Miracle-dz/UniFAR-FTUs huggingface dataset:
Apical ANG II-stimulated PLA2activity and Na+flux: a potential role for Ca2+-independent PLA2.

Type 1 angiotensin II (ANG II) receptors (AT1R), which mediate proximal tubule (PT) salt and water reabsorption, undergo endocytosis and recycling. Prior studies in a PT-like model (LLC-PKCl4 cells expressing rabbit AT1R) (LLC-PK-AT1R cells) determined that quinacrine, a nonspecific phospholipase A2(PLA2) inhibitor, and the haloenol lactone suicide substrate (HELSS), a Ca2+-independent PLA2 inhibitor, attenuated apical (AP) AT1R recycling. Further studies were undertaken to examine the association between AT1R endocytotic movement and PLA2 activity in this model. AP ANG II (100 nM) increased[Formula: see text]arachidonic acid ([Formula: see text]AA) release 4.4 ± 0.38-fold in LLC-PK-AT1R cells cultured on permeable supports. Basolateral (BL) ANG II had no significant effect. Reversed-phase high-performance liquid chromatography confirmed that AP ANG II stimulated free [Formula: see text]AA release. Quinacrine, HELSS, and palmitoyl trifluoromethyl ketone, another Ca2+-independent PLA2 inhibitor, inhibited AP ANG II-stimulated [Formula: see text]AA release, as did inhibiting AP AT1R internalization with phenylarsine oxide. The role of HELSS-inhibitable AA release in ANG II-mediated 22Na flux was examined, given the effects of AT1R-mediated PLA2 activity on salt and water reabsorption. AP ANG II (100 nM) stimulated22Na flux (AP → BL), a response inhibited by HELSS. Thus, in this model, AP AT1R activated PLA2 with concomitant22Na flux (AP → BL), suggesting a link between AP AT1R endocytotic movement, AT1R-stimulated PLA2 activity, and22Na flux in this model. The effects of HELSS suggest that Ca2+-independent PLA2 activity may be involved in this AP ANG II response.
Multi-lingual City Name Recognition for Indian Postal Automation

Under three-language formula, the destination address block of postal document of an Indian state is generally written in three languages: English, Hindi and the State official language. From the statistical analysis we found that 12.37%, 76.32% and 10.21% postal documents are written in Bangla, English and Devanagari script, respectively. Because of inter-mixing of these scripts in postal address writings, it is very difficult to identify the script by which a city name is written. To avoid such script identification difficulties, in this paper we proposed a lexicon-driven method for multi-lingual (English, Hindi and Bangla) city name recognition for Indian postal automation. In the proposed scheme, at first, to take care of slanted handwriting of different individuals a slant correction technique is performed. Next, a water reservoir concept is applied to pre-segment the slant corrected city names into possible primitive components (characters or its parts). Pre-segmented components of a city name are then merged into possible characters to get the best city name using the lexicon information. In order to merge these primitive components into characters and to find optimum character segmentation, dynamic programming (DP) is applied using total likelihood of the characters of a city name as an objective function. We tested our system on 16132 Indian trilingual city names and 92.25% overall recognition accuracy was obtained.
The bidirectional relationship between body mass index and treatment outcome in adolescents with treatment-resistant depression.

OBJECTIVE Depression and obesity are associated, but the impact of obesity on depression treatment outcome, or, conversely, the impact of treatment on body mass index (BMI) in depressed adolescents has not been reported. In this article, we examine the bidirectional relationships between BMI and treatment response in adolescents with treatment-resistant depression. METHOD Participants in the Treatment of Selective Serotonin Reuptake Inhibitor (SSRI) Resistant Depression in Adolescents (TORDIA) study had height and weight assessed at baseline, weekly for the first 6 weeks, biweekly for the next 6 weeks, and monthly from weeks 12 through 24. The impact of baseline BMI as a predictor and moderator of treatment response was assessed. In addition, participants' changes in BMI were assessed as a function of specific treatment assignment and treatment response. RESULTS Participants assigned to SSRIs had a greater increase in BMI-for-age-sex z-score and weight than did those assigned to venlafaxine. Post-hoc, those treated with paroxetine or citalopram had the biggest increases in BMI, relative to fluoxetine or venlafaxine. Overweight or obesity was neither a predictor nor a moderator of treatment outcome, nor of subsequent BMI change. CONCLUSIONS Overweight status does not appear to affect treatment response in adolescents with resistant depression. The successful treatment of depression does not appear to favorably affect weight or BMI. Fluoxetine and venlafaxine are less likely to cause an increase in BMI than paroxetine or citalopram.
Millisecond-scale molecular dynamics simulations on Anton

Anton is a recently completed special-purpose supercomputer designed for molecular dynamics (MD) simulations of biomolecular systems. The machine's specialized hardware dramatically increases the speed of MD calculations, making possible for the first time the simulation of biological molecules at an atomic level of detail for periods on the order of a millisecond-about two orders of magnitude beyond the previous state of the art. Anton is now running simulations on a timescale at which many critically important, but poorly understood phenomena are known to occur, allowing the observation of aspects of protein dynamics that were previously inaccessible to both computational and experimental study. Here, we report Anton's performance when executing actual MD simulations whose accuracy has been validated against both existing MD software and experimental observations. We also discuss the manner in which novel algorithms have been coordinated with Anton's co-designed, application-specific hardware to achieve these results.
Poor Physical Performance is Associated with Obesity Among University Students in China

Background The aim of this study was to explore the relationship between physical performance and BMI (body mass index) of university students in China. Material/Methods We conducted a cross-sectional study evaluating the physical performance and BMI of university students. BMI was calculated based on height and weight. Overweight and obesity were defined by the Working Group on Obesity references in China. Results A total of 2313 participants (978 males and 1335 females) were recruited in our study. The mean value of the 50-meter dash and standing long jump in male students was higher than in female students (P<0.05). The overall prevalences of overweight (including obesity) and obesity for male students were 17.9% and 4.2%, respectively, and 5.1% and 0.5%, respectively, for female university students. BMI was weakly positively associated with the 50-meter dash score, but was negatively associated with the score for standing long jump and pull-ups. Conclusions Our study suggested that overweight and obesity are associated with physical performance of university students, especially in male students. University students should exercise more to improve physical health.
The Potential of Isolation Source to Predict Colonization in Avian Hosts: A Case Study in Campylobacter jejuni Strains From Three Bird Species

Campylobacter jejuni is the primary cause of bacterial gastroenteritis worldwide, infecting humans mostly through consumption of contaminated poultry. C. jejuni is common in the gut of wild birds, and shows distinct strain-specific association to particular bird species. This contrasts with farm animals, in which several genotypes co-exist. It is unclear if the barriers restricting transmission between host species of such specialist strains are related to environmental factors such as contact between host species, bacterial survival in the environment, etc., or rather to strain specific adaptation to the intestinal environment of specific hosts. We compared colonization dynamics in vivo between two host-specific C. jejuni from a song thrush (ST-1304 complex) and a mallard (ST-995), and a generalist strain from chicken (ST-21 complex) in a wild host, the mallard (Anas platyrhynchos). In 18-days infection experiments, the song thrush strain showed only weak colonization and was cleared from all birds after 10 days, whereas both mallard and chicken strains remained stable. When the chicken strain was given 4 days prior to co-infection of the same birds with a mallard strain, it was rapidly outcompeted by the latter. In contrast, when the mallard strain was given 4 days prior to co-infection with the chicken strain, the mallard strain remained and expansion of the chicken strain was delayed. Our results suggest strain-specific differences in the ability of C. jejuni to colonize mallards, likely associated with host origin. This difference might explain observed host association patterns in C. jejuni from wild birds.
Mechanisms of TGFβ-Induced Epithelial–Mesenchymal Transition

Transitory phenotypic changes such as the epithelial–mesenchymal transition (EMT) help embryonic cells to generate migratory descendants that populate new sites and establish the distinct tissues in the developing embryo. The mesenchymal descendants of diverse epithelia also participate in the wound healing response of adult tissues, and facilitate the progression of cancer. EMT can be induced by several extracellular cues in the microenvironment of a given epithelial tissue. One such cue, transforming growth factor β (TGFβ), prominently induces EMT via a group of specific transcription factors. The potency of TGFβ is partly based on its ability to perform two parallel molecular functions, i.e. to induce the expression of growth factors, cytokines and chemokines, which sequentially and in a complementary manner help to establish and maintain the EMT, and to mediate signaling crosstalk with other developmental signaling pathways, thus promoting changes in cell differentiation. The molecules that are activated by TGFβ signaling or act as cooperating partners of this pathway are impossible to exhaust within a single coherent and contemporary report. Here, we present selected examples to illustrate the key principles of the circuits that control EMT under the influence of TGFβ.
Blockade by cAMP of native sodium channels of adult rat skeletal muscle fibers.

Although the skeletal muscle sodium channel is a good substrate for cAMP-dependent protein kinase (PKA), no functional consequence was observed for this channel expressed in heterologous systems. Therefore, we investigated the effect of 8-(4-chlorophenylthio)adenosine 3',5'-cyclic monophosphate (CPT-cAMP), a membrane-permeable cAMP analog, on the native sodium channels of freshly dissociated rat skeletal muscle fibers by means of the cell-attached patch-clamp technique. Externally applied CPT-cAMP (0.5 mM) reduced peak ensemble average currents by ∼75% with no change in kinetics. Single-channel conductance and normalized activation curves were unchanged by CPT-cAMP. In contrast, steady-state inactivation curves showed a reduction of the maximal available current and a negative shift of the half-inactivation potential. Similar effects were observed with dibutyryl adenosine 3',5'-cyclic monophosphate but not with cAMP, which does not easily permeate the cell membrane. Incubation of fibers for 1 h with 10 μM H-89, a PKA inhibitor, did not prevent the effect of CPT-cAMP. Finally, the β-adrenoreceptor agonist isoproterenol mimicked CPT-cAMP when applied at 0.5 mM but had no effect at 0.1 mM. These results indicate that cAMP inhibits native skeletal muscle sodium channels by acting within the fiber, independently of PKA activation.
Signal transduction and regulation of lung endothelial cell permeability. Interaction between calcium and cAMP.

Pulmonary endothelium forms a semiselective barrier that regulates fluid balance and leukocyte trafficking. During the course of lung inflammation, neurohumoral mediators and oxidants act on endothelial cells to induce intercellular gaps permissive for transudation of proteinaceous fluid from blood into the interstitium. Intracellular signals activated by neurohumoral mediators and oxidants that evoke intercellular gap formation are incompletely understood. Cytosolic Ca2+ concentration ([Ca2+]i) and cAMP are two signals that importantly dictate cell-cell apposition. Although increased [Ca2+]ipromotes disruption of the macrovascular endothelial cell barrier, increased cAMP enhances endothelial barrier function. Furthermore, during the course of inflammation, elevated endothelial cell [Ca2+]idecreases cAMP to facilitate intercellular gap formation. Given the significance of both [Ca2+]iand cAMP in mediating cell-cell apposition, this review addresses potential sites of cross talk between these two intracellular signaling pathways. Emerging data also indicate that endothelial cells derived from different vascular sites within the pulmonary circulation exhibit distinct sensitivities to permeability-inducing stimuli; that is, elevated [Ca2+]ipromotes macrovascular but not microvascular barrier disruption. Thus this review also considers the roles of [Ca2+]iand cAMP in mediating site-specific alterations in endothelial permeability.
High‐resolution definition of humoral immune response correlates of effective immunity against HIV

Defining correlates of immunity by comprehensively interrogating the extensive biological diversity in naturally or experimentally protected subjects may provide insights critical for guiding the development of effective vaccines and antibody‐based therapies. We report advances in a humoral immunoprofiling approach and its application to elucidate hallmarks of effective HIV‐1 viral control. Systematic serological analysis for a cohort of HIV‐infected subjects with varying viral control was conducted using both a high‐resolution, high‐throughput biophysical antibody profiling approach, providing unbiased dissection of the humoral response, along with functional antibody assays, characterizing antibody‐directed effector functions such as complement fixation and phagocytosis that are central to protective immunity. Profiles of subjects with varying viral control were computationally analyzed and modeled in order to deconvolute relationships among IgG Fab properties, Fc characteristics, and effector functions and to identify humoral correlates of potent antiviral antibody‐directed effector activity and effective viral suppression. The resulting models reveal multifaceted and coordinated contributions of polyclonal antibodies to diverse antiviral responses, and suggest key biophysical features predictive of viral control.
Linguistic profiles of children with CI as compared with children with hearing or specific language impairment.

BACKGROUND The spoken language difficulties of children with moderate or severe to profound hearing loss are mainly related to limited auditory speech perception. However, degraded or filtered auditory input as evidenced in children with cochlear implants (CIs) may result in less efficient or slower language processing as well. To provide insight into the underlying nature of the spoken language difficulties in children with CIs, linguistic profiles of children with CIs are compared with those of hard-of-hearing (HoH) children with conventional hearing aids and children with specific language impairment (SLI). AIMS To examine differences in linguistic abilities and profiles of children with CIs as compared with HoH children and children with SLI, and whether the spoken language difficulties of children with CIs mainly lie in limited auditory perception or in language processing problems. METHODS & PROCEDURE Differences in linguistic abilities and differential linguistic profiles of 47 children with CI, 66 HoH children with moderate to severe hearing loss, and 127 children with SLI are compared, divided into two age cohorts. Standardized Dutch tests were administered. Factor analyses and cluster analyses were conducted to find homogeneous linguistic profiles of the children. OUTCOMES & RESULTS The children with CIs were outperformed by their HoH peers and peers with SLI on most linguistic abilities. Concerning the linguistic profiles, the largest group of children with CIs and HoH children shared similar profiles. The profiles observed for most of the children with SLI were different from those of their peers with hearing loss in both age cohorts. CONCLUSIONS & IMPLICATIONS Results suggest that the underlying nature of spoken language problems in most children with CIs manifests in limited auditory perception instead of language processing difficulties. However, there appears to be a subgroup of children with CIs whose linguistic profiles resemble those of children with SLI.
Vulnerability study of myelinated and unmyelinated nerve fibers in acute ocular hypertension in rabbit

In the current study, it was aimed to evaluate the changes in myelinated and unmyelinated nerve fibers in retinal ischemia-reperfusion injuries caused by acute ocular hypertension and to determine the sequence of these changes. Adult healthy New Zealand white rabbits were randomized to the hemodynamic group [n=12; used to determine the optimal intraocular pressure (IOP) for the subsequent experiments] and the hypertension group (n=6; 70-mmHg hypertension induced in one eye). IOP was adjusted using a cannula and saline. Doppler ultrasound was used to measure the velocity of the optic artery under different intraocular pressures. Immunohistochemistry for myelin basic protein (MBP) was performed. Apoptosis of retinal cells was detected by terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling (TUNEL) assay. Electron microscopy was used to investigate the changes in myelinated and unmyelinated nerve fibers. IOP of the hypertension eyes was maintained at 70.2±1.0 mmHg, while IOP of control eyes was 7–14 mmHg. Doppler ultrasound demonstrated an obvious decline of peak systolic velocity and an increase of resistance index of retinal bloodstream under a 70-mmHg IOP. MBP immunohistochemistry and electron microscopy demonstrated obvious injuries to the myelin fibers. TUNEL indicated a significantly higher apoptosis rate in the hypertension eyes compared with control eyes. The apoptosis rate of retinal ganglion cells and bipolar cells in unmyelinated regions was higher than in myelinated regions. In conclusion, an IOP of 70 mmHg led to incomplete retinal ischemia but was the threshold for retinal ischemia, leading to obvious injuries to the myelin fibers.
Galectin-3 in Atrial Fibrillation: Mechanisms and Therapeutic Implications

Maintenance of atrial fibrillation is a complex mechanism, including extensive electrical and structural remodeling of the atria which involves progressive fibrogenesis. Galectin-3 is a biomarker of fibrosis, and, thus, may be involved in atrial remodeling in atrial fibrillation patients. We review the role of galectin-3 in AF mechanisms and its potential therapeutic implications.
Relationship between baroreceptor reflex function and end-organ damage in spontaneously hypertensive rats.

The purpose of this study was to further illustrate the relationship between baroreceptor reflex sensitivity (BRS) and hypertensive end-organ damage (EOD) and to test the hypothesis that impairment of BRS aggravates EOD in hypertension. We studied baroreflex-mediated changes in heart rate [expressed as baroreceptor sensitivity to heart rate control (BRSHR)] and blood pressure [expressed as baroreceptor sensitivity to blood pressure control (BRSBP)] in spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY) that were used as controls, both at the age of 50-52 wk. Rats were also instrumented to record BP, HR, and BP variability (BPV) in the conscious, unrestrained state. In SHR compared with WKY, BP and BPV were significantly increased, whereas BRSHR and BRSBP were significantly decreased. SHR had remarkable EOD when compared with WKY (EOD score: 6.3 ± 2.5 vs. 2.9 ± 0.8, P < 0.01). Univariate regressive analysis demonstrated that EOD score was increased with BP and BPV and decreased with BRS. In multivariate analysis, EOD score was predicted by greater systolic BP and lower BRS and HR variability. These results indicate that BRS is negatively related to BPV and EOD score, and impaired BRS might be one of the major causes for hypertensive EOD.
Assessing the bioaccumulation potential of ionizable organic compounds: Current knowledge and research priorities

The objective of the present study was to review the current knowledge regarding the bioaccumulation potential of ionizable organic compounds (IOCs), with a focus on the availability of empirical data for fish. Aspects of the bioaccumulation potential of IOCs in fish that can be characterized relatively well include the pH dependence of gill uptake and elimination, uptake in the gut, and sorption to phospholipids (membrane–water partitioning). Key challenges include the lack of empirical data for biotransformation and binding in plasma. Fish possess a diverse array of proteins that may transport IOCs across cell membranes. Except in a few cases, however, the significance of this transport for uptake and accumulation of environmental contaminants is unknown. Two case studies are presented. The first describes modeled effects of pH and biotransformation on the bioconcentration of organic acids and bases, while the second employs an updated model to investigate factors responsible for accumulation of perfluorinated alkyl acids. The perfluorinated alkyl acid case study is notable insofar as it illustrates the likely importance of membrane transporters in the kidney and highlights the potential value of read‐across approaches. Recognizing the current need to perform bioaccumulation hazard assessments and ecological and exposure risk assessment for IOCs, the authors provide a tiered strategy that progresses (as needed) from conservative assumptions (models and associated data) to more sophisticated models requiring chemical‐specific information. Environ Toxicol Chem 2017;36:882–897. © 2016 SETAC