Miracle-dz/UniFAR-FTUs huggingface dataset:
Human kallikrein gene delivery attenuates hypertension, cardiac hypertrophy, and renal injury in Dahl salt-sensitive rats.

The tissue kallikrein-kinin system has been documented to be involved in the pathogenesis of hypertension and renal diseases. To investigate the protective effects of kallikrein gene delivery on salt-induced renal damage, cardiac dysfunction, and hypertension, adenovirus harboring the human tissue kallikrein gene under the control of the cytomegalovirus promoter Ad.CMV-cHK was delivered into Dahl salt-sensitive (Dahl-SS) rats fed to a high-salt (4% NaCl) diet. A single intravenous injection of Ad.CMV-cHK resulted in a significant reduction of blood pressure beginning 2 days post injection and the effect lasted for 4 weeks. The human kallikrein mRNA was detected in rat heart, kidney, lung, liver, and adrenal gland; immunoreactive human kallikrein can be measured in the liver, kidney, sera, and urine of rats receiving kallikrein gene delivery. Following Ad.CMV-cHK injection, a significant increase in urine excretion, urinary sodium output, kinin, and cGMP level was observed. Kallikrein gene delivery caused a significant reduction in the left ventricular mass and cardiomyocyte size as well as inhibition of glomerular sclerotic lesions and tubular dilatation. This study shows that adenovirus-mediated gene delivery in Dahl-SS rats fed a high-salt diet resulted in (i) prolonged reduction of blood pressure and increased urinary kinin and cGMP levels, consistent with blood pressure reductions mediated via kinin through a cGMP-dependent signal transduction pathway, (ii) inhibition of cardiac hypertrophy, and (iii) attenuation of renal injury. The ability of kallikrein gene transfer to produce a wide spectrum of beneficial effects makes it an excellent candidate in treating salt-related hypertension as well as cardiovascular and renal diseases.
Electrocardiogram, Myocardial Oxygen and Contraction in Scar and Collaterally Supplied Muscle After Experimental Coronary Ligation

Studies of myocardial electrocardiograms, oxygen, and cinematographic muscle contraction were carried out in dogs during coronary branch ligation and after 2 to 12 weeks' recovery. Scars were found in 12 of 13 animals. Five were transmural at some point and seven entirely subendocardial. Myocardial electrocardiographic abnormalities were found in every animal with a scar. Epicardial electrocardiographic abnormalities (localized Q waves or low R waves) were roughly conterminous with the surface projection of the entire extent of all transmural scars and of six out of seven subendocardial scars. Precordial leads were abnormal in only three animals, all with transmural scars. Responses to oxygen inhalation, hypoxia, and levarterenol for these animals were within the range of normal variation, but there was a tendency to develop ventricular fibrillation, unrelated to the amount of scar. Study of the acute ischemic dysfunction consequent to coronary ligation is not of great value for the interpretation of the situation at re-exploration two or more weeks later. The behavior of recovered collaterally supplied muscle, assessable by the techniques employed in these studies (provided that epicardial thickening has been avoided by minimizing exposure and trauma at the time of ligation), has relevance to many human coronary disease situations in which regional circulation is carried on by intramyocardial or small caliber vessels.
Application of the Multi-Dimensional Positive Definite Advection Transport Algorithm ( MPDATA ) to Environmental Modeling on Adaptive Unstructured Grids

Twenty years ago, the multi-dimensional, positive definite, advection transport algorithm was introduced by Smolarkiewicz. Over the two decades since, it has been applied countless times to numerous problems, however almost always on rectilinear grids. One of the few exceptions is the Operational Multiscale Environment model with Grid Adaptivity (OMEGA), an atmospheric simulation system originally designed to simulate atmospheric dispersion in the planetary boundary layer, but since then used for both mesoscale (from meso-α to meso-γ) dispersion and weather forecasting. One of the unique aspects of OMEGA is the triangular unstructured grid geometry which leads in a natural way to the creation of a global grid with continuously variable resolution from roughly 100 km over the oceans to less than 10 km over regions of interest. Another unique aspect is the concept of dynamically adapting grid resolution – sometimes also called solution-adaptive grid resolution. A central element of the modeling system, however, is its advection solver – MPDATA. This paper presents the implementation of MPDATA on an unstructured grid and demonstrates its accuracy and efficiency using analytic and idealized test cases. Ahmad et al. Intl. J. of Num. Methods in Fluids 09/13/2005
Interactions of urate transporter URAT1 in human kidney with uricosuric drugs

Aim: Hyperuricaemia is a significant factor in a variety of diseases, including gout and cardiovascular diseases. The kidney plays a dominant role in maintaining plasma urate levels through the excretion process. Human renal urate transporter URAT1 is thought to be an essential molecule that mediates the reabsorption of urate on the apical side of the proximal tubule. In this study the pharmacological characteristics and clinical implications of URAT1 were elucidated.
A Critical Role for Ubiquitination in the Endocytosis of Glutamate Receptors*

Group I metabotropic glutamate receptors (mGluRs) play important roles in various neuronal processes and elicit changes in synaptic efficacy through AMPA receptor (AMPAR) endocytosis. Trafficking of mGluRs plays an important role in controlling the precise localization of these receptors at specific region of the cell; it also regulates the activity of these receptors. Despite this obvious significance, we know very little about the cellular mechanisms that control the trafficking of group I mGluRs. We show here that ligand-mediated internalization of group I mGluRs is ubiquitination-dependent. A lysine residue (Lys1112) at the C-terminal tail of mGluR1 (a member of the group I mGluR family) plays crucial role in this process. Our data suggest that Lys63-linked polyubiquitination is involved in the ligand-mediated endocytosis of mGluR1. We also show here that the mGluR1 internalization is dependent on a specific E3 ubiquitin ligase, Siah-1A. Furthermore, acute knockdown of Siah-1A enhances the mGluR-mediated AMPAR endocytosis. These studies reveal a novel function of ubiquitination in the regulation of group I mGluRs, as well as its role in mGluR-dependent AMPAR endocytosis.
HIV infection and cardiovascular disease.

AIMS With the success of antiretroviral therapy (ART), non-human immunodeficiency virus (HIV)-related comorbidities like cardiovascular diseases (CVDs) are of increasing concern. We describe important recent research developments on the epidemiology of CVD in HIV infection, ART-related metabolic changes, and cardioprotective anti-inflammatory mechanisms, and summarize management strategies for CVD risk reduction. METHODS AND RESULTS We systematically identified and analysed systematic reviews and most cited literature published in the last 3 years and supplemented findings with selected evidence based on clinical expertise. Among HIV-infected individuals, the prevalence of CVD risk factors and the risk for CVD is higher compared with HIV negatives. Antiretroviral drugs may induce dyslipidaemia, reduce insulin sensitivity, and promote body fat redistribution that additionally contributes to CVD risk. Some antiretroviral drugs may increase risk for CVD events, but the absolute risk increase is moderate and has to be put into perspective with the massive HIV-related benefits. Sustained HIV suppression reduces systemic inflammatory markers and is associated with a moderate reduction in CVD events. Regular CVD risk assessment and counselling to stop smoking must be regularly done in all HIV-infected individuals. Statins are effective for the treatment of dyslipidaemia in HIV infection, but drug interactions with ART need to be considered. CONCLUSION Human immunodeficiency virus-infected individuals are at increased risk for CVD. Timely initiation of ART with consequent viral suppression is likely to reduce CVD events and to offset potential side effects from ART-induced metabolic changes. Reduction in smoking in HIV-infected individuals is a public health priority.
The Microscopic Structure of the Omentum in Healthy Dogs: The Mystery Unravelled

The canine omentum has many valuable properties but is still an underestimated organ. It contributes in many ways to the protection of the peritoneal cavity through its versatility on immunological level, but also through its role during angiogenesis, absorption, adhesion and fat storage. Despite a wide range of applications, the basic structure of the omentum is not well documented. This study provides an insight in the microscopic structure of the canine omentum through both light microscopic and electron microscopic investigations. Two regions could be distinguished in the canine omentum: translucent and adipose‐rich regions. The translucent regions were composed of two different layers: a continuous flattened mesothelium on top of a submesothelial connective tissue matrix. The adipose‐rich regions consisted of a substantial layer of adipocytes on which a flattened continuous mesothelium was present. Between those two layers, a few strands of collagen fibres could be detected. Large aggregates of immune cells, the so‐called milky spots, were not observed in the omentum of healthy dogs. Only a limited number of leucocytes, macrophages and neutrophils were found, scattered throughout the connective tissue in the translucent regions. At the level of the adipose‐rich regions, the immunological population was virtually non‐existent.
Women's Health Initiative Results: Breast Cancer Risk in Perspective

T he results of the Women’s Health Initiative (WHI) study are widely regarded as evidence that hormone replacement therapy (HRT) use increases breast cancer risk (1). The study’s large number of subjects and randomized prospective design are cited as compelling reasons to accept its findings without further scrutiny. However, epidemiologic studies provide information about associations, not cause and effect. Their results must therefore be analyzed carefully to determine the likelihood that causality is present. When the WHI study is carefully scrutinized, it can be seen that the findings, specifically those pertaining to breast cancer risk, are by no means definitive. As discussed below, the exceedingly small and nonstatistically significant increase in breast cancer risk reported in this study may well not be due to HRT use.
The accuracy of patient history, wheezing, and laryngeal measurements in diagnosing obstructive airway disease. CARE-COAD1 Group. Clinical Assessment of the Reliability of the Examination-Chronic Obstructive Airways Disease.

CONTEXT The accuracy of the clinical examination in detecting obstructive airway disease (OAD) is largely unknown because of a paucity of methodologically rigorous studies. OBJECTIVE To determine the accuracy of patient history, wheezing, laryngeal height, and laryngeal descent in the diagnosis of OAD. DESIGN Comparison study conducted from November 3, 1998, to December 4, 1998, evaluating 4 clinical examination elements for diagnosis of OAD vs the gold standard of forced expiratory volume in 1 second (FEV1) and FEV1-forced vital capacity (FVC) ratio less than the fifth percentile (adjusted for patient height, age, and sex). SETTING Twenty-five sites, including primary care and referral practices, in 14 countries. PARTICIPANTS A total of 309 consecutive patients were recruited (mean age, 56 years; 43% female), 76 (25%) with known chronic OAD, 114 (37%) with suspected chronic OAD, and 119 (39%) with neither known nor suspected OAD. MAIN OUTCOME MEASURES Sensitivity, specificity, and likelihood ratios (LRs) for each of the 4 elements of the clinical examination compared with the gold standard. RESULTS Mean FEV1 and FVC values were 2.1 L/s and 2.9 L; 52% had an FEV1 and FEV1-FVC ratio less than the fifth percentile. The LR for wheezing was 2.7 (95% confidence interval [CI], 1.7-4.2) and was not statistically significant in the multivariate model. The LR for laryngeal descent ranged from 0.9 (95% CI, 0.5-1.4) to 1.2 (95% CI, 0.4-3.4), depending on the cut point chosen, and did not enter the multivariate model. Only 4 of the history or physical examination elements we tested were significantly associated with the diagnosis of OAD on multivariate analysis: smoking for more than 40 pack-years (LR, 8.3), self-reported history of chronic OAD (LR, 7.3), maximum laryngeal height of 4 cm [corrected] or less (LR, 2.8), and age at least 45 years (LR, 1.3). Patients having all 4 findings had an LR of 220 (ruling in OAD); those with none had an LR of 0.13 (ruling out OAD). The area under the receiver operating characteristic curve for the model incorporating these 4 factors was 0.86. CONCLUSIONS Further research is needed to validate our model, but in the meantime, our data suggest that less emphasis should be placed on the presence of individual symptoms or signs (such as wheezing or laryngeal descent) in the diagnosis of OAD.
Development of a chronically catheterized maternal‐fetal macaque model to study in utero mother‐to‐fetus HIV transmission: A preliminary report

Abstract: The lack of a representative animal model that permits frequent in utero fetal blood sampling is a major limiting factor for the study of maternal‐fetal HIV transmission. Therefore, we have developed a maternal‐fetal virus infection model using chronically catheterized macaques to simultaneously study the time‐course of viral infection in the mother and the response of the fetus to maternal HIV infection. Pregnant macaques were infected with 103 infectious units of HIV‐2287; every 3 days blood samples from both the mother and the fetus as well as amniotic fluid samples were collected. We found a varying degree of peak and time‐to‐peak virus load, virus‐infected PBMCs, and free virus (determined by QC‐RNA‐PCR method) in maternal blood. Two of the three mothers with more than 108 copies of viral RNA/ml of plasma at peak viremia transmitted the virus to their fetuses at about 14 days post‐infection. As observed with HIV‐2287 infected mothers, virus‐infected fetuses also produced a rapid rate of CD4+ cell decline in utero.
Association of Human Immunodeficiency Virus Type 1 Gag with Membrane Does Not Require Highly Basic Sequences in the Nucleocapsid: Use of a Novel Gag Multimerization Assay

ABSTRACT Human immunodeficiency virus type 1 (HIV-1) particle production, a process driven by the Gag polyprotein precursor, occurs on the plasma membrane in most cell types. The plasma membrane contains cholesterol-enriched microdomains termed lipid rafts, which can be isolated as detergent-resistant membrane (DRM). Previously, we and others demonstrated that HIV-1 Gag is associated with DRM and that disruption of Gag-raft interactions impairs HIV-1 particle production. However, the determinants of Gag-raft association remain undefined. In this study, we developed a novel epitope-based Gag multimerization assay to examine whether Gag assembly is essential for its association with lipid rafts. We observed that membrane-associated, full-length Gag is poorly detected by immunoprecipitation relative to non-membrane-bound Gag. This poor detection is due to assembly-driven masking of Gag epitopes, as denaturation greatly improves immunoprecipitation. Gag mutants lacking the Gag-Gag interaction domain located in the N terminus of the nucleocapsid (NC) were efficiently immunoprecipitated without denaturation, indicating that the epitope masking is caused by higher-order Gag multimerization. We used this assay to examine the relationship between Gag assembly and Gag binding to total cellular membrane and DRM. Importantly, a multimerization-defective NC mutant displayed wild-type levels of membrane binding and DRM association, indicating that NC-mediated Gag multimerization is dispensable for association of Gag with membrane or DRM. We also demonstrate that different properties of sucrose and iodixanol membrane flotation gradients may explain some discrepancies regarding Gag-raft interactions. This report offers new insights into the association of HIV-1 Gag with membrane and with lipid rafts.
Character-level Recurrent Text Prediction

Text prediction is an application of language models to mobile devices. Currently, the state of the art models use neural networks. Unfortunately, mobile devices are constrainted in both computing power and space and are thus unable to run most (if not all) neural networks. Recently, however, character-level architectures have appeared that have outperformed previous architectures for machine translation. They are advantageous in that they do not require a word embedding matrix and thus require a lot less space. This project evaluates one recent character-level architecture on the text prediction task. We find that the network performs qualitatively well, as well as achieving perplexity levels close to existing methods on the Brown corpus.
Origin of primordial germ cells, as characterized by the presence of nuage, in embryos of the teleost fish Barbus conchonius.

The presence, location and morphology of cells containing nuage, an ultrastructural characteristic of primordial germ cells (PGCs), is described from the moment of first morphological recognition of PGC (around 100% epiboly) in embryos of the teleost fish Barbus conchonius. Thus characterized cells were studied in relation to their cellular contacts with somatic germ layer cells, possibly involved in the determination of PGCs. The results show that from the very moment that cells, likely to be PGCs, can be light microscopically identified with morphological and positional criteria (from 10 h post fertilization (p.f.) onwards), they contain nuage near the nuclear envelope, which is a strong indication of their PGC-identity. During the studied period (9-12 h and 24 h p.f.) nuage-containing cells seem to translocate from the mesoderm towards the yolk syncytial layer (YSL). These PGCs usually appear not to be directly connected with the YSL but to remain separated from the YSL by one or more endodermal extensions, at least up to 12 h p.f. Also at 24 h p.f. somatic cells separate the PGCs from the YSL.
Acromegaly: Underdiagnosed in patients with prolactinoma

Prolactin secreting adenomas are very common and account for 50-60% of all functional pituitary adenomas. Medical history pertaining to reproductive and sexual function initiates the work up for prolactinoma. At the time of initial assessment other pituitary hormones may be evaluated, including growth hormone (GH). Thereafter, patients are treated medically with dopamine agonist, typically with no further assessment of GH hypersecretion. Review of the literature suggests that up to 4% of patients with an established diagnosis of prolactinoma can develop acromegaly even after many years of the initial evaluation. Acromegaly is a rare disease with mortality rates 2-3 times higher as compared to that of the general population. The interval from onset of symptoms to the diagnosis may range from one year to several decades. Thus, omitting IGF-1 measurements at the initial evaluation of prolactinoma, and/or in the follow up period, can miss mild and subtle cases of acromegaly. Therefore, biochemical evaluation for GH excess should be considered in patients with prolactinoma initially as well as in the remote follow up. Journal of Nature and Science (JNSCI), 3(8):e418, 2017
Can assimilating remotely-sensed surface soil moisture data improve root-zone soil moisture predictions in the CABLE land surface model?

The ability to quantify soil moisture content over depths including the root zone is important for predicting key hydrological processes for a range of applications in agriculture, emergency planning, and weather prediction. Remote-sensing provides a large amount of spatially distributed information related to water balance quantities. This includes brightness temperature data from passive microwave sensors such as the Advanced Microwave Scanning Radiometer for the Earth Observing System (AMSR-E), which is used to estimate surface soil moisture content. Such observations can add valuable information to hydrologic/land surface modelling when combined using data assimilation techniques. However soil moisture from sensors such as AMSR-E can only be retrieved for the top couple of centimetres of soil at most, so assimilating this information into the surface layer of a model needs to constrain soil moisture in deeper layers. This will depend partly on the accuracy of model structure in relating surface moisture dynamics to deeper soil profiles, and also on assumptions made about model errors that can affect how the assimilation algorithm adjusts the model. Here we assimilated AMSR-E soil moisture observations into a CSIRO Atmosphere Biosphere Land Exchange model (CABLE) simulation over the Yanco region in the Murrumbidgee catchment, Australia. We then examined the impact it had on deeper soil moisture profiles (0-30cm and 0-60cm) in CABLE compared to in-situ validation data for two sites. CABLE was not calibrated, however the AMSR-E data were rescaled to match CABLE’s soil moisture time series for the year 2005 (where annual rainfall was representative of long term climatology in the study region). The latest remotely-sensed Leaf Area Index (LAI) product from MODIS was also used as a key model parameter input. Initial results after perturbing this data and other inputs, to represent model error for the assimilation process, indicated the stability of assimilation applied to CABLE is sensitive to large perturbations. From subsequent experiments, the impact on predictions over 0-30cm and 0-60cm depth ranges from assimilating AMSR-E surface soil moisture was minimal compared to CABLE predictions with no assimilation, even though there were clear impacts on surface moisture predictions. This study provides direction for more focused research into understanding and representing model error and sensitivity with the help of remotely-sensed information. 19th International Congress on Modelling and Simulation, Perth, Australia, 12–16 December 2011 http://mssanz.org. au/modsim2011
Widespread recognition of 5' splice sites by noncanonical base-pairing to U1 snRNA involving bulged nucleotides.

An established paradigm in pre-mRNA splicing is the recognition of the 5' splice site (5'ss) by canonical base-pairing to the 5' end of U1 small nuclear RNA (snRNA). We recently reported that a small subset of 5'ss base-pair to U1 in an alternate register that is shifted by 1 nucleotide. Using genetic suppression experiments in human cells, we now demonstrate that many other 5'ss are recognized via noncanonical base-pairing registers involving bulged nucleotides on either the 5'ss or U1 RNA strand, which we term "bulge registers. " By combining experimental evidence with transcriptome-wide free-energy calculations of 5'ss/U1 base-pairing, we estimate that 10,248 5'ss (∼5% of human 5'ss) in 6577 genes use bulge registers. Several of these 5'ss occur in genes with mutations causing genetic diseases and are often associated with alternative splicing. These results call for a redefinition of an essential element for gene expression that incorporates these registers, with important implications for the molecular classification of splicing mutations and for alternative splicing.