Endogenous retinoids in rat epididymal tissue and rat and human spermatozoa

Recent work has demonstrated high levels of retinoid binding proteins in rat epididymis, and a lumenal retinoic acid binding protein has been purified. These findings suggested that vitamin A may be involved in spermatozoal maturation in the epididymis. We further addressed this question by quantifying retinol, retinyl esters, and retinoic acid isomers from perfused epididymal tissue, from rat testicular and epididymal spermatozoa, and from human ejaculate sperm. HPLC showed vitamin A levels to be higher in caput than in corpus or cauda tissue. Retinoic acid and 9-cis-retinoic acid were found to be graded from lowest levels in caput to highest in cauda. Spermatozoa from caput epididymidis and enriched testicular spermatozoa were found to have higher levels of vitamin A than did spermatozoa from corpus or cauda epididymidis. Spermatozoal retinyl esters had acyl substituents similar to those seen in whole epididymis, and diminished in quantity in sperm from distal segments. Human ejaculate sperm were found to retain high levels of retinyl palmitate and stearate. Retinol and retinoic acid were only marginally detectable in human sperm. Retention of retinoids in mature spermatozoa suggests roles for vitamin A in spermatozoal reproductive physiology beyond the epididymal stage

Prototype Database and User's Guide of Saturated Zone Hydraulic Properties forthe Hanford Site

Predicting the movement of contaminants in groundwater beneath the Hanford Site is important for both understanding the impacts of these contaminants and for planning effective cleanup activities. These predictions are based on knowledge of the distribution of hydraulic properties within the aquifers underlying the Hanford Site. The Characterization of Systems (CoS) Task, under the Groundwater/Vadose Integration Project, is responsible for establishing a consistent set of data, parameters, and conceptual models to support estimates contaminant migration and impact

Histidine switch controlling pH-dependent protein folding and DNA binding in a transcription factor at the core of synthetic network devices

© 2016 The Royal Society of Chemistry. Therapeutic strategies have been reported that depend on synthetic network devices in which a urate-sensing transcriptional regulator detects pathological levels of urate and triggers production or release of urate oxidase. The transcription factor involved, HucR, is a member of the multiple antibiotic resistance (MarR) protein family. We show that protonation of stacked histidine residues at the pivot point of long helices that form the scaffold of the dimer interface leads to reversible formation of a molten globule state and significantly attenuated DNA binding at physiological temperatures. We also show that binding of urate to symmetrical sites in each protein lobe is communicated via the dimer interface. This is the first demonstration of regulation of a MarR family transcription factor by pH-dependent interconversion between a molten globule and a compact folded state. Our data further suggest that HucR may be utilized in synthetic devices that depend on detection of pH changes

Results of Detailed Hydrologic Characterization Tests - Fiscal Year 1999

This report provides the results of detailed hydrologic characterization tests conducted within newly constructed Hanford Site wells during FY 1999. Detailed characterization tests performed during FY 1999 included: groundwater flow characterization, barometric response evaluation, slug tests, single-well tracer tests, constant-rate pumping tests, and in-well vertical flow tests. Hydraulic property estimates obtained from the detailed hydrologic tests include: transmissivity, hydraulic conductivity, specific yield, effective porosity, in-well lateral flow velocity, aquifer flow velocity, vertical distribution of hydraulic conductivity (within the well-screen section) and in-well vertical flow velocity. In addition, local groundwater flow characteristics (i.e., hydraulic gradient and flow direction) were determined for four sites where detailed well testing was performed

Hydrogeologic controls on ground-water and contaminant discharge to the Columbia River near the Hanford Townsite

The purpose of this study is to quantify ground-water and contaminant discharge to the Columbia River in the Hanford Townsite vicinity. The primary objectives of the work are to: describe the hydrogeologic setting and controls on ground-water movement and contaminant discharge to the Columbia River; understand the river/aquifer relationship and its effects on contaminant discharge to the Columbia River; quantify the ground-water and contaminant mass discharge to the Columbia River; and provide data that may be useful for a three-dimensional model of ground-water flow and contaminant transport in the Hanford Townsite study area. The majority of ground-water contamination occurs within the unconfined aquifer; therefore, ground-water and contaminant discharge from the unconfined aquifer is the emphasis of this study. The period of study is primarily from June 1990 through March 1992

The HERA-B Ring Imaging Cherenkov Counter

The HERA-B RICH uses a radiation path length of 2.8 m in C_4F_10 gas and a large 24 square meters spherical mirror for imaging Cherenkov rings. The photon detector consists of 2240 Hamamatsu multi-anode photomultipliers with about 27000 channels. A 2:1 reducing two-lens telescope in front of each PMT increases the sensitive area at the expense of increased pixel size, resulting in a contribution to the resolution which roughly matches that of dispersion. The counter was completed in January of 1999, and its performance has been steady and reliable over the years it has been in operation. The design performance of the RICH was fully reached: the average number of detected photons in the RICH for a beta=1 particle was found to be 33 with a single hit resolution of 0.7 mrad and 1 mrad in the fine and coarse granularity regions, respectively.Comment: 29 pages, 23 figure

Multi-omics investigation of Clostridioides difficile-colonized patients reveals pathogen and commensal correlates of C. difficile pathogenesis

Clostridioides difficile infection (CDI) imposes a substantial burden on the health care system in the United States. Understanding the biological basis for the spectrum of C. difficile-related disease manifestations is imperative to improving treatment and prevention of CDI. Here, we investigate the correlates of asymptomatic C. difficile colonization using a multi-omics approach. We compared the fecal microbiome and metabolome profiles of patients with CDI versus asymptomatically colonized patients, integrating clinical and pathogen factors into our analysis. We found that CDI patients were more likely to be colonized by strains with the binary toxin (CDT) locus or strains of ribotype 027, which are often hypervirulent. We find that microbiomes of asymptomatically colonized patients are significantly enriched for species in the class Clostridia relative to those of symptomatic patients. Relative to CDI microbiomes, asymptomatically colonized patient microbiomes were enriched with sucrose degradation pathways encoded by commensal Clostridia, in addition to glycoside hydrolases putatively involved in starch and sucrose degradation. Fecal metabolomics corroborates the carbohydrate degradation signature: we identify carbohydrate compounds enriched in asymptomatically colonized patients relative to CDI patients. Further, we reveal that across C. difficile isolates, the carbohydrates sucrose, rhamnose, and lactulose do not serve as robust growth substrates in vitro, consistent with their enriched detection in our metagenomic and metabolite profiling of asymptomatically colonized individuals. We conclude that pathogen genetic variation may be strongly related to disease outcome. More interestingly, we hypothesize that in asymptomatically colonized individuals, carbohydrate metabolism by other commensal Clostridia may prevent CDI by inhibiting C. difficile proliferation. These insights into C. difficile colonization and putative commensal competition suggest novel avenues to develop probiotic or prebiotic therapeutics against CDI

Geology, hydrology, chemistry, and microbiology of the in situ bioremediation demonstration site

This report summarizes characterization information on the geology, hydrology, microbiology, contaminant distribution, and ground-water chemistry to support demonstration of in situ bioremediation at the Hanford Site. The purpose of this information is to provide baseline conditions, including a conceptual model of the aquifer being utilized for in situ bioremediation. Data were collected from sampling and other characterization activities associated with three wells drilled in the upper part of the suprabasalt aquifer. Results of point-dilution tracer tests, conducted in the upper 9 m (30 ft) of the aquifer, showed that most ground-water flow occurs in the upper part of this zone, which is consistent with hydraulic test results and geologic and geophysical data. Other tracer test results indicated that natural ground-water flow velocity is equal to or less than about 0.03 m/d (0.1 ft/d). Laboratory hydraulic conductivity measurements, which represent the local distribution of vertical hydraulic conductivity, varied up to three orders of magnitude. Based on concentration data from both the vadose and saturated zone, it is suggested that most, if not all, of the carbon tetrachloride detected is representative of the aqueous phase. Concentrations of carbon tetrachloride, associated with a contaminant plume in the 200-West Area, ranged from approximately 500 to 3,800 {mu}g/L in the aqueous phase and from approximately 10 to 290 {mu}g/L in the solid phase at the demonstration site. Carbon tetrachloride gas was detected in the vadose zone, suggesting volatilization and subsequent upward migration from the saturated zone