The association between toenail metals and extracellular MicroRNAs (ex-miRNAs) among the participants of the Normative Aging study (NAS).

Background: Mechanistic studies of the effects of environmental risk factors have been exploring the potential role of microRNA(miRNAs) as a possible pathway to clinical disease. In this study we examine whether levels of toenail metals are associated with changes in extracellular miRNA(ex-miRNA) expression.

Methods: We used data derived from the Normative Aging Study from 1996 to 2014 to conduct our analyses.

Intermediate and long-term exposure to air pollution and temperature and the extracellular microRNA profile of participants in the normative aging study (NAS).

Background: The molecular effects of intermediate and long-term exposure to air pollution and temperature, such as those on extracellular microRNA (ex-miRNA) are not well understood but may have clinical consequences.

Objectives: To assess the association between exposure to ambient air pollution and temperature and ex-miRNA profiles.

Methods: Our study population consisted of 734 participants in the Normative Aging Study (NAS) between 1999 and 2015.

Air pollution and human endogenous retrovirus methylation in the school inner-city asthma intervention study.

Human endogenous retroviruses (HERVs) are transposable genomic elements generally repressed through DNA methylation. HERVs can be demethylated and expressed in response to environmental stimuli. Therefore, more research is needed to understand the influence of environmental exposures on HERV methylation.

Longitudinal transcriptomic analysis of mouse sciatic nerve reveals pathways associated with age-related muscle pathology.

Background: Sarcopenia, the age-associated decline in skeletal muscle mass and strength, has long been considered a disease of muscle only, but accumulating evidence suggests that sarcopenia could originate from the neural components controlling muscles. To identify early molecular changes in nerves that may drive sarcopenia initiation, we performed a longitudinal transcriptomic analysis of the sciatic nerve, which governs lower limb muscles, in aging mice.

Methods: Sciatic nerve and gastrocnemius muscle were obtained from female C57BL/6JN mice aged 5, 18, 21 and 24 months old (n = 6 per age group).

Short-term air pollution and temperature exposure and changes in the extracellular microRNA profile of Normative Aging Study (NAS) participants.

Background: While the health effects of air pollution and temperature are widely studied, the molecular effects are poorly understood. Extracellular microRNAs (ex-miRNAs) have the potential to serve as diagnostic or prognostic biomarkers and/or to act as intercellular signaling molecules that mediate the effects of environmental exposures on health outcomes.

Methods: We examined the relationship between short-term exposure to air pollution and ambient temperature and the ex-miRNA profiles of participants in the Normative Aging Study (NAS) from 1999 to 2015.

Extracellular microRNA and cognitive function in a prospective cohort of older men: The Veterans Affairs Normative Aging Study.

Background: Aging-related cognitive decline is an early symptom of Alzheimer's disease and other dementias, and on its own can have substantial consequences on an individual's ability to perform important everyday functions. Despite increasing interest in the potential roles of extracellular microRNAs (miRNAs) in central nervous system (CNS) pathologies, there has been little research on extracellular miRNAs in early stages of cognitive decline. We leverage the longitudinal Normative Aging Study (NAS) cohort to investigate associations between plasma miRNAs and cognitive function among cognitively normal men.

Isolation and characterization of extracellular vesicles in saliva of children with asthma.

Aim: To confirm the presence of extracellular vesicles (EVs) in cell-free saliva (CFS) of children with asthma and describe the isolated EV population.

Methods: A pooled sample of CFS EVs isolated from 180 participants using ExoQuick-TC was examined in downstream analyses. Transmission electron microscopy (TEM) was used to confirm the presence of EVs.

Sex-specific neurotoxic effects of heavy metal pollutants: Epidemiological, experimental evidence and candidate mechanisms.

The heavy metals lead (Pb), mercury (Hg), and cadmium (Cd) are ubiquitous environmental pollutants and are known to exert severe adverse impacts on the nervous system even at low concentrations. In contrast, the heavy metal manganese (Mn) is first and foremost an essential nutrient, but it becomes neurotoxic at high levels. Neurotoxic metals also include the less prevalent metalloid arsenic (As) which is found in excessive concentrations in drinking water and food sources in many regions of the world.

Nanoparticle Tracking Analysis for the Quantification and Size Determination of Extracellular Vesicles.

The physiological and pathophysiological roles of extracellular vesicles (EVs) have become increasingly recognized, making the EV field a quickly evolving area of research. There are many different methods for EV isolation, each with distinct advantages and disadvantages that affect the downstream yield and purity of EVs. Thus, characterizing the EV prep isolated from a given source by a chosen method is important for interpretation of downstream results and comparison of results across laboratories.

BAH domains and a histone-like motif in DNA methyltransferase 1 (DNMT1) regulate and maintenance methylation .

DNA methyltransferase 1 (DNMT1) is a multidomain protein believed to be involved only in the passive transmission of genomic methylation patterns via maintenance methylation. The mechanisms that regulate DNMT1 activity and targeting are complex and poorly understood. We used embryonic stem (ES) cells to investigate the function of the uncharacterized bromo-adjacent homology (BAH) domains and the glycine-lysine (GK) repeats that join the regulatory and catalytic domains of DNMT1.

Antisense oligonucleotides extend survival and reverse decrement in muscle response in ALS models.

Mutations in superoxide dismutase 1 (SOD1) are responsible for 20% of familial ALS. Given the gain of toxic function in this dominantly inherited disease, lowering SOD1 mRNA and protein is predicted to provide therapeutic benefit. An early generation antisense oligonucleotide (ASO) targeting SOD1 was identified and tested in a phase I human clinical trial, based on modest protection in animal models of SOD1 ALS.

Sex-Specific Neurotoxic Effects of Organophosphate Pesticides Across the Life Course.

Purpose Of Review: This review discusses the sex-specific effects of exposure to various organophosphate (OP) pesticides throughout the life course and potential reasons for the differential vulnerabilities observed across sexes.

Recent Findings: Sex is a crucial factor in the response to toxicants, yet the sex-specific effects of OP exposure, particularly in juveniles and adults, remain unresolved. This is largely due to study design and inconsistencies in exposure and outcome assessments.

Reprogramming cells from Gulf War veterans into neurons to study Gulf War illness.

Gulf War illness (GWI), which afflicts at least 25% of veterans who served in the 1990-1991 war in the Persian Gulf, is thought to be caused by deployment exposures to various neurotoxicants, including pesticides, anti-nerve gas pills, and low-level nerve agents including sarin/cyclosarin. GWI is a multisymptom disorder characterized by fatigue, joint pain, cognitive problems, and gastrointestinal complaints. The most prominent symptoms of GWI (memory problems, poor attention/concentration, chronic headaches, mood alterations, and impaired sleep) suggest that the disease primarily affects the CNS.