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Ray RS Corcoran AE Brust RD Kim JC Richerson GB Nattie E Dymecki SM 《Science (New York, N.Y.)》2011,333(6042):637-642
Physiological homeostasis is essential for organism survival. Highly responsive neuronal networks are involved, but their constituent neurons are just beginning to be resolved. To query brain serotonergic neurons in homeostasis, we used a neuronal silencing tool, mouse RC::FPDi (based on the synthetic G protein-coupled receptor Di), designed for cell type-specific, ligand-inducible, and reversible suppression of action potential firing. In mice harboring Di-expressing serotonergic neurons, administration of the ligand clozapine-N-oxide (CNO) by systemic injection attenuated the chemoreflex that normally increases respiration in response to tissue carbon dioxide (CO(2)) elevation and acidosis. At the cellular level, CNO suppressed firing rate increases evoked by CO(2) acidosis. Body thermoregulation at room temperature was also disrupted after CNO triggering of Di; core temperatures plummeted, then recovered. This work establishes that serotonergic neurons regulate life-sustaining respiratory and thermoregulatory networks, and demonstrates a noninvasive tool for mapping neuron function. 相似文献
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OBJECTIVE: To evaluate outcomes after attenuation of extrahepatic portosystemic shunts in dogs using surgical silk. DESIGN: Retrospective study. PROCEDURE: Case records were reviewed for degree of surgical attenuation, experience of the primary surgeon, perioperative mortality and problems related to persistent portosystemic shunting or shunt ligation. Presence of portosystemic shunting after surgery was evaluated by ammonia tolerance testing, measurement of postprandial serum bile acid, plasma urea and cholesterol concentrations and liver enzyme activity. The influence of age, postocclusion portal pressure, primary surgeon, degree of attenuation and postoperative biochemical findings on the occurrence of postoperative problems was assessed. RESULTS: The mortality rate was 2.1%. Shunt attenuation was complete in 34% and partial in 66% of dogs. Portal hypertension necessitating ligature removal was encountered in only one dog. Five dogs experienced neurological abnormalities (seizures or ataxia), possibly as a manifestation of 'postligation seizure syndrome'. Postoperative liver function was normal in 78% of dogs, including 70% with partial shunt attenuation. Experience of the surgeon was related positively to outcome after partial attenuation (P = 0.002). Postoperative biochemical evidence of abnormal liver function was the most sensitive predictor of recurrence of clinical signs referable to persistent portosystemic shunting. CONCLUSIONS: In the hands of an experienced surgeon, surgical attenuation of single extrahepatic shunts was safe and effective, even in animals with partial attenuation. Most dogs with biochemical evidence of persistent shunting suffer relapse of clinical signs within 18 months of surgery. Postligation neurological syndromes of variable intensity may be more common than previously thought. 相似文献
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In mature Merino rams, nutrition is one of the external cues that most strongly affects the reproductive centres of the preoptic-hypothalamic continuum. The signalling pathways that link dietary status and the activity of the neurones that produce gonadotrophin-releasing hormone signals are thought to be partly hormonal in nature to reflect the amount of body reserves. Among the hormones thought to be involved are insulin and leptin. This study tested whether recombinant bovine leptin infused (0.4 microg/h) into the third cerebral ventricle would stimulate pulsatile luteinizing hormone (LH) secretion in mature Merino rams when their energy status was low or decreasing, during both chronic (fasting) and acute reductions of energy balance. Leptin may interact with other hormones that depend on energy availability, so we also monitored changes in circulating concentrations of insulin, thyroid hormones, growth hormone, prolactin and adrenocorticotrophin. Overall, our data do not support this hypothesis. The dietary regimes induced clear responses in the metabolic profiles of the animals but there was no clear effect of central leptin administration on LH pulse frequency. The relationships between the hormonal systems measured in the present study add weight to the contention that leptin plays only a permissive role in the nutritional control of the reproductive axis and that other hormonal signals (particularly insulin) or pathways are acting in concert with leptin to stimulate the reproductive axis. 相似文献
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Appraisal and standardization of curvilinear velocity (VCL) cut‐off values for CASA analysis of Japanese quail (Coturnix japonica) sperm
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One of the basic steps in objective analysis of sperm motility is the subdivision of a motile sperm population into slow, medium and rapid categories based on their velocity. However, for CASA analysis of quail sperm, the velocity values for categorization of slow, medium and rapid sperm have not yet been standardized. To identify the cut‐off values of “velocity curvilinear” (VCL) for quail sperm categorization, we captured and analysed 22,300 tracks of quail sperm using SCA®‐CASA. The median and mean VCL values were 85 and 97 μm/s. To define the VCL cut‐off values, we used two methods. In the first, we identified the upper (rapid sperm) and lower (slow sperm) cut‐off values using: (i) median VCL ± 25% or ± 50% or ± 75% of median VCL value; (ii) first and third quartile values of VCL data (i.e. 25% cut‐off setting); and (iii) 33% and 66% of VCL data. Among these settings, sperm categories and their corresponding motility characteristics recorded using the “25%” setting (i.e. slow ≤36 ≤ medium ≤154 ≤ rapid) were found the most realistic and coherent with male ranking by fertility. In the second method, we calculated heteroscedasticity in the total VCL data using PCA and the two‐step clustering method. With this approach, the mean of the high and low clusters was 165 and 51 μm/s, respectively. Together, the mean from two methods suggested that, for SCA®‐CASA categorization of quail sperm, sperm should be classed as “rapid” at VCL ≥160 μm/s and “slow” at VCL ≤45 μm/s. 相似文献
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SUMMARY A haemodynamically significant ventricular septal defect was diagnosed in a 3-month-old male Cavalier King Charles Spaniel. A median sternotomy was performed and the 6.5 kg dog placed on cardiopulmonary bypass using pump-assisted cross-circulation. A 10 mm diameter peri-membranous ventricular septal defect was closed using a continuous suture of 4–0 polypropylene, via a 2.5 cm incision in the right ventricular outflow tract. The duration of cardiopulmonary bypass was 90 minutes. Complications in the immediate postoperative period were mild and easily managed. 相似文献