Long somatic DNA-repeat expansion drives neurodegeneration in Huntington's disease.

In Huntington's disease (HD), striatal projection neurons (SPNs) degenerate during midlife; the core biological question involves how the disease-causing DNA repeat (CAG) in the huntingtin (HTT) gene leads to neurodegeneration after decades of biological latency. We developed a single-cell method for measuring this repeat's length alongside genome-wide RNA expression. We found that the HTT CAG repeat expands somatically from 40-45 to 100-500+ CAGs in SPNs.

A personalized multi-platform assessment of somatic mosaicism in the human frontal cortex.

Somatic mutations in individual cells lead to genomic mosaicism, contributing to the intricate regulatory landscape of genetic disorders and cancers. To evaluate and refine the detection of somatic mosaicism across different technologies with personalized donor-specific assembly (DSA), we obtained tissue from the dorsolateral prefrontal cortex (DLPFC) of a post-mortem neurotypical 31-year-old individual. We sequenced bulk DLPFC tissue using Oxford Nanopore Technologies (~60X), NovaSeq (~30X), and linked-read sequencing (~28X).

A scoping review of diffuse hemispheric glioma, H3 G34-mutant: Epigenetic and molecular profiles, clinicopathology, and treatment avenues.

Background: Survival of pediatric and young adults with malignant glioma remains poor despite progress in treatment. This is especially true for diffuse hemispheric glioma (DHG), H3 G34-mutant, which is often present in adolescent and young adult patients. This scoping review consolidates existing knowledge of DHG H3 G34-mutant and identifies future targets and therapeutic options.

A new cell culture resource for investigations of reptilian gene function.

The establishment of CRISPR/Cas9 gene editing in Anolis sagrei has positioned this species as a powerful model for studies of reptilian gene function. To enhance this model, we developed an immortalized lizard fibroblast cell line (ASEC-1) for the exploration of reptilian gene function in cellular processes. We demonstrate the use of this cell line by scrutinizing the role of primary cilia in lizard Hedgehog (Hh) signaling.

Using the 12-item short-form health survey (SF-12) to evaluate self-rated health in an environmental justice community.

The Greater Fifth Ward (GFW) is a Northeast Houston, Texas, neighborhood with a legacy of industrial contamination and a confirmed cancer cluster. To understand self-rated health in the GFW, community-based participatory research (CBPR), was used to promote the inclusion of all partners. CBPR involves the community during each stage of the research process from design to research dissemination.

Acetabular Fracture and Triradiate Cartilage Injury in an Adolescent After a Motorcycle Crash: A Case Report.

The acetabular triradiate cartilage is the main structure that determines the development of the acetabulum. Furthermore, the paucity of data in the literature and lack of consensus amongst physicians following diagnosis regarding whether to treat these fractures operatively or non-operatively places the physician with a challenging choice. Here, we report a case of a 13-year-old boy who suffered a triradiate cartilage fracture from a high-energy motorcycle crash and presented with a displaced, left T-type acetabulum fracture.

The effect of the modified Atkins diet and anti-seizure medications on lipid marker levels in adults with epilepsy.

Objectives: Some anti-seizure medications (ASMs) are known to induce liver enzymes and impact lipid values that include total cholesterol (TC), low density lipoprotein cholesterol (LDL), high density lipoprotein cholesterol (HDL), and triglyceride (TG). In addition, use of ketogenic diet therapies, including the modified Atkins diet (MAD), has also influenced lipids. Here, we explored the combined impact of enzyme inducing ASMs (EIASMs) and MAD on lipid values in adults with epilepsy.

Factors associated with seizure response in adults with epilepsy on a modified Atkins diet.

Purpose: This study investigated factors associated with improved seizure control in adults with epilepsy following a modified Atkins diet (MAD).

Methods: Follow-up data collected from participants enrolled in a prospective study between March 2016 and November 2023 was analyzed. Demographic and clinical differences between diet responders and non-responders were evaluated.

Three-Level Concavity Apical Pediculectomy During Intraoperative Neuromonitoring Loss: Following the Checklist Resulted in an Ambulatory Patient.

Adolescent idiopathic scoliosis is the most common form of scoliosis, with severe cases leading to a decline in patients with worsening angulation of deformity. Technical nuances of spinal flexibility and cord type based on the extent of the deformity may impact operating safety and outcome, with risks including neurological loss during and after surgical intervention. Here we present a case of posterior osteotomy and correction of a patient with adolescent idiopathic scoliosis with a T2 - L3 fusion in which transcranial motor evoked potentials (TcMEPs) and somatosensory evoked potentials (SSEPs) were lost intraoperatively, thus requiring application of operative consensus guidelines for the loss of neuromonitoring data.

Reconstruction of single-cell lineage trajectories and identification of diversity in fates during the epithelial-to-mesenchymal transition.

Exploring the complexity of the epithelial-to-mesenchymal transition (EMT) unveils a diversity of potential cell fates; however, the exact timing and mechanisms by which early cell states diverge into distinct EMT trajectories remain unclear. Studying these EMT trajectories through single-cell RNA sequencing is challenging due to the necessity of sacrificing cells for each measurement. In this study, we employed optimal-transport analysis to reconstruct the past trajectories of different cell fates during TGF-beta-induced EMT in the MCF10A cell line.

Cation-induced morphological transitions and aggregation of thermoresponsive PNIPAM nanogels.

Poly(-isopropylacrylamide) (PNIPAM) nanogels are promising responsive colloidal particles that can be used in pharmaceutical applications as drug carriers. This work investigates the temperature-dependent morphological changes and agglomeration of PNIPAM nanogels in the presence of mono- and multi-valent cationic electrolytes. We described the deswelling, flocculation, thermal reversibility behaviour and aggregated morphology of PNIPAM nanogels over a range of electrolyte concentrations and temperatures revealing the critical transition points from stable suspension to spontaneous agglomeration.

Fish oil supplementation modifies the associations between genetically predicted and observed concentrations of blood lipids: a cross-sectional gene-diet interaction study in UK Biobank.

Background: Dyslipidemia is a well-known risk factor for cardiovascular disease, the leading cause of mortality worldwide. Although habitual intake of fish oil is associated with cardioprotective effects through triglyceride reduction, the interactions of fish oil with the genetic predisposition to dysregulated lipids remain elusive.

Objectives: We examined whether fish oil supplementation modifies the association between genetically predicted and observed concentrations of total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, and triglycerides.

Autoantibodies to Truncated GAD(96-585) Antigen Stratify Risk of Early Insulin Requirement in Adult-Onset Diabetes.

We investigated whether characterization of full-length GAD (f-GADA) antibody (GADA) responses could identify early insulin requirement in adult-onset diabetes. In 179 f-GADA-positive participants diagnosed with type 2 diabetes, we assessed associations of truncated GADA (t-GADA) positivity, f-GADA IgG subclasses, and f-GADA affinity with early insulin requirement (<5 years), type 1 diabetes genetic risk score (T1D GRS), and C-peptide. t-GADA positivity was lower in f-GADA-positive without early insulin in comparison with f-GADA-positive type 2 diabetes requiring insulin within 5 years, and T1D (75% vs.

Impact of haemoglobin variants on the diagnostic sensitivity of glycated haemoglobin (HbA1c) assay methodologies in sub-Saharan Africa: a laboratory-based method validation study.

Introduction: the utility of glycated haemoglobin (HbA1c) for the diagnosis and monitoring of diabetes in sub-Saharan Africa is uncertain due to limited data on the performance of the available HbA1c assay methods in this population, which has a high prevalence of haemoglobin variants. We aimed to compare the diagnostic accuracy of the major HbA1c methodologies (Boronate Affinity, Capillary Electrophoresis, High Performance Liquid Chromatography, Immunoassay) in an African population, and assess the impact of the common haemoglobin variant HbAS (sickle cell trait).

Methods: whole blood samples were obtained from 182 individuals living with type 2 diabetes in Uganda.

Associations between diabetes-related genetic risk scores and residual beta cell function in type 1 diabetes: the GUTDM1 study.

Aims/hypothesis: Use of genetic risk scores (GRS) may help to distinguish between type 1 diabetes and type 2 diabetes, but less is known about whether GRS are associated with disease severity or progression after diagnosis. Therefore, we tested whether GRS are associated with residual beta cell function and glycaemic control in individuals with type 1 diabetes.

Methods: Immunochip arrays and TOPMed were used to genotype a cross-sectional cohort (n=479, age 41.

Metabolites Associated with Polygenic Risk of Breast Cancer.

While hundreds of germline genetic variants have been associated with breast cancer risk, the mechanisms underlying the impacts of most of these variants on breast cancer remain uncertain. Metabolomics may offer valuable insights into the mechanisms underlying genetic risks of breast cancer. Among 143 cancer-free female participants, we used linear regression analyses to explore associations between the genetic risk of breast cancer, as determined by a previously developed polygenic risk score (PRS) that included 266 single-nucleotide polymorphisms (SNPs), and 223 measures of metabolites obtained from blood samples using nuclear magnetic resonance (NMR).

Symbionts out of sync: Decoupled physiological responses are widespread and ecologically important in lichen associations.

A core vulnerability in symbioses is the need for coordination between the symbiotic partners, which are often assumed to be closely physiologically integrated. We critically re-examine this assumed integration between symbionts in lichen symbioses, recovering a long overlooked yet fundamental physiological asymmetry in carbon balance. We examine the physiological, ecological, and transcriptional basis of this asymmetry in the lichen .