Increasing the utility of epidemiologic studies as key evidence in chemical risk assessment.

The Society of Toxicology 2024 meeting assembled risk assessors, epidemiologists, and toxicologists to discuss the utility of integrating epidemiologic data into the derivation of reference values. Advantages of the use of epidemiologic evidence include (i) human relevance; (ii) increased likelihood that exposure levels are relevant to risk assessment; and (iii) incorporation of uncertainties attributed to co-exposures or other population-based considerations. The workshop panelists discussed the challenges of incorporating epidemiologic evidence due to uncertain exposure measurements, confounding, heterogeneity, and inherent study design limitations.

IFNɣ but not IFNα increases recognition of insulin defective ribosomal product-derived antigen to amplify islet autoimmunity.

Aims/hypothesis: The inflammatory milieu characteristic of insulitis affects translation fidelity and generates defective ribosomal products (DRiPs) that participate in autoimmune beta cell destruction in type 1 diabetes. Here, we studied the role of early innate cytokines (IFNα) and late immune adaptive events (IFNɣ) in insulin DRiP-derived peptide presentation to diabetogenic CD8+ T cells.

Methods: Single-cell transcriptomics of human pancreatic islets was used to study the composition of the (immuno)proteasome.

Taxonomic diversity of microbial communities in sub-seafloor hydrothermal sediments of the active Santorini-Kolumbo volcanic field.

Introduction: Active hydrothermal vents of volcanic origin provide a remarkable manifestation of life on Earth under extreme conditions, which may have consequences for our understanding of habitability on other terrestrial bodies as well.

Methods: Here, we performed for the first time Illumina sequencing of bacterial and archaeal communities on sub-seafloor samples collected from the Santorini-Kolumbo volcanic field. A total of 19 (3-m long) gravity corers were collected and processed for microbial community analysis.

Do shale oil and gas production activities impact ambient air quality? A comprehensive study of 12Â years of chemical concentrations and well production data from the Barnett Shale region of Texas.

Starting around 2008, there was rapid expansion of oil and natural gas (ONG) production into more heavily populated areas within the Dallas-Fort Worth metroplex in the Barnett Shale region of Texas. This colocation raised concerns regarding the effect of ONG activities on chemical levels in the air. In the current study, we examined the potential impacts of ONG activity on the types and concentrations of chemicals in ambient air in the Barnett Shale.

The ABCs of Antigen Presentation by Stromal Non-Professional Antigen-Presenting Cells.

Professional antigen-presenting cells (APCs), such as dendritic cells and macrophages, are known for their ability to present exogenous antigens to T cells. However, many other cell types, including endothelial cells, fibroblasts, and lymph node stromal cells, are also capable of presenting exogenous antigens to either CD8+ or CD4+ T cells via cross-presentation or major histocompatibility complex (MHC) class II-mediated presentation, respectively. Antigen presentation by these stromal nonprofessional APCs differentially affect T cell function, depending on the type of cells that present the antigen, as well as the local (inflammatory) micro-environment.

DNA polymerase zeta contributes to heterochromatin replication to prevent genome instability.

The DNA polymerase zeta (Polζ) plays a critical role in bypassing DNA damage. REV3L, the catalytic subunit of Polζ, is also essential in mouse embryonic development and cell proliferation for reasons that remain incompletely understood. In this study, we reveal that REV3L protein interacts with heterochromatin components including repressive histone marks and localizes in pericentromeric regions through direct interaction with HP1 dimer.

Characterization of the Percival detector with soft X-rays.

In this paper the back-side-illuminated Percival 2-Megapixel (P2M) detector is presented, along with its characterization by means of optical and X-ray photons. For the first time, the response of the system to soft X-rays (250 eV to 1 keV) is presented. The main performance parameters of the first detector are measured, assessing the capabilities in terms of noise, dynamic range and single-photon discrimination capability.

Comparing apples to oranges: Interpreting ozone concentrations from observational studies in the context of the United States ozone regulatory standard.

In 2015, the United States Environmental Protection Agency (US EPA) set the ozone National Ambient Air Quality Standards (NAAQS) at 0.070 parts per million (ppm), for an annual 4th highest daily 8-hour (h) maximum average concentration, averaged over three years, with compliance based on the monitor with the highest concentrations. Numerous epidemiological studies have evaluated associations between ozone and health effects, but how the ozone concentrations derived from those studies can be compared to the ozone NAAQS is not clear, because of the complexity of the standard.

What Are the Net Benefits of Reducing the Ozone Standard to 65 ppb? An Alternative Analysis.

In October 2015, the United States Environmental Protection Agency (EPA) lowered the level of the ozone National Ambient Air Quality Standard (NAAQS) from 0.075 ppm to 0.070 ppm (annual 4th highest daily maximum 8-h concentration, averaged over three years).

DNA polymerase ζ deficiency causes impaired wound healing and stress-induced skin pigmentation.

DNA polymerase ζ (pol ζ) is a specialized enzyme important for DNA damage tolerance, facilitating synthesis past lesions caused by radiation or chemical damage. Here we report that disruption of (encoding the catalytic subunit of pol ζ) in mouse epidermis leads to a defect in proliferation that impairs cutaneous wound healing. A striking increase in epidermal skin pigmentation accompanied both wound healing and UV irradiation in these mice.

Development of an inhalation reference concentration for diethanolamine.

An inhalation reference concentration (RfC) was developed for diethanolamine (DEA), based principally on evaluation of three animal studies (Gamer et al., 1993, 1996, 2008). The RfC (25 μg/m) was based on statistically significantly increased relative liver weight in female rats in Gamer et al.

Ambient ozone and asthma hospital admissions in Texas: a time-series analysis.

Background: Many studies have evaluated associations between asthma emergency department (ED) visits, hospital admissions (HAs), and ambient ozone (O) across the US, but not in Texas. We investigated the relationship between O and asthma HAs, and the potential impacts of outdoor pollen, respiratory infection HAs, and the start of the school year in Texas.

Methods: We obtained daily time-series data on asthma HAs and ambient O concentrations for Dallas, Houston, and Austin, Texas for the years 2003-2011.

The perpetuation of the misconception that rats receive a 3-5 times lower lung tissue dose than humans at the same ozone concentration.

This paper highlights the pervasive misconception concerning 1994 findings from Hatch et al. about ozone (O) tissue dose in humans versus rats. That study exposed humans to 0.

Concentration-response of short-term ozone exposure and hospital admissions for asthma in Texas.

Background: Short-term exposure to ozone has been associated with asthma hospital admissions (HA) and emergency department (ED) visits, but the shape of the concentration-response (C-R) curve is unclear.

Methods: We conducted a time series analysis of asthma HAs and ambient ozone concentrations in six metropolitan areas in Texas from 2001 to 2013. Using generalized linear regression models, we estimated the effect of daily 8-hour maximum ozone concentrations on asthma HAs for all ages combined, and for those aged 5-14, 15-64, and 65+years.

DNA polymerase ζ limits chromosomal damage and promotes cell survival following aflatoxin exposure.

Routine dietary consumption of foods that contain aflatoxins is the second leading cause of environmental carcinogenesis worldwide. Aflatoxin-driven mutagenesis is initiated through metabolic activation of aflatoxin B (AFB) to its epoxide form that reacts with N7 guanine in DNA. The resulting AFB-N7-dG adduct undergoes either spontaneous depurination or imidazole-ring opening yielding formamidopyrimidine AFB (AFB-Fapy-dG).

DNA polymerase ι functions in the generation of tandem mutations during somatic hypermutation of antibody genes.

DNA polymerase ι (Pol ι) is an attractive candidate for somatic hypermutation in antibody genes because of its low fidelity. To identify a role for Pol ι, we analyzed mutations in two strains of mice with deficiencies in the enzyme: 129 mice with negligible expression of truncated Pol ι, and knock-in mice that express full-length Pol ι that is catalytically inactive. Both strains had normal frequencies and spectra of mutations in the variable region, indicating that loss of Pol ι did not change overall mutagenesis.

Inpatient and Day Hospital Treatment of Patients with Depression and Job-related Burnout.

Objective: Burnout is a process of physical and emotional exhaustion that often results in clinical depression. Detailed descriptions and evaluations of specialized psychosomatic treatment are rare. This pilot study investigates the feasibility of inpatient and day hospital treatment of patients with burnout syndrome.

The Polymerase Activity of Mammalian DNA Pol ζ Is Specifically Required for Cell and Embryonic Viability.

DNA polymerase ζ (pol ζ) is exceptionally important for maintaining genome stability. Inactivation of the Rev3l gene encoding the polymerase catalytic subunit causes a high frequency of chromosomal breaks, followed by lethality in mouse embryos and in primary cells. Yet it is not known whether the DNA polymerase activity of pol ζ is specifically essential, as the large REV3L protein also serves as a multiprotein scaffold for translesion DNA synthesis via multiple conserved structural domains.

Are the elements of the proposed ozone National Ambient Air Quality Standards informed by the best available science?

The United States Environmental Protection Agency (US EPA) issues National Ambient Air Quality Standards (NAAQS) for six criteria pollutants, including ozone. Each standard has four elements: an indicator, level, averaging time, and form. Ozone levels (i.

REV7 is essential for DNA damage tolerance via two REV3L binding sites in mammalian DNA polymerase ζ.

DNA polymerase zeta (pol ζ) is exceptionally important for controlling mutagenesis and genetic instability. REV3L comprises the catalytic subunit, while REV7 (MAD2L2) is considered an accessory subunit. However, it has not been established that the role of REV7 in DNA damage tolerance is necessarily connected with mammalian pol ζ, and there is accumulating evidence that REV7 and REV3L have independent functions.