Regulation Of Physiological Responses Research Articles

Fecal microbial composition associated with testosterone in the development of Meishan male pigs.

The gut microbiota closely relates to host health, whereas the relationship between gut microbiota and testosterone during the development of Meishan male pigs remains unclear. This study investigated the fecal microbiota composition and testosterone level during development in Meishan male pigs. Fresh fecal samples of 20 healthy Meishan male pigs were individually collected at 10 and 22 weeks (wk) of age for testosterone content detection and bacteria pyrosequencing analysis. Anaerobic culture experiment of fecal bacteria in vitro was performed for bacteria pyrosequencing analysis. The fecal testosterone content increased significantly from 10 weeks (wk) to 22 wk of age (P < 0.05). Meanwhile, the boars at 22 wk had a lower abundance of phylum Bacteroidetes and Proteobacteria, and genus Alloprevotella, Prevotella_1, Prevotellaceae_NK3B31_group, and Streptococcus in the fecal microbiota composition (P < 0.05). but higher proportions of the phylum Actinobacteria, Firmicutes, Kiritimatiellaeota, and Tenericutes, and genus Clostridium_sensu_stricto_1, Muribaculaceae and Terrisporobacter than that at 10 wk (P < 0.05), and the Firmicutes to Bacteroidetes ratio was higher at 22 wk than 10 wk (P < 0.05). Moreover, the fecal testosterone level significantly correlated with the relative abundance of the phylum Actinobacteria, Firmicutes, and Tencuteseri, and genus Alloprevotella, Clostridium_sensu_stricto_1, Muribaculaceae, Prevotella_1 and Streptococcus. Furthermore, the in vitro experiments indicated that the abundance of the phylum Proteobacteria and genus Escherichia-Shigella reduced with the increase of supplemental testosterone level. In contrast, the proportion of Firmicutes phylum increased with additional testosterone levels. Testosterone could modulate the microflora structure. Meanwhile, the bacteria could degrade the testosterone in a dose testosterone-dependent manner. These results provide us with new insights into the relationship between the gut microbiome and testosterone and the contributions of the gut microbiome in physiological regulation in response to gonad development.

Sense of purpose in life and allostatic load in two longitudinal cohorts

ObjectiveSense of purpose in life has been linked with better physical health, longevity, and reduced risk for disability and dementia, but the mechanisms linking sense of purpose with diverse health outcomes are unclear. Sense of purpose may promote better physiological regulation in response to stressors and health challenges, leading to lower allostatic load and disease risk over time. The current study examined the association between sense of purpose in life and allostatic load over time in adults over age 50. MethodsData from the nationally representative US Health and Retirement Study (HRS) and English Longitudinal Study of Ageing (ELSA) were used to examine associations between sense of purpose and allostatic load across 8 and 12 years of follow-up, respectively. Blood-based and anthropometric biomarkers were collected at four-year intervals and used to compute allostatic load scores based on clinical cut-off values representing low, moderate, and high risk. ResultsPopulation-weighted multilevel models revealed that sense of purpose in life was associated with lower overall levels of allostatic load in HRS, but not in ELSA after adjusting for relevant covariates. Sense of purpose in life did not predict rate of change in allostatic load in either sample. ConclusionsThe present investigation supports sense of purpose predicting preserved differentiation of allostatic regulation, with more purposeful individuals demonstrating consistently lower allostatic load over time. Persistent differences in allostatic burden may account for divergent health trajectories between individuals low and high in sense of purpose.

A novel heterozygote allele in caprine melanocortin 1 receptor (MC1R) gene: an association with heat stress traits.

Climate change negatively influences the productive and reproductive abilities of goats. There is a need to understand the relationship between heat stress and genes that may aid in the development of climate-resilient goats. Melanism variation in goats plays a role in thermoregulation, in which the melanogenic genes have a pleiotropic effect on the regulation of physiological responses and behavior that are altered due to heat stress in the animals. Thus, the present study was conducted to establish a possible association between the coat color gene (MC1R) and heat stress characteristics. The physiological responses and cortisol levels were recorded in forty different coat-colored goats. The genotyping of the animals revealed four SNPs at the 183rd (C/T), 332nd (C/G), 748th (G/T), and 801st (C/G) positions, among which the black and brown goat populations had novel SNPs at the 332nd position. Eight haplotypes were constructed, and an association study revealed that haplotypes (CCGG, TCGG, and CCTC) that were linked to white animals had lower cortisol values, rectal temperature, skin temperature, and respiration rate. The multivariate and cluster analyses revealed that the white goats were distinct from the rest of the goats. In addition, the docking results revealed the residues that were forming the interaction complex, which could play a role in melanogenesis in the animals and, in turn, the heat stress ability of the goats. Altogether, the results of the present study could pave the way for more research into coat color genes and their relationship with heat stress traits.

SENSE OF PURPOSE IN LIFE AND ALLOSTATIC BURDEN IN TWO LONGITUDINAL COHORTS

Abstract Sense of purpose in life has been linked with better physical health, longevity, and reduced risk for disability and dementia, but the mechanisms linking purposefulness with diverse health outcomes is unclear. Chronic activation and dysregulation of neural, immune, and other bodily systems, known as allostatic load, may contribute to these underlying mechanisms. Specifically, sense of purpose may promote better physiological regulation in response to stressors and health challenges, leading to lower allostatic burden and disease risk over time. Data from the nationally representative US Health and Retirement Study (HRS) and English Longitudinal Study on Ageing (ELSA) (Total N=5846; Mean Age=67.24, SD=10.68, 59.08% female) were used to examine associations between sense of purpose and repeated assessments of allostatic load across 8 and 12 years of follow-up. Allostatic load scores were constructed from 12 blood-based and anthropometric biomarkers of cardiovascular, metabolic, immune, and lung function, with higher scores representing higher allostatic burden. Population-weighted multilevel models revealed that sense of purpose in life was associated with lower overall levels of allostatic load in HRS (b = -0.22, 95% CI: -0.27,-0.17) and in ELSA (b = -0.19, 95% CI: -0.35,-0.03). Sense of purpose in life did not predict rate of change in allostatic load in either sample. Associations with sense of purpose were highest among cardiovascular and immune biomarkers, suggesting that preservation of these bodily systems may underlie associations between purposefulness and reduced risk for chronic health conditions. Discussion will focus on biological and behavioral pathways connecting sense of purpose in life and health.

Improvement in parasympathetic regulation is associated with engagement in classroom activity in primary school children experiencing poor classroom climate.

Self-regulation promotes engagement within the classroom. At a physiological level, a good indicator of the ability of the system to self-regulate is cardiac vagal tone (CVT). The present study aims to assess children's change over time (1year) in their parasympathetic regulation (by way of CVT) in response to a social and cognitive stressor. Moreover, it addresses whether, if present, this change over time in regulation influences students' engagement in classroom activities while also accounting for classroom climate. Forty-nine second graders were assessed at two time points: November 2018 (T1) and 1year later in 2019 (T2). Children's CVT was registered at rest and while performing a stressful task during which they were asked to cognitively perform while being socially evaluated. Children were also interviewed on how much they feel engaged in classroom activities and their perceptions of classroom climate. A repeated measures analysis of variance including 2Time Points ×2 Phases of CVT Registration (baseline and during the stressful task) revealed a significant decrease in cardiac vagal activity from baseline to the task at T1, indicating that initially most children were not able to self-regulate and gave way to a stress response when facing the stressful task. The pattern changed at T2 when an active regulation took place signalled by an increase in CVT from baseline to the stressful task. Data analysis also revealed that among children who perceived a poorer classroom climate, the display of greater parasympathetic regulation over time was linked with higher active engagement in classroom activities. Growth in physiological regulation in response to a challenging task is associated with better engagement in classroom activities. Interventions and educational practice promoting the development of self-regulation strategies are recommended.

Cardiac Startle Response and Clinical Outcomes in Preschool Children With Fragile X Syndrome and Autism Spectrum Disorder.

Objective: Poor physiological regulation in response to threat is linked to multiple negative developmental outcomes including anxiety, which is highly prevalent and impairing in young children with neurodevelopmental disabilities like fragile X syndrome (FXS) and autism spectrum disorder (ASD). The present study contrasted cardiac startle response in pre-school-aged children with FXS, with and without ASD, to children with non-syndromic ASD (nsASD) and neurotypical controls (NT). The relationship of cardiac startle to non-verbal mental age (NVMA), ASD severity, and parent-reported anxiety was also examined.Method: Four age-matched groups of pre-school children participated including those with FXS without ASD (FXS-Only, n = 21), FXS with ASD (FXS+ASD, n = 17), nsASD (n = 42), and NT children (n = 27). Participants viewed a silent movie during which a single 200 ms 98-decibel white noise burst occurred. Cardiac activity was analyzed for pre-stimulus respiratory sinus arrhythmia (RSA) and the inter-beat intervals (IBI) at the auditory stimulus and 10 s post-stimulus. The Spence Pre-school Anxiety Scale, Autism Diagnostic Observation Schedule-2nd Edition, and Mullen Scales of Early Learning were examined in relation to startle response.Results: The nsASD group demonstrated heightened cardiac activity at the auditory stimulus and 10 s post-stimulus compared to the NT controls. Neither of the FXS groups showed differences from any other group. Higher pre-stimulus RSA was associated with reduced cardiac response across groups, while the relationship between cognitive ability and ASD severity to cardiac response varied between groups. Parent-reported anxiety was not associated with cardiac response for any group.Conclusion: These findings demonstrate group distinctions in cardiac responses to auditory startle. Although FXS and ASD share behavioral characteristics, the nsASD group showed a heightened cardiac startle response compared to the NT group that was not present in the FXS groups with or without ASD. Non-verbal mental age was associated with greater stimulus or post-stimulus reactivity for all groups except the FXS+ASD group, which showed no association between startle response and any clinical outcomes. Increased understanding of the relationship between physiological regulation and clinical outcomes will assist in identifying the timing and targets for effective interventions for individuals with neurodevelopmental disabilities.

The effect of haptic stimulation simulating heartbeats on the regulation of physiological responses and prosocial behavior under stress: The influence of interoceptive accuracy

Research has discovered the modulatory effect of peripheral stimulation simulating altered bodily signals on emotion. Whether such an effect varies depending on one’s interoceptive accuracy (IAc) remains unclear. Therefore, we provided haptic stimulation simulating participants’ slowed-down heartbeats or no stimulation while they engaged in socially stressful tasks to examine whether participants reacted differently depending on their IAc. Results showed that haptic stimulation exhibited the opposite effect on participants with different levels of IAc for both heart rate and heart rate variability (HRV). When receiving the stimulation, participants with higher IAc showed less increased heart rate and more elevated HF than participants with lower IAc. In contrast, in the absence of stimulation, an opposite pattern of response depending on participants’ IAc was observed. The modulatory effect of stimuli and IAc on prosocial behavior was not significant. Individual differences in IAc were shown to affect how one perceives/responds to altered bodily signals.

Brassinosteroids modulate nitrogen physiological response and promote nitrogen uptake in maize (Zea mays L.)

Brassinosteroids (BRs) are steroid hormones that function in plant growth and development and response to environmental stresses and nutrient supplies. However, few studies have investigated the effect of BRs in modulating the physiological response to nitrogen (N) supply in maize. In the present study, BR signaling-deficient mutant zmbri1-RNAi lines and exogenous application of 2,4-epibrassinolide (eBL) were used to study the role of BRs in the regulation of physiological response in maize seedlings supplied with N. Exogenous application of eBL increased primary root length and plant biomass, but zmbri1 plants showed shorter primary roots and less plant biomass than wild-type plants under low N (LN) and normal N (NN) conditions. LN induced the expression of the BR signaling-associated genes ZmDWF4, ZmCPD, ZmDET2, and ZmBZR1 and the production of longer primary roots than NN. Knockdown of ZmBRI1 weakened the biological effects of LN-induced primary root elongation. eBL treatment increased N accumulation in shoots and roots of maize seedlings exposed to LN or NN treatment. Correspondingly, zmbri1 plants showed lower N accumulation in shoots and roots than wild-type plants. Along with reduced N accumulation, zmbri1 plants showed lower NO3− fluxes and 15NO3− uptake. The expression of nitrate transporter (NRT) genes (ZmNPF6.4, ZmNPF6.6, ZmNRT2.1, ZmNRT2.2) was lower in zmbri1 than in wild-type roots, but eBL treatments up-regulated the transcript expression of NRT genes. Thus, BRs modulated N physiological response and regulated the transcript expression of NRT genes to promote N uptake in maize.

The Microbiome-Metabolome Response in the Colon of Piglets Under the Status of Weaning Stress.

Weaning is stressful for piglets involving nutritional, physiological, and psychological challenges, leading to an increase in the secretion of cortisol, changes in gut microbiome and metabolites, whereas the underlying relationships remain unclear. To elucidate this, 14 Meishan female piglets were divided into the weaning group and the suckling group at the age of 21 days paired by litter and body weight. After 48 h of experiment, weaned piglets had lower body weight, but higher salivary cortisol level than that of their suckling litter mates (P < 0.05). The composition of the colonic bacterial community and metabolites were different between the two groups, and the first predominant genus of the suckling and weaned piglets colonic microbiome were Bacteroides and Prevotellaceae-NK3B31 group respectively. The suckling piglets had higher proportions of phylum Bacteroidetes and Lentisphaerae, and genus Bacteroides and Lactobacillus in the colonic microbial community, but lower abundance of genus Prevotellaceae-NK3B31 group than that of the weaned piglets (P < 0.05). Accordingly, there were 15 colonic metabolites differed between the two groups, in which 2 metabolites (phenylacetic acid and phenol) negatively related to the abundant of Lactobacillus genus (P < 0.05), while 9 metabolites (acetic acid, arabitol, benzoic acid, caprylic acid, cholesterol, dihydrocholesterol, galactinol, glucose phenol, phenylacetic acid, and oxamic acid, glycerol, propionic acid) positively associated with the proportion of Prevotellaceae-NK3B31 group genus (P < 0.05). Furthermore, the salivary cortisol level negatively associated with the abundance of phylum Lentisphaerae, but positively associated with the phylum Bacteroidetes and the genus Prevotellaceae-NK3B31 group (P < 0.05) respectively. These results provide us with new insights into the cause of the gut microbiome and stress, and the contributions of gut microbiome in metabolic and physiological regulation in response to weaning stress.

Physiological responses to cold and starvation stresses in the liver of yellow drum (Nibea albiflora) revealed by LC-MS metabolomics.

As global climate changes, mass mortality in farmed fish associated with the severely cold weather has aroused growing concerns. Yellow drum (Nibea albiflora) is an important maricultured fish in China, whereby its aquaculture suffered from overwinter mortality associated with cold and cold-induced-fasting stresses. Here, by using LC-MS metabolomics combined with transcriptomics, we investigated the physiological responses of yellow drum liver to cold and starvation stresses. The experiment involved four groups: 16°C fed group (CG1), 16°C unfed group (CG2), 8°C fed group (EG1), and 8°C unfed group (EG2). Under cold stress, a total of 308 and 257 differential metabolites were identified in EG1 vs. CG1 and EG2 vs. CG2, respectively, showing 5 overlapping significant pathways: glutathione metabolism, biosynthesis of unsaturated fatty acids, galactose metabolism, arginine and proline metabolism, and ABC transporters. Intersection analysis identified that glutamate, oxidized glutathione (GSSG), and eicosenoic acid were the common metabolites induced by cold stress. Under starvation stress, a total of 300 and 215 differential metabolites were identified in CG2 vs. CG1 and EG2 vs. EG1, respectively, showing 2 overlapping significant pathways: glutathione metabolism and galactose metabolism. Intersection analysis revealed that glutamate and GSSG were the common metabolites caused by fasting. Under cold and starvation combined stresses, 286 differential metabolites were identified in EG2 vs. CG1, showing 7 influenced pathways: glycerophospholipid metabolism, biosynthesis of unsaturated fatty acids, glutathione metabolism, sphingolipid metabolism, glycosylphosphatidylinositol (GPI)-anchor biosynthesis, autophagy, and purine metabolism. Interestingly, the glutamate and GSSG were induced by both single and combined stresses of cold and starvation treatments. These findings suggest that glutathione metabolism and its related metabolites (glutamate and GSSG) could be potential biomarkers of cold and starvation stresses in yellow drum. Overall, the results of this study provided insights into the physiological regulation in response to cold and starvation stresses in this fish.

DNA methylation in genes of longevity-regulating pathways: association with obesity and metabolic complications.

Aging is the main risk factor for most chronic diseases. Epigenetic mechanisms, such as DNA methylation (DNAm) plays a pivotal role in the regulation of physiological responses that can vary along lifespan. The aim of this research was to analyze the association between leukocyte DNAm in genes involved in longevity and the occurrence of obesity and related metabolic alterations in an adult population. Subjects from the MENA cohort (n=474) were categorized according to age (<45 vs 45>) and the presence of metabolic alterations: increased waist circumference, hypercholesterolemia, insulin resistance, and metabolic syndrome. The methylation levels of 58 CpG sites located at genes involved in longevity-regulating pathways were strongly correlated (FDR-adjusted< 0.0001) with BMI. Fifteen of them were differentially methylated (p<0.05) between younger and older subjects that exhibited at least one metabolic alteration. Six of these CpG sites, located at MTOR (cg08862778), ULK1 (cg07199894), ADCY6 (cg11658986), IGF1R (cg01284192), CREB5 (cg11301281), and RELA (cg08128650), were common to the metabolic traits, and CREB5, RELA, and ULK1 were statistically associated with age. In summary, leukocyte DNAm levels of several CpG sites located at genes involved in longevity-regulating pathways were associated with obesity and metabolic syndrome traits, suggesting a role of DNAm in aging-related metabolic alterations.

Physiological responses to cold stress in the gills of discus fish (Symphysodon aequifasciatus) revealed by conventional biochemical assays and GC-TOF-MS metabolomics

Discus fish (Symphysodon aequifasciatus) is a cichlid that is among the most popular fish for warm-water aquaria and also frequently used as the model animal for environmental science. However, little is known about the responses of S. aequifasciatus to low temperatures caused by environmental variation. Here, by using conventional biochemical assays and gas chromatography time-of-flight mass spectrometry metabolomics, we investigated the physiological responses of S. aequifasciatus gills exposed for 30 days to two temperature regimes: 28 °C and 20 °C. Low temperature resulted in elevated production of reactive oxygen species but not increased malondialdehyde. This might be partially related to protective responses in the antioxidant system, revealed by increased activities of superoxide dismutase and glutathione peroxidase, and level of reduced glutathione (GSH), compensating for the depletion of catalase activity. A total of 35 metabolites were identified as potential biomarkers of cold stress, showing the most influenced pathways including starch and sucrose metabolism, pentose phosphate pathway, glycerolipid metabolism, sphingolipid metabolism, glutathione metabolism, and arginine and proline metabolism. Moreover, the activation of glutathione metabolism agreed with the increased GSH level detected by biochemical assays. Overall, the results of this study suggest that low temperature can activate a protective antioxidant defence response and modify the metabolic pathways in gills of S. aequifasciatus, providing insights into the physiological regulation in response to cold stress in this tropical fish.

A Scalable Genome-Editing-Based Approach for Mapping Multiprotein Complexes in Human Cells.

Conventional affinity purification followed by mass spectrometry (AP-MS) analysis is a broadly applicable method used to decipher molecular interaction networks and infer protein function. However, it is sensitive to perturbations induced by ectopically overexpressed target proteins and does not reflect multilevel physiological regulation in response to diverse stimuli. Here, we developed an interface between genome editing and proteomics to isolate native protein complexes produced from their natural genomic contexts. We used CRISPR/Cas9 and TAL effector nucleases (TALENs) to tag endogenous genes and purified several DNA repair and chromatin-modifying holoenzymes to near homogeneity. We uncovered subunits and interactions among well-characterized complexes and report the isolation of MCM8/9, highlighting the efficiency and robustness of the approach. These methods improve and simplify both small- and large-scale explorations of protein interactions as well as the study of biochemical activities and structure-function relationships.

Multiple Days of Heat Exposure on Firefighters' Work Performance and Physiology.

This study assessed the accumulated effect of ambient heat on the performance of, and physiological and perceptual responses to, intermittent, simulated wildfire fighting tasks over three consecutive days. Firefighters (n = 36) were matched and allocated to either the CON (19°C) or HOT (33°C) condition. They performed three days of intermittent, self-paced simulated firefighting work, interspersed with physiological testing. Task repetitions were counted (and converted to distance or area) to determine work performance. Participants were asked to rate their perceived exertion and thermal sensation after each task. Heart rate, core temperature (Tc), and skin temperature (Tsk) were recorded continuously throughout the simulation. Fluids were consumed ad libitum. Urine volume was measured throughout, and urine specific gravity (USG) analysed, to estimate hydration. All food and fluid consumption was recorded. There was no difference in work output between experimental conditions. However, significant variation in performance responses between individuals was observed. All measures of thermal stress were elevated in the HOT, with core and skin temperature reaching, on average, 0.24 ± 0.08°C and 2.81 ± 0.20°C higher than the CON group. Participants’ doubled their fluid intake in the HOT condition, and this was reflected in the USG scores, where the HOT participants reported significantly lower values. Heart rate was comparable between conditions at nearly all time points, however the peak heart rate reached each circuit was 7 ± 3% higher in the CON trial. Likewise, RPE was slightly elevated in the CON trial for the majority of tasks. Participants’ work output was comparable between the CON and HOT conditions, however the performance change over time varied significantly between individuals. It is likely that the increased fluid replacement in the heat, in concert with frequent rest breaks and task rotation, assisted with the regulation of physiological responses (e.g., heart rate, core temperature).

Effects of seasonal seston and temperature changes on lake zooplankton fatty acids

We investigated how seston fatty acids (FA) and water temperature explained seasonal variation in cladoceran and copepod FA over three years in pre-alpine, oligotrophic Lake Lunz, Austria. Using the mostly algal-derived polyunsaturated FA (PUFA: arachidonic, ARA; eicosapentaenoic, EPA; docosahexaenoic acid, DHA), terrestrial FA (TFA, 22 : 0, 24 : 0), and bacterial FA (BAFA, 15 : 0, 17 : 0 and their branched homologues) as source-specific biomarkers, we show that cladocerans consistently contained more ARA and EPA and copepods more DHA than the available food (seston). None of these physiologically important PUFA were significantly related between zooplankton and seston across the entire study period but copepod DHA increased with seston DHA during the coldest months (< 8°C, based on a significant seston FA*temperature interaction). EPA, conversely, increased with decreasing water temperature in both zooplankton groups. For the nonessential FA, TFA were lower in zooplankton than in seston and not related to dietary supply or water temperature. However, cladoceran and copepod BAFA increased significantly with increasing seston BAFA and decreasing water temperature. These findings suggest that physiological regulation in response to changing water temperature had a significant impact on cladoceran and copepod EPA and the extent of dietary tracking for copepod DHA. TFA available in the seston may not have been consumed or were poorly incorporated by zooplankton, but BAFA were good indicators of available resources throughout multiple seasonal cycles. Based on our study, both FA type and water temperature impact the extent that dietary vs. nondietary processes govern cladoceran and copepod FA in oligotrophic lakes.

Antecedents of maternal sensitivity during distressing tasks: integrating attachment, social information processing, and psychobiological perspectives.

Predictors of maternal sensitivity to infant distress were examined among 259 primiparous mothers. The Adult Attachment Interview, self-reports of personality and emotional functioning, and measures of physiological, emotional, and cognitive responses to videotapes of crying infants were administered prenatally. Maternal sensitivity was observed during three distress-eliciting tasks when infants were 6 months old. Coherence of mind was directly associated with higher maternal sensitivity to distress. Mothers' heightened emotional risk was indirectly associated with lower sensitivity via mothers' self-focused and negative processing of infant cry cues. Likewise, high physiological arousal accompanied by poor physiological regulation in response to infant crying was indirectly associated with lower maternal sensitivity to distress through mothers' self-focused and negative processing of infant cry cues.

Quo vadis plant hormone analysis?

Plant hormones act as chemical messengers in the regulation of myriads of physiological processes that occur in plants. To date, nine groups of plant hormones have been identified and more will probably be discovered. Furthermore, members of each group may participate in the regulation of physiological responses in planta both alone and in concert with members of either the same group or other groups. The ideal way to study biochemical processes involving these signalling molecules is 'hormone profiling', i.e. quantification of not only the hormones themselves, but also their biosynthetic precursors and metabolites in plant tissues. However, this is highly challenging since trace amounts of all of these substances are present in highly complex plant matrices. Here, we review advances, current trends and future perspectives in the analysis of all currently known plant hormones and the associated problems of extracting them from plant tissues and separating them from the numerous potentially interfering compounds.

Effects of Antagonists of Mu and Kappa Opioid Receptors on Aggressivity in Male Mice with Repeated Experience of Aggression

Mu and kappa opioid receptors often show antagonism in the regulation of physiological responses and behavior, including aggressive behavior. We report here our studies of the effects of acute administration of the selective mu opioid receptor antagonist CTAP (1 and 2 mg/kg, s.c.) and the selective kappa opioid receptor antagonist nor-BNI (0.5 mg/kg, s.c.) on manifestations of aggressive behavior in male C57BL/6J mice with short (three days) and long (20 days) experience of victory in intermale confrontations. Animals with short experience of aggression were insensitive to blockade of both mu and kappa receptors. In males with long experience of aggression, administration of CTAP led to dose-dependent increases in the latent period of attacks but had no effect on attack duration. Administration of nor-BNI had no effect on the behavior of males with prolonged experience of aggression in antagonistic confrontations. Possible changes in the sensitivity of opioid receptors in male C57BL/6J mice following prolonged experience of aggression are discussed.

Allostasis in Nonalcoholic Fatty Liver Disease: Implications for Risk Assessment

Allostasis, a concept of anticipatory physiological regulation in response to external and internal challenges, was originally developed in the context of neuroendocrinology and behavioral medicine. Allostasis preserves function under changing conditions by abandoning physiological set points and developing new ones. Allostatic load refers to the aggregate effect of adaptation throughout life, and corresponds to the wear and tear associated with this process. In response to chronic stress, allostatic load may accumulate faster than expected if sustained activation of regulatory systems exceeds optimum operating ranges; this results in increased risk of disease. Used in a broader sense, the allostatic model of adaptive responses, trade-offs, feed-forward cycles, and collateral damage provides a framework for assessing the involvement of environmental-genetic interactions and co-morbidities in the course of chronic disease and developing a comprehensive score for personalized risk prediction. The utility of this approach is illustrated for nonalcoholic fatty liver disease, a prevalent condition with common and less common outcomes.

Interpreting physiological responses to environmental change through gene expression profiling

Identification of differentially expressed genes in response to environmental change offers insights into the roles of the transcriptome in the regulation of physiological responses. A variety of methods are now available to implement large-scale gene expression screens, and each method has specific advantages and disadvantages. Construction of custom cDNA microarrays remains the most popular route to implement expression screens in the non-model organisms favored by comparative physiologists, and we highlight some factors that should be considered when embarking along this path. Using a carp cDNA microarray, we have undertaken a broad, system-wide gene expression screen to investigate the physiological mechanisms underlying cold and hypoxia acclimation. This dataset provides a starting point from which to explore a range of specific mechanistic hypotheses at all levels of organization, from individual biochemical pathways to the level of the whole organism. We demonstrate the utility of two data analysis methods, Gene Ontology profiling and rank-based statistical methods, to summarize the probable physiological function of acclimation-induced gene expression changes, and to prioritize specific genes as candidates for further study.