Physiological zoology最新文献

Although most adults in the United States will drink alcohol in their life, only about 6% will go on to develop an alcohol use disorder (AUD). While a great deal of work has furthered our understanding of the cycle of addiction, it remains unclear why certain people transition to disordered drinking. Altered activity in regions implicated in AUDs, like the basolateral amygdala (BLA), has been suggested to play a role in the pathophysiology of AUDs, but how these networks contribute to alcohol misuse remains unclear. Our recent work demonstrated that alcohol can modulate BLA network states and that GABAergic parvalbumin (PV) interneurons are crucial modulators of network activity in the BLA. Further, our lab has demonstrated that δ subunit-containing GABA _A receptors, which are modulated by alcohol, are highly expressed on PV interneurons in the BLA. These receptors on PV interneurons have also been shown to influence alcohol intake in a voluntary binge drinking paradigm and anxiety-like behavior in withdrawal. Therefore, we hypothesized that alcohol may impact BLA network states via δ subunit-containing GABA _A receptors on PV interneurons to impact the extent of alcohol use. To test this hypothesis, we measured the impact of acute alcohol exposure on oscillatory states in the basolateral amygdala and then assessed the relationship to the extent of voluntary ethanol consumption in the Intermittent Access, Drinking-in-the-Dark-Multiple Scheduled Access, and Chronic Intermittent Ethanol exposure paradigms. Remarkably, we demonstrate that the average alcohol intake negatively correlates with δ subunit-containing GABA _A receptor expression on PV interneurons and gamma power in the BLA after the first exposure to alcohol. These data implicate δ subunit-containing GABA _A receptor expression on PV interneurons in the BLA in voluntary alcohol intake and suggest that BLA network states may serve as a useful biomarker for those at risk for alcohol misuse.

Significance statement: Oscillatory states in the BLA have been demonstrated to drive behavioral states involved in emotional processing, including negative valence processing. Given that negative emotional states/hyperkatifeia contribute to the cycle of AUDs, our previous work demonstrating the ability of alcohol to modulate BLA network states and thereby behavioral states suggests that this mechanism may influence alcohol intake. Here we demonstrate a relationship between the ability of alcohol to modulate oscillations in the BLA and future alcohol intake such that the extent to which alcohol influences BLA network states predict the extent of future voluntary alcohol intake. These findings suggest that individual variability in the sensitivity of the BLA network to alcohol influences voluntary alcohol consumption.

Several rheumatic diseases have a perplexing association with cancer. Unraveling this mysterious connection is likely to provide deeper understanding regarding mechanisms governing the onset of both autoimmunity and cancer immunity, in addition to providing clinicians much needed guidance around whom and when to screen for occult malignancy. Systemic sclerosis (scleroderma) and dermatomyositis are two diseases in which the association with internal malignancy is well-described and can be considered as models from which to gain important insights that likely have broader applicability. The past 15 years have witnessed a striking acceleration in understanding how these two diseases are related to cancer emergence-an important crack in this inscrutable armor has been the discovery and characterization of disease-specific autoantigens that are closely tied with risk of cancer emergence. The best-described examples of this are antibodies against anti-RNA polymerase III (anti-POL3) and transcription intermediary factor 1-gamma (anti-TIF1γ). Patients with systemic sclerosis and cancer that are diagnosed within a short time interval of each other frequently have anti-POL3 antibodies. Antibodies against the minor spliceosome protein RNA-Binding Region Containing 3 (RNPC3) are also associated with increased cancer incidence in systemic sclerosis. Similarly, in the dermatomyositis spectrum, the majority of anti-TIF1γ-associated cancers are detected around the time of DM onset (most often within 1 year). Antibodies against Nuclear Matrix Protein 2 are also potentially associated with increased cancer emergence in dermatomyositis. The systemic sclerosis/anti-POL3 connection with close cancer onset led to the first experiments directly supporting the concept that rheumatic disease may in fact be a manifestation of cancer. It is now clear that studying these diseases through the lens of autoantibodies can reveal relationships and insights that would otherwise remain obscured. Extending these studies, new findings show that antibodies against RNA polymerase I large subunit are associated with protection against short interval cancers in anti-POL3-positive systemic sclerosis patients. These insights highlight the fact that autoantigen discovery related to cancer emergence remains an important priority; such new tools will enable the testing of specific hypotheses regarding mechanisms governing disease emergence and development of effective anti-tumor responses. Autoantibody phenotype will likely play an important role in the development of cancer screening guidelines that are critically needed by clinicians taking care of these patients. In this review, we will summarize the current state of knowledge regarding the different ways in which autoantibodies are connected with systemic sclerosis/dermatomyositis and malignancy and highlight potential paths forward.

The Translational Brain Mapping Program at the University of Rochester is an interdisciplinary effort that integrates cognitive science, neurophysiology, neuroanesthesia, and neurosurgery. Patients who have tumors or epileptogenic tissue in eloquent brain areas are studied preoperatively with functional and structural MRI, and intraoperatively with direct electrical stimulation mapping. Post-operative neural and cognitive outcome measures fuel basic science studies about the factors that mediate good versus poor outcome after surgery, and how brain mapping can be further optimized to ensure the best outcome for future patients. In this article, we describe the interdisciplinary workflow that allows our team to meet the synergistic goals of optimizing patient outcome and advancing scientific understanding of the human brain.

Within steroid receptor heterocomplexes the large tetratricopeptide repeat-containing immunophilins, cyclophilin 40 (CyP40), FKBP51, and FKBP52, target a common interaction site in heat shock protein 90 (Hsp90) and act coordinately with Hsp90 to modulate receptor activity. The reversible nature of the interaction between the immunophilins and Hsp90 suggests that relative cellular abundance might be a key determinant of the immunophilin component within steroid receptor complexes. To investigate CyP40 gene regulation, we have isolated a 5-kilobase (kb) 5'-flanking region of the human gene and demonstrated that a approximately 50 base pair (bp) sequence adjacent to the transcription start site is essential for CyP40 basal expression. Three tandemly arranged Ets sites within this critical region were identified as binding elements for the multimeric Ets-related transcription factor, GA binding protein (GABP). Functional studies of this proximal promoter sequence, in combination with mutational analysis, confirmed these sites to be crucial for basal promoter function. Furthermore, overexpression of both GABP alpha and GABP beta subunits in Cos1 cells resulted in increased endogenous CyP40 mRNA levels. Significantly, a parallel increase in FKBP52 mRNA expression was not observed, highlighting an important difference in the mode of regulation of the CyP40 and FKBP52 genes. Our results identify GABP as a key regulator of CyP40 expression. GABP is a common target of mitogen and stress-activated pathways and may integrate these diverse extracellular signals to regulate CyP40 gene expression.

This study evaluated the role of diet, specifically the relative importance of salt content versus energy content, in the response of juvenile rainbow trout to environmental acid stress in soft water ([Ca2+] = 0.057 mmol L-1, [Na+] = 0.047 mmol L-1). Diets were formulated at two energy levels (regular, 16.3 MJ kg-1, and low, 9.8 MJ kg-1) and two levels of NaCl (regular, approximately 263 mmol kg-1, and low, approximately 64 mmol kg-1), yielding four treatment combinations, each fed at a ration of 0.6% body weight d-1. A fifth group of fish was not fed during the experiment. All groups were subjected to an initial acid challenge (24 h at pH 5.0 plus 12 h at pH 4.0), followed by 28 d of exposure to pH 5.2. Following the initial acid challenge, typical ionoregulatory disturbances were seen, but most effects had attenuated or disappeared by day 20 of chronic low-pH exposure. However, after 28 d, fish fed the regular-salt diets maintained the restored ionic homeostasis, whereas those fed low-salt diets did not, regardless of the energy content of the diet. Growth and food conversion efficiency were greatest in trout fed the regular-energy/regular-salt diet, negative in fish fed the low-energy/regular-salt diet, and intermediate in trout on the other diets; starved fish lost weight. Fish maintained on the regular-energy/low-salt diet exhibited the most deleterious effects, including elevated cortisol levels and a 4.1% d-1 mortality rate. Fish fed the low-energy/low-salt diet, those fed regular-salt diets, and starved fish were not as adversely affected by the acid stress. Following a regular-energy meal, fish tended to exhibit an elevated rate of oxygen consumption, but this did not occur after a low-energy meal, regardless of its salt content. Elevated oxygen consumption may be accompanied by a loss of ions via the osmorespiratory compromise. We hypothesize that fish fed the regular-energy/low-salt diets were most deleteriously affected in an acidified environment because they were unable to replace increased branchial ion losses with dietary salts. These results indicate that it is the salt content of the food rather than the energy content that is critical in protecting against the deleterious effects of low pH.

Our goal was to compare the internal physiological responses to acid challenge in an acidophilic tropical teleost endemic to dilute low-pH waters with those in nonacidophilic temperate species such as salmonids, which have been the subjects of most previous investigations. The Amazonian tambaqui (Colossoma macropomum), which migrates between circumneutral water and dilute acidic "blackwater" of the Rio Negro, was exposed to a graded low-pH and recovery regime in representative soft water (Na+ = 15, Cl- = 16, Ca2+ = 20 mumol L-1). Fish were fitted with arterial catheters for repetitive blood sampling. Water pH was altered from 6.5 (control) to 5.0, 4.0, 3.0, and back to 6.5 (recovery) on successive days. Some deaths occurred at pH 3.0. Throughout the regime, there were no disturbances of blood gases (O2 and CO2 tensions and contents) or lactate levels, and only very minor changes in acid-base status of plasma and red cells. However, erythrocytic guanylate and adenylate levels increased at pH's less than or equal to 5.0. Down to pH 4.0, plasma glucose, cortisol, and total ammonia levels remained constant, but all increased at pH 3.0, denoting a stress response. Plasma Na+ and Cl- levels declined and plasma protein concentration increased at pH 3.0, indicative of ionoregulatory and fluid volume disturbance, and neither recovered upon return to pH 6.5. Cortisol and ammonia elevations also persisted. Transepithelial potential changed progressively from highly negative values (inside) at pH 6.5 to highly positive values at pH 3.0; these alterations were fully reversible. Experimental elevations in water calcium levels drove the transepithelial potential positive at circumneutral pH, attenuated or prevented changes in transepithelial potential at low pH, and reduced Na+ and Cl- loss rates to the water during acute low-pH challenges. In general, tambaqui exhibited responses to low pH that were qualitatively similar but quantitatively more resistant than those previously documented in salmonids.

To assess how the high-sugar/low-protein content of fruit diets affects digestive function and nutrition of frugivorous birds, I compared intake, passage rate, sugar utilization, protein requirements, and mass changes of cedar waxwings (Bombycilla cedrorum), American robins (Turdus migratorius), and wood thrushes (Hylocichla mustelina) fed synthetic diets simulating the range of sugar (6.6%, 12.4%, and 22.0% solutes) and protein (4.5%, 3.0%, and 1.5% of dry matter) content of bird-dispersed fruits. The dietary emphasis on sugary fruits by cedar waxwings suggests the potential for digestive and physiological specializations to this food type. All birds increased volumetric food intake and passage rates as sugar concentration declined. Birds completely (22.0%-12.4% sugar solute concentration) or incompletely (12.4%-6.6% sugar solute concentration) compensated for dietary dilution. Cedar waxwings consumed each diet at higher rates than did thrushes, as they do when eating sugary fruits, demonstrating that interspecific differences in ingestion rates of sugary fruits are a consequence of nutrient composition, rather than seed bulk or secondary compounds of fruits. Passage rate was not responsible for interspecific differences in short-term food intake rate, implicating gut morphology as the key functional feature limiting intake. Most sugary fruits are nutritionally deficient in apparent protein for thrushes but are nutritionally adequate in protein for cedar waxwings because of this species' relatively high intake rates and low protein requirements. The digestive systems of frugivorous birds respond flexibly to dietary sugar concentration, but protein content of fruits can present a nutritional limitation, potentially influencing the proportions of fruit and animal foods in birds' diets.

The apneas of many torpid mammals can persist longer than estimated O2 stores allow. This suggests that some O2 is acquired during these apneas by either cutaneous uptake or by a nonventilatory flux down an open airway (tracheal flux). Previous experiments confirmed apneic O2 uptake in the bat Eptesicus fuscus with the conclusion that the uptake most likely occurred by tracheal flux. However, the bat's large cutaneous wing area remained a potential source of cutaneous O2 uptake, leaving uncertainty regarding the mechanism of O2 uptake, particularly in regard to some evidence suggesting that small mammals might be obligated to maintain a closed glottis during apnea. This study sought experimental confirmation of passive O2 uptake in the pocket mouse Perognathus parvus, torpid at a body temperature of 10 degrees C, body mass 16.0 +/- 0.6 g (N = 9). Ventilation bouts lasted 1.49 +/- 0.06 min, whereas apneas lasted 4.51 +/- 0.14 min, despite estimated O2 stores able to support apneas of only 1.0 min. The maximum predicted cutaneous O2 uptake was 0.67 mumol O2/h, whereas the theoretically calculated tracheal flux was 20.2 mumol O2/h. This theoretical rate of tracheal flux compared favorably to the measured plateau apneic O2 uptake rate of 16.7 mumol O2/h. However, the diffusional component of tracheal flux was 3.6 times greater than predicted, indicating an important contribution from cardiogenic mixing. Overall, apneic O2 uptake provided 10.2% of the mouse's total O2 uptake. We conclude that passive tracheal flux is the most likely mechanism by which this animal acquires O2 during apnea.

Relative to small embryos, large embryos may have longer developmental periods and, subsequently, relatively greater maintenance budgets. Because of the potentially increased metabolic costs of maintaining large embryos for long embryonic periods, Salthe and Mecham (1974) suggested that as ovum size increases among amphibians, ovum lipids (the primary stored metabolic energy reserves) should increase at a proportionally greater rate. To test Salthe and Mecham's hypothesis, we quantified egg lipids for 13 amphibian species from the southeastern United States. As ovum size increased among species, total, nonpolar, and polar lipids increased at rates uniform with or relatively lower than rates of increase in ovum size, in contrast to the hypothesis of Salthe and Mecham. However, variation in ovum lipids among species may be related to differences in breeding biology. Our results indicate that the amount of lipids allocated to ova do not merely depend on ovum size, but rather on the selective environments of the embryo and neonate.