ATP increases [Ca2+]i and activates a Ca2+-dependent Cl− current in rat ventricular fibroblasts

Key Points

• Fibroblasts isolated from adult rat ventricles consistently respond to (5–100 μM) ATP.
• ATP, ADP, and UTP all elicit similar dose-dependent increases in [Ca²⁺]_i.
• ATP also activates an outwardly rectifying Cl⁻ current; in contrast, ADP and UTP have much smaller electrophysiological effects.
• This ATP-dependent Cl⁻ current is markedly reduced when: i) [Ca²⁺]_i is buffered with BAPTA, or ii) the intrinsic phospholipase C activity in these fibroblasts is inhibited.
• PCR analysis suggests that the ATP-induced current is generated by the Ca²⁺-activated Cl⁻ current transcript TMEM 16F, also denoted ANO6.
• These findings reveal new physiological and pharmacological principles that regulate ventricular fibroblast function.

 

New Findings

• What is the central question of this study?

  Although electrophysiological and biophysical characteristics of heart fibroblasts have been studied in detail, their responses to prominent paracrine agents in the myocardium have not been adequately addressed. Our experiments characterize changes in cellular electrophysiology and intracellular calcium in response to ATP.

• What is the main finding and its importance?

  In rat ventricular fibroblasts maintained in cell culture we find that ATP activates a specific subset of Ca²⁺-activated Cl⁻ channels as a consequence of binding to P2Y purinoceptors and then activating phospholipase C. This response is not dependent on [Ca²⁺]_o but requires an increase in [Ca²⁺]_i and is modulated by the type of nucleotide that is the purinergic agonist.

Abstract

Effects of adenosine 5′-triphosphate (ATP) on enzymatically isolated rat ventricular fibroblasts maintained in short-term (36–72 hrs) cell culture were examined. Immunocytochemical staining of these cells revealed that a fibroblast, as opposed to a myofibroblast, phenotype was predominant. ATP, ADP or UTP all produced large increases in intracellular Ca²⁺ [Ca²⁺]_i. Voltage-clamp studies (amphotericin-perforated patch) showed that ATP (1–100 μM) activated an outwardly rectifying current, having a reversal potential very close to the Nernst potential for Cl⁻. In contrast, ADP was much less effective and UTP produced no detectable current. The nonselective Cl⁻ channel blockers niflumic acid, DIDS and NPPB (each at 100 μM), blocked the responses to 100 μM ATP. 2-MTATP, an agonist for P2Y purinoceptors activated a very similar outwardly rectifying C1⁻ current. The P2Y receptor antagonists, suramin and PPADS (100 μM each), significantly inhibited the Cl⁻ current produced by 100 μM ATP. ATP was able to activate this Cl⁻ current when [Ca²⁺]_o was removed, but not when [Ca²⁺]_i was buffered with BAPTA-AM. In the presence of the phospholipase C (PLC) inhibitor U73122, this Cl⁻ current could not be activated. PCR analysis revealed strong signals for a number of P2Y purinoceptors; and also for the Ca²⁺-activated Cl⁻ channel, TMEM 16F (also denoted ANO-6). In summary, these results demonstrate that activation of P2Y receptors by ATP causes a PLC-dependent increase in [Ca²⁺]_i, followed by activation of a Ca²⁺-dependent Cl⁻ current in rat ventricular fibroblasts.

This article is protected by copyright. All rights reserved

from Physiology via xlomafota13 on Inoreader http://ift.tt/2oGXl0t
via IFTTT

Whole-Genome Analysis of an Extensively Drug-Resistant Acinetobacter baumannii Strain XDR-BJ83: Insights into the Mechanisms of Resistance of an ST368 Strain from a Tertiary Care Hospital in China

Microbial Drug Resistance , Vol. 0, No. 0.


from Mary Ann Liebert, Inc. publishers via xlomafota13 on Inoreader http://ift.tt/2oHqMQ3
via IFTTT

Is There an Association Between Use of Amoxicillin-Clavulanate and Resistance to Third-Generation Cephalosporins in Klebsiella pneumoniae and Escherichia coli at the Hospital Level?

Microbial Drug Resistance , Vol. 0, No. 0.


from Mary Ann Liebert, Inc. publishers via xlomafota13 on Inoreader http://ift.tt/2HVyJtO
via IFTTT

First Description in Greece of mphC-Positive Staphylococci Causing Subclinical Mastitis in Ewes

Microbial Drug Resistance , Vol. 0, No. 0.


from Mary Ann Liebert, Inc. publishers via xlomafota13 on Inoreader http://ift.tt/2oGthSS
via IFTTT

Issue Information

from Physiology via xlomafota13 on Inoreader http://ift.tt/2GSdjwi
via IFTTT

Editorial Board

from Physiology via xlomafota13 on Inoreader http://ift.tt/2oE04I2
via IFTTT

Autonomic rhythms in health and disease

from Physiology via xlomafota13 on Inoreader http://ift.tt/2HW8Hqf
via IFTTT

A Nonsense Variant in the ACADVL Gene in German Hunting Terrier Dogs with Exercise Induced Metabolic Myopathy

Several enzymes are involved in fatty acid oxidation, which is a key process in mitochondrial energy production. Inherited defects affecting any step of fatty acid oxidation can result in clinical disease. We present here an extended family of German Hunting Terriers with 10 dogs affected by clinical signs of exercise induced weakness, muscle pain, and suspected rhabdomyolysis. The combination of clinical signs, muscle histopathology and acylcarnitine analysis with an elevated tetradecenoylcarnitine (C14:1) peak suggested a possible diagnosis of acyl-CoA dehydrogenase very long chain deficiency (ACADVLD). Whole genome sequence analysis of one affected dog and 191 controls revealed a nonsense variant in the ACADVL gene encoding acyl-CoA dehydrogenase very long chain, c.1728C>A or p.(Tyr576*). The variant showed perfect association with the phenotype in the 10 affected and more than 500 control dogs of various breeds. Pathogenic variants in the ACADVL gene have been reported in humans with similar myopathic phenotypes. We therefore considered the detected variant to be the most likely candidate causative variant for the observed exercise induced myopathy. To our knowledge, this is the first description of this disease in dogs, which we propose to name exercise induced metabolic myopathy (EIMM), and the identification of the first canine pathogenic ACADVL variant. Our findings provide a large animal model for a known human disease and will enable genetic testing to avoid the unintentional breeding of affected offspring.

from Genetics via xlomafota13 on Inoreader http://ift.tt/2HVgRiI
via IFTTT

African-American women’s Upward Economic Mobility and Small for Gestational Age Births: A Population-Based Study

Abstract

Background The relationship between African-American women's upward economic mobility and small for gestational age (weight for gestational < 10th percentile, SGA) rates is incompletely understood. Objective To ascertain the extent to which African-American women's upward economic mobility from early-life impoverishment is coupled with reduced SGA rates. Methods Stratified and multilevel logistic regression analyses were completed on the Illinois transgenerational dataset of African-American infants (1989–1991) and their Chicago-born mothers (1956–1976) with linked U.S. census income information. Results Impoverished-born (defined as lowest quartile of neighborhood income distribution) African-American women (n = 4891) who remained impoverished by the time of delivery had a SGA rate of 19.7%. Individuals who achieved low (n = 5827), modest (n = 2254), or high (n = 732) upward economic mobility by adulthood had lower SGA rates of 17.2, 14.8, and 13.7%, respectively; RR = 0.9 (0.8–0.9), 0.8 (0.7–0.8), and 0.7 (0.6–0.8), respectively. In adjusted (controlling for traditional individual-level risk factors) multilevel regression models, there was a decreasing linear trend in SGA rates with increasing levels of upward economic mobility; the adjusted RR of SGA birth for impoverished-born African-American women who experienced low, modest, of high (compared to no) upward mobility equaled 0.95 (0.91, 0.99), 0.90 (0.83, 0.98), and 0.86 (0.75, 0.98), respectively, p < 0.05. Conclusions African-American women's upward economic mobility from early-life residence in poor urban communities is associated with lower SGA rates independent of adulthood risk status.

from Health via xlomafota13 on Inoreader http://ift.tt/2F9NpHh
via IFTTT

Maternal Obesity and Risk of Preterm Birth and Low Birthweight in Hawaii PRAMS, 2000–2011

Abstract

Objective Maternal obesity is a risk factor for preterm birth, a leading cause of infant morbidity and mortality. Native Hawaiian and other Pacific Islanders (NHOPI) have high rates of poor birth outcomes. Despite the high rates of obesity in NHOPI in Hawaii, the association with preterm birth has not been examined in this population. Methods We performed a retrospective cohort study of 20,061 women using data collected by Hawaii's Pregnancy Risk Assessment Monitoring System (PRAMS) from 2000 to 2011. We investigated the contribution of maternal age, pre-pregnancy BMI, gestational diabetes, hypertension, race, socioeconomic status, and smoking to our primary outcomes of preterm birth and low birthweight using multivariable logistic regression, stratified by NHOPI versus non-NHOPI race. Results Pre-pregnancy obesity was more common in NHOPI than non-NHOPI women (23.9 and 10.5%, respectively; p < 0.01). Overall, the risk for preterm birth increased with maternal obesity (BMI ≥ 30.0; aOR = 1.24, 95% CI 1.06–1.45, p < 0.01), compared with normal weight women. Among NHOPI women, the prevalence of preterm birth was elevated compared with non-NHOPI women although the prevalence of low birth weight was lower. After adjusting for confounders, risk for preterm birth and low birth weight were elevated in NHOPI women compared with White women. Maternal obesity did not significantly affect the risk of prematurity within the NHOPI group. Conclusions for Practice Our study demonstrates an association between maternal pre-pregnancy obesity and preterm deliveries in Hawaii. NHOPI have high rates of pre-pregnancy obesity as well as increased risk of both preterm delivery and low birthweight when compared to White women. Further data are needed to assess interactions between race, maternal health, and neonatal morbidity, and to identify ways to improve birth outcomes for minority populations in the state of Hawaii.

from Health via xlomafota13 on Inoreader http://ift.tt/2F4JurM
via IFTTT

Assessment of health-related quality of life in spine treatment: conversion from SF-36 to VR-12

Health-related quality-of-life outcomes have been collected with the Medical Outcomes Study (MOS) Short Form 36 (SF-36) survey. Boston University School of Public Health has developed algorithms for the conversion of SF-36 to VR-12 physical component summary (PCS) and mental component summary (MCS).

from Sports Medicine via xlomafota13 on Inoreader http://ift.tt/2HTjzoR
via IFTTT

A novel preoperative trajectory evaluation method for l5-s1 transforaminal percutaneous endoscopic lumbar discectomy

L5-S1 transforaminal PELD is a demanding procedure due to structures like iliac crest, L5 transverse process, hypertrophic L5-S1 facet joint, and sacral ala. There has been no definite preoperative evaluation method to evaluate the surgical validity of L5-S1 transforaminal PELD.

from Sports Medicine via xlomafota13 on Inoreader http://ift.tt/2oDy9I8
via IFTTT

Rod fracture in adult spinal deformity surgery fused to the sacrum: prevalence, risk factors and impact on health related quality of life in 526 patients

Risk factors associated with rod fracture (RF) following adult spinal deformity (ASD) surgery fused to the sacrum remain debatable and the impact of RF on patient-reported outcomes (PROs) after ASD surgery has not been investigated.

from Sports Medicine via xlomafota13 on Inoreader http://ift.tt/2HSnKkP
via IFTTT

De novo transcriptomics reveal distinct phototransduction signaling components in the retina and skin of a color-changing vertebrate, the hogfish ( Lachnolaimus maximus )

Abstract

Across diverse taxa, an increasing number of photoreceptive systems are being discovered in tissues outside of the eye, such as in the skin. Dermal photoreception is believed to serve a variety of functions, including rapid color change via specialized cells called chromatophores. In vitro studies of this system among color-changing fish have suggested the use of a phototransduction signaling cascade that fundamentally differs from that of the retina. Thus, the goal of this study was to identify phototransduction genes and compare their expression in the retina and skin of a color-changing fish, the hogfish Lachnolaimus maximus. De novo transcriptomics revealed the expression of genes that may underlie distinct, yet complete phototransduction cascades in L. maximus retina and skin. In contrast to the five visual opsin genes and cGMP-dependent phototransduction components expressed in the retina of L. maximus, only a single short-wavelength sensitive opsin (SWS1) and putative cAMP-dependent phototransduction components were expressed in the skin. These data suggest a separate evolutionary history of phototransduction in the retina and skin of certain vertebrates and, for the first time, indicate an expression repertoire of genes that underlie a non-retinal phototransduction pathway in the skin of a color-changing fish.

from Physiology via xlomafota13 on Inoreader http://ift.tt/2F4h3dP
via IFTTT

Modulation of the frontal-parietal network by low intensity anti-phase 20 Hz transcranial electrical stimulation boosts performance in the attentional blink task

Publication date: Available online 27 February 2018
Source:International Journal of Psychophysiology
Author(s): Zachary Yaple, Roman Vakhrushev
Performance in the attentional blink task has been demonstrated to be directly influenced by alpha and beta neural oscillatory activity. In two experiments we stimulated the right parietal cortex and left frontal cortex with transcranial alternating current stimulation. For the first experiment we targeted only the right parietal cortex and found a non-significant increase in performance from 20 Hz stimulation. In the second experiment we applied two stimulators to the right parietal and left frontal cortex and found a significant increase in performance from 20 Hz tACS with a phase difference of 180°. Since low intensity stimulation has been shown to inhibit cortical excitability, and anti-phasic stimulation has been hypothesized to decrease presynaptic activation in one region and drive postsynaptic spikes in the other, we suggest that low intensity anti-phasic 20 Hz stimulation inhibited the parietal cortex, thereby disinhibiting the frontal cortex. This visual attention mechanism supposedly reduces processing of distractor stimuli and enhances processing of target stimuli. This study reveals that the frontal-parietal visual attention network may be modulated with low intensity 20 Hz anti-phase tACS.



from Physiology via xlomafota13 on Inoreader http://ift.tt/2F1cjFy
via IFTTT

Group III/IV muscle afferents plays an independent role for the arterial baroreflex resetting during exercise in humans: is it the end of the road?

Abstract

The cardiovascular response to exercise is governed by both central and peripheral mechanisms that promote alterations in parasympathetic and sympathetic neural activities to the heart and blood vessels to meet the metabolic demands of working skeletal muscle in an intensity-dependent manner.

This article is protected by copyright. All rights reserved

from Physiology via xlomafota13 on Inoreader http://ift.tt/2Fb2OHa
via IFTTT

QTL for tuber morphology traits in diploid potato

Abstract

A diploid, potato mapping population consisting of 149 individuals was assessed in three consecutive years for important agronomic and quality traits: tuber shape, regularity of tuber shape, eye depth, mean tuber weight, and tuber flesh color. Analysis of variance showed that the genotype had the largest influence on the phenotypic scores but effect of the genotype × year interactions was also strong. Using this data and an existing genetic map, a quantitative trait loci (QTL) analysis was conducted. From four to seven QTL were detected for each trait except tuber flesh color, which was determined by a major QTL on chromosome III explaining 76.8% of the trait variance. Additionally, a minor QTL for flesh color was localized on chromosome II. For the other traits, significant QTL were detected: for tuber shape on chromosome X, for regularity of tuber shape on chromosome III, for eye depth on chromosome IV, and for tuber weight on chromosome I. Some detected QTL confirmed previous studies, but new ones were also identified.

from Genetics via xlomafota13 on Inoreader http://ift.tt/2GQEpnq
via IFTTT

2p24.2 (rs7552) is a susceptibility locus for nonsyndromic cleft lip with or without cleft palate in the Brazilian population

The population of Brazil is highly admixed, with each individual showing variable levels of Amerindian, European and African ancestry, which may interfere in the genetic susceptibility of known risk loci to nonsyndromic cleft lip with or without cleft palate (NSCL±P). Here we investigated 5 reported genome-wide loci for NSCL±P in an ancestry-structured case-control study containing 1,697 Brazilian participants (831 NSCL±P and 866 healthy controls). SNPs rs7552 in 2q24.2, rs8049367 in 16p13.3, rs1880646, rs7406226, rs9891446 in 17p13, rs1588366 in 17q23.2 and rs73039426 in 19q13.11 were genotyped using TaqMan allelic discrimination assays and genomic ancestry was estimated using a panel of 40 biallelic short insertion/deletion polymorphic markers informative of the Brazilian population. Logistic regression analysis of the single-markers revealed rs7552 in 2p24.2 as a susceptibility risk marker for NSCL±P, yielding an OR of 1.71 (95% CI: 1.31-2.24, p=9x10^-6) in the homozygous state. Several SNP-SNP interactions containing rs7552 reached significance after adjustment for multiple tests (both Bonferroni assumption and 1000 permutation test), with the most significant interaction involving the 3-loci among rs7552, rs9891446 and rs73039426 (p=6.1x10^-9 and p_{1000 permutation}=0.001). Our study is the first to support the association of rs7552 in 2p24.2 with NSCL±P in the highly admixed Brazilian population.

from Genetics via xlomafota13 on Inoreader http://ift.tt/2GQJLzl
via IFTTT

Regulatory network analysis of LINC00472, a long noncoding RNA downregulated by DNA hypermethylation in colorectal cancer

Colorectal cancer (CRC), one of the common malignant cancers in the world, is caused by accumulated alterations of genetic and epigenetic factors over a long period of time. Along with that protein-coding genes being identified as oncogenes or tumor suppressors in CRC, a number of lncRNAs have also been found to be associated with CRC. Considering the important regulatory role of lncRNAs, the first goal of this study was to identify CRC-associated lncRNAs from a public database. One such lncRNA, LINC00472, was verified to be downregulated in CRC cell lines and cancer tissues compared with adjacent tissues. In addition, the silencing of LINC00472 seemed to be caused by DNA hypermethylation at its promoter region. Furthermore, the expression of LINC00472 and DNA methylation of promoter were significantly correlated with clinicopathological features. And DNA hypermethylation of LINC00472 may serve as a better diagnostic biomarker than its expression for CRC. Finally, we predicted the functions of LINC00472 and constructed a regulatory network to found LINC00472 may be involved in cell cycle and cell proliferation processes. Our results may provide a clue to further research into the function and regulatory machinism of LINC00472 in CRC.

from Genetics via xlomafota13 on Inoreader http://ift.tt/2CrHBb9
via IFTTT

Stretch-induced Ca2+-independent ATP release in hippocampal astrocytes

Abstract

Astrocytic ATP release is essential for brain functions such as synaptic long-term potentiation for learning and memory. However, whether/how ATP is released via exocytosis remains hotly debated. All previous studies of non-vesicular ATP release have used indirect assays. In contrast, two recent papers report vesicular ATP release using more direct assays. In the present work, by using patch-clamped "ATP-sniffer-cells", we re-investigated astrocytic ATP release at single-vesicle resolution in hippocampal astrocytes. Following an "on-cell-like" mechanical stimulus of a single astrocyte, a Ca²⁺-independent single large non-quantal ATP release occurred, in contrast to the Ca²⁺-dependent multiple small quantal ATP release in a chromaffin cell. The mechanical stimulation-induced ATP release from an astrocyte was inhibited by either exposure to a selective antagonist or genetic knock-down of P2 × 7 receptor channels. Functional P2 × 7 channel were expressed in astrocytes in hippocampal brain slices. Thus, in addition to small quantal ATP release, larger non-quantal ATP release depends on P2 × 7 channels in astrocytes.

This article is protected by copyright. All rights reserved

from Physiology via xlomafota13 on Inoreader http://ift.tt/2HQe4aq
via IFTTT

Neural predictors of gait stability when walking freely in the real-world

Gait impairments during real-world locomotion are common in neurological diseases. However, very little is currently known about the neural correlates of walking in the real world and on which regions of the b...

from Rehabilitation via xlomafota13 on Inoreader http://ift.tt/2t0lV1P
via IFTTT