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Experimental Physiology

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https://www.readbyqxmd.com/read/28303677/examination-of-crispr-cas9-design-tools-and-the-effect-of-target-site-accessibility-on-cas9-activity
#1
Ciaran M Lee, Timothy H Davis, Gang Bao
The recent adaptation of the CRISPR/Cas9 system for targeted genome engineering has led to its widespread applications in many fields worldwide. In order to better understand the design rules of CRISPR/Cas9 systems, several groups have carried out large library-based screens leading to some insight into sequence preferences among highly active target sites. To facilitate CRISPR/Cas9 design these studies have spawned a plethora of gRNA design tools with algorithms based solely on direct or indirect sequence features...
March 16, 2017: Experimental Physiology
https://www.readbyqxmd.com/read/28294453/a-translational-approach-for-nmda-receptor-profiling-as-a-vulnerability-biomarker-for-depression-and-schizophrenia
#2
Handan Gunduz-Bruce, Joshua Kenney, Suravi Changlani, Aldo Peixoto, Ralitza Gueorguieva, Cheryl Leone, Nina Stachenfeld
Altered N-methyl-D-aspartate (NMDA) receptor activity and glutamate signaling may underlie the pathogenesis of both schizophrenia and depression in subgroups of patients. In schizophrenia, pharmacologic modeling, postmortem and imaging data suggest reduced NMDA signaling. In contrast, recent clinical trials demonstrating the efficacy of the NMDA antagonist ketamine in severely depressed patients suggest increased NMDA receptor signaling. We conducted a proof of concept study to assess whether there is any in vivo evidence for an inverse association in depression and schizophrenia with respect to the NMDA receptor function...
March 13, 2017: Experimental Physiology
https://www.readbyqxmd.com/read/28295786/stat3-potentiates-the-ability-of-airway-smooth-muscle-cells-to-promote-angiogenesis-by-regulating-vegf-signaling
#3
Jing Lv, Baohua Sun, Zhitao Mai, Mingming Jiang, Junfeng Du
Airway angiogenesis indicates the specific vascular structure remodeling that occurs in asthma. Airway smooth muscle (ASM) cells have been reported to be capable of promoting airway angiogenesis; however, the potential mechanism is yet not fully defined. Herein, we investigated the role of signal transducer and activator of transcription 3 (STAT3), in the progress of airway angiogenesis. Western blot analysis showed that STAT3 activation was aberrantly up-regulated in ASM tissues of patients with asthma and ASM cells that were exposed to cytokines to imitate the airway conditions in patients with asthma...
March 10, 2017: Experimental Physiology
https://www.readbyqxmd.com/read/28295755/evidence-for-a-functional-vasoconstrictor-role-for-atp-in-the-human-cutaneous-microvasculature
#4
James A Lang, Alex C Krajek, Kevin A Smaller
Noradrenaline is responsible for eliciting ∼60% of the reflex cutaneous vasoconstriction (VC) response in young adults, whereas the remainder is due to one or more unidentified coreleased sympathetic adrenergic neurotransmitter(s). Inconsistent evidence has placed neuropeptide Y in this role; however, other putative cotransmitters have yet to be tested. We hypothesize that ATP contributes to the reflex cutaneous VC response. Two protocols were conducted in young adults (n = 10); both involved the placement of three microdialysis (MD) probes in forearm skin and whole-body cooling (Tsk  = 30...
March 10, 2017: Experimental Physiology
https://www.readbyqxmd.com/read/28273684/stress-sensitive-arterial-hypertension-hemodynamic-changes-and-brain-metabolites-in-hypertensive-isiah-rats-mri-investigation
#5
A A Seryapina, O B Shevelev, M P Moshkin, A L Markel, A E Akulov
The study of early development of the arterial hypertension in association with emotional stress is of great importance for better understanding of etiolody and pathogenesis of the hypertensive disease. MRI technique was applied to evaluate the hemodynamic and brain metabolites changes in 1- and 3-Mo-old ISIAH rats (10 male rats) with stress-sensitive arterial hypertension and in control normotensive WAG rats (8 male rats). In the 3-Mo-old ISIAH rats, age-dependent increase in the blood pressure was associated with increased blood flow through the renal arteries and decreased blood flow in the lower part of abdominal aorta...
March 8, 2017: Experimental Physiology
https://www.readbyqxmd.com/read/28271571/gene-editing-for-skin-diseases-designer-nucleases-as-tools-for-gene-therapy-of-skin-fragility-disorders
#6
Oliver P March, Julia Reichelt, Ulrich Koller
The current treatment of inherited blistering skin diseases, such as epidermolysis bullosa (EB) is largely restricted to wound care and pain management. More effective therapeutic strategies are urgently required and targeting the genetic basis of these severe diseases is now within reach. Here we describe current gene editing tools and their potential to correct gene function in monogenetic blistering skin diseases. We present the features of the most frequently used gene editing techniques TALEN and CRISPR/Cas9, determining their preferential application under specific genetic conditions, including the type of mutational inheritance, the targeting site within the gene or the possibility to specifically target the mutation...
March 7, 2017: Experimental Physiology
https://www.readbyqxmd.com/read/28271565/prostacyclin-does-not-affect-sweating-but-induces-skin-vasodilatation-to-a-greater-extent-in-older-versus-younger-women-roles-of-no-and-kca-channels
#7
Naoto Fujii, Brendan D McNeely, Takeshi Nishiyasu, Glen P Kenny
We previously reported that prostacyclin induces cutaneous vasodilatation, but not sweating, in younger and older men. Further, we demonstrated that nitric oxide synthase (NOS) and calcium-activated potassium (KCa ) channels contribute to the prostacyclin-induced cutaneous vasodilatation in younger men, although these contributions are diminished in older men. Given the effects of ageing may differ between men and women, the above results cannot be simply applied to women. In this study, cutaneous vascular conductance (CVC) and sweat rate were evaluated in younger (22 ± 3 years) and older (55 ± 7 years) women (10 per group) at four intradermal forearm skin sites treated with either: (1) lactated Ringers without any drug (Control), (2) 10 mm L-NNA, a non-specific NOS inhibitor, (3) 50 mm tetraethylammonium (TEA), a non-specific KCa channel blocker, or (4) 10 mm L-NNA + 50 mm TEA...
March 7, 2017: Experimental Physiology
https://www.readbyqxmd.com/read/28261888/endurance-performance-in-well-trained-mice-is-enhanced-by-short-duration-intermittent-hypoxia-via-improved-muscle-fatty-acid-metabolism
#8
Junichi Suzuki
The author previously reported that short-duration intermittent hypoxia had additive effects on improvements in endurance capacity by enhancing fatty acid metabolism. The present study was designed to investigate the effects of short-duration intermittent hypoxia on endurance capacity in well-trained mice. Mice in the training group were housed in a cage with a wheel activity device for 7 weeks from 5 weeks old. Voluntary running markedly increased maximal exercise capacity (by 5.9-fold). Trained mice were then subjected to either normoxic treadmill training (Tr) or training with short-duration intermittent hypoxia (12% O2 for 15 min, 20...
March 5, 2017: Experimental Physiology
https://www.readbyqxmd.com/read/28240387/linear-and-nonlinear-contributions-to-oxygen-transport-and-utilization-during-moderate-random-exercise-in-humans
#9
T Beltrame, R L Hughson
The assumption of the aerobic system linearity implies that the pulmonary oxygen uptake (pV̇O2) dynamic during exercise transitions present a first-order characteristic. The main objective of this study was to test the linearity of the oxygen delivery-utilization balance during random moderate exercise. The cardiac output (Q̇) and deoxygenated hemoglobin (HHb) were measured to infer about the central and local O2 availability, respectively. Thirteen healthy men performed two consecutive pseudorandom binary sequence cycling exercises followed by an incremental protocol...
February 27, 2017: Experimental Physiology
https://www.readbyqxmd.com/read/28239923/we-know-that-horses-sweat-and-men-perspire-but-do-ladies-merely-glow
#10
Daniel Gagnon
For some time, the euphemism "horses sweat, men perspire, but ladies merely glow" was scientifically supported. Initial studies examining gender differen0063es in sweat production generally observed that women sweat less than men during heat exposure (i.e. they merely glow). This article is protected by copyright. All rights reserved.
February 26, 2017: Experimental Physiology
https://www.readbyqxmd.com/read/28231604/variations-in-body-morphology-explain-gender-differences-in-thermoeffector-function-during-compensable-heat-stress
#11
Sean R Notley, Joonhee Park, Kyoko Tagami, Norikazu Ohnishi, Nigel A S Taylor
Gender is sometimes thought to independently modulate cutaneous vasomotor and sudomotor function during heat exposure. Nevertheless, it was hypothesised that, when assessed during compensable exercise that evoked equal heat-loss requirements across participants, gender differences in those thermoeffectors would be explained by variations in the ratio between body surface area and mass (specific surface area). To evaluate that possibility, vasomotor and sudomotor functions were assessed in sixty individuals (36 males, 24 females) with widely varying (overlapping) specific surface areas (range: 232...
February 23, 2017: Experimental Physiology
https://www.readbyqxmd.com/read/28205317/oxidative-stress-and-immunosenescence-in-spleen-of-obese-mice-can-be-reversed-by-2-hydroxyoleic-acid
#12
Alina Gheorghe, Fátima Pérez de Heredia, Caroline Hunsche, Noemí Redondo, Ligia Esperanza Díaz, Oskarina Hernández, Ascensión Marcos, Mónica De la Fuente
We aimed to investigate the effects of obesity on oxidative stress and leukocyte function in spleen of mice, and to assess whether supplementation with 2-hydroxyoleic acid (2-OHOA) or n-3 polyunsaturated fatty acids (PUFA) could reverse those effects. Female ICR/CD1 mice (8 weeks old, n = 24) received an obesogenic diet (22% fat for 4 weeks and 60% fat for 14 weeks). After 6 weeks, mice were split in three groups (n = 8/group): no supplementation, 2-OHOA supplementation (1500 mg kg(-1) ) and n-3 PUFA supplementation (EPA + DHA, 3000 mg kg(-1) diet)...
February 15, 2017: Experimental Physiology
https://www.readbyqxmd.com/read/28205264/the-influence-of-patellar-tendon-and-muscle-tendon-unit-stiffness-on-quadriceps-explosive-strength-in-man
#13
Garry J Massey, Thomas G Balshaw, Thomas M Maden-Wilkinson, Neale A Tillin, Jonathan P Folland
The influence of musculotendinous tissue stiffness on contractile rate of torque development (RTD) remains opaque. This study examined the relationships between both patellar tendon (PT) and vastus lateralis (VL) muscle-tendon unit (MTU) stiffness, and voluntary and evoked knee extension RTD. Fifty-two healthy untrained males completed duplicate laboratory sessions. Absolute and relative RTD was measured at 50 Nm/25%MVT increments from onset and sequentially during explosive voluntary and evoked octet (supramaximal stimulation: [8 pulses at 300 Hz]) isometric contractions...
February 15, 2017: Experimental Physiology
https://www.readbyqxmd.com/read/28194830/parasternal-intercostal-muscle-activity-during-methacholine-induced-bronchoconstriction
#14
Victoria MacBean, Claire L Pringle, Alan C Lunt, Keith D Sharp, Ashraf Ali, Anne Greenough, John Moxham, Gerrard F Rafferty
Neural respiratory drive, measured via the parasternal intercostal electromyogram (EMGpara), provides a non-invasive index of the load-capacity balance of the respiratory muscle pump. Previous studies in patients with obstructive lung disease have shown strong relationships between EMGpara and the extent of both airflow obstruction and hyperinflation. The relative influence of the two factors has not, however, been described. Airflow obstruction was induced via methacholine challenge testing in twenty-five adult humans...
February 14, 2017: Experimental Physiology
https://www.readbyqxmd.com/read/28194824/left-intraventricular-pressure-gradients-improvement-after-aortic-valve-replacement-in-aortic-stenosis-patients
#15
Miguel Guerra, Pedro Mendes-Ferreira, Rui Adão, Eulália Pereira, Manuela Vieira, André P Lourenço, Carmen Brás-Silva, Pedro Bastos, Luís Vouga, Adelino F Leite-Moreira
The present study was conducted to characterize left intraventicular pressure gradients, a marker of normal cardiac function, in patients with severe aortic stenosis, a condition which interferes with ventricular filling and emptying. In 10 patients (4 male; mean age 71.3 ± 4.8 years old) undergoing aortic valve replacement, 2 high-fidelity pressure catheters were inserted inside the left ventricle cavity through an apical puncture and positioned in the apex and outflow-tract below the aortic valve. Pressures were continuously acquired and gradients were calculated as apical minus outflow-tract pressure, before and immediately after aortic valve replacement...
February 14, 2017: Experimental Physiology
https://www.readbyqxmd.com/read/28192862/long-term-dietary-quercetin-enrichment-as-a-cardioprotective-countermeasure-in-mdx-mice
#16
Christopher Ballmann, Thomas Denney, Ronald J Beyers, Tiffany Quindry, Matthew Romero, Joshua T Selsby, John C Quindry
Duchenne Muscular Dystrophy (DMD) causes declines in cardiac health resulting in premature mortality. As a potential countermeasure, quercetin is a polyphenol possessing inherent anti-inflammatory and antioxidant effects that activate proliferator-activated γ coactivator 1α (PGC-1α) increasing mitochondrial biogenesis protein abundance. We investigated the extent to which lifelong 0.2% dietary quercetin enrichment attenuates dystrophic cardiopathology in mdx mice. Dystrophic animals were fed quercetin or control diet for 12 months while control C57 mice were fed a control diet...
February 13, 2017: Experimental Physiology
https://www.readbyqxmd.com/read/28166612/acute-exercise-activates-p38-mapk-and-increases-the-expression-of-telomere-protective-genes-in-cardiac-muscle
#17
Andrew T Ludlow, Laila Gratidao, Lindsay W Ludlow, Espen E Spangenburg, Stephen M Roth
Age is the greatest risk factor for cardiovascular disease. Telomere length is shorter in the hearts of aged mice compared to young mice, and short telomere length has been associated with an increased risk of cardiovascular disease. One year of voluntary wheel running exercise attenuates the age-associated loss of telomere length and results in altered gene expression of telomere length maintaining and genome stabilizing proteins in heart tissue of mice. Understanding the early adaptive response of the heart to an endurance exercise bout is paramount to understanding the impact of endurance exercise on heart tissue and cells...
February 6, 2017: Experimental Physiology
https://www.readbyqxmd.com/read/28155247/flow-mediated-dilation-assessment-in-the-superficial-femoral-artery-using-a-sustained-shear-stress-stimulus-via-calf-plantar-flexion-exercise
#18
T J King, S M Schmitter, K E Pyke
The superficial femoral artery (SFA) is susceptible to vascular disease, and a technique to assess flow mediated dilation (FMD) in this vessel in response to a sustained shear stress stimulus could provide important information about endothelial function. PURPOSE: To establish the ability of a newly designed SFA leg exercise-FMD (LEX-FMD) technique to produce sustained elevations in shear rate which stimulate FMD, and to determine the repeat trial stability of the FMD response. METHODS: SFA FMD stimulated by reactive hyperemia (RH) and calf plantar-flexion exercise (LEX) was assessed via ultrasound in 19 healthy men (n = 10) and women (n = 9)...
February 2, 2017: Experimental Physiology
https://www.readbyqxmd.com/read/28150462/tongxinluo-exerts-protective-effects-via-anti-apoptotic-and-pro-autophagic-mechanisms-by-activating-ampk-pathway-in-infarcted-rat-hearts
#19
Qing Li, Na Li, He-He Cui, Xia-Qiu Tian, Chen Jin, Gui-Hao Chen, Yue-Jin Yang
Tongxinluo (TXL) has been demonstrated to have a protective role during ischemia/reperfusion after acute myocardial infarction (AMI), but the long-term effects and the underlying mechanisms are still unknown. This study aimed to investigate whether TXL could have an effect on apoptosis or autophagy of cardiomyocytes through the AMP-activated protein kinase (AMPK) pathway. Male, Sprague-Dawley rats (n = 75) were randomly divided to sham, control, TXL (4 mg kg(-1)  d(-1) orally), compound C (intraperitoneal injection at 10 mg kg(-1)  d(-1) ), and TXL + compound C groups...
February 1, 2017: Experimental Physiology
https://www.readbyqxmd.com/read/28139019/from-single-cells-single-columns-to-cortical-networks-dendritic-excitability-coincidence-detection-and-synaptic-transmission-in-brain-slices-and-brains
#20
Bert Sakmann
While patch pipettes were initially designed to record extracellularly elementary current events from muscle and neuron membrane, the whole-cell (eg Sakmann, 1992) and loose cell-attached recording configurations proved to be useful tools for examining signaling within and between nerve cells. In this Paton Lecture I will summarize first work on electrical signaling within single neurons, describing communication between its dendritic compartments, soma and nerve terminals via forward and backward propagating action potentials...
January 31, 2017: Experimental Physiology
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