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PubMed2006

Regulation of protein phosphatase 1gamma activity in hypoxia through increased interaction with NIPP1: implications for cellular metabolism.

Eukaryotic cells sense decreased oxygen levels and respond by altering their metabolic strategy to sustain non-respiratory ATP production through glycolysis, and thus promote cell survival in a hypoxic environment. Protein phosphatase 1 (PP1) has been recently implicated in the governance of the rational use of energy when metabolic substrates are abundant and contributes to cellular recovery following metabolic stress. Under conditions of hypoxia, the expression of the gamma isoform of PP1 (PP1gamma), is diminished, an event we have hypothesized to be involved in the adaptive cellular response to hypoxia. Decreased PP1gamma activity in hypoxia has a profound impact on the activity of the cAMP response element binding protein (CREB), a major transcriptional regulator of metabolic genes and processes. Here, we demonstrate a further mechanism leading to inhibition of PP1 activity in hypoxia which occurs at least in part through increased association with the nuclear inhibitor of PP1 (NIPP1), an event dependent upon decreased basal cAMP/PKA-dependent signaling. Using a dominant negative NIPP1 construct, we provide evidence that NIPP1 plays a major role in the regulation of both CREB protein expression and CREB-dependent transcription in hypoxia. Furthermore, we demonstrate functional sequellae of such events including altered gene expression and recovery of cellular ATP levels. In summary, we demonstrate that interaction with NIPP1 mediates decreased PP1gamma activity in hypoxia, an event which may constitute an inherent part of the cellular oxygen-sensing machinery and may play a role in physiologic adaptation to hypoxia.

CREB-Binding Protein↗
PubMed1992

Immunoregulatory mechanisms of the eye.

Immune-privileged sites, such as the the internal compartments of the eye, and perhaps the brain, are physiological adaptations that act to modify systemic immune responses such that effector mechanisms that invoke locally destructive inflammation are suppressed. In the case of the eye, the parenchymal cells of the iris and ciliary body create an intraocular microenvironment that alters both the induction and expression of immunity to antigens placed within the eye. The immunosuppressive properties of the intraocular microenvironment are mediated by cytokines, especially transforming growth factor-beta (TGF beta). This cytokine has been demonstrated to endow intraocular antigen-presenting cells with the capacity to induce an atypical or deviant form of immunity to intraocular antigens which is selectively deficient in T cells that mediate delayed hypersensitivity. Moreover, TGF beta, along with other intraocular factors, can impair the intraocular expression of pre-existing cell-mediated immunity by inhibiting antigen-driven activation of primed T cells. The strategies employed by the eye to engender specialized immune responses appropriate to its physiological functions are discussed in terms of other privileged sites such as the brain.

Animals↗
PubMed1992

Central nervous system influences on lymphocyte migration.

The immune response network is only one of many physiologic adaptive responses to environmental change and there is now substantial evidence that adaptive responses involving the central nervous system have an impact on immune outcome. Effective immune function depends upon a highly mobile population of precursor and effector cells of the lymphoid system. In this review it is proposed that many of the alterations in immunity resulting from CNS activity may be explained in terms of changes in lymphocyte migration patterns in response to endocrine signals, neural signals via neurotransmitter release, or direct contacts between nerves and cells of the immune system.

Animals↗
PubMed1984

The importance of plasma volume expansion and nutrition in twin pregnancy.

Physiological adaptation including expansion in plasma volume is exaggerated in women with twin pregnancies. In singleton pregnancy and multiparous twin pregnancies there is an association between plasma volume expansion and birth weight, but this is not so in primigravid twin pregnancies. Women with twin pregnancies have a similar dietary intake to singleton pregnancies, but it is not known whether there are differences with parity or zygosity. Absorption and utilisation of nutrients may be increased to meet demands for extra fetal growth. Nutrient supply and plasma volume expansion will be further discussed and their association with birth weight presented.

Birth Weight↗
PubMed2005

The neonate cry after cesarean section and vaginal delivery during the first minutes of life.

Although the option for vaginal delivery is most physiological, the achievement of cesarean section is very common in Brazil. The neonate cry represents the beginning of both processes, physiological adaptation and human vocal communication. The cry emission depends on the functioning of respiratory and laryngeal muscles, which are controlled by the nervous system. The acoustic analysis of neonate cry is useful in the assessment of healthy babies and can be used to characterize the signals of diseases through a previously multidisciplinary diagnosis, with immediate medical intervention. The present study compared the acoustic cry characteristics of 30 healthy newborn after a cesarean section and 30 healthy newborn after a vaginal delivery, of both genders, from the exact moment of birth until the first 5 min of life. Using the softwares VOXMETRIA and GRAM, it was possible to analyze the duration, frequency, intensity, occurrence, localization and inspiratory phonation, besides the type of spectrographic tracings. The acoustic cry characteristics of newborns after a C section and a vaginal delivery could evidence not only harmonic, expiratory, acute and strong emissions, but also emissions rich in sounds and varied in types of melody. The differences found can be related to the physiology of birth.

Acoustics↗
PubMed1998

Modified mesh for hernia repair that is adapted to the physiology of the abdominal wall.

OBJECTIVE: To develop a new mesh for hernia repair that is adapted to the physiological forces. DESIGN: Animal experiment. SETTING: Surgical Department of the RWTH-Aachen. ANIMALS: Wistar rats MAIN OUTCOME MEASURES: Textile analysis, tensile strength, bending stiffness, histology and morphometry. RESULTS: After textile analysis of commercially available meshes in clinical use we defined the physiological forces and constructed a new mesh (Soft Hernia Mesh, SHM) based on a combination of non-absorbable polypropylene and absorbable polyglactin 910. The amount of non-absorbable material could be reduced to < 30% compared with Marlex while still guaranteeing the necessary pulling force of 16 N/cm. Improvements of the hosiery structure improved the symmetrical distribution of the retaining forces in all directions. Compared with the considerable restriction of the abdominal wall mobility by Prolene (polypropylene) and Mersilene (polyester) meshes there was no increase in the bending stiffness after the implantation of the new mesh. Histological examination showed a pronounced reduction of the inflammatory reaction in the tissues, and the collagen bundles were orientated merely around the mesh filaments instead of forming a scar plate that completely embedded the mesh. CONCLUSION: Different meshes caused specific histological reactions with changes of their mechanical properties after implantation in rodents. A new mesh with a reduced amount of polypropylene showed both less inflammation and less restriction in the mobility of the abdominal wall though it exceeded the required tensile strength of 16 N/cm.

Abdominal Muscles↗
PubMed2004

Behavioural and neuroendocrine adaptations to repeated stress during puberty in male golden hamsters.

In adult animals, the consequences of stress are often severe and long lasting. Repeated subjugation in adult male golden hamsters inhibits aggression and increases submissive and avoidant behaviours. By contrast, subjugation during puberty enhances offensive aggression. The goals of this study were to characterize behavioural and neuroendocrine responses of naïve and repeatedly subjugated juveniles to social defeat and to assess potential recovery from social stress. From the onset of puberty on postnatal day 28 (P28) to mid puberty (P42), animals were either socially subjugated or placed in a clean and empty cage for 20 min daily. The subjugated and control groups were further divided into subgroups and sacrificed under basal conditions or after social defeat on P28, P35 (early puberty), P45 (mid puberty) and P70 (early adulthood). On P35 and P45, repeatedly subjugated juveniles showed a complete inhibition of olfactory investigation (i.e. risk assessment) towards aggressive adults. Repeatedly subjugated also animals had lower postdefeat cortisol levels than controls on P45. Interestingly, basal cortisol levels increased gradually during puberty but did not differ between treatment groups at any point. Repeated subjugation was also associated with increased tyrosine hydroxylase immunoreactivity (ir-TH) within the extended medial amygdala. After a 4-week recovery period, none of these variables differed between subjugated and control groups. In an additional experiment, subjugated adults also had increased ir-TH in the medial extended amygdala, suggesting that these neurones are particularly responsive to social stress. In conclusion, puberty may be a developmental period characterized by behavioural and neuroendocrine plasticity in stress responsiveness. Furthermore, peri-pubertal changes in stress hormones may explain why juvenile hamsters are more resilient to social stress than adults.

Adaptation, Physiological↗
PubMed1979

Altered sleep/wake patterns and circadian rhythms. Laboratory and field studies of sympathoadrenomedullary and related variables.

Six studies on sleep/wake patterns and circadian rhythms were carried out. In summary: (1) Adrenaline excretion, self-rated activation, and body temperature rhythms persisted during sleep deprivation, resisted adjustment to rotating shift work, but adjusted rather well to permanent night work. Noradrenaline adjusted to most schedules and lost its rhythm during sleep deprivation. When night sleep was reintroduced the noradrenaline rhythm reappeared while the existing adrenaline rhythm was accentuated. (2) Exposure to a performance stressor at the trough raised adrenaline to daytime levels. An equally large response was seen at the peak. (3) Interindividual day-to-day consistency of 3 and 24 hour levels was high for both catecholamines. Intraindividual consistency of the 24-hour pattern was high for adrenaline but low for noradrenaline. Cosine estimates of adrenaline phase showed a considerable intraindividual consistency while interindividual consistency was poor. Noradrenaline had poor cosine fit. (4) Sleep deprivation did not change catecholamine excretion either during the vigil or during recovery sleep. (5) It was concluded that adrenaline excretion, rated alertness, and body temperature exhibited self-sustained circadian rhythms which made adjustment to new sleep/wake patterns very difficult, and that the noradrenaline excretion rhythm depended on exogenous factors.

Adaptation, Physiological↗
PubMed2001

Physiological rationale for responsiveness of mouse embryonic stem cells to gp130 cytokines.

Embryonic stem cells are established directly from the pluripotent epiblast of the preimplantation mouse embryo. Their derivation and propagation are dependent upon cytokine-stimulated activation of gp130 signal transduction. Embryonic stem cells maintain a close resemblance to epiblast in developmental potency and gene expression profile. The presumption of equivalence between embryonic stem cells and epiblast is challenged, however, by the finding that early embryogenesis can proceed in the absence of gp130. To explore this issue further, we have examined the capacity of gp130 mutant embryos to accommodate perturbation of normal developmental progression. Mouse embryos arrest at the late blastocyst stage when implantation is prevented. This process of diapause occurs naturally in lactating females or can be induced experimentally by removal of the ovaries. We report that gp130(-/-) embryos survive unimplanted in the uterus after ovariectomy but, in contrast to wild-type or heterozygous embryos, are subsequently unable to resume development. Inner cell masses explanted from gp130(-/-) delayed blastocysts produce only parietal endoderm, a derivative of the hypoblast. Intact mutant embryos show an absence of epiblast cells, and Hoechst staining and TUNEL analysis reveal a preceding increased incidence of cell death. These findings establish that gp130 signalling is essential for the prolonged maintenance of epiblast in vivo, which is commonly required of mouse embryos in the wild. We propose that the responsiveness of embryonic stem cells to gp130 signalling has its origin in this adaptive physiological function.

Animals↗
PubMed1997

Chronic food restriction and streptozotocin-induced diabetes differentially alter prodynorphin mRNA levels in rat brain regions.

It was previously reported that chronic food restriction and streptozotocin-induced diabetes lead to brain region-specific changes in levels of Prodyn-derived peptides. These changes parallel behavioral adaptations that are reversed by opioid antagonists. In the present study, effects of food restriction and diabetes on Prodyn gene expression were measured in rat brain regions using a quantitative solution hybridization mRNA assay. Picogram amounts of Prodyn mRNA were determined in extracts of five brain regions. The highest density of Prodyn mRNA was observed in extracts of nucleus accumbens (4.68 pg/microg total RNA), bed nucleus of the stria terminalis (4.18 pg/microg), and in caudate nucleus (3.51 pg/microg). Lower levels were observed in the lateral hypothalamus (1.87 pg/microg) and central nucleus of the amygdala (1.22 pg/microg). Food restriction and diabetes both markedly increased the levels of Prodyn mRNA in the central amygdala (163% and 93%, respectively). Levels in the lateral hypothalamus were also increased (35% and 29%, respectively), though only the food-restriction effect was statistically significant. Neither treatment altered prodynorphin mRNA levels in the caudate nucleus, nucleus accumbens or bed nucleus of the stria terminalis. These results suggest that dynorphin neurons in central amygdala and lateral hypothalamus may be involved in behavioral or physiological adaptations to sustained metabolic need.

Animals↗
PubMed1996

Submaximal running economy in run-trained pre-pubertal boys.

There is an increasing tendency for young children to participate in training and competitive running. The impact long-term training has upon stimulating functional physiological adaptation has yet to be fully understood. In this study cardio-respiratory and kinematic differences were assessed at submaximal and maximal exercise intensities in run-trained and non-run-trained boys. Thirty three pre-pubertal boys volunteered to take part in the study. The subjects were in two groups: 15 run-trained subjects [age 11.7 +/- 1.06 yrs, mean +/- SD] and 18 non-run-trained (control) subjects [age 11.3 +/- 0.90 yrs]. Two separate (4 x 3 min) submaximal protocols were used for the trained and non-run-trained groups, with two of the speeds overlapping for comparison purposes. In addition, all boys also performed a maximal oxygen consumption test. Mean VO2max value for the run trained group was 60.5 +/- 3.3 ml/kg/min and for the control group 51.1 +/- 4.3 ml/kg/min, (p < 0.001). No significant differences were found for submaximal running economy at either comparison speed. In addition, no significant (p > 0.05) differences were noted between the groups for any of the kinematic variables at the two comparison speeds. However, selected physiological differences did exist at the submaximal running speeds. The source of the differences that did exist between the two groups may be the result of training, genetic pre-selection or developmental differences between the groups.

Child↗
PubMed2001

Chronic orofacial pain: is the puzzle unraveling?

Conditions involving chronic orofacial pain represent a major health problem, and patients with persistent pain are difficult to manage successfully. These conditions are often comorbid with additional health issues such as sleep disturbances, cardiovascular, gastrointestinal and reproductive system complaints, weight loss or weight gain, swelling, numbness, sweating and flushing, and concerns regarding loss of libido, drive, attention, and memory. Neuroendocrine and autonomic pain-stress responsivity and the consequences of pain for sensory, motor, immune and reproductive functions, and mood seem to account for the broad range of comorbid complaints. Susceptibility to a particular response appears to explain intra-individual differences in disease expression. Understanding of these regulatory, mostly adaptive processes will support novel treatments to manage many troublesome comorbid complaints for which current approaches are unsatisfactory.

Adaptation, Physiological↗
PubMed2004

Stress-induced alternative gene splicing in mind-body medicine.

Recent research documents how psychosocial stress can alter the expression of the acetylcholinesterase gene to generate at least 3 alternative proteins that are implicated in a wide variety of normal mind-body functions, as well as pathologies. These range from early embryological development, plasticity of the brain in adulthood, post-traumatic stress disorder (PTSD), and stress-associated dysfunctions of the central nervous, endocrine, and immune systems, to age-related neuropathologies. Such stress-induced alternative gene splicing is proposed here as a major mind-body pathway of psychosocial genomics-the modulation of gene expression by creative psychological, social, and cultural processes. We explore the types of research that are now needed to investigate how stress-induced alternative splicing of the acetylcholinesterase gene may play a pivotal role in the deep psychobiology of psychotherapy, meditation, spiritual rituals, and the experiencing of positive humanistic values that have been associated with mind-body medicine, such as compassion, beneficence, serenity, forgiveness, and gratitude.

Acetylcholinesterase↗