Troponin T3 regulates nuclear localization of the calcium channel Cavβ1a subunit in skeletal muscle

The voltage-gated calcium channel (Cav) β1a subunit (Cavβ1a) plays an important role in excitation-contraction coupling (ECC), a process in the myoplasm that leads to muscle-force generation. Recently, we discovered that the Cavβ1a subunit travels to the nucleus of skeletal muscle cells where it helps to regulate gene transcription. To determine how it travels to the nucleus, we performed a yeast two-hybrid screening of the mouse fast skeletal muscle cDNA library and identified an interaction with troponin T3 (TnT3), which we subsequently confirmed by co-immunoprecipitation and co-localization assays in mouse skeletal muscle in vivo and in cultured C2C12 muscle cells. Interacting domains were mapped to the leucine zipper domain in TnT3 COOH-terminus (160-244 aa) and Cavβ1a NH2-terminus (1-99 aa), respectively. The double fluorescence assay in C2C12 cells co-expressing TnT3/DsRed and Cavβ1a/YFP shows that TnT3 facilitates Cavβ1a nuclear recruitment, suggesting that the two proteins play a heretofore unknown role during early muscle differentiation in addition to their classical role in ECC regulation.Fil: Zhang, Tan. Wake Forest School of Medicine; Estados UnidosFil: Taylor, Jackson. Wake Forest School of Medicine; Estados UnidosFil: Jiang, Yang. Wake Forest School of Medicine; Estados UnidosFil: Pereyra, Andrea Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Instituto de Investigaciones Bioquímicas de La Plata ; ArgentinaFil: Messi, Maria Laura. Wake Forest School of Medicine; Estados UnidosFil: Wang, Zhong Min. Wake Forest School of Medicine; Estados UnidosFil: Hereñú, Claudia Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Instituto de Investigaciones Bioquímicas de La Plata ; ArgentinaFil: Delbono, Osvaldo. Wake Forest School of Medicine; Estados Unido

Global Precipitation Nowcasting of Integrated Multi-satellitE Retrievals for GPM: A U-Net Convolutional LSTM Architecture

This paper presents a deep learning architecture for nowcasting of precipitation almost globally every 30 min with a 4-hour lead time. The architecture fuses a U-Net and a convolutional long short-term memory (LSTM) neural network and is trained using data from the Integrated MultisatellitE Retrievals for GPM (IMERG) and a few key precipitation drivers from the Global Forecast System (GFS). The impacts of different training loss functions, including the mean-squared error (regression) and the focal-loss (classification), on the quality of precipitation nowcasts are studied. The results indicate that the regression network performs well in capturing light precipitation (below 1.6 mm/hr), but the classification network can outperform the regression network for nowcasting of precipitation extremes (>8 mm/hr), in terms of the critical success index (CSI).. Using the Wasserstein distance, it is shown that the predicted precipitation by the classification network has a closer class probability distribution to the IMERG than the regression network. It is uncovered that the inclusion of the physical variables can improve precipitation nowcasting, especially at longer lead times in both networks. Taking IMERG as a relative reference, a multi-scale analysis in terms of fractions skill score (FSS), shows that the nowcasting machine remains skillful (FSS > 0.5) at the resolution of 10 km compared to 50 km for GFS. For precipitation rates greater than 4~mm/hr, only the classification network remains FSS-skillful on scales greater than 50 km within a 2-hour lead time

Performance of IMERG as a Function of Spatiotemporal Scale

The Integrated Multi-satellitE Retrievals for GPM (IMERG), a global high resolution gridded precipitation data set, will enable a wide range of applications, ranging from studies on precipitation characteristics to applications in hydrology to evaluation of weather and climate models. These applications focus on different spatial and temporal scale and thus average the precipitation estimates to coarser resolutions. Such a modification of scale will impact the reliability of IMERG. In this study, the performance of the Final run of IMERG is evaluated against ground-based measurements as a function of increasing spatial resolution (from 0.1 deg to 2.5 deg) and accumulation periods (from 0.5 h to 24 h) over a region in the southeastern US. For ground reference, a product derived from the Multi-Radar/Multi-Sensor suite, a radar- and gauge based operational precipitation dataset, is used. The TRMM Multisatellite Precipitation Analysis (TMPA) is also included as a benchmark. In general, both IMERG and TMPA improve when scaled up to larger areas and longer time periods, with better identification of rain occurrences and consistent improvements in systematic and random errors of rain rates. Between the two satellite estimates, IMERG is slightly better than TMPA most of the time. These results will inform users on the reliability of IMERG over the scales relevant to their studies

Contrasting the Co-Variability of Daytime Cloud and Precipitation over Tropical Land and Ocean

The co-variability of cloud and precipitation in the extended tropics (35 deg N35 deg S) is investigated using contemporaneous datasets for a 13-year period. The goal is to quantify potential relationships between cloud type amounts and precipitation events of particular strength. Particular attention is paid to whether the relationships exhibit different characteristics over tropical land and ocean. A primary analysis metric is the correlation coefficient between fractions of individual cloud types and frequencies within precipitation histogram bins that have been matched in time and space. The cloud type fractions are derived from Moderate Resolution Imaging Spectroradiometer (MODIS) joint histograms of cloud top pressure and cloud optical thickness in one-degree grid cells, and the precipitation frequencies come from the Tropical Rainfall Measuring Mission (TRMM) Multi-satellite Precipitation Analysis (TMPA) dataset aggregated to the same grid. It is found that the strongest coupling (positive correlation) between clouds and precipitation occurs over ocean for cumulonimbus clouds and the heaviest rainfall. While the same cloud type and rainfall bin are also best correlated over land compared to other combinations, the correlation magnitude is weaker than over ocean. The difference is attributed to the greater size of convective systems over ocean. It is also found that both over ocean and land the anti-correlation of strong precipitation with weak (i.e., thin and/or low) cloud types is of greater absolute strength than positive correlations between weak cloud types and weak precipitation. Cloud type co-occurrence relationships explain some of the cloud-precipitation anti-correlations. Weak correlations between weaker rainfall and clouds indicate poor predictability for precipitation when cloud types are known, and this is even more true over land than over ocean

A rare case of Aeromonas hydrophila catheter related sepsis in a patient with chronic kidney disease receiving steroids and dialysis: a case report and review of Aeromonas infections in chronic kidney disease patients

Aeromonas hydrophila (AH) is an aquatic bacterium. We present a case of fifty-five-year-old gentleman with chronic kidney disease (CKD) due to crescentic IgA nephropathy who presented to us with fever. He was recently pulsed with methyl prednisolone followed by oral prednisolone and discharged on maintenance dialysis through a double lumen dialysis catheter. Blood culture from peripheral vein and double lumen dialysis catheter grew AH. We speculate low immunity due to steroids and uremia along with touch contamination of dialysis catheter by the patient or dialysis nurse could have led to this rare infection. Dialysis catheter related infection by AH is rare. We present our case here and take the opportunity to give a brief review of AH infections in CKD patients

Predictors of hospital stay and mortality in dengue virus infection-experience from Aga Khan University Hospital Pakistan

Background: Dengue virus infection (DVI) is very common infection. There is scarcity of data on factor associated with increased hospitalstay and mortality in dengue virus infection (DVI). This study was done to know about factors associated with increased hospital stay and mortality in patients admitted with DVI. Results: Out of 532 patients, two third (72.6%) had stay ≤3 days while one third (27.4%) had stay greater than 3 days. The mean length of hospital stay was 3.46 ± 3.45 days. Factors associated with increased hospital stay (\u3e3 days) included AKI (acute kidney injury) (Odd ratio 2.98; 95% CI 1.66-5.34), prolonged prothrombin time (Odd ratio 2.03; 95% CI 1.07-3.84), prolonged activated partial thromboplastin time (aPTT) (Odd ratio 1.80; CI 95% 1.15-2.83) and increased age of \u3e 41.10 years (Odd ratio 1.03; CI 95% 1.01-1.04).Mortality was 1.5%. High mortality was found in those with AKI (P \u3c0.01), dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS) (P \u3c0.001), respiratory failure (P0.01), prolong PT (P 0.001), prolong aPTT (P0.01) and increased hospital stay (P0.04). Conclusion: Increasing age, coagulopathy and acute kidney injury in patients with DVI is associated with increased hospital stay. Morality was more in patients with AKI, DHF and DSS, respiratory failure, coagulopathy and these patients had more prolonged hospitalization

Cathepsin B contributes to Na + hyperabsorption in cystic fibrosis airway epithelial cultures: Cathepsin B and ENaC

In cystic fibrosis (CF) lung disease, the absence of functional CF transmembrane conductance regulator results in Cl−/HCO3− hyposecretion and triggers Na+ hyperabsorption through the epithelial Na+ channel (ENaC), which contribute to reduced airway surface liquid (ASL) pH and volume. Prostasin, a membrane-anchored serine protease with trypsin-like substrate specificity has previously been shown to activate ENaC in CF airways. However, prostasin is typically inactive below pH 7.0, suggesting that it may be less relevant in acidic CF airways. Cathepsin B (CTSB) is present in both normal and CF epithelia and is secreted into ASL, but little is known about its function in the airways. We hypothesized that the acidic ASL seen in CF airways may stimulate CTSB to activate ENaC, contributing to Na+ hyperabsorption and depletion of CF ASL volume. In Xenopus laevis oocytes, CTSB triggered α- and γENaC cleavage and induced an increase in ENaC activity. In bronchial epithelia from both normal and CF donor lungs, CTSB localized to the apical membrane. In normal and CF human bronchial epithelial cultures, CTSB was detected at the apical plasma membrane and in the ASL. CTSB activity was significantly elevated in acidic ASL, which correlated with increased abundance of ENaC in the plasma membrane and a reduction in ASL volume. This acid/CTSB-dependent activation of ENaC was ameliorated with the cell impermeable, CTSB-selective inhibitor CA074, suggesting that CTSB inhibition may have therapeutic relevance. Taken together, our data suggest that CTSB is a pathophysiologically relevant protease that activates ENaC in CF airways

Epistemic Akrasia and Belief‐Credence Dualism

We call attention to certain cases of epistemic akrasia, arguing that they support belief-credence dualism. Belief-credence dualism is the view that belief and credence are irreducible, equally fundamental attitudes. Consider the case of an agent who believes p, has low credence in p, and thus believes that they shouldn’t believe p. We argue that dualists, as opposed to belief-firsters (who say credence reduces to belief) and credence-firsters (who say belief reduces to credence) can best explain features of akratic cases, including the observation that akratic beliefs seem to be held despite possessing a defeater for those beliefs, and that, in akratic cases, one can simultaneously believe and have low confidence in the very same proposition