Basic Science and Pathogenesis.

Background: Mitochondrial reactive oxygen species (mROS), such as superoxide and hydrogen peroxide (HO), are implicated in aging-associated neurological disorders, including Alzheimer's Disease and frontotemporal dementia. Mitochondrial complex III of the respiratory chain has the highest capacity for mROS production and generates mROS toward the cytosol, poising it to regulate intracellular signaling and disease mechanisms. However, the exact triggers of complex III-derived ROS (CIII-ROS), its downstream molecular targets, and its functional roles in dementia-related pathogenesis remain unclear.

The validation of an LC-MS/MS method for the quantification of vitamin D metabolites in human milk and their biological variability in Gambian women.

Vitamin D is required for healthy growth and development, but data on human milk vitamin D content is limited. We describe a liquid chromatography tandem mass spectrometry (LC-MS/MS) method for the analysis of vitamin D metabolites in human milk, and its application in samples collected on two consecutive days from women in rural Gambia. Vitamin D compounds were extracted from 1 mL of milk by liquid-liquid extraction and derivatised with 4-phenyl-1,2,4-triazoline-3,5-dione (PTAD) prior to analysis by LC-MS/MS.

CDK6-mediated endothelial cell cycle acceleration drives arteriovenous malformations in hereditary hemorrhagic telangiectasia.

Increased endothelial cell proliferation is a hallmark of arteriovenous malformations (AVMs) in hereditary hemorrhagic telangiectasia (HHT). Here, we report a cyclin-dependent kinase 6 (CDK6)-driven mechanism of cell cycle deregulation involved in endothelial cell proliferation and HHT pathology. Specifically, endothelial cells from the livers of HHT mice bypassed the G1/S checkpoint and progressed through the cell cycle at an accelerated pace.

Rain Gardens and Rain Gauges: Students Get Hands on With Data While Evaluating Green Infrastructure at Their School.

Two modules were designed for high school science students to investigate the performance of a rain garden installed on school property. The rain garden, a green infrastructure system which allows soil infiltration, was installed to reduce impacts to urban streams and can increase the community's resilience to flooding. By involving students in the analysis of this mitigation strategy, students learned new technical skills, gained varied experiences in collecting and analyzing data, were exposed to new STEM careers, and learned about local issues that impact their community while collaborating with local professionals.

Mitochondrial complex III-derived ROS amplify immunometabolic changes in astrocytes and promote dementia pathology.

Neurodegenerative disorders alter mitochondrial functions, including the production of reactive oxygen species (ROS). Mitochondrial complex III (CIII) generates ROS implicated in redox signaling, but its triggers, targets, and disease relevance are not clear. Using site-selective suppressors and genetic manipulations together with mitochondrial ROS imaging and multiomic profiling, we found that CIII is the dominant source of ROS production in astrocytes exposed to neuropathology-related stimuli.

Loss of Zmiz1 in mice leads to impaired cortical development and autistic-like behaviors.

De novo mutations in transcriptional regulators are emerging as key risk factors contributing to the etiology of neurodevelopmental disorders. Human genetic studies have recently identified ZMIZ1 and its de novo mutations as causal of a neurodevelopmental syndrome strongly associated with intellectual disability, autism, ADHD, microcephaly, and other developmental anomalies. However, the role of ZMIZ in brain development or how ZMIZ1 mutations cause neurological phenotypes is unknown.

The effect of an acute bout of exercise on circulating vitamin D metabolite concentrations: a randomised crossover study in healthy adults.

The effect of acute exercise on circulating concentrations of vitamin D metabolites is unclear. To address this knowledge gap, we examined the effect of a bout of treadmill-based exercise versus rest on circulating concentrations of 25(OH)D, 25(OH)D, 3-epi-25(OH)D, 24,25(OH)D, 1,25(OH)D, and vitamin D and D in healthy men and women. Thirty-three healthy adults (14 females, 41 (15) years, body mass index 26.

Endothelial Zmiz1 modulates physiological and pathophysiological angiogenesis during retinal development.

Angiogenesis is a highly coordinated process involving the control of various endothelial cell behaviors. Mechanisms for transcription factor involvement in the regulation of endothelial cell dynamics and angiogenesis have become better understood, however much remains unknown, especially the role of non-DNA binding transcriptional cofactors. Here, we show that Zmiz1, a transcription cofactor, is enriched in the endothelium and critical for embryonic vascular development, postnatal retinal angiogenesis, and pathological angiogenesis in oxygen induced retinopathy (OIR).

The Impact of Delayed Processing of Chilled Whole Blood Specimens on the Measurement of Nutritional Biomarkers in the United Kingdom National Diet and Nutrition Survey Rolling Programme.

Background: The logistics of timely processing of blood specimens remains a barrier in population health studies to the generation of micronutrient status data.

Objectives: To test a blood specimen processing protocol that includes overnight postage with cooling and its effect on nutritional biomarker concentrations.

Methods: This study was embedded within the United Kingdom National Diet and Nutrition Survey.

Assessment of Erythrocyte Transketolase, Whole Blood Thiamine Diphosphate, and Human Milk Thiamine Concentrations to Identify Infants and Young Children Responding Favorably to Therapeutic Thiamine Administration: Findings from the Lao Thiamine Study, a Prospective Cohort Study.

Background: There is limited information on relationships among biomarkers of thiamine status (whole blood thiamine diphosphate [ThDP], erythrocyte transketolase activity coefficient [ETKac], and human milk thiamine [MTh]) and clinical manifestations of thiamine deficiency.

Objectives: This study aimed to explore correlations among these biomarkers and thiamine responsive disorders (TRDs), a diagnosis based on favorable clinical response to thiamine.

Methods: Hospitalized infants and young children (aged 21 d to <18 mo) with respiratory, cardiac, and/or neurological symptoms suggestive of thiamine deficiency were treated with parenteral thiamine (100 mg daily) for ≥3 d alongside other treatments and re-examined systematically.

ADH1B, the adipocyte-enriched alcohol dehydrogenase, plays an essential, cell-autonomous role in human adipogenesis.

Alcohol dehydrogenase 1B (ADH1B) is a primate-specific enzyme which, uniquely among the ADH class 1 family, is highly expressed both in adipose tissue and liver. Its expression in adipose tissue is reduced in obesity and increased by insulin stimulation. Interference with expression has also been reported to impair adipocyte function.

Group-based exercise for Parkinson's: a qualitative study of participants and partners' perceptions of an exercise class delivered through a community-university collaboration.

Background: Community-based exercise programmes (CBEPs) offer a practical and viable approach to providing people with Parkinson's disease (PwP) the opportunity to exercise as an ancillary therapeutic benefit to pharmacological management. This study explores the perceptions of exercising participants (PwP) and non-participating partners involved in an exercise class delivered through a community-university partnership.

Methods: Two separate focus group discussions were conducted: one with class participants (PwP: n = 7, H&Y scale I to III), and the other with non-participating partners of PwP (n = 4).

Hippocampal astrocytes induce sex-dimorphic effects on memory.

Astrocytic receptors influence cognitive function and can promote behavioral deficits in disease. These effects may vary based on variables such as biological sex, but it is not known if the effects of astrocytic receptors are dependent on sex. We leveraged in vivo gene editing and chemogenetics to examine the roles of astrocytic receptors in spatial memory and other processes.

Zmiz1 is a novel regulator of lymphatic endothelial cell gene expression and function.

Zinc Finger MIZ-Type Containing 1 (Zmiz1), also known as ZIMP10 or RAI17, is a transcription cofactor and member of the Protein Inhibitor of Activated STAT (PIAS) family of proteins. Zmiz1 is critical for a variety of biological processes including vascular development. However, its role in the lymphatic vasculature is unknown.

Zmiz1 is a novel regulator of brain development associated with autism and intellectual disability.

Neurodevelopmental disorders (NDDs) are a class of pathologies arising from perturbations in brain circuit formation and maturation with complex etiological triggers often classified as environmental and genetic. Neuropsychiatric conditions such as autism spectrum disorders (ASD), intellectual disability (ID), and attention deficit hyperactivity disorders (ADHD) are common NDDs characterized by their hereditary underpinnings and inherent heterogeneity. Genetic risk factors for NDDs are increasingly being identified in non-coding regions and proteins bound to them, including transcriptional regulators and chromatin remodelers.

ISOLATION FROM HOWLER () AND SPIDER MONKEYS () AT A ZOOLOGIC FACILITY IN CENTRAL ILLINOIS.

was initially isolated from an asymptomatic black howler monkey () in a routine fecal culture examination. Fecal cultures from other individuals in this group and an adjacently housed black-headed spider monkey () group recovered from all but one of the individuals sampled (1.1 spider monkeys and 2.

Quantification and reporting of vitamin D concentrations measured in human milk by LC-MS/MS.

Vitamin D is essential for optimal bone health, and vitamin D deficiency has been associated with an increased risk of adverse pregnancy, growth and developmental outcomes. In early life, and in the absence of endogenous vitamin D production from UVB light, infants are reliant on vitamin D stores established and the vitamin D supply from human milk (HM). However, comprehensive data on vitamin D in HM is lacking.

Dermatophytosis is uncommon in asymptomatic wild eastern cottontail rabbits in Illinois, Midwestern United States.

Objective: To investigate the presence of dermatophytes on the haircoat of wild eastern cottontail rabbits (ECR) (Sylvilagus floridanus) with and without skin lesions.

Animals: 2-week-old or older ECR admitted to a Wildlife Medical Clinic (WMC) in central Illinois, Midwest United States, from September 2021 to August 2022.

Methods: ECR were surveyed over a 1-year period to assess the prevalence and seasonality of dermatophytosis.

Executive summary of the 14th HHT international scientific conference.

Hereditary Hemorrhagic Telangiectasia (HHT) is an autosomal dominant vascular disorder characterized by small, dilated clustered vessels (telangiectasias) and by larger visceral arteriovenous malformations (AVMs), which directly connect the feeding arteries with the draining veins. These lesions are fragile, prone to rupture, and lead to recurrent epistaxis and/or internal hemorrhage among other complications. Germline heterozygous loss-of-function (LOF) mutations in Bone Morphogenic Protein 9 (BMP9) and BMP10 signaling pathway genes (endoglin-ENG, activin like kinase 1 ACVRL1 aka ALK1, and SMAD4) cause different subtypes of HHT (HHT1, HHT2 and HHT-juvenile polyposis (JP)) and have a worldwide combined incidence of about 1:5000.

Zmiz1 is a novel regulator of lymphatic endothelial cell gene expression and function.

Zinc Finger MIZ-Type Containing 1 (Zmiz1), also known as ZIMP10 or RAI17, is a transcription cofactor and member of the Protein Inhibitor of Activated STAT (PIAS) family of proteins. Zmiz1 is critical for a variety of biological processes including vascular development. However, its role in the lymphatic vasculature is unknown.

Effectors of anterior morphogenesis in C. elegans embryos.

During embryogenesis the nascent Caenorhabditis elegans epidermis secretes an apical extracellular matrix (aECM) that serves as an external stabilizer, preventing deformation of the epidermis by mechanical forces exerted during morphogenesis. At present, the factors that contribute to aECM function are mostly unknown, including the aECM components themselves, their posttranslational regulators, and the pathways required for their secretion. Here we showed that two proteins previously linked to aECM function, SYM-3/FAM102A and SYM-4/WDR44, colocalize to intracellular and membrane-associated puncta and likely function in a complex.

Sexual Assault Experiences in the Active-Component Army: Variation by Year, Gender, Sexual Orientation, and Installation Risk Level.

To better understand the circumstances surrounding sexual assault in the Army, RAND Arroyo Center researchers created descriptions of active-component soldiers' most serious sexual assault experiences using data from the 2016 and 2018 Workplace and Gender Relations Survey of Active Duty Members. In this study, researchers describe the most common types of behaviors that occurred, characteristics of alleged perpetrators, and times and places in which the experiences occurred. They also explore differences by gender, sexual orientation, and installation risk level.

PRDM16 regulates arterial development and vascular integrity.

Proper vascular formation is regulated by multiple signaling pathways. The vascular endothelial growth factor (VEGF) signaling promotes endothelial proliferation. Notch and its downstream targets act to lead endothelial cells toward an arterial fate through regulation of arterial gene expression.