Analysis of recent shared ancestry in a familial cohort identifies coding and noncoding autism spectrum disorder variants.

Autism spectrum disorder (ASD) is a collection of neurodevelopmental disorders characterized by deficits in social communication and restricted, repetitive patterns of behavior or interests. ASD is highly heritable, but genetically and phenotypically heterogeneous, reducing the power to identify causative genes. We performed whole genome sequencing (WGS) in an ASD cohort of 68 individuals from 22 families enriched for recent shared ancestry.

Huntington's disease genotype suppresses global manganese-responsive processes in pre-manifest and manifest YAC128 mice.

Manganese (Mn) is an essential micronutrient required for the proper function of several enzymes. Accumulating evidence demonstrates a selective decrease of bioavailable Mn in vulnerable cell types of Huntington's Disease (HD), an inherited progressive neurodegenerative disorder with no cure. Amelioration of underlying pathophysiology, such as alterations in Mn-dependent biology, may be therapeutic.

Microglia Activation and Gene Expression Alteration of Neurotrophins in the Hippocampus Following Early-Life Exposure to E-Cigarette Aerosols in a Murine Model.

Recent epidemiological data indicate that the popularity of electronic cigarettes (e-cigarettes), and consequently nicotine use, is rising in both adolescent and adult populations. As nicotine is a known developmental neurotoxin, these products present a potential threat for those exposed during early life stages. Despite this, few studies have evaluated the toxicity of e-cigarettes on the developing central nervous system.

Metals and Circadian Rhythms.

Circadian rhythms describe the behavioral and physiological changes that occur in living organisms in order to attune to a 24 hour cycle of day and night. The most striking aspect of circadian function is the sleep-wake cycle, however many other physiological processes are regulated in 24 hour oscillations, including blood pressure, body temperature, appetite, urine production, and the transcription and translation of thousands of circadian dependent genes. Circadian disruption and sleep disorders are strongly connected to neurodegenerative diseases including Parkinson's disease, Alzheimer's disease, and Huntington's disease as well as others.

Untangling the Manganese-α-Synuclein Web.

Neurodegenerative diseases affect a significant portion of the aging population. Several lines of evidence suggest a positive association between environmental exposures, which are common and cumulative in a lifetime, and development of neurodegenerative diseases. Environmental or occupational exposure to manganese (Mn) has been implicated in neurodegeneration due to its ability to induce mitochondrial dysfunction, oxidative stress, and α-synuclein (α-Syn) aggregation.

Manganese and aging.

Manganese (Mn) is an essential metal that is required as a cofactor for many enzymes and is necessary for optimal biological function. Mn is abundant in the earth's crust and is present in soil and well water. Mn is also found in industrial settings, including mining, welding, and battery manufacture.

RNASeq in C. elegans Following Manganese Exposure.

Manganese is a metal that is required for optimal biological functioning of organisms. Absorption, cellular import and export, and excretion of manganese are all tightly regulated. While some genes involved in regulation, such as DMT-1 and ferroportin, are known, it is presumed that many more are involved and as yet unknown.

Identification of a potential susceptibility locus for macular telangiectasia type 2.

Macular Telangiectasia type 2 (MacTel) is a relatively rare macular disease of adult onset presenting with distortions in the visual field and leading to progressive loss of visual acuity. For the purpose of a gene mapping study, several pedigrees were ascertained with multiple affected family members. Seventeen families with a total of 71 individuals (including 45 affected or possibly affected) were recruited at clinical centers in 7 countries under the auspices of the MacTel Project.

Analysis of candidate genes for macular telangiectasia type 2.

Purpose: To find the gene(s) responsible for macular telangiectasia type 2 (MacTel) by a candidate-gene screening approach.

Methods: Candidate genes were selected based on the following criteria: those known to cause or be associated with diseases with phenotypes similar to MacTel, genes with known function in the retinal vasculature or macular pigment transport, genes that emerged from expression microarray data from mouse models designed to mimic MacTel phenotype characteristics, and genes expressed in the retina that are also related to diabetes or hypertension, which have increased prevalence in MacTel patients. Probands from eight families with at least two affected individuals were screened by direct sequencing of 27 candidate genes.

Wnt signaling in angiogenesis.

Although progress has been made in understanding the role of growth factors and their receptors in angiogenesis, little is known about how the Wnt family of growth factors function in the vasculature. Wnts are multifunctional factors that act through the frizzled receptors to regulate proliferation, apoptosis, branching morphogenesis, inductive processes, and cell polarity. All of these processes must occur as developing vascular structures are formed and maintained.

Wnt5a signaling induces proliferation and survival of endothelial cells in vitro and expression of MMP-1 and Tie-2.

Wnts are lipid-modified secreted glycoproteins that regulate diverse biological processes. We report that Wnt5a, which functions in noncanonical Wnt signaling, has activity on endothelial cells. Wnt5a is endogenously expressed in human primary endothelial cells and is expressed in murine vasculature at several sites in mouse embryos and tissues.