Homeostatic Regulatory Mechanisms Research Articles

The Influence of Stress and Inactivity on Health: An Ayurvedic Perspective

Sedentary behavior, defined as activity that involves little to no movement of the body and, consequently, low energy expenditure, has recently gained attention as a potential indicator of the physical and mental health of adult populations. Sedentary behavior has been linked to mental health problems like anxiety, depression, and low self-esteem. These days, life is extremely busy - almost chaotic. Despite our increased productivity, we still feel there is never enough time to accomplish our true goals. This extremely rapid pace and the pressure that follows to "get things done" are serious issues that have a deeper impact on our bodies and minds than we may realize. We are all making ourselves sick by stressing about something that is not even a small inconvenience. The body contains thousands of homeostatic regulatory mechanisms. Among the most crucial ones are the control of body temperature, the maintenance of cell nutrition, the removal of waste, and the proper balance of hormones. So, the term "stress" is fairly wide and can take many various forms, it can interfere with several vital physiological processes.

Time-dependent changes in feeding behavior and energy balance associated with weight gain in mice fed obesogenic diets.

Obesity is characterized by dysregulated homeostatic mechanisms resulting in positive energy balance; however, when this dysregulation occurs is unknown. We assessed the time course of alterations to behaviors promoting weight gain in male and female mice switched to an obesogenic high-fat diet (HFD). Male and female C57BL/6J mice were housed in metabolic chambers and were switched from chow to a 60% or 45% HFD for 4 and 3 weeks, respectively. Food intake, meal patterns, energy expenditure (EE), and body weight were continuously measured. A separate cohort of male mice was switched from chow to a 60% HFD and was given access to locked or unlocked running wheels. Switching mice to obesogenic diets promotes transient bouts of hyperphagia during the first 2 weeks followed by persistent caloric hyperphagia. EE increases but not sufficiently enough to offset increased caloric intake, resulting in a sustained net positive energy balance. Hyperphagia is associated with consumption of calorically larger meals (impaired satiation) more frequently (impaired satiety), particularly during the light cycle. Running wheel exercise delays weight gain in male mice fed a 60% HFD by enhancing satiation and increasing EE. However, exercise effects on satiation are no longer apparent after 2 weeks, coinciding with weight gain. Exposure to obesogenic diets engages homeostatic regulatory mechanisms for ~2 weeks that ultimately fail, and consequent weight gain is characterized by impaired satiation and satiety. Insights into the etiology of obesity can be obtained by investigating changes to satiation and satiety mechanisms during the initial ~2 weeks of HFD exposure.

Homeostasis and evolution in relation to regeneration and repair.

Homeostasis constitutes a key concept in physiology and refers to self-regulating processes that maintain internal stability when adjusting to changing external conditions. It diminishes internal entropy constituting a driving force behind evolution. Natural selection might act on homeostatic regulatory mechanisms and control mechanisms including homeodynamics, allostasis, hormesis and homeorhesis, where different stable stationary states are reached. Regeneration is under homeostatic control through hormesis. Damage to tissues initiates a response to restore the impaired equilibrium caused by mild stress using cell proliferation, cell differentiation and cell death to recover structure and function. Repair is a homeorhetic change leading to a new stable stationary state with decreased functionality and fibrotic scarring without reconstruction of the 3-D pattern. Mechanisms determining entrance of the tissue or organ to regeneration or repair include the balance between innate and adaptive immune cells in relation to cell plasticity and stromal stem cell responses, and redox balance. The regenerative and reparative capacities vary in different species, distinct tissues and organs, and at different stages of development including ageing. Many cell signals and pathways play crucial roles determining regeneration or repair by regulating protein synthesis, cellular growth, inflammation, proliferation, autophagy, lysosomal function, metabolism and metalloproteinase cell signalling. Attempts to favour the entrance of damaged tissues to regeneration in those with low proliferative rates have been made; however, there are evolutionary constraint mechanisms leading to poor proliferation of stem cells in unfavourable environments or tumour development. More research is required to better understand the regulatory processes of these mechanisms.

A wider spectrum of avoidance and tolerance mechanisms explained ozone sensitivity of two white poplar ploidy levels.

Polyploidization can improve plant mass yield for bioenergy support, yet few studies have investigated ozone (O3) sensitivity linked to internal regulatory mechanisms at different ploidy levels. Diploid and triploid Populus tomentosa plants were exposed to ambient and ambient plus 60 ppb [O3]. We explored their differences in sensitivity (leaf morphological, physiological and biochemical traits, and plant mass) as well as mechanisms of avoidance (stomatal conductance, xanthophyll cycle, thermal dissipation) and tolerance (ROS scavenging system) in response to O3 at two developmental phases. Triploid plants had the highest plant growth under ambient O3, even under O3 fumigation. However, triploid plants were the most sensitive to O3 and under elevated O3 showed the largest decreases in photosynthetic capacity and performance, as well as increased shoot:root ratio, and the highest lipid peroxidation. Thus, plant mass production could be impacted in triploid plants under long-term O3 contamination. Both diploid and triploid plants reduced stomatal aperture in response to O3, thereby reducing O3 entrance, yet only in diploid plants was reduced stomatal aperture associated with minimal (non-significant) damage to photosynthetic pigments and lower lipid peroxidation. Tolerance mechanisms of plants of both ploidy levels mainly focused on the enzymatic reduction of hydrogen peroxide through catalase and peroxidase, yet these homeostatic regulatory mechanisms were higher in diploid plants. Our study recommends triploid white poplar as a bioenergy species only under short-term O3 contamination. Under continuously elevated O3 over the long term, diploid white poplar may perform better.

Insight into the regulatory networks underlying the high lipid perennial ryegrass growth under different irradiances.

Under favourable conditions, perennial ryegrass (Lolium perenne) engineered to accumulated high lipid (HL) carbon sink in their leaves was previously shown to also enhance photosynthesis and growth. The greater aboveground biomass was found to be diminished in a dense canopy compared to spaced pots. Besides, the underlying genetic regulatory network linking between leaf lipid sinks and these physiological changes remains unknown. In this study, we demonstrated that the growth advantage was not displayed in HL Lolium grown in spaced pots under low lights. Under standard lights, analysis of differentiating transcripts in HL Lolium reveals that the plants had elevated transcripts involved in lipid metabolism, light capturing, photosynthesis, and sugar signalling while reduced expression of genes participating in sugar biosynthesis and transportation. The plants also had altered several transcripts involved in mitochondrial oxidative respiration and redox potential. Many of the above upregulated or downregulated transcript levels were found to be complemented by growing the plants under low light. Overall, this study emphasizes the importance of carbon and energy homeostatic regulatory mechanisms to overall productivity of the HL Lolium through photosynthesis, most of which are significantly impacted by low irradiances.

104 Epigenetic Changes Due to Environmental Toxicants: An Animal Health Concern

Abstract Endocrine disrupting chemicals (EDCs) mimic natural hormones in the body, but they are not subject to normal homeostatic regulatory mechanisms. One such EDC that is particularly important in animal and human health is bisphenol A (BPA) that is an industrial chemical used to harden plastic, and thus, it is prevalent in many common household items. Notably, BPA, and likely other EDCs, persist in the environment. Besides binding to steroid and non-steroid receptors, BPA and other EDCs may induce epigenetic changes directly or by affecting gut bacteria that can promote such host changes. The objective of current studies was to determine whether developmental exposure to BPA and/or genistein, a phytoestrogen, induce persistent epigenetic and transcriptomic changes in various brain regions and the placenta. Additionally, the ability of these chemicals to alter gut microbiota and gut metabolites that may trigger such epigenetic alterations were investigated. Animal models used to examine for such effects included California mice (Peromyscus californicus), deer mice (Peromyscus maniculatus), laboratory mice (Mus musculus), and eastern painted turtles (Chrysemys picta). To link these ‘omics changes to actual phenotypic modifications, several behavioral domains were assessed in these species following developmental exposure to these compounds. Results across taxa clearly show that BPA and genistein leads to behavioral deficits, including cognitive and social impairments, anxiogenic behaviors, and reduced voluntary physical activity. Correspondingly, both chemicals transformed the epigenome and transcriptome in key brain regions and the placenta. Gut dysbiosis and stimulation of harmful bacterial metabolites ensued following early EDC exposure, and such effects persisted through adulthood. By using a one health medicine approached that evaluated various vertebrate animal species, there is solid evidence that perinatal exposure to BPA and genistein reprograms the epigenome and thereby lead to longstanding health consequences. Such findings have important veterinary and human health ramifications.

Bioindicators of the constants of homeostasis of the internal environment of crustaceans, cultured in different environmental conditions for the purpose of obtaining commodity products

The study of the composition and properties of the internal environment (hemolymph) of crustaceans grown in various conditions has an important ecological and physiological aspect, since a number of characteristics of the physiological status of objects can be used to assess the state of the environment, thus, they can be included in the number of bioindicators. However, the nature of the observed differences between objects grown under different conditions, the features of homeostatic regulatory mechanisms and the limits of the reference values of individual homeostasis constants are often not known. To formulate recommendations regarding the technological process of growing objects of warm-water aquaculture, taking into account the assessment of environmental conditions in dynamics through the analysis of indicators of the state of individuals — bioindicators — it is necessary to compare the state of individuals kept in different conditions. The object of the study was the Australian red claw crayfish Cherax quadricarinatus (Von Martens, 1868), cultivated under various conditions of intensive and semi-intensive cultivation. The studies have revealed that throughout the entire period of cultivation, individuals grown in ponds retained a high level of total protein, cholesterol and β-lipoproteins, in contrast to crayfish cultivated in pools. The values of these indicators as bioindicators indicate a high degree of compliance of the growing conditions with the needs of the studied object. Comparative assessment of fluctuations in the ratio of hemolymph shaped elements in the hemocyte composition between cancers grown under different conditions did not reveal significant differences. It was found that significantly higher growth rates are characteristic of crayfish grown in ponds, in contrast to the group of individuals cultivated in pools. The comparative analysis of bioindicators in different growing conditions presented by the authors of the article supplements information that is of significant interest for monitoring the growing conditions of this representative of warm water aquaculture, which will be valuable for specialists engaged in crustacean breeding.

Behaviorally and environmentally induced non-24-hour sleep-wake rhythm disorder in sighted patients.

To determine whether there was evidence of circadian or sleep-regulatory dysfunction in sighted individuals with non-24-hour sleep-wake rhythm disorder. Three sighted individuals with signs and/or symptoms of non-24-hour sleep-wake rhythm disorder were studied. Thirty-five- to 332-day laboratory and home-based assessments of sleep-wake and circadian timing, endogenous circadian period, photic input to the circadian pacemaker, and/or circadian and sleep-wake-dependent regulation of sleep were conducted. No evidence of circadian dysfunction was found in these individuals. Instead, sleep-wake timing appeared to dissociate from the circadian timing system, and/or self-selected sleep-wake and associated light/dark timing shifted the circadian pacemaker later, rather than the circadian pacemaker determining sleep-wake timing. These findings suggest that the etiology of this disorder may be light- and/or behaviorally induced in some sighted people, which has implications for the successful treatment of this disorder. Emens JS, St Hilaire MA, Klerman EB, etal. Behaviorally and environmentally induced non-24-hour sleep-wake rhythm disorder in sighted patients. J Clin Sleep Med. 2022;18(2):453-459.

Decoding the Role of Gut-Microbiome in the Food Addiction Paradigm.

Eating behaviour is characterised by a solid balance between homeostatic and hedonic regulatory mechanisms at the central level and highly influenced by peripheral signals. Among these signals, those generated by the gut microbiota have achieved relevance in recent years. Despite this complex regulation, under certain circumstances eating behaviour can be deregulated becoming addictive. Although there is still an ongoing debate about the food addiction concept, studies agree that patients with eating addictive behaviour present similar symptoms to those experienced by drug addicts, by affecting central areas involved in the control of motivated behaviour. In this context, this review tries to summarise the main data regarding the role of the gut microbiome in eating behaviour and how a gut dysbiosis can be responsible for a maladaptive behaviour such as “food addiction”.

Dietary Phytase and Lactic Acid-Treated CerealGrains Differently Affected Calcium and PhosphorusHomeostasis from Intestinal Uptake to SystemicMetabolism in a Pig Model.

High intestinal availability of dietary phosphorus (P) may impair calcium (Ca) homeostasis and bone integrity. In the present study, we investigated the effect of phytase supplementation in comparison to the soaking of cereal grains in 2.5% lactic acid (LA) on intestinal Ca and P absorption; intestinal, renal, and bone gene expression regarding Ca and P homeostasis; bone parameters; and serum levels of regulatory hormones in growing pigs. Thirty-two pigs were randomly assigned to one of four diets in a 2 × 2 factorial design in four replicate batches for 19 days. The diets comprised either untreated or LA-treated wheat and maize without and with phytase supplementation (500 phytase units/kg). Although both treatments improved the P balance, phytase and LA-treated cereals differently modulated gene expression related to intestinal absorption, and renal and bone metabolism of Ca and P, thereby altering homeostatic regulatory mechanisms as indicated by serum Ca, P, vitamin D, and fibroblast growth factor 23 levels. Moreover, phytase increased the gene expression related to reabsorption of Ca in the kidney, whereas LA-treated cereals decreased the expression of genes for osteoclastogenesis in bones, indicating an unbalanced systemic availability of minerals. In conclusion, high intestinal availability of dietary P may impair Ca homeostasis and bone integrity.

Effects of different transcranial direct current stimulation protocols on visuo-spatial contextual learning formation: evidence of homeostatic regulatory mechanisms

In the present study we tested the effects of different transcranial direct current stimulation (tDCS) protocols in the formation of visuo-spatial contextual learning (VSCL). The study comprised three experiments designed to evaluate tDCS-induced changes in VSCL measures collected during the execution of a visual search task widely used to examine statistical learning in the visuo-spatial domain. In Experiment 1, we probed for the effects of left-posterior parietal cortex (PPC) anodal-tDCS (AtDCS) at different timings (i.e. offline and online) and intensities (i.e. 3 mA and 1.5 mA). The protocol producing the more robust effect in Experiment 1 was used in Experiment 2 over the right-PPC, while in Experiment 3, cathodal-tDCS (CtDCS) was applied over the left-PPC only at a high intensity (i.e. 3 mA) but varying timing of application (offline and online). Results revealed that high intensity offline AtDCS reduced VSCL regardless of the stimulation side (Experiment 1 and 2), while no significant behavioral changes were produced by both online AtDCS protocols (Experiment 1) and offline/online CtDCS (Experiment 3). The reduced VSCL could result from homeostatic regulatory mechanisms hindering normal task-related neuroplastic phenomena.

Sleep, Aging, and Cellular Health: Aged-Related Changes in Sleep and Protein Homeostasis Converge in Neurodegenerative Diseases.

Many neurodegenerative diseases manifest in an overall aged population, the pathology of which is hallmarked by abnormal protein aggregation. It is known that across aging, sleep quality becomes less efficient and protein homeostatic regulatory mechanisms deteriorate. There is a known relationship between extended wakefulness and poorly consolidated sleep and an increase in cellular stress. In an aged population, when sleep is chronically poor, and proteostatic regulatory mechanisms are less efficient, the cell is inundated with misfolded proteins and suffers a collapse in homeostasis. In this review article, we explore the interplay between aging, sleep quality, and proteostasis and how these processes are implicated in the development and progression of neurodegenerative diseases like Alzheimer’s disease (AD). We also present data suggesting that reducing cellular stress and improving proteostasis and sleep quality could serve as potential therapeutic solutions for the prevention or delay in the progression of these diseases.

Mast cell quantification in the skin of dogs with hormonal dermatosis

The mast cells are important in physiological and pathological skin events. They play an important role in the homeostatic regulatory mechanisms in the skin and thyroid gland. Mast cells present a barrier to difference external environmental stimuli and play a mediating role in the presence of infectious agents under the epidermis. This study aimed to quantify the number of mast cells in histological sections of the skin of healthy dogs and dogs with hypothyroidism and hyperadrenocorticism and to determine the distribution of mast cell numbers in the superficial dermis and deep dermis. When we compared the total mast cell count per high power field in dogs with hypothyroidism, hyperadrenocorticism and healthy dogs, only dogs with hypothyroidism had a significant difference in the quantification of mast cells per high power field, (p < 0.05). After analyzing our results, it was possible to conclude that animals with hypothyroidism produce greater amount of mast cells in the superficial dermis than patients with hyperadrenocorticism and healthy animals.

Critical Role for the Microbiota in CX3CR1+ Intestinal Mononuclear Phagocyte Regulation of Intestinal T Cell Responses

The intestinal barrier is vulnerable to damage by microbiota-induced inflammation that is normally restrained through mechanisms promoting homeostasis. Such disruptions contribute to autoimmune and inflammatory diseases including inflammatory bowel disease. We identified a regulatory loop whereby, in the presence of the normal microbiota,intestinal antigen-presenting cells (APCs) expressing the chemokine receptor CX3CR1 reduced expansion of intestinal microbe-specific T helper 1 (Th1) cells and promoted generation of regulatory Tcells responsive to food antigens andthe microbiota itself. We identified that disruption of the microbiota resulted in CX3CR1+ APC-dependent inflammatory Th1 cell responses with increased pathology after pathogen infection. Colonization with microbes that can adhere to theepithelium was able to compensate for intestinal microbiota loss, indicating that although microbial interactions with the epithelium can be pathogenic, they can also activate homeostatic regulatory mechanisms. Our results identify a cellular mechanism by which the microbiota limitsintestinal inflammation and promotes tissue homeostasis.

1046 ASSESSMENT OF SLEEP AND INFLAMMATION IN CHRONIC OROFACIAL PAIN: A PRELIMINARY STUDY

Sleep disturbances, which are commonly reported in Temporomandibular disorder (TMD), may confer increased risk for the development, progression, and persistence of pain through changes in homeostatic regulatory mechanisms including the immune system. The primary purpose of the current pilot study was to examine case-control differences in subjective and objective sleep measures and its relationship with the inflammatory cytokine, Interleukin 6 (IL-6). Twenty-five individuals with TMD and 24 healthy controls completed a sleep diary and actigraphy (ActiGraph wGT3X; non-dominat wrist) over a 7-day period. On day 7, blood was collected for analysis of IL-6 levels. Group differences in IL-6 and self-reported sleep quality (0–4 scale) and efficiency in addition to actigraphy-based measures (sleep efficiency; wake after sleep onset, WASO) were averaged and evaluated as dependent variables in analyses of covariance controlling for body mass index (BMI). Data was presented as means and 95% confidence intervals (CI). Associations between sleep and IL-6 were assessed with partial correlations. Self-reported sleep differed between TMD and healthy controls (HC) such that TMD participants reported poor sleep quality (TMD: 3.39, 3.34-3.45 95%CI; HC: 3.86, 3.81-3.91 95%CI; p<0.001) and lower sleep efficiency (TMD: 86.81, 86.23-87.38 95%CI; HC: 91.99, 91.44-92.56 95%CI; p<0.001). In addition, similar differences were observed for actigraphy-based outcomes including poorer sleep efficiency (TMD: 82.73, 82.32-83.14 95%CI; HC: 85.40, 85.00-85.79 95%CI; p<0.001) and longer WASO (TMD: 76.53, 74.50-78.55 95%CI; HC: 56.74, 54.78-58.68 95%CI; p<0.001) in TMD participants compared to HC. TMD participants also had higher levels of IL-6 (TMD: 13.49, 13.06-13.94 95%CI; HC: 3.67, 3.25-4.09 95%CI; p<0.001). Additionally, IL-6 was associated with self-reported measures whereby higher levels of IL-6 were associated with poorer sleep quality (r=-0.27, p=0.02) and efficiency (r=-0.42, p<0.001). Associations with actigraphy outcomes were not significant. The current study supports previous studies that individuals with chronic pain commonly report disturbed sleep, which may contribute to clinical pain through a pro-inflammatory imbalance (i.e., enhanced IL-6 roduction). While further analysis regarding the discrepancy between objective and subjective parameters on IL-6 is needed, sleep behaviors should be considered as a method to manage TMD. K99DE022368 (NIDCR)

Recent advances in therapeutic strategies that focus on the regulation of ion channel expression.

A number of different ion channel types are involved in cell signaling networks, and homeostatic regulatory mechanisms contribute to the control of ion channel expression. Profiling of global gene expression using microarray technology has recently provided novel insights into the molecular mechanisms underlying the homeostatic and pathological control of ion channel expression. It has demonstrated that the dysregulation of ion channel expression is associated with the pathogenesis of neural, cardiovascular, and immune diseases as well as cancers. In addition to the transcriptional, translational, and post-translational regulation of ion channels, potentially important evidence on the mechanisms controlling ion channel expression has recently been accumulated. The regulation of alternative pre-mRNA splicing is therefore a novel therapeutic strategy for the treatment of dominant-negative splicing disorders. Epigenetic modification plays a key role in various pathological conditions through the regulation of pluripotency genes. Inhibitors of pre-mRNA splicing and histone deacetyalase/methyltransferase have potential as potent therapeutic drugs for cancers and autoimmune and inflammatory diseases. Moreover, membrane-anchoring proteins, lysosomal and proteasomal degradation-related molecules, auxiliary subunits, and pharmacological agents alter the protein folding, membrane trafficking, and post-translational modifications of ion channels, and are linked to expression-defect channelopathies. In this review, we focused on recent insights into the transcriptional, spliceosomal, epigenetic, and proteasomal regulation of ion channel expression: Ca(2+) channels (TRPC/TRPV/TRPM/TRPA/Orai), K(+) channels (voltage-gated, KV/Ca(2+)-activated, KCa/two-pore domain, K2P/inward-rectifier, Kir), and Ca(2+)-activated Cl(-) channels (TMEM16A/TMEM16B). Furthermore, this review highlights expression of these ion channels in expression-defect channelopathies.

A physiologist's view of homeostasis.

Homeostasis is a core concept necessary for understanding the many regulatory mechanisms in physiology. Claude Bernard originally proposed the concept of the constancy of the "milieu interieur," but his discussion was rather abstract. Walter Cannon introduced the term "homeostasis" and expanded Bernard's notion of "constancy" of the internal environment in an explicit and concrete way. In the 1960s, homeostatic regulatory mechanisms in physiology began to be described as discrete processes following the application of engineering control system analysis to physiological systems. Unfortunately, many undergraduate texts continue to highlight abstract aspects of the concept rather than emphasizing a general model that can be specifically and comprehensively applied to all homeostatic mechanisms. As a result, students and instructors alike often fail to develop a clear, concise model with which to think about such systems. In this article, we present a standard model for homeostatic mechanisms to be used at the undergraduate level. We discuss common sources of confusion ("sticky points") that arise from inconsistencies in vocabulary and illustrations found in popular undergraduate texts. Finally, we propose a simplified model and vocabulary set for helping undergraduate students build effective mental models of homeostatic regulation in physiological systems.

Influence of Aging and Gender Differences on Feeding Behavior and Ghrelin-Related Factors during Social Isolation in Mice.

Psychological stress due to social isolation is known to cause abnormal feeding behaviors, but the influences of gender and aging on subchronic stress-induced changes in feeding behaviors are unknown. Thus, we examined the changes in body weight, food intake, and orexigenic ghrelin-related factors during 2 weeks of isolation stress in young and aged mice. Food intake increased significantly in young mice in the isolation group compared with the group-housed control throughout the experimental period. This isolation-induced increase in food intake was not observed in aged mice. In young mice, there were no significant differences in body weight between the isolated group and group-housed control up to 2 weeks. However, aged male mice exhibited significant weight loss at 2 weeks and a similar tendency was observed in aged female mice. Young male mice, but not female mice, had significantly increased (2.2-fold) plasma acylated ghrelin levels after 1 week of isolation compared with the group-housed control. A significant but lower increase (1.3-fold) was also observed in aged male mice. Hypothalamic preproghrelin gene expression decreased significantly with isolation in young male mice, whereas it increased significantly in female mice. The expression levels of NPY and AGRP in the hypothalamus, which are transmitted by elevated peripheral ghrelin signals, increased significantly in isolated young male mice, whereas the AGRP expression levels decreased significantly in young female mice. Isolation caused no significant differences in the expression levels of these genes in aged mice. In isolation, young female mice exhibited markedly increased dark- and light-phase locomotor activities compared with male mice, whereas male and female aged mice exhibited no obvious increases in activity immediately after the dark phase started. We conclude that the gender-specific homeostatic regulatory mechanisms required to maintain body weight operated during subchronic psychological stress in young mice but not in aged mice.

Genetic and functional studies of the intervertebral disc: a novel murine intervertebral disc model.

Intervertebral disc (IVD) homeostasis is mediated through a combination of micro-environmental and biomechanical factors, all of which are subject to genetic influences. The aim of this study is to develop and characterize a genetically tractable, ex vivo organ culture model that can be used to further elucidate mechanisms of intervertebral disc disease. Specifically, we demonstrate that IVD disc explants (1) maintain their native phenotype in prolonged culture, (2) are responsive to exogenous stimuli, and (3) that relevant homeostatic regulatory mechanisms can be modulated through ex-vivo genetic recombination. We present a novel technique for isolation of murine IVD explants with demonstration of explant viability (CMFDA/propidium iodide staining), disc anatomy (H&E), maintenance of extracellular matrix (ECM) (Alcian Blue staining), and native expression profile (qRT-PCR) as well as ex vivo genetic recombination (mT/mG reporter mice; AdCre) following 14 days of culture in DMEM media containing 10% fetal bovine serum, 1% L-glutamine, and 1% penicillin/streptomycin. IVD explants maintained their micro-anatomic integrity, ECM proteoglycan content, viability, and gene expression profile consistent with a homeostatic drive in culture. Treatment of genetically engineered explants with cre-expressing adenovirus efficaciously induced ex vivo genetic recombination in a variety of genetically engineered mouse models. Exogenous administration of IL-1ß and TGF-ß3 resulted in predicted catabolic and anabolic responses, respectively. Genetic recombination of TGFBR1fl/fl explants resulted in constitutively active TGF-ß signaling that matched that of exogenously administered TGF-ß3. Our results illustrate the utility of the murine intervertebral disc explant to investigate mechanisms of intervertebral disc degeneration.

Toward a Human Emotions Taxonomy (Based on Their Automatic vs. Reflective Origin)

Certain emotional processes “bypass the will” and even awareness, whereas others arise due to the deliberative evaluation of objects, states, and events. It is important to differentiate between the automatic versus reflective origins of emotional processes, and sensory versus conceptual bases of diverse negative and positive emotions. A taxonomy of emotions based on different origins is presented. This taxonomy distinguishes between negative and positive automatic versus reflective emotions. The automatic emotions are connected with the (a) homeostatic and (b) hedonistic regulatory mechanisms. The reflective emotions—uniquely human—are described in reference to deliberative processes and appraisals based on two types of conceptual and verbalized evaluative standards: (a) ideal self-standards and (b) general, axiological standards of good and evil.