Bacterial dealkylation of benzalkonium chlorides in wastewater produces benzyldimethylamine, a potent N-nitrosodimethylamine precursor.

N-nitrosodimethylamine (NDMA) is a carcinogenic disinfection byproduct that forms during chloramine disinfection of municipal wastewater effluents which are increasingly used to augment drinking water supplies due to growing water scarcity. Knowledge of wastewater NDMA precursors is limited and the known pool of NDMA precursors has not closed the mass balance between precursor loading, precursor NDMA yield, and formed NDMA. Benzalkonium chlorides (BACs) are the most prevalent quaternary ammonium surfactants and have antimicrobial properties.

CLIP-Seq analysis enables the design of protective ribosomal RNA bait oligonucleotides against ALS/FTD poly-GR pathophysiology.

Amyotrophic lateral sclerosis and frontotemporal dementia patients with a hexanucleotide repeat expansion in (C9-HRE) accumulate poly-GR and poly-PR aggregates. The pathogenicity of these arginine-rich dipeptide repeats (R-DPRs) is thought to be driven by their propensity to bind low-complexity domains of multivalent proteins. However, the ability of R-DPRs to bind native RNA and the significance of this interaction remain unclear.

The Tubulin Code, from Molecules to Health and Disease.

Microtubules are essential dynamic polymers composed of α/β-tubulin heterodimers. They support intracellular trafficking, cell division, cellular motility, and other essential cellular processes. In many species, both α-tubulin and β-tubulin are encoded by multiple genes with distinct expression profiles and functionality.

Analysis of proteome-wide degradation dynamics in ALS SOD1 iPSC-derived patient neurons reveals disrupted VCP homeostasis.

Mutations in SOD1 cause amyotrophic lateral sclerosis (ALS) through gain-of-function effects, yet the mechanisms by which misfolded mutant SOD1 (mutSOD1) protein impairs human motor neurons (MNs) remain unclear. Here, we use induced-pluripotent-stem-cell-derived MNs coupled to metabolic stable isotope labeling and mass spectrometry to investigate proteome-wide degradation dynamics. We find several proteins, including the ALS-causal valosin-containing protein (VCP), which predominantly acts in proteasome degradation and autophagy, that degrade slower in mutSOD1 relative to isogenic control MNs.

Loss of function of the ALS-associated NEK1 kinase disrupts microtubule homeostasis and nuclear import.

Loss-of-function variants in NIMA-related kinase 1 (NEK1) constitute a major genetic cause of amyotrophic lateral sclerosis (ALS), accounting for 2 to 3% of all cases. However, how mutations cause motor neuron (MN) dysfunction is unknown. Using mass spectrometry analyses for NEK1 interactors and NEK1-dependent expression changes, we find functional enrichment for proteins involved in the microtubule cytoskeleton and nucleocytoplasmic transport.

Attenuation characteristics of an extended-wear hearing aid: Impulse and continuous noise.

The extended-wear hearing aid (EWHA) is a hearing assistive device that combines a low-power analog amplification circuit with a soft biocompatible foam plug that allows it to remain in the ear canal for several months at a time without replacement. EWHAs fit snugly in the ear canal and are not vented and so produce insertion losses comparable to a passive earplug when inserted into the ear canal with the active circuitry turned off. However, EWHAs are not marketed as hearing protection devices, and other than a general warning to users that the device will have impaired auditory awareness when the device is inserted in the "off" mode, relatively little has been reported about the attenuation characteristics of EWHAs.

Hearing conservation measures of effectiveness across the Department of Defense.

This article summarizes the findings from the first report of the new, standard Measures of Effectiveness developed by the Department of Defense (DoD) Hearing Conservation Program Working Group in 2018. When examining periodic hearing test results of DoD personnel, the overall risk of potential hearing injury/illness was stable from 2012 through 2018. The National Guard and Reserve components showed a higher potential risk of hearing loss, possibly related to lower compliance on follow-up tests when a shift in hearing occurred.

Habits of courage: Reconceptualizing risk in social movement organizing.

We examine the types of risk that organizers seeking to build people-based political power take and describe how organizers cultivate habits of courage in themselves and others to regularly confront these risks. While prior literature emphasizes the degree of risk (high vs. low), we identify and elaborate two qualitatively different types of risk: internal and external.

Summation of disinfection by-product CHO cell relative toxicity indices: sampling bias, uncertainty, and a path forward.

The cyto- and genotoxic potencies of disinfection by-products (DBPs) have been evaluated in published literature by measuring the response of exposed Chinese hamster ovary cells. In recent publications, DBP concentrations divided by their individual toxicity indices are summed to predict the relative toxicity of a water sample. We hypothesized that the omission or inclusion of certain DBPs over others is equivalent to statistical sampling bias and may result in biased conclusions.

I'm Wearing My Hearing Protection - Am I Still At Risk for Hearing Loss? Lurking Ototoxins in the Military Environment.

Objective: Information is summarized from the overall body of published literature regarding ototoxic chemicals encountered outside of clinical exposures, largely in occupational settings. While summarizing the most common non-pharmaceutical ototoxins, this review provides clinically relevant information and recommendations such that hearing health professionals may adopt a more comprehensive and appropriate diagnostic case history, test battery, documentation scheme, and education delivery.

Methods: Solvents, metals, and asphyxiants literature was reviewed using PubMed, national and international agency websites, and communications with known ototoxicity experts.

Prevalence of permanent threshold shifts in the United States Air Force hearing conservation program by career field, 2005-2011.

The purpose of this study was to describe changes in hearing, using the permanent threshold shift metric, among United States Air Force servicemembers, including active duty, Reserve and Air National Guard components, for demographics, job categories, and career fields. In the United States Air Force, only servicemembers who are occupationally exposed routinely to hazardous noise are monitored. Audiogram records and demographic variables were analyzed for servicemembers from 2005-2011 using data from the Department of Defense system that captures occupational hearing tests worldwide.

Epigenetic inactivation of the tumor suppressor BIN1 drives proliferation of SNF5-deficient tumors.

Emerging evidence demonstrates that subunits of the SWI/SNF chromatin remodeling complex are specifically mutated at high frequency in a variety of human cancer types. SNF5 (SMARCB1/INI1/BAF47), a core subunit of the SWI/SNF complex, is inactivated in the vast majority of rhabdoid tumors (RT), an aggressive type of pediatric cancer. SNF5-deficient cancers are diploid and genomically stable, suggesting that epigenetically based changes in transcription are key drivers of tumor formation caused by SNF5 loss.

Loss of the tumor suppressor Snf5 leads to aberrant activation of the Hedgehog-Gli pathway.

Aberrant activation of the Hedgehog (Hh) pathway can drive tumorigenesis. To investigate the mechanism by which glioma-associated oncogene family zinc finger-1 (GLI1), a crucial effector of Hh signaling, regulates Hh pathway activation, we searched for GLI1-interacting proteins. We report that the chromatin remodeling protein SNF5 (encoded by SMARCB1, hereafter called SNF5), which is inactivated in human malignant rhabdoid tumors (MRTs), interacts with GLI1.

Epigenetic antagonism between polycomb and SWI/SNF complexes during oncogenic transformation.

Epigenetic alterations have been increasingly implicated in oncogenesis. Analysis of Drosophila mutants suggests that Polycomb and SWI/SNF complexes can serve antagonistic developmental roles. However, the relevance of this relationship to human disease is unclear.

Epigenetics and cancer without genomic instability.

Genomic instability is often considered a hallmark of cancer. However, it remains unclear whether chromosomal disorganization is most frequently a cause or a consequence of tumorigenesis. The fact that subsets of many cancers lack chromosomal or microsatellite instability argues against the hypothesis that genomic instability plays an essential role in the initiation and maintenance of oncogenesis.

Loss of the epigenetic tumor suppressor SNF5 leads to cancer without genomic instability.

There is a growing appreciation of the role that epigenetic alterations can play in oncogenesis. However, given the large number of genetic anomalies present in most cancers, it has been difficult to evaluate the extent to which epigenetic changes contribute to cancer. SNF5 (INI1/SMARCB1/BAF47) is a tumor suppressor that regulates the epigenome as a core member of the SWI/SNF chromatin remodeling complex.

Estrogen receptor-beta regulates transcript levels for oxytocin and arginine vasopressin in the hypothalamic paraventricular nucleus of male mice.

Estrogen receptor (ER)-beta, unlike ER-alpha, is localized in the hypothalamic paraventricular nucleus (PVN) which also contains neuropeptide synthesizing neurons, such as oxytocin (OT), arginine vasopressin (AVP) and corticotropin-releasing hormone (CRH). Although it is known that some ER-beta containing neurons co-express OT and AVP, but not CRH, in the PVN, it is not yet determined whether ER-beta activation may indeed play a role in estrogenic regulation on syntheses of these neuropeptides. In the present study, we tested this hypothesis by comparing the effects of estrogen on the levels of OT, AVP and CRH messenger RNA (mRNA) between ER-beta knockout (betaERKO) and wild type (WT) control male mice.