Datasets from a ground based model of microgravity

Recherche Data Gouv repositoryData presentation Sequential 11 day data of a murin model for hindlimb suspension subdivided as a 3-day control period, a 5-day suspension period, a 2-day recovery period and a brief re-suspension. Physiological parameters (Sys(mmHg):Pressure, Dia(mmHg):Pressure, Mean(mmHg):Pressure, +dP/dt(mmHg/ms):Pressure, -dP/dt(mmHg/ms):Pressure, HR(bpm):Pressure, HR(bpm):ECG, RR-I(ms):ECG, R-H(mV):ECG, QRS(ms):ECG, QT-I(ms):ECG, QTcb(ms):ECG, QTcf(ms):ECG, QTcv(ms):ECG, T_NPMN(Celsius):Temp, A_NPMN(Counts):Activity) are provided as two-hour time bins datasets from HD-X11 transmitters (Data Science International®, DSI, Saint Paul MN, USA) and telemetric receivers (RPC-1 PhysioTelTM Receivers, DSI). Research purpose It remains unclear how the autonomic nervous system adapts to short and long duration missions. On board studies are limited due to high costs and difficulties in obtaining data during missions; therefore, our data is mainly from ground-based models. Yet, the hemodynamic and autonomic responses during simulated microgravity using these models remain controversial. The controversy is likely rooted in the heterogeneity between species, the differences in both the duration of microgravity exposure as well as the choice of time points for recorded measures. We sought to clarify various controversial aspects of these forms of experiments by devising a murine hindlimb unloading (HU) model with continuous monitoring of relevant parameters. We aimed to define the kinetics of cardiovascular adaptation and recovery using a murine HU model during three phases over 10 days: 3 days of control, 5 days of HU and 2 days of recovery. Using implantable radio telemetry devices, we continuously collected data on mouse subcutaneous temperature and locomotor activity, as well as cardiac parameters, arterial blood pressure (ABP), heart rate (HR). The cardiac parameters were further exploited to calculate heart rate variability (HRV) and baroreflex sensitivity (BRS). We also performed complementary experiments on 6 subjects to monitor temperature fluctuations. We found that HU induced an immediate, dramatic and persistent decrease in locomotor activity and temperature (subcutaneous and central recorded temperature). On the other hand, the cardiac response was varied. We observed an initial bradycardia associated with an increase in vagal activity and baroreflex sensitivity together with a decrease in water intake. These findings indicate early adaptation to fluid redistribution. Analyses of the complete data set revealed effects on cardiovascular circadian rhythms during HU that are exacerbated during the recovery phase. Our investigation with continuous monitoring has both provided a degree of clarity with regard to the conflicting information in the literature and provided us with insights into how to better design these types of experiments in the future

Analysis of acoustic emissions recorded during a mine-by experiment in an underground research laboratory in clay shales

International audienceDuring a mine-by experiment performed at the Mont Terri Underground Research Laboratory located at the transition between the sandy and the shaly facies of the Opalinus Clay formation, excavation induced micro-acoustic events were recorded in the so-called Gallery 08 (the EZ-G experiment). A first cluster of events occurred in the vicinity of the eastern sidewall of Gallery 08, and a second cluster was observed ahead of the advancing tunnel face. For each recorded micro-acoustic event (AE), all located in the sandy facies of the Opalinus Clay formation, the total stresses associated with the onset of inelastic deformations were estimated using a three-dimensional numerical model. The numerical analysis is based on the assumption that the rock mass behavior in the vicinity of the excavation is essentially elastic before the stress redistribution causes damage evidenced by the triggered AE activity. For the cluster located at the tunnel sidewall, the source mechanism analysis reveals the predominance of extensional failure (tensile) events. The numerical analysis of each individual micro-acoustic event suggests that the differential stresses at the onset of damage range between 3 and 10 MPa. These values are in reasonable agreement with crack initiation thresholds obtained in the laboratory from samples of the various sub-facies types of the sandy facies in the Opalinus Clay formation, which range between 2 and 18 MPa. For the cluster located ahead of the tunnel face, the source mechanism analysis indicates the predominance of local shear failure events. This is consistent with observed shear dislocations on bedding planes within weak beds in the sandy facies that have similar strength properties as the shaly facies. Thus, the modelled shear and total normal stresses acting across the average bedding plane orientation at each event location were modelled and used to estimate the in situ shear strength along the bedding planes. The model suggests a friction angle of 33.4° and a cohesion of 0.43 MPa. The results are overall consistent with the bedding plane strength obtained through undrained direct shear tests on specimens of the shaly facies, suggesting that the observed weak beds with a strength similar to the shaly facies govern the behavior at the tunnel face

Autonomic Nervous System Adaptation and Circadian Rhythm Disturbances of the Cardiovascular System in a Ground-Based Murine Model of Spaceflight

Whether in real or simulated microgravity, Humans or animals, the kinetics of cardiovascular adaptation and its regulation by the autonomic nervous system (ANS) remain controversial. In this study, we used hindlimb unloading (HU) in 10 conscious mice. Blood pressure (BP), heart rate (HR), temperature, and locomotor activity were continuously monitored with radio-telemetry, during 3 days of control, 5 days of HU, and 2 days of recovery. Six additional mice were used to assess core temperature. ANS activity was indirectly determined by analyzing both heart rate variability (HRV) and baroreflex sensitivity (BRS). Our study showed that HU induced an initial bradycardia, accompanied by an increase in vagal activity markers of HRV and BRS, together with a decrease in water intake, indicating the early adaptation to fluid redistribution. During HU, BRS was reduced; temperature and BP circadian rhythms were altered, showing a loss in day/night differences, a decrease in cycle amplitude, a drop in core body temperature, and an increase in day BP suggestive of a rise in sympathetic activity. Reloading induced resting tachycardia and a decrease in BP, vagal activity, and BRS. In addition to cardiovascular deconditioning, HU induces disruption in day/night rhythmicity of locomotor activity, temperature, and BP

Galanin enhances systemic glucose metabolism through enteric Nitric Oxide Synthase-expressed neurons.

Objective: Decreasing duodenal contraction is now considered as a major focus for the treatment of type 2 diabetes. Therefore, identifying bioactive molecules able to target the enteric nervous system, which controls the motility of intestinal smooth muscle cells, represents a new therapeutic avenue. For this reason, we chose to study the impact of oral galanin on this system in diabetic mice. Methods: Enteric neurotransmission, duodenal contraction, glucose absorption, modification of gutebrain axis, and glucose metabolism (glucose tolerance, insulinemia, glucose entry in tissue, hepatic glucose metabolism) were assessed. Results: We show that galanin, a neuropeptide expressed in the small intestine, decreases duodenal contraction by stimulating nitric oxide release from enteric neurons. This is associated with modification of hypothalamic nitric oxide release that favors glucose uptake in metabolic tissues such as skeletal muscle, liver, and adipose tissue. Oral chronic gavage with galanin in diabetic mice increases insulin sensitivity, which is associated with an improvement of several metabolic parameters such as glucose tolerance, fasting blood glucose, and insulin. Conclusion: Here, we demonstrate that oral galanin administration improves glucose homeostasis via the enteric nervous system and could be considered a therapeutic potential for the treatment of T2D

Adipose tissue and breast epithelial cells: a dangerous dynamic duo in breast cancer.

International audienceAmong the many different cell types surrounding breast cancer cells, the most abundant are those that compose mammary adipose tissue, mainly mature adipocytes and progenitors. New accumulating recent evidences bring the tumor-surrounding adipose tissue into the light as a key component of breast cancer progression. The purpose of this review is to emphasize the role that adipose tissue might play by locally affecting breast cancer cell behavior and subsequent clinical consequences arising from this dialog. Two particular clinical aspects are addressed: obesity that was identified as an independent negative prognostic factor in breast cancer and the oncological safety of autologous fat transfer used in reconstructive surgery for breast cancer patients. This is preceded by the overall description of adipose tissue composition and function with special emphasis on the specificity of adipose depots and the species differences, key experimental aspects that need to be taken in account when cancer is considered

Apelin targets gut contraction to control glucose metabolism via the brain

Published by the BMJ Publishing Group Limited. This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/Objective The gut–brain axis is considered as a major regulatory checkpoint in the control of glucose homeostasis. The detection of nutrients and/or hormones in the duodenum informs the hypothalamus of the host's nutritional state. This process may occur via hypothalamic neurons modulating central release of nitric oxide (NO), which in turn controls glucose entry into tissues. The enteric nervous system (ENS) modulates intestinal contractions in response to various stimuli, but the importance of this interaction in the control of glucose homeostasis via the brain is unknown. We studied whether apelin, a bioactive peptide present in the gut, regulates ENS-evoked contractions, thereby identifying a new physiological partner in the control of glucose utilisation via the hypothalamus. Design We measured the effect of apelin on electrical and mechanical duodenal responses via telemetry probes and isotonic sensors in normal and obese/diabetic mice. Changes in hypothalamic NO release, in response to duodenal contraction modulated by apelin, were evaluated in real time with specific amperometric probes. Glucose utilisation in tissues was measured with orally administrated radiolabeled glucose. Results In normal and obese/diabetic mice, glucose utilisation is improved by the decrease of ENS/contraction activities in response to apelin, which generates an increase in hypothalamic NO release. As a consequence, glucose entry is significantly increased in the muscle. Conclusions Here, we identify a novel mode of communication between the intestine and the hypothalamus that controls glucose utilisation. Moreover, our data identified oral apelin administration as a novel potential target to treat metabolic disorders

The Chemokine Receptor CCR3 Is Potentially Involved in the Homing of Prostate Cancer Cells to Bone: Implication of Bone-Marrow Adipocytes

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Central Apelin Controls Glucose Homeostasis via a Nitric Oxide-Dependent Pathway in Mice.

International audienceAbstract Aims: Apelin and its receptor have emerged as promising targets for the treatment of insulin resistance. Indeed, peripheral administration of apelin stimulates glucose utilization and insulin sensitivity via a nitric oxide (NO) pathway. In addition to being expressed on peripheral metabolically active adipose tissues, apelin is also found in the brain. However, no data are available on the role of central effects of apelin on metabolic control. We studied glucose metabolism in response to acute and chronic intracerebroventricular (i.c.v.) injection of apelin performed in normal and obese/diabetic mice. Results: We demonstrate that i.c.v. injection of apelin into fed mice improves glucose control via NO-dependent mechanisms. These results have been strengthened by transgenic (eNOS-KO mice), pharmacological (L-NMMA i.c.v. treated mice), and real-time measurement of NO release with amperometric probes detection. High-fat diet-fed mice displayed a severely blunted response to i.c.v. apelin associated with a lack of NO response by the hypothalamus. Moreover, central administration of high dose apelin in fasted normal mice provoked hyperinsulinemia, hyperglycemia, glucose intolerance, and insulin resistance. Conclusion: These data provide compelling evidence that central apelin participates in the regulation of glucose homeostasis and suggest a novel pathophysiological mechanism involved in the transition from normal to diabetic state. Antioxid. Redox Signal. 15, 1477-1496

Chronic apelin treatment improves hepatic lipid metabolism in obese and insulin-resistant mice by an indirect mechanism

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