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Bisphenol A (BPA) is an endocrine-disrupting compound, used as the key monomer of polycarbonate plastics and epoxy resins. BPA has been detected in both humans and farm animals and has been correlated with decreased sperm counts and motility. BPS and BPF are structural analogs of BPA and are increasingly being used in manufacturing as BPA substitutes. In this study, we aim to assess the direct outcomes of BPA, bisphenol S (BPS), and bisphenol F (BPF) exposure on bovine sperm parameters in vitro to elucidate how they affect sperm quality and fertilization potential, and to assess whether BPS and/or BPF are less harmful than BPA. Sperm from three or more bulls was obtained from either fresh samples or cryopreserved straws and exposed to 0.05 mg/mL of BPA, BPS, and BPF in vitro. After 4 h incubation, motility, capacitation, apoptosis/necrosis, and mitochondrial membrane potential levels were measured by computer-assisted sperm analysis or computational flow cytometry. Results showed that BPA exposure significantly reduced both fresh and cryopreserved sperm motility, capacitation, viability and mitochondrial membrane potential levels. Furthermore, BPF significantly decreased motility, capacitation and mitochondrial membrane potential in cryopreserved sperm only. BPS did not have any significant effects on any of the parameters measured. Our results suggest that BPA is the most harmful to sperm, while BPF is toxic under certain conditions, and BPS seems to be the least detrimental. Overall, this study provides an understanding of how the ubiquitous environmental chemicals, bisphenols, may impact male fertility even after ejaculation.

Abstract Background Delta-9-tetrahydrocannabinol (THC) is the primary phytocannabinoid responsible for the psychoactive properties of cannabis and is known to interact with the endocannabinoid system, which is functionally present in the male reproductive system. Since cannabis consumption is the highest among reproductive aged males, the current study aimed to further investigate the effects of THC exposure to phenotypical, physiological, and molecular parameters in sperm. Bull sperm of known fertility were used as a translational model for human sperm and subjected to in vitro treatment with physiologically relevant experimental doses of THC. Sperm parameters, capacitation, apoptosis, and transcript levels were evaluated following treatment. Results Motility, morphology, and viability of bovine sperm was unaltered from THC exposure. However, 0.32µM of THC caused an increased proportion of capacitating sperm (p

Elevated molecular stress in women is known to have negative impacts on the reproductive development of oocytes and the embryos prior to implantation. In recent years, the prevalence of cannabis use among women of reproductive age has risen due to its ability to relieve psychological stress and nausea, which are mediated by its psychoactive component, ∆-9-tetrahydrocannabinol (THC). Although cannabis is the most popular recreational drug of the 21st century, much is unknown about its influence on molecular stress in reproductive tissues. The current literature has demonstrated that THC causes dose- and time-dependent alterations in glucocorticoid signaling, which have the potential to compromise morphology, development, and quality of oocytes and embryos. However, there are inconsistencies across studies regarding the mechanisms for THC-dependent changes in stress hormones and how either compounds may drive or arrest development. Factors such as variability between animal models, physiologically relevant doses, and undiscovered downstream gene targets of both glucocorticoids and THC could account for such inconsistencies. This review evaluates the results of studies which have investigated the effects of glucocorticoids on reproductive development and how THC may alter stress signaling in relevant tissues.

In October of 2015, a large underground storage well at the Aliso Canyon natural gas storage facility experienced a massive methane leak (also referred to as “natural gas blowout”), which resulted in the largest ever anthropogenic release of methane from a single point source in the United States. Additional sampling conducted during the event revealed unique gas and particle concentrations in ambient air and a characteristic “fingerprint” of metals in the indoor dust samples similar to samples taken at the blowout site. We further investigated the association between the Aliso Canyon natural gas storage site and several measured air pollutants by: (a) conducting additional emission source studies using meteorological data and correlations between particulate matter, methane, and hazardous air pollutants (HAPs) collected during the natural gas blowout at distances ranging from 1.2 to 7.3 km due south of well SS25, (b) identifying the unique i/n-pentane ratio signature associated with emissions from the blowout event, and (c) identifying characteristics unique to the homes that tested positive for air pollutants using data collected from extensive indoor environmental assessment surveys. Results of air quality samples collected near Aliso Canyon during the final weeks of the event revealed that elevated levels of several HAP compounds were likely influenced by the active natural gas blowout. Furthermore, the final attempts to plug the well during the days preceding the well kill were associated with particle emissions likely from the well site. Together, this investigation suggests uncontrolled leaks or blowout events at natural gas storage facilities have the potential to release harmful pollutants with adverse health and environmental consequences into proximate communities. With this evidence, our recommendations include facility-specific meteorological and air quality data-collection equipment installed at natural gas storage facilities and support of environmental surveillance after severe off-normal operation events. Keywords: Natural gas storage, Hazardous air pollutants (HAPs), Particulate matter (PM), Methane, Air quality, Aliso Canyon

Abstract Therapy-related acute myeloid leukemia (t-AML) often exhibits adverse (genetic) features. There is ongoing discussion on the impact of t-AML on long-term outcome in AML. Therefore, we retrospectively analyzed clinical and biological characteristics of 1133 AML patients (225 t-AML patients and 908 de novo AML patients) with a median follow-up of 81.8 months. T-AML patients showed more adverse genetic alterations, higher age and more comorbidities as compared to de novo AML. Median OS in intensively treated t-AML patients was 13.7 months as compared to 39.4 months in de novo AML (p

Abstract Cell-cell junctions, and specifically desmosomes, are crucial for robust intercellular adhesion. Desmosomal function is compromised in the autoimmune blistering skin disease pemphigus vulgaris. We combine whole-genome knockout screening and a promotor screen of the desmosomal gene desmoglein 3 in human keratinocytes to identify novel regulators of intercellular adhesion. Kruppel-like-factor 5 (KLF5) directly binds to the desmoglein 3 regulatory region and promotes adhesion. Reduced levels of KLF5 in patient tissue indicate a role in pemphigus vulgaris. Autoantibody fractions from patients impair intercellular adhesion and reduce KLF5 levels in in vitro and in vivo disease models. These effects were dependent on increased activity of histone deacetylase 3, leading to transcriptional repression of KLF5. Inhibiting histone deacetylase 3 increases KLF5 levels and protects against the deleterious effects of autoantibodies in murine and human pemphigus vulgaris models. Together, KLF5 and histone deacetylase 3 are regulators of desmoglein 3 gene expression and intercellular adhesion and represent potential therapeutic targets in pemphigus vulgaris.

ABSTRACT For over a century, the filamentous Ascomycete fungus Aspergillus niger has played a pivotal role in the industrial production of citric acid. A critical fermentation parameter that sustains high-yield citric acid accumulation is the suboptimal concentration of manganese(II) ions in the culture broth at the early stages of the process. However, the requirement for this deficiency has not been investigated on a functional genomics level. In this study, we compared the transcriptome of the citric acid hyper-producer A. niger NRRL2270 strain grown under citric acid-producing conditions in 6-L scale bioreactors at Mn2+ ion-deficient (5 ppb) and Mn2+ ion-sufficient (100 ppb) conditions at three early time points of cultivation. Of the 11,846 genes in the genome, 963 genes (8.1% of the total) were identified as significantly differentially expressed under these conditions. Disproportionately high number of differentially regulated genes encode predicted extracellular and membrane proteins. The most abundant gene group that was upregulated in Mn2+ ion deficiency condition encodes enzymes acting on polysaccharides. In contrast, six clusters of genes encoding secondary metabolites showed downregulation under manganese deficiency. Mn2+ deficiency also triggers upregulation of the cexA gene, which encodes the citrate exporter. We provide functional evidence that the upregulation of cexA is caused by the intracellular accumulation of citrate or acetyl-CoA and is a major factor in triggering citrate overflow.IMPORTANCECitric acid is produced on industrial scale by batch fermentation of the filamentous fungus Aspergillus niger. High-yield citric acid production requires a low (

This newsletter contains items of interest to anyone concerned with science and society interactions. The first section of this issue contains 28 news items including program descriptions, information about meetings and publications, and discussions of issues related to science. The feature articles included are a legislative report on the U.S. House of Representatives and recombinant DNA; a personal commentary on science, the media, and the public; the Office of Technology Assessment looks at emerging technologies, and a discussion of the right to know and the right to create. Also included in this issue are a meetings calendar and a general bibliography. (BB)

This publication contains many news items such as meeting and conference descriptions and dates, proposed and current legislative action, publication descriptions, and topical articles. The items all pertain to the impact on humanity of science and technology. In this issue, news items include NSF, NEH, and AAAS meeting and seminar notices, notices and descriptions of programs being offered at various universities, and descriptions of recent publications. Sections containing news from societies and a meetings calendar are included as are two feature sections. The first feature section deals with recombinant DNA, reviewing recent books, discussing the U.S. Senate interest in recombinant DNA research, and relating notes on a recent conference on recombinant DNA. The second section contains articles on professional ethics; these articles consider the role of the professional scientist in our society, and include a bibliography on professional ethics. A general bibliography is included. (MR)