Angiotensin mediates renal fibrosis in the nephropathy of glycogen storage disease type Ia

Patients with glycogen storage disease type Ia (GSD-Ia) develop renal disease of unknown etiology despite intensive dietary therapies. This renal disease shares many clinical and pathological similarities to diabetic nephropathy. We studied the expression of angiotensinogen, angiotensin type 1 receptor, transforming growth factor-β1, and connective tissue growth factor in mice with GSD-Ia and found them to be elevated compared to controls. While increased renal expression of angiotensinogen was evident in 2-week-old mice with GSD-Ia, the renal expression of transforming growth factor-β and connective tissue growth factor did not increase for another week; consistent with upregulation of these factors by angiotensin II. The expression of fibronectin and collagens I, III, and IV was also elevated in the kidneys of mice with GSD-Ia, compared to controls. Renal fibrosis was characterized by a marked increase in the synthesis and deposition of extracellular matrix proteins in the renal cortex and histological abnormalities including tubular basement membrane thickening, tubular atrophy, tubular dilation, and multifocal interstitial fibrosis. Our results suggest that activation of the angiotensin system has an important role in the pathophysiology of renal disease in patients with GSD-Ia

Neurobiological origin of spurious brain morphological changes: A quantitative MRI study.

The high gray-white matter contrast and spatial resolution provided by T1-weighted magnetic resonance imaging (MRI) has made it a widely used imaging protocol for computational anatomy studies of the brain. While the image intensity in T1-weighted images is predominantly driven by T1, other MRI parameters affect the image contrast, and hence brain morphological measures derived from the data. Because MRI parameters are correlates of different histological properties of brain tissue, this mixed contribution hampers the neurobiological interpretation of morphometry findings, an issue which remains largely ignored in the community. We acquired quantitative maps of the MRI parameters that determine signal intensities in T1-weighted images (R1 (=1/T1), R2 *, and PD) in a large cohort of healthy subjects (n = 120, aged 18-87 years). Synthetic T1-weighted images were calculated from these quantitative maps and used to extract morphometry features-gray matter volume and cortical thickness. We observed significant variations in morphometry measures obtained from synthetic images derived from different subsets of MRI parameters. We also detected a modulation of these variations by age. Our findings highlight the impact of microstructural properties of brain tissue-myelination, iron, and water content-on automated measures of brain morphology and show that microstructural tissue changes might lead to the detection of spurious morphological changes in computational anatomy studies. They motivate a review of previous morphological results obtained from standard anatomical MRI images and highlight the value of quantitative MRI data for the inference of microscopic tissue changes in the healthy and diseased brain. Hum Brain Mapp 37:1801-1815, 2016. © 2016 The Authors. Human Brain Mapping Published by Wiley Periodicals, Inc

Does Puget Sound have a long-term memory?

More than a decade of high-resolution, full-water column data collected by profiling UW ORCA/NANOOS moorings in several Puget Sound Basins are used to investigate interannual variability of near-surface and deep water properties. Although there are no significant trends in temperature, salinity, density and dissolved oxygen spanning the last decade, measurements show steady and relatively strong trends in these variables over periods of 3 to 5 years in both South Sound near bottom waters and in south Hood Canal deep water. For example, the annual minimum density in south Hood Canal deep water increased four years in a row from 2006 to 2009, then this trend reversed for three years. In Carr Inlet the annual maximum deep temperature increased five years in a row from 2011 to 2015, with deep salinity following a similar trend. As these trends are significantly longer than expected flushing and residence times (\u3c year), this hints at potential interannual dynamical feedbacks, longer-term system “memory”, and/or similar trends in ocean and atmospheric forcing. Using archived National Data Buoy Center, National Weather Service and UW Atmospheric Sciences data we explore and report on potential factors contributing to these trends

A Black Ring with two Angular Momenta in Taub-NUT

We use the recently-constructed explicit duality transformation that relates a rotating anti-D6-D4-D2-D0 black hole solution to a rotating M5-M2-P black string to construct a non-supersymmetric black ring in Taub-NUT that has two angular momenta, as well as M2 charges and M5 dipole moments. This is the first black ring solution that has both dipole charges and rotation along the S^2 of the horizon, and hence can be thought of as the "Pomeransky-Senkov" version of the M5-M2 black ring in Taub-NUT. Its physics should provide a testing ground for the applicability of the blackfold approach to charged rotating black branes, and should elucidate the phase space of charged dipole rings in various backgrounds.Comment: 20 pages, LaTe

Patterns and variability in ocean acidification conditions in Puget Sound and the Strait of Juan de Fuca

The Washington Ocean Acidification Center is working with NOAA and other partners to increase understanding of ocean acidification dynamics and spatial variability in the Salish Sea, and how these correlate with planktonic responses. These data are critical for assessing water quality, areas with higher or lower OA stress, and to understand effects on the food web. Two main strategies are employed; seasonal ship cruises provide spatial coverage and the ability to collect plankton, while mooring buoys provide information on mechanisms and the range of variation due to the high-resolution and constant coverage they provide. Results show a strong degree of depth, seasonal, and spatial variation in pH and aragonite saturation state. In general, the lowest pH and aragonite saturation state values are at depth, particularly in stratified areas, though this can shift during seasonal localized upwelling, e.g., Southern Hood Canal, and in mixed water columns, e.g., the Main Basin. Seasonal patterns are spatially diverse, with stratified areas exhibiting strong vertical gradients with depth during summer and more homogenous conditions during winter; well-mixed areas show less variation year-round. This implies that species encounter quite different OA conditions in various parts of the Salish Sea between the seasons. Mooring CO2 data reveal higher variation during late fall through early spring at sites within the Salish Sea, due to winter mixing of stratified waters, yet the reverse pattern off the Washington coast, due to summer upwelling. In both cases, these mechanisms (winter mixing and summer upwelling) operate across a gradient, bringing relatively deeper lower pH / aragonite saturation state waters in contact with surface waters with higher values. Such changes in the spatial and depth distribution of corrosive conditions have broad implications for sensitive marine life

Treatment options of invasive fungal infections in adults.

A panel of infectious disease specialists, clinical microbiologists and hospital epidemiologists of the five Swiss university hospitals reviewed the current literature on the treatment of invasive fungal infections in adults and formulated guidelines for the management of patients in Switzerland. For empirical therapy of Candida bloodstream infection, fluconazole is the drug of choice in non-neutropenic patients with no severe sepsis or septic shock or recent exposure to azoles. Amphotericin B deoxycholate or caspofungin would be the treatment option for patients with previous azole exposure. In neutropenic patients, empirical therapy with amphotericin B deoxycholate is considered first choice. In patients with severe sepsis and septic shock, caspofungin is the drug of first choice. For therapy of microbiologically-documented Candida infection, fluconazole is the drug of choice for infections due to C. albicans, C. tropicalis or C. parapsilosis. When infections are caused by C. glabrata or by C. krusei, caspofungin or amphotericin B deoxycholate are first line therapies. Treatment guidelines for invasive aspergillosis (IA) were stratified into primary therapy, salvage therapy and combination therapy in critically ill patients. Voriconazole is recommended for primary (ie upfront) therapy. Caspofungin, voriconazole (if not used for primary therapy) or liposomal amphotericin B are recommended for salvage therapy for refractory disease. Combination therapy with caspofungin plus voriconazole or liposomal amphotericin B should be considered in critically ill patients. Amphotericin B deoxycholate is recommended as initial therapy for the empirical therapy in patients with neutropenia and persistent fever with close monitoring of adverse events

Construction and accessibility of a cross-species phenotype ontology along with gene annotations for biomedical research

Phenotype analyses, e.g. investigating metabolic processes, tissue formation, or organism behavior, are an important element of most biological and medical research activities. Biomedical researchers are making increased use of ontological standards and methods to capture the results of such analyses, with one focus being the comparison and analysis of phenotype information between species. We have generated a cross-species phenotype ontology for human, mouse and zebrafish that contains classes from the Human Phenotype Ontology, Mammalian Phenotype Ontology, and generated classes for zebrafish phenotypes. We also provide up-to-date annotation data connecting human genes to phenotype classes from the generated ontology. We have included the data generation pipeline into our continuous integration system ensuring stable and up-to-date releases. This article describes the data generation process and is intended to help interested researchers access both the phenotype annotation data and the associated cross-species phenotype ontology. The resource described here can be used in sophisticated semantic similarity and gene set enrichment analyses for phenotype data across species. The stable releases of this resource can be obtained from http://purl.obolibrary.org/obo/hp/uberpheno/

A (Running) Bolt for New Reasons

We construct a four-parameter family of smooth, horizonless, stationary solutions of ungauged five-dimensional supergravity by using the four-dimensional Euclidean Schwarzschild metric as a base space and "magnetizing" its bolt. We then generalize this to a five-parameter family based upon the Euclidean Kerr-Taub-Bolt. These "running Bolt" solutions are necessarily non-static. They also have the same charges and mass as a non-extremal black hole with a classically-large horizon area. Moreover, in a certain regime their mass can decrease as their charges increase. The existence of these solutions supports the idea that the singularities of non-extremal black holes are resolved by low-mass modes that correct the singularity of the classical black hole solution on large (horizon-sized) scales.Comment: 25 pages, 3 figures, LaTeX; v2: minor changes, references adde