Developing Topics.

Background: Alzheimer's disease (AD) is a devastating form of dementia, and its prevalence is rising as human lifespan increases. Our lab created the AD-BXD mouse model, which expresses AD mutations across a genetically diverse reference panel (BXD), to identify factors that confer resilience to cognitive decline in AD. This model mimics key characteristics of human AD including variation in age of onset and severity of cognitive decline.

Developing Topics.

Background: Sleep dysfunctions are highly comorbid with Alzheimer's disease (AD), though often associated with later stages of AD, sleep disruptions have been noted to appear decades before the onset of cognitive symptoms. Here, we provide the first evidence that genetic factors interact with AD mutations to influence sleep behavior even before the onset of cognitive symptoms.

Method: To identify novel genetic factors underlying disordered sleep that precede cognitive decline in our AD-BXD mouse genetic reference panel (n = 179 mice across 25 strains, 7-months-old), we first used sleep phenotypes measured in the PiezoSleep chambers and performed quantitative trait loci (QTL) mapping and discovered Kirrel3 as the novel gene candidate associated with disordered sleep.

A prognostic molecular signature of hepatic steatosis is spatially heterogeneous and dynamic in human liver.

Hepatic steatosis is a central phenotype in multi-system metabolic dysfunction and is increasing in parallel with the obesity pandemic. We use a translational approach integrating clinical phenotyping and outcomes, circulating proteomics, and tissue transcriptomics to identify dynamic, functional biomarkers of hepatic steatosis. Using multi-modality imaging and broad proteomic profiling, we identify proteins implicated in the progression of hepatic steatosis that are largely encoded by genes enriched at the transcriptional level in the human liver.

This is your brain on drug education: Putting young people with lived experience at the center of drug education.

Get Sensible, a project by Canadian Students for Sensible Drug Policy (CSSDP), is an entirely youth-led cannabis education initiative funded by Health Canada that challenges traditional approaches to cannabis education by prioritizing harm reduction, evidence-based information, lived experience, and non-judgmental conversations through innovative peer-to-peer models. In this narrative reflection, the Get Sensible team explores the necessity of centering young people in the development and implementation of cannabis education initiatives, drawing on their experience developing and disseminating the "Sensible Cannabis Education Booklets", an illustrated series covering a range of cannabis topics in an accessible, intersectional and engaging manner. The positive reception and impact of this campaign is a reflection of the power of truly youth-led projects for authentically connecting with young people to mobilize information in language they relate to and through mediums that resonate with them.

Association between mosaic loss of chromosome Y and pulmonary fibrosis susceptibility and severity.

Unlabelled: Background Pulmonary fibrosis (PF) is a rare lung disease with diverse pathogenesis and multiple interconnected underlying biological mechanisms. Mosaic loss of chromosome Y (mLOY) is one of the most common forms of acquired chromosome abnormality in men, which has been reported to be associated with increased risk of various chronic progressive diseases including fibrotic diseases. However, the exact role of mLOY in the development of PF remains elusive and to be elucidated.

Detecting the effect of genetic diversity on brain composition in an Alzheimer's disease mouse model.

Alzheimer's disease (AD) is broadly characterized by neurodegeneration, pathology accumulation, and cognitive decline. There is considerable variation in the progression of clinical symptoms and pathology in humans, highlighting the importance of genetic diversity in the study of AD. To address this, we analyze cell composition and amyloid-beta deposition of 6- and 14-month-old AD-BXD mouse brains.

Evaluation of normal range of serum 25 hydroxyvitamin d in iraqi healthy adults: demographic and socioeconomic effects.

Objective: Aim: To determine the normal range of serum levels of total 25(OH)VD in Iraqi healthy adult subjects and to relate its level with demographic profile and socioeconomic status..

Patients And Methods: Materials and Methods: This cross sectional study was carried out at Iraq and the samples were collected during the period from August 2019 to January 2020.

A prognostic molecular signature of hepatic steatosis is spatially heterogeneous and dynamic in human liver.

Metabolic dysfunction-associated steatotic liver disease (MASLD) prevalence is increasing in parallel with an obesity pandemic, calling for novel strategies for prevention and treatment. We defined a circulating proteome of human MASLD across ≈7000 proteins in ≈5000 individuals from diverse, at-risk populations across the metabolic health spectrum, demonstrating reproducible diagnostic performance and specifying both known and novel metabolic pathways relevant to MASLD (central carbon and amino acid metabolism, hepatocyte regeneration, inflammation, fibrosis, insulin sensitivity). A parsimonious proteomic signature of MASLD was associated with a protection from MASLD and its related multi-system metabolic consequences in >26000 free-living individuals, with an additive effect to polygenic risk.

Hippocampus Glutathione S Reductase Potentially Confers Genetic Resilience to Cognitive Decline in the AD-BXD Mouse Population.

Alzheimer's disease (AD) is a prevalent and costly age-related dementia. Heritable factors account for 58-79% of variation in late-onset AD, but substantial variation remains in age-of- onset, disease severity, and whether those with high-risk genotypes acquire AD. To emulate the diversity of human populations, we utilized the AD-BXD mouse panel.

Carbon Electrode Sensor for the Measurement of Cortisol with Fast-Scan Cyclic Voltammetry.

Cortisol is a vital steroid hormone that has been known as the "stress hormone", which is elevated during times of high stress and anxiety and has a significant impact on neurochemistry and brain health. The improved detection of cortisol is critically important as it will help further our understanding of stress during several physiological states. Several methods exist to detect cortisol; however, they suffer from low biocompatibility and spatiotemporal resolution, and they are relatively slow.

Detecting the effect of genetic diversity on brain composition in an Alzheimer's disease mouse model.

Alzheimer's disease (AD) is characterized by neurodegeneration, pathology accumulation, and progressive cognitive decline. There is significant variation in age at onset and severity of symptoms highlighting the importance of genetic diversity in the study of AD. To address this, we analyzed cell and pathology composition of 6- and 14-month-old AD-BXD mouse brains using the semi-automated workflow (QUINT); which we expanded to allow for nonlinear refinement of brain atlas-registration, and quality control assessment of atlas-registration and brain section integrity.

Hypoparathyroidism-Retardation-Dysmorphism Syndrome due to a Variant in the Tubulin-Specific Chaperone E Gene as a Cause of Combined Immune Deficiency.

Background: Hypoparathyroidism-retardation-dysmorphism (HRD) syndrome is a disease composed of hypoparathyroidism, growth retardation, severe developmental delay, and typical dysmorphic features caused by the tubulin-specific chaperone E gene variant. Many patients succumb in infancy to HRD due to overwhelming infections mainly caused by Pneumococcus spp. Knowledge related to the immune system in these patients is scarce.

Life-long dietary restrictions have negligible or damaging effects on late-life cognitive performance: A key role for genetics in outcomes.

Several studies report that caloric restriction (CR) or intermittent fasting (IF) can improve cognition, while others report limited or no cognitive benefits. Here, we compare the effects of 20% CR, 40% CR, 1-day IF, and 2-day IF feeding paradigms to ad libitum controls on Y-maze working memory (WM) and contextual fear memory (CFM) in a large population of Diversity Outbred mice that model the genetic diversity of humans. While CR and IF interventions improve lifespan, we observed no enhancement of working memory or CFM in mice on these feeding paradigms, and report 40% CR to be damaging to recall of CFM.

Problematic Smartphone Use: Prevalence and Associated Factors Among Health Sciences Students in Saudi Arabia.

Excessive smartphone use leads to several physical and psychological disorders, particularly among young adults. This study aimed to investigate the prevalence and the associated factors of problematic smartphone use (PSU) among health sciences students in Jeddah, Saudi Arabia. During the 2019 academic year, a cross-sectional analytic study randomly recruited 408 health sciences students (67.

Differential Regulation of Mouse Hippocampal Gene Expression Sex Differences by Chromosomal Content and Gonadal Sex.

Common neurological disorders, like Alzheimer's disease (AD), multiple sclerosis (MS), and autism, display profound sex differences in prevalence and clinical presentation. However, sex differences in the brain with health and disease are often overlooked in experimental models. Sex effects originate, directly or indirectly, from hormonal or sex chromosomal mechanisms.

Characterization of the binding of cytosolic phospholipase A alpha and NOX2 NADPH oxidase in mouse macrophages.

Background: Previous studies have demonstrated that cytosolic phospholipase Aα (cPLAα) is required for NOX2 NADPH oxidase activation in human and mouse phagocytes. Moreover, upon stimulation, cPLAα translocates to the plasma membranes by binding to the assembled oxidase, forming a complex between its C2 domain and the PX domain of the cytosolic oxidase factor, p47 in human phagocytes. Intravenous administration of antisense against cPLAα that significantly inhibited its expression in mouse peritoneal neutrophils and macrophages also inhibited superoxide production, in contrast to cPLAα knockout mice that showed normal superoxide production.

Early upregulation of cytosolic phospholipase Aα in motor neurons is induced by misfolded SOD1 in a mouse model of amyotrophic lateral sclerosis.

Background: Amyotrophic lateral sclerosis (ALS) is a fatal multifactorial neurodegenerative disease characterized by the selective death of motor neurons. Cytosolic phospholipase A alpha (cPLAα) upregulation and activation in the spinal cord of ALS patients has been reported. We have previously shown that cPLAα upregulation in the spinal cord of mutant SOD1 transgenic mice (SOD1) was detected long before the development of the disease, and inhibition of cPLAα upregulation delayed the disease's onset.

A large beam high efficiency radio frequency neutron spin flipper.

A design for a radio frequency (RF) neutron spin flipper obtained from magneto-static and neutron spin transport simulations is presented. The RF flipper constructed from this design provides a flipping probability of 0.999 or better for a beam size 6 cm wide and 15 cm high and a wavelength band between 0.

Lumenato protects normal human dermal fibroblasts from neutrophil-induced collagen-3 damage in co-cultures.

Collagen is the major structural protein in the extracellular matrix of skin produced by fibroblasts. UV exposure results in infiltration of neutrophils within the epidermis and dermis, inducing collagen damage and contributing to the process of photo-aging. Collagen-3 is an integral structural component with collagen-1, and is an important regulator of collagen-1 fibrillogenesis.

A novel zeta-associated protein 70 homozygous mutation causing combined immunodeficiency presenting as neonatal autoimmune hemolytic anemia.

Biallelic mutations in the zeta-associated protein 70 (ZAP70) gene cause combined immunodeficiency (CID). Neonatal screening for severe CID in Israel is implemented since 2015. We report on clinical, flow cytometry, and genetic data of an unusual ZAP70 deficiency patient.

Cold neutron radiation dose effects on a LiF:ZnS(Ag) neutron detector with wavelength shifting fibers and SiPM photodetector.

A LiF:ZnS(Ag) based cold neutron detector with wavelength shifting (WLS) fibers and SiPM photodetector was developed at the NIST Center for Neutron Research for the CANDoR instrument (Chromatic Analysis Neutron Diffractometer or Reflectometer). A series of detectors were irradiated with neutron doses ranging between 1E+11 n/cm to 6E+12 n/cm. It was found that the neutron absorbing Li isotope was not measurably depleted, but the photonic yield of the detector deteriorated with increasing neutron dose.

Health benefits attributed to 17α-estradiol, a lifespan-extending compound, are mediated through estrogen receptor α.

Metabolic dysfunction underlies several chronic diseases, many of which are exacerbated by obesity. Dietary interventions can reverse metabolic declines and slow aging, although compliance issues remain paramount. 17α-estradiol treatment improves metabolic parameters and slows aging in male mice.

Identifying Mechanisms of Normal Cognitive Aging Using a Novel Mouse Genetic Reference Panel.

Developing strategies to maintain cognitive health is critical to quality of life during aging. The basis of healthy cognitive aging is poorly understood; thus, it is difficult to predict who will have normal cognition later in life. Individuals may have higher baseline functioning (cognitive reserve) and others may maintain or even improve with age (cognitive resilience).

Cross-Species Analyses Identify Dlgap2 as a Regulator of Age-Related Cognitive Decline and Alzheimer's Dementia.

Genetic mechanisms underlying age-related cognitive decline and dementia remain poorly understood. Here, we take advantage of the Diversity Outbred mouse population to utilize quantitative trait loci mapping and identify Dlgap2 as a positional candidate responsible for modifying working memory decline. To evaluate the translational relevance of this finding, we utilize longitudinal cognitive measures from human patients, RNA expression from post-mortem brain tissue, data from a genome-wide association study (GWAS) of Alzheimer's dementia (AD), and GWAS results in African Americans.