Surface membrane polarity of proximal tubular cells: Alterations as a basis for malfunction

Surface membrane polarity of proximal tubular cells: Alterations as a basis for malfunction. The surface membrane of proximal tubular cells is organized into distinct apical and basolateral membrane domains. The establishment and maintenance of these biochemically, structurally and physiologically distinct domains involves a multi-stage process involving cell-cell, cell-ECM interactions, and polarized targeting mechanisms. Ischemia, via cellular ATP depletion, results in a series of structural, biochemical and functional alterations that lead to loss of proximal tubular cell surface membrane polarity. Of central importance is the rapidly-occurring, duration-dependent disruption and dissociation of the actin cytoskeleton and associated surface membrane structures. This results in numerous cellular alterations including loss of cell-cell contact, cell-extracellular matrix adhesion and surface membrane polarity. Redistribution of surface membrane proteins and lipids into the alternate domain results in the cells inability to function properly. Repair of these disorders involves re-establishment of the actin cytoskeleton and apical and basolateral surface membrane domains. Recent information indicates growth factors may play a role in hastening this repair process

Software for optimization of SNP and PCR-RFLP genotyping to discriminate many genomes with the fewest assays

BACKGROUND: Microbial forensics is important in tracking the source of a pathogen, whether the disease is a naturally occurring outbreak or part of a criminal investigation. RESULTS: A method and SPR Opt (SNP and PCR-RFLP Optimization) software to perform a comprehensive, whole-genome analysis to forensically discriminate multiple sequences is presented. Tools for the optimization of forensic typing using Single Nucleotide Polymorphism (SNP) and PCR-Restriction Fragment Length Polymorphism (PCR-RFLP) analyses across multiple isolate sequences of a species are described. The PCR-RFLP analysis includes prediction and selection of optimal primers and restriction enzymes to enable maximum isolate discrimination based on sequence information. SPR Opt calculates all SNP or PCR-RFLP variations present in the sequences, groups them into haplotypes according to their co-segregation across those sequences, and performs combinatoric analyses to determine which sets of haplotypes provide maximal discrimination among all the input sequences. Those set combinations requiring that membership in the fewest haplotypes be queried (i.e. the fewest assays be performed) are found. These analyses highlight variable regions based on existing sequence data. These markers may be heterogeneous among unsequenced isolates as well, and thus may be useful for characterizing the relationships among unsequenced as well as sequenced isolates. The predictions are multi-locus. Analyses of mumps and SARS viruses are summarized. Phylogenetic trees created based on SNPs, PCR-RFLPs, and full genomes are compared for SARS virus, illustrating that purported phylogenies based only on SNP or PCR-RFLP variations do not match those based on multiple sequence alignment of the full genomes. CONCLUSION: This is the first software to optimize the selection of forensic markers to maximize information gained from the fewest assays, accepting whole or partial genome sequence data as input. As more sequence data becomes available for multiple strains and isolates of a species, automated, computational approaches such as those described here will be essential to make sense of large amounts of information, and to guide and optimize efforts in the laboratory. The software and source code for SPR Opt is publicly available and free for non-profit use at

Status and Distribution of the Gapped Ringed Crayfish, Orconectes neglectus chaenodactylus, in Arkansas

Orconectes neglectus chaenodactylus, the gapped ringed crayfish, is an uncommon and poorly-known, stream-dwelling crayfish that is endemic to the central White River basin of Arkansas and Missouri. This study surveyed a semi-random selection of stream sites in the Arkansas portion of this range in order to characterize the crayfish communities and evaluate the status of O. n. chaenodactylus in Arkansas. Collections of a total of 1,107 individual crayfish specimens were made at 45 sites, including 497 O. n. chaenodactylus from 21 sites. Orconectes punctimanus was the crayfish species most commonly associated with O. n. chaenodactylus, occurring at 71% of sites occupied by O. n. chaenodactylus. Orconectes n. chaenodactylus was found in streams not significantly different from the median characteristics of streams sampled in the study. It is our opinion that O. n. chaenodactylus is uncommon in Arkansas, and of only moderate concern due to its limited distribution in the state

Nova Sagittarii 1994 #1 (V4332 Sagittarii): The Discovery and Evolution of an Unusual Luminous Red Variable Star

We report photometry and spectroscopy of the evolution of Nova Sagittarii 1994 #1 (V4332 Sagittarii) during outburst. We compare the photometric and spectral evolution of this outburst to known classes of outbursts -- including classical novae and outbursts occurring on symbiotic stars -- and find this object does NOT conform to any known class of outburst. The closest match to the behavior of this unusual object is M31 RV, an extremely luminous and red variable object discovered in the bulge of M31 in 1988. However, the temporal behavior and maximum luminosity of the two events differ by several orders of magnitude, requiring substantial intrinsic variation if these two events are members the same type of outburst. Our model of the spectroscopic evolution of this outburst shows that the effective temperature cooled from 4400 K to 2300 K over the three month span of our observations. In combination with line diagnostics in our later spectra, including [OI] lambda 5577 and the dramatic increase in the Halpha to Hbeta ratio, we infer the existence of a cool, dense (N_e ~ 10^{8-9} cm^{-3}) envelope that is optically thick in the Hydrogen Balmer recombination lines (case C). We suggest that a nuclear event in a single star, in which a slow shock drove the photosphere outwards, can power the observed luminosity evolution and the emission spectrum.Comment: Accepted for publication in AJ. 24 pages including 8 embedded postscript figures. Also available at http://www.astronomy.ohio-state.edu/~martini/pub

NASA Center for Climate Simulation (NCCS) Advanced Technology AT5 Virtualized Infiniband Report

The NCCS is part of the Computational and Information Sciences and Technology Office (CISTO) of Goddard Space Flight Center's (GSFC) Sciences and Exploration Directorate. The NCCS's mission is to enable scientists to increase their understanding of the Earth, the solar system, and the universe by supplying state-of-the-art high performance computing (HPC) solutions. To accomplish this mission, the NCCS (https://www.nccs.nasa.gov) provides high performance compute engines, mass storage, and network solutions to meet the specialized needs of the Earth and space science user communitie

The theophylline‐enoxacin interaction: I. Effect of enoxacin dose size on theophylline disposition

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/110004/1/cptclpt1988197.pd

Evaluation of LactiproFLX in an Acidosis Challenge Model

An acidosis challenge study was conducted comparing different administration techniques for LactiproFLX, a direct fed microbial product containing Megaspharea elsdenii (a lactate-utilizing bacteria) for the prevention of acidosis. Four treatments were utilized in a randomized block design with 24 ruminally cannulated steers. Treatments consisted of a control group which did not receive the product, a group which received the commercial dose of the product four days before the acidosis challenge, one which received the commercial dose of the product one day before the challenge, and one which received ten times the commercial dose one day before the challenge. No differences were detected for rumination time or dry matter intake. Similarly, no differences were detected in the millimolar (mM) concentrations of propionate, valerate, or isovalerate. Several differences, however, were detected for total volatime fatty acid (VFA), acetate, isobutyrate, and butyrate during different periods of the study. Additionally, several differences were detected for ruminal pH parameters with the treatment dosed 4 days before the challenge having the greatest minimum and maximum pH when compared to the other treatments. The group dosed with ten times the commercial dose displayed lower pH variance and magnitude of change when compared to the other treatments. Therefore, if using exogenous Megaspharea elsdenii as an acidosis mitigation strategy, giving the bacteria time to establish in the rumen before an acidotic event could increase the effectiveness of the treatment. If giving the treatment closer to a possible acidotic event, giving a higher dose could be beneficial

AutoMorph: Automated Retinal Vascular Morphology Quantification Via a Deep Learning Pipeline

Purpose: To externally validate a deep learning pipeline (AutoMorph) for automated analysis of retinal vascular morphology on fundus photographs. AutoMorph has been made publicly available, facilitating widespread research in ophthalmic and systemic diseases. Methods: AutoMorph consists of four functional modules: image preprocessing, image quality grading, anatomical segmentation (including binary vessel, artery/vein, and optic disc/cup segmentation), and vascular morphology feature measurement. Image quality grading and anatomical segmentation use the most recent deep learning techniques. We employ a model ensemble strategy to achieve robust results and analyze the prediction confidence to rectify false gradable cases in image quality grading. We externally validate the performance of each module on several independent publicly available datasets. Results: The EfficientNet-b4 architecture used in the image grading module achieves performance comparable to that of the state of the art for EyePACS-Q, with an F1-score of 0.86. The confidence analysis reduces the number of images incorrectly assessed as gradable by 76%. Binary vessel segmentation achieves an F1-score of 0.73 on AV-WIDE and 0.78 on DR HAGIS. Artery/vein scores are 0.66 on IOSTAR-AV, and disc segmentation achieves 0.94 in IDRID. Vascular morphology features measured from the AutoMorph segmentation map and expert annotation show good to excellent agreement. Conclusions: AutoMorph modules perform well even when external validation data show domain differences from training data (e.g., with different imaging devices). This fully automated pipeline can thus allow detailed, efficient, and comprehensive analysis of retinal vascular morphology on color fundus photographs. Translational Relevance: By making AutoMorph publicly available and open source, we hope to facilitate ophthalmic and systemic disease research, particularly in the emerging field of oculomics

Biologically relevant oxidants and terminology, classification and nomenclature of oxidatively generated damage to nucleobases and 2-deoxyribose in nucleic acids

A broad scientific community is involved in investigations aimed at delineating the mechanisms of formation and cellular processing of oxidatively generated damage to nucleic acids. Perhaps as a consequence of this breadth of research expertise, there are nomenclature problems for several of the oxidized bases including 8-oxo-7,8-dihydroguanine (8-oxoGua), a ubiquitous marker of almost every type of oxidative stress in cells. Efforts to standardize the nomenclature and abbreviations of the main DNA degradation products that arise from oxidative pathways are reported. Information is also provided on the main oxidative radicals, non-radical oxygen species, one-electron agents and enzymes involved in DNA degradation pathways as well in their targets and reactivity. A brief classification of oxidatively generated damage to DNA that may involve single modifications, tandem base modifications, intrastrand and interstrand cross-links together with DNA-protein cross-links and base adducts arising from the addition of lipid peroxides breakdown products is also included