Miracle-dz/UniFAR-FTUs huggingface dataset:
Brainstem oxytocinergic modulation of heart rate control in rats: effects of hypertension and exercise training

Oxytocinergic brainstem projections participate in the autonomic control of the circulation. We investigated the effects of hypertension and training on cardiovascular parameters after oxytocin (OT) receptor blockade within the nucleus tractus solitarii (NTS) and NTS OT and OT receptor expression. Male spontaneously hypertensive rats (SHR) and Wistar–Kyoto (WKY) rats were trained (55% of maximal exercise capacity) or kept sedentary for 3 months and chronically instrumented (NTS and arterial cannulae). Mean arterial blood pressure (MAP) and heart rate (HR) were measured at rest and during an acute bout of exercise after NTS pretreatment with vehicle or OT antagonist (20 pmol of OT antagonist (200 nl of vehicle)–1). Oxytocin and OT receptor were quantified (35S‐oligonucleotide probes, in situ hybridization) in other groups of rats. The SHR exhibited high MAP and HR (P < 0.05). Exercise training improved treadmill performance and reduced basal HR (on average −11%) in both groups, but did not change basal MAP. Blockade of NTS OT receptor increased exercise tachycardia only in trained groups, with a larger effect on trained WKY rats (+31 ± 9 versus+12 ± 3 beats min−1 in the trained SHR). Hypertension specifically reduced NTS OT receptor mRNA density (–46%versus sedentary WKY rats, P < 0.05); training did not change OT receptor density, but significantly increased OT mRNA expression (+2.5‐fold in trained WKY rats and +15% in trained SHR). Concurrent hypertension‐ and training‐induced plastic (peptide/receptor changes) and functional adjustments (HR changes) of oxytocinergic control support both the elevated basal HR in the SHR group and the slowing of the heart rate (rest and exercise) observed in trained WKY rats and SHR.
A respiratory response to the activation of the muscle metaboreflex during concurrent hypercapnia in man

In this study, we aimed to assess the ventilatory and cardiovascular responses to the combined activation of the muscle metaboreflex and the ventilatory chemoreflex, achieved by postexercise circulatory occlusion (PECO) and euoxic hypercapnia (end‐tidal partial pressure of CO2 7 mmHg above normal), respectively. Eleven healthy subjects (4 women and 7 men; 29 ± 4.4 years old; mean ±s.d.) undertook the following four trials, in random order: 2 min of isometric handgrip exercise followed by 2 min of PECO with hypercapnia; 2 min of isometric handgrip exercise followed by 2 min of PECO while breathing room air; 4 min of rest with hypercapnia; and 4 min of rest while breathing room air. Ventilation was significantly increased during exercise in both the hypercapnic (+3.17 ± 0.82 l min−1) and the room air breathing trials (+2.90 ± 0.26 l min−1; all P < 0.05). During PECO, ventilation returned to pre‐exercise levels when breathing room air (+0.52 ± 0.37 l min−1; P > 0.05), but it remained elevated during hypercapnia (+3.77 ± 0.23 l min−1; P < 0.05). The results indicate that the muscle metaboreflex stimulates ventilation with concurrent chemoreflex activation. These findings have implications for disease states where effort intolerance and breathlessness are linked.
Experimental Physiology - Research Paper A hypoxia complement differentiates the muscle response to endurance exercise

Metabolicstressisbelievedtoconstituteanimportantsignalfortraining-inducedadjustments of gene expression and oxidative capacity in skeletal muscle. We hypothesized that the effects of endurance training on expression of muscle-relevant transcripts and ultrastructure would be specifically modified by a hypoxia complement during exercise due to enhanced glycolytic strain. Endurance training of untrained male subjects in conditions of hypoxia increased subsarcolemmal mitochondrial density in the recruited vastus lateralis muscle and power output in hypoxia more than training in normoxia, i.e. 169 versus 91% and 10 versus 6%, respectively, and tended to differentially elevate sarcoplasmic volume density (42 versus 20%, P =0.07). The hypoxia-specific ultrastructural adjustments with training corresponded to differential regulation of the muscle transcriptome by single and repeated exercise between both oxygenation conditions. Fine-tuning by exercise in hypoxia comprised gene ontologies connectedtoenergyprovisionbyglycolysisandfatmetabolisminmitochondria,remodelling of capillaries and the extracellular matrix, and cell cycle regulation, but not fibre structure. In the untrained state, the transcriptome response during the first 24 h of recovery from a single exercise bout correlated positively with changes in arterial oxygen saturation during exercise and negatively with blood lactate. This correspondence was inverted in the trained state.Theobservationshighlightthattheexpressionresponseofmyocellularenergypathways to endurance work is graded with regard to metabolic stress and the training state. The exposed mechanistic relationship implies that the altitude specificity of improvements in aerobic performance with a ‘living low‐training high’ regime has a myocellular basis.
Proteomic characterization of the abdominal ganglion of Aplysia californica—A protein resource for neuroscience

Aplysia californica (AC) is a widely used model for testing learning and memory. Although ESTs have been generated, proteomics studies on AC proteins are limited. Studies at the protein level, however, are mandatory, not only due to the fact that studies at the nucleic acid level are not allowing conclusions about PTMs. A gel‐based proteomics method was therefore applied to carry out protein profiling in abdominal ganglia from AC. Abdominal ganglia were extirpated, proteins extracted and run on 2DE with subsequent in‐gel digestion with trypsin, chymotrypsin, and partially by subtilisin. Peptides were identified using a nano‐LC‐ESI‐LTQ‐FT‐mass spectrometer. MS/MS data were analyzed by searching the NCBI nonredundant public AC EST database and the NCBI nonredundant public AC protein database. A total of 477 different proteins represented by 363 protein spots were detected and were assigned to different protein pathways as for instance signaling (receptors, protein kinases, and phosphatases), metabolism, protein synthesis, handling and degradation, cytoskeleton and structural, oxido‐redox, heat shock and chaperone, hypothetical, predicted and unnamed proteins. The generation of a protein map of soluble proteins shows the existence of so far hypothetical and predicted proteins and is allowing and challenging further work at the protein level, in particular in the field of neuroscience.
The acetylproteome of Gram‐positive model bacterium Bacillus subtilis

Nε‐lysine acetylation, a reversible and highly regulated PTM, has been shown to occur in the model Gram‐negative bacteria Escherichia coli and Salmonella enterica. Here, we extend this acetylproteome analysis to Bacillus subtilis, a model Gram‐positive bacterium. Through anti‐acetyllysine antibody‐based immunoseparation of acetylpeptides followed by nano‐HPLC/MS/MS analysis, we identified 332 unique lysine‐acetylated sites on 185 proteins. These proteins are mainly involved in cellular housekeeping functions such as central metabolism and protein synthesis. Fifity‐nine of the lysine‐acetylated proteins showed homology with lysine‐acetylated proteins previously identified in E. coli, suggesting that acetylated proteins are more conserved. Notably, acetylation was found at or near the active sites predicted by Prosite signature, including SdhA, RocA, Kbl, YwjH, and YfmT, indicating that lysine acetylation may affect their activities. In 2‐amino‐3‐ketobutyrate CoA ligase Kbl, a class II aminotransferase, a lysine residue involved in pyridoxal phosphate attachment was found to be acetylated. This data set provides evidence for the generality of lysine acetylation in eubacteria and opens opportunities to explore the consequences of acetylation modification on the molecular physiology of B. subtilis.
Dynamic characteristics of heart rate control by the autonomic nervous system in rats

We estimated the transfer function of autonomic heart rate (HR) control by using random binary sympathetic or vagal nerve stimulation in anaesthetized rats. The transfer function from sympathetic stimulation to HR response approximated a second‐order, low‐pass filter with a lag time (gain, 4.29 ± 1.55 beats min−1 Hz−1; natural frequency, 0.07 ± 0.03 Hz; damping coefficient, 1.96 ± 0.64; and lag time, 0.73 ± 0.12 s). The transfer function from vagal stimulation to HR response approximated a first‐order, low‐pass filter with a lag time (gain, 8.84 ± 4.51 beats min−1 Hz−1; corner frequency, 0.12 ± 0.06 Hz; and lag time, 0.12 ± 0.08 s). These results suggest that the dynamic characteristics of HR control by the autonomic nervous system in rats are similar to those of larger mammals.
Optogenetic probing of functional brain circuitry

Recently developed optogenetic technologies offer the promise of high‐speed mapping of brain circuitry. Genetically targeted light‐gated channels and pumps, such as channelrhodopsins and halorhodopsin, allow optical control of neuronal activity with high spatial and temporal resolution. Optogenetic probes of neuronal activity, such as Clomeleon and Mermaid, allow light to be used to monitor the activity of a genetically defined population of neurons. Combining these two complementary sets of optogenetic probes will make it possible to perform all‐optical circuit mapping. Owing to the improved efficiency and higher speed of data acquisition, this hybrid approach should enable high‐throughput mapping of brain circuitry.
Insights into the Epidemiology of Postmenopausal Osteoporosis: The Women's Health Initiative

Abstract Osteoporosis and its associated increased risk for fragility fracture is one of the most disabling consequences of aging in women. To successfully reduce the public health burden of this pervasive disease, it is necessary to develop strategies that permit the earlier identification of women at risk for fracture and ensure that preventive interventions to reduce the risk for fracture are both safe and effective. The Women's Health Initiative offers the unprecedented opportunity to systematically address both of these issues. Eleven clinically available risk factors (age, race/ethnicity, self-reported health, weight, height, physical activity, parental hip fracture, fracture history after age 54, current smoking, corticosteroid use, and history of treated diabetes), have been identified to predict 5-year hip fracture risk in white women. Two of these factors (age and fracture history) also predict risk for total fractures in women irrespective of race-ethnicity. Biomarkers including low vitamin D or bioavailable testosterone and/or high cystatin C, pro-inflammatory cytokines, osteoprotegerin and sex hormone-binding globulin also predict risk for hip fracture independent of clinical risk factors. Two cornerstones of therapy for postmenopausal osteoporosis-postmenopausal hormone therapy and calcium plus vitamin D supplementation- were rigorously studied. Estrogen with or without a progestin was effective at preventing bone loss and reducing risk for hip, clinical vertebral and total fractures but the balance of risks and benefits failed to show an overall benefit of taking estrogen-alone or estrogen plus progestin as a preventive strategy for skeletal health. Calcium plus vitamin D supplementation also demonstrated a small but significant favorable effect on hip bone density but in contrast, the modest effect did not translate into a significant reduction in the risk of fractures in intent-to-treat analyses. Data such as these have helped to lay a foundation for the more effective management of postmenopausal osteoporosis.
Human investigations into the arterial and cardiopulmonary baroreflexes during exercise

After considerable debate and key experimental evidence, the importance of the arterial baroreflex in contributing to and maintaining the appropriate neural cardiovascular adjustments to exercise is now well accepted. Indeed, the arterial baroreflex resets during exercise in an intensity‐dependent manner to continue to regulate blood pressure as effectively as at rest. Studies have indicated that the exercise resetting of the arterial baroreflex is mediated by both the feedforward mechanism of central command and the feedback mechanism associated with skeletal muscle afferents (the exercise pressor reflex). Another perhaps less appreciated neural mechanism involved in evoking and maintaining neural cardiovascular responses to exercise is the cardiopulmonary baroreflex. The limited information available regarding the cardiopulmonary baroreflex during exercise provides evidence for a role in mediating sympathetic nerve activity and blood pressure responses. In addition, recent investigations have demonstrated an interaction between cardiopulmonary baroreceptors and the arterial baroreflex during dynamic exercise, which contributes to the magnitude of exercise‐induced increases in blood pressure as well as the resetting of the arterial baroreflex. Furthermore, neural inputs from the cardiopulmonary baroreceptors appear to play an important role in establishing the operating point of the arterial baroreflex. This symposium review highlights recent studies in these important areas indicating that the interactions of four neural mechanisms (central command, the exercise pressor reflex, the arterial baroreflex and cardiopulmonary baroreflex) are integral in mediating the neural cardiovascular adjustments to exercise.
Ageing‐dependent remodelling of ion channel and Ca2+ clock genes underlying sino‐atrial node pacemaking

The function of the sino‐atrial node (SAN), the pacemaker of the heart, is known to decline with age, resulting in pacemaker disease in the elderly. The aim of the study was to investigate the effects of ageing on the SAN by characterizing electrophysiological changes and determining whether changes in gene expression are involved. In young and old rats, SAN function was characterized in the anaesthetized animal, isolated heart and isolated right atrium using ECG and action potential recordings; gene expression was characterized using quantitative PCR. The SAN function declined with age as follows: the intrinsic heart rate declined by 18 ± 3%; the corrected SAN recovery time increased by 43 ± 13%; and the SAN action potential duration increased by 11 ± 3% (at 75% repolarization). Gene expression in the SAN changed considerably with age, e.g. there was an age‐dependent decrease in the Ca2+ clock gene, RYR2, and changes in many ion channels (e.g. increases in Nav1.5, Navβ1 and Cav1.2 and decreases in Kv1.5 and HCN1). In conclusion, with age, there are changes in the expression of ion channel and Ca2+ clock genes in the SAN, and the changes may provide a partial explanation for the age‐dependent decline in pacemaker function.
Study of the hormones controlling food intake (leptin and agouti related protein "AgRP") in cannabis smokers.

Background: Leptin is an adipocyte derived hormone which is thought to be a key regulator of food intake and body weight. Agouti-related protein also called Agouti-related peptide (AgRP) is a neuropeptide produced in the brain by the AgRP/NPY neuron. It is one of the most potent and long-lasting of appetite stimulators. The appetite stimulating effects of AgRP are inhibited by the hormone leptin. There is a public perception that exposure to cannabis produces an increase of appetite (a phenomenon referred to as the 'munchies'). This phenomenon needs an exploration of the role of the endocannabinoid system in the regulation of obesity and associated metabolic syndrome Aim: This study aimed to find out the food intake style, of subjects smoking cannabis by studing the relationship between the most two popular hormones controlling food intake (leptin hormone, and agouti related protein hormone) compared with healthy subjects. Methods: The study compared two groups of personells; the test group (Group II) included ten males aged 37.40±2.67 years (mean age ±SD) with positive 9-carboxyTetrahydrocanabinol (THC) detected in their urine by qualitative analysis using Gas Chromatography-Mass spectrometry. And control group (GroupI) included ten healthy males aged 38.67±2.35 years (mean age ± SD) as volunteers with negative 9-carboxyOriginal Research Article British Journal of Medicine & Medical Research, 4(29): 4844-4854, 2014 4845 Tetrahydrocanabinol (THC). In both groups, age and body mass index (BMI) were matched, diabetic subjects were excluded. Plasma leptin concentration was measured by quantitative radio immunoassay (RIA). Human plasma AgRP hormone was quantitatively measured by using a kit supplied from Quantikine R&D systems INC. Results: In group I (GI), there was an increase in mean plasma leptin concentrations ±SD (6.39±1.93) ng/ml, than that found, in group II (GII) (4.49±1.40) ng/ml, but it's statistically insignificant (P>0.05). There was an elevation, in mean plasma AgRP concentrations (27.77±2.17) pg/ml in GII, comparing with mean plasma AgRP concentrations (25.84±1.93) pg/ml, in GI but it's statistically insignificant (P>0.05). There was a statistically significant inversely correlation between plasma leptin concentrations and plasma AgRP concentrations in GI (P 0.05). Conclusion: The relationship between plasma leptin concentrations and plasma AgRP concentrations affected by smoking cannabis, and that may change the mechanism of food intake in cannabis smokers.
Extracellular vesicles as prospective carriers of oncogenic protein signatures in adult and paediatric brain tumours

Extracellular vesicles (EVs), including exosomes, act as biological effectors and as carriers of oncogenic signatures in human cancer. The molecular composition and accessibility of EVs in biofluids open unprecedented diagnostic opportunities in malignancies where tumour tissue is difficult to sample, especially in primary and metastatic brain tumours. The ongoing genetic discovery of driver mutations defines the ever increasing numbers of distinct molecular subtypes of brain tumours (orphan diseases), a complexity that may soon be translated into alterations in functional proteins and their oncogenic networks. This may likely be extended to real time changes engendered by the disease progression, tumour heterogeneity, inter‐individual variations and therapeutic responses. Meeting these challenges through EV analysis is dependent on technological progress in such areas as generation of mutation‐ and phospho‐specific antibodies, antibody array platforms, nanotechnology, microfluidics, NMR spectroscopy, MS and MRM approaches of quantitative proteomics, which should not be underestimated. Still, vesiculation emerges as a unique process that could be harnessed for the benefit of more individualised patient care.
Populus cathayana males are less affected than females by excess manganese: Comparative proteomic and physiological analyses

The comprehension of sexually different responses in dioecious plants to excess manganese (Mn) stress requires molecular explanation. Physiological and proteomic changes in leaves of Populus cathayana males and females were analyzed after 4 wk of exposure to Mn stress. Under excess Mn conditions, shoot height and photosynthesis decreased more in females than in males. Females also showed severe browning and subcellular damage, higher Mn2+ absorption, and different antioxidant enzyme activities compared with males. There were ten differently regulated protein spots induced by excess Mn stress. They were mainly related to photosynthesis, ROS cleaning, and cell signaling associated to ROS, plant cell death, heat shock, cell defense and rescue, and gene expression and regulation. Variation in protein expression between the sexes clearly showed that males have evolved more efficient photosynthesis capacity, more stable gene expression and regulation, and better cell defense and rescue to prevent further injury under excess Mn stress.
High skin temperature and hypohydration impair aerobic performance

This paper reviews the roles of hot skin (>35°C) and body water deficits (>2% body mass; hypohydration) in impairing submaximal aerobic performance. Hot skin is associated with high skin blood flow requirements and hypohydration is associated with reduced cardiac filling, both of which act to reduce aerobic reserve. In euhydrated subjects, hot skin alone (with a modest core temperature elevation) impairs submaximal aerobic performance. Conversely, aerobic performance is sustained with core temperatures >40°C if skin temperatures are cool‐warm when euhydrated. No study has demonstrated that high core temperature (∼40°C) alone, without coexisting hot skin, will impair aerobic performance. In hypohydrated subjects, aerobic performance begins to be impaired when skin temperatures exceed 27°C, and even warmer skin exacerbates the aerobic performance impairment (–1.5% for each 1°C skin temperature). We conclude that hot skin (high skin blood flow requirements from narrow skin temperature to core temperature gradients), not high core temperature, is the ‘primary’ factor impairing aerobic exercise performance when euhydrated and that hypohydration exacerbates this effect.
Shotgun proteomics study of early biofilm formation process of Acidithiobacillus ferrooxidans ATCC 23270 on pyrite

Acidithiobacillus ferrooxidans is a chemolithoautotrophic, mesophilic Gram‐negative bacterium able to oxidize ferrous iron, sulfur, and metal sulfides. It forms monolayer biofilms where extracellular polymeric substances are essential for cell attachment and metal sulfide leaching. High‐throughput proteomics has been applied to study the early process of biofilm formation on pyrite by At. ferrooxidans ATCC 23270. After 24 h contact with the mineral, planktonic and sessile (biofilm) cell subpopulations were separated and proteins extracted. In total, 1319 proteins were detected in both samples. Sixty‐two of these were found to be increased in biofilms. Additionally, 25 proteins were found to be decreased in the biofilm cell subpopulation. Three transcriptional factors were found to be increased or decreased among both cell subpopulations, suggesting their potential involvement in the regulation of these processes. Although no significant differences were observed for the known proteins related to ferrous iron and sulfur oxidation pathways among both cell subpopulations, the results presented here show that the early steps of At. ferrooxidans biofilm formation consist of a set of metabolic adaptations following cell attachment to the mineral surface. Functions such as extracellular polymeric substances biosynthesis seem to be pivotal. This first high‐throughput proteomic study may also contribute to the annotation of several unknown At. ferrooxidans proteins found.