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Proteomic investigation of signaling dynamics: from static maps to network rewiring

11 hours 39 minutes ago
Cellular processes are controlled by interconnected networks of protein-protein interactions that can be dynamically regulated by post-translational modifications such as phosphorylation. Dysregulation of signaling pathways can drive cellular transformation and contribute to cancer treatment resistance. Mass spectrometry (MS)-based approaches have emerged as key technologies to study both protein function and their dynamic regulation at a network level. Modern proteomics allows investigators to...
Ugo Dionne

Systematic investigation reveals extensive Epstein-Barr virus transcriptional regulation of the human genome

1 day 11 hours ago
We systematically investigate interactions between Epstein-Barr virus (EBV) transcriptional regulators (viral transcriptional regulators [vTRs]) and the human genome. Starting with 16 known and candidate vTRs, we identify nine whose introduction into human cells results in substantial alterations to host gene expression. Genome-scale profiling of vTR binding, chromatin accessibility alterations, and gene expression impact reveals extensive EBV functional interactions with the human genome,...
Phillip J Dexheimer

The complexities of comprehensive exams in epidemiology

1 day 11 hours ago
Comprehensive exams are a standard component of doctoral-level training programs in epidemiology. In this manuscript, we describe current practices in the administration of comprehensive examinations across doctoral programs in epidemiology and discuss variation in the content, format, and structure of these exams. We present results from a survey about the comprehensive exam process at thirty-three different epidemiology programs. We also discuss a symposium focused on comprehensive exams that...
Hailey R Banack

Vitronectin Modulates Plasma Aβ Oligomerization Propensity Within Altered Albumin Interactome Networks in Alzheimer's Disease

1 day 11 hours ago
Amyloid beta (Aβ) oligomers are key mediators of synaptic dysfunction and neural circuit impairment in Alzheimer's disease (AD). While plasma Aβ oligomerization propensity (OAβ) correlates with cerebral amyloid pathology and cognitive decline, the systemic modulators of OAβ remain poorly understood. In this study, we identified the albumin interactome (albumin and its associated proteins) as a critical regulator of OAβ. Selective depletion of the albumin interactome from plasma eliminated the...
Hojin Kang

Canadian Network for Mood and Anxiety Treatments (CANMAT) and International College of Obsessive-Compulsive Spectrum Disorders (ICOCS) 2025 international guidelines for the management of patients with obsessive-compulsive disorder

3 days 11 hours ago
CONCLUSIONS: The CANMAT/ICOCS 2025 OCD International Guidelines synthesize the evidence on the efficacy, safety, and tolerability of the range of interventions available for the management of OCD. It is anticipated that these new OCD guidelines will enable psychiatrists and other clinicians to provide systematic, evidence-based care for their patients with OCD across the lifespan.
Michael Van Ameringen

Role of Pbr1, a putative oxidoreductase, in the ER quality control and folding of yeast Fks1 glucan synthase

3 days 11 hours ago
The biogenesis of multipass membrane proteins challenges the endoplasmic reticulum (ER) quality control, particularly when transmembrane segments contain polar or charged residues required for function. Fks1, the catalytic subunit of yeast β-(1,3)-glucan synthase, exemplifies this challenge because its large multipass transmembrane architecture must support glucan synthesis at the plasma membrane while also undergoing efficient biogenesis in the ER. Here, we investigate the cellular role of PBR1...
Keisuke Obara

Durum Wheat cv. Svevo Reference Genome Rel.2.0: A Comprehensive Tool for Wheat Genomics

3 days 11 hours ago
Advancements in plant genome sequencing and assembly have enabled the production of increasingly accurate and contiguous genome sequences. Here, we present the chromosome-level assembly of the durum wheat (Triticum turgidum L. ssp. durum, cv. Svevo) reference genome produced using accurate long-reads, optical mapping and Hi-C. The new assembly (Svevo Rel.2.0) comprises 263 hybrid scaffolds with an N50 value of 112.3 Mb, arranged into 14 contiguous pseudomolecules spanning 10.4 Gb. The Svevo...
Elisabetta Mazzucotelli

Critical Dialogues for Action: A Research Methodology for Transforming Engagement into Impact

3 days 11 hours ago
Critical Dialogues for Action (CDFA) is a structured, equity-centered methodology designed to transform dialogue into systemic change in health professions education and health systems. Developed over five years, it integrates lived expertise, structured facilitation, and implementation science into the dialogue process. CDFA operates through three levels: Foundational Elements, Process and Engagement, and Action and Impact. These levels establish conditions to foster connection, disrupt power...
Lyn K Sonnenberg

"It Wasn't Nonadherence": Administrative Workload for Families and Inequitable Outcomes

4 days 11 hours ago
Administrative workload, the work required to understand systems and complete tasks and associated with navigating complex care for families, is an underrecognized yet powerful driver of inequity in pediatric hospital care. We present the case of Mateo, a 7-year-old child with medical complexity admitted with respiratory distress whose hospitalization and subsequent readmission were shaped not by caregiver disengagement but by the cumulative effects of fragmented systems, language barriers, and...
Victor Do

Scaled Multidimensional Assays of Variant Effect Identify Sequence-Function Relationships in Hypertrophic Cardiomyopathy

4 days 11 hours ago
CONCLUSIONS: This work provides a platform for extending genome engineering in induced pluripotent stem cells to multiplexed assays of variant effects across diverse disease-relevant cellular phenotypes, enhancing our understanding of variant pathogenicity and uncovering novel biological mechanisms that could inform therapeutic strategies.
Yuta Yamamoto

Evolutionary Transitions Drive Molecular Adaptation in Sculpin Rhodopsin

5 days 11 hours ago
Evolutionary habitat transitions are known to drive rapid evolution. In fishes, switches between marine and freshwater can promote adaptation in sensory systems; in particular, the disparate visual environments in these aquatic habitats can lead to evolution at all levels of the visual system. We investigate the evolution of dim light-sensitive rhodopsin genes within the sculpin (Cottoidea), a species-rich group of fishes occupying diverse benthic habitats. Two main families include...
Esmé S B Macpherson

El Agente Cuántico: Automating quantum simulations

6 days 11 hours ago
Quantum simulation is central to understanding and designing quantum systems across physics and chemistry. However, its practical use is often limited by the exponential growth of Hilbert space and by the increasing complexity of modern quantum-simulation software. Here we introduce{\cinzel El Agente Cuántico}, a multi-agent AI system that automates quantum-simulation workflows by translating natural-language scientific intent into executed and validated computations across heterogeneous...
Ignacio Gustin

Staphylococcal scalded skin syndrome: a pediatric dermatology emergency

1 week ago
Staphylococcal scalded skin syndrome (SSSS) is a rare, toxin-mediated skin disorder of childhood, caused by the exfoliative toxins ETA and ETB released by Staphylococcus aureus. We report on a 4-year-old boy who presented with a 5-day history of painful, progressive blistering of the face, trunk and anogenital region. Clinical examination revealed widespread erythema with coarse lamellar desquamation, flaccid blisters and a positive Nikolsky sign; the mucous membranes were spared, an important...
Mohammed Mitwalli

Aneuploidy selects for the acquisition of driver genes in breast cancer

1 week 1 day ago
Chromosome instability is highly prevalent in cancer and drives large-scale chromosomal imbalances, known as aneuploidies^(1-4). How aneuploidy contributes to tumorigenesis remains difficult to study due to the vast numbers of genes affected. Here we established a CRISPR knockout- and activation-linked assay (CRISPR-KOALA), enabling high-throughput bidirectional genetic screens in immunocompetent mouse models of cancer. We developed a compendium of the ten most frequent human...
Khalid N Al-Zahrani

Dysregulation of Human ClpP Using Small Molecules with Piperazine-Based Scaffold for Diffuse Intrinsic Pontine Glioma Therapy Validated by Patient-Derived Tumor Organoids

1 week 1 day ago
Diffuse intrinsic pontine glioma (DIPG) is a dismal pediatric brainstem tumor with a median survival of approximately 12 months and no curative treatments. ONC201, the most clinically characterized small-molecule, selectively activates human caseinolytic protease P (hClpP). Guided by X-ray structure of the hClpP:ONC201 complex, piperazine-based derivatives were designed and identified compound 26 (DA29) as a lead. Structural studies confirmed its binding to the enzyme hydrophobic allosteric...
Morena Miciaccia

Integrating diversity, equity, and inclusion in generative AI applications for healthcare education: a scoping review

1 week 3 days ago
CONCLUSION: By identifying these gaps, this review offers a foundation for developing frameworks that support systematic DEI integration across the GenAI lifecycle, from innovation development and implementation through to evaluation, and informs future research directions by calling for multi-perspective collaboration and institutional accountability in how GenAI is monitored and evaluated. This scoping review represents an important first step upon which future efforts can build to advance the...
Hwayeon Danielle Shin

A joint model for a longitudinal outcome and a progressive multistate model under a mixed observation scheme

1 week 6 days ago
Joint models for longitudinal and event-time data can be used to understand the co-development of multiple correlated non-fatal outcomes, such as those encountered when studying diabetic microvascular complications. However, such models were not developed for event-times characterized by a multistate process where the entry time into certain states is interval-censored, which is an important feature of interval cohort study designs. Our aim was to develop a joint model for this setting....
Leif Erik Lovblom