Incomplete remyelination via therapeutically enhanced oligodendrogenesis is sufficient to recover visual cortical function.

Myelin loss induces neural dysfunction and contributes to the pathophysiology of neurodegenerative diseases, injury conditions, and aging. Because remyelination is often incomplete, better understanding endogenous remyelination and developing remyelination therapies that restore neural function are clinical imperatives. Here, we use in vivo two-photon microscopy and electrophysiology to study the dynamics of endogenous and therapeutic-induced cortical remyelination and functional recovery after cuprizone-mediated demyelination in mice.

BK channels mediate a presynaptic form of mGluR-LTD in the neonatal hippocampus.

BK channels can control neuronal function, but their functional relevance in activity-dependent changes of synaptic function remains elusive. Here, we report that repetitive low-frequency stimulation activates BK channels through 12(S)HPETE, an arachidonic acid metabolite, produced downstream of postsynaptic metabotropic glutamate receptors (mGluRs) to trigger long-term depression (LTD) at CA3-CA1 synapses in hippocampal slices from P7-P10 mice. Activation of BK channels is subunit specific, as paxilline but not iberiotoxin blocked mGluR-LTD.

A multiplex method for rapidly identifying viral protease inhibitors.

With current treatments addressing only a fraction of pathogens and new viral threats constantly evolving, there is a critical need to expand our existing therapeutic arsenal. To speed the rate of discovery and better prepare against future threats, we establish a high-throughput platform capable of screening compounds against 40 diverse viral proteases simultaneously. This multiplex approach is enabled by using cellular biosensors of viral protease activity combined with DNA-barcoding technology, as well as several design innovations that increase assay sensitivity and correct for plate-to-plate variation.

Development of small molecule non-covalent coronavirus 3CL protease inhibitors from DNA-encoded chemical library screening.

Variants of SARS-CoV-2 have continued to emerge across the world and cause hundreds of deaths each week. Due to the limited efficacy of vaccines against SARS-CoV-2 and resistance to current therapies, additional anti-viral therapeutics with pan-coronavirus activity are of high interest. Here, we screen 2.

Religion, spirituality, and DNA methylation in HPA-axis genes among Hispanic/Latino adults.

Aim: Investigate associations between religion and spirituality (R&S) and DNA methylation of four HPA-axis genes (i.e. 14 CpG sites) among 992 adults from the Hispanic Community Health Study/Study of Latinos cohorts.

Health systems responsiveness towards needs of pregnant women in Vietnam.

Background: Health systems that are responsive to maternal mental health recognise the importance of integrating mental health services into maternal care. Studies from Vietnam have reported particularly high rates of common perinatal mental health disorders (CPMDs) in both rural and urban areas of the country. Despite the increasing burden of maternal mental health conditions, there is currently no guidance on the screening for CPMDs within maternal care, both antenatal and postnatal.

Hyperactive neuronal networks facilitate tau spread in an Alzheimer's disease mouse model.

Pathological tau spreads throughout the brain along neuronal connections in Alzheimer's disease (AD), but the mechanisms that underlie this process are poorly understood. Given the high incidence and deleterious consequences of epileptiform activity in AD, we hypothesized neuronal hyperactivity and seizures are key factors in tau spread. To examine these interactions, we created a novel mouse model involving the cross of targeted recombination in active populations (TRAP) mice and the 5 times familial AD (5XFAD; 5X-TRAP) model allowing for the permanent fluorescent labelling of neuronal activity.

Effect of dapagliflozin on renal haemodynamics in hyperfiltering T2D patients.

Aims: To investigate the effect of sodium-glucose co-transporter 2 inhibitor [SGLT-2i] therapy on renal haemodynamics in T2D patients with glomerular hyperfiltration.

Materials And Methods: Sixty T2D patients with elevated [HYPER] and normal [NORMO] GFR were randomized to dapagliflozin 10 mg/day [DAPA/HYPER, n = 15; DAPA/NORMO, n = 15] or to metformin/glipizide [CONTROL/HYPER, n = 15; CONTROL/NORMO, n = 15] to reach similar glycaemic control after 4 months. GFR was measured with Iohexol and hyperfiltration was empirically defined as >125 mL/min/1.

Mitral Annular Disjunction Associated with Ventricular Dilation in Pediatric Marfan Syndrome: A Cardiovascular Magnetic Resonance Study.

Background: Mitral annular disjunction (MAD) has increasingly been recognized as a marker for adverse cardiovascular events in Marfan syndrome (MFS). As recent adult data links MFS with left ventricular (LV) dilation and reduced ejection fraction (LVEF), we hypothesized that MAD may be associated with LV dilation in pediatric MFS patients.

Methods: A retrospective analysis was performed among MFS patients < 19 years old at initial cardiac MRI (CMR).

Assessing Rapid Adaptation Through Epigenetic Inheritance: A New Experimental Approach.

Epigenetic inheritance is hypothesized to lead to rapid adaptation, yet evidence is scarce, possibly because of the current experimental approaches. We propose a new approach to simultaneously assess whether species adapt through selection of epimutations or formation of stress‐induced epialleles.

Results of a Pilot Trial Assessing the Effects of Proper Oral Hygiene and a Probiotic Dietary Supplement on Oral Health in Volunteers with Oral Malodor.

Persistent malodor affects many people worldwide and is usually associated with poor dental hygiene. This pilot trial aimed to determine whether proper dental hygiene (DH) and a probiotic dietary supplement support oral health in volunteers with persistent malodor. Volunteers ( = 35) were randomly assigned to the probiotic or placebo cohort.

Downscaling precipitation and temperature in the Andes: applied methods and performance-a systematic review protocol.

Background: Global warming and climate change are threats to the world. Warmer temperatures and changes in precipitation patterns alter water availability and increase the occurrence of extreme weather events. South America and the Andes are vulnerable regions to climate change due to inequity and the uneven distribution of resources.

Kinetic modelling of UV and UV/HO oxidation of an aqueous mixture of antibiotics in a completely mixed batch photoreactor.

The removal kinetics of an aqueous mixture of thirteen antibiotics (i.e., ampicillin, cefuroxime, ciprofloxacin, flumequine, metronidazole, ofloxacin, oxytetracycline, sulfadimethoxine, sulfamethoxazole, sulfamethazine, tetracycline, trimethoprim and tylosin) by batch UV and UV/HO processes has been modeled in this work.

Impact of KDM6B mosaic brain knockout on synaptic function and behavior.

Autism spectrum disorders (ASD) are complex neurodevelopmental conditions characterized by impairments in social communication, repetitive behaviors, and restricted interests. Epigenetic modifications serve as critical regulators of gene expression playing a crucial role in controlling brain function and behavior. Lysine (K)-specific demethylase 6B (KDM6B), a stress-inducible H3K27me3 demethylase, has emerged as one of the highest ASD risk genes, but the precise effects of KDM6B mutations on neuronal activity and behavioral function remain elusive.

Effects of a Single Session of Mindfulness and Compassion on Skin Temperature in Breast Cancer Survivors.

Previous studies have suggested that mindfulness programs can be useful, in a significant sector of the population, to reduce stress when practiced for at least 8 weeks. The objective of the present investigation was to explore the effect of a single session of mindfulness practice in reducing stress in female cancer survivors. Two repeated measures studies were applied; in the first one, it was performed individually, while in the second one, it was performed in a group.

Testing the PEST hypothesis using relevant Rett mutations in MeCP2 E1 and E2 isoforms.

Mutations in methyl-CpG binding protein 2 (MeCP2), such as the T158M, P152R, R294X, and R306C mutations, are responsible for most Rett syndrome (RTT) cases. These mutations often result in altered protein expression that appears to correlate with changes in the nuclear size; however, the molecular details of these observations are poorly understood. Using a C2C12 cellular system expressing human MeCP2-E1 isoform as well as mouse models expressing these mutations, we show that T158M and P152R result in a decrease in MeCP2 protein, whereas R306C has a milder variation, and R294X resulted in an overall 2.

Improving Public Health Emergency Communication Along the U.S. Southern Border: Insights From a COVID-19 Pilot Campaign With Truck Drivers.

Tens of thousands of trucks cross the U.S.-Mexico border every day.

Prevalence of Self-Reported COVID-19 Infection in Persons with Complicated Mild to Severe Traumatic Brain Injury (TBI): A TBI Model Systems Study.

Objective: To describe the incidence of self-reported COVID-19 history in a longitudinal cohort of individuals with complicated mild to severe traumatic brain injury (TBI) and describe demographic, injury and functional differences based on history of COVID-19 infection.

Design: Individuals with complicated mild to severe TBI aged 16 or older at time of injury who were enrolled in the TBI Model Systems longitudinal cohort study, completed a baseline or follow-up interview between October 1, 2021-March 31, 2023, and provided information about COVID-19 history and timing of COVID-19 infection was collected.

Results: Of the 3,627 individuals included in the analysis, 29.

Bidirectional modulation of negative emotional states by parallel genetically-distinct basolateral amygdala pathways to ventral striatum subregions.

Distinct basolateral amygdala (BLA) cell populations influence emotional responses in manners thought important for anxiety and anxiety disorders. The BLA contains numerous cell types which can broadcast information into structures that may elicit changes in emotional states and behaviors. BLA excitatory neurons can be divided into two main classes, one of which expresses (encoding protein phosphatase 1 regulatory inhibitor subunit 1B) which is downstream of the genes encoding the D1 and D2 dopamine receptors ( and respectively).

Deletion of VPS50 protein in mouse brain impairs synaptic function and behavior.

Background: The VPS50 protein functions in synaptic and dense core vesicle acidification, and perturbations of VPS50 function produce behavioral changes in Caenorhabditis elegans. Patients with mutations in VPS50 show severe developmental delay and intellectual disability, characteristics that have been associated with autism spectrum disorders (ASDs). The mechanisms that link VPS50 mutations to ASD are unknown.

Retrograde adenosine/A receptor signaling facilitates excitatory synaptic transmission and seizures.

Retrograde signaling at the synapse is a fundamental way by which neurons communicate and neuronal circuit function is fine-tuned upon activity. While long-term changes in neurotransmitter release commonly rely on retrograde signaling, the mechanisms remain poorly understood. Here, we identified adenosine/A receptor (AR) as a retrograde signaling pathway underlying presynaptic long-term potentiation (LTP) at a hippocampal excitatory circuit critically involved in memory and epilepsy.