WDR26 depletion alters chromatin accessibility and gene expression profiles in mammalian cells.

WD-repeat containing protein 26 (WDR26) is an essential component of the CTLH E3 ligase complex. Mutations in WDR26 lead to Skraban-Deardorff, an intellectual disability syndrome with clinical features resembling other disorders arising from defects in transcriptional regulation and chromatin structure. However, the role of WDR26 and its associated CTLH complex in regulating chromatin or transcription has not been elucidated.

Activation of protein kinase C decreases equilibrative nucleobase transporter 1-mediated substrate uptake via phosphorylation of threonine 231.

Protein kinase C (PKC) signalling has been shown to be dysregulated in various cancers including acute lymphoblastic leukemia (ALL). We have previously determined that changes in the expression levels of SLC43A3-encoded equilibrative nucleobase transporter 1 (ENBT1) can significantly alter 6-mercaptopurine (6-MP) toxicity in ALL cells. 6-MP is a common drug used in ALL chemotherapy.

Exploring the Influence of Interorganization Networks on the Dissemination of National Health Behavior Guidelines.

Background: Interorganization partnerships are important for the development and knowledge mobilization of national health behavior guidelines. However, little is known about how to improve the dissemination of guidelines across professional networks. Social network analysis may offer unique insight into the social structure of interorganization networks and provide guidance for how network features may be harnessed for effective dissemination.

Viscous fingering and interface splitting instabilities in air-water-oil systems.

Hypothesis: Viscous fingering instabilities of air displacing water displacing mineral oil is controlled by the air injection rate. Given the lower viscosity of the water, air would tend to finger through the water and then after it reaches the oil, proceed to finger through the oil.

Experiments: In a radial Hele-Shaw cell, experiments were conducted on air injection into mineral oil and air injection into a volume of water at the center of the cell which in turn is surrounded by mineral oil.

Cyclist safety assessment using autonomous vehicles.

Proactive and holistic safety management approaches should consider multi-modal crash risk. Cyclist crash risk should be prioritized given the high-severity of vehicle-cyclist crashes. Cyclist crash risk is difficult to quantify given the sparse nature of cyclist collisions and collisions in general.

Immune responses to avian influenza viruses in chickens.

Chickens are a key species in both the manifestation of avian influenza and the potential for zoonotic transmission. Avian influenza virus (AIV) infection in chickens can range from asymptomatic or mild disease with low pathogenic AIVs (LPAIVs) to systemic fatal disease with high pathogenic AIVs (HPAIVs). During AIV infection in chickens, Toll-like receptor 7 and melanoma differentiation-associated gene 5 are upregulated to detect the single-stranded ribonucleic acid genomes of AIV, triggering a signaling cascade that produces interferons (IFNs) and pro-inflammatory cytokines.

Reappraising beliefs about losing control: An experimental investigation.

Background And Objectives: Beliefs about losing control over one's thoughts, emotions, behaviours, and/or bodily functions have been shown to cause obsessive-compulsive symptoms. The cognitive model of obsessive-compulsive disorder (OCD) suggests that catastrophic misappraisals of intrusions will lessen if underlying maladaptive beliefs are effectively reduced. The primary aim of this study was to experimentally investigate whether preexisting negative appraisals about losing control could be reduced by reappraising a previous perceived loss of control.

Assessing foraging landscape quality in Quebec's commercial beekeeping through remote sensing, machine learning, and survival analysis.

Honey bees (Apis mellifera) play an important role in our agricultural systems. In recent years, beekeepers have reported high colony mortality rates in several parts of the world. Inadequate foraging landscapes are often cited as a major factor deterring honey bee colony health.

A generalizable normative deep autoencoder for brain morphological anomaly detection: application to the multi-site StratiBip dataset on bipolar disorder in an external validation framework.

The heterogeneity of psychiatric disorders makes researching disorder-specific neurobiological markers an ill-posed problem. Here, we face the need for disease stratification models by presenting a generalizable multivariate normative modelling framework for characterizing brain morphology, applied to bipolar disorder (BD). We used deep autoencoders in an anomaly detection framework, combined for the first time with a confounder removal step that integrates training and external validation.

Solution NMR goes big: Atomic resolution studies of protein components of molecular machines and phase-separated condensates.

The tools of structural biology have undergone remarkable advances in the past decade. These include new computational and experimental approaches that have enabled studies at a level of detail - and ease - that were not previously possible. Yet, significant deficiencies in our understanding of biomolecular function remain and new challenges must be overcome to go beyond static pictures towards a description of function in terms of structural dynamics.

Study of the TOFPET2c ASIC in time-of-flight detection of x-rays for scatter rejection in medical imaging applications.

Integrating time-of-flight (ToF) measurements in radiography and computed tomography (CT) enables an approach for scatter rejection in imaging systems that eliminates the need for anti-scatter grids, potentially increasing system sensitivity and image quality. However, present hardware dedicated to the time-correlated measurement of X-rays is limited to a small scale and low density. A switch to highly integrated electronics and detectors is needed to progress towards a medium-scale system capable of acquiring images, while offering a timing resolution below 300 ps FWHM to achieve scatter rejection comparable to current grids.

Disitamab vedotin in preclinical models of HER2-positive breast and gastric cancers resistant to trastuzumab emtansine and trastuzumab deruxtecan.

Background: Most HER2-positive breast or gastric cancers eventually become resistant to the approved anti-HER2 antibody-drug conjugates (ADC) trastuzumab emtansine (T-DM1) and trastuzumab deruxtecan (T-DXd). Disitamab vedotin (DV) is a novel anti-HER2 ADC that binds to a different epitope on HER2 compared to trastuzumab. We assessed the efficacy of DV in breast and gastric cancer cell lines and xenografts, including tumor models resistant to T-DM1 and T-DXd.

Peripheral blood age-sensitive immune markers in multiple sclerosis: relation to sex, cytomegalovirus status, and treatment.

Background: Immunosenescence is accelerated by chronic infectious and autoimmune diseases and could contribute to the pathobiology of multiple sclerosis (MS). How MS and disease-modifying therapies (DMTs) impact age-sensitive immune biomarkers is only partially understood.

Methods: We analyzed 771 serum samples from 147 healthy controls and 289 people with MS (PwMS) by multiplex immunoassays.

Probing Autism and ADHD subtypes using cortical signatures of the T1w/T2w-ratio and morphometry.

Autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) are neurodevelopmental conditions that share genetic etiology and frequently co-occur. Given this comorbidity and well-established clinical heterogeneity, identifying individuals with similar brain signatures may be valuable for predicting clinical outcomes and tailoring treatment strategies. Cortical myelination is a prominent developmental process, and its disruption is a candidate mechanism for both disorders.

Understanding the Glycosylation Pathways Involved in the Biosynthesis of the Sulfated Glycan Ligands for Siglecs.

Carbohydrate sulfation plays a pivotal role in modulating the strength of Siglec-glycan interactions. Recently, new aspects of Siglec binding to sulfated cell surface carbohydrates have been discovered, but the class of glycan presenting these sulfated Siglec ligands has not been fully elucidated. In this study, the contribution of different classes of glycans to and Siglec ligands was investigated within cells expressing the carbohydrate sulfotransferase 1 (CHST1) or CHST2.

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El trastorno por déficit de atención e hiperactividad (TDAH) ha sido tradicionalmente concebido como una condición privativa de la infancia. Sin embargo, una creciente evidencia sugiere que el TDAH persiste en la vida adulta, manifestándose de diversas maneras. A pesar de su prevalencia y de las significativas consecuencias en la vida cotidiana, el TDAH en adultos ha sido considerablemente subestimado y subdiagnosticado, lo que resulta en una carga sustancial tanto para los individuos afectados como para su entorno familiar y social.

Deep Learning-Enabled Assessment of Right Ventricular Function Improves Prognostication After Transcatheter Edge-to-Edge Repair for Mitral Regurgitation.

Background: Right ventricular (RV) function has a well-established prognostic role in patients with severe mitral regurgitation (MR) undergoing transcatheter edge-to-edge repair (TEER) and is typically assessed using echocardiography-measured tricuspid annular plane systolic excursion. Recently, a deep learning model has been proposed that accurately predicts RV ejection fraction (RVEF) from 2-dimensional echocardiographic videos, with similar diagnostic accuracy as 3-dimensional imaging. This study aimed to evaluate the prognostic value of the deep learning-predicted RVEF values in patients with severe MR undergoing TEER.

Balancing central control and sensory feedback produces adaptable and robust locomotor patterns in a spiking, neuromechanical model of the salamander spinal cord.

This study introduces a novel neuromechanical model employing a detailed spiking neural network to explore the role of axial proprioceptive sensory feedback, namely stretch feedback, in salamander locomotion. Unlike previous studies that often oversimplified the dynamics of the locomotor networks, our model includes detailed simulations of the classes of neurons that are considered responsible for generating movement patterns. The locomotor circuits, modeled as a spiking neural network of adaptive leaky integrate-and-fire neurons, are coupled to a three-dimensional mechanical model of a salamander with realistic physical parameters and simulated muscles.

Feasibility, safety and tolerability of estrogen and/or probiotics for improving vaginal health in Canadian African, Caribbean, and Black women: A pilot phase 1 clinical trial.

Background: A dysbiotic vaginal microbiome (VMB) is associated with clinical conditions such as bacterial vaginosis (BV) and an increased risk of human immunodeficiency virus (HIV-1) infection. Considering the high prevalence of BV among African, Caribbean and Black (ACB) women, we conducted a prospective, randomized, open-label phase 1 clinical trial to determine the feasibility, safety and tolerability of administering low-dose estrogen, probiotics or both in combination to improve vaginal health and decrease HIV-1 susceptibility.

Methods: ACB women aged 18-49 from the Greater Toronto Area (GTA) were randomized to one of four study arms: intravaginal estradiol (Estring©; 7.