An Aurora kinase A-BOD1L1-PP2A B56 axis promotes chromosome segregation fidelity.

Cancer cells are often aneuploid and frequently display elevated rates of chromosome mis-segregation, called chromosomal instability (CIN). CIN is caused by hyperstable kinetochore-microtubule (K-MT) attachments that reduce the correction efficiency of erroneous K-MT attachments. UMK57, a chemical agonist of the protein MCAK (mitotic centromere-associated kinesin), improves chromosome segregation fidelity in CIN cancer cells by destabilizing K-MT attachments, but cells rapidly develop resistance.

DNA-based cell typing in menstrual effluent identifies cell type variation by sample collection method: toward noninvasive biomarker development for women's health.

Menstrual effluent cell profiles have potential as noninvasive biomarkers of female reproductive and gynecological health and disease. We used DNA methylation-based cell type deconvolution (methylation cytometry) to identify cell type profiles in self-collected menstrual effluent. During the second day of their menstrual cycle, healthy participants collected menstrual effluent using a vaginal swab, menstrual cup, and pad.

Lung-kidney axis in cystic fibrosis: Early urinary markers of kidney injury correlate with neutrophil activation and worse lung function.

Background: Adult people with cystic fibrosis (PwCF) have a higher risk of end-stage kidney disease than the general population. The nature and mechanism of kidney disease in CF are unknown. This study quantifies urinary kidney injury markers and examines the hypothesis that neutrophil activation and lung infection are associated with early kidney injury in CF.

Lung-Kidney Axis in Cystic Fibrosis: Early Urinary Markers of Kidney Injury Correlate with Neutrophil Activation and Worse Lung Function.

Background: Adult people with cystic fibrosis (PwCF) have a higher risk of end-stage kidney disease than the general population. The nature and mechanism of kidney disease in CF are unknown. This study quantifies urinary kidney injury markers and examines the hypothesis that neutrophil activation and lung infection are associated with early kidney injury in CF.

An Aurora kinase A-BOD1L1-PP2A B56 Axis promotes chromosome segregation fidelity.

Cancer cells are often aneuploid and frequently display elevated rates of chromosome missegregation in a phenomenon called chromosomal instability (CIN). CIN is commonly caused by hyperstable kinetochore-microtubule (K-MT) attachments that reduces the efficiency of correction of erroneous K-MT attachments. We recently showed that UMK57, a chemical agonist of MCAK (alias KIF2C) improves chromosome segregation fidelity in CIN cancer cells although cells rapidly develop adaptive resistance.

A Novel Home-Based Study of Circadian Rhythms: Design, Rationale, and Methods for the Circadia Study.

The Circadia Study (Circadia) is a novel "direct-to-participant" research study investigating the genetics of circadian rhythm disorders of advanced and delayed sleep phase and non-24 hour rhythms. The goals of the Circadia Study are twofold: (i) to create an easy-to-use toolkit for at-home circadian phase assessment for patients with circadian rhythm disorders through the use of novel in-home based surveys, tests, and collection kits; and (ii) create a richly phenotyped patient resource for genetic studies that will lead to new genetic loci associated with circadian rhythm disorders revealing possible loci of interest to target in the development of therapeutics for circadian rhythm disorders. Through these goals, we aim to broaden our understanding and elucidate the genetics of circadian rhythm disorders across a diverse patient population while increasing accessibility to circadian rhythm disorder diagnostics reducing health disparities through self-directed at-home dim light melatonin onset (DLMO) collections.

Normal gastric tissue infection is associated with epigenetic age acceleration, increased mitotic tick rate, tissue cell composition, and Natural Killer cell methylation alterations.

Background: Gastric adenocarcinomas are a leading cause of global mortality, associated with chronic infection with . The mechanisms by which infection with contributes to carcinogenesis are not well understood. Recent studies from subjects with and without gastric cancer have identified significant DNA methylation alterations in normal gastric mucosa associated with infection and gastric cancer risk.

Mobile Apps for Dietary and Food Timing Assessment: Evaluation for Use in Clinical Research.

Background: Over the last decade, health mobile apps have become an increasingly popular tool used by clinicians and researchers to track food consumption and exercise. However, many consumer apps lack the technological features for facilitating the capture of critical food timing details.

Objective: This study aimed to introduce users to 11 apps from US app stores that recorded both dietary intake and food timing to establish which one would be the most appropriate for clinical research.

Association of DAT1 genetic variants with habitual sleep duration in the UK Biobank.

Short sleep duration has been linked to negative health effects, but is a complex phenotype with many contributing factors, including genetic. We evaluated 27 common single nucleotide polymorphisms (SNPs) in candidate genes previously reported to be associated with other sleep variables for association with self-reported habitual sleep duration in the UK Biobank in 111 975 individuals of European ancestry. Genetic variation in DAT1 (rs464049) was significantly associated with sleep duration after correction for multiple testing (p = 4.

Circadian Rhythms in Plasma Brain-derived Neurotrophic Factor Differ in Men and Women.

The measurement of circulating levels of brain-derived neurotrophic factor (BDNF) has been proposed to be a marker of disease and an indicator of recovery. Thus, knowing the temporal pattern and influence of potential circadian rhythms is important. Although several studies have measured BDNF at different times of day, no studies have done so while controlling for potential masking influences such as sleep and activity.

Genome-wide association analyses of sleep disturbance traits identify new loci and highlight shared genetics with neuropsychiatric and metabolic traits.

Chronic sleep disturbances, associated with cardiometabolic diseases, psychiatric disorders and all-cause mortality, affect 25-30% of adults worldwide. Although environmental factors contribute substantially to self-reported habitual sleep duration and disruption, these traits are heritable and identification of the genes involved should improve understanding of sleep, mechanisms linking sleep to disease and development of new therapies. We report single- and multiple-trait genome-wide association analyses of self-reported sleep duration, insomnia symptoms and excessive daytime sleepiness in the UK Biobank (n = 112,586).

CSF1R mosaicism in a family with hereditary diffuse leukoencephalopathy with spheroids.

Mutations in the colony stimulating factor 1 receptor (CSF1R) have recently been discovered as causal for hereditary diffuse leukoencephalopathy with axonal spheroids. We identified a novel, heterozygous missense mutation in CSF1R [c.1990G > A p.

Genome-wide association analysis identifies novel loci for chronotype in 100,420 individuals from the UK Biobank.

Our sleep timing preference, or chronotype, is a manifestation of our internal biological clock. Variation in chronotype has been linked to sleep disorders, cognitive and physical performance, and chronic disease. Here we perform a genome-wide association study of self-reported chronotype within the UK Biobank cohort (n=100,420).