TRPC4 regulates limbic behavior and neuronal development by stabilizing dendrite branches through actomyosin-driven integrin activation.

Transient Receptor Potential Canonical 4 (TRPC4) channels have been implicated in multiple neurological functions, including anxiety and sociability. TRPC4 variants were also found in patients with autism. However, the contributions of TRPC4 to neurodevelopment remain undefined.

Cell free RNA detection of pancreatic cancer in pre diagnostic high risk and symptomatic patients.

Pancreatic ductal adenocarcinomas (PDAC) are among the most fatal cancers, in part due to frequent detection at advanced stages. Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA), the most sensitive diagnostic method of PDAC in current standard clinical practice, is invasive, costly, with access limited to major healthcare settings. Here, we present a non-invasive evaluation of plasma cell-free RNA (cfRNA) for PDAC detection in pre-diagnostic high-risk and de novo symptomatic patients presenting for EUS-FNA.

Neuraminidase 1 secondary deficiency contributes to CNS pathology in neurological mucopolysaccharidoses via brain protein hypersialylation.

Mucopolysaccharidoses (MPS) are lysosomal storage diseases caused by defects in catabolism of glycosaminoglycans. MPS I, II, III, and VII, which are associated with lysosomal accumulation of heparan sulphate (HS), manifest with neurological deterioration and currently lack effective treatments. We report that neuraminidase 1 (NEU1) activity is drastically reduced in brain tissues of patients with neurological MPS and mouse models but not in neurological lysosomal disorders without HS storage.

Unveiling the intercompartmental signaling axis: Mitochondrial to ER Stress Response (MERSR) and its impact on proteostasis.

Maintaining protein homeostasis is essential for cellular health. Our previous research uncovered a cross-compartmental Mitochondrial to Cytosolic Stress Response, activated by the perturbation of mitochondrial proteostasis, which ultimately results in the improvement of proteostasis in the cytosol. Here, we found that this signaling axis also influences the unfolded protein response of the endoplasmic reticulum (UPRER), suggesting the presence of a Mitochondria to ER Stress Response (MERSR).

Background color matching influences sexual behavior, growth, and mortality rate in an African cichlid fish.

Phenotypic plasticity allows organisms to adapt to changing environments within their lifetimes. The cost of plastic adaptations may constrain the persistence of plasticity over evolutionary time. One potential cost is the possibility that phenotypic adjustment to specific environments can cause correlated responses that are not necessarily adaptive.

Applying Community-based System Dynamics to promote child health equity: the case of healthy and fit kids in Milwaukee, WI.

Background: Child health equity is influenced by complex systemic factors, including structural racism, socioeconomic disparities, and access to resources. Traditional public health interventions often target individual behaviors, but there is a growing need for systems approaches that address these root causes. This study examines coalition members' perspectives on promoting child health equity in Milwaukee as a result of participating in an intervention that includes Community-based System Dynamics (CBSD).

Changes in systems thinking and health equity considerations across four communities participating in Catalyzing Communities.

Childhood obesity is a persistent public health concern, and community-based interventions have become crucial for addressing it by engaging local communities and implementing comprehensive evidence-based strategies. The Catalyzing Communities intervention takes a "whole-of-community"approach to involve leaders from diverse sectors in thinking systematically about child healthy weights and implementing evidence-based solutions. Using systems thinking and the Getting to Equity framework to guide interview analysis, this study examines changes in participants' use of systems thinking concepts and health equity in 43 participants across four U.

The CAMPUS Study: A Systems Approach to Alcohol-Involved Sexual Violence on College Campuses.

Objective: Developing a better mechanistic and multilevel understanding of sexual violence on college campuses can help us evaluate and implement existing interventions, as well as develop new ones. We brought together scientists, practitioners, and college students to collaboratively characterize the systems surrounding alcohol-involved sexual violence on college campuses. Using collaborative model-building, they created models that highlight interconnected and multilevel influences and consequences of sexual violence.

Searching for the Scale-Able Weight Loss Intervention: Can One Size Fit All? Lessons to Be Learned from the EQUAL Trial.

Overweight and obesity affect 71.2% of adults in the United States, with cancer survivors not far behind at 70.3%.

A Scaled Proteomic Discovery Study for Prostate Cancer Diagnostic Markers Using Proteograph and Trapped Ion Mobility Mass Spectrometry.

There is a significant unmet need for clinical reflex tests that increase the specificity of prostate-specific antigen blood testing, the longstanding but imperfect tool for prostate cancer diagnosis. Towards this endpoint, we present the results from a discovery study that identifies new prostate-specific antigen reflex markers in a large-scale patient serum cohort using differentiating technologies for deep proteomic interrogation. We detect known prostate cancer blood markers as well as novel candidates.

Mitochondrial permeability transition dictates mitochondrial maturation upon switch in cellular identity of hematopoietic precursors.

The mitochondrial permeability transition pore (mPTP) is a supramolecular channel that regulates exchange of solutes across cristae membranes, with executive roles in mitochondrial function and cell death. The contribution of the mPTP to normal physiology remains debated, although evidence implicates the mPTP in mitochondrial inner membrane remodeling in differentiating progenitor cells. Here, we demonstrate that strict control over mPTP conductance shapes metabolic machinery as cells transit toward hematopoietic identity.

Secondary deficiency of neuraminidase 1 contributes to CNS pathology in neurological mucopolysaccharidoses via hypersialylation of brain glycoproteins.

Mucopolysaccharidoses (MPS) are lysosomal storage diseases caused by defects in catabolism of glycosaminoglycans. MPS I, II, III and VII are associated with lysosomal accumulation of heparan sulphate and manifest with neurological deterioration. Most of these neurological MPS currently lack effective treatments.

Intracellular Lactate Dynamics in Glutamatergic Neurons.

Rates of lactate production and consumption reflect the metabolic state of many cell types, including neurons. Here, we investigate the effects of nutrient deprivation on lactate dynamics in glutamatergic neurons by leveraging the limiting effects of the diffusion barrier surrounding cells in culture. We found that neurons constitutively consume lactate when availability of trehalose, the glucose disaccharide preferred by insects, is limited by the diffusion barrier.

NDUFS4 regulates cristae remodeling in diabetic kidney disease.

The mitochondrial electron transport chain (ETC) is a highly adaptive process to meet metabolic demands of the cell, and its dysregulation has been associated with diverse clinical pathologies. However, the role and nature of impaired ETC in kidney diseases remains poorly understood. Here, we generate diabetic mice with podocyte-specific overexpression of Ndufs4, an accessory subunit of mitochondrial complex I, as a model investigate the role of ETC integrity in diabetic kidney disease (DKD).

Accessible high-throughput single-cell whole-genome sequencing with paired chromatin accessibility.

Single-cell whole-genome sequencing (scWGS) enables the assessment of genome-level molecular differences between individual cells with particular relevance to genetically diverse systems like solid tumors. The application of scWGS was limited due to a dearth of accessible platforms capable of producing high-throughput profiles. We present a technique that leverages nucleosome disruption methodologies with the widely adopted 10× Genomics ATAC-seq workflow to produce scWGS profiles for high-throughput copy-number analysis without new equipment or custom reagents.

Relational sanctification, communal coping, and depression among African American couples.

Despite the common use of religious buffers, African Americans are disproportionately affected by depressive symptoms. Communal coping may serve as one factor in helping religious African American couples alleviate the symptoms of depression. This study examines the association between relational sanctification and depressive symptoms as mediated by the communal coping of 467 African American married and cohabiting couples.

NDUFS4 Regulates Cristae Remodeling in Diabetic Kidney Disease.

The mitochondrial electron transport chain (ETC) is a highly adaptive process to meet metabolic demands of the cell, and its dysregulation has been associated with diverse clinical pathologies. However, the role and nature of impaired ETC in kidney diseases remains poorly understood. Here, we generated diabetic mice with podocyte-specific overexpression of Ndufs4, an accessory subunit of mitochondrial complex I, as a model to investigate the role of ETC integrity in diabetic kidney disease (DKD).

Exploratory Analysis of Social Networks Linked to the Provision of Beverages in Costa Rican Schools.

Sugar-sweetened beverages (SSBs) are implicated in weight gain and adverse cardiometabolic heath. Social networks of stakeholders involved in providing potable water and sugar-sweetened beverages (SSBs) in high schools in Costa Rica were studied using social analysis network. In public and private schools, the interactions between the stakeholders in charge of providing beverages are fragmented and their role in preventing the availability of SSBs is weak.

Implementing a stakeholder-driven community diffusion-informed intervention to create healthier, more equitable systems: a community case study in Greenville County, South Carolina.

This case study describes the application of a theory-informed, stakeholder-driven intervention with a group of 19 multi-sector stakeholders from an existing coalition to promote whole-of-community change that supports childhood obesity prevention. The intervention applied community-based system dynamics to design and implement activities that promoted insights into the systems driving childhood obesity prevalence and helped participants prioritize actions to influence those systems. This led to three new priority areas for the coalition: addressing food insecurity; building power among historically marginalized voices within the community; and supporting advocacy efforts to promote community-wide change beyond the coalition's previous focus on organizational-level policy, systems and environment change.

Acute depletion of human core nucleoporin reveals direct roles in transcription control but dispensability for 3D genome organization.

The nuclear pore complex (NPC) comprises more than 30 nucleoporins (NUPs) and is a hallmark of eukaryotes. NUPs have been suggested to be important in regulating gene transcription and 3D genome organization. However, evidence in support of their direct roles remains limited.

Tracing coalition changes in knowledge in and engagement with childhood obesity prevention to improve intervention implementation.

Background: While most coalition research focuses on studying the effects of peer relationship structure, this study examines the coevolution of coalition structure and behavior across three communities in the U.S. with the goal of identifying coalition dynamics that impact a childhood obesity prevention intervention.