Evaluation of synaptotagmin-1 action models by all-atom molecular dynamics simulations.

Neurotransmitter release is triggered in microseconds by the two C domains of the Ca sensor synaptotagmin-1 and by SNARE complexes, which form four-helix bundles that bridge the vesicle and plasma membranes. The synaptotagmin-1 CB domain binds to the SNARE complex via a 'primary interface', but the mechanism that couples Ca-sensing to membrane fusion is unknown. Widespread models postulate that the synaptotagmin-1 Ca-binding loops accelerate membrane fusion by inducing membrane curvature, perturbing lipid bilayers or helping bridge the membranes, but these models do not seem compatible with SNARE binding through the primary interface, which orients the Ca-binding loops away from the fusion site.

Machine Learning Quantum Mechanical/Molecular Mechanical Potentials: Evaluating Transferability in Dihydrofolate Reductase-Catalyzed Reactions.

Integrating machine learning potentials (MLPs) with quantum mechanical/molecular mechanical (QM/MM) free energy simulations has emerged as a powerful approach for studying enzymatic catalysis. However, its practical application has been hindered by the time-consuming process of generating the necessary training, validation, and test data for MLP models through QM/MM simulations. Furthermore, the entire process needs to be repeated for each specific enzyme system and reaction.

Structural Transformation and Degradation of Cu Oxide Nanocatalysts during Electrochemical CO Reduction.

The electrochemical CO reduction reaction (CORR) holds enormous potential as a carbon-neutral route to the sustainable production of fuels and platform chemicals. The durability for long-term operation is currently inadequate for commercialization, however, and the underlying deactivation process remains elusive. A fundamental understanding of the degradation mechanism of electrocatalysts, which can dictate the overall device performance, is needed.

Genome-wide association studies are enriched for interacting genes.

Background: With recent advances in single cell technology, high-throughput methods provide unique insight into disease mechanisms and more importantly, cell type origin. Here, we used multi-omics data to understand how genetic variants from genome-wide association studies influence development of disease. We show in principle how to use genetic algorithms with normal, matching pairs of single-nucleus RNA- and ATAC-seq, genome annotations, and protein-protein interaction data to describe the genes and cell types collectively and their contribution to increased risk.

Resilience in maternal, newborn, and child health in low- and middle-income countries: findings from a scoping review.

Objectives: The research objectives were to identify and synthesise prevailing definitions and indices of resilience in maternal, newborn, and child health (MNCH) and propose a harmonised definition of resilience in MNCH research and health programmes in low- and middle-income countries (LMICs).

Design: Scoping review using Arksey and O'Malley's framework and a Delphi survey for consensus building.

Participants: Mothers, new-borns, and children living in low- and middle-income countries were selected as participants.

Nurse workforce change and metropolitan medically underserved areas in the United States.

Background: The continued healthcare crisis in the United States (US) is worrisome, especially as workforce shortages, particularly for nurses, are highlighted, often in some of the highest need areas. As the need for healthcare services grows, especially for services that nurses can deliver, the inability to meet those needs exacerbates existing disparities in access to care and can jeopardize the quality and timeliness of healthcare delivery in underserved communities. Prior investigations have used varying definitions to describe underserved, under-resourced, rural, or health professional shortage areas to examine the relationship between these areas and workforce shortages.

Chronic and infectious respiratory mortality and short-term exposures to four types of pollen taxa in older adults in Michigan, 2006-2017.

Introduction: Levels of plant-based aeroallergens are rising as growing seasons lengthen and intensify with anthropogenic climate change. Increased exposure to pollens could increase risk for mortality from respiratory causes, particularly among older adults. We determined short-term, lag associations of four species classes of pollen (ragweed, deciduous trees, grass pollen and evergreen trees) with respiratory mortality (all cause, chronic and infectious related) in Michigan, USA.

Copper Tantalate by a Sodium-Driven Flux-Mediated Synthesis for Photoelectrochemical CO Reduction.

Copper-tantalate, CuTaO (CTO), shows significant promise as an efficient photocathode for multi-carbon compounds (C) production through photoelectrochemical (PEC) CO reduction, owing to its suitable energy bands and catalytic surface. However, synthesizing CTO poses a significant challenge due to its metastable nature and thermal instability. In this study, this challenge is addressed by employing a flux-mediated synthesis technique using a sodium-based flux to create sodium-doped CTO (Na-CTO) thin films, providing enhanced nucleation and stabilization for the CTO phase.

"The Forgotten Minority": Perpetuation of Ableism in Medical Education.

Background: Accounting for approximately 1 in 4 community-dwelling adults in the United States (US), people with disabilities (PWD) experience significant disparities in health care quality, access, and outcomes. At the same time, US physicians have reported feeling unprepared to care for PWD and have revealed significant negative bias about this population.

Objective: To understand how physicians are trained to care for PWD in US medical schools.

In a visual inverted pendulum balancing task avoiding impending falls gets harder as we age.

Younger adults (YA) and older adults (OA) used a joystick to stabilize an unstable visual inverted pendulum (VIP) with a fundamental frequency (.27 Hz) of half that of bipedal human sway. Their task was to keep the VIP upright and to avoid ± 60° "fall" boundaries.

Recent trends in scientific research in chest radiology: What to do or not to do? That is the critical question in research.

Hereby inviting young rising stars in chest radiology in Japan for contributing what they are working currently, we would like to show the potentials and directions of the near future research trends in the research field. I will provide a reflection on my own research topics. At the end, we also would like to discuss on how to choose the themes and topics of research: What to do or not to do? We strongly believe it will stimulate and help investigators in the field.

The impact of kidney disease on peri-operative outcomes of novel BPH surgeries across the board: a propensity score matched analysis using the ACS-NSQIP database.

Background: Pre-operative kidney disease was shown to impact peri-operative outcomes of endoscopic BPH surgeries. We aim to assess the effect of novel surgical techniques (Laser Enucleation of the Prostate (LEP) and Laser Vaporization of the Prostate (LVP)) compared to Transurethral Resection of Prostate (TURP), on post-operative outcomes stratified based on kidney function.

Methods: The ACS-NSQIP database was reviewed from 2008 to 2021 for 83,020 patients that underwent TURP, LEP, and LVP.

Noninvasive Vagus Nerve Stimulation Protects Neurons in the Perihematomal Region and Improves the Outcomes in a Rat Model of Intracerebral Hemorrhage.

Background: Intracranial hemorrhage (ICH) is a devastating stroke subtype with a high rate of mortality and disability. Therapeutic options available are primarily limited to supportive care and blood pressure control, whereas the surgical approach remains controversial. In this study, we explored the effects of noninvasive vagus nerve stimulation (nVNS) on hematoma volume and outcome in a rat model of collagenase-induced ICH.

Resolving tissue complexity by multimodal spatial omics modeling with MISO.

Spatial molecular profiling has provided biomedical researchers valuable opportunities to better understand the relationship between cellular localization and tissue function. Effectively modeling multimodal spatial omics data is crucial for understanding tissue complexity and underlying biology. Furthermore, improvements in spatial resolution have led to the advent of technologies that can generate spatial molecular data with subcellular resolution, requiring the development of computationally efficient methods that can handle the resulting large-scale datasets.

Probing the physical hallmarks of cancer.

The physical microenvironment plays a crucial role in tumor development, progression, metastasis and treatment. Recently, we proposed four physical hallmarks of cancer, with distinct origins and consequences, to characterize abnormalities in the physical tumor microenvironment: (1) elevated compressive-tensile solid stresses, (2) elevated interstitial fluid pressure and the resulting interstitial fluid flow, (3) altered material properties (for example, increased tissue stiffness) and (4) altered physical micro-architecture. As this emerging field of physical oncology is being advanced by tumor biologists, cell and developmental biologists, engineers, physicists and oncologists, there is a critical need for model systems and measurement tools to mechanistically probe these physical hallmarks.

Separate orexigenic hippocampal ensembles shape dietary choice by enhancing contextual memory and motivation.

The hippocampus (HPC) has emerged as a critical player in the control of food intake, beyond its well-known role in memory. While previous studies have primarily associated the HPC with food intake inhibition, recent research suggests a role in appetitive processes. Here we identified spatially distinct neuronal populations within the dorsal HPC (dHPC) that respond to either fats or sugars, potent natural reinforcers that contribute to obesity development.

Racial and Educational Isolation are Associated with Worse Outcomes in Congenital Heart Disease.

Sociodemographic factors influence outcomes in children with congenital heart disease (CHD). We predict an association between measures of social isolation and outcomes in infants with complex CHD. These measures, racial (RI) and educational (EI) isolation range from 0 to 1, with 0 being no isolation and 1 being fully isolated within a specific population.

Lung endothelial cell senescence impairs barrier function and promotes neutrophil adhesion and migration.

Cellular senescence contributes to inflammation and organ dysfunction during aging. While this process is generally characterized by irreversible cell cycle arrest, its morphological features and functional impacts vary in different cells from various organs. In this study, we examined the expression of multiple senescent markers in the lungs of young and aged humans and mice, as well as in mouse lung endothelial cells cultured with a senescence inducer, suberoylanilide hydroxamic acid (SAHA), or doxorubicin (DOXO).

Physical activity and quality of life among breast cancer survivors: Pink SWAN.

Purpose: To describe physical activity (PA) trajectories across 10 years post-breast cancer diagnosis and examine their association with quality of life (QoL).

Methods: Participants from the longitudinal Study of Women's Health Across the Nation who developed incident breast cancer completed the Quality of Life in Adult Cancer Survivors scale (QLACS) which has 12 domains. Breast cancer survivors (BCS) with at least one post-diagnosis measure of the Kaiser Physical Activity Survey (PA) were included (n = 96).

MRI-guided focused ultrasound for treating Parkinson's disease with human mesenchymal stem cells.

Parkinson's disease (PD) is a progressive disorder that affects the nervous system and causes regions of the brain to deteriorate. In this study, we investigated the effects of MR-guided focused ultrasound (MRgFUS) for the delivery of human mesenchymal stem cells (MSCs) on the 6-hydroxydopamine (6-HODA)-induced PD rat model. MRgFUS-induced blood-brain barrier (BBB) permeability modulation was conducted using an acoustic controller with the targets at the striatum (ST) and SN.

New Frontiers: Umbilical Cord Mesenchymal Stem Cells Uncover Developmental Roots and Biological Underpinnings of Obesity Susceptibility.

Purpose Of Review: To review evidence supporting human umbilical cord mesenchymal stem cells (UC-MSC) as an innovative model system advancing obesity precision medicine.

Recent Findings: Obesity prevalence is increasing rapidly and exposures during fetal development can impact individual susceptibility to obesity. UC-MSCs exhibit heterogeneous phenotypes associated with maternal exposures and predictive of child cardiometabolic outcomes.

"They knew the same struggles": perceptions of a group coping skills intervention in patients with chronic graft-versus-host disease.

Purpose: Chronic graft-versus-host-disease (cGVHD), an inflammatory condition affecting allogeneic hematopoietic cell transplantation (HCT) survivors, is associated with a range of debilitating physical and psychological sequela. Yet HCT recipients with cGVHD are virtually absent from survivorship intervention research. We conducted a randomized clinical trial to evaluate the feasibility and preliminary efficacy of a multidisciplinary group coping skills intervention (Horizons) tailored to meet these patients' unique needs.

Ticam2 ablation facilitates monocyte exhaustion recovery after sepsis.

Sepsis is a leading cause of death worldwide, with most patient mortality stemming from lingering immunosuppression in sepsis survivors. This is due in part to immune dysfunction resulting from monocyte exhaustion, a phenotype of reduced antigen presentation, altered CD14/CD16 inflammatory subtypes, and disrupted cytokine production. Whereas previous research demonstrated improved sepsis survival in Ticam2 mice, the contribution of TICAM2 to long-term exhaustion memory remained unknown.

Advancing pancreatic cancer research and therapeutics: the transformative role of organoid technology.

Research on pancreatic cancer has transformed with the advent of organoid technology, providing a better platform that closely mimics cancer biology in vivo. This review highlights the critical advancements facilitated by pancreatic organoid models in understanding disease progression, evaluating therapeutic responses, and identifying biomarkers. These three-dimensional cultures enable the proper recapitulation of the cellular architecture and genetic makeup of the original tumors, providing insights into the complex molecular and cellular dynamics at various stages of pancreatic ductal adenocarcinoma (PDAC).

Long-lived entanglement of molecules in magic-wavelength optical tweezers.

Realizing quantum control and entanglement of particles is crucial for advancing both quantum technologies and fundamental science. Substantial developments in this domain have been achieved in a variety of systems. In this context, ultracold polar molecules offer new and unique opportunities because of their more complex internal structure associated with vibration and rotation, coupled with the existence of long-range interactions.