African ancestry neurodegeneration risk variant disrupts an intronic branchpoint in .

Recently, a novel African ancestry specific Parkinson's disease (PD) risk signal was identified at the gene encoding glucocerebrosidase (). This variant (rs3115534-G) is carried by ~50% of West African PD cases and imparts a dose-dependent increase in risk for disease. The risk variant has varied frequencies across African ancestry groups, but is almost absent in European and Asian ancestry populations.

Human longevity and Alzheimer's disease variants act via microglia and oligodendrocyte gene networks.

Ageing underlies functional decline of the brain and is the primary risk factor for several neurodegenerative conditions, including Alzheimer's disease (AD). However, the molecular mechanisms that cause functional decline of the brain during ageing, and how these contribute to AD pathogenesis, are not well understood. The objective of this study was to identify biological processes that are altered during ageing in the hippocampus and that modify Ad risk and lifespan, and then to identify putative gene drivers of these programmes.

Characterization and Genomics of Pectinolytic Bacteria Isolated from Soft Rot Symptomatic Produce.

Bacterial soft rot causes major crop losses annually and can be caused by several species from multiple genera. These bacteria have a broad host range and often infect produce through contact with soil. The main genera causing bacterial soft rot are and , both of which have widespread geographical distribution.

Bullet characterization using Photon-Counting detector CT: A phantom study with intact bullets.

Objectives: Photon-counting detector CT (PCD-CT) is expected to substantially improve and expand CT-imaging applicability due to its intrinsic spectral capabilities, increased spatial resolution, reduced electronic noise, and improved image contrast. The current study aim is to evaluate PCD-CT efficacy in characterizing bullets based on their dimensions, shape, and material composition.

Materials And Methods: This is an observational phantom study examining 11 unfired, intact bullets of various common calibers, placed in ballistic gelatin.

Amelioration of signaling deficits underlying metabolic shortfall in TREM2 human iPSC-derived microglia.

The microglial triggering receptor expressed on myeloid cells 2 (TREM2) is required for diverse microglia responses in neurodegeneration, including immunometabolic plasticity, phagocytosis, and survival. We previously identified that patient iPSC-derived microglia (iPS-Mg) harboring the Alzheimer's disease (AD) TREM2 hypomorph display several functional deficits linked to metabolism. To investigate whether these deficits are associated with disruptions in metabolite signaling, we generated common variant, TREM2 and TREM2 variant human iPS-Mg.

Orally dissolving pilocarpine tablets for xerostomia in advanced cancer: A pilot N-of-1 feasibility study.

Background: Xerostomia is a common and difficult symptom experienced by patients with cancer. Pilocarpine is a cholinergic agent that stimulates salivation.

Aim: To assess the feasibility of conducting a N-of-1 trial to determine the efficacy of pilocarpine orally dissolving tablets in patients with xerostomia.

The nucleocapsid architecture and structural atlas of the prototype baculovirus define the hallmarks of a new viral realm.

Baculovirus is the most studied insect virus owing to a broad ecological distribution and ease of engineering for biotechnological applications. However, its structure and evolutionary place in the virosphere remain enigmatic. Using cryo-electron microscopy, we show that the nucleocapsid forms a covalently cross-linked helical tube protecting a highly compacted 134-kilobase pair DNA genome.

African ancestry neurodegeneration risk variant disrupts an intronic branchpoint in GBA1.

Recently, an African ancestry-specific Parkinson disease (PD) risk signal was identified at the gene encoding glucocerebrosidase (GBA1). This variant ( rs3115534 -G) is carried by ~50% of West African PD cases and imparts a dose-dependent increase in risk for disease. The risk variant has varied frequencies across African ancestry groups but is almost absent in European and Asian ancestry populations.

Transethnic analysis identifies SORL1 variants and haplotypes protective against Alzheimer's disease.

Introduction: The SORL1 locus exhibits protective effects against Alzheimer's disease (AD) across ancestries, yet systematic studies in diverse populations are sparse.

Methods: Logistic regression identified AD-associated SORL1 haplotypes in East Asian (N = 5249) and European (N = 8588) populations. Association analysis between SORL1 haplotypes and AD-associated traits or plasma biomarkers was conducted.

The ZFHX3 GGC Repeat Expansion Underlying Spinocerebellar Ataxia Type 4 has a Common Ancestral Founder.

Background: The identification of a heterozygous exonic GGC repeat expansion in ZFHX3 underlying spinocerebellar ataxia type 4 (SCA4) has solved a 25-year diagnostic conundrum. We used adaptive long-read sequencing to decipher the pathogenic expansion in the index Utah family and an unrelated family from Iowa of Swedish ancestry. Contemporaneous to our discovery, other groups identified the same repeat expansion in affected individuals from Utah, Sweden, and Germany, highlighting the current pivotal time for detection of novel repeat expansion disorders.

FRET Probes for Detection of Both Active and Inactive Zika Virus Protease.

Proteases are a privileged class of enzymes due to their catalysis of an irreversible post translational modification, namely cleavage of substrate proteins. Protease activity is essential for human pathways including inflammation, blood clotting, and apoptosis. Proteases are also essential for the propagation of many viruses due to their role in cleavage of the viral polyprotein.

Age- and amyloid-β-dependent initiation of neurofibrillary tau tangles: an improved mouse model of Alzheimer's disease without mutations in .

Introducing heterozygous humanized tau to App knock-in mice results in the first mouse model of Alzheimer's disease in which age and amyloid-β pathology interact to initiate neurofibrillary tau tangle pathology, not dependent on mutations in MAPT. Gradual progression from amyloid-β to tau pathology in NLFTau mice opens possibilities for understanding processes precipitating clinical stages of Alzheimer's disease and development of translatable therapies to prevent the onset of tau pathology.

Shallow defects and optical properties of CsPbBrthin films through noble gas ion beam defect engineering.

Ion implantation is widely utilised for the modification of inorganic semiconductors; however, the technique has not been extensively applied to lead halide perovskites. In this report, we demonstrate the modification of the optical properties of caesium lead bromide (CsPbBr) thin films via noble gas ion implantation. We observed that the photoluminescence (PL) lifetimes of CsPbBrthin films can be doubled by low fluences (<1 × 10at·cm) of ion implantation with an acceleration voltage of 20 keV.

Microglia contribute to the production of the amyloidogenic ABri peptide in familial British dementia.

Mutations in ITM2B cause familial British, Danish, Chinese, and Korean dementias. In familial British dementia (FBD), a mutation in the stop codon of the ITM2B gene (also known as BRI2) causes a C-terminal cleavage fragment of the ITM2B/BRI2 protein to be extended by 11 amino acids. This fragment, termed amyloid-Bri (ABri), is highly insoluble and forms extracellular plaques in the brain.

Articular cartilage loss is an unmitigated risk of human spaceflight.

Microgravity and space radiation are hazards of spaceflight that have deleterious effects on articular cartilage. Since it is not widely monitored or protected through dedicated countermeasures, articular cartilage loss is an unmitigated risk of human spaceflight. Spaceflight-induced cartilage loss will affect an astronaut's performance during a mission and long-term health after a mission.

Drug Interactions in People on Cannabidiol: Is There Cause for Concern?

Cannabidiol (CBD) exhibits multiple therapeutic properties, but its use in advanced cancer patients raises concerns about potential drug-drug interactions (DDIs) due to polypharmacy. This study aims to look for evidence of DDIs between concomitant medications and CBD oil in a randomized placebo-controlled trial of CBD oil for symptom control (MedCan-1 parent study). Surrogate measures were used to identify possible drug interactions: (1) the maximum mL of oil self-selected by patients in CBD or placebo groups in relation to opioids, specific drug groups, or individual agents; (2) the occurrence of any new or worse adverse effect in relation to the study arm and the concomitant medication classes/medications of interest.

Decreased DNA density is a better indicator of a nuclear bleb than lamin B loss.

Nuclear blebs are herniations of the nucleus that occur in diseased nuclei that cause nuclear rupture leading to cellular dysfunction. Chromatin and lamins are two of the major structural components of the nucleus that maintain its shape and function, but their relative roles in nuclear blebbing remain elusive. To determine the composition of nuclear blebs, we compared the immunofluorescence intensity of DNA and lamin B in the main nucleus body to the nuclear bleb across cell types and perturbations.

Non-contact lower limb injuries in Rugby Union: A two-year pattern recognition analysis of injury risk factors.

The cause of sport injuries are multifactorial and necessitate sophisticated statistical approaches for accurate identification of risk factors predisposing athletes to injury. Pattern recognition analyses have been adopted across sporting disciplines due to their ability to account for repeated measures and non-linear interactions of datasets, however there are limited examples of their use in injury risk prediction. This study incorporated two-years of rigorous monitoring of athletes with 1740 individual weekly data points across domains of training load, performance testing, musculoskeletal screening, and injury history parameters, to be one of the first to employ a pattern recognition approach to predict the risk factors of specific non-contact lower limb injuries in Rugby Union.

Assessing clinical progression measures in Alzheimer's disease trials: A systematic review and meta-analysis.

Introduction: Assessing treatments for Alzheimer's disease (AD) relies on reliable tools for measuring AD progression. In this analysis, we evaluate the sensitivity of clinical progression measures in AD within randomized controlled trials (RCTs) with confirmed positive amyloid (Aβ+) status prior to trial enrollment.

Methods: Excluding trials targeting non-cognitive symptoms, we conducted meta-analyses on progression measures from 25 selected RCTs using R version 4.

Progress in Multiscale Modeling of Silk Materials.

As a result of their hierarchical structure and biological processing, silk fibers rank among nature's most remarkable materials. The biocompatibility of silk-based materials and the exceptional mechanical properties of certain fibers has inspired the use of silk in numerous technical and medical applications. In recent years, computational modeling has clarified the relationship between the molecular architecture and emergent properties of silk fibers and has demonstrated predictive power in studies on novel biomaterials.