reviewed recent progress in the field and provides a comprehensive assessment of the current understanding of aGPCR biology here. This includes a focus on human and mammalian aGPCRs, their evolutionary origins, methodological approaches and model systems for their investigation, as well as...

Exploring Space‐Time Interactions in Fatal Opioid Overdoses

Thu, 29 Jan 2026 00:00:00 +0000

ABSTRACT This study investigates fatal opioid overdoses in Riverside County, California, between January 2020 and March 2023, employing advanced spatial‐temporal analysis methods to uncover significant clusters and their underlying contexts. By integrating global and local Knox tests, the research identifies both broad trends and specific hotspots of fatal overdoses. The findings reveal substantial spatial disparities, with higher overdose rates in rural areas and neighborhoods characterized by lower socioeconomic status and larger Hispanic populations. Despite a lower overall overdose risk among Hispanics, their neighborhoods exhibit a higher occurrence of fatal overdoses, highlighting complex interactions between individual and environmental factors. These insights underscore the need for targeted, contextually informed public health interventions and policies to effectively address the opioid crisis.

Identifying indicators of consciousness in AI systems

Thu, 15 Jan 2026 00:00:00 +0000

Rapid progress in artificial intelligence (AI) capabilities has drawn fresh attention to the prospect of consciousness in AI. There is an urgent need for rigorous methods to assess AI systems for consciousness, but significant uncertainty about relevant issues in consciousness science. We present a method for assessing AI systems for consciousness that involves exploring what follows from existing or future neuroscientific theories of consciousness. Indicators derived from such theories can be used to inform credences about whether particular AI systems are conscious. This method allows us to make meaningful progress because some influential theories of consciousness, notably including computational functionalist theories, have implications for AI that can be investigated empirically.

Eukaryotic MAGs recovered from deep metagenomic sequencing of the seagrass, Zostera marina, include a novel chytrid in the order Lobulomycetales

Wed, 24 Dec 2025 00:00:00 +0000

Abstract Fungi play pivotal roles in terrestrial ecosystems as decomposers, pathogens, and endophytes, yet their significance in marine environments is often understudied. Seagrasses, as globally distributed marine flowering plants, have critical ecological functions, but knowledge about their associated fungal communities remains relatively limited. Previous amplicon surveys of the fungal community associated with the seagrass, Zostera marina have revealed an abundance of potentially novel chytrids. In this study, we employed deep metagenomic sequencing to extract metagenome-assembled genomes (MAGs) from these chytrids and other microbial eukaryotes associated with Z. marina leaves. Our efforts resulted in the recovery of five eukaryotic MAGs, including a single fungal MAG in the order Loubulomycetales (65% BUSCO completeness), three MAGs representing diatoms in the family Bacillariaceae (93%, 70% and 31% BUSCO completeness) and a single MAG representing a haptophyte algae in...

A cholesterol-responsive hepatic tRNA-derived small RNA regulates cholesterol homeostasis and atherosclerosis development

Mon, 22 Dec 2025 00:00:00 +0000

Transfer RNA-derived small RNAs (tsRNAs) have emerged as crucial players in diverse biological processes. Yet, their involvement in lipid metabolism and cardiovascular disease remains elusive. Using an advanced PANDORA-seq method, we identify tsRNA-Glu-CTC as the most abundant tsRNA in mouse liver. Intriguingly, tsRNA-Glu-CTC is cholesterol responsive. Overexpression of tsRNA-Glu-CTC elicits hypercholesterolemia and hepatic steatosis, whereas its knockdown protects against diet-induced hypercholesterolemia and atherosclerosis in mice. Mechanistically, tsRNA-Glu-CTC regulates key hepatic lipogenic genes including Srebp2, a master regulator of lipid metabolism. tsRNA-Glu-CTC interacts with SREBP2 to regulate its own transcription through an E-box motif. We further identify site-specific RNA modifications of endogenous tsRNA-Glu-CTC by a mass spectrometry-based MLC-seq and demonstrate the modified tsRNA-Glu-CTC as a more potent regulator of cholesterol homeostasis compared to its...

Renewing Multicultural Education: An Ancient Mariner’s Manifesto

Tue, 9 Dec 2025 00:00:00 +0000

Renewing Multicultural Education: An Ancient Mariner’s Manifesto

Durable humoral immunity and long-term protection induced by a Crimean-Congo hemorrhagic fever virus replicon particle vaccine in mice

Mon, 8 Dec 2025 00:00:00 +0000

A Crimean-Congo hemorrhagic fever virus replicon particle vaccine was evaluated for long-term immunity and efficacy in mice. IgG responses persisted up to 18 months, with similar titers across dosing strategies through 12 months. Protective efficacy reached ≥75% at 6 months (prime-only) and up to 12 months (prime-boost). Booster dosing enhanced antibody avidity, effector function, and improved long-term protection. These findings support durable immunity from single or boosted vaccination.

Fine-tuned protein language model identifies antigen-specific B cell receptors from immune repertoires

Thu, 4 Dec 2025 00:00:00 +0000

Abstract Scalable identification of antigen-specific antibodies from whole immune repertoire V(D)J sequences is a central challenge in biomedical engineering. We show that protein language models (PLMs) fine-tuned on antibody heavy-chain sequences can directly predict antigen specificity from unselected immune repertoires. We assessed our model, Antigen Specificity Predictor (ASPred), against SARS-CoV-2, influenza, and HIV-AIDS antigens, observing comparable predictive performance. In the whole immune repertoire V(D)J sequences of mice immunized with the SARS-CoV-2 spike protein’s receptor-binding domain (RBD), ASPred identified antibody sequences specific to RBD. Several candidate sequences were validated, including one as a heavy chain-only nanobody with 20.7 nM dissociation constant. Molecular dynamics simulations supported the predicted interactions at coarse-grained and atomic levels. Benchmarking against Barcode-Enabled Antigen Mapping (BEAM) of B cell receptor sequence...

SHICEDO: single-cell Hi-C data enhancement with reduced over-smoothing

Thu, 4 Dec 2025 00:00:00 +0000

MOTIVATION: Single-cell Hi-C (scHi-C) technologies have significantly advanced our understanding of the 3D genome organization. However, scHi-C data are often sparse and noisy, leading to substantial computational challenges in downstream analyses. RESULTS: In this study, we introduce SHICEDO, a novel deep-learning model specifically designed to enhance scHi-C contact matrices by imputing missing or sparsely captured chromatin contacts through a generative adversarial framework. SHICEDO leverages the unique structural characteristics of scHi-C matrices to derive customized features that enable effective data enhancement. Additionally, the model incorporates a channel-wise attention mechanism to mitigate the over-smoothing issue commonly associated with scHi-C enhancement methods. Through simulations and real-data applications, we demonstrate that SHICEDO outperforms the state-of-the-art methods, achieving superior quantitative and qualitative results. Moreover, SHICEDO enhances...

Reference-informed prediction of alternative splicing and splicing-altering mutations from sequences

Thu, 4 Dec 2025 00:00:00 +0000

Alternative splicing plays a crucial role in protein diversity and gene expression regulation in higher eukaryotes, and mutations causing dysregulated splicing underlie a range of genetic diseases. Computational prediction of alternative splicing from genomic sequences not only provides insight into gene-regulatory mechanisms but also helps identify disease-causing mutations and drug targets. However, the current methods for the quantitative prediction of splice site usage still have limited accuracy. Here, we present DeltaSplice, a deep neural network model optimized to learn the impact of mutations on quantitative changes in alternative splicing from the comparative analysis of homologous genes. The model architecture enables DeltaSplice to perform "reference-informed prediction" by incorporating the known splice site usage of a reference gene sequence to improve its prediction on splicing-altering mutations. We benchmarked DeltaSplice and several other state-of-the-art methods...

Reference-informed prediction of alternative splicing and splicing-altering mutations from sequences

Thu, 4 Dec 2025 00:00:00 +0000

Alternative splicing plays a crucial role in protein diversity and gene expression regulation in higher eukaryotes and mutations causing dysregulated splicing underlie a range of genetic diseases. Computational prediction of alternative splicing from genomic sequences not only provides insight into gene-regulatory mechanisms but also helps identify disease-causing mutations and drug targets. However, the current methods for the quantitative prediction of splice site usage still have limited accuracy. Here, we present DeltaSplice, a deep neural network model optimized to learn the impact of mutations on quantitative changes in alternative splicing from the comparative analysis of homologous genes. The model architecture enables DeltaSplice to perform "reference-informed prediction" by incorporating the known splice site usage of a reference gene sequence to improve its prediction on splicing-altering mutations. We benchmarked DeltaSplice and several other state-of-the-art methods...

Precocene-I mediated reduction of juvenile hormone titers and ovarian activity is ephemeral in a bumble bee

Thu, 4 Dec 2025 00:00:00 +0000

Juvenile hormones (JHs) are key insect endocrine signals regulating pre-adult development and adult life history strategies, physiology, and behavior. The importance of this endocrine signal has led to the development of insecticides targeting JH signaling pathways. While effective against target pests, they can also affect beneficial insects, such as pollinators and natural pest enemies, many of which are hymenopterans. Research on JH, which is crucial for understanding the physiology, behavior, and organization of social insects, requires effective means to manipulate JH signaling pathways. A common method for reducing JH titers includes applying the phytotoxin precocene-I (P-I), which abolishes JH biosynthesis in the corpora allata (CA). However, achieving consistently effective topical treatments has proven challenging. Here, we investigated the dynamics of the effect of P-I manipulations on JH titers and reproductive development in orphan worker groups of a key pollinator...

PTBP1 depletion in mature astrocytes reveals distinct splicing alterations without neuronal features

Tue, 25 Nov 2025 00:00:00 +0000

Astrocyte-to-neuron reprogramming via depletion of PTBP1, a potent repressor of neuronal splicing, has been proposed as a therapeutic strategy, but its efficacy remains debated. While some reported successful conversion, others disputed this, citing a lack of neuronal gene expression as evidence of failed reprogramming. This interpretation was further challenged, attributed to incomplete PTBP1 inactivation, fueling ongoing controversy. Mechanistic understanding of the conversion, or the lack thereof, requires investigating, in conjunction with lineage tracing, the effect of Ptbp1 loss of function in mature astrocytes on RNA splicing, which has not yet been examined. Here, we genetically ablated PTBP1 in adult Aldh1l1-Cre/ERT2 Ai14 mice to determine whether lineage-traced Ptbp1 knockout astrocytes exhibited RNA splicing alterations congruent with neuronal differentiation. We found no widespread induction of neurons, despite a minuscule fraction of knockout cells showing...

Coordinated regulation of Mdr1- and Cdr1-mediated protection from antifungals by the Mrr1 transcription factor in emerging Candida spp.

Fri, 21 Nov 2025 00:00:00 +0000

Infections caused by the emerging pathogenic yeast Clavispora (Candida) lusitaniae can be difficult to manage due to multi-drug resistance. Resistance to the frontline antifungal fluconazole (FLZ) in Candida spp. is commonly acquired through gain-of-function (GOF) mutations in the gene encoding the transcription factor Mrr1. These activated Mrr1 variants enhance FLZ efflux via upregulation of the multi-drug transporter gene MDR1. Recently, it was reported that, unlike in the well-studied Candida albicans species, C. lusitaniae and Candida parapsilosis with activated Mrr1 also have high expression of CDR1, which encodes another multi-drug transporter with overlapping but distinct transported substrate profiles and Cdr1-dependent FLZ resistance. To better understand the mechanisms of Mrr1 regulation of MDR1 and CDR1, and other co-regulated genes, we performed Cleavage Under Targets and Release Using Nuclease (CUT&RUN)...

Specialized metabolites of the herptile gut fungus, Basidiobolus

Fri, 21 Nov 2025 00:00:00 +0000

Specialized metabolites of the herptile gut fungus, Basidiobolus

A haplotype-resolved chromatin landscape connects cis-regulatory variants to trait variation in Citrus

Fri, 21 Nov 2025 00:00:00 +0000

BackgroundGenetic and epigenetic perturbation of cis-regulatory sequences can shift patterns of gene expression and result in novel phenotypes. Phased genome assemblies now enable the local dissection of linkages between cis-regulatory sequences, including their epigenetic state, and allele-specific gene expression to further characterize gene regulation and resulting phenotypes in heterozygous genomes.ResultsWe assembled a locally phased genome for a mandarin hybrid named ‘Fairchild’ to explore the molecular signatures of allele-specific gene expression. With local genome phasing, genes with allele-specific expression were paired with haplotype-specific chromatin states, including levels of chromatin accessibility, histone modifications, and DNA methylation. We found that 30% of variation in allele-specific expression could be attributed to haplotype associated factors, with allelic levels of chromatin accessibility and three histone modifications in gene bodies having the most...

Urinary Biomarkers in Bladder Cancer: FDA-Approved Tests and Emerging Tools for Diagnosis and Surveillance

Thu, 20 Nov 2025 00:00:00 +0000

Bladder cancer is a prevalent malignancy with high morbidity and mortality, particularly when diagnosed at an advanced stage. Early detection is critical, as it significantly improves prognosis and the patient’s outcomes. Bladder cancer also has a high recurrence rate, necessitating long-term surveillance. While cystoscopy remains the gold standard for diagnosis and monitoring, it is invasive and costly. Urine cytology, though widely used, has high specificity for detecting high-grade urothelial carcinoma but suffers from low sensitivity and limited effectiveness as a stand-alone diagnostic tool. Urinary biomarkers offer a promising, noninvasive alternative for early detection and disease surveillance. This review examines FDA-approved urinary biomarker tests, including NMP 22, UroVysion, and BTA, highlighting their clinical utility and limitations. Additionally, we explore emerging biomarkers such as DNA methylation assays, genomic alterations, and proteomic signatures as well...

Emergency Department Survey of Vaccination Knowledge, Vaccination Coverage, and Willingness to Receive Vaccines in an Emergency Department Among Underserved Populations - Eight US Cities, April-December, 2024

Thu, 20 Nov 2025 00:00:00 +0000

Emergency Department Survey of Vaccination Knowledge, Vaccination Coverage, and Willingness to Receive Vaccines in an Emergency Department Among Underserved Populations - Eight US Cities, April-December, 2024

The I-ACTED study (investigating action civics training through an experimental design): a cluster randomized controlled trial of a school-based action civics education intervention on adolescent wellbeing

Thu, 6 Nov 2025 00:00:00 +0000

BackgroundObservational studies have found that youth civic engagement is associated with positive mental health, education, and socioeconomic outcomes. However, access to civic opportunities is not evenly distributed. Many classrooms in the United States of America (USA) do not have access to high-quality civics education. Action civics approaches to civic education prepare students for civic engagement by developing the necessary civic skills, knowledge, and character. Through action civics, classes take action on a real-world issue students choose together. Some evidence suggests that action civics may positively affect participants’ wellbeing through the feelings of civic connection and empowerment. The aim of this study is to investigate, through a randomized controlled trial, the impact of a school-based action civics education intervention on civic and wellbeing outcomes, and the mechanisms of any impact observed, among middle and high school students in the USA.MethodsThis...

Upholding the Human Rights and Well-Being of Refugee Children Through Effective Clinical Care

Wed, 29 Oct 2025 00:00:00 +0000

Refugee children are often exposed to adversities and traumatic experiences that can harm the mental health and well-being of refugee children. These include human trafficking and exploitation and dangers in detention centers and refugee camps. All these adverse events can be traumatic and contribute to poor mental health, including posttraumatic stress, anxiety, depression, and substance use disorders. Therefore, the assessment of refugee children and adolescents should include screening and identification for these experiences, provision of evidence-based trauma treatment, and social supports to promote their well-being and thriving.

A conserved long-range RNA interaction in SARS-CoV-2 recruits ADAR1 to enhance virus proliferation

Thu, 23 Oct 2025 00:00:00 +0000

Long-range RNA-RNA pairing impacts the genome structure and function of SARS-CoV-2 variants. To understand the structure and function relationships of different SARS-CoV-2 variants that have emerged during the COVID-19 pandemic, we perform high-throughput structure probing and modelling of the genomic structures of the wildtype (WT), Alpha, Beta, Delta and Omicron variants of SARS-CoV-2. We observe that genomes of SARS-CoV-2 variants are generally structurally conserved, and that single-nucleotide variations and interactions with RNA binding proteins can impact RNA structures across the viruses. Importantly, using proximity ligation sequencing, we identify many conserved ultra-long-range RNA-RNA interactions, including one that spans more than 17 kb in both the WT virus and the Omicron variant. We show that mutations that disrupt this 17 kb long-range interaction reduce viral fitness at later stages of its infection cycle, while compensatory mutations partially restore virus fitness....

A drug repurposing approach reveals targetable epigenetic pathways in Plasmodium vivax hypnozoites

Thu, 23 Oct 2025 00:00:00 +0000

Radical cure of Plasmodium vivax malaria must include elimination of quiescent 'hypnozoite' forms in the liver; however, the only FDA-approved treatments are contraindicated in many vulnerable populations. To identify new drugs and drug targets for hypnozoites, we screened the Repurposing, Focused Rescue, and Accelerated Medchem (ReFRAME) library and a collection of epigenetic inhibitors against P. vivax liver stages. From both libraries, we identified inhibitors targeting epigenetics pathways as selectively active against P. vivax and P. cynomolgi hypnozoites. These include DNA methyltransferase inhibitors as well as several inhibitors targeting histone post-translational modifications. Immunofluorescence staining of Plasmodium liver forms showed strong nuclear 5-methylcystosine signal, indicating liver stage parasite DNA is methylated. Using bisulfite sequencing, we mapped genomic DNA methylation in sporozoites, revealing DNA methylation signals...

Comparison of 5-year incidence of subsequent primary malignancies among patients with melanoma vs basal cell carcinoma: A gender-stratified propensity score-matched cohort study

Thu, 9 Oct 2025 00:00:00 +0000

Comparison of 5-year incidence of subsequent primary malignancies among patients with melanoma vs basal cell carcinoma: A gender-stratified propensity score-matched cohort study

Pediatric Non-Cystic Fibrosis Pulmonary Nontuberculous Mycobacterium Infections: A Global Population Based Study

Thu, 9 Oct 2025 00:00:00 +0000

Background: Nontuberculous mycobacteria (NTM) are Mycobacterial pathogens that cause pulmonary infections among children, particularly those with underlying lung conditions or immunosuppression. Clinical presentations include chronic cough, weight loss, and fatigue. Diagnosis involves clinical assessment, radiographic imaging, and microbiological confirmation, while treatment often requires prolonged, multidrug antibiotic regimens. This study aimed to analyze the epidemiology and clinical outcomes of pulmonary NTM infections in a non-cystic fibrosis pediatric population from four distinct age groups. Methods: A retrospective study as cross-sectional design for data collection from the TriNetX platform, a global electronic health record database. Inclusion criteria targeted pediatric patients aged 0-18 years with pulmonary NTM, while exclusion criteria included cystic fibrosis, tuberculosis, smoking history, and cutaneous NTM infections. The cohort comprised 109 cases among 0-2...

Soil drivers of fungal, bacterial and plant diversity in contaminated Southern Californian sites: Implications for dryland bioremediation

Wed, 24 Sep 2025 00:00:00 +0000

This exploratory study surveyed seven contaminated brownfields and Superfund sites in Southern California to identify locally adapted species tolerant of mixed organic and metal contamination under arid and semi-arid conditions. Five novel native plants, including Brickellia californica, Baccharis salicifolia, Baccharis sarothroides, Eriogonum fasciculatum, and Heterotheca grandiflora were identified as hyperaccumulators of copper (Cu), alongside a non-native species from the Asteraceae family, Helminthotheca echioides. Additional metal-accumulating plants (including native plants) for lead (Pb), chromium (Cr), arsenic (As), and nickel (Ni) were identified, and warrant further evaluation for their phytoremediation potential. Dominant microbial communities included fungal taxa from the Ascomycota and bacterial taxa from the Proteobacteria, with bioremediation candidates detected across sites. Redundancy and principal component analyses revealed that site variability, water-extractable...

Policy stakeholders' perspectives and use of data, research evidence, and misinformation in three counties in California, USA during the COVID-19 pandemic, 2020–2022

Wed, 24 Sep 2025 00:00:00 +0000

Objective: This study investigates how local policy stakeholders viewed and used research evidence, data, and (mis)information in county policy discussions during the COVID-19 pandemic. Method: We employed document and exploratory content analysis methods to examine Board of Supervisor materials (N = 534 policy documents) from general and special/emergency meetings (March 2020 - December 2022). We purposefully selected three jurisdictions from California, USA with varying socio-demographic, political, and health care characteristics as case studies. Results: Many residents who commented during local policy discussions contested the: 1) validity of health data provided (i.e., mortality rates), and 2) efficacy of proposed preventive measures like mask wearing and vaccine receipt. While government officials and healthcare personnel referenced research evidence and data as justification for these measures, several stakeholders expressed skepticism about the information...

Dynamic remodeling of centrioles and the microtubule cytoskeleton in the lifecycle of chytrid fungi.

Thu, 11 Sep 2025 00:00:00 +0000

Cell movement and division are complex behaviors driven by a dynamic internal cytoskeleton. The molecular components and principles of cytoskeletal assembly are well studied, but less is known about cytoskeletal remodeling events, including how centrioles transition from ciliary base to centrosome. Here, we address this using the chytrid Rhizoclosmatium globosum, a zoosporic fungus that has centrioles and cilia, lost in most fungal lineages. Chytrids undergo reorganization of their microtubule cytoskeleton as they grow from zoospore to multinucleated coenocyte. We use evolutionary comparison, RNA-sequencing, and expansion microscopy to understand this reorganization and further develop this organism as a model for evolutionary cell biology. We find that when motile zoospores transition to sessile sporangia, cilia are retracted into the cytoplasm and degraded, while centrioles detach from the ciliary axoneme yet persist. During the mitotic cycles, short centrioles are associated...

Effect of Oceanic Islands on an Insect Symbiont Genome in Transition to a Host-Restricted Lifestyle

Fri, 29 Aug 2025 00:00:00 +0000

Islands offer unique opportunities to study adaptive radiations and their impacts on host genome evolution. In Hawaiian Pariaconus psyllids, all species harbor the ancient nutritional symbiont Carsonella, while only free-living and open-gall species on younger islands host a second stable cosymbiont, Makana. In contrast, a third cosymbiont, Malihini, appears to be in an early stage of host restriction and genome degradation, making it a valuable model for understanding symbiont evolution during island radiations. Here, we examine Malihini genome evolution across multiple Pariaconus lineages using 16S rRNA sequencing, metagenomics, phylogenetic reconstruction, and microscopy. We find that Malihini is codiversifying with its hosts on the oldest island Kaua'i (kamua group; open- and closed-gall makers) and on the younger islands only in free-living species (bicoloratus group). Comparison of five Malihini genomes-including three newly assembled in this study-shows ongoing genome reduction...

Kingdom-wide CRISPR guide design with ALLEGRO

Thu, 28 Aug 2025 00:00:00 +0000

Designing CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) single guide RNA (sgRNA) libraries targeting entire kingdoms of life will significantly advance genetic research in diverse and underexplored taxa. Current sgRNA design tools are often species-specific and fail to scale to large, phylogenetically diverse datasets, limiting their applicability to comparative genomics, evolutionary studies, and biotechnology. Here, we introduce ALLEGRO, a combinatorial optimization algorithm designed to compose minimal, yet highly effective sgRNA libraries targeting thousands of species at the same time. Leveraging integer linear programming, ALLEGRO identified compact sgRNA sets simultaneously targeting multiple genes of interest for over 2000 species across the fungal kingdom. We experimentally validated sgRNAs designed by ALLEGRO in Kluyveromyces marxianus, Komagataella phaffii, Yarrowia lipolytica, and Saccharomyces cerevisiae, confirming successful genome...

Genome annotation of Aspergillus melleus strain CBS 546.65

Thu, 28 Aug 2025 00:00:00 +0000

The fungus Aspergillus melleus is an important biosynthesis host for varied commercial applications. Gene annotation of a previously published genome produced 12,841 protein-coding genes and identified 102 biosynthetic gene clusters.

Epistasis between Na+/K+-ATPase Substitutions May Influence Salinity Tolerance in Steinernema Entomopathogenic Nematodes

Thu, 28 Aug 2025 00:00:00 +0000

Soil salinity varies widely across geographies both due to natural factors and human activities, including agriculture, road salt application, sea level rise, and desertification. Increases in soil salinity may affect organisms widely and particularly impact soil foodwebs. As parasites, entomopathogenic nematodes (EPNs) occupy crucial links in soil foodwebs and are important for agriculture as biological control agents of insect pests. Previous research found that the EPN Steinernema carpocapsae may exhibit higher salt tolerance than several of its congeners. We recently identified that S. carpocapsae uniquely evolved two amino acid substitutions in the first extracellular loop of the sodium pump (Na⁺/K⁺-ATPase). Here, we tested if these substitutions explain S. carpocapsae's reported lower sensitivity to salt. Our results confirm that S. carpocapsae exhibits higher salt tolerance and show it can more effectively locate and infect...

Absolute abundance unveils Basidiobolus as a cross-domain bridge indirectly bolstering gut microbiome homeostasis

Thu, 28 Aug 2025 00:00:00 +0000

The host microbiome is integral to metabolism, immune function, and pathogen resistance. Yet, reliance on relative abundance in microbiome studies introduces compositional biases that obscure ecological interpretation, while the absence of robust tools for absolute abundance quantification has limited biological discovery. Here, we apply absolute abundance profiling to uncover host-specific microbial patterns across herpetofauna orders that are masked in relative abundance data. Relative- and absolute abundance-derived bacterial and fungal microbiomes exhibit divergent profiles shaped by compositional bias and multifactorial effects. Absolute abundance identified key genera, Lactococcus, Parabacteroides, and Cetobacterium in salamanders, and Basidiobolus and Mortierella in lizards, turtles, snakes, and tortoises, that consistently emerged as core taxa, revealing host-associated patterns previously obscured by compositional constraints. In closely related Desmognathus species,...

Activation of the Trichodimerol Pathway through Deletion of mcrA in Marine Penicillium rubens YAP001

Thu, 28 Aug 2025 00:00:00 +0000

Fungal secondary metabolites (SMs) are complex organic compounds comprising a variety of biological activities that are essential in medicine. These natural products can be found in various environments, with studies demonstrating the importance of studying marine-sourced fungi due to the increased potency of the compounds they produce. In this study, we sourced a Penicillium rubens YAP001 strain isolated from Exaiptasia diaphana and explored an avenue for the upregulation of its SMs by combining the one-strain-many-compounds (OSMAC) strategy with genetic manipulation of negative global regulator of secondary metabolism, mcrA. Here, we generated a mcrAΔ strain of marine P. rubens (YAP001), which led to the detection of sorbicillinoids, which is significant due to the prior discovery that these compounds illicit cytotoxic effects that have the potential as an anticancer agent. Specifically, we found that sorbicillin was not only upregulated but...

Predicting Antibody–Antigen Interactions with Structure-Aware LLMs: Insights from SARS-CoV‑2 Variants

Thu, 28 Aug 2025 00:00:00 +0000

Predicting antibody-antigen interactions is a critical step in developing new therapeutics to defend against viral infections. However, measuring the extent of these interactions in vitro is costly and time-consuming. With the increased availability of experimental data, predictive methods using machine learning, particularly large language models (LLMs), have emerged as a powerful alternative to wet lab experiments. Here we focus on antibodies targeting SARS-CoV-2 variants, given the abundance of data on this highly contagious virus and the impact of COVID-19 on human life. The objective of this work is to predict the binding and the neutralizing properties of SARS-CoV-2 antibodies. While there are many studies on predicting binding, to the best of our knowledge, we are the first to address the problem of predicting the neutralizing properties of SARS-CoV-2 antibodies. Here we propose a new classifier that combines LLMs with structural information. Extensive experimental...

Revisiting the ‘sterilising cure’ terminology: a call for more patient-centred perspectives on HIV cure-related research

Wed, 20 Aug 2025 00:00:00 +0000

The literature on HIV therapeutics research is rife with terminology associating 'sterilisation' with HIV cure. We find connotations of the word 'sterilising' problematic for the HIV cure research field. In this viewpoint, we review associations of sterilising with concepts of disinfection or cleansing, as well as coerced sterilisation. We discuss emerging findings from socio-behavioural research that show aversion from people living with HIV towards the 'sterilising cure' nomenclature. We call for more collaborations with people with HIV as partners to help define what would be a more acceptable terminology for describing an HIV cure.

Phyling: phylogenetic inference from annotated genomes

Thu, 14 Aug 2025 00:00:00 +0000

Phyling is a fast, scalable, and user-friendly tool supporting phylogenomic reconstruction of species phylogenies directly from protein-encoded genomic data. It identifies orthologous genes by searching a sample's protein sequences against a Hidden Markov Models marker set, containing single-copy orthologs, retrieved from the BUSCO database. In the final step, users can choose between consensus and concatenation strategies to construct the species tree from the aligned orthologs. Phyling efficiently resolves large phylogenies by optimizing memory usage and data processing. Its checkpoint system enables users to incrementally add or remove samples without repeating the entire search process. For analyses involving closely related taxa, Phyling supports the use of nucleotide coding sequences, which may capture phylogenetic signals missed by protein sequences. The benchmark results show that Phyling substantially runs faster than OrthoFinder, a Reciprocal Best Hit based method, while...

Giant transposons promote strain heterogeneity in a major fungal pathogen

Thu, 14 Aug 2025 00:00:00 +0000

Fungal infections are difficult to prevent and treat in large part due to strain heterogeneity, which confounds diagnostic predictability. Yet, the genetic mechanisms driving strain-to-strain variation remain poorly understood. Here, we determined the extent to which Starships-giant transposons capable of mobilizing numerous fungal genes-generate genetic and phenotypic variability in the opportunistic human pathogen Aspergillus fumigatus. We analyzed 519 diverse strains, including 11 newly sequenced with long-read technology and multiple isolates of the same reference strain, to reveal 20 distinct Starships that are generating genomic heterogeneity over timescales relevant for experimental reproducibility. Starship-mobilized genes encode diverse functions, including known biofilm-related virulence factors and biosynthetic gene clusters, and many are differentially expressed during infection and antifungal exposure in a strain-specific manner. These...