The effect of replication protein A inhibition and post-translational modification on ATR kinase signaling.

The ATR kinase responds to elevated levels of single-stranded DNA (ssDNA) to activate the G2/M checkpoint, regulate origin utilization, preserve fork stability, and allow DNA repair to ensure genome integrity. The intrinsic replication stress in cancer cells makes this pathway an attractive therapeutic target. The ssDNA that drives ATR signaling is sensed by the ssDNA-binding protein replication protein A (RPA), which acts as a platform for ATRIP recruitment and subsequent ATR activation by TopBP1.

Revealing the Fates of Proteins in the Gas Phase.

The ability to observe intact proteins by native mass spectrometry allows measurements of size, oligomeric state, numbers and types of ligands and post translational modifications bound, among many other characteristics. These studies have the potential to, and in some cases are, advancing our understanding of the role of structure in protein biology and biochemistry. However, there are some long-unresolved questions about to what extent solution-like structures persist without solvent in the vacuum of the mass spectrometer.

Celiac disease in North America: What is the current practice of pediatric gastroenterology providers?

Objectives: While guidelines exist for the diagnosis and management of pediatric celiac disease (CeD), current practices in North America are not well-described. This study aimed to explore current practice patterns to identify gaps and direct future clinical, training and research initiatives.

Methods: A 23-item survey designed by the Celiac Disease Special Interest Group was distributed electronically to its members.

Depressive symptom clusters and biomarkers of monocyte activation, inflammation, and coagulation in people with HIV and depression.

We assess associations of somatic and cognitive/affective depressive symptom clusters with monocyte activation (soluble (s)CD14, sCD163), systemic inflammation (interleukin-6 (IL-6), high-sensitivity C-reactive protein (hsCRP)), and coagulation (D-dimer, fibrinogen) in people with HIV (PWH) on suppressive antiretroviral therapy with depression. Utilizing baseline data from a randomized controlled trial, we found no significant associations in linear regression models examining individual depressive symptom clusters; however, models examining both clusters simultaneously showed that the somatic cluster was positively associated with inflammation biomarkers, while the cognitive/affective cluster was negatively associated with inflammation and coagulation biomarkers (suggesting a cooperative suppression effect). Our findings indicate a differential association with depressive symptom clusters and biological mechanisms underlying cardiovascular disease (CVD) in HIV, which may be driven by unique components of each depressive symptom cluster.

A mean-field theory for characterizing the closing rates of DNA origami hinges.

The evolution of dynamic DNA nanostructures has propelled DNA nanotechnology into a robust and versatile field, offering groundbreaking applications in nanoscale communication, drug delivery, and molecular computing. Yet, the full potential of this technology awaits further enhancement through optimization of kinetic properties governing conformational changes. In this work, we introduce a mean-field theory to characterize the kinetic behavior of a dynamic DNA origami hinge where each arm bears complementary single-stranded DNA overhangs of different lengths, which can latch the hinge at a closed conformation.

The acute hypoalgesic effects of active head-mounted display virtual reality games.

The purpose of this study was to determine: (1) whether physically active virtual reality (VR) games exert an acute hypoaglesic effect on the thigh and bicep compared to a non-active VR game and an exercise only condition matched for exercise intensity in healthy individuals, and (2) whether movement variables during gameplay are associated with the hypoalgesic effect of the games. Twenty young adults completed five separate study sessions, with each session devoted to playing one head-mounted display VR game or stationary cycling for 15 minutes. The games included Holopoint at level 2 and level 3, Hot Squat, and Relax Walk.

Targeting Rural Adolescent Pregnancy: Modifiable Protective Factors and Contraceptive Use.

Purpose: Rural adolescent pregnancy is a serious public health issue, largely due to low contraceptive use. Existing data focuses on urban populations. Using a positive youth development framework, we examine associations between modifiable protective factors and birth control use in a rural population.

Sex-specific trisomic Dyrk1a-related skeletal phenotypes during development in a Down syndrome model.

Skeletal insufficiency affects all individuals with Down syndrome (DS) or trisomy 21 and may alter bone strength throughout development due to a reduced period of bone formation and early attainment of peak bone mass compared to those in typically developing individuals. Appendicular skeletal deficits also appear in males before females with DS. In femurs of male Ts65Dn DS model mice, cortical deficits were pronounced throughout development, but trabecular deficits and Dyrk1a overexpression were transitory until postnatal day (P) 30, when there were persistent trabecular and cortical deficits and Dyrk1a was trending toward overexpression.

Trajectory Analysis for Identifying Classes of Attention Deficit Hyperactivity Disorder (ADHD) in Children of the United States.

Background: Attention Deficit Hyperactivity Disorder (ADHD) is a mental health disorder that affects attention and behavior. People with ADHD frequently encounter challenges in social interactions, facing issues, like social rejection and difficulties in interpersonal relationships, due to their inattention, impulsivity, and hyperactivity.

Methods: A National Longitudinal Survey of Youth (NLSY) database was employed to identify patterns of ADHD symptoms.

Recent Advances in Synthetic Methods by Photocatalytic Single-Electron Transfer Chemistry of Pyridine -Oxides.

By adoption of the enabling technology of modern photoredox catalysis and photochemistry, the generation of reactive and versatile pyridine -oxy radicals can be facilely achieved from single-electron oxidation of pyridine -oxides. This Synopsis highlights recent methodologies mediated by pyridine -oxy radicals in developing (1) pyridine -oxide-based hydrogen atom transfer catalysts for C(sp)-H functionalizations and (2) β-oxyvinyl radical-mediated cascade reactions. In addition, recent research revealed that direct photoexcitation of pyridine -oxides allowed for the generation of alkyl carbon radicals from alkylboronic acids.

Sodium butyrate prevents cytokine-induced β-cell dysfunction through restoration of stromal interaction molecule 1 expression and activation of store-operated calcium entry.

Sodium butyrate (NaB) improves β-cell function in preclinical models of diabetes; however, the mechanisms underlying these beneficial effects have not been fully elucidated. In this study, we investigated the impact of NaB on β-cell function and calcium (Ca) signaling using ex vivo and in vitro models of diabetes. Our results show that NaB significantly improved glucose-stimulated insulin secretion in islets from human organ donors with type 2 diabetes and in cytokine-treated INS-1 β cells.

Unforeseen plant phenotypic diversity in a dry and grazed world.

Earth harbours an extraordinary plant phenotypic diversity that is at risk from ongoing global changes. However, it remains unknown how increasing aridity and livestock grazing pressure-two major drivers of global change-shape the trait covariation that underlies plant phenotypic diversity. Here we assessed how covariation among 20 chemical and morphological traits responds to aridity and grazing pressure within global drylands.

Pancreatic Crosstalk in the Disease Setting: Understanding the Impact of Exocrine Disease on Endocrine Function.

The exocrine and endocrine are functionally distinct compartments of the pancreas that have traditionally been studied as separate entities. However, studies of embryonic development, adult physiology, and disease pathogenesis suggest there may be critical communication between exocrine and endocrine cells. In fact, the incidence of the endocrine disease diabetes secondary to exocrine disease/dysfunction ranges from 25% to 80%, depending on the type and severity of the exocrine pathology.

The effect of dysmenorrhea severity and interference on reactions to experimentally-induced pain.

Introduction: Dysmenorrhea is associated with increased risk of chronic pain and hyperalgesia. Menstruating individuals with dysmenorrhea are more likely to have elevated pain reactivity when experiencing experimental pain, than those without. However, no study has examined intragroup differences in reactions to experimentally induced pain for individuals with dysmenorrhea.

The Effect of Replication Protein A Inhibition and Post-Translational Modification on ATR Kinase Signaling.

The ATR kinase responds to elevated levels of single-stranded DNA (ssDNA) to activate the G2/M checkpoint, regulate origin utilization, preserve fork stability, and allow DNA repair towards ensuring genome integrity. The intrinsic replication stress in cancer cells makes this pathway an attractive therapeutic target. The ssDNA that drives ATR signaling is sensed by the ssDNA-binding protein replication protein A (RPA), which acts as a platform for ATRIP recruitment and subsequent ATR activation by TopBP1.

Impact of COVID-19 on vaccine confidence and uptake: A systematic literature review.

During the coronavirus disease 2019 (COVID-19) pandemic, scheduled vaccinations were postponed, mass vaccination programmes were suspended and opportunities for healthcare workers to administer vaccines ad hoc decreased. The aims of this systematic literature review were to determine the impact of the COVID-19 pandemic on vaccine confidence, intent and uptake in preexisting routine childhood or adult vaccination programmes, and to identify factors associated with changes in acceptance, intent and uptake of preexisting vaccines. Medline and Embase were searched for studies in Australia, Brazil, Canada, China, Japan, the USA, and European countries, published between 1 January 2021 and 4 August 2022.

Greater ventral striatal functional connectivity in cigarette smokers relative to non-smokers across a spectrum of alcohol consumption.

Cigarette smoking is associated with elevated risk of disease and mortality and contributes to heavy healthcare-related economic burdens. The nucleus accumbens is implicated in numerous reward-related behaviors, including reinforcement learning and incentive salience. The established functional connectivity of the accumbens includes regions associated with motivation, valuation, and affective processing.

A review on the performance of brain-computer interface systems used for patients with locked-in and completely locked-in syndrome.

Patients with locked-in syndrome (LIS) and complete locked-in syndrome (CLIS) own a fully functional brain restricted within a non-functional body. In order to help LIS patients stay connected with their surroundings, brain-computer interfaces (BCIs) and related technologies have emerged. BCIs translate brain activity into actions that can be performed by external devices enabling LIS patients to communicate, leading to an increase in their quality of life.

Induction of astrocyte reactivity promotes neurodegeneration in human pluripotent stem cell models.

Reactive astrocytes are known to exert detrimental effects upon neurons in several neurodegenerative diseases, yet our understanding of how astrocytes promote neurotoxicity remains incomplete, especially in human systems. In this study, we leveraged human pluripotent stem cell (hPSC) models to examine how reactivity alters astrocyte function and mediates neurodegeneration. hPSC-derived astrocytes were induced to a reactive phenotype, at which point they exhibited a hypertrophic profile and increased complement C3 expression.

Estimating price elasticities of demand for pain relief drugs: evidence from Medicare Part D.

Overdose deaths from prescription opioids remain elevated, and policymakers seek solutions to curb opioid misuse. Recent proposals call for price-based solutions, such as opioid taxes and removal of opioids from insurance formularies. However, there is limited evidence on how opioid consumption responds to price stimuli.

Preventing Surgeon Work-Related Musculoskeletal Disorders: A Pilot Study of the Comprehensive Operating Room Ergonomics (CORE) Program.

Importance: Work-related musculoskeletal disorders (WMSDs) among surgeons are markedly increasing. Several proposed interventions to reduce WMSDs among surgeons have been studied, but few follow an occupational therapy-oriented approach addressing biomechanical, psychophysical, and psychosocial risk factors.

Objective: To design, implement, and assess the potential of the Comprehensive Operating Room Ergonomics (CORE) program for surgeons, a holistic evidence-based ergonomics and wellness intervention grounded in occupational therapy principles.