Identification and Characterization of Pheasant and Quail Avian Beta Defensin 2
USDA-ARS?s Scientific Manuscript database
Peptides play significant roles in physiology as hormones, neurotransmitters, growth, antimicrobial, and signal transducing factors. Identification of their tissue specific occurrence and abundance may lead to a better understanding of their physiological significance. Previously, we identified matu...
Clarifying the Roles of Homeostasis and Allostasis in Physiological Regulation
Ramsay, Douglas S.; Woods, Stephen C.
2014-01-01
Homeostasis, the dominant explanatory framework for physiological regulation, has undergone significant revision in recent years, with contemporary models differing significantly from the original formulation. Allostasis, an alternative view of physiological regulation, goes beyond its homeostatic roots, offering novel insights relevant to our understanding and treatment of several chronic health conditions. Despite growing enthusiasm for allostasis, the concept remains diffuse, due in part to ambiguity as to how the term is understood and used, impeding meaningful translational and clinical research on allostasis. Here we provide a more focused understanding of homeostasis and allostasis by explaining how both play a role in physiological regulation, and a critical analysis of regulation suggests how homeostasis and allostasis can be distinguished. Rather than focusing on changes in the value of a regulated variable (e.g., body temperature, body adiposity, or reward), research investigating the activity and relationship among the multiple regulatory loops that influence the value of these regulated variables may be the key to distinguishing homeostasis and allostasis. The mechanisms underlying physiological regulation and dysregulation are likely to have important implications for health and disease. PMID:24730599
Physiological significance of TRPV2 as a mechanosensor, thermosensor and lipid sensor.
Shibasaki, Koji
2016-09-01
This review provides a summary of the physiological significance of the TRPV2 ion channel. While TRPV2 was initially characterized as a noxious heat sensor, we found that TRPV2 can also act as a mechanosensor in embryonic neurons or adult myenteric neurons. Here, we summarize the newly characterized functions of TRPV2, including the research progress that has been made toward our understanding of TRPV2 physiology, and discuss other recent data pertaining to TRPV2. It is thought that TRPV2 may be an important drug target based on its broad expression patterns and important physiological roles. The possible associations between diseases and TRPV2 are also discussed.
Prymaczok, Natalia C; Pasqualino, Valeria M; Viau, Verónica E; Rodríguez, Enrique M; Medesani, Daniel A
2016-02-01
This study was aimed at determining the role of the crustacean hyperglycemic hormone (CHH) in the physiological compensation to both saline and thermal stress, in the freshwater crayfish Cherax quadricarinatus. By determining the expression of the CHH gene in the eyestalk of juvenile crayfish, we found that maximal induction of CHH was induced at high salinity (10 g/L) and low temperature (20 °C). In order to investigate the role of CHH in the physiological compensation to such stressful conditions, recombinant CHH was supplied to stressed animals. CHH-injected crayfish showed increased hemolymphatic levels of glucose, in accordance with a significant utilization of glycogen reserves from the hepatopancreas. Furthermore, CHH administration allowed stressed animals to regulate hemolymphatic sodium and potassium at more constant levels than controls. Taken together, these results suggest a relevant role of CHH in increasing the energy available intended for processes involved in the physiological compensation of C. quadricarinatus to both saline and thermal stress.
Ramajo, Laura; Marbà, Núria; Prado, Luis; Peron, Sophie; Lardies, Marco A; Rodriguez-Navarro, Alejandro B; Vargas, Cristian A; Lagos, Nelson A; Duarte, Carlos M
2016-06-01
Future ocean acidification (OA) will affect physiological traits of marine species, with calcifying species being particularly vulnerable. As OA entails high energy demands, particularly during the rapid juvenile growth phase, food supply may play a key role in the response of marine organisms to OA. We experimentally evaluated the role of food supply in modulating physiological responses and biomineralization processes in juveniles of the Chilean scallop, Argopecten purpuratus, that were exposed to control (pH ~ 8.0) and low pH (pH ~ 7.6) conditions using three food supply treatments (high, intermediate, and low). We found that pH and food levels had additive effects on the physiological response of the juvenile scallops. Metabolic rates, shell growth, net calcification, and ingestion rates increased significantly at low pH conditions, independent of food. These physiological responses increased significantly in organisms exposed to intermediate and high levels of food supply. Hence, food supply seems to play a major role modulating organismal response by providing the energetic means to bolster the physiological response of OA stress. On the contrary, the relative expression of chitin synthase, a functional molecule for biomineralization, increased significantly in scallops exposed to low food supply and low pH, which resulted in a thicker periostracum enriched with chitin polysaccharides. Under reduced food and low pH conditions, the adaptive organismal response was to trade-off growth for the expression of biomineralization molecules and altering of the organic composition of shell periostracum, suggesting that the future performance of these calcifiers will depend on the trajectories of both OA and food supply. Thus, incorporating a suite of traits and multiple stressors in future studies of the adaptive organismal response may provide key insights on OA impacts on marine calcifiers. © 2015 John Wiley & Sons Ltd.
NUCLEAR FACTOR-Y: still complex after all these years?
Myers, Zachary A; Holt, Ben F
2018-06-11
The NUCLEAR FACTOR-Y (NF-Y) families of transcription factors are important regulators of plant development and physiology. Though NF-Y regulatory roles have recently been suggested for numerous aspects of plant biology, their roles in flowering time, early seedling development, stress responses, hormone signaling, and nodulation are the best characterized. The past few years have also seen significant advances in our understanding of the mechanistic function of the NF-Y, and as such, increasingly complex and interesting questions are now more approachable. This review will primarily focus on these developmental, physiological, and mechanistic roles of the NF-Y in recent research. Copyright © 2018 Elsevier Ltd. All rights reserved.
Woodall, Benjamin P.; Woodall, Meryl C.; Luongo, Timothy S.; Grisanti, Laurel A.; Tilley, Douglas G.; Elrod, John W.; Koch, Walter J.
2016-01-01
GRK2, a G protein-coupled receptor kinase, plays a critical role in cardiac physiology. Adrenergic receptors are the primary target for GRK2 activity in the heart; phosphorylation by GRK2 leads to desensitization of these receptors. As such, levels of GRK2 activity in the heart directly correlate with cardiac contractile function. Furthermore, increased expression of GRK2 after cardiac insult exacerbates injury and speeds progression to heart failure. Despite the importance of this kinase in both the physiology and pathophysiology of the heart, relatively little is known about the role of GRK2 in skeletal muscle function and disease. In this study we generated a novel skeletal muscle-specific GRK2 knock-out (KO) mouse (MLC-Cre:GRK2fl/fl) to gain a better understanding of the role of GRK2 in skeletal muscle physiology. In isolated muscle mechanics testing, GRK2 ablation caused a significant decrease in the specific force of contraction of the fast-twitch extensor digitorum longus muscle yet had no effect on the slow-twitch soleus muscle. Despite these effects in isolated muscle, exercise capacity was not altered in MLC-Cre:GRK2fl/fl mice compared with wild-type controls. Skeletal muscle hypertrophy stimulated by clenbuterol, a β2-adrenergic receptor (β2AR) agonist, was significantly enhanced in MLC-Cre:GRK2fl/fl mice; mechanistically, this seems to be due to increased clenbuterol-stimulated pro-hypertrophic Akt signaling in the GRK2 KO skeletal muscle. In summary, our study provides the first insights into the role of GRK2 in skeletal muscle physiology and points to a role for GRK2 as a modulator of contractile properties in skeletal muscle as well as β2AR-induced hypertrophy. PMID:27566547
The Body and the Beautiful: Health, Attractiveness and Body Composition in Men’s and Women’s Bodies
Brierley, Mary-Ellen; Brooks, Kevin R.; Mond, Jonathan; Stevenson, Richard J.
2016-01-01
The dominant evolutionary theory of physical attraction posits that attractiveness reflects physiological health, and attraction is a mechanism for identifying a healthy mate. Previous studies have found that perceptions of the healthiest body mass index (weight scaled for height; BMI) for women are close to healthy BMI guidelines, while the most attractive BMI is significantly lower, possibly pointing to an influence of sociocultural factors in determining attractive BMI. However, less is known about ideal body size for men. Further, research has not addressed the role of body fat and muscle, which have distinct relationships with health and are conflated in BMI, in determining perceived health and attractiveness. Here, we hypothesised that, if attractiveness reflects physiological health, the most attractive and healthy appearing body composition should be in line with physiologically healthy body composition. Thirty female and 33 male observers were instructed to manipulate 15 female and 15 male body images in terms of their fat and muscle to optimise perceived health and, separately, attractiveness. Observers were unaware that they were manipulating the muscle and fat content of bodies. The most attractive apparent fat mass for female bodies was significantly lower than the healthiest appearing fat mass (and was lower than the physiologically healthy range), with no significant difference for muscle mass. The optimal fat and muscle mass for men’s bodies was in line with the healthy range. Male observers preferred a significantly lower overall male body mass than did female observers. While the body fat and muscle associated with healthy and attractive appearance is broadly in line with physiologically healthy values, deviations from this pattern suggest that future research should examine a possible role for internalization of body ideals in influencing perceptions of attractive body composition, particularly in women. PMID:27257677
The Body and the Beautiful: Health, Attractiveness and Body Composition in Men's and Women's Bodies.
Brierley, Mary-Ellen; Brooks, Kevin R; Mond, Jonathan; Stevenson, Richard J; Stephen, Ian D
2016-01-01
The dominant evolutionary theory of physical attraction posits that attractiveness reflects physiological health, and attraction is a mechanism for identifying a healthy mate. Previous studies have found that perceptions of the healthiest body mass index (weight scaled for height; BMI) for women are close to healthy BMI guidelines, while the most attractive BMI is significantly lower, possibly pointing to an influence of sociocultural factors in determining attractive BMI. However, less is known about ideal body size for men. Further, research has not addressed the role of body fat and muscle, which have distinct relationships with health and are conflated in BMI, in determining perceived health and attractiveness. Here, we hypothesised that, if attractiveness reflects physiological health, the most attractive and healthy appearing body composition should be in line with physiologically healthy body composition. Thirty female and 33 male observers were instructed to manipulate 15 female and 15 male body images in terms of their fat and muscle to optimise perceived health and, separately, attractiveness. Observers were unaware that they were manipulating the muscle and fat content of bodies. The most attractive apparent fat mass for female bodies was significantly lower than the healthiest appearing fat mass (and was lower than the physiologically healthy range), with no significant difference for muscle mass. The optimal fat and muscle mass for men's bodies was in line with the healthy range. Male observers preferred a significantly lower overall male body mass than did female observers. While the body fat and muscle associated with healthy and attractive appearance is broadly in line with physiologically healthy values, deviations from this pattern suggest that future research should examine a possible role for internalization of body ideals in influencing perceptions of attractive body composition, particularly in women.
AlMatar, Manaf; AlMandeal, Husam; Makky, Essam A; Kayar, Begum; Yarar, Emel; Var, Isıl; Koksal, Fatih
2017-01-01
Vitamin D, a molecular precursor of the potent steroid hormone calcitriol, has crucial functions and roles in physiology and pathophysiology. Tellingly, calcitriol has been shown to regulate various cellular signalling networks and cascades that have crucial role in cancer biology and diagnostics. Mounting lines of evidences from previous clinical and preclinical investigations indicate that the deficiency of vitamin D may contribute to the carcinogenesis risk. Concomitantly, recent reports suggested that significant reduction in the cancer occurrence and progression is more likely to appear after vitamin D supplementation. Furthermore, a pivotal role functioned by vitamin D in cardiovascular physiology indicates that the deficiency of vitamin D is significantly correlated with enhanced prevalence of stroke, hypertension and myocardial infarction. Notably, vitamin D status is more likely to be used as a lifestyle biomarker, since poor and unhealthy lifestyles are correlated with the deficiency of vitamin D, a feature which may result in cardiovascular complications. Moreover, recent reports revealed that the effect of vitamin D is to cover not only cardiovascular system but also skeletal system. Herein, we are highlighting the recent knowledge of vitamin D roles and functions with respect to pathophysiological disorders such as cancer, cardiovascular diseases, rheumatoid arthritis (RA) and debate the potential avails of vitamin D on slowing cancer, cardiovascular disease and RA progression. The findings of this review confirm that the importance of vitamin D metabolites or analogues which can provide a helpful platform to target some kinds of cancer, particularly when used in combination with existing therapies. Moreover, the correlation between vitamin D deficiencies with cardiovascular diseases and rheumatoid arthritis (RA) progression might suggest a pivotal role of vitamin D in either initiation or progression of these diseases. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.
Sturges, Diana; Maurer, Trent W; Cole, Oladipo
2009-06-01
This study investigated the effectiveness of role play in a large undergraduate science class. The targeted population consisted of 298 students enrolled in 2 sections of an undergraduate Human Anatomy and Physiology course taught by the same instructor. The section engaged in the role-play activity served as the study group, whereas the section presented with a traditional lecture served as the control group. A pretest/posttest assessment and a survey were administered to both sections and used in data analysis. In addition, overall test scores and item analysis were examined. The analysis revealed that participants in both groups improved significantly from pretest to posttest, but there were no significant differences between the groups in posttest scores. Neither group showed a significant change from posttest to the exam. However, there was a moderate positive effect on engagement and satisfaction survey questions from being in the study group (based on 255 total surveys returned by both groups). The role-play activity was at least as effective as the lecture in terms of student performance on the above-mentioned assessments. In addition, it proved successful in engaging students in the learning process and increasing their satisfaction.
Gonadal steroids and bone metabolism in men.
Leder, Benjamin
2007-06-01
Over the past decade, our increasing awareness of the clinical importance of osteoporosis in men has stimulated intense interest in trying to better understand male skeletal physiology and pathophysiology. The present review focuses on a major focus of research in this area, namely the attempt to define the influence and therapeutic potential of gonadal steroids in male bone metabolism. Building on previous work defining the relative roles of androgens and estrogens in the developing male skeleton and in maintaining normal bone turnover, recent studies have begun to define these issues from epidemiologic, physiologic and therapeutic perspectives. With access to data from large prospectively defined populations of men, investigators are confirming and challenging existing hypotheses and forwarding new concepts. Clinical trials have expanded beyond standard androgen replacement studies to explore more complex hormonal interventions. Physiologic investigation has continued to probe the mechanisms underlying the differential and independent roles of androgens and estrogens in male bone metabolism. Recent work has added significantly to our understanding of the role of gonadal steroids in male skeletal physiology. Nonetheless, further research is necessary to build on these initial human studies and to capitalize on rapidly emerging advances in our understanding of the basic biology of bone metabolism.
Ishikawa, Takanori; Nishida, Takashi; Ono, Mitsuaki; Takarada, Takeshi; Nguyen, Ha Thi; Kurihara, Shinnosuke; Furumatsu, Takayuki; Murase, Yurika; Takigawa, Masaharu; Oohashi, Toshitaka; Kamioka, Hiroshi; Kubota, Satoshi
2018-06-01
A vast number of long-noncoding RNAs (lncRNA) are found expressed in human cells, which RNAs have been developed along with human evolution. However, the physiological functions of these lncRNAs remain mostly unknown. In the present study, we for the first time uncovered the fact that one of such lncRNAs plays a significant role in the differentiation of chondrocytes and, possibly, of osteoblasts differentiated from mesenchymal stem cells, which cells eventually construct the human skeleton. The urothelial cancer-associated 1 (UCA1) lncRNA is known to be associated with several human malignancies. Firstly, we confirmed that UCA1 was expressed in normal human chondrocytes, as well as in a human chondrocytic cell line; whereas it was not detected in human bone marrow mesenchymal stem cells (hBMSCs). Of note, although UCA1 expression was undetectable in hBMSCs, it was markedly induced along with the differentiation toward chondrocytes, suggesting its critical role in chondrogenesis. Consistent with this finding, silencing of the UCA1 gene significantly repressed the expression of chondrogenic genes in human chondrocytic cells. UCA1 gene silencing and hyper-expression also had a significant impact on the osteoblastic phenotype in a human cell line. Finally, forced expression of UCA1 in a murine chondrocyte precursor, which did not possess a UCA1 gene, overdrove its differentiation into chondrocytes. These results indicate a physiological and important role of this lncRNA in the skeletal development of humans, who require more sustained endochondral ossification and osteogenesis than do smaller vertebrates. © 2017 Wiley Periodicals, Inc.
The liver in regulation of iron homeostasis.
Rishi, Gautam; Subramaniam, V Nathan
2017-09-01
The liver is one of the largest and most functionally diverse organs in the human body. In addition to roles in detoxification of xenobiotics, digestion, synthesis of important plasma proteins, gluconeogenesis, lipid metabolism, and storage, the liver also plays a significant role in iron homeostasis. Apart from being the storage site for excess body iron, it also plays a vital role in regulating the amount of iron released into the blood by enterocytes and macrophages. Since iron is essential for many important physiological and molecular processes, it increases the importance of liver in the proper functioning of the body's metabolism. This hepatic iron-regulatory function can be attributed to the expression of many liver-specific or liver-enriched proteins, all of which play an important role in the regulation of iron homeostasis. This review focuses on these proteins and their known roles in the regulation of body iron metabolism. Copyright © 2017 the American Physiological Society.
Pustovit, Ruslan V; Callaghan, Brid; Ringuet, Mitchell T; Kerr, Nicole F; Hunne, Billie; Smyth, Ian M; Pietra, Claudio; Furness, John B
2017-08-01
In laboratory animals and in human, centrally penetrant ghrelin receptor agonists, given systemically or orally, cause defecation. Animal studies show that the effect is due to activation of ghrelin receptors in the spinal lumbosacral defecation centers. However, it is not known whether there is a physiological role of ghrelin or the ghrelin receptor in the control of defecation. Using immunohistochemistry and immunoassay, we detected and measured ghrelin in the stomach, but were unable to detect ghrelin by either method in the lumbosacral spinal cord, or other regions of the CNS In rats in which the thoracic spinal cord was transected 5 weeks before, the effects of a ghrelin agonist on colorectal propulsion were significantly enhanced, but defecation caused by water avoidance stress (WAS) was reduced. In knockout rats that expressed no ghrelin and in wild-type rats, WAS-induced defecation was reduced by a ghrelin receptor antagonist, to similar extents. We conclude that the ghrelin receptors of the lumbosacral defecation centers have a physiological role in the control of defecation, but that their role is not dependent on ghrelin. This implies that a transmitter other than ghrelin engages the ghrelin receptor or a ghrelin receptor complex. © 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.
Gut Melatonin in Vertebrates: Chronobiology and Physiology.
Mukherjee, Sourav; Maitra, Saumen Kumar
2015-01-01
Melatonin, following discovery in the bovine pineal gland, has been detected in several extra-pineal sources including gastrointestinal tract or gut. Arylalkylamine N-acetyltransferase (AANAT) is the key regulator of its biosynthesis. Melatonin in pineal is rhythmically produced with a nocturnal peak in synchronization with environmental light-dark cycle. A recent study on carp reported first that melatonin levels and intensity of a ~23 kDa AANAT protein in each gut segment also exhibit significant daily variations but, unlike pineal, show a peak at midday in all seasons. Extensive experimental studies ruled out direct role of light-dark conditions in determining temporal pattern of gut melatoninergic system in carp, and opened up possible role of environmental non-photic cue(s) as its synchronizer. Based on mammalian findings, physiological significance of gut-derived melatonin also appears unique because its actions at local levels sharing paracrine and/or autocrine functions have been emphasized. The purpose of this mini review is to summarize the existing data on the chronobiology and physiology of gut melatonin and to emphasize their relation with the same hormone derived in the pineal in vertebrates including fish.
Duberstein, Jamie A.; Krauss, Ken W.; Conner, William H.; Bridges, William C.; Shelburne, Victor B.
2013-01-01
Hummock and hollow microtopography is pervasive in tidal freshwater swamps. Many tree species grow atop hummocks significantly more than in hollows, leading to the hypothesis that hummocks provide preferred locations for maximizing physiological proficiency of inhabiting trees that experience repeated flooding. We used thermal dissipation probes to measure the ecophysiological proficiency of a very flood-tolerant tree, Taxodium distichum, as manifested through in-situ changes in sapflow (a proxy for transpiration) in 11 trees on hummocks and 11 trees in hollows. Overall, sapflow increased significantly by 3.3 g H2O m−2 s−1 (11 %) in trees on both hummocks and hollows during flooding, contrary to our expectations. We found no significant differences in sapflow rates between T. distichum trees positioned on hummocks versus hollows in relation to discrete flood events. Coincidentally, hummock elevations were equivalent to the flood depths that promoted greatest physiological proficiency in T. distichum, suggesting a physiological role for the maintenance of hummock height in tidal swamps. While we reject our original hypotheses that flooding and positioning in hollows will reduce sapflow in T. distichum, this research reveals a potentially important feedback between hummock height, flood depth, and maximum tree physiological response.
Protective role of Parkin in skeletal muscle contractile and mitochondrial function.
Gouspillou, Gilles; Godin, Richard; Piquereau, Jérome; Picard, Martin; Mofarrahi, Mahroo; Mathew, Jasmin; Purves-Smith, Fennigje M; Sgarioto, Nicolas; Hepple, Russell T; Burelle, Yan; Hussain, Sabah N A
2018-04-22
Parkin, an E3 ubiquitin ligase encoded by the Park2 gene, has been implicated in the regulation of mitophagy, a quality control process in which defective mitochondria are degraded. The exact physiological significance of Parkin in regulating mitochondrial function and contractility in skeletal muscle remains largely unexplored. Using Park2 -/- mice, we show that Parkin ablation causes a decrease in muscle specific force, a severe decrease in mitochondrial respiration, mitochondrial uncoupling and an increased susceptibility to opening of the permeability transition pore. These results demonstrate that Parkin plays a protective role in the maintenance of normal mitochondrial and contractile functions in skeletal muscles. Parkin is an E3 ubiquitin ligase encoded by the Park2 gene. Parkin has been implicated in the regulation of mitophagy, a quality control process in which defective mitochondria are sequestered in autophagosomes and delivered to lysosomes for degradation. Although Parkin has been mainly studied for its implication in neuronal degeneration in Parkinson disease, its role in other tissues remains largely unknown. In the present study, we investigated the skeletal muscles of Park2 knockout (Park2 -/- ) mice to test the hypothesis that Parkin plays a physiological role in mitochondrial quality control in normal skeletal muscle, a tissue highly reliant on mitochondrial content and function. We first show that the tibialis anterior (TA) of Park2 -/- mice display a slight but significant decrease in its specific force. Park2 -/ - muscles also show a trend for type IIB fibre hypertrophy without alteration in muscle fibre type proportion. Compared to Park2 +/+ muscles, the mitochondrial function of Park2 -/- skeletal muscles was significantly impaired, as indicated by the significant decrease in ADP-stimulated mitochondrial respiratory rates, uncoupling, reduced activities of respiratory chain complexes containing mitochondrial DNA (mtDNA)-encoded subunits and increased susceptibility to opening of the permeability transition pore. Muscles of Park2 -/- mice also displayed a decrease in the content of the mitochondrial pro-fusion protein Mfn2 and an increase in the pro-fission protein Drp1 suggesting an increase in mitochondrial fragmentation. Finally, Park2 ablation resulted in an increase in basal autophagic flux in skeletal muscles. Overall, the results of the present study demonstrate that Parkin plays a protective role in the maintenance of normal mitochondrial and contractile functions in normal skeletal muscles. © 2018 The Authors. The Journal of Physiology © 2018 The Physiological Society.
Oestrogens and spermatogenesis
Carreau, Serge; Hess, Rex A.
2010-01-01
The role of oestrogens in male reproductive tract physiology has for a long time been a subject of debate. The testis produces significant amounts of oestrogenic hormones, via aromatase, and oestrogen receptors (ERs)α (ESR1) and ERβ (ESR2) are selectively expressed in cells of the testis as well as the epididymal epithelium, depending upon species. This review summarizes the current knowledge concerning the presence and activity of aromatase and ERs in testis and sperm and the potential roles that oestrogens may have in mammalian spermatogenesis. Data show that physiology of the male gonad is in part under the control of a balance of androgens and oestrogens, with aromatase serving as a modulator. PMID:20403867
Woodall, Benjamin P; Woodall, Meryl C; Luongo, Timothy S; Grisanti, Laurel A; Tilley, Douglas G; Elrod, John W; Koch, Walter J
2016-10-14
GRK2, a G protein-coupled receptor kinase, plays a critical role in cardiac physiology. Adrenergic receptors are the primary target for GRK2 activity in the heart; phosphorylation by GRK2 leads to desensitization of these receptors. As such, levels of GRK2 activity in the heart directly correlate with cardiac contractile function. Furthermore, increased expression of GRK2 after cardiac insult exacerbates injury and speeds progression to heart failure. Despite the importance of this kinase in both the physiology and pathophysiology of the heart, relatively little is known about the role of GRK2 in skeletal muscle function and disease. In this study we generated a novel skeletal muscle-specific GRK2 knock-out (KO) mouse (MLC-Cre:GRK2 fl/fl ) to gain a better understanding of the role of GRK2 in skeletal muscle physiology. In isolated muscle mechanics testing, GRK2 ablation caused a significant decrease in the specific force of contraction of the fast-twitch extensor digitorum longus muscle yet had no effect on the slow-twitch soleus muscle. Despite these effects in isolated muscle, exercise capacity was not altered in MLC-Cre:GRK2 fl/fl mice compared with wild-type controls. Skeletal muscle hypertrophy stimulated by clenbuterol, a β 2 -adrenergic receptor (β 2 AR) agonist, was significantly enhanced in MLC-Cre:GRK2 fl/fl mice; mechanistically, this seems to be due to increased clenbuterol-stimulated pro-hypertrophic Akt signaling in the GRK2 KO skeletal muscle. In summary, our study provides the first insights into the role of GRK2 in skeletal muscle physiology and points to a role for GRK2 as a modulator of contractile properties in skeletal muscle as well as β 2 AR-induced hypertrophy. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.
Iron-Tolerant Cyanobacteria: Ecophysiology and Fingerprinting
NASA Technical Reports Server (NTRS)
Brown, I. I.; Mummey, D.; Lindsey, J.; McKay, D. S.
2006-01-01
Although the iron-dependent physiology of marine and freshwater cyanobacterial strains has been the focus of extensive study, very few studies dedicated to the physiology and diversity of cyanobacteria inhabiting iron-depositing hot springs have been conducted. One of the few studies that have been conducted [B. Pierson, 1999] found that cyanobacterial members of iron depositing bacterial mat communities might increase the rate of iron oxidation in situ and that ferrous iron concentrations up to 1 mM significantly stimulated light dependent consumption of bicarbonate, suggesting a specific role for elevated iron in photosynthesis of cyanobacteria inhabiting iron-depositing hot springs. Our recent studies pertaining to the diversity and physiology of cyanobacteria populating iron-depositing hot springs in Great Yellowstone area (Western USA) indicated a number of different isolates exhibiting elevated tolerance to Fe(3+) (up to 1 mM). Moreover, stimulation of growth was observed with increased Fe(3+) (0.02-0.4 mM). Molecular fingerprinting of unialgal isolates revealed a new cyanobacterial genus and species Chroogloeocystis siderophila, an unicellular cyanobacterium with significant EPS sheath harboring colloidal Fe(3+) from iron enriched media. Our preliminary data suggest that some filamentous species of iron-tolerant cyanobacteria are capable of exocytosis of iron precipitated in cytoplasm. Prior to 2.4 Ga global oceans were likely significantly enriched in soluble iron [Lindsay et al, 2003], conditions which are not conducive to growth of most contemporary oxygenic cyanobacteria. Thus, iron-tolerant CB may have played important physiological and evolutionary roles in Earths history.
Physiological functions of MTA family of proteins.
Sen, Nirmalya; Gui, Bin; Kumar, Rakesh
2014-12-01
Although the functional significance of the metastasic tumor antigen (MTA) family of chromatin remodeling proteins in the pathobiology of cancer is fairly well recognized, the physiological role of MTA proteins continues to be an understudied research area and is just beginning to be recognized. Similar to cancer cells, MTA1 also modulates the expression of target genes in normal cells either by acting as a corepressor or coactivator. In addition, physiological functions of MTA proteins are likely to be influenced by its differential expression, subcellular localization, and regulation by upstream modulators and extracellular signals. This review summarizes our current understanding of the physiological functions of the MTA proteins in model systems. In particular, we highlight recent advances of the role MTA proteins play in the brain, eye, circadian rhythm, mammary gland biology, spermatogenesis, liver, immunomodulation and inflammation, cellular radio-sensitivity, and hematopoiesis and differentiation. Based on the growth of knowledge regarding the exciting new facets of the MTA family of proteins in biology and medicine, we speculate that the next burst of findings in this field may reveal further molecular regulatory insights of non-redundant functions of MTA coregulators in the normal physiology as well as in pathological conditions outside cancer.
RNA-Seq Reveals an Integrated Immune Response in Nucleated Erythrocytes
Morera, Davinia; Roher, Nerea; Ribas, Laia; Balasch, Joan Carles; Doñate, Carmen; Callol, Agnes; Boltaña, Sebastian; Roberts, Steven; Goetz, Giles; Goetz, Frederick W.; MacKenzie, Simon A.
2011-01-01
Background Throughout the primary literature and within textbooks, the erythrocyte has been tacitly accepted to have maintained a unique physiological role; namely gas transport and exchange. In non-mammalian vertebrates, nucleated erythrocytes are present in circulation throughout the life cycle and a fragmented series of observations in mammals support a potential role in non-respiratory biological processes. We hypothesised that nucleated erythrocytes could actively participate via ligand-induced transcriptional re-programming in the immune response. Methodology/Principal Findings Nucleated erythrocytes from both fish and birds express and regulate specific pattern recognition receptor (PRR) mRNAs and, thus, are capable of specific pathogen associated molecular pattern (PAMP) detection that is central to the innate immune response. In vitro challenge with diverse PAMPs led to de novo specific mRNA synthesis of both receptors and response factors including interferon-alpha (IFNα) that exhibit a stimulus-specific polysomal shift supporting active translation. RNA-Seq analysis of the PAMP (Poly (I∶C), polyinosinic∶polycytidylic acid)-erythrocyte response uncovered diverse cohorts of differentially expressed mRNA transcripts related to multiple physiological systems including the endocrine, reproductive and immune. Moreover, erythrocyte-derived conditioned mediums induced a type-1 interferon response in macrophages thus supporting an integrative role for the erythrocytes in the immune response. Conclusions/Significance We demonstrate that nucleated erythrocytes in non-mammalian vertebrates spanning significant phylogenetic distance participate in the immune response. RNA-Seq studies highlight a mRNA repertoire that suggests a previously unrecognized integrative role for the erythrocytes in other physiological systems. PMID:22046430
Astrocytic glycogen metabolism in the healthy and diseased brain.
Bak, Lasse K; Walls, Anne B; Schousboe, Arne; Waagepetersen, Helle S
2018-05-11
The brain contains a fairly low amount of glycogen, mostly located in astrocytes, a fact that has prompted the suggestion that glycogen does not have a significant physiological role in the brain. However, glycogen metabolism in astrocytes is essential for several key physiological processes and is adversely affected in disease. For instance, diminished ability to break down glycogen impinges on learning, and epilepsy, Alzheimer's disease, and type 2 diabetes are all associated with abnormal astrocyte glycogen metabolism. Glycogen metabolism supports astrocytic K + and neurotransmitter glutamate uptake and subsequent glutamine synthesis-three fundamental steps in excitatory signaling at most brain synapses. Thus, there is abundant evidence for a key role of glycogen in brain function. Here, we summarize the physiological brain functions that depend on glycogen, discuss glycogen metabolism in disease, and investigate how glycogen breakdown is regulated at the cellular and molecular levels. © 2018 by The American Society for Biochemistry and Molecular Biology, Inc.
Wilson, K S; Matrone, G; Livingstone, D E W; Al-Dujaili, E A S; Mullins, J J; Tucker, C S; Hadoke, P W F; Kenyon, C J; Denvir, M A
2013-01-01
While glucocorticoids (GCs) are known to be present in the zebrafish embryo, little is known about their physiological roles at this stage. We hypothesised that GCs play key roles in stress response, hatching and swim activity during early development. To test this, whole embryo cortisol (WEC) and corticosteroid-related genes were measured in embryos from 6 to 120 h post fertilisation (hpf) by enzyme linked immunosorbent assay (ELISA) and quantitative real-time polymerase chain reaction (qRT-PCR). Stress response was assessed by change in WEC following stirring, hypoxia or brief electrical impulses applied to the bathing water. The impact of pharmacological and molecular GC manipulation on the stress response, spontaneous hatching and swim activity at different stages of development was also assessed. WEC levels demonstrated a biphasic pattern during development with a decrease from 0 to 36 hpf followed by a progressive increase towards 120 hpf. This was accompanied by a significant and sustained increase in the expression of genes encoding cyp11b1 (GC biosynthesis), hsd11b2 (GC metabolism) and gr (GC receptor) from 48 to 120 hpf. Metyrapone (Met), an inhibitor of 11β-hydroxylase (encoded by cyp11b1), and cyp11b1 morpholino (Mo) knockdown significantly reduced basal and stress-induced WEC levels at 72 and 120 hpf but not at 24 hpf. Spontaneous hatching and swim activity were significantly affected by manipulation of GC action from approximately 48 hpf onwards. We have identified a number of key roles of GCs in zebrafish embryos contributing to adaptive physiological responses under adverse conditions. The ability to alter GC action in the zebrafish embryo also highlights its potential value for GC research. PMID:24167225
Functional significance of GnRH and kisspeptin, and their cognate receptors in teleost reproduction.
Gopurappilly, Renjitha; Ogawa, Satoshi; Parhar, Ishwar S
2013-01-01
Guanine nucleotide binding protein (G-protein)-coupled receptors (GPCRs) are eukaryotic transmembrane proteins found in all living organisms. Their versatility and roles in several physiological processes make them the single largest family of drug targets. Comparative genomic studies using various model organisms have provided useful information about target receptors. The similarity of the genetic makeup of teleosts to that of humans and other vertebrates aligns with the study of GPCRs. Gonadotropin-releasing hormone (GnRH) represents a critical step in the reproductive process through its cognate GnRH receptors (GnRHRs). Kisspeptin (Kiss1) and its cognate GPCR, GPR54 (=kisspeptin receptor, Kiss-R), have recently been identified as a critical signaling system in the control of reproduction. The Kiss1/Kiss-R system regulates GnRH release, which is vital to pubertal development and vertebrate reproduction. This review highlights the physiological role of kisspeptin-Kiss-R signaling in the reproductive neuroendocrine axis in teleosts through the modulation of GnRH release. Moreover, we also review the recent developments in GnRHR and Kiss-R with respect to their structural variants, signaling mechanisms, ligand interactions, and functional significance. Finally, we discuss the recent progress in identifying many teleost GnRH-GnRHR and kisspeptin-Kiss-R systems and consider their physiological significance in the control of reproduction.
Let's 'play' with molecular pharmacology.
Choudhury, Supriyo; Pradhan, Richeek; Sengupta, Gairik; Das, Manisha; Chatterjee, Manojit; Roy, Ranendra Kumar; Chatterjee, Suparna
2015-01-01
Understanding concepts of molecular mechanisms of drug action involves sequential visualization of physiological processes and drug effects, a task that can be difficult at an undergraduate level. Role-play is a teaching-learning methodology whereby active participation of students as well as clear visualization of the phenomenon is used to convey complex physiological concepts. However, its use in teaching drug action, a process that demands understanding of a second level of complexity over the physiological process, has not been investigated. We hypothesized that role-play can be an effective and well accepted method for teaching molecular pharmacology. In an observational study, students were guided to perform a role-play on a selected topic involving drug activity. Students' gain in knowledge was assessed comparing validated pre- and post-test questionnaires as well as class average normalized gain. The acceptance of role-play among undergraduate medical students was evaluated by Likert scale analysis and thematic analysis of their open-ended written responses. Significant improvement in knowledge (P < 0.001) was noted in the pre- to post-test knowledge scores, while a high gain in class average normalized score was evident. In Likert scale analysis, most students (93%) expressed that role-play was an acceptable way of teaching. In a thematic analysis, themes of both strengths and weaknesses of the session emerged. Role-play can be effectively utilized while teaching selected topics of molecular pharmacology in undergraduate medical curricula.
Neurotransmitters: The Critical Modulators Regulating Gut-Brain Axis.
Mittal, Rahul; Debs, Luca H; Patel, Amit P; Nguyen, Desiree; Patel, Kunal; O'Connor, Gregory; Grati, M'hamed; Mittal, Jeenu; Yan, Denise; Eshraghi, Adrien A; Deo, Sapna K; Daunert, Sylvia; Liu, Xue Zhong
2017-09-01
Neurotransmitters, including catecholamines and serotonin, play a crucial role in maintaining homeostasis in the human body. Studies on these neurotransmitters mainly revolved around their role in the "fight or flight" response, transmitting signals across a chemical synapse and modulating blood flow throughout the body. However, recent research has demonstrated that neurotransmitters can play a significant role in the gastrointestinal (GI) physiology. Norepinephrine (NE), epinephrine (E), dopamine (DA), and serotonin have recently been a topic of interest because of their roles in the gut physiology and their potential roles in GI and central nervous system pathophysiology. These neurotransmitters are able to regulate and control not only blood flow, but also affect gut motility, nutrient absorption, GI innate immune system, and the microbiome. Furthermore, in pathological states, such as inflammatory bowel disease (IBD) and Parkinson's disease, the levels of these neurotransmitters are dysregulated, therefore causing a variety of GI symptoms. Research in this field has shown that exogenous manipulation of catecholamine serum concentrations can help in decreasing symptomology and/or disease progression. In this review article, we discuss the current state-of-the-art research and literature regarding the role of neurotransmitters in regulation of normal GI physiology, their impact on several disease processes, and novel work focused on the use of exogenous hormones and/or psychotropic medications to improve disease symptomology. J. Cell. Physiol. 232: 2359-2372, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.
Transcription elongation. Heterogeneous tracking of RNA polymerase and its biological implications.
Imashimizu, Masahiko; Shimamoto, Nobuo; Oshima, Taku; Kashlev, Mikhail
2014-01-01
Regulation of transcription elongation via pausing of RNA polymerase has multiple physiological roles. The pausing mechanism depends on the sequence heterogeneity of the DNA being transcribed, as well as on certain interactions of polymerase with specific DNA sequences. In order to describe the mechanism of regulation, we introduce the concept of heterogeneity into the previously proposed alternative models of elongation, power stroke and Brownian ratchet. We also discuss molecular origins and physiological significances of the heterogeneity.
Heme oxygenase-1 system and gastrointestinal tumors
Zhu, Xiao; Fan, Wen-Guo; Li, Dong-Pei; Lin, Marie CM; Kung, Hsiangfu
2010-01-01
Heme oxygenase-1 (HO-1) system catabolizes heme into three products: carbon monoxide, biliverdin/bilirubin and free iron. It is involved in many physiological and pathophysiological processes. A great deal of data has demonstrated the roles of HO-1 in the formation, growth and metastasis of tumors. The interest in this system by investigators involved in gastrointestinal tumors is fairly recent, and few papers on HO-1 have touched upon this subject. This review focuses on the current understanding of the physiological significance of HO-1 induction and its possible roles in the gastrointestinal tumors studied to date. The implications for possible therapeutic manipulation of HO-1 in gastrointestinal tumors are also discussed. PMID:20518085
Singers' interest and knowledge levels of vocal function and dysfunction: survey findings.
Braun-Janzen, Colleen; Zeine, Lina
2009-07-01
A questionnaire investigating the levels of interest in and knowledge of vocal function and dysfunction was completed by 129 singers. Those with professional singing experience indicated significantly greater interest and higher perceived knowledge levels than amateurs in areas of vocal anatomy and physiology, vocal hygiene, and functional vocal pathologies. Greater interest levels, but not higher perceived knowledge levels were reported by professional singers (PSs) in the area of the role of the speech-language pathologist (SLP) and the voice. Professionals answered significantly more knowledge-based questions correctly than amateurs in all areas except the role of the SLP and the voice. However, findings indicated wide variability in knowledge levels of both groups. Singing teachers (STs) within the group significantly outperformed the remainder of the group in areas of vocal anatomy and physiology, vocal hygiene, and functional vocal pathologies. Scores of the choir directors (CDs) within the group were not significantly superior to the remainder of the group except in the area of functional vocal pathologies. Implications for a preventative approach to vocal health are discussed.
Naskar, Shaon; Datta, Kaberi; Mitra, Arkadeep; Pathak, Kanchan; Datta, Ritwik; Bansal, Trisha; Sarkar, Sagartirtha
2014-01-01
A cardiac hypertrophy is defined as an increase in heart mass which may either be beneficial (physiological hypertrophy) or detrimental (pathological hypertrophy). This study was undertaken to establish the role of different protein kinase-C (PKC) isoforms in the regulation of cardiac adaptation during two types of cardiac hypertrophy. Phosphorylation of specific PKC-isoforms and expression of their downstream proteins were studied during physiological and pathological hypertrophy in 24 week male Balb/c mice (Mus musculus) models, by reverse transcriptase-PCR, western blot analysis and M-mode echocardiography for cardiac function analysis. PKC-δ was significantly induced during pathological hypertrophy while PKC-α was exclusively activated during physiological hypertrophy in our study. PKC-δ activation during pathological hypertrophy resulted in cardiomyocyte apoptosis leading to compromised cardiac function and on the other hand, activation of PKC-α during physiological hypertrophy promoted cardiomyocyte growth but down regulated cellular apoptotic load resulting in improved cardiac function. Reversal in PKC-isoform with induced activation of PKC-δ and simultaneous inhibition of phospho-PKC-α resulted in an efficient myocardium to deteriorate considerably resulting in compromised cardiac function during physiological hypertrophy via augmentation of apoptotic and fibrotic load. This is the first report where PKC-α and -δ have been shown to play crucial role in cardiac adaptation during physiological and pathological hypertrophy respectively thereby rendering compromised cardiac function to an otherwise efficient heart by conditional reversal of their activation. PMID:25116170
[Regulatory role of the immune system in the organism].
Alekseev, L P; Khaitov, R M
2010-08-01
The paper presents modern idea of regulatory role of the human immune system in performing a number of physiological functions including intercellular interactions, reproductive process, and forming of protection against external and internal aggression. Significance of the immune system is considered and substantiated, that of genes of the human immune response in particular in provision of human survival as a biological species.
The Cajal school and the physiological role of astrocytes: a way of thinking
Navarrete, Marta; Araque, Alfonso
2014-01-01
Cajal is widely recognized by the scientific community for his important contributions to our knowledge of the neuronal organization of the nervous system. His studies on neuroglial cells are less recognized, yet they are no less relevant to our current understanding of the cellular bases of brain structure. Two pioneering studies published a century ago –“Something about the physiological significance of neuroglia” (Ramón y Cajal, 1897) and “A contribution to the understanding of neuroglia in the human brain” (Ramón y Cajal, 1913)—focused on glial cells and their role in brain physiology. Novel findings obtained using state-of-the-art and sophisticated technologies largely confirm many of the groundbreaking hypotheses proposed by Cajal related to the structural-functional properties of neuroglia. Here we propose to the reader a journey guided by the ideas of Cajal through the recent findings on the functional significance of astrocytes, the most abundant neuroglial cell type in the nervous system. Astrocyte–neuron interaction, which represents an emerging field in current neuroscience with important implications for our understanding of the cellular processes underlying brain function, has its roots in many of the original concepts proposed by Cajal. PMID:24904302
Genetic approaches in comparative and evolutionary physiology.
Storz, Jay F; Bridgham, Jamie T; Kelly, Scott A; Garland, Theodore
2015-08-01
Whole animal physiological performance is highly polygenic and highly plastic, and the same is generally true for the many subordinate traits that underlie performance capacities. Quantitative genetics, therefore, provides an appropriate framework for the analysis of physiological phenotypes and can be used to infer the microevolutionary processes that have shaped patterns of trait variation within and among species. In cases where specific genes are known to contribute to variation in physiological traits, analyses of intraspecific polymorphism and interspecific divergence can reveal molecular mechanisms of functional evolution and can provide insights into the possible adaptive significance of observed sequence changes. In this review, we explain how the tools and theory of quantitative genetics, population genetics, and molecular evolution can inform our understanding of mechanism and process in physiological evolution. For example, lab-based studies of polygenic inheritance can be integrated with field-based studies of trait variation and survivorship to measure selection in the wild, thereby providing direct insights into the adaptive significance of physiological variation. Analyses of quantitative genetic variation in selection experiments can be used to probe interrelationships among traits and the genetic basis of physiological trade-offs and constraints. We review approaches for characterizing the genetic architecture of physiological traits, including linkage mapping and association mapping, and systems approaches for dissecting intermediary steps in the chain of causation between genotype and phenotype. We also discuss the promise and limitations of population genomic approaches for inferring adaptation at specific loci. We end by highlighting the role of organismal physiology in the functional synthesis of evolutionary biology. Copyright © 2015 the American Physiological Society.
Breaux, Rosanna P; McQuade, Julia D; Harvey, Elizabeth A; Zakarian, Rebecca J
2018-05-01
Theory and research suggest that parents' reactions to children's emotions play a critical role in teaching children effective emotion regulation (ER) skills, but no studies have directly examined the role that parent emotion socialization plays in the development of ER in children with ADHD. Gaining insight into the causes of impaired ER, particularly in youth with ADHD who are known to have poor ER, has important theoretical and translational significance. The present study is the first to longitudinally examine whether emotion socialization predicts later physiological and adult-reported measures of ER in children with and without ADHD. It also sought to determine if these relations are moderated by ADHD symptoms. Participants were 61 children (31 girls, 30 boys; M = 10.67 years, SD = 1.28) with and without clinically significant ADHD symptoms. At Time 1, parent reports of emotion socialization and parent- and teacher-report of child ADHD symptoms were collected. At Time 2, child ER measures were collected based on parent- and teacher-report and physiological reactivity during an impossible puzzle and a social rejection task. Physiological measures included respiratory sinus arrhythmia and skin conductance level (SCL). Supportive parenting practices were associated with better parent-rated emotion regulation skills for all children and greater SCL reactivity for children with high ADHD symptoms. Non-supportive parenting reactions were associated with greater adult-rated emotional lability for children with high ADHD symptoms. Results highlight the importance of considering multiple aspects of ER, including physiological manifestations. Findings suggest that parents' use of adaptive emotion socialization practices may serve as a protective factor for children's ER development and may be particularly critical for youth with ADHD. Our findings support the use of interventions addressing parent emotion socialization to help foster better ER in children.
Endogenous opioid systems: physiological role in the self-limitation of seizures.
Tortella, F C; Long, J B; Holaday, J W
1985-04-15
Immediately following a seizure, the severity of subsequent seizures is significantly reduced. The involvement of endogenous opioid systems as a physiological regulator of this postseizure inhibition was studied in rats using repeated maximal electroshock (MES) seizures. Both the opiate antagonist (-)-naloxone and morphine tolerance abolished the progressive seizure protection associated with repeated MES. We propose that endogenous opioids, activated by a prior seizure, provide a central homeostatic inhibitory mechanism which may be responsible for the initiation of a postictal refractory state in the epileptic.
Functional Significance of GnRH and Kisspeptin, and Their Cognate Receptors in Teleost Reproduction
Gopurappilly, Renjitha; Ogawa, Satoshi; Parhar, Ishwar S.
2012-01-01
Guanine nucleotide binding protein (G-protein)-coupled receptors (GPCRs) are eukaryotic transmembrane proteins found in all living organisms. Their versatility and roles in several physiological processes make them the single largest family of drug targets. Comparative genomic studies using various model organisms have provided useful information about target receptors. The similarity of the genetic makeup of teleosts to that of humans and other vertebrates aligns with the study of GPCRs. Gonadotropin-releasing hormone (GnRH) represents a critical step in the reproductive process through its cognate GnRH receptors (GnRHRs). Kisspeptin (Kiss1) and its cognate GPCR, GPR54 (=kisspeptin receptor, Kiss-R), have recently been identified as a critical signaling system in the control of reproduction. The Kiss1/Kiss-R system regulates GnRH release, which is vital to pubertal development and vertebrate reproduction. This review highlights the physiological role of kisspeptin-Kiss-R signaling in the reproductive neuroendocrine axis in teleosts through the modulation of GnRH release. Moreover, we also review the recent developments in GnRHR and Kiss-R with respect to their structural variants, signaling mechanisms, ligand interactions, and functional significance. Finally, we discuss the recent progress in identifying many teleost GnRH-GnRHR and kisspeptin-Kiss-R systems and consider their physiological significance in the control of reproduction. PMID:23482509
Genetic approaches in comparative and evolutionary physiology
Bridgham, Jamie T.; Kelly, Scott A.; Garland, Theodore
2015-01-01
Whole animal physiological performance is highly polygenic and highly plastic, and the same is generally true for the many subordinate traits that underlie performance capacities. Quantitative genetics, therefore, provides an appropriate framework for the analysis of physiological phenotypes and can be used to infer the microevolutionary processes that have shaped patterns of trait variation within and among species. In cases where specific genes are known to contribute to variation in physiological traits, analyses of intraspecific polymorphism and interspecific divergence can reveal molecular mechanisms of functional evolution and can provide insights into the possible adaptive significance of observed sequence changes. In this review, we explain how the tools and theory of quantitative genetics, population genetics, and molecular evolution can inform our understanding of mechanism and process in physiological evolution. For example, lab-based studies of polygenic inheritance can be integrated with field-based studies of trait variation and survivorship to measure selection in the wild, thereby providing direct insights into the adaptive significance of physiological variation. Analyses of quantitative genetic variation in selection experiments can be used to probe interrelationships among traits and the genetic basis of physiological trade-offs and constraints. We review approaches for characterizing the genetic architecture of physiological traits, including linkage mapping and association mapping, and systems approaches for dissecting intermediary steps in the chain of causation between genotype and phenotype. We also discuss the promise and limitations of population genomic approaches for inferring adaptation at specific loci. We end by highlighting the role of organismal physiology in the functional synthesis of evolutionary biology. PMID:26041111
Robertson, Sarah M C; Swickert, Rhonda J; Connelly, Kathryn; Galizio, Ann
2015-01-01
Physiological reactivity (PR) describes the change in physiological functioning (e.g., heart rate, blood pressure, pulse pressure) that occurs after the induction of a stressful task. This study aims to understand the influence of mental health symptoms on patterns of PR during autobiographical narratives in an older adult sample. Eighty older adults completed self-report measures regarding their symptoms of depression and anxiety. Next, their blood pressure was recorded while they completed two verbal autobiographical narratives. During the positive narrative, anxiety was positively associated with increased PR while depression was negatively associated with PR. During the negative narrative, a significant interaction occurred whereby anxiety was significantly positively associated with PR for those participants low in depression. The above results are explained in the context of the Tripartite Model of Depression and Anxiety, which predicts different patterns of PR as a function of mental health symptoms. Limitations and future directions are also discussed.
Students' motivation toward laboratory work in physiology teaching.
Dohn, Niels Bonderup; Fago, Angela; Overgaard, Johannes; Madsen, Peter Teglberg; Malte, Hans
2016-09-01
The laboratory has been given a central role in physiology education, and teachers report that it is motivating for students to undertake experimental work on live animals or measuring physiological responses on the students themselves. Since motivation is a critical variable for academic learning and achievement, then we must concern ourselves with questions that examine how students engage in laboratory work and persist at such activities. The purpose of the present study was to investigate how laboratory work influences student motivation in physiology. We administered the Lab Motivation Scale to assess our students' levels of interest, willingness to engage (effort), and confidence in understanding (self-efficacy). We also asked students about the role of laboratory work for their own learning and their experience in the physiology laboratory. Our results documented high levels of interest, effort, and self-efficacy among the students. Correlation analyses were performed on the three motivation scales and exam results, yet a significant correlation was only found between self-efficacy in laboratory work and academic performance at the final exam. However, almost all students reported that laboratory work was very important for learning difficult concepts and physiological processes (e.g., action potential), as the hands-on experiences gave a more concrete idea of the learning content and made the content easier to remember. These results have implications for classroom practice as biology students find laboratory exercises highly motivating, despite their different personal interests and subject preferences. This highlights the importance of not replacing laboratory work by other nonpractical approaches, for example, video demonstrations or computer simulations. Copyright © 2016 The American Physiological Society.
Transcription termination factor Rho: a hub linking diverse physiological processes in bacteria.
Grylak-Mielnicka, Aleksandra; Bidnenko, Vladimir; Bardowski, Jacek; Bidnenko, Elena
2016-03-01
Factor-dependent termination of transcription in bacteria relies on the activity of a specific RNA helicase, the termination factor Rho. Rho is nearly ubiquitous in bacteria, but the extent to which its physiological functions are conserved throughout the different phyla remains unknown. Most of our current knowledge concerning the mechanism of Rho's activity and its physiological roles comes from the model micro-organism Escherichia coli, where Rho is essential and involved in the control of several important biological processes. However, the rather comprehensive knowledge about the general mechanisms of action and activities of Rho based on the E. coli paradigm cannot be directly extrapolated to other bacteria. Recent studies performed in different species favour the view that Rho-dependent termination plays a significant role even in bacteria where Rho is not essential. Here, we summarize the current state of the ever-increasing knowledge about the various aspects of the physiological functions of Rho, such as limitation of deleterious foreign DNA expression, control of gene expression, suppression of pervasive transcription, prevention of R-loops and maintenance of chromosome integrity, focusing on similarities and differences of the activities of Rho in various bacterial species.
Jones, B A; Gores, G J
1997-12-01
Cell death of gastrointestinal epithelial cells occurs by a process referred to as apoptosis. In this review, we succinctly define apoptosis and summarize the role of apoptosis in the physiology and pathophysiology of epithelial cells in the liver, pancreas, and small and large intestine. The physiological mediators regulating apoptosis in gastrointestinal epithelial cells, when known, are discussed. Selected pathophysiological consequences of excessive apoptosis and inhibition of apoptosis are used to illustrate the significance of apoptosis in disease processes. These examples demonstrate that excessive apoptosis may result in epithelial cell atrophy, injury, and dysfunction, whereas inhibition of apoptosis results in hyperplasia and promotes malignant transformation. The specific cellular mechanisms responsible for dysregulation of epithelial cell apoptosis during pathophysiological disturbances are emphasized. Potential future areas of physiological research regarding apoptosis in gastrointestinal epithelia are highlighted when appropriate.
Platelets and their interactions with other immune cells
Lam, Fong W.; Vijayan, K. Vinod; Rumbaut, Rolando E.
2015-01-01
Platelets are anucleate blood cells, long known to be critically involved in hemostasis and thrombosis. In addition to their role in blood clots, increasing evidence reveals significant roles for platelets in inflammation and immunity. However, the notion that platelets represent immune cells is not broadly recognized in the field of Physiology. This manuscript reviews the role of platelets in inflammation and immune responses, and highlights their interactions with other immune cells, including examples of major functional consequences of these interactions. PMID:26140718
The evolution of water balance in Glossina (Diptera: Glossinidae): correlations with climate.
Kleynhans, Elsje; Terblanche, John S
2009-02-23
The water balance of tsetse flies (Diptera: Glossinidae) has significant implications for understanding biogeography and climate change responses in these African disease vectors. Although moisture is important for tsetse population dynamics, evolutionary responses of Glossina water balance to climate have been relatively poorly explored and earlier studies may have been confounded by several factors. Here, using a physiological and GIS climate database, we investigate potential interspecific relationships between traits of water balance and climate. We do so in conventional and phylogenetically independent approaches for both adults and pupae. Results showed that water loss rates (WLR) were significantly positively related to precipitation in pupae even after phylogenetic adjustment. Adults showed no physiology-climate correlations. Ancestral trait reconstruction suggests that a reduction in WLR and increased size probably evolved from an intermediate ancestral state and may have facilitated survival in xeric environments. The results of this study therefore suggest an important role for water balance physiology of pupae in determining interspecific variation and lend support to conclusions reached by early studies of tsetse physiology.
Dopamine receptors – IUPHAR Review 13
Beaulieu, Jean-Martin; Espinoza, Stefano; Gainetdinov, Raul R
2015-01-01
The variety of physiological functions controlled by dopamine in the brain and periphery is mediated by the D1, D2, D3, D4 and D5 dopamine GPCRs. Drugs acting on dopamine receptors are significant tools for the management of several neuropsychiatric disorders including schizophrenia, bipolar disorder, depression and Parkinson's disease. Recent investigations of dopamine receptor signalling have shown that dopamine receptors, apart from their canonical action on cAMP-mediated signalling, can regulate a myriad of cellular responses to fine-tune the expression of dopamine-associated behaviours and functions. Such signalling mechanisms may involve alternate G protein coupling or non-G protein mechanisms involving ion channels, receptor tyrosine kinases or proteins such as β-arrestins that are classically involved in GPCR desensitization. Another level of complexity is the growing appreciation of the physiological roles played by dopamine receptor heteromers. Applications of new in vivo techniques have significantly furthered the understanding of the physiological functions played by dopamine receptors. Here we provide an update of the current knowledge regarding the complex biology, signalling, physiology and pharmacology of dopamine receptors. PMID:25671228
Corey, Emily; Linnansaari, Tommi; Cunjak, Richard A; Currie, Suzanne
2017-01-01
The frequency of extreme thermal events in temperate freshwater systems is expected to increase alongside global surface temperature. The Miramichi River, located in eastern Canada, is a prominent Atlantic salmon ( Salmo salar ) river where water temperatures can exceed the proposed upper thermal limit for the species (~27°C). Current legislation closes the river to recreational angling when water temperatures exceed 20°C for two consecutive nights. We aimed to examine how natural thermal variation, representative of extreme high thermal events, affected the thermal tolerance and physiology of wild, juvenile Atlantic salmon. We acclimated fish to four thermal cycles, characteristic of real-world thermal conditions while varying daily thermal minima (16°C, 18°C, 20°C or 22°C) and diel thermal fluctuation (e.g. Δ5°C-Δ9°C). In each cycling condition, we assessed the role that thermal minima played on the acute thermal tolerance (critical thermal maximum, (CTMax)), physiological (e.g. heat shock protein 70 (HSP70), ubiquitin) and energetic (e.g. hepatic glycogen, blood glucose and lactate) status of juvenile Atlantic salmon throughout repeated thermal cycles. Exposure to 16-21°C significantly increased CTMax (+0.9°C) compared to a stable acclimation temperature (16°C), as did exposure to diel thermal fluctuations of 18-27°C, 20-27°C and 22-27°C, yet repeated exposure provided no further increases in acute thermal tolerance. In comparison to the reference condition (16-21°C), consecutive days of high temperature cycling with different thermal minima resulted in significant increases in HSP70 and ubiquitin, a significant decrease in liver glycogen, and no significant cumulative effect on either blood glucose or lactate. However, comparison between thermally taxed treatments suggested the diel thermal minima had little influence on the physiological or energetic response of juvenile salmon, despite the variable thermal cycling condition. Our results suggest that relatively cooler night temperatures in the summer months may play a limited role in mitigating physiological stress throughout warm diel cycle events.
Harte, Christopher B; Meston, Cindy M
2008-05-01
Extensive research suggests that long-term cigarette smoking is an independent risk factor for the introduction of sexual dysfunction in men. However, results of limited data investigating this relationship in women are mixed. No studies have examined the acute effects of tobacco or nicotine on physiological sexual response in women. Controlled experimental studies examining acute effects of isolated nicotine intake on female physiological sexual responses are necessary in order to help elucidate tobacco's potential role in the development and/or maintenance of sexual impairment in women. To examine whether isolated nicotine intake acutely affects sexual arousal responses in nonsmoking women. Twenty-five sexually functional women (mean age = 20 years) each with less than 100 direct exposures to nicotine completed two counterbalanced conditions in which they were randomized to received either nicotine gum (6 mg) or placebo gum, both administered double-blind and matched for appearance, taste, and consistency, approximately 40 minutes prior to viewing an erotic film. Physiological (changes in vaginal pulse amplitude via vaginal photoplethysmography) and subjective (continuous self-report) sexual responses to erotic stimuli were examined, as well as changes in mood. Nicotine significantly reduced genital responses to the erotic films (P = 0.05), corresponding to a 30% attenuation in physiological sexual arousal. This occurred in 11 of 18 women with valid physiological assessments. Nicotine had no significant effect on continuous self-report ratings of sexual arousal (P = 0.45), or on mood (all Ps > 0.05). Acute nicotine intake significantly attenuates physiological sexual arousal in healthy nonsmoking women. Our findings provide support to the hypothesis that nicotine may be the primary pharmacological agent responsible for genital hemodynamic disruption, thereby facilitating a cascade of biochemical and vascular events which may impair normal sexual arousal responses.
Cardiometabolic Features of Polycystic Ovary Syndrome: Role of Androgens.
Yanes Cardozo, Licy L; Romero, Damian G; Reckelhoff, Jane F
2017-09-01
Polycystic ovary syndrome (PCOS) is the most common endocrine disorder that affects reproductive-age women. Hyperandrogenemia is present in a significant fraction (~80%) of women with PCOS. Increased prevalence of cardiometabolic risk factors is frequently observed in PCOS women. The present review aims to highlight the key role of androgens in mediating the negative cardiometabolic profile observed in PCOS women. Copyright © 2017 the American Physiological Society.
The emerging physiological roles of the SLC14A family of urea transporters
Stewart, Gavin
2011-01-01
In mammals, urea is the main nitrogenous breakdown product of protein catabolism and is produced in the liver. In certain tissues, the movement of urea across cell membranes is specifically mediated by a group of proteins known as the SLC14A family of facilitative urea transporters. These proteins are derived from two distinct genes, UT-A (SLC14A2) and UT-B (SLC14A1). Facilitative urea transporters play an important role in two major physiological processes – urinary concentration and urea nitrogen salvaging. Although UT-A and UT-B transporters both have a similar basic structure and mediate the transport of urea in a facilitative manner, there are a number of significant differences between them. UT-A transporters are mainly found in the kidney, are highly specific for urea, have relatively lower transport rates and are highly regulated at both gene expression and cellular localization levels. In contrast, UT-B transporters are more widespread in their tissue location, transport both urea and water, have a relatively high transport rate, are inhibited by mercurial compounds and currently appear to be less acutely regulated. This review details the fundamental research that has so far been performed to investigate the function and physiological significance of these two types of urea transporters. PMID:21449978
Physiological effects and therapeutic potential of proinsulin C-peptide
Maric-Bilkan, Christine; Luppi, Patrizia; Wahren, John
2014-01-01
Connecting Peptide, or C-peptide, is a product of the insulin prohormone, and is released with and in amounts equimolar to those of insulin. While it was once thought that C-peptide was biologically inert and had little biological significance beyond its role in the proper folding of insulin, it is now known that C-peptide binds specifically to the cell membranes of a variety of tissues and initiates specific intracellular signaling cascades that are pertussis toxin sensitive. Although it is now clear that C-peptide is a biologically active molecule, controversy still remains as to the physiological significance of the peptide. Interestingly, C-peptide appears to reverse the deleterious effects of high glucose in some tissues, including the kidney, the peripheral nerves, and the vasculature. C-peptide is thus a potential therapeutic agent for the treatment of diabetes-associated long-term complications. This review addresses the possible physiologically relevant roles of C-peptide in both normal and disease states and discusses the effects of the peptide on sensory nerve, renal, and vascular function. Furthermore, we highlight the intracellular effects of the peptide and present novel strategies for the determination of the C-peptide receptor(s). Finally, a hypothesis is offered concerning the relationship between C-peptide and the development of microvascular complications of diabetes. PMID:25249503
Biostable beta-amino acid PK/PBAN analogs: Agonist and antagonist properties
USDA-ARS?s Scientific Manuscript database
The pyrokinin/pheromone biosynthesis activating neuropeptide (PK/PBAN) family plays a significant role in a multifunctional array of important physiological processes in insects. PK/PBAN analogs incorporating beta-amino acids were synthesized and evaluated in a pheromonotropic assay in Heliothis pe...
Physiological arousal deficits in addicted gamers differ based on preferred game genre.
Metcalf, Olivia; Pammer, Kristen
2014-01-01
There has been significant discussion surrounding the psychopathology of excessive gaming and whether it constitutes an addiction. The current study investigated physiological and subjective levels of arousal in gamers of two genres and the relationship between sensation seeking and gaming addiction. Heart rate (HR), blood pressure (BP) and skin conductance were recorded at baseline, during gaming for 15 min and after gaming in 30 massively multiplayer online role-playing game (MMORPG) and 30 first-person shooter (FPS) male gamers. Gamers were identified as addicted using the Addiction-Engagement Questionnaire. Sensation seeking was measured using the Arnett Inventory of Sensation Seeking. Addicted MMORPG gamers (n=16) displayed significant decreases in cardiovascular activity during gaming compared to baseline and showed significant increases after gaming. Addicted FPS gamers (n=13) had significant increases in BP during gaming which decreased significantly after gaming. In comparison, non-addicted MMORPG gamers (n=14) had significant decreases in HR during gaming, whereas BP in non-addicted MMORPG and FPS gamers (n=17) increased during gaming and after gaming. There were no significant relationships between sensation seeking and addiction. There are physiological arousal deficits in addicted gamers, and these patterns differ according to the genre of game played. Copyright © 2013 S. Karger AG, Basel.
Nielsen, Dorte Guldbrand; Gotzsche, Ole; Sonne, Ole; Eika, Berit
2012-10-01
Two major views on the relationship between basic science knowledge and clinical knowledge stand out; the Two-world view seeing basic science and clinical science as two separate knowledge bases and the encapsulated knowledge view stating that basic science knowledge plays an overt role being encapsulated in the clinical knowledge. However, resent research has implied that a more complex relationship between the two knowledge bases exists. In this study, we explore the relationship between immediate relevant basic science (physiology) and clinical knowledge within a specific domain of medicine (echocardiography). Twenty eight medical students in their 3rd year and 45 physicians (15 interns, 15 cardiology residents and 15 cardiology consultants) took a multiple-choice test of physiology knowledge. The physicians also viewed images of a transthoracic echocardiography (TTE) examination and completed a checklist of possible pathologies found. A total score for each participant was calculated for the physiology test, and for all physicians also for the TTE checklist. Consultants scored significantly higher on the physiology test than did medical students and interns. A significant correlation between physiology test scores and TTE checklist scores was found for the cardiology residents only. Basic science knowledge of immediate relevance for daily clinical work expands with increased work experience within a specific domain. Consultants showed no relationship between physiology knowledge and TTE interpretation indicating that experts do not use basic science knowledge in routine daily practice, but knowledge of immediate relevance remains ready for use.
CO2 Permeability of Biological Membranes and Role of CO2 Channels
Endeward, Volker; Arias-Hidalgo, Mariela; Al-Samir, Samer; Gros, Gerolf
2017-01-01
We summarize here, mainly for mammalian systems, the present knowledge of (a) the membrane CO2 permeabilities in various tissues; (b) the physiological significance of the value of the CO2 permeability; (c) the mechanisms by which membrane CO2 permeability is modulated; (d) the role of the intracellular diffusivity of CO2 for the quantitative significance of cell membrane CO2 permeability; (e) the available evidence for the existence of CO2 channels in mammalian and artificial systems, with a brief view on CO2 channels in fishes and plants; and, (f) the possible significance of CO2 channels in mammalian systems. PMID:29064458
Magder, Sheldon
2007-12-01
Discussions of cardiac physiology and pathophysiology most often emphasise the function of the left heart. However, right heart dysfunction plays an important role in critically ill patients and is often not recognised. This is probably because the role of the right ventricle is for generating flow more than pressure, and flow is not easy to evaluate. Of importance, when right ventricular function limits cardiac output, assessing left ventricular function gives little indication of overall cardiac performance. It has recently become evident that the right ventricle also has different genetic origins and characteristics from the left ventricle. The right and left ventricles interact through series effects, diastolic interactions and systolic interactions. The mechanisms of these, and their physiological and pathological significance are discussed.
Roles and regulation of the matrix metalloproteinase system in parturition.
Geng, Junnan; Huang, Cong; Jiang, Siwen
2016-04-01
Significant tissue destruction, repair, and remodeling are involved in parturition, which involves fetal membrane rupture, cervical ripening, and uterine contraction and its subsequent involution. Extracellular matrix degradation and remodeling by proteolytic enzymes, such as matrix metalloproteinases (MMPs), are required for the final steps of parturition. MMPs participate in physiological degradation and remodeling through their proteolytic activities on specific substrates, and are balanced by the action of their inhibitors. Disruption to this balance can result in pathological stress that ends with preterm or post-term birth or pre-eclampsia. In this review, we examine the roles and regulation of the MMP system in physiological and pathological labor, and propose a model that illustrates the mechanisms by which the MMP system contributes to these processes. © 2016 Wiley Periodicals, Inc.
Pasqualone, Antonella; Summo, Carmine; Centomani, Isabella; Lacolla, Giovanni; Caranfa, Gianraffaele; Cucci, Giovanna
2017-03-01
Several studies have evaluated the effects of composted sewage sludge on barley and found a positive influence on crop productivity. No studies have investigated the effects of composted sewage sludge on functional compounds of the caryopsis, such as phenolics and β-glucans. The former play a role in plant defence mechanisms and both could be influenced by variations of kernel size related to fertilization intensity. The present study aimed to evaluate the effect of different doses (3-12 mg ha -1 ) of composted sewage sludge applied alone or in combination with mineral fertilization on morpho-physiological and yield qualitative parameters, especially phenolics and β-glucans contents of grains, in barley. Increasing fertilization rates, irrespective of fertilizer type, improved morpho-physiological and yield parameters, whereas the phenolic compounds and the related antioxidant activity significantly decreased (P < 0.05). The β-glucans and the main color indices did not show significant differences. The combined application of 6 mg ha -1 sewage sludge and nitrogen was not significantly different from mineral fertilization. Morpho-physiological and qualitative parameters, as well as bioactive compounds, were all significantly correlated with nutrient levels, with higher r values for nitrogen. Composted sewage sludge had a similar effect compared to mineral fertilization. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.
Lazovic, Biljana; Zlatkovic Svenda, Mirjana; Durmic, Tijana; Stajic, Zoran; Duric, Vesna; Zugic, Vladimir
2016-11-01
The major oxygen sensors in the human body are peripheral chemoreceptors. also known as interoreceptors- as connected with internal organs, located in the aortic arch and in the body of the common carotid artery. Chemoreceptor function under physiological conditions. Stimulation of peripheral chemoreceptors during enviromental hypoxia causes a reflex-mediated increased ventilation, followed by the increase of the muscle sympatic activity, aiming to maintain tissue oxygen homeostatis, as well as glucosae, homeostatis. Besides that, peripheral chemoreceptors interact with central chemoreceptors. responsible for carbon dioxide changes . and they are able to modulate each other. Chemoreceptor function in pathophysiological conditions. Investigations of respiratory function in many pathological processes, such as hypertension, obstructive sleep apnea, congestive heart failure and many other diseases that are presented with enhanced peripheral chemosensitivity and impaired functional sy mpatholysis ultimately determine the peripheral chemorcceptor role and significance of peripheral chemoreceptors in the process of those pathological conditions development. Considering this, the presumed influence of peripheral chemoreceptors is important in patients having the above mentioned pathology. The importance and the role of peripheral chemoreceptors in the course of the breathing control is still controversial, despite many scientific attempts to solve this problem. The main objective of this review is to give the latest data on the peripheral chemoreceptor role and to highlight the importance of peripheral chemoreceptors for maintaining of oxygen homeostasis in pateints with hypoxia caused by either physiological or pathological conditions.
The role of mitochondrial superoxide anion (O2(-)) on physiological aging in C57BL/6J mice.
Miyazawa, Masaki; Ishii, Takamasa; Yasuda, Kayo; Noda, Setsuko; Onouchi, Hiromi; Hartman, Philip S; Ishii, Naoaki
2009-01-01
Much attention has been focused on the mitochondrial superoxide anion (O2(-)), which is also a critical free radial produced by ionizing radiation. The specific role of the mitochondrial O2(-) on physiological aging in mammals is still unclear despite wide-spread evidence that oxidative stress is involved in aging and age-related diseases. The major endogenous source of O2(-) is generated as a byproduct of energy metabolism from mitochondria. In order to better understand how O2(-)relates to metazoan aging, we have comprehensively examined age-related changes in the levels of oxidative damage, mitochondrial O2(-) production, mitochondrial antioxidant enzyme activity and apoptosis induction in key organs of an inbred mouse strain (C57BL/6J). Oxidative damage accumulated and excess apoptosis occurred in the brain, oculus and kidney with aging, but comparatively little occurred in the heart and muscle. These rates are correlated with O2(-) levels. Mitochondrial O2(-) production levels increased with aging in the brain, oculus and kidney, and did not significantly increased in the heart and muscle. In contrast to O2(-) production, mitochondrial SOD activities increased in heart and muscle, and remained unchanged in the brain, oculus and kidney with aging. These results suggest that O2(-) production has high organ specificity, and oxidative damage by O2(-) from mitochondria mediated apoptosis can lead to organ atrophy and physiological dysfunction. In addition, O2(-) from mitochondria plays a core role in physiological aging.
Circulatory Insufficiency and Hypotension Related to the Ductus Arteriosus in Neonates
Rios, Danielle R.; Bhattacharya, Soume; Levy, Philip T.; McNamara, Patrick J.
2018-01-01
The biological role of the ductus arteriosus (DA) in neonates varies from an innocent bystander role during normal postnatal transition, to a supportive role when there is compromise to either systemic or pulmonary blood flow, to a pathological state in the presence of hemodynamically significant systemic to pulmonary shunts, as occurs in low birth weight infants. Among a wide array of clinical manifestations arising due to the ductal entity, systemic circulatory insufficiency and hypotension are of significant concern as they are particularly challenging to manage. An understanding of the physiologic interplay between the DA and the circulatory system is the key to developing appropriate targeted therapeutic strategies. In this review, we discuss the relationship of systemic hypotension to the DA, emphasizing the importance of critical thinking and a precise individual approach to intensive care support. We particularly focus on the variable states of hypotension arising directly due to a hemodynamically significant DA or seen in the period following successful surgical ligation. In addition, we explore the mechanistic contributions of the ductus to circulatory insufficiency that may manifest during the transitional period, states of maladapted transition (such as acute pulmonary hypertension of the newborn), and congenital heart disease (both ductal dependent and non-ductal dependent lesions). Understanding the dynamic modulator role of the ductus according to the ambient physiology enables a more precise approach to management. We review the pathophysiology, clinical manifestations, diagnosis, monitoring, and therapeutic intervention for the spectrum of DA-related circulatory compromise. PMID:29600242
Ai, Todd
2012-01-01
There has been limited attention given to the physiological demands of pushing and pulling, especially in industrially developing countries such as South Africa. Two key factors affecting the physiological demands of these tasks are the hand forces exerted and the start/stop frequency. The purpose of the current study was therefore to investigate the physiological responses to pushing and pulling at various loads and start/stop frequencies. 36 male subjects participated in the study and were required to complete a total of 18 conditions (three techniques: pushing, two- and one-handed pulling; three loads: 200, 350 and 500 kg; and two frequencies: 2 and 4 stops per minute). During each condition the heart rate, oxygen uptake and energy expenditure were measured. Pushing was found to elicit significantly lower responses for all three dependent variables than either form of pulling. The start/stop frequency was also found to have a significant impact on subject responses. The findings of this study indicate that the technique adopted to maneuver loads is critical in determining the physical demands placed on the human operator. Furthermore increasing the frequency of start/stops plays an important role, thus the forces exerted during these two phases are important from a physiological perspective.
NASA Astrophysics Data System (ADS)
Ning, Xuhui; Peng, Chuanqi; Li, Eric S.; Xu, Jing; Vinluan, Rodrigo D.; Yu, Mengxiao; Zheng, Jie
2017-05-01
Efficient renal clearance has been observed from ultrasmall zwitterionic glutathione-coated gold nanoparticles (GS-AuNPs), which have broad preclinical applications in cancer diagnosis and kidney functional imaging. However, origin of such efficient renal clearance is still not clear. Herein, we conducted head-to-head comparison on physiological stability and renal clearance of two zwitterionic luminescent AuNPs coated with cysteine and glycine-cysteine (Cys-AuNPs and Gly-Cys-AuNPs), respectively. While both of them exhibited similar surface charges and the same core sizes, additional glycine slightly increased the hydrodynamic diameter of the AuNPs by 0.4 nm but significantly enhanced physiological stability of the AuNPs as well as altered their clearance pathways. These studies indicate that the ligand length, in addition to surface charges and size, also plays a key role in the physiological stability and renal clearance of ultrasmall zwitterionic inorganic NPs.
Ajayi, Oyeyemi O; Adefenwa, Mufliat A; Agaviezor, Brilliant O; Ikeobi, Christian O N; Wheto, Matthew; Okpeku, Moses; Amusan, Samuel A; Yakubu, Abdulmojeed; De Donato, Marcos; Peters, Sunday O; Imumorin, Ikhide G
2014-02-01
The tenascin-XB (TNXB) gene has antiadhesive effects, functions in matrix maturation in connective tissues, and localizes to the major histocompatibility complex class III region. We hypothesized that it may influence adaptive physiological response through an effect on blood vessel function. We identified a novel g.1324 A→G polymorphism at a TaqI recognition site in a 454 bp fragment of ovine TNXB and genotyped it in 150 Nigerian sheep using PCR-RFLP. The missense mutation changes glutamic acid (GAA) to glycine (GGA). Among SNP genotypes, significant differences (P < 0.05) were observed in body weight and fore cannon bone length. Interaction effects of breed, SNP genotype, and geographic location had a significant effect (P < 0.05) on chest girth. The SNP genotype was significantly (P < 0.05) associated with physiological traits of pulse rate and skin temperature. The observed effect of this novel polymorphism may be mediated through its role in connective tissue biology, requiring further association and functional studies.
Navarro, Jorge M.; González, Katerina; Cisternas, Barbara; López, Jorge A.; Chaparro, Oscar R.; Segura, Cristian J.; Córdova, Marco; Suárez-Isla, Benjamín; Fernandez-Reiriz, María J.; Labarta, Uxio
2014-01-01
This study describes the physiological performance of two populations of the razor clam Tagelus dombeii from two geographic areas with different histories of exposure to paralytic shellfish poisoning (PSP) linked to the toxic dinoflagellate Alexandrium catenella. Clams from Melinka-Aysén, which are frequently exposed to PSP, were not affected by the presence of toxins in the diet. However, clams from Corral-Valdivia, which have never been exposed to PSP, exhibited significantly reduced filtration activity and absorption, affecting the energy allocated to scope for growth (SFG). Ammonia excretion and oxygen uptake were not affected significantly by the presence of A. catenella in the diet. Measurements of energy acquisition and expenditure were performed during a 12-day intoxication period. According to three-way repeated measure ANOVAs, the origin of the clams had a highly significant effect on all physiological variables, and the interaction between diet and origin was significant for the clearance and absorption rates and for the scope for growth. The scope for growth index showed similar positive values for both the toxic and non-toxic individuals from the Melinka-Aysén population. However, it was significantly reduced in individuals from Corral-Valdivia when exposed to the diet containing A. catenella. The absence of differences between the physiological response of the toxic and non-toxic clams from Melinka-Aysén may be related to the frequent presence of A. catenella in the environment, indicating that this bivalve does not suffer negative consequences from PSP. By contrast, A. catenella has a negative effect on the physiological performance, primarily on the energy gained from the environment, on T. dombeii from Corral-Valdivia. This study supports the hypothesis that the history of PSP exposure plays an important role in the physiological performance and fitness of filter feeding bivalves. PMID:25153329
Lee, Min-sun; Park, Bum-jin; Lee, Juyoung; Park, Kun-tae; Ku, Ja-hyeong; Lee, Jun-woo; Oh, Kyung-ok; Miyazaki, Yoshifumi
2013-10-10
Despite increasing attention and a growing volume of research data, little physiological evidence is available on the benefits of horticultural activity and the different effects on individuals. Therefore, the aim of the present study was to investigate the physiological effects of horticultural activity and to examine how differences in personality alter these effects. The effects of transplanting real flowers (horticultural activity) and handling artificial flowers (control activity) on human physiological activity were compared. On the first day, eight participants engaged in horticultural activity and another eight in the control activity. On the second day, participants switched roles. Participants' physiological conditions during each activity were assessed by measuring the heart rate and heart rate variability (HRV). Psychological responses, which were measured using a semantic differential rating scale, showed that the horticultural activity promoted comfortable, soothed, and natural feelings, compared to the control activity. Analysis of physiological responses using two-way repeated measures analysis of variance (ANOVA) revealed that sympathetic nervous activity significantly decreased in the late time period (11 to 15 minutes) of horticultural activity only in the type A group. This study supports the fact that the horticultural activity can enhance psychological and physiological relaxation effects, although these physiological effects can differ among individuals with different personalities.
2013-01-01
Background Despite increasing attention and a growing volume of research data, little physiological evidence is available on the benefits of horticultural activity and the different effects on individuals. Therefore, the aim of the present study was to investigate the physiological effects of horticultural activity and to examine how differences in personality alter these effects. Results The effects of transplanting real flowers (horticultural activity) and handling artificial flowers (control activity) on human physiological activity were compared. On the first day, eight participants engaged in horticultural activity and another eight in the control activity. On the second day, participants switched roles. Participants’ physiological conditions during each activity were assessed by measuring the heart rate and heart rate variability (HRV). Psychological responses, which were measured using a semantic differential rating scale, showed that the horticultural activity promoted comfortable, soothed, and natural feelings, compared to the control activity. Analysis of physiological responses using two-way repeated measures analysis of variance (ANOVA) revealed that sympathetic nervous activity significantly decreased in the late time period (11 to 15 minutes) of horticultural activity only in the type A group. Conclusions This study supports the fact that the horticultural activity can enhance psychological and physiological relaxation effects, although these physiological effects can differ among individuals with different personalities. PMID:24112302
USDA-ARS?s Scientific Manuscript database
Flavonoids such as anthocyanins possess significant health benefits to humans and play important physiological roles in plants. An interesting Purple gene mutation in cauliflower confers an abnormal pattern of anthocyanin accumulation, giving intense purple color in very young leaves, curds, and see...
USDA-ARS?s Scientific Manuscript database
The mitochondrion is the organelle responsible for generation of most usable energy in a cell. It also plays an important role in a series of physiological processes such as apoptosis and proliferation. Although previous studies have demonstrated that nicotine modulates the morphology and function ...
USDA-ARS?s Scientific Manuscript database
Calmodulin, a ubiquitous calcium sensor, plays an important role in decoding the stress-triggered intracellular calcium changes and regulates the functions of numerous target proteins involved in various physiological responses in plants. To determine the functional significance of calmodulin in fl...
Brown adipose tissue activation is linked to distinct systemic effects on lipid metabolism in humans
USDA-ARS?s Scientific Manuscript database
Recent studies suggest that brown adipose tissue (BAT) plays a role in energy and glucose metabolism in humans. However, the physiological significance of human BAT in lipid metabolism remains unknown. We studied 16 overweight/obese men during prolonged, non-shivering cold and thermoneutral conditio...
Acylcarnitines: old actors auditioning for new roles in metabolic physiology
USDA-ARS?s Scientific Manuscript database
A number of challenges or perturbations in metabolic pathways lead to significant increases in plasma and tissue long-chain acylcarnitines (LCAC). The LCAC and other acylcarnitines rise, for instance, in the blood and muscle during exercise bouts, as tissue acyl-CoA pools change with accelerated met...
ERIC Educational Resources Information Center
Physician and Sportsmedicine, 1987
1987-01-01
In a roundtable format, five doctors explore the reasons why regular physical activity should continue to play a significant role in the rehabilitation of patients with coronary artery disease. Endurance exercise training improves aerobic capacity, reduces blood pressure, and decreases risk. (Author/MT)
Empathy Based on Gender in Dissertations Submitted in Turkey: A Meta-Analysis Study
ERIC Educational Resources Information Center
Demir, Yasin; Atli, Abdullah; Kis, Ali
2016-01-01
Problem Statement: Today, where the relationships among people have increased and concentrated, maintaining powerful communication channels with the individual(s) is significant for conducting healthy and sustainable relationships with others. Social roles assigned to gender and physiological differences determine the understanding of individuals…
This report describes the in vitro inactivation of endotoxin by various tissues of the guinea pig , and attempts to assess the physiological role of the spleen in the response of normal animals and those with liver damage to administration of endotoxin.
Physiological Role of Gap-Junctional Hemichannels
Quist, Arjan Pieter; Rhee, Seung Keun; Lin, Hai; Lal, Ratneshwar
2000-01-01
Hemichannels in the overlapping regions of apposing cells plasma membranes join to form gap junctions and provide an intercellular communication pathway. Hemichannels are also present in the nonjunctional regions of individual cells and their activity is gated by several agents, including calcium. However, their physiological roles are unknown. Using techniques of atomic force microscopy (AFM), fluorescent dye uptake assay, and laser confocal immunofluorescence imaging, we have examined the extracellular calcium-dependent modulation of cell volume. In response to a change in the extracellular physiological calcium concentration (1.8 to ≤1.6 mM) in an otherwise isosmotic condition, real-time AFM imaging revealed a significant and reversible increase in the volume of cells expressing gap-junctional proteins (connexins). Volume change did not occur in cells that were not expressing connexins. However, after the transient or stable transfection of connexin43, volume change did occur. The volume increase was accompanied by cytochalasin D-sensitive higher cell stiffness, which helped maintain cell integrity. These cellular physical changes were prevented by gap-junctional blockers, oleamide and β-glycyrrhetinic acid, or were reversed by returning extracellular calcium to the normal level. We conclude that nongap-junctional hemichannels regulate cell volume in response to the change in extracellular physiological calcium in an otherwise isosmotic situation. PMID:10704454
The role of pleiotrophin in bone repair.
Lamprou, Margarita; Kaspiris, Angelos; Panagiotopoulos, Elias; Giannoudis, Peter V; Papadimitriou, Evangelia
2014-12-01
Bone has an enormous capacity for growth, regeneration, and remodelling, largely due to induction of osteoblasts that are recruited to the site of bone formation. Although the pathways involved have not been fully elucidated, it is well accepted that the immediate environment of the cells is likely to play a role via cell–matrix interactions, mediated by several growth factors. Formation of new blood vessels is also significant and interdependent to bone formation, suggesting that enhancement of angiogenesis could be beneficial during the process of bone repair. Pleiotrophin (PTN), also called osteoblast-specific factor 1, is a heparin-binding angiogenic growth factor, with a well-defined and significant role in both physiological and pathological angiogenesis. In this review we summarise the existing evidence on the role of PTN in bone repair.
The Plasma Membrane Calcium ATPases and Their Role as Major New Players in Human Disease.
Stafford, Nicholas; Wilson, Claire; Oceandy, Delvac; Neyses, Ludwig; Cartwright, Elizabeth J
2017-07-01
The Ca 2+ extrusion function of the four mammalian isoforms of the plasma membrane calcium ATPases (PMCAs) is well established. There is also ever-increasing detail known of their roles in global and local Ca 2+ homeostasis and intracellular Ca 2+ signaling in a wide variety of cell types and tissues. It is becoming clear that the spatiotemporal patterns of expression of the PMCAs and the fact that their abundances and relative expression levels vary from cell type to cell type both reflect and impact on their specific functions in these cells. Over recent years it has become increasingly apparent that these genes have potentially significant roles in human health and disease, with PMCAs1-4 being associated with cardiovascular diseases, deafness, autism, ataxia, adenoma, and malarial resistance. This review will bring together evidence of the variety of tissue-specific functions of PMCAs and will highlight the roles these genes play in regulating normal physiological functions and the considerable impact the genes have on human disease. Copyright © 2017 the American Physiological Society.
Lysophosphatidic acid as a lipid mediator with multiple biological actions.
Aikawa, Shizu; Hashimoto, Takafumi; Kano, Kuniyuki; Aoki, Junken
2015-02-01
Lysophosphatidic acid (LPA) is one of the simplest glycerophospholipids with one fatty acid chain and a phosphate group as a polar head. Although LPA had been viewed just as a metabolic intermediate in de novo lipid synthetic pathways, it has recently been paid much attention as a lipid mediator. LPA exerts many kinds of cellular processes, such as cell proliferation and smooth muscle contraction, through cognate G protein-coupled receptors. Because lipids are not coded by the genome directly, it is difficult to know their patho- and physiological roles. However, recent studies have identified several key factors mediating the biological roles of LPA, such as receptors and producing enzymes. In addition, studies of transgenic and gene knockout animals for these LPA-related genes, have revealed the biological significance of LPA. In this review we will summarize recent advances in the studies of LPA production and its roles in both physiological and pathological conditions. © The Authors 2014. Published by Oxford University Press on behalf of the Japanese Biochemical Society. All rights reserved.
Grubbs, Kirk J; Bleich, Rachel M; Santa Maria, Kevin C; Allen, Scott E; Farag, Sherif; Shank, Elizabeth A; Bowers, Albert A
2017-01-01
Bacteria possess an amazing capacity to synthesize a diverse range of structurally complex, bioactive natural products known as specialized (or secondary) metabolites. Many of these specialized metabolites are used as clinical therapeutics, while others have important ecological roles in microbial communities. The biosynthetic gene clusters (BGCs) that generate these metabolites can be identified in bacterial genome sequences using their highly conserved genetic features. We analyzed an unprecedented 1,566 bacterial genomes from Bacillus species and identified nearly 20,000 BGCs. By comparing these BGCs to one another as well as a curated set of known specialized metabolite BGCs, we discovered that the majority of Bacillus natural products are comprised of a small set of highly conserved, well-distributed, known natural product compounds. Most of these metabolites have important roles influencing the physiology and development of Bacillus species. We identified, in addition to these characterized compounds, many unique, weakly conserved BGCs scattered across the genus that are predicted to encode unknown natural products. Many of these "singleton" BGCs appear to have been acquired via horizontal gene transfer. Based on this large-scale characterization of metabolite production in the Bacilli , we go on to connect the alkylpyrones, natural products that are highly conserved but previously biologically uncharacterized, to a role in Bacillus physiology: inhibiting spore development. IMPORTANCE Bacilli are capable of producing a diverse array of specialized metabolites, many of which have gained attention for their roles as signals that affect bacterial physiology and development. Up to this point, however, the Bacillus genus's metabolic capacity has been underexplored. We undertook a deep genomic analysis of 1,566 Bacillus genomes to understand the full spectrum of metabolites that this bacterial group can make. We discovered that the majority of the specialized metabolites produced by Bacillus species are highly conserved, known compounds with important signaling roles in the physiology and development of this bacterium. Additionally, there is significant unique biosynthetic machinery distributed across the genus that might lead to new, unknown metabolites with diverse biological functions. Inspired by the findings of our genomic analysis, we speculate that the highly conserved alkylpyrones might have an important biological activity within this genus. We go on to validate this prediction by demonstrating that these natural products are developmental signals in Bacillus and act by inhibiting sporulation.
USDA-ARS?s Scientific Manuscript database
Biogenic amines in all organisms including plants affect a myriad of growth and developmental processes. Therefore, there is continued interest in understanding their (here polyamines) biosynthesis and functional roles in regulating plant metabolism, physiology and development. The role of polyamine...
Recent Advances in the Chemical Biology of Nitroxyl (HNO) Detection and Generation
Miao, Zhengrui; King, S. Bruce
2016-01-01
Nitroxyl or azanone (HNO) represents the redox-related (one electron reduced and protonated) relative of the well-known biological signaling molecule nitric oxide (NO). Despite the close structural similarity to NO, defined biological roles and endogenous formation of HNO remain unclear due to the high reactivity of HNO with itself, soft nucleophiles and transition metals. While significant work has been accomplished in terms of the physiology, biology and chemistry of HNO, important and clarifying work regarding HNO detection and formation has occurred within the last 10 years. This review summarizes advances in the areas of HNO detection and donation and their application to normal and pathological biology. Such chemical biological tools allow a deeper understanding of biological HNO formation and the role that HNO plays in a variety of physiological systems. PMID:27108951
Phelps, Kendra L; Kingston, Tigga
2018-06-01
Environmental and biological context play significant roles in modulating physiological stress responses of individuals in wildlife populations yet are often overlooked when evaluating consequences of human disturbance on individual health and fitness. Furthermore, most studies gauge individual stress responses based on a single physiological biomarker, typically circulating glucocorticoid concentrations, which limits interpretation of the complex, multifaceted responses of individuals to stressors. We selected four physiological biomarkers to capture short-term and prolonged stress responses in a widespread cave-roosting bat, Hipposideros diadema, across multiple gradients of human disturbance in and around caves in the Philippines. We used conditional inference trees and random forest analysis to determine the role of environmental quality (cave complexity, available roosting area), assemblage composition (intra- and interspecific associations and species richness), and intrinsic characteristics of individuals (sex and reproductive status) in modulating responses to disturbance. Direct cave disturbance (hunting pressure and human visitation) was the primary driver of neutrophil-to-lymphocyte ratios, with lower ratios associated with increased disturbance, while context-specific factors were more important in explaining total leukocyte count, body condition, and ectoparasite load. Moreover, conditional inference trees revealed complex interactions among human disturbance and modulating factors. Cave complexity often ameliorated individual responses to human disturbance, whereas conspecific abundance often compounded responses. Our study demonstrates the importance of an integrated approach that incorporates environmental and biological context when identifying drivers of physiological responses, and that assesses responses to gradients of direct and indirect disturbance using multiple complementary biomarkers.
Acid-sensing ion channels in pain and disease
Wemmie, John A.; Taugher, Rebecca J.; Kreple, Collin J.
2015-01-01
Why do neurons sense extracellular acid? In large part, this question has driven increasing investigation on acid-sensing ion channels (ASICs) in the CNS and the peripheral nervous system for the past two decades. Significant progress has been made in understanding the structure and function of ASICs at the molecular level. Studies aimed at clarifying their physiological importance have suggested roles for ASICs in pain, neurological and psychiatric disease. This Review highlights recent findings linking these channels to physiology and disease. In addition, it discusses some of the implications for therapy and points out questions that remain unanswered. PMID:23783197
Acid-sensing ion channels in pain and disease.
Wemmie, John A; Taugher, Rebecca J; Kreple, Collin J
2013-07-01
Why do neurons sense extracellular acid? In large part, this question has driven increasing investigation on acid-sensing ion channels (ASICs) in the CNS and the peripheral nervous system for the past two decades. Significant progress has been made in understanding the structure and function of ASICs at the molecular level. Studies aimed at clarifying their physiological importance have suggested roles for ASICs in pain, neurological and psychiatric disease. This Review highlights recent findings linking these channels to physiology and disease. In addition, it discusses some of the implications for therapy and points out questions that remain unanswered.
Setting sail for glucose homeostasis with the AKAP150-PP2B-anchor.
Teo, Adrian Kee Keong; Kulkarni, Rohit N
2012-10-17
Glucose-stimulated insulin secretion, controlled by multiple protein phosphorylation events, is critical for the regulation of glucose homeostasis. Protein kinase A (PKA) is known to play a role in β cell physiology, but the role of its anchoring protein is not fully understood. Hinke et al (2012) illustrate the significance of A-kinase anchoring protein 150 in tethering protein phosphatase 2B to mediate nutrient-stimulated insulin secretion and thus modulate glucose homeostasis.
McClusky, Leon Mendel
2012-01-01
The traditional presentation of the Reproductive Physiology component in an Anatomy and Physiology course to nursing undergraduates focuses on the broad aspects of hormonal regulation of reproduction and gonadal anatomy, with the role of the higher centres of the brain omitted. An introductory discussion is proposed which could precede the lectures on the reproductive organs. The discussion gives an overview of the biological significance of human pleasure, the involvement of the neurotransmitter dopamine, and the role of pleasure in the survival of the individual and even species. Pleasure stimuli (positive and negative) and the biological significance of naturally-induced pleasurable experiences are briefly discussed in the context of reproduction and the preservation of genetic material with an aim to foster relevancy between subject material and human behaviour in any type of society. The tenderness of this aspect of the human existence is well-understood because of its invariable association with soul-revealing human expressions such as love, infatuation, sexual flirtations, all of which are underpinned by arousal, desire and/or pleasure. Assuming that increased knowledge correlates with increased confidence, the proposed approach may provide the nurse with an adequate knowledge base to overcome well-known barriers in communicating with their patients about matters of sexual health and intimacy. Copyright © 2011 Elsevier Ltd. All rights reserved.
Assessment and management of patients with ankle injuries.
Walker, Jennie
2014-08-19
Foot and ankle injuries are common and can have a significant effect on an individual's daily activities. Nurses have an important role in the assessment, management, ongoing care and support of patients with ankle injuries. An understanding of the anatomy and physiology of the ankle enables nurses to identify significant injuries, which may result in serious complications, and communicate effectively with the multidisciplinary team to improve patient care and outcomes.
Peptidase inhibitors in tick physiology.
Parizi, L F; Ali, A; Tirloni, L; Oldiges, D P; Sabadin, G A; Coutinho, M L; Seixas, A; Logullo, C; Termignoni, C; DA Silva Vaz, I
2018-06-01
Peptidase inhibitors regulate a wide range of physiological processes involved in the interaction between hematophagous parasites and their hosts, including tissue remodeling, the immune response and blood coagulation. In tick physiology, peptidase inhibitors have a crucial role in adaptation to improve parasitism mechanisms, facilitating blood feeding by interfering with defense-related host peptidases. Recently, a larger number of studies on this topic led to the description of several new tick inhibitors displaying interesting novel features, for example a role in pathogen transmission to the host. A comprehensive review discussing these emerging concepts can therefore shed light on peptidase inhibitor functions, their relevance to tick physiology and their potential applications. Here, we summarize and examine the general characteristics, functional diversity and action of tick peptidase inhibitors with known physiological roles in the tick-host-pathogen interaction. © 2017 The Royal Entomological Society.
NASA Astrophysics Data System (ADS)
Potter, Lucas; Arikatla, Sreekanth; Bray, Aaron; Webb, Jeff; Enquobahrie, Andinet
2017-03-01
Stenosis of the upper airway affects approximately 1 in 200,000 adults per year1 , and occurs in neonates as well2 . Its treatment is often dictated by institutional factors and clinicians' experience or preferences 3 . Objective and quantitative methods of evaluating treatment options hold the potential to improve care in stenosis patients. Virtual surgical planning software tools are critically important for this. The Virtual Pediatric Airway Workbench (VPAW) is a software platform designed and evaluated for upper airway stenosis treatment planning. It incorporates CFD simulation and geometric authoring with objective metrics from both that help in informed evaluation and planning. However, this planner currently lacks physiological information which could impact the surgical planning outcomes. In this work, we integrated a lumped parameter, model based human physiological engine called BioGears with VPAW. We demonstrated the use of physiology informed virtual surgical planning platform for patient-specific stenosis treatment planning. The preliminary results show that incorporating patient-specific physiology in the pretreatment plan would play important role in patient-specific surgical trainers and planners in airway surgery and other types of surgery that are significantly impacted by physiological conditions during surgery.
Thoma, M V; Scholz, U; Ehlert, U; Nater, U M
2012-01-01
Music listening has been suggested to have short-term beneficial effects. The aim of this study was to investigate the association and potential mediating mechanisms between various aspects of habitual music-listening behaviour and physiological and psychological functioning. An internet-based survey was conducted in university students, measuring habitual music-listening behaviour, emotion regulation, stress reactivity, as well as physiological and psychological functioning. A total of 1230 individuals (mean = 24.89 ± 5.34 years, 55.3% women) completed the questionnaire. Quantitative aspects of habitual music-listening behaviour, i.e. average duration of music listening and subjective relevance of music, were not associated with physiological and psychological functioning. In contrast, qualitative aspects, i.e. reasons for listening (especially 'reducing loneliness and aggression', and 'arousing or intensifying specific emotions') were significantly related to physiological and psychological functioning (all p = 0.001). These direct effects were mediated by distress-augmenting emotion regulation and individual stress reactivity. The habitual music-listening behaviour appears to be a multifaceted behaviour that is further influenced by dispositions that are usually not related to music listening. Consequently, habitual music-listening behaviour is not obviously linked to physiological and psychological functioning.
Neuropeptide physiology in helminths.
Mousley, Angela; Novozhilova, Ekaterina; Kimber, Michael J; Day, Tim A
2010-01-01
Parasitic worms come from two distinct, distant phyla, Nematoda (roundworms) and Platyhelminthes (flatworms). The nervous systems of worms from both phyla are replete with neuropeptides and there is ample physiological evidence that these neuropeptides control vital aspects of worm biology. In each phyla, the physiological evidence for critical roles for helminth neuropeptides is derived from both parasitic and free-living members. In the nematodes, the intestinal parasite Ascaris suum and the free-living Caenorhabditis elegans have yielded most of the data; in the platyhelminths, the most physiological data has come from the blood fluke Schistosoma mansoni. FMRFamide-like peptides (FLPs) have many varied effects (excitation, relaxation, or a combination) on somatic musculature, reproductive musculature, the pharynx and motor neurons in nematodes. Insulin-like peptides (INSs) play an essential role in nematode dauer formation and other developmental processes. There is also some evidence for a role in somatic muscle control for the somewhat heterogeneous grouping ofpeptides known as neuropeptide-like proteins (NLPs). In platyhelminths, as in nematodes, FLPs have a central role in somatic muscle function. Reports of FLP physiological action in platyhelminths are limited to a potent excitation of the somatic musculature. Platyhelminths are also abundantly endowed with neuropeptide Fs (NPFs), which appear absent from nematodes. There is not yet any data linking platyhelminth NPF to any particular physiological outcome, but this neuropeptide does potently and specifically inhibit cAMP accumulation in schistosomes. In nematodes and platyhelminths, there is an abundance of physiological evidence demonstrating that neuropeptides play critical roles in the biology of both free-living and parasitic helminths. While it is certainly true that there remains a great deal to learn about the biology of neuropeptides in both phyla, physiological evidence presently available points to neuropeptidergic signaling as a very promising field from which to harvest future drug targets.
Narayanan, Sareesh Naduvil; Kumar, Raju Suresh; Nayak, Satheesha
2011-01-01
It is quite difficult to teach complex topics like the physiology of vestibular apparatus to undergraduate students. Understanding the orientation and mode of stimulation of receptors in vestibular apparatus is also quite challenging for the students. As faculty we attempt to use innovative methods to teach physiology and enhance student learning. This article describes a simple and innovative method (student-involved demonstration approach, or SID) to teach the physiology of the vestibular apparatus to the undergraduate medical students. The current study describes a protocol where students engage in role-play sessions in the middle of the regular didactic lectures. Effectiveness of the sessions was later evaluated by using a questionnaire and by comparing the pre-SID and post-SID test results of the students. The posttest score of the students was significantly higher than the pretest score, and this indicates the usefulness of SID sessions on enhancing the student learning in the class. Students also found this method very interesting and useful in better understanding the physiology of the vestibular apparatus.
Arousal, working memory capacity, and sexual decision-making in men.
Spokes, Tara; Hine, Donald W; Marks, Anthony D G; Quain, Peter; Lykins, Amy D
2014-08-01
This study investigated whether working memory capacity (WMC) moderated the relationship between physiological arousal and sexual decision making. A total of 59 men viewed 20 consensual and 20 non-consensual images of heterosexual interaction while their physiological arousal levels were recorded using skin conductance response. Participants also completed an assessment of WMC and a date-rape analogue task for which they had to identify the point at which an average Australian male would cease all sexual advances in response to verbal and/or physical resistance from a female partner. Participants who were more physiologically aroused by and spent more time viewing the non-consensual sexual imagery nominated significantly later stopping points on the date-rape analogue task. Consistent with our predictions, the relationship between physiological arousal and nominated stopping point was strongest for participants with lower levels of WMC. For participants with high WMC, physiological arousal was unrelated to nominated stopping point. Thus, executive functioning ability (and WMC in particular) appears to play an important role in moderating men's decision making with regard to sexually aggressive behavior.
Circulating Endocannabinoid Concentrations and Sexual Arousal in Women
Klein, Carolin; Hill, Matthew N.; Chang, Sabrina C.H.; Hillard, Cecilia J.; Gorzalka, Boris B.
2013-01-01
Introduction Several lines of evidence point to the potential role of the endocannabinoid system in female sexual functioning. These include results from studies describing the subjective effects of exogenous cannabinoids on sexual functioning in humans and the observable effects of exogenous cannabinoids on sexual functioning in other species, as well as results from studies investigating the location of cannabinoid receptors in the brain and periphery, and the effects of cannabinoid receptor activation on neurotransmitters implicated in sexual functioning. While these lines of research suggest a role for the endocannabinoid system in female sexual functioning, no studies investigating the relationship between concentrations of endogenous cannabinoids (i.e., arachidonoylethanolamide [AEA] and 2-arachidonoylglycerol [2-AG]) and sexual functioning have been conducted in any species. Aim To measure circulating endocannabinoid concentrations in relation to subjective and physiological indices of sexual arousal in women (n = 21). Methods Serum endocannabinoid (AEA and 2-AG) concentrations were measured immediately prior to, and immediately following, viewing of neutral (control) and erotic (experimental) film stimuli in a repeated measures design. Physiological sexual arousal was measured via vaginal photoplethysmography. Subjective sexual arousal was measured both continuously and non-continuously. Pearson’s correlations were used to investigate the relationships between endocannabinoid concentrations and sexual arousal. Main Outcome Measures Changes in AEA and 2-AG concentrations from pre- to post-film and in relation to physiological and subjective indices of sexual arousal. Results Results revealed a significant relationship between endocannabinoid concentrations and female sexual arousal, whereby increases in both physiological and subjective indices of sexual arousal were significantly associated with decreases in AEA, and increases in subjective indices of sexual arousal were significantly associated with decreases in 2-AG. Conclusions These findings support the hypothesis that the endocannabinoid system is involved in female sexual functioning, with implications for furthering understanding of the biological mechanisms underlying female sexual functioning. PMID:22462722
Gut Microbiota: Modulation of Host Physiology in Obesity
Allen, Jacob M.; Mailing, Lucy J.; Kashyap, Purna C.; Woods, Jeffrey A.
2016-01-01
Many factors are involved in weight gain and metabolic disturbances associated with obesity. The gut microbiota has been of particular interest in recent years, since both human and animal studies have increased our understanding of the delicate symbiosis between the trillions of microbes that reside in the GI tract and the host. It has been suggested that disruption of this mutual tolerance may play a significant role in modulating host physiology during obesity. Environmental influences such as diet, exercise, and early life exposures can significantly impact the composition of the microbiota, and this dysbiosis can in turn lead to increased host adiposity via a number of different mechanisms. The ability of the microbiota to regulate host fat deposition, metabolism, and immune function makes it an attractive target for achieving sustained weight loss. PMID:27511459
Stress and the multiple-role woman: taking a closer look at the "superwoman".
Sumra, Monika K; Schillaci, Michael A
2015-01-01
In the academic literature there is debate as to whether women who engage in multiple social roles experience more or less stress than women in fewer roles. For the present research we examined the relationship between levels of engagement in seven distinct roles and perceived stress and life satisfaction in a small non-random sample of women in North America (N = 308). We did not find a significant correlation between role engagement and perceived stress, though we did find a small but significant positive correlation between role engagement and life satisfaction. Similarly, in a subset of the participants (N = 31), there was not a significant relationship between the level of role engagement and physiological stress as measured by hair or urinary cortisol levels. We found a significant negative correlation between perceived stress and life satisfaction, and role satisfaction. The results from multiple regression models did not identify the level of role engagement as a significant predictor of either perceived stress or life satisfaction. Role satisfaction in addition to several life style variables such as the frequency of sex and exercise were identified as significant predictors of both outcome variables. We also examined the popularized notion of the "superwoman", which we defined as women who fell within the 4th quartile of role engagement, or those engaged in the wife/mother/worker/homemaker role combination. Based on popular discourses surrounding the superwoman we expected that superwomen would exhibit higher levels of perceived stress. Our results revealed that superwomen do not experience a significantly higher level of perceived stress than non-superwomen. The results of our study therefore suggest that multiple role engagement in women, even at a relatively high level as experienced by "superwomen", is not associated with significantly higher stress, or reduced life satisfaction.
Role of cholesterol and lipid organization in disease
NASA Astrophysics Data System (ADS)
Maxfield, Frederick R.; Tabas, Ira
2005-12-01
Membrane lipids are essential for biological functions ranging from membrane trafficking to signal transduction. The composition of lipid membranes influences their organization and properties, so it is not surprising that disorders in lipid metabolism and transport have a role in human disease. Significant recent progress has enhanced our understanding of the molecular and cellular basis of lipid-associated disorders such as Tangier disease, Niemann-Pick disease type C and atherosclerosis. These insights have also led to improved understanding of normal physiology.
Sato, M; Chihara, K; Kita, T; Kashio, Y; Okimura, Y; Kitajima, N; Fujita, T
1989-08-01
In mammals including human, it is generally accepted that growth hormone (GH) can regulate its own secretion through an autofeedback mechanism in which somatostatin (SRIF) may be involved. To explore a physiological role of SRIF-mediated GH autoregulation, the effect of exogenous human GH administration on plasma rat GH response to [D-Ala2, Nle27]-human GH-releasing hormone-(1-28)-agmatine (hGHRH-analog), which does not crossreact with anti-rat GH-releasing hormone gamma-globulin (GHRH-Ab), was examined in conscious male rats treated with GHRH-Ab in the absence and presence of anti-SRIF gamma-globulin (SRIF-Ab). Enhanced SRIF release during a trough period of natural pulsatile GH secretion, suggested by the blunted GH response to exogenous hGHRH-analog, no longer occurred when major GH secretory bursts were abolished by GHRH-Ab treatment. On the other hand, when hGH was administered in GHRH-Ab-treated rats so as to simulate the quantity and dynamic change of GH in hypophysial portal circulation in rats exhibiting pulsatile GH secretion, hGHRH-analog-induced GH rises were significantly suppressed during the period corresponding to a GH trough. This suppression was completely prevented by simultaneous treatment with SRIF-Ab. Furthermore, administration of bovine GH, but not ovine prolactin, resulted in significant suppression of hGHRH-analog-provoked GH rises. These findings suggest that enhanced SRIF release during a trough period of spontaneous GH secretory rhythm is induced by the preceding GH secretory burst, and also suggest a possible role for SRIF-mediated GH autoregulation in a physiological state.
Ueno, Takayuki; Kawasaki, Kiyoshi; Kubo, Takeo
2016-09-06
Honeybee workers are engaged in various tasks related to maintaining colony activity. The tasks of the workers change according to their age (age-related division of labor). Young workers are engaged in nursing the brood (nurse bees), while older workers are engaged in foraging for nectar and pollen (foragers). The physiology of the workers changes in association with this role shift. For example, the main function of the hypopharyngeal glands (HPGs) changes from the secretion of major royal jelly proteins (MRJPs) to the secretion of carbohydrate-metabolizing enzymes. Because worker tasks change as the workers age in typical colonies, it is difficult to discriminate the physiological changes that occur with aging from those that occur with the role shift. To study the physiological changes in worker tissues, including the HPGs, in association with the role shift, it would be useful to manipulate the honeybee colony population by preparing single-cohort colonies in which workers of almost the same age perform different tasks. Here we describe a detailed protocol for preparing single-cohort colonies for this analysis. Six to eight days after single-cohort colony preparation, precocious foragers that perform foraging tasks earlier than usual appear in the colony. Representative results indicated role-associated changes in HPG gene expression, suggesting role-associated HPG function. In addition to manipulating the colony population, analysis of the endocrine system is important for investigating role-associated physiology. Here, we also describe a detailed protocol for treating workers with 20-hydroxyecdysone (20E), an active form of ecdysone, and methoprene, a juvenile hormone analogue. The survival rate of treated bees was sufficient to examine gene expression in the HPGs. Gene expression changes were observed in response to 20E- and/or methoprene-treatment, suggesting that hormone treatments induce physiological changes of the HPGs. The protocol for hormone treatment described here is appropriate for examining hormonal effects on worker physiology.
Mesa, M.G.; Poe, T.P.; Maule, A.G.; Schreck, C.B.
1998-01-01
We experimentally infected juvenile chinook salmon (Oncorhynchus tshawytscha) with Renibacterium salmoninarum (Rs), the causative agent of bacterial kidney disease (BKD), to examine the vulnerability to predation of fish with differing levels of Rs infection and assess physiological change during progression of the disease. Immersion challenges conducted during 1992 and 1994 produced fish with either a low to moderate (1992) or high (1994) infection level of Rs during the 14-week postchallenge rearing period. When equal numbers of treatment and unchallenged control fish were subjected to predation by either northern squaw fish (Ptychocheilus oregonensis) or smallmouth bass (Micropterus dolomieui), Rs-challenged fish were eaten in significantly greater numbers than controls by nearly two to one. In 1994, we also sampled fish every 2 weeks after the challenge to determine some stressful effects of Rs infection. During disease progression in fish, plasma cortisol and lactate increased significantly whereas glucose decreased significantly. Our results indicate the role that BKD may play in predator-prey interactions, thus ascribing some ecological significance to this disease beyond that of direct pathogen-related mortality. In addition, the physiological changes observed in our fish during the chronic progression of BKD indicate that this disease is stressful, particularly during the later stages.
Integrins in T Cell Physiology
Alabiso, Oscar; Galetto, Alessandra Silvia; Baldanzi, Gianluca
2018-01-01
From the thymus to the peripheral lymph nodes, integrin-mediated interactions with neighbor cells and the extracellular matrix tune T cell behavior by organizing cytoskeletal remodeling and modulating receptor signaling. LFA-1 (αLβ2 integrin) and VLA-4 (α4β1 integrin) play a key role throughout the T cell lifecycle from thymocyte differentiation to lymphocyte extravasation and finally play a fundamental role in organizing immune synapse, providing an essential costimulatory signal for the T cell receptor. Apart from tuning T cell signaling, integrins also contribute to homing to specific target organs as exemplified by the importance of α4β7 in maintaining the gut immune system. However, apart from those well-characterized examples, the physiological significance of the other integrin dimers expressed by T cells is far less understood. Thus, integrin-mediated cell-to-cell and cell-to-matrix interactions during the T cell lifespan still represent an open field of research. PMID:29415483
Chronic Pain and Chronic Stress: Two Sides of the Same Coin?
Abdallah, Chadi G; Geha, Paul
2017-02-01
Pain and stress share significant conceptual and physiological overlaps. Both phenomena challenge the body's homeostasis and necessitate decision-making to help animals adapt to their environment. In addition, chronic stress and chronic pain share a common behavioral model of failure to extinguish negative memories. Yet, they also have discrepancies such that the final brain endophenotype of posttraumatic stress disorder, depression, and chronic pain appears to be different among the three conditions, and the role of the hypothalamic-pituitary-adrenal axis remains unclear in the physiology of pain. Persistence of either stress or pain is maladaptive and could lead to compromised well-being. In this brief review, we highlight the commonalities and differences between chronic stress and chronic pain, while focusing particularly on the central role of the limbic brain. We assess the current attempts in the field to conceptualize and understand chronic pain, within the context of knowledge gained from the stress literature. The limbic brain-including hippocampus, amygdala, and ventromedial pre-frontal cortex-plays a critical role in learning. These brain areas integrate incoming nociceptive or stress signals with internal state, and generate learning signals necessary for decision-making. Therefore, the physiological and structural remodeling of this learning circuitry is observed in conditions such as chronic pain, depression, and posttraumatic stress disorder, and is also linked to the risk of onset of these conditions.
Monomeric Alpha-Synuclein Exerts a Physiological Role on Brain ATP Synthase
Ludtmann, Marthe H.R.; Angelova, Plamena R.; Ninkina, Natalia N.; Gandhi, Sonia
2016-01-01
Misfolded α-synuclein is a key factor in the pathogenesis of Parkinson's disease (PD). However, knowledge about a physiological role for the native, unfolded α-synuclein is limited. Using brains of mice lacking α-, β-, and γ-synuclein, we report that extracellular monomeric α-synuclein enters neurons and localizes to mitochondria, interacts with ATP synthase subunit α, and modulates ATP synthase function. Using a combination of biochemical, live-cell imaging and mitochondrial respiration analysis, we found that brain mitochondria of α-, β-, and γ-synuclein knock-out mice are uncoupled, as characterized by increased mitochondrial respiration and reduced mitochondrial membrane potential. Furthermore, synuclein deficiency results in reduced ATP synthase efficiency and lower ATP levels. Exogenous application of low unfolded α-synuclein concentrations is able to increase the ATP synthase activity that rescues the mitochondrial phenotypes observed in synuclein deficiency. Overall, the data suggest that α-synuclein is a previously unrecognized physiological regulator of mitochondrial bioenergetics through its ability to interact with ATP synthase and increase its efficiency. This may be of particular importance in times of stress or PD mutations leading to energy depletion and neuronal cell toxicity. SIGNIFICANCE STATEMENT Misfolded α-synuclein aggregations in the form of Lewy bodies have been shown to be a pathological hallmark in histological staining of Parkinson's disease (PD) patient brains. It is known that misfolded α-synuclein is a key driver in PD pathogenesis, but the physiological role of unfolded monomeric α-synuclein remains unclear. Using neuronal cocultures and isolated brain mitochondria of α-, β-, and γ-synuclein knock-out mice and monomeric α-synuclein, this current study shows that α-synuclein in its unfolded monomeric form improves ATP synthase efficiency and mitochondrial function. The ability of monomeric α-synuclein to enhance ATP synthase efficiency under physiological conditions may be of importance when α-synuclein undergoes the misfolding and aggregation reported in PD. PMID:27733604
Hasan, Shirin; Fatima, Naureen; Bilal, Nayeem; Suhail, Nida; Fatima, Sabiha; Morgan, Enas N; Aldebasy, Yousef; Alzohairy, Mohammad A; Banu, Naheed
2013-06-01
Dietary restriction (DR) lowers steady-state levels of oxidative stress and alters behavioral, physiological and biochemical responses in mammals. However, various factors effect its application in humans like socio-cultural, appetite and the daily life stress. Physiological and psychological stress owing to fast-paced lifestyles, translates into oxidative stress. In this work, the role of chronic unpredictable stress (CUS) on the effects of short term DR in mice in terms of biochemical and oxidative stress parameters was investigated. Further, the modulatory role of multivitamin-mineral supplement (MVM) on CUS and DR induced biochemical changes was studied to delineate the role of micronutrient supplementation. DR treatment increased the antioxidant status in the circulation and liver of mice but in the presence of chronic stressors there was a significant shift towards the pro-oxidant state. A decrease was found in the activities of antioxidant enzymes superoxide dismutase, catalase, and glutathione-S-transferase and glutathione reductase in the rats exposed to CUS with DR (CUS+DR), with an increased malondialdehyde and a decreased glutathione (GSH) levels as compared to the controls. Liver function enzymes-glutamate oxaloacetate transaminase and glutamate pyruvate transaminase were increased and a significant DNA damage was observed. Oral MVM supplement significantly improved this oxidative deterioration. Hence, MVM supplementation appears to potentially offer an effective intervention in the DR regimen to combat daily life physical and mental stress. Copyright © 2013 Elsevier Ltd. All rights reserved.
NASA Astrophysics Data System (ADS)
Dong, Y.; Li, X.; Choi, F.; Willams, G.; Somero, G. N.; Helmuth, B.
2016-12-01
Changing patterns of species' biogeographic distributions are driven by cumulative effects of much smaller scale processes. Specifically, vulnerability of animals to thermal stress is the result of physiological sensitivities to body temperature (Tb), local microclimatic conditions, and abilities to anticipate extreme conditions and move to cooler refugia. These variables have rarely been quantified simultaneously over large geographic scales. We analyzed the thermal tolerances of three species of rocky intertidal snails from eight sites spanning 11.5 degrees of latitude along the Chinese coast. Using a biophysical model, we estimated potential Tb in sun-exposed and shaded microhabitats for all species at these sites for 30 years. We then compared maximum predicted Tb against the temperatures at which cardiac function was impaired (Arrhenius Break Temperatures, ABT) and lethal limits were reached (cardiac Flat Line Temperatures, FLT) to calculate thermal Safety Margins (TSM) for normal physiological function (TSMABT) and heat death (TSMFLT). Regular exceedance of FLT in sun-exposed microhabitats was predicted for only one site in the middle of the geographic gradient. However, ABT was exceeded at sun-exposed microhabitats in most sites, suggesting significant physiological impairment for snails that fail to move into the shade. An autocorrelation analysis of snail Tb showed that predictability of extreme temperatures was lowest at the hottest sites, an indication that reliance on behavioral thermoregulation may be a risky strategy. Observed large differences in ABT and FLT among conspecifics emphasize the critical role of physiological polymorphisms in governing the vulnerability of populations to heat stress.
Yamabe, Daisuke; Murakami, Hideki; Chokan, Kou; Endo, Hirooki; Oikawa, Ryosuke; Sawamura, Shoitsu; Doita, Minoru
2017-12-15
T2 mapping was used to quantify the water content of lumbar spine intervertebral discs (IVDs) and facet joints before and after physiological loading. The aim of this study was to clarify the interaction between lumbar spine IVD and facet joints as load-bearing structures by measuring the water content of their matrix after physiological loading using T2 mapping magnetic resonance imaging (MRI). To date, few reports have functionally evaluated lumbar spine IVD and facet joints, and their interaction in vivo. T2 mapping may help detect changes in the water content of IVD and articular cartilage of facet joints before and after physiological loading, thereby enabling the evaluation of changes in interacted water retention between IVD and facet joints. Twenty asymptomatic volunteers (10 female and 10 male volunteers; mean age, 19.3 years; age range, 19-20 years) underwent MRI before and after physiological loading such as lumbar flexion, extension, and rotation. Each IVD from L1/2 to L5/S1 was sliced at center of the disc space, and the T2 value was measured at the nucleus pulposus (NP), anterior annulus fibrosus (AF), posterior AF, and bilateral facet joints. In the NP, T2 values significantly decreased after exercise at every lumbar spinal level. In the anterior AF, there were no significant differences in T2 values at any level. In the posterior AF, T2 values significantly increased only at L4/5. In the bilateral facet joints, T2 values significantly decreased after exercise at every level. There was a significant decrease in the water content of facet joints and the NP at every lumbar spinal level after dynamic loading by physical lumbar exercise. These changes appear to play an important and interactional role in the maintenance of the interstitial matrix in the IVD NP and cartilage in the facet joint. 3.
David A. Galvez; M.T. Tyree
2009-01-01
Physiological mechanisms behind plant-herbivore interactions are commonly approached as input-output systems where the role of plant physiology is viewed as a black box. Studies evaluating impacts of defoliation on plant physiology have mostly focused on changes in photosynthesis while the overall impact on plant water relations is largely unknown. Stem hydraulic...
Role of Klotho in Osteoporosis and Renal Osteodystrophy
2014-10-01
about the complex physiology of bone development and maintenance including the endocrine regulation of mineral homeostasis that is absolutely...percentage of bone. This should enhance the effects we have already seen in other lines and enable us to delve further into physiology of the phenotype...Klotho and FGFRs [11,12]. To dissect the role of parathyroid gland resident Klotho in physiology and in pathophysiological states such as CKD, we
Role of ROS and RNS Sources in Physiological and Pathological Conditions
Victor, Victor Manuel
2016-01-01
There is significant evidence that, in living systems, free radicals and other reactive oxygen and nitrogen species play a double role, because they can cause oxidative damage and tissue dysfunction and serve as molecular signals activating stress responses that are beneficial to the organism. Mitochondria have been thought to both play a major role in tissue oxidative damage and dysfunction and provide protection against excessive tissue dysfunction through several mechanisms, including stimulation of opening of permeability transition pores. Until recently, the functional significance of ROS sources different from mitochondria has received lesser attention. However, the most recent data, besides confirming the mitochondrial role in tissue oxidative stress and protection, show interplay between mitochondria and other ROS cellular sources, so that activation of one can lead to activation of other sources. Thus, it is currently accepted that in various conditions all cellular sources of ROS provide significant contribution to processes that oxidatively damage tissues and assure their survival, through mechanisms such as autophagy and apoptosis. PMID:27478531
Kambeitz, Joseph P; Bhattacharyya, Sagnik; Kambeitz-Ilankovic, Lana M; Valli, Isabel; Collier, David A; McGuire, Philip
2012-10-01
Brain derived neurotrophic factor (BDNF) is a critical component of the molecular mechanism of memory formation. Variation in the BDNF gene, particularly the rs6265 (val(66)met) single nucleotide polymorphism (SNP), has been linked to variability in human memory performance and to both the structure and physiological response of the hippocampus, which plays a central role in memory processing. However, these effects have not been consistently reported, which may reflect the modest size of the samples studied to date. Employing a meta-analytic approach, we examined the effect of the BDNF val(66)met polymorphism on human memory (5922 subjects) and hippocampal structure (2985 subjects) and physiology (362 subjects). Our results suggest that variations in the rs6265 SNP of the BDNF gene have a significant effect on memory performance, and on both the structure and physiology of the hippocampus, with carriers of the met allele being adversely affected. These results underscore the role of BDNF in moderating variability between individuals in human memory performance and in mediating some of the neurocognitive impairments underlying neuropsychiatric disorders. Copyright © 2012 Elsevier Ltd. All rights reserved.
The Anti-Mullerian hormone and ovarian cancer.
La Marca, Antonio; Volpe, Annibale
2007-01-01
The Anti-Mullerian hormone (AMH), which is produced by fetal Sertoli cells, is responsible for regression of Mullerian ducts, the anlagen for uterus and Fallopian tubes, during male sex differentiation. Ovarian granulosa cells also secrete AMH from late in fetal life. The patterns of expression of AMH and its type II receptor in the post-natal ovary indicate that AMH may play an important role in ovarian folliculogenesis. Recent advances in the physiological role of AMH has stimulated interest in the significance of AMH as a diagnostic marker and therapeutic agent for ovarian cancer. Currently, AMH has been shown to be a circulating marker specifically for granulosa cell tumour (GCT). Its diagnostic performance seems to be very good, with a sensitivity ranging between 76 and 93%. In patients treated for GCT, AMH may be used post-operatively as marker for the efficacy of surgery and for disease recurrence. Based on the physiological inhibitory role of AMH in the Mullerian ducts, it has been proposed that AMH may inhibit epithelial ovarian cancer cell both in vitro and in vivo. These observations will be the basis for future research aiming to investigate the possible clinical role of AMH as neo-adjuvant, or most probably adjuvant, therapy for ovarian cancer.
Yang, Mo; Fukui, Hirokazu; Eda, Hirotsugu; Xu, Xin; Kitayama, Yoshitaka; Hara, Ken; Kodani, Mio; Tomita, Toshihiko; Oshima, Tadayuki; Watari, Jiro; Miwa, Hiroto
2017-04-01
The microbiota in the gut is known to play a pivotal role in host physiology by interacting with the immune and neuroendocrine systems in gastrointestinal (GI) tissues. Glucagon-like peptide 1 (GLP-1), a gut hormone, is involved in metabolism as well as GI motility. We examined how gut microbiota affects the link between GLP-1/GLP-1 receptor (GLP-1R) expression and motility of the GI tract. Germ-free (GF) mice (6 wk old) were orally administered a fecal bacterial suspension prepared from specific pathogen-free (SPF) mice, and then after fecal transplantation (FT) GI tissues were obtained from the GF mice at various time points. The expression of GLP-1 and its receptor was examined by immunohistochemistry, and gastrointestinal transit time (GITT) was measured by administration of carmine red solution. GLP-1 was expressed in endocrine cells in the colonic mucosa, and GLP-1R was expressed in myenteric neural cells throughout the GI wall. GLP-1R-positive cells throughout the GI wall were significantly fewer in GF mice with FT than in GF mice without gut microbiota reconstitution. GITT was significantly shorter in GF mice with FT than in control GF mice without FT and correlated with the number of GLP-1R-positive cells throughout the GI wall. GITT was significantly longer in GF control mice than in SPF mice. When those mice were treated with GLP-1 agonist extendin4, GITT was significantly longer in the GF mice. The gut microbiota may accelerate or at least modify GI motility while suppressing GLP-1R expression in myenteric neural cells throughout the GI tract. NEW & NOTEWORTHY The gut microbiota has been intensively studied, because it plays a pivotal role in various aspects of host physiology. On the other hand, glucagon-like peptide 1 (GLP-1) plays important roles in metabolism as well as gastrointestinal motility. In the present study, we have suggested that the gut microbiota accelerates gastrointestinal motility while suppressing the expression of GLP-1 receptor in myenteric neural cells throughout the gastrointestinal tract. We believe that this article is very timely and suggestive work. Copyright © 2017 the American Physiological Society.
Schmidt, John E; Carlson, Charles R
2009-01-01
To investigate (1) differences in heart rate variability (HRV) indices between masticatory muscle pain (MMP) patients and pain-free controls at rest, during a stressor condition, and during a post-stressor recovery period, and (2) factors including psychological distress, social environment, and family-of-origin characteristics in the MMP sample compared to a pain-free matched control sample. Physiological activation and emotional reactivity were assessed in 22 MMP patients and 23 controls during baseline, stressor, and recovery periods. Physiological activity was assessed with frequency domain HRV indices. Emotional reactivity was assessed with the Emotional Assessment Scale. Analytic strategy began with overall 2 x 3 multivariate analyses of variance on physiological data followed by focused contrasts to test specific hypotheses regarding physiological and emotional status. Hypothesized differences between study groups on psychological and social-environmental variables were compared with univariate analyses of variance. The MMP patients showed physiological activation during the baseline period and significantly more physiological activation during the recovery period compared to the controls. This pattern was also present in emotional reactivity between the groups. The emotional and physiological differences between the groups across study periods were more pronounced in pain patients reporting a traumatic stressor. These results provide further evidence of physiological activation and emotional responding in MMP patients that differentiates them from matched pain-free controls. The use of HRV indices to measure physiological functioning quantifies the degree of sympathetic and parasympathetic activation. Study results suggest the use of these HRV indices may improve understanding of the role of excitatory and inhibitory mechanisms in patients with MMP conditions.
Role of vitamin D in ovarian physiology and its implication in reproduction: a systematic review.
Irani, Mohamad; Merhi, Zaher
2014-08-01
To report an update on the role of vitamin D (VD) in ovarian physiology with a focus on genes involved in steroidogenesis, follicular development, and ovarian reserve, as well as ovulatory dysfunction associated with polycystic ovary syndrome (PCOS), and ovarian response to assisted reproductive technology (ART). Systematic review. Not applicable. Human, animal, and cell culture models. Pubmed literature search. Granulosa cell function, serum antimüllerian hormone (AMH), AMH and its receptor gene expression, soluble receptor for advanced glycation end-products (sRAGE), PCOS parameters, and ART outcome. In human granulosa cells, VD alters AMH signaling, FSH sensitivity, and progesterone production and release, indicating a possible physiologic role for VD in ovarian follicular development and luteinization. In the serum, 25-hydroxyvitamin D (25OH-D) is positively correlated with AMH, and appropriate VD supplementation in VD-depleted women can suppress the seasonal changes that occur in serum AMH. In VD-deficient women with PCOS, VD supplementation lowers the abnormally elevated serum AMH levels, possibly indicating a mechanism by which VD improves folliculogenesis. The antiinflammatory sRAGE serum levels significantly increase in women with PCOS after VD replacement. Although follicular fluid 25OH-D correlates with IVF outcomes, there is a lack of data pertaining to the impact of VD supplementation on pregnancy rates following IVF. This review underscores the need for understanding the mechanistic actions of VD in ovarian physiology and the critical need for randomized trials to elucidate the impact of VD supplementation on controlled ovarian hyperstimulation/IVF outcome and ovulatory dysfunction associated with PCOS. Copyright © 2014 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.
Position of the American Dietetic Association: functional foods.
Hasler, Clare M; Brown, Amy C
2009-04-01
All foods are functional at some physiological level, but it is the position of the American Dietetic Association (ADA) that functional foods that include whole foods and fortified, enriched, or enhanced foods have a potentially beneficial effect on health when consumed as part of a varied diet on a regular basis, at effective levels. ADA supports research to further define the health benefits and risks of individual functional foods and their physiologically active components. Health claims on food products, including functional foods, should be based on the significant scientific agreement standard of evidence and ADA supports label claims based on such strong scientific substantiation. Food and nutrition professionals will continue to work with the food industry, allied health professionals, the government, the scientific community, and the media to ensure that the public has accurate information regarding functional foods and thus should continue to educate themselves on this emerging area of food and nutrition science. Knowledge of the role of physiologically active food components, from plant, animal, and microbial food sources, has changed the role of diet in health. Functional foods have evolved as food and nutrition science has advanced beyond the treatment of deficiency syndromes to reduction of disease risk and health promotion. This position paper reviews the definition of functional foods, their regulation, and the scientific evidence supporting this evolving area of food and nutrition. Foods can no longer be evaluated only in terms of macronutrient and micronutrient content alone. Analyzing the content of other physiologically active components and evaluating their role in health promotion will be necessary. The availability of health-promoting functional foods in the US diet has the potential to help ensure a healthier population. However, each functional food should be evaluated on the basis of scientific evidence to ensure appropriate integration into a varied diet.
Prieto, Isabel; Hidalgo, Marina; Segarra, Ana Belén; Martínez-Rodríguez, Ana María; Cobo, Antonio; Ramírez, Manuel; Abriouel, Hikmate; Gálvez, Antonio; Martínez-Cañamero, Magdalena
2018-01-01
The type of fat in the diet determinates the characteristics of gut microbiota, exerting a major role in the development of metabolic syndrome. We hypothesize that a diet enriched with extra virgin olive oil (EVOO) has a distinctive effect on the intestinal microbiome in comparison with an enriched butter diet (BT) and this effect is related to the physiological benefits exerted by EVOO. Swiss Webster mice were fed standard (SD) or two high fat diets enriched with EVOO or butter. Hormonal, physiological and metabolic parameters were evaluated. At the end of the feeding period, DNA was extracted from faeces and the 16S rRNA genes were pyrosequenced. Among the main significant differences found, BT triggered the highest values of systolic blood pressure, correlating positively with the percentage of Desulfovibrio sequences in faeces, which in turn showed significantly higher values in BT than in EVOO. EVOO had the lowest values of plasmatic insulin, correlating inversely with Desulfovibrio, and had the lowest plasmatic values of leptin which correlated inversely with Sutterellaceae, Marispirillum and Mucilaginibacter dageonensis, the three showing significantly higher percentages in EVOO. The lowest total cholesterol levels in plasma were detected in SD, correlating positively with Prevotella and Fusicatenibacter, both taxa with significantly greater presence in SD. These results may be indicative of a link between specific diets, certain physiological parameters and the prevalence of some taxa, supporting the possibility that in some of the proposed effects of virgin olive oil the modulation of intestinal microbiota could be involved.
Prieto, Isabel; Hidalgo, Marina; Segarra, Ana Belén; Martínez-Rodríguez, Ana María; Cobo, Antonio; Ramírez, Manuel; Abriouel, Hikmate; Gálvez, Antonio
2018-01-01
The type of fat in the diet determinates the characteristics of gut microbiota, exerting a major role in the development of metabolic syndrome. We hypothesize that a diet enriched with extra virgin olive oil (EVOO) has a distinctive effect on the intestinal microbiome in comparison with an enriched butter diet (BT) and this effect is related to the physiological benefits exerted by EVOO. Swiss Webster mice were fed standard (SD) or two high fat diets enriched with EVOO or butter. Hormonal, physiological and metabolic parameters were evaluated. At the end of the feeding period, DNA was extracted from faeces and the 16S rRNA genes were pyrosequenced. Among the main significant differences found, BT triggered the highest values of systolic blood pressure, correlating positively with the percentage of Desulfovibrio sequences in faeces, which in turn showed significantly higher values in BT than in EVOO. EVOO had the lowest values of plasmatic insulin, correlating inversely with Desulfovibrio, and had the lowest plasmatic values of leptin which correlated inversely with Sutterellaceae, Marispirillum and Mucilaginibacter dageonensis, the three showing significantly higher percentages in EVOO. The lowest total cholesterol levels in plasma were detected in SD, correlating positively with Prevotella and Fusicatenibacter, both taxa with significantly greater presence in SD. These results may be indicative of a link between specific diets, certain physiological parameters and the prevalence of some taxa, supporting the possibility that in some of the proposed effects of virgin olive oil the modulation of intestinal microbiota could be involved. PMID:29293629
Uptake of /sup 3/H-choline and synthesis of /sup 3/H-acetylcholine by human penile corpus cavernosum
DOE Office of Scientific and Technical Information (OSTI.GOV)
Blanco, R.; Saenz de Tejada, I.; Azadzoi, K.
1986-03-05
The neuroeffectors which relax penile smooth muscle and lead to erection are unknown; physiological studies of human corpus cavernosum, in vitro, have suggested a significant role of cholinergic neurotransmission. To further characterize the importance of cholinergic nerves, biopsies of human corpus cavernosum were obtained at the time of penile prosthesis implantation. Tissues were incubated in /sup 3/H-choline (10/sup -5/M, 80 Ci/mmol) in oxygenated physiological salt solution at 37/sup 0/C, pH 7.4 for 1 hour. Radiolabelled compounds were extracted with perchloric acid (0.4 M) and acetylcholine and choline were separated by HPLC; /sup 14/C-acetylcholine was used as internal standard. /sup 3/H-cholinemore » was accumulated by the tissues (20 +/- 1.9 fmol/mg), and /sup 3/H-acetylcholine was synthesized (4.0 +/- 1.1 fmol/mg). In control experiments, heating of the tissue blocked synthesis of /sup 3/H-acetylcholine. Inhibition of high affinity choline transport by hemicholinium-3 (10/sup -5/M) diminished tissue accumulation of /sup 3/H-choline and significantly reduced the synthesis of /sup 3/H-acetylcholine (0.5 +/ 0.2 fmol/mg, p < 0.05). These results provide direct evidence of neuronal accumulation of choline and enzymatic conversion to acetylcholine in human corpus cavernosum. Taken together with the physiological studies, it can be concluded that cholinergic neurotransmission in human corpus cavernosum plays a role in penile erection.« less
Circulating androgens in women: exercise-induced changes.
Enea, Carina; Boisseau, Nathalie; Fargeas-Gluck, Marie Agnès; Diaz, Véronique; Dugué, Benoit
2011-01-01
Physical exercise is known to strongly stimulate the endocrine system in both sexes. Among these hormones, androgens (e.g. testosterone, androstenedione, dehydroepiandrosterone) play key roles in the reproductive system, muscle growth and the prevention of bone loss. In female athletes, excessive physical exercise may lead to disorders, including delay in the onset of puberty, amenorrhoea and premature osteoporosis. The free and total fractions of circulating androgens vary in response to acute and chronic exercise/training (depending on the type), but the physiological role of these changes is not completely understood. Although it is commonly accepted that only the free fraction of steroids has a biological action, this hypothesis has recently been challenged. Indeed, a change in the total fraction of androgen concentration may have a significant impact on cells (inducing genomic or non-genomic signalling). The purpose of this review, therefore, is to visit the exercise-induced changes in androgen concentrations and emphasize their potential effects on female physiology. Despite some discrepancies in the published studies (generally due to differences in the types and intensities of the exercises studied, in the hormonal status of the group of women investigated and in the methods for androgen determination), exercise is globally able to induce an increase in circulating androgens. This can be observed after both resistance and endurance acute exercises. For chronic exercise/training, the picture is definitely less clear and there are even circumstances where exercise leads to a decrease of circulating androgens. We suggest that those changes have significant impact on female physiology and physical performance.
Extracellular Matrix Reorganization During Wound Healing and Its Impact on Abnormal Scarring
Xue, Meilang; Jackson, Christopher J.
2015-01-01
Significance: When a cutaneous injury occurs, the wound heals via a dynamic series of physiological events, including coagulation, granulation tissue formation, re-epithelialization, and extracellular matrix (ECM) remodeling. The final stage can take many months, yet the new ECM forms a scar that never achieves the flexibility or strength of the original tissue. In certain circumstances, the normal scar is replaced by pathological fibrotic tissue, which results in hypertrophic or keloid scars. These scars cause significant morbidity through physical dysfunction and psychological stress. Recent Advances and Critical Issues: The cutaneous ECM comprises a complex assortment of proteins that was traditionally thought to simply provide structural integrity and scaffolding characteristics. However, recent findings show that the ECM has multiple functions, including, storage and delivery of growth factors and cytokines, tissue repair and various physiological functions. Abnormal ECM reconstruction during wound healing contributes to the formation of hypertrophic and keloid scars. Whereas adult wounds heal with scarring, the developing foetus has the ability to heal wounds in a scarless fashion by regenerating skin and restoring the normal ECM architecture, strength, and function. Recent studies show that the lack of inflammation in fetal wounds contributes to this perfect healing. Future Directions: Better understanding of the exact roles of ECM components in scarring will allow us to produce therapeutic agents to prevent hypertrophic and keloid scars. This review will focus on the components of the ECM and their role in both physiological and pathological (hypertrophic and keloid) cutaneous scar formation. PMID:25785236
Spaceflight and Neurosurgery: A Comprehensive Review of the Relevant Literature.
Swinney, Christian C; Allison, Zain
2018-01-01
Spaceflight and the associated gravitational fluctuations may impact various components of the central nervous system. These include changes in intracranial pressure, the spine, and neurocognitive performance. The implications of altered astronaut performance on critical spaceflight missions are potentially significant. The current body of research on this important topic is extremely limited, and a comprehensive review has not been published. Herein, the authors address this notable gap, as well as the role of the neurosurgeon in optimizing potential diagnostic and therapeutic modalities. A literature search was conducted using the PubMed, EMBASE, and Google Scholar databases, with no time constraints. Significant manuscripts on physiologic changes associated with spaceflight and microgravity were identified and reviewed. Manifestations were separated into 1 of 3 general categories, including changes in intracranial pressure, the spine, and neurocognitive performance. A comprehensive literature review yielded 27 studies with direct relevance to the impact of microgravity and spaceflight on nervous system physiology. This included 7 studies related to intracranial pressure fluctuations, 17 related to changes in the spinal column, and 3 related to neurocognitive change. The microgravity environment encountered during spaceflight impacts intracranial physiology. This includes changes in intracranial pressure, the spinal column, and neurocognitive performance. Herein, we present a systematic review of the published literature on this issue. Neurosurgeons should have a key role in the continued study of this important topic, contributing to both diagnostic and therapeutic understanding. Copyright © 2017 Elsevier Inc. All rights reserved.
Aslanukov, Azamat; Bhowmick, Reshma; Guruju, Mallikarjuna; Oswald, John; Raz, Dorit; Bush, Ronald A; Sieving, Paul A; Lu, Xinrong; Bock, Cheryl B; Ferreira, Paulo A
2006-10-01
The Ran-binding protein 2 (RanBP2) is a large multimodular and pleiotropic protein. Several molecular partners with distinct functions interacting specifically with selective modules of RanBP2 have been identified. Yet, the significance of these interactions with RanBP2 and the genetic and physiological role(s) of RanBP2 in a whole-animal model remain elusive. Here, we report the identification of two novel partners of RanBP2 and a novel physiological role of RanBP2 in a mouse model. RanBP2 associates in vitro and in vivo and colocalizes with the mitochondrial metallochaperone, Cox11, and the pacemaker of glycolysis, hexokinase type I (HKI) via its leucine-rich domain. The leucine-rich domain of RanBP2 also exhibits strong chaperone activity toward intermediate and mature folding species of Cox11 supporting a chaperone role of RanBP2 in the cytosol during Cox11 biogenesis. Cox11 partially colocalizes with HKI, thus supporting additional and distinct roles in cell function. Cox11 is a strong inhibitor of HKI, and RanBP2 suppresses the inhibitory activity of Cox11 over HKI. To probe the physiological role of RanBP2 and its role in HKI function, a mouse model harboring a genetically disrupted RanBP2 locus was generated. RanBP2(-/-) are embryonically lethal, and haploinsufficiency of RanBP2 in an inbred strain causes a pronounced decrease of HKI and ATP levels selectively in the central nervous system. Inbred RanBP2(+/-) mice also exhibit deficits in growth rates and glucose catabolism without impairment of glucose uptake and gluconeogenesis. These phenotypes are accompanied by a decrease in the electrophysiological responses of photosensory and postreceptoral neurons. Hence, RanBP2 and its partners emerge as critical modulators of neuronal HKI, glucose catabolism, energy homeostasis, and targets for metabolic, aging disorders and allied neuropathies.
[The biological and clinical relevance of estrogen metabolome].
Kovács, Krisztián; Vásárhelyi, Barna; Mészáros, Katalin; Patócs, Attila; Karvaly, Gellért
2017-06-01
Considerable knowledge has been gathered on the physiological role of estrogens. However, fairly little information is available on the role of compounds produced in the breakdown process of estrone and estradiol wich may play a role in various diseases associated with estrogen impact. To date, approximately 15 extragonadal estrogen-related compounds have been identified. These metabolites may exert protective, or, instead, pro-inflammatory and/or pro-oncogenic activity in a tissue-specific manner. Systemic and local estrogen metabolite levels are not necesserily correlated, which may promote the diagnostic significance of the locally produced estrogen metabolites in the future. The aim of the present study is a bibliographic review of the extragonadal metabolome in peripheral tissues, and to highlight the role of the peripheral tissue homeostasis of estrogens as well as the non-hormonal biological activity and clinical significance of the estrogen metabolome. Orv Hetil. 2017; 158(24): 929-937.
Polyamines in plant physiology
NASA Technical Reports Server (NTRS)
Galston, A. W.; Sawhney, R. K.
1990-01-01
The diamine putrescine, the triamine spermidine, and the tetramine spermine are ubiquitous in plant cells, while other polyamines are of more limited occurrence. Their chemistry and pathways of biosynthesis and metabolism are well characterized. They occur in the free form as cations, but are often conjugated to small molecules like phenolic acids and also to various macromolecules. Their titer varies from approximately micromolar to more than millimolar, and depends greatly on environmental conditions, especially stress. In cereals, the activity of one of the major polyamine biosynthetic enzymes, arginine decarboxylase, is rapidly and dramatically increased by almost every studied external stress, leading to 50-fold or greater increases in putrescine titer within a few hours. The physiological significance of this increase is not yet clear, although most recent work suggests an adaptive, protective role. Polyamines produced through the action of ornithine decarboxylase, by contrast, seem essential for DNA replication and cell division. The application of exogenous polyamines produces effects on patterns of senescence and morphogenesis, suggesting but not proving a regulatory role for polyamines in these processes. The evidence for such a regulatory role is growing.
Hernandez, Arturo; Morte, Beatriz; Belinchón, Mónica M; Ceballos, Ainhoa; Bernal, Juan
2012-06-01
Thyroid hormones regulate brain development and function through the control of gene expression, mediated by binding of T(3) to nuclear receptors. Brain T(3) concentration is tightly controlled by homeostatic mechanisms regulating transport and metabolism of T(4) and T(3). We have examined the role of the inactivating enzyme type 3 deiodinase (D3) in the regulation of 43 thyroid hormone-dependent genes in the cerebral cortex of 30-d-old mice. D3 inactivation increased slightly the expression of two of 22 positively regulated genes and significantly decreased the expression of seven of 21 negatively regulated genes. Administration of high doses of T(3) led to significant changes in the expression of 12 positive genes and three negative genes in wild-type mice. The response to T(3) treatment was enhanced in D3-deficient mice, both in the number of genes and in the amplitude of the response, demonstrating the role of D3 in modulating T(3) action. Comparison of the effects on gene expression observed in D3 deficiency with those in hypothyroidism, hyperthyroidism, and type 2 deiodinase (D2) deficiency revealed that the negative genes are more sensitive to D2 and D3 deficiencies than the positive genes. This observation indicates that, in normal physiological conditions, D2 and D3 play critical roles in maintaining local T(3) concentrations within a very narrow range. It also suggests that negatively and positively regulated genes do not have the same physiological significance or that their regulation by thyroid hormone obeys different paradigms at the molecular or cellular levels.
Liang, Shuang; Xu, Xuanwei; Lu, Zhongbin
2018-04-01
The impact of fungicide azoxystrobin, applied as foliar spray, on the physiological and biochemical indices and ginsenoside contents of ginseng was studied in ginseng ( Panax ginseng Mey. cv. "Ermaya") under natural environmental conditions. Different concentrations of 25% azoxystrobin SC (150 g a.i./ha and 225 g a.i./ha) on ginseng plants were sprayed three times, and the changes in physiological and biochemical indices and ginsenoside contents of ginseng leaves were tested. Physiological and biochemical indices were measured using a spectrophotometer (Shimadzu UV-2450). Every index was determined three times per replication. Extracts of ginsenosides were analyzed by HPLC (Shimadzu LC20-AB) utilizing a GL-Wondasil C 18 column. Chlorophyll and soluble protein contents were significantly ( p = 0.05) increased compared with the control by the application of azoxystrobin. Additionally, activities of superoxide dismutase, catalase, ascorbate peroxidase, peroxidase, and ginsenoside contents in azoxystrobin-treated plants were improved, and malondialdehyde content and O 2 - contents were reduced effectively. Azoxystrobin treatments to ginseng plants at all growth stages suggested that the azoxystrobin-induced delay of senescence was due to an enhanced antioxidant enzyme activity protecting the plants from harmful active oxygen species. When the dose of azoxystrobin was 225 g a.i./ha, the effect was more significant. This work suggested that azoxystrobin played a role in delaying senescence by changing physiological and biochemical indices and improving ginsenoside contents in ginseng leaves.
Focus on the emerging new fields of network physiology and network medicine
NASA Astrophysics Data System (ADS)
Ivanov, Plamen Ch; Liu, Kang K. L.; Bartsch, Ronny P.
2016-10-01
Despite the vast progress and achievements in systems biology and integrative physiology in the last decades, there is still a significant gap in understanding the mechanisms through which (i) genomic, proteomic and metabolic factors and signaling pathways impact vertical processes across cells, tissues and organs leading to the expression of different disease phenotypes and influence the functional and clinical associations between diseases, and (ii) how diverse physiological systems and organs coordinate their functions over a broad range of space and time scales and horizontally integrate to generate distinct physiologic states at the organism level. Two emerging fields, network medicine and network physiology, aim to address these fundamental questions. Novel concepts and approaches derived from recent advances in network theory, coupled dynamical systems, statistical and computational physics show promise to provide new insights into the complexity of physiological structure and function in health and disease, bridging the genetic and sub-cellular level with inter-cellular interactions and communications among integrated organ systems and sub-systems. These advances form first building blocks in the methodological formalism and theoretical framework necessary to address fundamental problems and challenges in physiology and medicine. This ‘focus on’ issue contains 26 articles representing state-of-the-art contributions covering diverse systems from the sub-cellular to the organism level where physicists have key role in laying the foundations of these new fields.
ERIC Educational Resources Information Center
Sturges, Diana; Maurer, Trent W.; Cole, Oladipo
2009-01-01
This study investigated the effectiveness of role play in a large undergraduate science class. The targeted population consisted of 298 students enrolled in 2 sections of an undergraduate Human Anatomy and Physiology course taught by the same instructor. The section engaged in the role-play activity served as the study group, whereas the section…
Translational Perspective on the Role of Testosterone in Sexual Function and Dysfunction.
Podlasek, Carol A; Mulhall, John; Davies, Kelvin; Wingard, Christopher J; Hannan, Johanna L; Bivalacqua, Trinity J; Musicki, Biljana; Khera, Mohit; González-Cadavid, Nestor F; Burnett, Arthur L
2016-08-01
The biological importance of testosterone is generally accepted by the medical community; however, controversy focuses on its relevance to sexual function and the sexual response, and our understanding of the extent of its role in this area is evolving. To provide scientific evidence examining the role of testosterone at the cellular and molecular levels as it pertains to normal erectile physiology and the development of erectile dysfunction and to assist in guiding successful therapeutic interventions for androgen-dependent sexual dysfunction. In this White Paper, the Basic Science Committee of the Sexual Medicine Society of North America assessed the current basic science literature examining the role of testosterone in sexual function and dysfunction. Testosterone plays an important role in sexual function through multiple processes: physiologic (stimulates activity of nitric oxide synthase), developmental (establishes and maintains the structural and functional integrity of the penis), neural (development, maintenance, function, and plasticity of the cavernous nerve and pelvic ganglia), therapeutically for dysfunctional regulation (beneficial effect on aging, diabetes, and prostatectomy), and phosphodiesterase type 5 inhibition (testosterone supplement to counteract phosphodiesterase type 5 inhibitor resistance). Despite controversies concerning testosterone with regard to sexual function, basic science studies provide incontrovertible evidence for a significant role of testosterone in sexual function and suggest that properly administered testosterone therapy is potentially advantageous for treating male sexual dysfunction. Published by Elsevier Inc.
Zifarelli, Giovanni
2015-01-01
Abstract The CLC protein family comprises both Cl− channels and H+-coupled anion transporters. The understanding of the critical role of CLC proteins in a number of physiological functions has greatly contributed to a revision of the classical paradigm that attributed to Cl− ions only a marginal role in human physiology. The endosomal ClC-5 and the lysosomal ClC-7 are the best characterized human CLC transporters. Their dysfunction causes Dent’s disease and osteopetrosis, respectively. It had been originally proposed that they would provide a Cl− shunt conductance allowing efficient acidification of intracellular compartments. However, this model seems to conflict with the transport properties of these proteins and with recent physiological evidence. Currently, there is no consensus on their specific physiological role. CLC proteins present also a number of peculiar biophysical properties, such as the dimeric architecture, the co-existence of intrinsically different thermodynamic modes of transport based on similar structural principles, and the gating mechanism recently emerging for the transporters, just to name a few. This review focuses on the biophysical properties and physiological roles of ClC-5 and ClC-7. PMID:26036722
Vinnakota, Kalyan C; Dash, Ranjan K; Beard, Daniel A
2011-09-02
Mitochondrial TCA cycle dehydrogenase enzymes have been shown to be stimulated by Ca(2+) under various substrate and ADP incubation conditions in an attempt to determine and understand the role of Ca(2+) in maintaining energy homeostasis in working hearts. In this study, we tested the hypothesis that, at physiological temperature and 1 mM extramitochondrial free magnesium, Ca(2+) can stimulate the overall mitochondrial NAD(P)H generation flux in rat heart mitochondria utilizing pyruvate and malate as substrates at both subsaturating and saturating concentrations. In both cases, we found that, in the physiological regime of mitochondrial oxygen consumption observed in the intact animal and in the physiological range of cytosolic Ca(2+) concentration averaged per beat, Ca(2+) had no observable stimulatory effect. A modest apparent stimulatory effect (22-27%) was observable at supraphysiological maximal ADP-stimulated respiration at 2.5 mM initial phosphate. The stimulatory effects observed over the physiological Ca(2+) range are not sufficient to make a significant contribution to the control of oxidative phosphorylation in the heart in vivo.
Vinnakota, Kalyan C.; Dash, Ranjan K.; Beard, Daniel A.
2011-01-01
Mitochondrial TCA cycle dehydrogenase enzymes have been shown to be stimulated by Ca2+ under various substrate and ADP incubation conditions in an attempt to determine and understand the role of Ca2+ in maintaining energy homeostasis in working hearts. In this study, we tested the hypothesis that, at physiological temperature and 1 mm extramitochondrial free magnesium, Ca2+ can stimulate the overall mitochondrial NAD(P)H generation flux in rat heart mitochondria utilizing pyruvate and malate as substrates at both subsaturating and saturating concentrations. In both cases, we found that, in the physiological regime of mitochondrial oxygen consumption observed in the intact animal and in the physiological range of cytosolic Ca2+ concentration averaged per beat, Ca2+ had no observable stimulatory effect. A modest apparent stimulatory effect (22–27%) was observable at supraphysiological maximal ADP-stimulated respiration at 2.5 mm initial phosphate. The stimulatory effects observed over the physiological Ca2+ range are not sufficient to make a significant contribution to the control of oxidative phosphorylation in the heart in vivo. PMID:21757763
Proteomics Improves the New Understanding of Honeybee Biology.
Hora, Zewdu Ararso; Altaye, Solomon Zewdu; Wubie, Abebe Jemberie; Li, Jianke
2018-04-11
The honeybee is one of the most valuable insect pollinators, playing a key role in pollinating wild vegetation and agricultural crops, with significant contribution to the world's food production. Although honeybees have long been studied as model for social evolution, honeybee biology at the molecular level remained poorly understood until the year 2006. With the availability of the honeybee genome sequence and technological advancements in protein separation, mass spectrometry, and bioinformatics, aspects of honeybee biology such as developmental biology, physiology, behavior, neurobiology, and immunology have been explored to new depths at molecular and biochemical levels. This Review comprehensively summarizes the recent progress in honeybee biology using proteomics to study developmental physiology, task transition, and physiological changes in some of the organs, tissues, and cells based on achievements from the authors' laboratory in this field. The research advances of honeybee proteomics provide new insights for understanding of honeybee biology and future research directions.
Endocannabinoids: Effectors of glucocorticoid signaling.
Balsevich, Georgia; Petrie, Gavin N; Hill, Matthew N
2017-10-01
For decades, there has been speculation regarding the interaction of cannabinoids with glucocorticoid systems. Given the functional redundancy between many of the physiological effects of glucocorticoids and cannabinoids, it was originally speculated that the biological mechanisms of cannabinoids were mediated by direct interactions with glucocorticoid systems. With the discovery of the endocannabinoid system, additional research demonstrated that it was actually the opposite; glucocorticoids recruit endocannabinoid signaling, and that the engagement of endocannabinoid signaling mediated many of the neurobiological and physiological effects of glucocorticoids. With the development of advances in pharmacology and genetics, significant advances in this area have been made, and it is now clear that functional interactions between these systems are critical for a wide array of physiological processes. The current review acts a comprehensive summary of the contemporary state of knowledge regarding the biological interactions between glucocorticoids and endocannabinoids, and their potential role in health and disease. Copyright © 2017 Elsevier Inc. All rights reserved.
[K+ channels and lung epithelial physiology].
Bardou, Olivier; Trinh, Nguyen Thu Ngan; Brochiero, Emmanuelle
2009-04-01
Transcripts of more than 30 different K(+) channels have been detected in the respiratory epithelium lining airways and alveoli. These channels belong to the 3 main classes of K(+) channels, i.e. i) voltage-dependent or calcium-activated, 6 transmembrane segments (TM), ii) 2-pores 4-TM and iii) inward-rectified 2-TM channels. The physiological and functional significance of this high molecular diversity of lung epithelial K(+) channels is not well understood. Surprisingly, relatively few studies are focused on K(+) channel function in lung epithelial physiology. Nevertheless, several studies have shown that KvLQT1, KCa and K(ATP) K(+) channels play a crucial role in ion and fluid transport, contributing to the control of airway and alveolar surface liquid composition and volume. K(+) channels are involved in other key functions, such as O(2) sensing or the capacity of the respiratory epithelia to repair after injury. This mini-review aims to discuss potential functions of lung K(+) channels.
Treatment of ARDS With Prone Positioning.
Scholten, Eric L; Beitler, Jeremy R; Prisk, G Kim; Malhotra, Atul
2017-01-01
Prone positioning was first proposed in the 1970s as a method to improve gas exchange in ARDS. Subsequent observations of dramatic improvement in oxygenation with simple patient rotation motivated the next several decades of research. This work elucidated the physiological mechanisms underlying changes in gas exchange and respiratory mechanics with prone ventilation. However, translating physiological improvements into a clinical benefit has proved challenging; several contemporary trials showed no major clinical benefits with prone positioning. By optimizing patient selection and treatment protocols, the recent Proning Severe ARDS Patients (PROSEVA) trial demonstrated a significant mortality benefit with prone ventilation. This trial, and subsequent meta-analyses, support the role of prone positioning as an effective therapy to reduce mortality in severe ARDS, particularly when applied early with other lung-protective strategies. This review discusses the physiological principles, clinical evidence, and practical application of prone ventilation in ARDS. Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.
A Laparoscopic Swine Model of Noncompressible Torso Hemorrhage
2014-01-01
Various porcine models of hemorrhage have been developed for civilian and military trauma research. However, the predominant contemporary models lack...significant predictors of mortality. CONCLUSION: This study describes a model of NCTH that reflects clinically relevant physiology in trauma and...uncontrolled hemorrhage. In addition, it quantitatively assesses the role of the swine contractile spleen in the described model. (J Trauma Acute Care Surg
[Disperse endocrine system and APUD concept].
Mil'to, I V; Sukhodolo, I V; Gereng, E A; Shamardina, L A
2011-01-01
This review describes the problems of disperse endocrine system and APUD-system morphology, summarizes some debatable issues of single endocrine cell biology. The data presented refer to the history of both systems discovery, morphological methods of their study, developmental sources, their structural organization and physiological roles of their cells. The significance of single endocrine cells in the regulation of the organism functions is discussed.
Circulating endothelial and progenitor cells: Evidence from acute and long-term exercise effects
Koutroumpi, Matina; Dimopoulos, Stavros; Psarra, Katherini; Kyprianou, Theodoros; Nanas, Serafim
2012-01-01
Circulating bone-marrow-derived cells, named endothelial progenitor cells (EPCs), are capable of maintaining, generating, and replacing terminally differentiated cells within their own specific tissue as a consequence of physiological cell turnover or tissue damage due to injury. Endothelium maintenance and restoration of normal endothelial cell function is guaranteed by a complex physiological procedure in which EPCs play a significant role. Decreased number of peripheral blood EPCs has been associated with endothelial dysfunction and high cardiovascular risk. In this review, we initially report current knowledge with regard to the role of EPCs in healthy subjects and the clinical value of EPCs in different disease populations such as arterial hypertension, obstructive sleep-apnea syndrome, obesity, diabetes mellitus, peripheral arterial disease, coronary artery disease, pulmonary hypertension, and heart failure. Recent studies have introduced the novel concept that physical activity, either performed as a single exercise session or performed as part of an exercise training program, results in a significant increase of circulating EPCs. In the second part of this review we provide preliminary evidence from recent studies investigating the effects of acute and long-term exercise in healthy subjects and athletes as well as in disease populations. PMID:23272272
The role of nitric oxide in the physiology and pathophysiology of the exocrine pancreas.
Hegyi, Péter; Rakonczay, Zoltán
2011-11-15
Nitric oxide (NO), a ubiquitous gaseous signaling molecule, contributes to both pancreatic physiology and pathophysiology. The present review provides a general overview of NO synthesis, signaling, and function. Further, it specifically discusses NO metabolism and its effects in the exocrine pancreas and focuses on the role of NO in the pathogenesis of acute pancreatitis and pancreatic ischemia/reperfusion injury. Unfortunately, the role of NO in pancreatic physiology and pathophysiology remains controversial in numerous areas. Many questions regarding the messenger molecule still remain unanswered. Probably the least is known about the downstream targets of NO, which need to be identified, especially at the molecular level.
A simulation study on the constancy of cardiac energy metabolites during workload transition.
Saito, Ryuta; Takeuchi, Ayako; Himeno, Yukiko; Inagaki, Nobuya; Matsuoka, Satoshi
2016-12-01
The cardiac energy metabolites such as ATP, phosphocreatine, ADP and NADH are kept relatively constant during physiological cardiac workload transition. How this is accomplished is not yet clarified, though Ca 2+ has been suggested to be one of the possible mechanisms. We constructed a detailed mathematical model of cardiac mitochondria based on experimental data and studied whether known Ca 2+ -dependent regulation mechanisms play roles in the metabolite constancy. Model simulations revealed that the Ca 2+ -dependent regulation mechanisms have important roles under the in vitro condition of isolated mitochondria where malate and glutamate were mitochondrial substrates, while they have only a minor role and the composition of substrates has marked influence on the metabolite constancy during workload transition under the simulated in vivo condition where many substrates exist. These results help us understand the regulation mechanisms of cardiac energy metabolism during physiological cardiac workload transition. The cardiac energy metabolites such as ATP, phosphocreatine, ADP and NADH are kept relatively constant over a wide range of cardiac workload, though the mechanisms are not yet clarified. One possible regulator of mitochondrial metabolism is Ca 2+ , because it activates several mitochondrial enzymes and transporters. Here we constructed a mathematical model of cardiac mitochondria, including oxidative phosphorylation, substrate metabolism and ion/substrate transporters, based on experimental data, and studied whether the Ca 2+ -dependent activation mechanisms play roles in metabolite constancy. Under the in vitro condition of isolated mitochondria, where malate and glutamate were used as mitochondrial substrates, the model well reproduced the Ca 2+ and inorganic phosphate (P i ) dependences of oxygen consumption, NADH level and mitochondrial membrane potential. The Ca 2+ -dependent activations of the aspartate/glutamate carrier and the F 1 F o -ATPase, and the P i -dependent activation of Complex III were key factors in reproducing the experimental data. When the mitochondrial model was implemented in a simple cardiac cell model, simulation of workload transition revealed that cytoplasmic Ca 2+ concentration ([Ca 2+ ] cyt ) within the physiological range markedly increased NADH level. However, the addition of pyruvate or citrate attenuated the Ca 2+ dependence of NADH during the workload transition. Under the simulated in vivo condition where malate, glutamate, pyruvate, citrate and 2-oxoglutarate were used as mitochondrial substrates, the energy metabolites were more stable during the workload transition and NADH level was almost insensitive to [Ca 2+ ] cyt . It was revealed that mitochondrial substrates have a significant influence on metabolite constancy during cardiac workload transition, and Ca 2+ has only a minor role under physiological conditions. © 2016 The Authors. The Journal of Physiology © 2016 The Physiological Society.
Chen, Jing; Chen, Lihong; Sanseau, Philippe; Freudenberg, Johannes M; Rajpal, Deepak K
2016-05-01
The gastrointestinal (GI) tract can have significant impact on the regulation of the whole-body metabolism and may contribute to the development of obesity and diabetes. To systemically elucidate the role of the GI tract in obesity, we performed a transcriptomic analysis in different parts of the GI tract of two obese mouse models: ob/ob and high-fat diet (HFD) fed mice. Compared to their lean controls, significant changes in the gene expression were observed in both obese mouse groups in the stomach (ob/ob: 959; HFD: 542). In addition, these changes were quantitatively much higher than in the intestine. Despite the difference in genetic background, the two mouse models shared 296 similar gene expression changes in the stomach. Among those genes, some had known associations to obesity, diabetes, and insulin resistance. In addition, the gene expression profiles strongly suggested an increased gastric acid secretion in both obese mouse models, probably through an activation of the gastrin pathway. In conclusion, our data reveal a previously unknown dominant connection between the stomach and obesity in murine models extensively used in research. © 2016 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.
Wang, Jun-ling; Li, Tao; Liu, Gao-yuan; Smith, Joshua M; Zhao, Zhi-wei
2016-02-25
A growing body of evidence suggests that plant root-associated fungi such as dark septate endophytes (DSE) can help plants overcome many biotic and abiotic stresses, of great interest is DSE-plant metal tolerance and alleviation capabilities on contaminated soils. However, the tolerance and alleviation mechanisms involved have not yet been elucidated. In the current study, the regulation and physiological response of Zea mays to its root-associated DSE, Exophiala pisciphila was analyzed under increased soil Cd stress (0, 10, 50, 100 mg kg(-1)). Under Cd stress, DSE inoculation significantly enhanced the activities of antioxidant enzymes and low-molecular weight antioxidants, while also inducing increased Cd accumulation in the cell wall and conversion of Cd into inactive forms by shoot and root specific regulation of genes related to metal uptake, translocation and chelation. Our results showed that DSE colonization resulted in a marked tolerance to Cd, with a significant decrease in cadmium phytotoxicity and a significant increase in maize growth by triggering antioxidant systems, altering metal chemical forms into inactive Cd, and repartitioning subcellular Cd into the cell wall. These results provide comprehensive evidence for the mechanisms by which DSE colonization bioaugments Cd tolerance in maize at physiological, cytological and molecular levels.
NASA Astrophysics Data System (ADS)
Wang, Jun-Ling; Li, Tao; Liu, Gao-Yuan; Smith, Joshua M.; Zhao, Zhi-Wei
2016-02-01
A growing body of evidence suggests that plant root-associated fungi such as dark septate endophytes (DSE) can help plants overcome many biotic and abiotic stresses, of great interest is DSE-plant metal tolerance and alleviation capabilities on contaminated soils. However, the tolerance and alleviation mechanisms involved have not yet been elucidated. In the current study, the regulation and physiological response of Zea mays to its root-associated DSE, Exophiala pisciphila was analyzed under increased soil Cd stress (0, 10, 50, 100 mg kg-1). Under Cd stress, DSE inoculation significantly enhanced the activities of antioxidant enzymes and low-molecular weight antioxidants, while also inducing increased Cd accumulation in the cell wall and conversion of Cd into inactive forms by shoot and root specific regulation of genes related to metal uptake, translocation and chelation. Our results showed that DSE colonization resulted in a marked tolerance to Cd, with a significant decrease in cadmium phytotoxicity and a significant increase in maize growth by triggering antioxidant systems, altering metal chemical forms into inactive Cd, and repartitioning subcellular Cd into the cell wall. These results provide comprehensive evidence for the mechanisms by which DSE colonization bioaugments Cd tolerance in maize at physiological, cytological and molecular levels.
Brožíčková, C; Mikulecká, A; Otáhal, J
2014-01-01
The role of brain derived nitric oxide in the physiology and behavior remains disputable. One of the reasons of the controversies might be systemic side effects of nitric oxide synthase inhibitors. Therefore, under nNOS inhibition by 7-nitroindazole (7-NI) we carried out recordings of blood gasses, blood pressure and spontaneous EEG in conscious adult rats. Locomotion and spontaneous behavior were assessed in an open field. In addition skilled walking and limb coordination were evaluated using a ladder rung walking test. The blood gas analysis revealed a significant increase in pCO(2) 180 min and 240 min after the application of 7-NI. The power and entropy decreased simultaneously with a shift of the mean frequency of the spontaneous EEG toward slow oscillations after 7-NI treatment. The thresholds of evoked potentials underwent a significant drop and a trend towards a slight increase in the I-O curve slope was observed. 7-NI significantly suppressed open field behavior expressed as distance moved, exploratory rearing and grooming. As for the ladder rung walking test the 7-NI treated animals had more errors in foot placement indicating impairment in limb coordination. Therefore our findings suggest that 7-NI increased cortical excitability and altered some physiological and behavioral parameters.
Chen, Hsin-Yung; Yang, Hsiang; Chi, Huang-Ju; Chen, Hsin-Ming
2014-02-01
Anxiety induced by dental treatment can become a serious problem, especially for patients with special needs. Application of deep touch pressure, which is a sensory adaptation technique, may ameliorate anxiety in disabled patients. However, few empiric studies have investigated the possible links between the clinical effects of deep touch pressure and its behavioral and physiologic aspects. Equally little progress has been made concerning theoretical development. The current study is a crossover intervention trial to investigate the behavioral and physiological effects of deep touch pressure for participants receiving dental treatment. Nineteen disabled participants, who were retrospectively subclassified for positive trend or negative trend, were recruited to receive the papoose board as an application of deep touch pressure. Quantitative analyses of behavioral assessments and physiological measurements, including electrodermal activity and heart rate variability, were conducted. We sought to understand the modulation of the autonomic nervous system and the orchestration of sympathetic and parasympathetic (PsNS) nervous systems. Behavioral assessments reported that higher levels of anxiety were induced by the dental treatment for participants with both groups of positive and negative trends. Although no significant differences were found in the SNS activity, physiologic responses indicated that significantly changes of PsNS activity were observed under the stress condition (dental treatment) when deep touch pressure intervention was applied, especially for participants in the group of positive trend. Our results suggest that the PsNS activation plays a critical role in the process of ANS modulation. This study provides not only physiologic evidence for the modulation effects of deep touch pressure on stressful conditions in dental environments but also the evidence that the application of papoose board, as a sensory adaptation technique, is not harmful for dental patients with special needs. Copyright © 2012. Published by Elsevier B.V.
Sugar for the brain: the role of glucose in physiological and pathological brain function
Mergenthaler, Philipp; Lindauer, Ute; Dienel, Gerald A.; Meisel, Andreas
2013-01-01
The mammalian brain depends upon glucose as its main source of energy, and tight regulation of glucose metabolism is critical for brain physiology. Consistent with its critical role for physiological brain function, disruption of normal glucose metabolism as well as its interdependence with cell death pathways forms the pathophysiological basis for many brain disorders. Here, we review recent advances in understanding how glucose metabolism sustains basic brain physiology. We aim at synthesizing these findings to form a comprehensive picture of the cooperation required between different systems and cell types, and the specific breakdowns in this cooperation which lead to disease. PMID:23968694
Cardiorespiratory interactions in humans and animals: Rhythms for life.
Elstad, Maja; O'Callaghan, Erin L; Smith, Alexander J; Ben-Tal, A; Ramchandra, Rohit
2018-03-09
The cardiorespiratory system exhibits oscillations from a range of sources. One of the most studied oscillations is heart rate variability, which is thought to be beneficial and can serve as an index of a healthy cardiovascular system. Heart rate variability is dampened in many diseases including depression, autoimmune diseases, hypertension and heart failure. Thus, understanding the interactions that lead to heart rate variability, and its physiological role, could help with prevention, diagnosis and treatment of cardiovascular diseases. In this review we consider three types of cardiorespiratory interactions; Respiratory Sinus Arrhythmia - variability in heart rate at the frequency of breathing, Cardioventilatory Coupling - synchronization between the heart beat and the onset of inspiration, and Respiratory Stroke Volume Synchronization - constant phase difference between the right and the left stroke volumes over one respiratory cycle. While the exact physiological role of these oscillations continues to be debated, the redundancies in the mechanisms responsible for its generation and its strong evolutionary conservation point to the importance of cardiorespiratory interactions. The putative mechanisms driving cardiorespiratory oscillations as well as the physiological significance of these oscillations will be reviewed. We suggest that cardiorespiratory interactions have the capacity to both dampen the variability in systemic blood flow as well as improve the efficiency of work done by the heart while maintaining physiological levels of arterial CO 2 . Given that reduction in variability is a prognostic indicator of disease, we argue that restoration of this variability via pharmaceutical or device-based approaches may be beneficial in prolonging life.
Urra, Javier A; Villaroel-Espíndola, Franz; Covarrubias, Alejandra A; Rodríguez-Gil, Joan Enric; Ramírez-Reveco, Alfredo; Concha, Ilona I
2014-01-01
Dopamine is a catecholamine with multiple physiological functions, playing a key role in nervous system; however its participation in reproductive processes and sperm physiology is controversial. High dopamine concentrations have been reported in different portions of the feminine and masculine reproductive tract, although the role fulfilled by this catecholamine in reproductive physiology is as yet unknown. We have previously shown that dopamine type 2 receptor is functional in boar sperm, suggesting that dopamine acts as a physiological modulator of sperm viability, capacitation and motility. In the present study, using immunodetection methods, we revealed the presence of several proteins important for the dopamine uptake and signalling in mammalian sperm, specifically monoamine transporters as dopamine (DAT), serotonin (SERT) and norepinephrine (NET) transporters in equine sperm. We also demonstrated for the first time in equine sperm a functional dopamine transporter using 4-[4-(Dimethylamino)styryl]-N-methylpyridinium iodide (ASP(+)), as substrate. In addition, we also showed that dopamine (1 mM) treatment in vitro, does not affect sperm viability but decreases total and progressive sperm motility. This effect is reversed by blocking the dopamine transporter with the selective inhibitor vanoxerine (GBR12909) and non-selective inhibitors of dopamine reuptake such as nomifensine and bupropion. The effect of dopamine in sperm physiology was evaluated and we demonstrated that acrosome integrity and thyrosine phosphorylation in equine sperm is significantly reduced at high concentrations of this catecholamine. In summary, our results revealed the presence of monoamine transporter DAT, NET and SERT in equine sperm, and that the dopamine uptake by DAT can regulate sperm function, specifically acrosomal integrity and sperm motility.
Covarrubias, Alejandra A.; Rodríguez-Gil, Joan Enric; Ramírez-Reveco, Alfredo; Concha, Ilona I.
2014-01-01
Dopamine is a catecholamine with multiple physiological functions, playing a key role in nervous system; however its participation in reproductive processes and sperm physiology is controversial. High dopamine concentrations have been reported in different portions of the feminine and masculine reproductive tract, although the role fulfilled by this catecholamine in reproductive physiology is as yet unknown. We have previously shown that dopamine type 2 receptor is functional in boar sperm, suggesting that dopamine acts as a physiological modulator of sperm viability, capacitation and motility. In the present study, using immunodetection methods, we revealed the presence of several proteins important for the dopamine uptake and signalling in mammalian sperm, specifically monoamine transporters as dopamine (DAT), serotonin (SERT) and norepinephrine (NET) transporters in equine sperm. We also demonstrated for the first time in equine sperm a functional dopamine transporter using 4-[4-(Dimethylamino)styryl]-N-methylpyridinium iodide (ASP+), as substrate. In addition, we also showed that dopamine (1 mM) treatment in vitro, does not affect sperm viability but decreases total and progressive sperm motility. This effect is reversed by blocking the dopamine transporter with the selective inhibitor vanoxerine (GBR12909) and non-selective inhibitors of dopamine reuptake such as nomifensine and bupropion. The effect of dopamine in sperm physiology was evaluated and we demonstrated that acrosome integrity and thyrosine phosphorylation in equine sperm is significantly reduced at high concentrations of this catecholamine. In summary, our results revealed the presence of monoamine transporter DAT, NET and SERT in equine sperm, and that the dopamine uptake by DAT can regulate sperm function, specifically acrosomal integrity and sperm motility. PMID:25402186
Samuels, E. R; Szabadi, E
2008-01-01
The locus coeruleus (LC), the major noradrenergic nucleus of the brain, gives rise to fibres innervating most structures of the neuraxis. Recent advances in neuroscience have helped to unravel the neuronal circuitry controlling a number of physiological functions in which the LC plays a central role. Two such functions are the regulation of arousal and autonomic activity, which are inseparably linked largely via the involvement of the LC. Alterations in LC activity due to physiological or pharmacological manipulations or pathological processes can lead to distinct patterns of change in arousal and autonomic function. Physiological manipulations considered here include the presentation of noxious or anxiety-provoking stimuli and extremes in ambient temperature. The modification of LC-controlled functions by drug administration is discussed in detail, including drugs which directly modify the activity of LC neurones (e.g., via autoreceptors, storage, reuptake) or have an indirect effect through modulating excitatory or inhibitory inputs. The early vulnerability of the LC to the ageing process and to neurodegenerative disease (Parkinson’s and Alzheimer’s diseases) is of considerable clinical significance. In general, physiological manipulations and the administration of stimulant drugs, α2-adrenoceptor antagonists and noradrenaline uptake inhibitors increase LC activity and thus cause heightened arousal and activation of the sympathetic nervous system. In contrast, the administration of sedative drugs, including α2-adrenoceptor agonists, and pathological changes in LC function in neurodegenerative disorders and ageing reduce LC activity and result in sedation and activation of the parasympathetic nervous system. PMID:19506724
ARG1 Functions in the Physiological Adaptation of Undifferentiated Plant Cells to Spaceflight
NASA Astrophysics Data System (ADS)
Zupanska, Agata K.; Schultz, Eric R.; Yao, JiQiang; Sng, Natasha J.; Zhou, Mingqi; Callaham, Jordan B.; Ferl, Robert J.; Paul, Anna-Lisa
2017-11-01
Scientific access to spaceflight and especially the International Space Station has revealed that physiological adaptation to spaceflight is accompanied or enabled by changes in gene expression that significantly alter the transcriptome of cells in spaceflight. A wide range of experiments have shown that plant physiological adaptation to spaceflight involves gene expression changes that alter cell wall and other metabolisms. However, while transcriptome profiling aptly illuminates changes in gene expression that accompany spaceflight adaptation, mutation analysis is required to illuminate key elements required for that adaptation. Here we report how transcriptome profiling was used to gain insight into the spaceflight adaptation role of Altered response to gravity 1 (Arg1), a gene known to affect gravity responses in plants on Earth. The study compared expression profiles of cultured lines of Arabidopsis thaliana derived from wild-type (WT) cultivar Col-0 to profiles from a knock-out line deficient in the gene encoding ARG1 (ARG1 KO), both on the ground and in space. The cell lines were launched on SpaceX CRS-2 as part of the Cellular Expression Logic (CEL) experiment of the BRIC-17 spaceflight mission. The cultured cell lines were grown within 60 mm Petri plates in Petri Dish Fixation Units (PDFUs) that were housed within the Biological Research In Canisters (BRIC) hardware. Spaceflight samples were fixed on orbit. Differentially expressed genes were identified between the two environments (spaceflight and comparable ground controls) and the two genotypes (WT and ARG1 KO). Each genotype engaged unique genes during physiological adaptation to the spaceflight environment, with little overlap. Most of the genes altered in expression in spaceflight in WT cells were found to be Arg1-dependent, suggesting a major role for that gene in the physiological adaptation of undifferentiated cells to spaceflight.
Appraisal and control of sexual and non-sexual intrusive thoughts in university students.
Clark, D A; Purdon, C; Byers, E S
2000-05-01
This study examined differences in the appraisal and thought control strategies associated with the perceived control of unwanted sexual and non-sexual intrusive thoughts. Eleven appraisal dimensions, subjective physiological arousal and 10 thought control strategies were measured in 171 university students who were administered the Revised Obsessive Intrusions Inventory-Sex Version, a self-report measure of unwanted intrusive thoughts. Thought-action fusion (TAF) likelihood was a significant unique predictor of the perceived controllability of respondents' most upsetting sexual and non-sexual intrusive thought. Moreover greater subjective physiological arousal was a significant predictor of reduced control over sexual intrusions, whereas worry that one might act on an intrusive thought and greater effort to control the intrusion were significant unique predictors of the control of non-sexual intrusive thoughts. Various thought control strategies were more often used in response to non-sexual than sexual cognitions. The results are discussed in terms of the differential role of various appraisal processes in the control of unwanted sexual and non-sexual thoughts.
Boosting Endogenous Resistance of Brain to Ischemia
Sun, Fen; Johnson, Stephen R.; Jin, Kunlin; Uteshev, Victor V.
2016-01-01
Most survivors of ischemic stroke remain physically disabled and require prolonged rehabilitation. However, some stroke victims achieve a full neurological recovery suggesting that human brain can defend itself against ischemic injury, but the protective mechanisms are unknown. This study used selective pharmacological agents and a rat model of cerebral ischemic stroke to detect endogenous brain protective mechanisms that require activation of α7 nicotinic acetylcholine receptors (nAChRs). This endogenous protection was found to be: 1) limited to less severe injuries; 2) significantly augmented by intranasal administration of a positive allosteric modulator of α7 nAChRs, significantly reducing brain injury and neurological deficits after more severe ischemic injuries; and 3) reduced by inhibition of calcium/calmodulin-dependent kinase-II. The physiological role of α7 nAChRs remains largely unknown. The therapeutic activation of α7 nAChRs after cerebral ischemia may serve as an important physiological responsibility of these ubiquitous receptors and holds a significant translational potential. PMID:26910820
Stress and the Multiple-Role Woman: Taking a Closer Look at the “Superwoman”
Sumra, Monika K.; Schillaci, Michael A.
2015-01-01
In the academic literature there is debate as to whether women who engage in multiple social roles experience more or less stress than women in fewer roles. For the present research we examined the relationship between levels of engagement in seven distinct roles and perceived stress and life satisfaction in a small non-random sample of women in North America (N = 308). We did not find a significant correlation between role engagement and perceived stress, though we did find a small but significant positive correlation between role engagement and life satisfaction. Similarly, in a subset of the participants (N = 31), there was not a significant relationship between the level of role engagement and physiological stress as measured by hair or urinary cortisol levels. We found a significant negative correlation between perceived stress and life satisfaction, and role satisfaction. The results from multiple regression models did not identify the level of role engagement as a significant predictor of either perceived stress or life satisfaction. Role satisfaction in addition to several life style variables such as the frequency of sex and exercise were identified as significant predictors of both outcome variables. We also examined the popularized notion of the “superwoman”, which we defined as women who fell within the 4th quartile of role engagement, or those engaged in the wife/mother/worker/homemaker role combination. Based on popular discourses surrounding the superwoman we expected that superwomen would exhibit higher levels of perceived stress. Our results revealed that superwomen do not experience a significantly higher level of perceived stress than non-superwomen. The results of our study therefore suggest that multiple role engagement in women, even at a relatively high level as experienced by “superwomen”, is not associated with significantly higher stress, or reduced life satisfaction. PMID:25816317
Early Childcare, Executive Functioning, and the Moderating Role of Early Stress Physiology
ERIC Educational Resources Information Center
Berry, Daniel; Willoughby, Michael T.; Blair, Clancy; Ursache, Alexandra; Granger, Douglas A.
2014-01-01
Intervention studies indicate that children's childcare experiences can be leveraged to support the development of executive functioning (EF). The role of more normative childcare experiences is less clear. Increasingly, theory and empirical work suggest that individual differences in children's physiological stress systems may be associated with…
The role of freshwater alterations and seasonal changes on the ecological and physiological responses of oysters were investigated in the Caloosahatchee River, Estero Bay and Faka-Union estuaries in SW Florida. Condition index, oyster density, and disease incidence of Perkinsus m...
The Role of Id2 Protein in Neuroblatoma in Children.
Wieczorek, Aleksandra; Balwierz, Walentyna
2015-09-01
Id (DNA binding and/or differentiation) proteins occur physiologically during ontogenesis and negatively regulate the activity of other helix-loop-helix (HLH) proteins. Id2 protein causes block of cells differentiation in the S phase of the cell cycle and regulates the activity of Rb protein. The role of Id2 protein in physiological cell cycle progression and in neuroblastoma (NBL) pathogenesis was proposed by Lasorella. The aim of the study was evaluation of Id2 expression and its prognostic significance in NBL cells coming from primary tumors and evaluation of its prognostic significance, and correlation of Id2 expression with known prognostic factors. Sixty patients with primary NBL treated from 1991 to 2005 were included in the analysis. We found 50 patients with high and 10 patients with low intensity of Id2 expression. The median percentage of NBL cells with Id2 expression was 88 %. We found no correlation between the number of NBL cells or the intensity of Id2 expression and OS and DFS. In patients with stage 4 NBL, almost all patients had high expression of Id2 and it was significantly more common than in other disease stages (p = 0,03). We found no correlation between Id2 expression and other known prognostic factor in NBL patients. We assume that Id2 is not prognostic factor. However, due to its abundant expression in most of NBL cells and its role in cell cycle, it may be potential therapeutic target. Exact knowledge of expression time may be helpful in explaining mechanisms of oncogenesis.
Yang, Yimu; Schmidt, Eric P.
2013-01-01
Once thought to be a structure of small size and uncertain significance, the endothelial glycocalyx is now known to be an important regulator of endothelial function. Studies of the systemic vasculature have demonstrated that the glycocalyx forms a substantial in vivo endothelial surface layer (ESL) critical to inflammation, barrier function and mechanotransduction. The pulmonary ESL is significantly thicker than the systemic ESL, suggesting unique physiologic function. We have recently demonstrated that the pulmonary ESL regulates exposure of endothelial surface adhesion molecules, thereby serving as a barrier to neutrophil adhesion and extravasation. While the pulmonary ESL is not a critical structural component of the endothelial barrier to fluid and protein, it serves a major role in the mechanotransduction of vascular pressure, with impact on the active regulation of endothelial permeability. It is likely that the ESL serves numerous additional functions in vascular physiology, representing a fertile area for future investigation. PMID:24073386
Niu, Furong; Duan, Dongping; Chen, Ji; Xiong, Peifeng; Zhang, He; Wang, Zhi; Xu, Bingcheng
2016-01-01
Altered precipitation regimes significantly affect ecosystem structure and function in arid and semi-arid regions. In order to investigate effects of precipitation changes on natural grassland community in the semi-arid Loess Plateau, the current research examined eco-physiological characteristics of two co-dominant species (i.e., Bothriochloa ischaemum and Lespedeza davurica) and community composition following two watering instances (i.e., precipitation pulses, July and August, 2011, respectively) in a natural grassland community. Results showed that the photosynthetic rate, transpiration rate, stomatal conductance and intercellular CO2 concentration rapidly increased on the first to third day following watering in both species, and both months. Under watering treatments, the maximum net photosynthetic rates appeared on the second to third day after watering, which increased 30–80% in B. ischaemum and 40–50% in L. davurica compared with non-watering treatments, respectively. Leaf water use efficiency kept stable or initially decreased in both species under watering treatments. Watering in July produced more promoting effects on grass photosynthesis than in August, particularly in B. ischaemum. Community above-ground biomass at the end of the growing season increased after watering, although no significant changes in species diversity were observed. Our results indicated that timing and magnitude of watering could significantly affect plant eco-physiological processes, and there were species-specific responses in B. ischaemum and L. davurica. Pulsed watering increased community productivity, while did not significantly alter community composition after one growing season. The outcomes of this study highlight eco-physiological traits in dominant species may playing important roles in reshaping community composition under altered precipitation regimes. PMID:27242864
A personal historic perspective on the role of chloride in skeletal and cardiac muscle.
Hutter, Otto F
2017-03-01
During the early decades of the last century, skeletal muscle was held to be impermeable to chloride ions. This theory, based on shaky grounds, was famously falsified by Boyle and Conway in 1941. Two decades later and onwards, the larger part of the resting conductance of skeletal muscle was found to be due to chloride ions, sensitive to the chemical environment, and to be time-and-voltage dependent. So, much of the groundwork for the physiological role of chloride ions in skeletal muscle was laid before the game-changing discovery of chloride channels. The early history of the role of chloride in cardiac muscle, and work on the relative permeability to foreign anions of different muscles are also here covered from a personal perspective. © 2017 The Author. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.
The unusual amino acid l-ergothioneine is a physiologic cytoprotectant
Paul, BD; Snyder, SH
2010-01-01
Ergothioneine (ET) is an unusual sulfur-containing derivative of the amino acid, histidine, which is derived exclusively through the diet. Although ET was isolated a century ago, its physiologic function has not been clearly established. Recently, a highly specific transporter for ET (ETT) was identified in mammalian tissues, which explains abundant tissue levels of ET and implies a physiologic role. Using RNA interference, we depleted cells of its transporter. Cells lacking ETT are more susceptible to oxidative stress, resulting in increased mitochondrial DNA damage, protein oxidation and lipid peroxidation. ETT is concentrated in mitochondria, suggesting a specific role in protecting mitochondrial components such as DNA from oxidative damage associated with mitochondrial generation of superoxide. In combating cytotoxic effects of pyrogallol, a known superoxide generator, ET is as potent as glutathione. Because of its dietary origin and the toxicity associated with its depletion, ET may represent a new vitamin whose physiologic roles include antioxidant cytoprotection. PMID:19911007
ARG1 Functions in the Physiological Adaptation of Undifferentiated Plant Cells to Spaceflight.
Zupanska, Agata K; Schultz, Eric R; Yao, JiQiang; Sng, Natasha J; Zhou, Mingqi; Callaham, Jordan B; Ferl, Robert J; Paul, Anna-Lisa
2017-11-01
Scientific access to spaceflight and especially the International Space Station has revealed that physiological adaptation to spaceflight is accompanied or enabled by changes in gene expression that significantly alter the transcriptome of cells in spaceflight. A wide range of experiments have shown that plant physiological adaptation to spaceflight involves gene expression changes that alter cell wall and other metabolisms. However, while transcriptome profiling aptly illuminates changes in gene expression that accompany spaceflight adaptation, mutation analysis is required to illuminate key elements required for that adaptation. Here we report how transcriptome profiling was used to gain insight into the spaceflight adaptation role of Altered response to gravity 1 (Arg1), a gene known to affect gravity responses in plants on Earth. The study compared expression profiles of cultured lines of Arabidopsis thaliana derived from wild-type (WT) cultivar Col-0 to profiles from a knock-out line deficient in the gene encoding ARG1 (ARG1 KO), both on the ground and in space. The cell lines were launched on SpaceX CRS-2 as part of the Cellular Expression Logic (CEL) experiment of the BRIC-17 spaceflight mission. The cultured cell lines were grown within 60 mm Petri plates in Petri Dish Fixation Units (PDFUs) that were housed within the Biological Research In Canisters (BRIC) hardware. Spaceflight samples were fixed on orbit. Differentially expressed genes were identified between the two environments (spaceflight and comparable ground controls) and the two genotypes (WT and ARG1 KO). Each genotype engaged unique genes during physiological adaptation to the spaceflight environment, with little overlap. Most of the genes altered in expression in spaceflight in WT cells were found to be Arg1-dependent, suggesting a major role for that gene in the physiological adaptation of undifferentiated cells to spaceflight. Key Words: ARG1-Spaceflight-Gene expression-Physiological adaptation-BRIC. Astrobiology 17, 1077-1111.
Physiological mechanisms drive differing foliar calcium content in ferns and angiosperms.
Funk, Jennifer L; Amatangelo, Kathryn L
2013-09-01
Recent evidence points to ferns containing significantly lower contents of foliar calcium and other cations than angiosperms. This is especially true of more ancient 'non-polypod' fern lineages, which predate the diversification of angiosperms. Calcium is an important plant nutrient, the lack of which can potentially slow plant growth and litter decomposition, and alter soil invertebrate communities. The physiological mechanisms limiting foliar calcium (Ca) content in ferns are unknown. While there is a lot we do not know about Ca uptake and transport in plants, three physiological processes are likely to be important. We measured transpiration rate, cation exchange capacity, and leaching loss to determine which process most strongly regulates foliar Ca content in a range of fern and co-occurring understory angiosperm species from a montane Hawaiian rainforest. We found higher instantaneous and lifetime (corrected for leaf lifespan) transpiration rates in angiosperms relative to ferns. Ferns preferentially incorporated Ca into leaves relative to strontium, which suggests that root or stem cation exchange capacity differs between ferns and angiosperms, potentially affecting calcium transport in plants. There were no differences in foliar Ca leaching loss between groups. Among the physiological mechanisms measured, foliar Ca was most strongly correlated with leaf-level transpiration rate and leaf lifespan. This suggests that inter-specific differences in a leaf's lifetime transpiration may play a significant role in determining plant nutrition.
Long Non-coding RNAs and their Role in Metastasis
WEIDLE, ULRICH H; BIRZELE, FABIAN; KOLLMORGEN, GWEN; RÜGER, RÜDIGER
2017-01-01
The perception of long non-coding RNAs as chunk RNA and transcriptional noise has been steadily replaced by their role as validated targets for a diverse set of physiological processes in the past few years. However, for the vast majority of lncRNAs their precise mode of action and physiological function remain to be uncovered. A large body of evidence has revealed their essential role in all stages of cancirogenesis and metastasis. In this review we focus on the role of lncRNAs in metastasis. We grouped selected lncRNAs into three categories based on in vitro and in vivo mode of action-related studies and clinical relevance for metastasis. Grouped according to their mode of action, in category I we discuss lncRNAs such as CCAT2, DREH, LET, NKILA, treRNA, HOTAIR, H19, FENDRR, lincROR, MALAT, GClnc1, BCAR4, SCHLAP1 and lncRNA ATP, all lncRNAs with in vitro and in vivo metastasis-related data and clinical significance. In category II we discuss lncRNAs CCAT1, PCAT1, PTENgp1, GPLINC, MEG3, ZEB2-AS, LCT13, ANRIL, NBAT1 and lncTCF7 all characterized by their mode of action in vitro and clinical significance, but pending or preliminary in vivo data. Finally, under category III, we discuss lncRNAs BANCR, FRLnc1, SPRY4-IT1 and LIMT with partially or poorly-resolved mode of action and varying degree of validation in clinical metastasis. Finally we discuss metastasis-related translational aspects of lncRNAs. PMID:28446530
Ito, Junko; Ito, Masahiko; Nambu, Hirohide; Fujikawa, Toru; Tanaka, Kenichi; Iwaasa, Hisashi; Tokita, Shigeru
2009-11-01
G-protein-coupled receptors (GPCRs) constitute the largest family of transmembrane receptors and regulate a variety of physiological and disease processes. Although the roles of many non-odorant GPCRs have been identified in vivo, several GPCRs remain orphans (oGPCRs). The gastrointestinal (GI) tract is the largest endocrine organ and is a promising target for drug discovery. Given their close link to physiological function, the anatomical and histological expression profiles of benchmark GI-related GPCRs, such as the cholecystokinin-1 receptor and GPR120, and 106 oGPCRs were investigated in the mucosal and muscle-myenteric nerve layers in the GI tract of C57BL/6J mice by quantitative real-time polymerase chain reaction. The mRNA expression patterns of these benchmark molecules were consistent with previous in situ hybridization and immunohistochemical studies, validating the experimental protocols in this study. Of 96 oGPCRs with significant mRNA expression in the GI tract, several oGPCRs showed unique expression patterns. GPR85, GPR37, GPR37L1, brain-specific angiogenesis inhibitor (BAI) 1, BAI2, BAI3, and GPRC5B mRNAs were preferentially expressed in the muscle-myenteric nerve layer, similar to GPCRs that are expressed in both the central and enteric nerve systems and that play multiple regulatory roles throughout the gut-brain axis. In contrast, GPR112, trace amine-associated receptor (TAAR) 1, TAAR2, and GPRC5A mRNAs were preferentially expressed in the mucosal layer, suggesting their potential roles in the regulation of secretion, immunity, and epithelial homeostasis. These anatomical and histological mRNA expression profiles of oGPCRs provide useful clues about the physiological roles of oGPCRs in the GI tract.
A Dual Role for NOTCH Signaling in Joint Cartilage Maintenance and Osteoarthritis
Liu, Zhaoyang; Chen, Jianquan; Mirando, Anthony; Wang, Cuicui; Zuscik, Michael J.; O’Keefe, Regis J.; Hilton, Matthew J.
2015-01-01
Loss of NOTCH signaling in postnatal murine joints results in osteoarthritis (OA), indicating a requirement for NOTCH during joint cartilage maintenance. Unexpectedly, NOTCH components are significantly up-regulated in human and murine post-traumatic OA, suggesting either a reparative or pathological role for NOTCH activation in OA. Here we investigated the potential dual role for NOTCH in joint maintenance and OA by generating two mouse models overexpressing the NOTCH1 intracellular domain within postnatal joint cartilage; one with sustained NOTCH activation that likely resembles pathological NOTCH signaling and one with transient NOTCH activation that more closely reflects physiological NOTCH signaling. Sustained NOTCH signaling in joint cartilage leads to an early and progressive OA pathology, while on the contrary, transient NOTCH activation enhances cartilage matrix synthesis and promotes joint maintenance under normal physiological conditions. Using RNA-seq, immunohistochemical, and biochemical approaches we identified several novel targets potentially responsible for NOTCH-mediated cartilage degradation, fibrosis, and OA progression, including components of the IL6/STAT3 and ERK/p38 MAPK pathways; factors that may also contribute to post-traumatic OA development. Collectively, these data demonstrate a dual role for the NOTCH pathway in joint cartilage and identify important downstream NOTCH effectors as potential targets for disease modifying osteoarthritis drugs (DMOADs). PMID:26198357
Phylogenetically distant barley legumains have a role in both seed and vegetative tissues.
Julián, Israel; Gandullo, Jacinto; Santos-Silva, Ludier K; Diaz, Isabel; Martinez, Manuel
2013-07-01
Legumains or vacuolar processing enzymes are cysteine peptidases (C13 family, clan CD) with increasingly recognized physiological significance in plants. They have previously been classified as seed and vegetative legumains. In this work, the entire barley legumain family is described. The eight members of this family belong to the two phylogenetic clades in which the angiosperm legumains are distributed. An in-depth molecular and functional characterization of a barley legumain from each group, HvLeg-2 and HvLeg-4, was performed. Both legumains contained a signal peptide and were located in the endoplasmic reticulum, were expressed in seeds and vegetative tissues, and when expressed as recombinant proteins showed legumain and caspase proteolytic activities. However, the role of each protein seemed to be different in their target tissues. HvLeg-2 responded in leaves to biotic and abiotic stimuli, such as salicylic acid, jasmonic acid, nitric oxide, abscisic acid, and aphid infestation, and was induced by gibberellic acid in seeds, where the protein is able to degrade storage globulins. HvLeg-4 responded in leaves to wounding, nitric oxide, and abscisic acid treatments, and had an unknown role in the germinating seed. From these results, a multifunctional role was assumed for these two phylogenetically distant legumains, achieving different physiological functions in both seed and vegetative tissues.
The role of the commensal microbiota in adaptive and maladaptive stressor-induced immunomodulation
Mackos, Amy R.; Maltz, Ross; Bailey, Michael T.
2016-01-01
Over the past decade, it has become increasingly evident that there are extensive bidirectional interactions between the body and its microbiota. These interactions are evident during stressful periods, where it is recognized that commensal microbiota community structure is significantly changed. Many different stressors, ranging from early life stressors to stressors administered during adulthood, lead to significant, community-wide differences in the microbiota. The mechanisms through which this occurs are not yet known, but it is known that commensal microbes can recognize, and respond to, mammalian hormones and neurotransmitters, including those that are involved with the physiological response to stressful stimuli. In addition, the physiological stress response also changes many aspects of gastrointestinal physiology that can impact microbial community composition. Thus, there are many routes through which microbial community composition might be disrupted during stressful periods. The implications of these disruptions in commensal microbial communities for host health are still not well understood, but the commensal microbiota have been linked to stressor-induced immunopotentiation. The role of the microbiota in stressor-induced immunopotentiation can be adaptive, such as when these microbes stimulate innate defenses against bacterial infection. However, the commensal microbiota can also lead to maladaptive immune responses during stressor-exposure. This is evident in animal models of colonic inflammation where stressor exposure increases the inflammation through mechanisms involving the microbiota. It is likely that during stressor exposure, immune cell functioning is regulated by combined effects of both neurotransmitters/hormones and commensal microbes. Defining this regulation should be a focus of future studies. PMID:27760302
The role of the commensal microbiota in adaptive and maladaptive stressor-induced immunomodulation.
Mackos, Amy R; Maltz, Ross; Bailey, Michael T
2017-02-01
Over the past decade, it has become increasingly evident that there are extensive bidirectional interactions between the body and its microbiota. These interactions are evident during stressful periods, where it is recognized that commensal microbiota community structure is significantly changed. Many different stressors, ranging from early life stressors to stressors administered during adulthood, lead to significant, community-wide differences in the microbiota. The mechanisms through which this occurs are not yet known, but it is known that commensal microbes can recognize, and respond to, mammalian hormones and neurotransmitters, including those that are involved with the physiological response to stressful stimuli. In addition, the physiological stress response also changes many aspects of gastrointestinal physiology that can impact microbial community composition. Thus, there are many routes through which microbial community composition might be disrupted during stressful periods. The implications of these disruptions in commensal microbial communities for host health are still not well understood, but the commensal microbiota have been linked to stressor-induced immunopotentiation. The role of the microbiota in stressor-induced immunopotentiation can be adaptive, such as when these microbes stimulate innate defenses against bacterial infection. However, the commensal microbiota can also lead to maladaptive immune responses during stressor-exposure. This is evident in animal models of colonic inflammation where stressor exposure increases the inflammation through mechanisms involving the microbiota. It is likely that during stressor exposure, immune cell functioning is regulated by combined effects of both neurotransmitters/hormones and commensal microbes. Defining this regulation should be a focus of future studies. Copyright © 2016 Elsevier Inc. All rights reserved.
The role of growth hormone in lines of mice divergently selected on body weight.
Hastings, I M; Bootland, L H; Hill, W G
1993-04-01
An understanding of the physiological and genetic changes which determine the response to selection is critical for both evolutionary theory and to assess the application of new molecular techniques to commercial animal breeding. We investigated an aspect of physiology, growth hormone (GH) metabolism, which might a priori have been expected to play a large part in the response of mouse lines selected for high or low body weight. Disruption of endogenous GH or addition of exogenous GH had similar proportionate effects on body weight in both lines of mice (although differences in body composition arose) suggesting that neither the production of GH nor receptor sensitivity to GH had been altered as a result of selection. This supports a 'pleiotropic model' of the response to selection: that many genes with diverse metabolic roles all contribute to the divergent phenotype. This result has significant commercial implications as it suggests that artificial selection, transgenic technology and environmental manipulation may be synergistic rather than antagonistic strategies.
Mechanisms underlying astringency: introduction to an oral tribology approach
NASA Astrophysics Data System (ADS)
Upadhyay, Rutuja; Brossard, Natalia; Chen, Jianshe
2016-03-01
Astringency is one of the predominant factors in the sensory experience of many foods and beverages ranging from wine to nuts. The scientific community is discussing mechanisms that explain this complex phenomenon, since there are no conclusive results which correlate well with sensory astringency. Therefore, the mechanisms and perceptual characteristics of astringency warrant further discussion and investigation. This paper gives a brief introduction of the fundamentals of oral tribology forming a basis of the astringency mechanism. It discusses the current state of the literature on mechanisms underlying astringency describing the existing astringency models. The review discusses the crucial role of saliva and its physiology which contributes significantly in astringency perception in the mouth. It also provides an overview of research concerned with the physiological and psychophysical factors that mediate the perception of this sensation, establishing the ground for future research. Thus, the overall aim of the review is to establish the critical roles of oral friction (thin-film lubrication) in the sensation of astringency and possibly of some other specific sensory features.
NF-κB signaling pathways: role in nervous system physiology and pathology.
Mincheva-Tasheva, Stefka; Soler, Rosa M
2013-04-01
Intracellular pathways related to cell survival regulate neuronal physiology during development and neurodegenerative disorders. One of the pathways that have recently emerged with an important role in these processes is nuclear factor-κB (NF-κB). The activity of this pathway leads to the nuclear translocation of the NF-κB transcription factors and the regulation of anti-apoptotic gene expression. Different stimuli can activate the pathway through different intracellular cascades (canonical, non-canonical, and atypical), contributing to the translocation of specific dimers of the NF-κB transcription factors, and each of these dimers can regulate the transcription of different genes. Recent studies have shown that the activation of this pathway regulates opposite responses such as cell survival or neuronal degeneration. These apparent contradictory effects depend on conditions such as the pathway stimuli, the origin of the cells, or the cellular context. In the present review, the authors summarize these findings and discuss their significance with respect to survival or death in the nervous system.
Role of growth differentiation factor 11 in development, physiology and disease
Zhang, Yonghui; Wei, Yong; Liu, Dan; Liu, Feng; Li, Xiaoshan; Pan, Lianhong; Pang, Yi; Chen, Dilong
2017-01-01
Growth differentiation factor (GDF11) is a member of TGF-β/BMP superfamily that activates Smad and non-Smad signaling pathways and regulates expression of its target nuclear genes. Since its discovery in 1999, studies have shown the involvement of GDF11 in normal physiological processes, such as embryonic development and erythropoiesis, as well as in the pathophysiology of aging, cardiovascular disease, diabetes mellitus, and cancer. In addition, there are contradictory reports regarding the role of GDF11 in aging, cardiovascular disease, diabetes mellitus, osteogenesis, skeletal muscle development, and neurogenesis. In this review, we describe the GDF11 signaling pathway and its potential role in development, physiology and disease. PMID:29113418
Kramer, Andrew A; Higgins, Thomas L; Zimmerman, Jack E
2015-02-01
To compare ICU performance using standardized mortality ratios generated by the Acute Physiology and Chronic Health Evaluation IVa and a National Quality Forum-endorsed methodology and examine potential reasons for model-based standardized mortality ratio differences. Retrospective analysis of day 1 hospital mortality predictions at the ICU level using Acute Physiology and Chronic Health Evaluation IVa and National Quality Forum models on the same patient cohort. Forty-seven ICUs at 36 U.S. hospitals from January 2008 to May 2013. Eighty-nine thousand three hundred fifty-three consecutive unselected ICU admissions. None. We assessed standardized mortality ratios for each ICU using data for patients eligible for Acute Physiology and Chronic Health Evaluation IVa and National Quality Forum predictions in order to compare unit-level model performance, differences in ICU rankings, and how case-mix adjustment might explain standardized mortality ratio differences. Hospital mortality was 11.5%. Overall standardized mortality ratio was 0.89 using Acute Physiology and Chronic Health Evaluation IVa and 1.07 using National Quality Forum, the latter having a widely dispersed and multimodal standardized mortality ratio distribution. Model exclusion criteria eliminated mortality predictions for 10.6% of patients for Acute Physiology and Chronic Health Evaluation IVa and 27.9% for National Quality Forum. The two models agreed on the significance and direction of standardized mortality ratio only 45% of the time. Four ICUs had standardized mortality ratios significantly less than 1.0 using Acute Physiology and Chronic Health Evaluation IVa, but significantly greater than 1.0 using National Quality Forum. Two ICUs had standardized mortality ratios exceeding 1.75 using National Quality Forum, but nonsignificant performance using Acute Physiology and Chronic Health Evaluation IVa. Stratification by patient and institutional characteristics indicated that units caring for more severely ill patients and those with a higher percentage of patients on mechanical ventilation had the most discordant standardized mortality ratios between the two predictive models. Acute Physiology and Chronic Health Evaluation IVa and National Quality Forum models yield different ICU performance assessments due to differences in case-mix adjustment. Given the growing role of outcomes in driving prospective payment patient referral and public reporting, performance should be assessed by models with fewer exclusions, superior accuracy, and better case-mix adjustment.
Farkas, L
1981-09-01
This study sought to identify adaptation problems on the part of elderly persons and significant others that were associated with nursing home applications for elderly persons. Within the framework of the Roy Adaptation Nursing Model, an ex post facto research design was utilized to identify these adaptation problems. The four adaptive modes in this model are: physiological, self-concept, role function, and interdependence. The study group (n = 22) and a control group of elderly persons living in Calgary, as well as their significant others, were administered a structured questionnaire. Five hypotheses relating to overall adaptation problems, powerlessness, role reversal, guilt, and knowledge and utilization of services were formulated and tested. Only the hypothesis indicating role reversal on the part of the significant others was accepted. Adaptation problems encountered by the elderly which were associated with nursing home applications occurred in the self-concept and interdependence adaptive modes. The adaptation problems perceived by the significant others, which were associated with nursing home applications for their elderly, occurred in the self-concept, role function, and interdependence modes. Adaptation problems from the significant others' perception rather than from the elderly persons' perception appear to be more significantly associated with nursing home applications.
The concept of function in modern physiology.
Roux, Etienne
2014-06-01
An overview of the scientific literature shows that the concept of function is central in physiology. However, the concept itself is not defined by physiologists. On the other hand, the teleological, namely, the 'goal-directed' dimension of function, and its subsequent explanatory relevance, is a philosophical problem. Intuitively, the function of a trait in a system explains why this trait is present, but, in the early 1960s, Ernest Nagel and Carl Hempel have shown that this inference cannot be logically founded. However, they showed that self-regulated systems are teleological. According to the selectionist theories, the function of an item is its effect that has been selected by natural selection, a process that explains its presence. As they restrict the functional attribution of a trait to its past selective value and not its current properties, these theories are inconsistent with the concept of function in physiology. A more adequate one is the causal role theory, for which a function of a trait in a system is its causal contribution to the functional capacity of the system. However, this leaves unsolved the question of the 'surplus meaning' of the teleological dimension of function. The significance of considering organisms as 'purpose-like' (teleological) systems may reside not in its explanatory power but in its methodological fruitfulness in physiology. In this view, the teleological dimension of physiological functions is convergent to but not imported from, the teleological dimension of evolutionary biology. © 2014 The Authors. The Journal of Physiology © 2014 The Physiological Society.
Nia, Masoud Saghafi; Naffisi, Nahid; Mohebbi, Hassan Ali; Moharamzadeh, Yashar
2008-09-01
To evaluate the impact of animal model based medical training courses for village healthcare workers on prehospital physiologic condition and prognosis of patients with penetrating injuries. Experimental study. This study was carried out in Mehran city and its neighbouring rural districts in western part of Iran from 2002 to 2004. Seventy-six village healthcare workers were trained and equipped to deliver in-field medical first cares. First group (226 patients) consisted of those who received this cares by the trained group and second group (245 patients) were those who received no in-field cares and were transported directly to the trauma center in provincial capital, Ilam. Physiologic Severity Score (PSS) was calculated to determine the physiologic condition of patients in both groups. The most prevalent cause of trauma in both groups was car accidents (61.6%). Controlling of hemorrhage was the most frequent provided initial medical care (40.6%). A significant improvement regarding the PSS score was observed in the first group of patients compared to the second group (7.505 vs. 6.799, 95% CI for difference: 0.3 to 0.9). The mortality rates of the first and second group of patients were 3% and 7.3%, respectively (p=0.051). Performing life support courses in rural areas of low-income countries where there is no pre-hospital triage and emergency medical system and provision of classic resuscitative measures are limited, has a significant impact on improvement of pre-hospital physiologic condition and prognosis of patients with penetrating injuries.
[SIGNIFICANCE OF MAGNESIUM IN PHISIOLOGY AND PATHOLOGY OF THE DIGESTIVE SYSTEM].
Grigus, Ya I; Mikhaylova, O D; Gorbunov A Yu; Vakhrushev, Ya M
2015-01-01
The article describes the physiological role of magnesium in the human body and its importance for metabolic processes. The reasons for the development of magnesium deficiency and hypermagnesaemia and its clinical symptoms are shown. The specialties of magnesium metabolism disturbances in gastroenterological pathology are described. Particular attention paid to the correction of magnesium levels with deviations of its content in the organism.
M. V. DiLeo; R. M. Bostock; D.M. Rizzo
2009-01-01
California bay laurel trees (Umbellularia californica) play a crucial role in the reproduction and survival of Phytophthora ramorum in coastal California forests by supporting sporulation during the rainy season and by providing a means for the pathogen to survive the dry, Mediterranean summer. While bay laurel is thus critical to the epidemiology of sudden oak death...
Significance of phytohormones in Siberian larch-bud gall midge interaction
Rida M. Matrenina
1991-01-01
Interrelations of the bud gall midge and the Siberian larch are of scientific and practical interest because of the bud gall midge's role as a plant endoparasite. We know that attack by the gall midge sets off a reaction in the entire plant. Invasion by the insect results in a certain interaction between physiological mechanisms of the insect and the plant which...
Azarmi, Somayeh; Farsi, Zahra
2015-10-01
Any defect in extremities of the body can affect different life aspects. The purpose of this study was to investigate the effect of Roy's adaptation model-guided education on promoting the adaptation of veterans with lower extremities amputation. In a randomized clinical trial, 60 veterans with lower extremities amputation referring to Kowsar Orthotics and Prosthetics Center of veterans clinic in Tehran, Iran, were recruited with convenience method and were randomly assigned to intervention and control groups during 2013 - 2014. For data collection, Roy's adaptation model questionnaire was used. After completing the questionnaires in both groups, maladaptive behaviors were determined in the intervention group and an education program based on Roy's adaptation model was implemented. After two months, both groups completed the questionnaires again. Data was analyzed with SPSS software. Independent t-test showed statistically significant differences between the two groups in the post-test stage in terms of the total score of adaptation (P = 0.001) as well as physiologic (P = 0.0001) and role function modes (P = 0.004). The total score of adaptation (139.43 ± 5.45 to 127.54 ± 14.55, P = 0.006) as well as the scores of physiologic (60.26 ± 5.45 to 53.73 ± 7.79, P = 0.001) and role function (20.30 ± 2.42 to 18.13 ± 3.18, P = 0.01) modes in the intervention group significantly increased, whereas the scores of self-concept (42.10 ± 4.71 to 39.40 ± 5.67, P = 0.21) and interdependence (16.76 ± 2.22 to 16.30 ± 2.57, P = 0.44) modes in the two stages did not have a significant difference. Findings of this research indicated that the Roy's adaptation model-guided education promoted the adaptation level of physiologic and role function modes in veterans with lower extremities amputation. However, this intervention could not promote adaptation in self-concept and interdependence modes. More intervention is advised based on Roy's adaptation model for improving the adaptation of veterans with lower extremities.
Sugar for the brain: the role of glucose in physiological and pathological brain function.
Mergenthaler, Philipp; Lindauer, Ute; Dienel, Gerald A; Meisel, Andreas
2013-10-01
The mammalian brain depends upon glucose as its main source of energy, and tight regulation of glucose metabolism is critical for brain physiology. Consistent with its critical role for physiological brain function, disruption of normal glucose metabolism as well as its interdependence with cell death pathways forms the pathophysiological basis for many brain disorders. Here, we review recent advances in understanding how glucose metabolism sustains basic brain physiology. We synthesize these findings to form a comprehensive picture of the cooperation required between different systems and cell types, and the specific breakdowns in this cooperation that lead to disease. Copyright © 2013 Elsevier Ltd. All rights reserved.
NASA Astrophysics Data System (ADS)
Liao, Fang-Tsu; Chang, Cheng-Yi; Su, Ming-Tsan; Kuo, Wen-Chuan
2014-01-01
Prior studies have established the necessity of an angiotensin-converting enzyme-related (ACER) gene for heart morphogenesis of Drosophila. Nevertheless, the physiology of ACER has yet to be comprehensively understood. Herein, we employed RNA interference to down-regulate the expression of ACER in Drosophila's heart and swept source optical coherence tomography to assess whether ACER is required for cardiac functions in living adult flies. Several contractile parameters of Drosophila heart, including the heart rate (HR), end-diastolic diameter (EDD), end-systolic diameter (ESD), percent fractional shortening (%FS), and stress-induced cardiac performance, are shown, which are age dependent. These age-dependent cardiac functions declined significantly when ACER was down-regulated. Moreover, the lifespans of ACER knock-down flies were significantly shorter than those of wild-type control flies. Thus, we posit that ACER, the Drosophila ortholog of mammalian angiotensin-converting enzyme 2 (ACE2), is essential for both heart physiology and longevity of animals. Since mammalian ACE2 controls many cardiovascular physiological features and is implicated in cardiomyopathies, our findings that ACER plays conserved roles in genetically tractable animals will pave the way for uncovering the genetic pathway that controls the renin-angiotensin system.
USDA-ARS?s Scientific Manuscript database
Fish meal may contain “unknown growth factors” that have yet to be identified for their physiological role. Carnosine is a histidine-ß-alanine dipeptide found in muscle and nervous system tissue which has been demonstrated to have biological activity, but its physiological role is not well defined. ...
ERIC Educational Resources Information Center
Willemen, Agnes M.; Schuengel, Carlo; Koot, Hans M.
2009-01-01
Background: Psychopathology in youth appears to be linked to deficits in regulating affective responses to stressful situations. In children, high-quality parental support facilitates affect regulation. However, in adolescence, the role of parent-child interaction in the regulation of affect is unclear. This study examined physiological reactivity…
Tissue Physiology and Pathology of Aromatase
Stocco, Carlos
2011-01-01
Summary Aromatase is expressed in multiple tissues, indicating a crucial role for locally produced oestrogens in the differentiation, regulation and normal function of several organs and processes. This review is an overview of the role of aromatase in different tissues under normal physiological conditions and its contribution to the development of some oestrogen-related pathologies. PMID:22108547
Yan, Hui; Filardo, Fiona; Hu, Xiaotao; Zhao, Xiaomin; Fu, DongHui
2016-02-01
In order to understand the physiological response of oilseed rape (Brassica napus L.) leaves to cadmium (Cd) stress and exploit the physiological mechanisms involved in Cd tolerance, macro-mineral and chlorophyll concentrations, reactive oxygen species (ROS) accumulation, activities of enzymatic antioxidants, nonenzymatic compounds metabolism, endogenous hormonal changes, and balance in leaves of oilseed rape exposed to 0, 100, or 200 μM CdSO4 were investigated. The results showed that under Cd exposure, Cd concentrations in the leaves continually increased while macro-minerals and chlorophyll concentrations decreased significantly. Meanwhile, with increased Cd stress, superoxide anion (O2(• -)) production rate and hydrogen peroxide (H2O2) concentrations in the leaves increased significantly, which caused malondialdehyde (MDA) accumulation and oxidative stress. For scavenging excess accumulated ROS and alleviating oxidative injury in the leaves, the activity of enzymatic antioxidants, such as superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT), was increased significantly at certain stress levels. However, with increased Cd stress, the antioxidant enzyme activities all showed a trend towards reduction. The nonenzymatic antioxidative compounds, such as proline and total soluble sugars, accumulated continuously with increased Cd stress to play a long-term role in scavenging ROS. In addition, ABA levels also increased continuously with Cd stress while ZR decreased and the ABA/ZR ratio increased, which might also be providing a protective role against Cd toxicity.
Pisano, Umberto; Irvine, Lesley; Szczachor, Justina; Jawad, Ahsin; MacLeod, Andrew; Lim, Michael
2016-10-01
Anismus is a functional disorder featuring obstructive symptoms and paradoxical contractions of the pelvic floor. This study aims to establish diagnosis agreement between physiology and radiology, associate anismus with morphological outlet obstruction, and explore the role of sphincteric pressure and rectal volumes in the radiological diagnosis of anismus. Consecutive patients were evaluated by using magnetic resonance imaging proctography/fluoroscopic defecography and anorectal physiology. Morphological radiological features were associated with physiology tests. A categorical analysis was performed using the chi-square test, and agreement was assessed via the kappa coefficient. A Mann-Whitney test was used to assess rectal volumes and sphincterial pressure distributions between groups of patients. A P-value of <0.05 was significant. Forty-three patients (42 female patients) underwent anorectal physiology and radiology imaging. The median age was 54 years (interquartile range, 41.5-60 years). Anismus was seen radiologically and physiologically in 18 (41.8%) and 12 patients (27.9%), respectively. The agreement between modalities was 0.298 (P = 0.04). Using physiology as a reference, radiology had positive and negative predictive values of 44% and 84%, respectively. Rectoceles, cystoceles, enteroceles and pathological pelvic floor descent were not physiologically predictive of animus (P > 0.05). The sphincterial straining pressure was 71 mmHg in the anismus group versus 12 mmHg. Radiology was likely to identify anismus when the straining pressure exceeded 50% of the resting pressure (P = 0.08). Radiological techniques detect pelvic morphological abnormalities, but lead to overdiagnoses of anismus. No proctographic pathological feature predicts anismus reliably. A stronger pelvic floor paradoxical contraction is associated with a greater likelihood of detection by proctography.
Irvine, Lesley; Szczachor, Justina; Jawad, Ahsin; MacLeod, Andrew; Lim, Michael
2016-01-01
Purpose Anismus is a functional disorder featuring obstructive symptoms and paradoxical contractions of the pelvic floor. This study aims to establish diagnosis agreement between physiology and radiology, associate anismus with morphological outlet obstruction, and explore the role of sphincteric pressure and rectal volumes in the radiological diagnosis of anismus. Methods Consecutive patients were evaluated by using magnetic resonance imaging proctography/fluoroscopic defecography and anorectal physiology. Morphological radiological features were associated with physiology tests. A categorical analysis was performed using the chi-square test, and agreement was assessed via the kappa coefficient. A Mann-Whitney test was used to assess rectal volumes and sphincterial pressure distributions between groups of patients. A P-value of <0.05 was significant. Results Forty-three patients (42 female patients) underwent anorectal physiology and radiology imaging. The median age was 54 years (interquartile range, 41.5–60 years). Anismus was seen radiologically and physiologically in 18 (41.8%) and 12 patients (27.9%), respectively. The agreement between modalities was 0.298 (P = 0.04). Using physiology as a reference, radiology had positive and negative predictive values of 44% and 84%, respectively. Rectoceles, cystoceles, enteroceles and pathological pelvic floor descent were not physiologically predictive of animus (P > 0.05). The sphincterial straining pressure was 71 mmHg in the anismus group versus 12 mmHg. Radiology was likely to identify anismus when the straining pressure exceeded 50% of the resting pressure (P = 0.08). Conclusion Radiological techniques detect pelvic morphological abnormalities, but lead to overdiagnoses of anismus. No proctographic pathological feature predicts anismus reliably. A stronger pelvic floor paradoxical contraction is associated with a greater likelihood of detection by proctography. PMID:27847787
Neurological perspectives on voltage-gated sodium channels
Linley, John E.; Baker, Mark D.; Minett, Michael S.; Cregg, Roman; Werdehausen, Robert; Rugiero, François
2012-01-01
The activity of voltage-gated sodium channels has long been linked to disorders of neuronal excitability such as epilepsy and chronic pain. Recent genetic studies have now expanded the role of sodium channels in health and disease, to include autism, migraine, multiple sclerosis, cancer as well as muscle and immune system disorders. Transgenic mouse models have proved useful in understanding the physiological role of individual sodium channels, and there has been significant progress in the development of subtype selective inhibitors of sodium channels. This review will outline the functions and roles of specific sodium channels in electrical signalling and disease, focusing on neurological aspects. We also discuss recent advances in the development of selective sodium channel inhibitors. PMID:22961543
Nutrition and orthomolecular supplementation in lung cancer patients.
Campos, Diana; Austerlitz, Carlos; Allison, Ron R; Póvoa, Helion; Sibata, Claudio
2009-12-01
This article reviews updates and provides some data related to nutritional and orthomolecular supplementation in oncology patients with an emphasis on lung cancer, a commonly diagnosed tumor with significant nutritional disturbances. Cancer and its treatment play a significant role in nutritional imbalance which likely has negative impact on the patient both in terms of quality and quantity of life. Nutritional supplementation may correct these imbalances with significant clinical benefit both physiologically and psychologically. This review will help assist in providing clinically useful data to assess the cancer patient's nutritional status and to guide nutritional intervention to assist these patients' recovery.
Ortega, Eduardo; Hinchado, M D; Martín-Cordero, L; Asea, A
2009-05-01
We studied the physiological role of the 72 kDa extracellular heat shock protein (Hsp72, a stress-inducible protein) in modulating neutrophil chemotaxis during a single bout of intense exercise performed by sedentary women, together with various cell mechanisms potentially involved in the modulation. For each volunteer, we evaluated neutrophil chemotaxis and serum Hsp72 concentration before and immediately after a single bout of exercise (1 h on a cycle ergometer at 70% VO(2) max), and 24 h later. Both parameters were found to be stimulated by the exercise, and had returned to basal values 24 h later. In vitro, there was a dose-dependent increase in chemotaxis when neutrophils were incubated both with physiological Hsp72 concentrations and with a 100 x greater concentration. The chemotaxis was greater when the neutrophils were incubated with the post-exercise Hsp72 concentration than with the basal concentration, suggesting a physiological role for this protein in the context of the stimulation of neutrophil chemotaxis by intense exercise. The 100 x Hsp72 concentration stimulated chemotaxis even more strongly. In addition, Hsp72 was found to have chemoattractant and chemokinetic effects on the neutrophils at physiological concentrations, with these effects being significantly greater with the post-exercise than with the basal Hsp72 concentration. The Hsp72-induced stimulation of neutrophil chemotaxis disappeared when the toll-like receptor 2 (TLR-2) was blocked, and phosphatidylinositol-3-kinase (PI3K), extracellular signal-regulated kinase (ERK), and nuclear transcription factor kappa B (NF-kappaB) were also found to be involved in the signaling process. No changes were observed, however, in neutrophil intracellular calcium levels in response to Hsp72. In conclusion, physiological concentrations of the stress protein Hsp72 stimulate human neutrophil chemotaxis through TLR-2 with its cofactor CD14, involving ERK, NF-kappaB, and PI3K, but not iCa(2 + ), as intracellular messengers. In addition, Hsp72 seems to participate in the stimulation of chemotaxis induced by a single bout of intense exercise performed by sedentary women.
The Role of Adenosine A2A Receptor, CYP450s, and PPARs in the Regulation of Vascular Tone
Khayat, Maan T.
2017-01-01
Adenosine is an endogenous mediator involved in a myriad of physiologic functions, including vascular tone regulation. It is also implicated in some pathologic conditions. Four distinct receptor subtypes mediate the effects of adenosine, such as its role in the regulation of the vascular tone. Vascular tone regulation is a complex and continuous process which involves many mechanisms and mediators that are not fully disclosed. The vascular endothelium plays a pivotal role in regulating blood flow to and from all body organs. Also, the vascular endothelium is not merely a physical barrier; it is a complex tissue with numerous functions. Among adenosine receptors, A2A receptor subtype (A2AAR) stands out as the primary receptor responsible for the vasodilatory effects of adenosine. This review focuses on important effectors of the vascular endothelium, including adenosine, adenosine receptors, EETs (epoxyeicosatrienoic acids), HETEs (hydroxyeicosatetraenoic acids), PPARs (peroxisome proliferator-activated receptors), and KATP channels. Given the impact of vascular tone regulation in cardiovascular physiology and pathophysiology, better understanding of the mechanisms affecting it could have a significant potential for developing therapeutic agents for cardiovascular diseases. PMID:28884118
A mini review on immune role of chemokines and its receptors in snakehead murrel Channa striatus.
Bhatt, Prasanth; Kumaresan, Venkatesh; Palanisamy, Rajesh; Ravichandran, Gayathri; Mala, Kanchana; Amin, S M Nurul; Arshad, Aziz; Yusoff, Fatimah Md; Arockiaraj, Jesu
2018-01-01
Chemokines are ubiquitous cytokine molecules involved in migration of cells during inflammation and normal physiological processes. Though the study on chemokines in mammalian species like humans have been extensively studied, characterization of chemokines in teleost fishes is still in the early stage. The present review provides an overview of chemokines and its receptors in a teleost fish, Channa striatus. C. striatus is an air breathing freshwater carnivore, which has enormous economic importance. This species is affected by an oomycete fungus, Aphanomyces invadans and a Gram negative bacteria Aeromonas hydrophila is known to cause secondary infection. These pathogens impose immune changes in the host organism, which in turn mounts several immune responses. Of these, the role of cytokines in the immune response is immense, due to their involvement in several activities of inflammation such as cell trafficking to the site of inflammation and antigen presentation. Given that importance, chemokines in fishes do have significant role in the immunological and other physiological functions of the organism, hence there is a need to understand the characteristics, activities and performace of these small molecules in details. Copyright © 2017 Elsevier Ltd. All rights reserved.
The Alzheimer's Amyloid-Degrading Peptidase, Neprilysin: Can We Control It?
Nalivaeva, N. N.; Belyaev, N. D.; Zhuravin, I. A.; Turner, A. J.
2012-01-01
The amyloid cascade hypothesis of Alzheimer's disease (AD) postulates that accumulation in the brain of amyloid β-peptide (Aβ) is the primary trigger for neuronal loss specific to this pathology. In healthy brain, Aβ levels are regulated by a dynamic equilibrium between Aβ release from the amyloid precursor protein (APP) and its removal by perivascular drainage or by amyloid-degrading enzymes (ADEs). During the last decade, the ADE family was fast growing, and currently it embraces more than 20 members. There are solid data supporting involvement of each of them in Aβ clearance but a zinc metallopeptidase neprilysin (NEP) is considered as a major ADE. NEP plays an important role in brain function due to its role in terminating neuropeptide signalling and its decrease during ageing or after such pathologies as hypoxia or ischemia contribute significantly to the development of AD pathology. The recently discovered mechanism of epigenetic regulation of NEP by the APP intracellular domain (AICD) opens new avenues for its therapeutic manipulation and raises hope for developing preventive strategies in AD. However, consideration needs to be given to the diverse physiological roles of NEP. This paper critically evaluates general biochemical and physiological functions of NEP and their therapeutic relevance. PMID:22900228
Ryu, Ji-Hwan; Ha, Eun-Mi; Oh, Chun-Taek; Seol, Jae-Hong; Brey, Paul T; Jin, Ingnyol; Lee, Dong Gun; Kim, Jaesang; Lee, Daekee; Lee, Won-Jae
2006-08-09
In the Drosophila gut, reactive oxygen species (ROS)-dependent immunity is critical to host survival. This is in contrast to the NF-kappaB pathway whose physiological function in the microbe-laden epithelia has yet to be convincingly demonstrated despite playing a critical role during systemic infections. We used a novel in vivo approach to reveal the physiological role of gut NF-kappaB/antimicrobial peptide (AMP) system, which has been 'masked' in the presence of the dominant intestinal ROS-dependent immunity. When fed with ROS-resistant microbes, NF-kappaB pathway mutant flies, but not wild-type flies, become highly susceptible to gut infection. This high lethality can be significantly reduced by either re-introducing Relish expression to Relish mutants or by constitutively expressing a single AMP to the NF-kappaB pathway mutants in the intestine. These results imply that the local 'NF-kappaB/AMP' system acts as an essential 'fail-safe' system, complementary to the ROS-dependent gut immunity, during gut infection with ROS-resistant pathogens. This system provides the Drosophila gut immunity the versatility necessary to manage sporadic invasion of virulent pathogens that somehow counteract or evade the ROS-dependent immunity.
Minireview: The Roles of Small RNA Pathways in Reproductive Medicine
Buchold, Gregory M.
2011-01-01
The discovery of small noncoding RNA, including P-element-induced wimpy testis-interacting RNA, small interfering RNA, and microRNA, has energized research in reproductive medicine. In the two decades since the identification of small RNA, first in Caenorhabditis elegans and then in other animals, scientists in many disciplines have made significant progress in elucidating their biology. A powerful battery of tools, including knockout mice and small RNA mimics and antagonists, has facilitated investigation into the functional roles and therapeutic potential of these small RNA pathways. Current data indicate that small RNA play significant roles in normal development and physiology and pathological conditions of the reproductive tracts of females and males. Biologically plausible mRNA targets for these microRNA are aggressively being discovered. The next phase of research will focus on elucidating the clinical utility of small RNA-selective agonists and antagonists. PMID:21546411
Clase, Kari L; Hein, Patrick W; Pelaez, Nancy J
2008-12-01
Physiology as a discipline is uniquely positioned to engage undergraduate students in interdisciplinary research in response to the 2006-2011 National Science Foundation Strategic Plan call for innovative transformational research, which emphasizes multidisciplinary projects. To prepare undergraduates for careers that cross disciplinary boundaries, students need to practice interdisciplinary communication in academic programs that connect students in diverse disciplines. This report surveys policy documents relevant to this emphasis on interdisciplinary training and suggests a changing role for physiology courses in bioscience and engineering programs. A role for a physiology course is increasingly recommended for engineering programs, but the study of physiology from an engineering perspective might differ from the study of physiology as a basic science. Indeed, physiology laboratory courses provide an arena where biomedical engineering and bioscience students can apply knowledge from both fields while cooperating in multidisciplinary teams under specified technical constraints. Because different problem-solving approaches are used by students of engineering and bioscience, instructional innovations are needed to break down stereotypes between the disciplines and create an educational environment where interdisciplinary teamwork is used to bridge differences.
Ergothioneine Is a Secreted Antioxidant in Mycobacterium smegmatis
Williams, Monique J.; Wiid, Ian J.; Hiten, Nicholas F.; Viljoen, Albertus J.; Pietersen, Ray-Dean D.; van Helden, Paul D.
2013-01-01
Ergothioneine (ERG) and mycothiol (MSH) are two low-molecular-weight thiols synthesized by mycobacteria. The role of MSH has been extensively investigated in mycobacteria; however, little is known about the role of ERG in mycobacterial physiology. In this study, quantification of ERG at various points in the growth cycle of Mycobacterium smegmatis revealed that a significant portion of ERG is found in the culture media, suggesting that it is actively secreted. A mutant of M. smegmatis lacking egtD (MSMEG_6247) was unable to synthesize ERG, confirming its role in ERG biosynthesis. Deletion of egtD from wild-type M. smegmatis and an MSH-deficient mutant did not affect their susceptibility to antibiotics tested in this study. The ERG- and MSH-deficient double mutant was significantly more sensitive to peroxide than either of the single mutants lacking either ERG or MSH, suggesting that both thiols play a role in protecting M. smegmatis against oxidative stress and that ERG is able to partly compensate for the loss of MSH. PMID:23629716
The Physiology and Biochemistry of Receptors.
ERIC Educational Resources Information Center
Spitzer, Judy A., Ed.
1983-01-01
The syllabus for a refresher course on the physiology and biochemistry of receptors (presented at the 1983 American Physiological Society meeting) is provided. Topics considered include receptor regulation, structural/functional aspects of receptors for insulin and insulin-like growth factors, calcium channel inhibitors, and role of lipoprotein…
Biernatowska, Agnieszka; Augoff, Katarzyna; Podkalicka, Joanna; Tabaczar, Sabina; Gajdzik-Nowak, Weronika; Czogalla, Aleksander; Sikorski, Aleksander F
2017-11-01
Flotillins are prominent, oligomeric protein components of erythrocyte (RBC) membrane raft domains and are considered to play an important structural role in lateral organization of the plasma membrane. In our previous work on erythroid membranes and giant plasma membrane vesicles (GPMVs) derived from them we have shown that formation of functional domains (resting state rafts) depends on the presence of membrane palmitoylated protein 1 (MPP1/p55), pointing to its new physiological role. Exploration of the molecular mechanism of MPP1 function in organizing membrane domains described here, through searching for its molecular partners in RBC membrane by using different methods, led to the identification of the raft-marker proteins, flotillin 1 and flotillin 2, as hitherto unreported direct MPP1 binding-partners in the RBC membrane. These proteins are found in high molecular-weight complexes in native RBC membrane and, significantly, their presence was shown to be separate from the well-known protein 4.1-dependent interactions of MPP1 with membrane proteins. Furthermore, FLIM analysis revealed that loss of the endogenous MPP1-flotillins interactions resulted in significant changes in RBC membrane-fluidity, emphasizing the physiological importance of such interactions in vivo. Therefore, our data establish a new perspective on the role of MPP1 in erythroid cells and suggests that direct MPP1-flotillins interactions could be the major driving-force behind the formation of raft domains in RBC. Copyright © 2017 The Author(s). Published by Elsevier B.V. All rights reserved.
Frecska, Ede; Szabo, Attila; Winkelman, Michael J; Luna, Luis E; McKenna, Dennis J
2013-09-01
N,N-dimethyltryptamine (DMT) is classified as a naturally occurring serotonergic hallucinogen of plant origin. It has also been found in animal tissues and regarded as an endogenous trace amine transmitter. The vast majority of research on DMT has targeted its psychotropic/psychedelic properties with less focus on its effects beyond the nervous system. The recent discovery that DMT is an endogenous ligand of the sigma-1 receptor may shed light on yet undiscovered physiological mechanisms of DMT activity and reveal some of its putative biological functions. A three-step active uptake process of DMT from peripheral sources to neurons underscores a presumed physiological significance of this endogenous hallucinogen. In this paper, we overview the literature on the effects of sigma-1 receptor ligands on cellular bioenergetics, the role of serotonin, and serotoninergic analogues in immunoregulation and the data regarding gene expression of the DMT synthesizing enzyme indolethylamine-N-methyltransferase in carcinogenesis. We conclude that the function of DMT may extend central nervous activity and involve a more universal role in cellular protective mechanisms. Suggestions are offered for future directions of indole alkaloid research in the general medical field. We provide converging evidence that while DMT is a substance which produces powerful psychedelic experiences, it is better understood not as a hallucinogenic drug of abuse, but rather an agent of significant adaptive mechanisms that can also serve as a promising tool in the development of future medical therapies.
NASA Technical Reports Server (NTRS)
Greenleaf, John E.
1989-01-01
The results of studies on the physiological changes of body fluids and electrolytes during bed rest with and without exercise training are overviewed to determine the effect of exercise and to assess the role of hormonal regulation in fluid-electrolyte responses to hypogravity. Special attention is given to fluid shifts observed in spacecraft personnel during space missions. It is concluded that, despite an apparent uncoupling of prominent hormonal interactions during bed-rest deconditioning (and, possibly, during microgravity), the exercise-training-induced hypervolemia helps to counter the hypohydrostatic-induced dehydration. Thus, it was found that, after nearly a year of spaceflight during which one cosmonaut exercised for about 4 hr per day, the water balance and physiological functioning were not disturbed significantly.
Principles and management of adrenal cancer
DOE Office of Scientific and Technical Information (OSTI.GOV)
Javadpour, N.
1987-01-01
This book provides information on adrenal diseases of latest developments and guides the clinicians in the care of their patients. The book is divided into two parts. The first section gives an overview of the embryology, anatomy, physiology, markers, pathology, imaging and the current progress in the field. The second edition covers specific diseases of the adrenal cortex and medulla. The increasingly significant roles played by steroids, catecholamines, blockers, computed tomography and magnetic resonance are elucidated and discussed. The contents include: Overview of progress; current problems, and perspectives - embryology anatomy, physiology, and biologic markers; pathology; advances in diagnosis; imagingmore » techniques; adrenal disorders in childhood; primary aldosteronism; Cushing's syndrome; carcinoma; pheochromocytoma; neuroblastoma; metastatic disease; surgical management; and subject index.« less
Smith, Kiersten S.; Rudolph, Uwe
2012-01-01
GABAA receptors mediate fast synaptic inhibitory neurotransmission throughout the central nervous system. Recent work indicates a role for GABAA receptors in physiologically modulating anxiety and depression levels. In this review, we summarize research that led to the identification of the essential role of GABAA receptors in counteracting trait anxiety and depression-related behaviors, and research aimed at identifying individual GABAA receptor subtypes involved in physiological and pharmacological modulation of emotions. PMID:21810433
Weeks, E N I; Logan, J G; Birkett, M A; Pickett, J A; Cameron, M M
2013-02-01
The common bed bug, Cimex lectularius, feeds on the blood of mammal and bird hosts, and is a pest of global importance. Semiochemicals are chemicals involved in animal communication that may affect behaviour and/or physiology. Attractive semiochemicals that play a role in mediating bed bug behaviour could be exploited for the development of a highly effective novel monitoring device. Tracking software was used to record the response of bed bugs to volatiles from paper previously exposed to conspecific bugs in a still-air olfactometer illuminated by infrared lights, through a variety of activity variables. The effect of time of day as an extrinsic factor, and sex, stage, mating status and nutritional status as physiological factors on the response of bed bugs to the volatiles was examined. Bed bugs of both sexes and all stages responded to the volatiles from bed bug-exposed papers, showing significant attraction and orientation towards the volatile source whether they were starved or engorged. Confirmation that the physiological factors examined do not affect the response of bed bugs to the volatiles from bed bug-exposed papers provides evidence that these bed bug-derived volatiles contain aggregation cues, as semiochemicals that promote aggregation should by definition be detected by both sexes and all life stages. A device baited with such semiochemicals could play a major role in limiting the impact of the current bed bug resurgence by enabling timely detection of infestations, along with quantitative evaluation of control and effective surveillance of the geographical distribution of the pest species.
What have we learned about GPER function in physiology and disease from knockout mice?
Prossnitz, Eric R.; Hathaway, Helen J.
2015-01-01
Estrogens, predominantly 17β-estradiol, exert diverse effects throughout the body in both normal and patho-physiology, during development and in reproductive, metabolic, endocrine, cardiovascular, nervous, musculoskeletal and immune systems. Estrogen and its receptors also play important roles in carcinogenesis and therapy, particularly for breast cancer. In addition to the classical nuclear estrogen receptors (ERα and ERβ) that traditionally mediate predominantly genomic signaling, the G protein-coupled estrogen receptor GPER has become recognized as a critical mediator of rapid signaling in response to estrogen. Mouse models, and in particular knockout (KO) mice, represent an important approach to understand the functions of receptors in normal physiology and disease. Whereas ERα KO mice display multiple significant defects in reproduction and mammary gland development, ERβ KO phenotypes are more limited, and GPER KO exhibit no reproductive deficits. However, the study of GPER KO mice over the last six years has revealed that GPER deficiency results in multiple physiological alterations including obesity, cardiovascular dysfunction, insulin resistance and glucose intolerance. In addition, the lack of estrogen-mediated effects in numerous tissues of GPER KO mice, studied in vivo or ex vivo, including those of the cardiovascular, endocrine, nervous and immune systems, reveals GPER as a genuine mediator of estrogen action. Importantly, GPER KO mice have also revealed roles for GPER in breast carcinogenesis and metastasis. In combination with the supporting effects of GPER-selective ligands and GPER knockdown approaches, GPER KO mice demonstrate the therapeutic potential of targeting GPER activity in diseases as diverse as obesity, diabetes, multiple sclerosis, hypertension, atherosclerosis, myocardial infarction, stroke and cancer. PMID:26189910
Role of Ergothioneine in Microbial Physiology and Pathogenesis
Cumming, Bridgette M.; Chinta, Krishna C.; Reddy, Vineel P.
2018-01-01
Abstract Significance: L-ergothioneine is synthesized in actinomycetes, cyanobacteria, methylobacteria, and some fungi. In contrast to other low-molecular-weight redox buffers, glutathione and mycothiol, ergothioneine is primarily present as a thione rather than a thiol at physiological pH, which makes it resistant to autoxidation. Ergothioneine regulates microbial physiology and enables the survival of microbes under stressful conditions encountered in their natural environments. In particular, ergothioneine enables pathogenic microbes, such as Mycobacterium tuberculosis (Mtb), to withstand hostile environments within the host to establish infection. Recent Advances: Ergothioneine has been reported to maintain bioenergetic homeostasis in Mtb and protect Mtb against oxidative stresses, thereby enhancing the virulence of Mtb in a mouse model. Furthermore, ergothioneine augments the resistance of Mtb to current frontline anti-TB drugs. Recently, an opportunistic fungus, Aspergillus fumigatus, which infects immunocompromised individuals, has been found to produce ergothioneine, which is important in conidial health and germination, and contributes to the fungal resistance against redox stresses. Critical Issues: The molecular mechanisms of the functions of ergothioneine in microbial physiology and pathogenesis are poorly understood. It is currently not known if ergothioneine is used in detoxification or antioxidant enzymatic pathways. As ergothioneine is involved in bioenergetic and redox homeostasis and antibiotic susceptibility of Mtb, it is of utmost importance to advance our understanding of these mechanisms. Future Directions: A clear understanding of the role of ergothioneine in microbes will advance our knowledge of how this thione enhances microbial virulence and resistance to the host's defense mechanisms to avoid complete eradication. Antioxid. Redox Signal. 28, 431–444. PMID:28791878
Voisin, Tiphaine; Bourinet, Emmanuel; Lory, Philippe
2016-07-01
In this study, we describe a new knock-in (KI) mouse model that allows the study of the H191-dependent regulation of T-type Cav3.2 channels. Sensitivity to zinc, nickel and ascorbate of native Cav3.2 channels is significantly impeded in the dorsal root ganglion (DRG) neurons of this KI mouse. Importantly, we describe that this H191-dependent regulation has discrete but significant effects on the excitability properties of D-hair (down-hair) cells, a sub-population of DRG neurons in which Cav3.2 currents prominently regulate excitability. Overall, this study reveals that the native H191-dependent regulation of Cav3.2 channels plays a role in the excitability of Cav3.2-expressing neurons. This animal model will be valuable in addressing the potential in vivo roles of the trace metal and redox modulation of Cav3.2 T-type channels in a wide range of physiological and pathological conditions. Cav3.2 channels are T-type voltage-gated calcium channels that play important roles in controlling neuronal excitability, particularly in dorsal root ganglion (DRG) neurons where they are involved in touch and pain signalling. Cav3.2 channels are modulated by low concentrations of metal ions (nickel, zinc) and redox agents, which involves the histidine 191 (H191) in the channel's extracellular IS3-IS4 loop. It is hypothesized that this metal/redox modulation would contribute to the tuning of the excitability properties of DRG neurons. However, the precise role of this H191-dependent modulation of Cav3.2 channel remains unresolved. Towards this goal, we have generated a knock-in (KI) mouse carrying the mutation H191Q in the Cav3.2 protein. Electrophysiological studies were performed on a subpopulation of DRG neurons, the D-hair cells, which express large Cav3.2 currents. We describe an impaired sensitivity to zinc, nickel and ascorbate of the T-type current in D-hair neurons from KI mice. Analysis of the action potential and low-threshold calcium spike (LTCS) properties revealed that, contrary to that observed in WT D-hair neurons, a low concentration of zinc and nickel is unable to modulate (1) the rheobase threshold current, (2) the afterdepolarization amplitude, (3) the threshold potential necessary to trigger an LTCS or (4) the LTCS amplitude in D-hair neurons from KI mice. Together, our data demonstrate that this H191-dependent metal/redox regulation of Cav3.2 channels can tune neuronal excitability. This study validates the use of this Cav3.2-H191Q mouse model for further investigations of the physiological roles thought to rely on this Cav3.2 modulation. © 2016 The Authors. The Journal of Physiology © 2016 The Physiological Society.
Savage, Jessica A; Clearwater, Michael J; Haines, Dustin F; Klein, Tamir; Mencuccini, Maurizio; Sevanto, Sanna; Turgeon, Robert; Zhang, Cankui
2016-04-01
Despite the crucial role of carbon transport in whole plant physiology and its impact on plant-environment interactions and ecosystem function, relatively little research has tried to examine how phloem physiology impacts plant ecology. In this review, we highlight several areas of active research where inquiry into phloem physiology has increased our understanding of whole plant function and ecological processes. We consider how xylem-phloem interactions impact plant drought tolerance and reproduction, how phloem transport influences carbon allocation in trees and carbon cycling in ecosystems and how phloem function mediates plant relations with insects, pests, microbes and symbiotes. We argue that in spite of challenges that exist in studying phloem physiology, it is critical that we consider the role of this dynamic vascular system when examining the relationship between plants and their biotic and abiotic environment. © 2015 John Wiley & Sons Ltd.
The barley anion channel, HvALMT1, has multiple roles in guard cell physiology and grain metabolism.
Xu, Muyun; Gruber, Benjamin D; Delhaize, Emmanuel; White, Rosemary G; James, Richard A; You, Jiangfeng; Yang, Zhenming; Ryan, Peter R
2015-01-01
The barley (Hordeum vulgare) gene HvALMT1 encodes an anion channel in guard cells and in certain root tissues indicating that it may perform multiple roles. The protein localizes to the plasma membrane and facilitates malate efflux from cells when constitutively expressed in barley plants and Xenopus oocytes. This study investigated the function of HvALMT1 further by identifying its tissue-specific expression and by generating and characterizing RNAi lines with reduced HvALMT1 expression. We show that transgenic plants with 18-30% of wild-type HvALMT1 expression had impaired guard cell function. They maintained higher stomatal conductance in low light intensity and lost water more rapidly from excised leaves than the null segregant control plants. Tissue-specific expression of HvALMT1 was investigated in developing grain and during germination using transgenic barley lines expressing the green fluorescent protein (GFP) with the HvALMT1 promoter. We found that HvALMT1 is expressed in the nucellar projection, the aleurone layer and the scutellum of developing barley grain. Malate release measured from isolated aleurone layers prepared from imbibed grain was significantly lower in the RNAi barley plants compared with control plants. These data provide molecular and physiological evidence that HvALMT1 functions in guard cells, in grain development and during germination. We propose that HvALMT1 releases malate and perhaps other anions from guard cells to promote stomatal closure. The likely roles of HvALMT1 during seed development and grain germination are also discussed. © 2014 Scandinavian Plant Physiology Society.
Nitric oxide: a physiologic messenger.
Lowenstein, C J; Dinerman, J L; Snyder, S H
1994-02-01
To review the physiologic role of nitric oxide, an unusual messenger molecule that mediates blood vessel relaxation, neurotransmission, and pathogen suppression. A MEDLINE search of articles published from 1987 to 1993 that addressed nitric oxide and the enzyme that synthesizes it, nitric oxide synthase. Animal and human studies were selected from 3044 articles to analyze the clinical importance of nitric oxide. Descriptions of the structure and function of nitric oxide synthase were selected to show how nitric oxide acts as a biological messenger molecule. Biochemical and physiologic studies were analyzed if the same results were found by three or more independent observers. Two major classes of nitric oxide synthase enzymes produce nitric oxide. The constitutive isoforms found in endothelial cells and neurons release small amounts of nitric oxide for brief periods to signal adjacent cells, whereas the inducible isoform found in macrophages releases large amounts of nitric oxide continuously to eliminate bacteria and parasites. By diffusing into adjacent cells and binding to enzymes that contain iron, nitric oxide plays many important physiologic roles. It regulates blood pressure, transmits signals between neurons, and suppresses pathogens. Excess amounts, however, can damage host cells, causing neurotoxicity during strokes and causing the hypotension associated with sepsis. Nitric oxide is a simple molecule with many physiologic roles in the cardiovascular, neurologic, and immune systems. Although the general principles of nitric oxide synthesis are known, further research is necessary to determine what role it plays in causing disease.
Yan, Cai-Feng; Han, Shi-Jie; Zhou, Yu-Mei; Wang, Cun-Guo; Dai, Guan-Hua; Xiao, Wen-Fa; Li, Mai-He
2012-01-01
For both ecologists and physiologists, foliar physioecology as a function of spatially and temporally variable environmental factors such as sunlight exposure within a tree crown is important for understanding whole tree physiology and for predicting ecosystem carbon balance and productivity. Hence, we studied concentrations of nitrogen (N), non-structural carbohydrates (NSC = soluble sugars + starch), and δ13C in different-aged needles within Pinus koraiensis tree crowns, to understand the needle age- and crown position-related physiology, in order to test the hypothesis that concentrations of N, NSC, and δ13C are needle-age and crown position dependent (more light, more photosynthesis affecting N, NSC, and δ13C), and to develop an accurate sampling strategy. The present study indicated that the 1-yr-old needles had significantly higher concentration levels of mobile carbohydrates (both on a mass and an area basis) and Narea (on an area basis), as well as NSC-N ratios, but significantly lower levels of Nmass (on a mass basis) concentration and specific leaf area (SLA), compared to the current-year needles. Azimuthal (south-facing vs. north-facing crown side) effects were found to be significant on starch [both on a mass (STmass) and an area basis (STarea)], δ13C values, and Narea, with higher levels in needles on the S-facing crown side than the N-facing crown side. Needle Nmass concentrations significantly decreased but needle STmass, STarea, and δ13C values significantly increased with increasing vertical crown levels. Our results suggest that the sun-exposed crown position related to photosynthetic activity and water availability affects starch accumulation and carbon isotope discrimination. Needle age associated with physiological activity plays an important role in determining carbon and nitrogen physiology. The present study indicates that across-scale sampling needs to carefully select tissue samples with equal age from a comparable crown position. PMID:22493732
Role of plasma kallikrein in diabetes and metabolism.
Feener, E P; Zhou, Q; Fickweiler, W
2013-09-01
Plasma kallikrein (PK) is a serine protease generated from plasma prekallikrein, an abundant circulating zymogen expressed by the Klkb1 gene. The physiological actions of PK have been primarily attributed to its production of bradykinin and activation of coagulation factor XII, which promotes inflammation and the intrinsic coagulation pathway. Recent genetic, molecular, and pharmacological studies of PK have provided further insight into its role in physiology and disease. Genetic analyses have revealed common Klkb1 variants that are association with blood metabolite levels, hypertension, and coagulation. Characterisation of animal models with Klkb1 deficiency and PK inhibition have demonstrated effects on inflammation, vascular function, blood pressure regulation, thrombosis, haemostasis, and metabolism. These reports have also identified a host of PK substrates and interactions, which suggest an expanded physiological role for this protease beyond the bradykinin system and coagulation. The review summarises the mechanisms that contribute to PK activation and its emerging role in diabetes and metabolism.
van den Bogaard, Ellen; Podolsky, Michael; Smits, Jos; Cui, Xiao; John, Christian; Gowda, Krishne; Desai, Dhimant; Amin, Shantu; Schalkwijk, Joost; Perdew, Gary H.
2015-01-01
Stimulation of the aryl hydrocarbon receptor (AHR) by xenobiotics is known to affect epidermal differentiation and skin barrier formation. The physiological role of endogenous AHR signaling in keratinocyte differentiation is not known. We used murine and human skin models to address the hypothesis that AHR activation is required for normal keratinocyte differentiation. Using transcriptome analysis of Ahr-/- and Ahr+/+ murine keratinocytes, we found significant enrichment of differentially expressed genes linked to epidermal differentiation. Primary Ahr-/- keratinocytes showed a significant reduction in terminal differentiation gene and protein expression, similar to Ahr+/+ keratinocytes treated with AHR antagonists GNF351 and CH223191, or the selective AHR modulator (SAhRM), SGA360. In vitro keratinocyte differentiation led to increased AHR levels and subsequent nuclear translocation, followed by induced CYP1A1 gene expression. Monolayer cultured primary human keratinocytes treated with AHR antagonists also showed an impaired terminal differentiation program. Inactivation of AHR activity during human skin equivalent development severely impaired epidermal stratification, terminal differentiation protein expression and stratum corneum formation. As disturbed epidermal differentiation is a main feature of many skin diseases, pharmacological agents targeting AHR signaling or future identification of endogenous keratinocyte-derived AHR ligands should be considered as potential new drugs in dermatology. PMID:25602157
Role of right pregenual anterior cingulate cortex in self-conscious emotional reactivity
Sollberger, Marc; Seeley, William W.; Rankin, Katherine P.; Ascher, Elizabeth A.; Rosen, Howard J.; Miller, Bruce L.; Levenson, Robert W.
2013-01-01
Self-conscious emotions such as embarrassment arise when one’s actions fail to meet salient social expectations and are accompanied by marked physiological and behavioral activation. We investigated the neural correlates of self-conscious emotional reactivity in 27 patients with behavioral variant frontotemporal dementia (bvFTD), a neurodegenerative disease that disrupts self-conscious emotion and targets brain regions critical for emotional functioning early in the disease course, and in 33 healthy older controls. Subjects participated in an embarrassing karaoke task in which they watched a video clip of themselves singing. They also watched a sad film clip; these data were used to control for non-self-conscious emotional reactivity in response to audiovisual stimuli. Using Freesurfer to quantify regional brain volumes from structural magnetic resonance imaging, right pregenual anterior cingulate cortex (pACC) gray matter volume was the only brain region that was a significant predictor of self-conscious emotion. Smaller pACC volume was associated with attenuated physiological and behavioral self-conscious emotional reactivity, and this relationship was not specific to diagnosis. We argue that these results reflect the significant role that right pACC plays in the visceromotor responding that accompanies self-conscious emotion and that neurodegeneration in this region may underlie the self-conscious emotional decline seen in bvFTD. PMID:22345371
Role of right pregenual anterior cingulate cortex in self-conscious emotional reactivity.
Sturm, Virginia E; Sollberger, Marc; Seeley, William W; Rankin, Katherine P; Ascher, Elizabeth A; Rosen, Howard J; Miller, Bruce L; Levenson, Robert W
2013-04-01
Self-conscious emotions such as embarrassment arise when one's actions fail to meet salient social expectations and are accompanied by marked physiological and behavioral activation. We investigated the neural correlates of self-conscious emotional reactivity in 27 patients with behavioral variant frontotemporal dementia (bvFTD), a neurodegenerative disease that disrupts self-conscious emotion and targets brain regions critical for emotional functioning early in the disease course, and in 33 healthy older controls. Subjects participated in an embarrassing karaoke task in which they watched a video clip of themselves singing. They also watched a sad film clip; these data were used to control for non-self-conscious emotional reactivity in response to audiovisual stimuli. Using Freesurfer to quantify regional brain volumes from structural magnetic resonance imaging, right pregenual anterior cingulate cortex (pACC) gray matter volume was the only brain region that was a significant predictor of self-conscious emotion. Smaller pACC volume was associated with attenuated physiological and behavioral self-conscious emotional reactivity, and this relationship was not specific to diagnosis. We argue that these results reflect the significant role that right pACC plays in the visceromotor responding that accompanies self-conscious emotion and that neurodegeneration in this region may underlie the self-conscious emotional decline seen in bvFTD.
Chu, Xin-Ling; Feng, Ming-Guang; Ying, Sheng-Hua
2016-02-01
Protein ubiquitination is an evolutionarily conserved post-translational modification process in eukaryotes, and it plays an important role in many biological processes. Aspergillus nidulans, a model filamentous fungus, contributes to our understanding of cellular physiology, metabolism and genetics, but its ubiquitination is not completely revealed. In this study, the ubiquitination sites in the proteome of A. nidulans were identified using a highly sensitive mass spectrometry combined with immuno-affinity enrichment of the ubiquitinated peptides. The 4816 ubiquitination sites were identified in 1913 ubiquitinated proteins, accounting for 18.1% of total proteins in A. nidulans. Bioinformatic analysis suggested that the ubiquitinated proteins associated with a number of biological functions and displayed various sub-cellular localisations. Meanwhile, seven motifs were revealed from the ubiquitinated peptides, and significantly over-presented in the different pathways. Comparison of the enriched functional catalogues indicated that the ubiquitination functions divergently during growth of A. nidulans and Saccharomyces cerevisiae. Additionally, the proteins in A. nidulans-specific sub-category (cell growth/morphogenesis) were subjected to the protein interaction analysis which demonstrated that ubiquitination is involved in the comprehensive protein interactions. This study presents a first proteomic view of ubiquitination in the filamentous fungus, and provides an initial framework for exploring the physiological roles of ubiquitination in A. nidulans.
Schumacher, Joseph W.; Schneider, David M.
2011-01-01
The majority of sensory physiology experiments have used anesthesia to facilitate the recording of neural activity. Current techniques allow researchers to study sensory function in the context of varying behavioral states. To reconcile results across multiple behavioral and anesthetic states, it is important to consider how and to what extent anesthesia plays a role in shaping neural response properties. The role of anesthesia has been the subject of much debate, but the extent to which sensory coding properties are altered by anesthesia has yet to be fully defined. In this study we asked how urethane, an anesthetic commonly used for avian and mammalian sensory physiology, affects the coding of complex communication vocalizations (songs) and simple artificial stimuli in the songbird auditory midbrain. We measured spontaneous and song-driven spike rates, spectrotemporal receptive fields, and neural discriminability from responses to songs in single auditory midbrain neurons. In the same neurons, we recorded responses to pure tone stimuli ranging in frequency and intensity. Finally, we assessed the effect of urethane on population-level representations of birdsong. Results showed that intrinsic neural excitability is significantly depressed by urethane but that spectral tuning, single neuron discriminability, and population representations of song do not differ significantly between unanesthetized and anesthetized animals. PMID:21543752
Steenhaut, Priska; Demeyer, Ineke; De Raedt, Rudi; Rossi, Gina
2018-04-01
This study brings more clarity on the inconsistent findings on emotional reactivity differences between older (OA) and younger (YA) adults, by examining the influence of (mal)adaptive personality traits on emotional reactivity and by applying several assessment methods. We recruited 60 YA (25-50 years) and 60 OA (65+ years) from a nonclinical population. We used Visual Analogue Scales to measure subjective reactivity, and facial electromyography (corrugator and zygomaticus reactivity), heart rate, heart rate variability, and skin conductance level to assess physiological reactivity during happy and sad film clips. Results showed that personality influences on emotional reactivity in OA were largely comparable to YA, although the influence of negative emotionality and neuroticism on subjective reactivity in response to the sad film was significantly stronger in OA. It is thus important to assess both subjective and physiological reactivity when comparing age-related differences in OA and YA given the differential relation with personality features.
Dehkhoda, Farhad; Lee, Christine M. M.; Medina, Johan; Brooks, Andrew J.
2018-01-01
The growth hormone receptor (GHR), although most well known for regulating growth, has many other important biological functions including regulating metabolism and controlling physiological processes related to the hepatobiliary, cardiovascular, renal, gastrointestinal, and reproductive systems. In addition, growth hormone signaling is an important regulator of aging and plays a significant role in cancer development. Growth hormone activates the Janus kinase (JAK)–signal transducer and activator of transcription (STAT) signaling pathway, and recent studies have provided a new understanding of the mechanism of JAK2 activation by growth hormone binding to its receptor. JAK2 activation is required for growth hormone-mediated activation of STAT1, STAT3, and STAT5, and the negative regulation of JAK–STAT signaling comprises an important step in the control of this signaling pathway. The GHR also activates the Src family kinase signaling pathway independent of JAK2. This review covers the molecular mechanisms of GHR activation and signal transduction as well as the physiological consequences of growth hormone signaling. PMID:29487568
The effect of choice on the physiology of emotion: An affective startle modulation study
Genevsky, Alexander; Gard, David E.
2014-01-01
The affective startle modulation task has been an important measure in understanding physiological aspects of emotion and motivational responses. Research utilizing this method has relied primarily on a ‘passive’ viewing paradigm, which stands in contrast to everyday life where much of emotion and motivation involves some active choice or agency. The present study investigated the role of choice on the physiology of emotion. Eighty-four participants were randomized into ‘choice’ (n=44) or ‘no-choice’ (n=40) groups distinguished by the ability to choose between stimuli. EMG eye blink responses were recorded in both anticipation and stimulus viewing. Results indicated a significant attenuation of the startle magnitude in choice condition trials (relative to no-choice) across all picture categories and probe times. We interpret these findings as an indication that the act of choice may decrease one’s defensive response, or conversely, lacking choice may heighten the defensive response. Implications for future research are discussed. PMID:22285891
The effect of choice on the physiology of emotion: an affective startle modulation study.
Genevsky, Alexander; Gard, David E
2012-04-01
The affective startle modulation task has been an important measure in understanding physiological aspects of emotion and motivational responses. Research utilizing this method has relied primarily on a 'passive' viewing paradigm, which stands in contrast to everyday life where much of emotion and motivation involves some active choice or agency. The present study investigated the role of choice on the physiology of emotion. Eighty-four participants were randomized into 'choice' (n=44) or 'no-choice' (n=40) groups distinguished by the ability to choose between stimuli. EMG eye blink responses were recorded in both anticipation and stimulus viewing. Results indicated a significant attenuation of the startle magnitude in choice condition trials (relative to no-choice) across all picture categories and probe times. We interpret these findings as an indication that the act of choice may decrease one's defensive response, or conversely, lacking choice may heighten the defensive response. Implications for future research are discussed. Copyright © 2012 Elsevier B.V. All rights reserved.
[Neurogenesis in the adult brain: the demise of a dogma and the advent of new treatments].
Crespel, A; Baldy-Moulinier, M; Lerner Natoli, M
2004-12-01
Since the early sixties, many concepts concerning neurogenesis have been progressively ruled out. Proof of the persistence of a physiological neurogenesis in adult mammals, including humans, raised the concept of a unique precursor cell giving birth to neurons and glial cells. According to this concept, a real continuum between neuroepithelial cells, radial glia and astrocytes exists from the embryonic period to adult age and generates both neurons and glial cells. Different factors, either secreted in situ or transported by blood, can influence this physiological neurogenesis process. The targets and role of newborn neurons are not clearly understood. In pathological conditions (ischemia, epilepsy, lesions), the physiological neurogenesis process is enhanced; however the significance of this neurogenesis excess (beneficial or deleterious) is not completely known. Advances in understanding the regulation of neurogenesis in these different conditions represent hopes of new therapeutic procedures, not only by improving the control of differentiation and survival of transplanted stem cells, but also by the possibility of modifying the processes of "endogenous neurogenesis".
Lathe, R
2001-05-01
Hippocampal lesions produce memory deficits, but the exact function of the hippocampus remains obscure. Evidence is presented that its role in memory may be ancillary to physiological regulation. Molecular studies demonstrate that the hippocampus is a primary target for ligands that reflect body physiology, including ion balance and blood pressure, immunity, pain, reproductive status, satiety and stress. Hippocampal receptors are functional, probably accessible to their ligands, and mediate physiological and cognitive changes. This argues that an early role of the hippocampus may have been in sensing soluble molecules (termed here 'enteroception') in blood and cerebrospinal fluid, perhaps reflecting a common evolutionary origin with the olfactory system ('exteroception'). Functionally, hippocampal enteroception may reflect feedback control; evidence is reviewed that the hippocampus modulates body physiology, including the activity of the hypothalamus-pituitary-adrenal axis, blood pressure, immunity, and reproductive function. It is suggested that the hippocampus operates, in parallel with the amygdala, to modulate body physiology in response to cognitive stimuli. Hippocampal outputs are predominantly inhibitory on downstream neuroendocrine activity; increased synaptic efficacy in the hippocampus (e.g. long-term potentiation) could facilitate throughput inhibition. This may have implications for the role of the hippocampus and long-term potentiation in memory.
Students' Motivation toward Laboratory Work in Physiology Teaching
ERIC Educational Resources Information Center
Dohn, Niels Bonderup; Fago, Angela; Overgaard, Johannes; Madsen, Peter Teglberg; Malte, Hans
2016-01-01
The laboratory has been given a central role in physiology education, and teachers report that it is motivating for students to undertake experimental work on live animals or measuring physiological responses on the students themselves. Since motivation is a critical variable for academic learning and achievement, then we must concern ourselves…
Fedorov, V I
2007-01-01
Description of the history of cybernetics origin and physiology influence on it is given. Role of Russian and foreign physiologists in becoming and development of cybernetics and contribution of cybernetic theorists (N. Wiener and A.A. Lyapunov) to physiology are shown. Becoming and a modern state of various sections of cybernetic physiology and perspective of connection of cybernetics with integrative physiology are considered.
Zhang, Y T; Frank, C B; Rangayyan, R M; Bell, G D
1992-09-01
Analysis of vibration signals emitted by the knee joint has the potential for the development of a noninvasive procedure for the diagnosis and monitoring of knee pathology. In order to obtain as much information as possible from the power density spectrum of the knee vibration signal, it is necessary to identify the physiological factors (or physiologically relevant parameters) that shape the spectrum. This paper presents a mathematical model for knee vibration signals, in particular the physiological patello-femoral pulse (PFP) train produced by slow knee movement. It demonstrates through the mathematical model that the repetition rate of the physiological PFP train introduces repeated peaks in the power spectrum, and that it affects the spectrum mainly at low frequencies. The theoretical results also show that the spectral peaks at multiples of the PFP repetition rate become more evident when the variance of the interpulse interval (IPI) is small, and that these spectral peaks shift toward higher frequencies with increasing PFP repetition rates. To evaluate the mathematical model, a simulation algorithm was developed, which generates PFP signals with adjustable repetition rate and IPI variance. Signals generated by simulation were seen to possess representative spectral characteristics typically observed in physiological PFP signals. This simulation procedure allows an interactive examination of several factors which affect the PFP train spectrum. Finally, in vivo measurements of physiological PFP signals of normal volunteers are presented. Results of simulations and analysis of signals recorded from human subjects support the mathematical model's prediction that the IPI statistics play a very significant role in determining the low-end power spectrum of the physiological PFP signal.(ABSTRACT TRUNCATED AT 250 WORDS)
Deliberate acquisition of competence in physiological breech birth: A grounded theory study.
Walker, Shawn; Scamell, Mandie; Parker, Pam
2018-06-01
Research suggests that the skill and experience of the attendant significantly affect the outcomes of vaginal breech births, yet practitioner experience levels are minimal within many contemporary maternity care systems. Due to minimal experience and cultural resistance, few practitioners offer vaginal breech birth, and many practice guidelines and training programmes recommend delivery techniques requiring supine maternal position. Fewer practitioners have skills to support physiological breech birth, involving active maternal movement and choice of birthing position, including upright postures such as kneeling, standing, squatting, or on a birth stool. How professionals learn complex skills contrary to those taught in their local practice settings is unclear. How do professionals develop competence and expertise in physiological breech birth? Nine midwives and five obstetricians with experience facilitating upright physiological breech births participated in semi-structured interviews. Data were analysed iteratively using constructivist grounded theory methods to develop an empirical theory of physiological breech skill acquisition. Among the participants in this research, the deliberate acquisition of competence in physiological breech birth included stages of affinity with physiological birth, critical awareness, intention, identity and responsibility. Expert practitioners operating across local and national boundaries guided less experienced practitioners. The results depict a specialist learning model which could be formalised in sympathetic training programmes, and evaluated. It may also be relevant to developing competence in other specialist/expert roles and innovative practices. Deliberate development of local communities of practice may support professionals to acquire elusive breech skills in a sustainable way. Copyright © 2017 Australian College of Midwives. Published by Elsevier Ltd. All rights reserved.
Physiological response of BSC phototrophic community to EPS removal
NASA Astrophysics Data System (ADS)
Adessi, Alessandra; Cruz de Carvalho, Ricardo; Silvestre, Susana; Rossi, Federico; Mugnai, Gianmarco; Marques da Silva, Jorge; Branquinho, Cristina; De Philippis, Roberto
2015-04-01
Biological Soil Crusts (BSCs) are associations between soil particles and varying proportions of cyanobacteria, heterotrophic bacteria, algae, fungi, lichens and mosses. BSCs play a major role in soil stabilization, and in drylands have been well acknowledged for mitigating desertification effects. Amongst the wide diversity of organisms that compose BSCs, cyanobacteria are the first primary producers: they colonize nutrient-limited soils, modifying the micro-environment through the excretion of large amounts of extracellular polymeric substances (EPSs). EPSs represent a huge carbon and nitrogen source for other inhabitants of the crust, are three-dimensionally spread through the first millimeters of the soil, and have a recognized role in influencing the hydrological behavior of the crust. The aim of this study was to investigate the possible role that EPSs play in the physiology of the phototrophic community residing on a light crust (without mosses or lichens, thus mainly inhabited by cyanobacteria and algae). In particular it was investigated whether the three-dimensional matrix in which EPSs are organized allowed light distribution and diffusion inside the crust, thus influencing photosynthesis. Non-invasive techniques were used to extract the polymeric matrix and to analyze photosynthetic performances in native and extracted BSC samples. Preliminary results suggested that the mild extraction protocol allowed to remove a portion of the matrix, and that this treatment revealed highly significant differences in the optical properties of the crusts comparing native and extracted samples. The extraction did not affect cell viability, as samples after the extraction were still photosynthetically active. However, chlorophyll variable fluorescence was significantly lower in the extracted samples than in native ones, and susceptibility to photoinhibition was significantly modified. Evaluating the role of the EPSs in the community is essential to further understand the equilibrium of such fragile systems as BSCs. Indeed, an effect on the photosynthetic activity would be linked to primary production, thus to the existence, survival, and development of BSCs themselves. Acknowledgments: The Authors would like to acknowledge COST Action ES1104 for funding an STSM on this topic.
Initiation of TNF Inhibitor Therapy and Change in Physiologic Measures in Psoriasis
Wu, Jashin J.; Liu, Liyan; Asgari, Maryam M.; Curtis, Jeffrey R.; Harrold, Leslie; Salman, Craig; Herrinton, Lisa J.
2014-01-01
Background Psoriasis may predispose to cardiovascular disease and diabetes. However, the role of TNF inhibitor in mediating this risk is controversial. Objective To assess this relationship, we estimated change in metabolic physiologic measures before and after initiation of TNF inhibitor therapy compared with methotrexate therapy among psoriasis patients. Methods We conducted a retrospective cohort study, 2007–2012, using computerized clinical data for 1,274 new users of TNF inhibitor and 979 new users of methotrexate therapy to compare change in blood pressure, lipids, triglycerides, fasting plasma glucose, and body mass index before and after start of TNF inhibitors or methotrexate. The study was restricted to new users. We computed within-person change in each measure, so that each patient served as their own control. In addition, we compared TNF inhibitor patients to methotrexate patients, by computing the adjusted difference in their group means. In secondary analyses, we examined phototherapy as a comparator. Results Among starters of TNF inhibitor and MTX therapy, within-person change in physiologic measures at 6 months did not differ significantly. We observed no important or significant changes in any of the physiologic measures with initiation of TNF inhibitor compared with methotrexate. The same results were found in subgroup analyses focused on men, and on those with hypertension, diabetes mellitus, or obesity. The same results were observed with phototherapy, except that diastolic blood pressure declined by 0.6 mm Hg within-person during the 6 months after starting phototherapy (p<0.05). Conclusions The study provides no evidence for improvement of physiologic measures associated with the metabolic syndrome resulting from TNF inhibitor use for psoriasis. PMID:24708441
Komosinska-Vassev, Katarzyna; Olczyk, Pawel; Winsz-Szczotka, Katarzyna; Kuznik-Trocha, Kornelia; Klimek, Katarzyna; Olczyk, Krystyna
2012-02-13
The authors studied the role of increased oxidative stress in the development of oxidative protein damage and extracellular matrix (ECM) components in ageing. The age- and gender-associated disturbances in connective tissue metabolism were evaluated by the plasma chondroitin sulphated glycosaminoglycans (CS-GAG) and non-sulphated GAG-hyaluronan (HA) measurements. Plasma concentration of advanced oxidation protein products (AOPP) was analysed in order to assess oxidative protein damage and evaluate the possible deleterious role of oxidative phenomenon on tissue proteoglycans' metabolism during the physiological ageing process. Sulphated and non-sulphated GAGs as well as AOPP were quantified in plasma samples from 177 healthy volunteers. A linear age-related decline of plasma CS-GAG level was found in this study (r=-0.46; p<0.05). In contrast, HA concentrations rise gradually with age (r=0.44; p<0.05) in plasma samples. For both ECM components, the observed differences were not gender-specific. A strong age-dependent relationship has been shown in regard to AOPP. AOPP levels significantly increased with age (r=0.63; p<0.05), equally strongly in both men (r=0.69; p<0.05) and women (r=0.57; p<0.05) during physiological ageing. A significant correlation was found between the concentrations of AOPP and both CS-GAG (r=-0.31; p<0.05) and HA (r=0.33; p<0.05). Proceeding with age changes in the ECM are reflected by CS-GAG and HA plasma levels. Strong correlations between AOPP and ECM components indicate that oxidative stress targets protein and non-protein components of the connective tissue matrix during human ageing.
Wu, Tao; Sun, Lu; ZhuGe, Fen; Guo, Xichao; Zhao, Zhining; Tang, Ruiqi; Chen, Qinping; Chen, Lin; Kato, Hisanori; Fu, Zhengwei
2011-12-01
The timing of meals has been suggested to play an important role in circadian regulation and metabolic health. Three meals a day is a well-established human feeding habit, which in today's lifestyle may or may not be followed. The aim of this study was to test whether the absence of breakfast or supper significantly affects the circadian system and physiological function. The authors developed a rat model for their daily three meals study, whereby animals were divided into three groups (three meals, TM; no first meal, NF; no last meal, NL) all fed with the same amount of food every day. Rats in the NF group displayed significantly decreased levels of plasma triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and glucose in the activity phase, accompanied by delayed circadian phases of hepatic peripheral clock and downstream metabolic genes. Rats in the NL group showed lower concentration of plasma TC, HDL-C, and glucose in the rest phase, plus reduced adipose tissue accumulation and body weight gain. Real-time polymerase chain reaction (PCR) analysis indicated an attenuated rhythm in the food-entraining pathway, including down-regulated expression of the clock genes Per2, Bmal1, and Rev-erbα, which may further contribute to the delayed and decreased expression of FAS in lipogenesis in this group. Our findings are consistent with the conclusion that the daily first meal determines the circadian phasing of peripheral clocks, such as in the liver, whereas the daily last meal tightly couples to lipid metabolism and adipose tissue accumulation, which suggests differential physiological effects and function of the respective meal timings.
Enhanced production of IGF-I in the lungs of fibroproliferative ARDS patients.
Andonegui, Graciela; Krein, Peter M; Mowat, Connie; Brisebois, Ronald; Doig, Christopher; Green, Francis H Y; Léger, Caroline; Winston, Brent W
2014-11-01
Insulin-Like Growth Factor I (IGF-I) has been identified in the lungs of individuals with fibrotic lung diseases. In a previous retrospective study, we showed enhanced IGF-I immunoreactivity in individuals with fibroproliferative acute respiratory distress syndrome (FP-ARDS), but we were unable to determine if this correlation was causative. This study was undertaken to prospectively investigate whether IGF-I expression correlated with the fibroproliferative process and whether IGF-I was induced and made in the lungs. We measured IGF-I and procollagen III peptide (PCP-III) in the epithelial lining fluid (ELF) from controls, early ALI/ARDS patients and FP-ARDS patients. We also measured IGF-I mRNA and immunoreactivity from controls and FP-ARDS patient lung biopsies. We determined the level of lung permeability by measuring albumin and urea levels in ELF and serum. Our data show that IGF-I is significantly increased in the ELF in FP-ARDS patients. A significant correlation between IGF-I and PCP-III in the ELF of FP-ARDS patients is found. IGF-I mRNA is elevated in the FP-ARDS lung biopsies. Our data suggest that IGF-I found in the lungs of FP-ARDS patients results from both increased lung permeability and local production of IGF-I. The role of IGF-I in the fibroproliferative process in the lungs has recently been confirmed in an animal model of lung fibroproliferation. This study importantly suggest that IGF-I protein is made in the lungs of FP-ARDS patients and correlates with increased levels of ELF PCP-III, implicating a role for IGF-I in the fibroproliferative process in humans. © 2014 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.
Murata, Takayuki; Isomura, Hiroki; Yamashita, Yoriko; Toyama, Shigenori; Sato, Yoshitaka; Nakayama, Sanae; Kudoh, Ayumi; Iwahori, Satoko; Kanda, Teru; Tsurumi, Tatsuya
2009-06-20
The Epstein-Barr virus (EBV) BGLF4 gene product is the only protein kinase encoded by the virus genome. In order to elucidate its physiological roles in viral productive replication, we here established a BGLF4-knockout mutant and a revertant virus. While the levels of viral DNA replication of the deficient mutant were equivalent to those of the wild-type and the revertant, virus production was significantly impaired. Expression of the BGLF4 protein in trans fully complemented the low yield of the mutant virus, while expression of a kinase-dead (K102I) form of the protein failed to restore the virus titer. These results demonstrate that BGLF4 plays a significant role in production of infectious viruses and that the kinase activity is crucial.
Developments in neonatal care and nursing responses.
Healy, Patricia; Fallon, Anne
This article reviews the origins and evolution of neonatology and considers the role of the neonatal nurse within this specialty. Neonatal nurses are a vital part of the neonatal team that provides care for sick babies. The nursing care required by sick babies and their families on a neonatal unit can be variable and complex. The past century has seen significant changes in the role of the neonatal nurse. This has come about through dramatic technological developments on neonatal units, an increased understanding of neonatal physiology and pathology, changes in the education of neonatal nurses, and active and ongoing clinical research within the specialty. The resulting significant advances in neonatal care, including that provided by neonatal nurses, have made a crucial and steadfast contribution to marked improvements in neonatal outcomes.
2012-01-01
Background Melatonin regulates several physiological processes and its powerful action as antioxidant has been widely reported. Melatonin acts modulating the immune system, showing a protective effect on the cardiovascular system and improving vaccine administration as an adjuvant-like agent. Here, we have investigated the role of melatonin as an adjuvant of the Clostridium perfringens vaccine in prepartum sheep and whether melatonin modulates platelet physiology during peripartum. Results The experiments were carried out in peripartum sheep from a farm located in an area of Mediterranean-type ecosystem. Plasma melatonin levels were determined by ELISA and sheep platelet aggregation was monitored using an aggregometer. Here we demonstrated for the first time that plasma melatonin concentration were higher in pregnant (125 pg/mL) than in non-pregnant sheep (15 pg/mL; P < 0.05). Administration of melatonin prepartum did not significantly modify platelet function but significantly improved the immune response to vaccination against C. perfringens. Conclusion Administration of melatonin as an adjuvant provides a significant improvement in the immune response to vaccine administration prepartum against C. perfringens. PMID:22716226
The Roles of Glutamine in the Intestine and Its Implication in Intestinal Diseases
Kim, Min-Hyun; Kim, Hyeyoung
2017-01-01
Glutamine, the most abundant free amino acid in the human body, is a major substrate utilized by intestinal cells. The roles of glutamine in intestinal physiology and management of multiple intestinal diseases have been reported. In gut physiology, glutamine promotes enterocyte proliferation, regulates tight junction proteins, suppresses pro-inflammatory signaling pathways, and protects cells against apoptosis and cellular stresses during normal and pathologic conditions. As glutamine stores are depleted during severe metabolic stress including trauma, sepsis, and inflammatory bowel diseases, glutamine supplementation has been examined in patients to improve their clinical outcomes. In this review, we discuss the physiological roles of glutamine for intestinal health and its underlying mechanisms. In addition, we discuss the current evidence for the efficacy of glutamine supplementation in intestinal diseases. PMID:28498331
Gibson, Carolyn; Matthews, Karen; Thurston, Rebecca
2014-01-01
Objective To examine the role of physical activity in menopausal hot flashes. Competing models conceptualize physical activity as a risk or protective factor for hot flashes. Few studies have examined this relationship prospectively using physiologic measures of hot flashes and physical activity. Design Over two 48 hour-periods, 51 participants wore a physiologic hot flash monitor and activity monitor, and reported their hot flashes in an electronic diary. Physiologic hot flashes, reported hot flashes and reported hot flashes without physiological corroboration were related to activity changes using hierarchical generalized linear modeling, adjusting for potential confounders. Setting Community. Patients Midlife women. Interventions None. Main Outcome Measures Physiologically-detected hot flashes and reported hot flashes with and without physiologic corroboration. Results Hot flash reports without physiologic corroboration were more likely after activity increases (OR 1.04, 95% CI: 1.00-1.10, p=.01), particularly among women with higher levels of depressive symptoms (interaction p=.02). No other types of hot flashes were related to physical activity. Conclusion Acute increases in physical activity were associated with increased reporting of hot flashes lacking physiologic corroboration, particularly among women with depressive symptoms. Clinicians should consider the role of symptom perception and reporting in relations between physical activity and hot flashes. PMID:24491454
Chen, Jinghua; Ren, Yichao; Wang, Guodong; Xia, Bin; Li, Yuquan
2018-01-01
Bioflocs are rich in various probiotics and bioactive compounds, which play an important role in improving growth and health status of aquatic organisms. A 60-day experiment was conducted to investigate the effects of dietary supplementation of biofloc on growth performance, digestive enzyme activity, physiological stress, antioxidant status, expression of immune-related genes and disease resistance of sea cucumber Apostichopus japonicus. Juvenile sea cucumbers were fed five experimental diets containing graded levels of biofloc from 0% to 20% (referred as B0, B5, B10, B15 and B20, respectively). The results showed that the sea cucumbers at dietary supplementation levels of 10%-15% biofloc had significantly higher specific growth rate (SGR) compared to control group (diet B0). Digestive enzyme activity increased with the increasing of dietary biofloc level, while no significant difference was found between diets B15 and B20. Dietary supplementation of biofloc also had significant influences on physiological stress parameters except for lactate. There was no significant discrepancy in total coelomocytes counts (TCC) in coelomic fluid of sea cucumber between the treatments. Phagocytosis and respiratory burst of cellular immune at 15% and 20% biofloc levels were significantly higher than those of control group. Significant increases in superoxide dismutase (SOD), total nitric oxide synthase (T-NOS), lysozyme (LSZ), acid phosphatase (ACP) and alkaline phosphatase (AKP) activities of sea cucumber were found at highest dietary supplementation level of 20% biofloc. The expression patterns of immune-related genes (i.e., Hsp90, Hsp70, p105, Rel, NOS and LSZ) in tissues of sea cucumber were analyzed between the experimental diets, and a general trend of up-regulation was observed at higher biofloc levels. Furthermore, dietary 10%-20% biofloc significantly reduced cumulative mortality of sea cucumber after being challenged with Vibrio splendidus. In conclusion, dietary supplementation of biofloc could improve growth performance of A. japonicus, by increasing digestive enzyme activity, releasing physiological stress, enhancing immune response and disease resistance of sea cucumber. The suitable supplemental level of approximately 15% biofloc was recommended in the present study. Copyright © 2017 Elsevier Ltd. All rights reserved.
Calcium antagonists. A role in the management of cyanide poisoning
DOE Office of Scientific and Technical Information (OSTI.GOV)
Maduh, E.U.; Porter, D.W.; Baskin, S.I.
1993-12-31
The physiological role of calcium was demonstrated by Ringer (1883) when he linked the omission of calcium (Ca++) from the bathing medium to the induction of cardiac arrest in the isolated frog heart. This observation established that Ca++ controlled muscle contraction but it was not until the autumn of 1963 that the specific pharmacological significance of this contribution was realised by Fleckenstein (1964), leading to the development of Ca++ antagonism as a concept in drug action (Fleckenstein 1977). Identifying the precise role of Ca++ ions in toxic cell injury and tissue death attributable to drug and chemical intoxication has laggedmore » behind developments in Ca++ physiology and pharmacology and to date, much remains to be learned, although studies aimed at characterising the role of Ca++ in cytotoxic cell injury are receiving intense attention (Bondy Komulainen 1988; Maduh et al. l988a, l99Oa,b; Orrenius et al. 1989; Trump et al. 1989). On the other hand, the importance of cyanide as a poison has been known from antiquity (for references to earlier literature see Baskin Fricke 1992; Solomonson 1981). In experimental cyanide poisoning, recent studies have examined alterations in cell Ca++ and the influence of Ca++ antagonists in the management of this chemical toxicological emergency. These efforts have principally focused on the cellular Ca++ homeostasis system, its interrelationship with cellular components, and its susceptibility to cyanide action.« less
Moulin, Thierry
2013-01-01
Balzac wrote his novels during a time of great literary and scientific change. Romanticism gave way to the school of realism, of which Balzac could be considered the founder. It was via realism, where both the positive and negative aspects of life were depicted, that doctors naturally gained a much more active role in novels. In conjunction with this was the development of science and medicine, which fascinated Balzac, also leading to the significant and prevalent role of doctors in his works. His fascination with the sciences led to him to gain many acquaintances and much knowledge in the medical domain, especially in neuropsychiatry and physiology. His fictional doctors, such as Desplein and Bianchon, thus demonstrate considerable knowledge of pathology, physiology, and neuropsychiatry. The doctors in Balzac's novels can be grouped into four categories: provincial doctors, Parisian doctors, country doctors, and military doctors. They were most often fictitious representations of real individuals (e.g. Guillaume Dupuytren), and often symbolize schools of thought which were in vogue at the time. In addition to the accurate scientific depiction of doctors, it must be noted that his doctors not only played an active role in clinically assessing their patients, but also had a sociological role in assessing society; it is through his doctors that Balzac gave his opinion of the world in which he lived. Copyright © 2013 S. Karger AG, Basel.
Physiological Importance of Hydrogen Sulfide: Emerging Potent Neuroprotector and Neuromodulator
Chung, Hyung-Joo
2016-01-01
Hydrogen sulfide (H2S) is an emerging neuromodulator that is considered to be a gasotransmitter similar to nitrogen oxide (NO) and carbon monoxide (CO). H2S exerts universal cytoprotective effects and acts as a defense mechanism in organisms ranging from bacteria to mammals. It is produced by the enzymes cystathionine β-synthase (CBS), cystathionine ϒ-lyase (CSE), 3-mercaptopyruvate sulfurtransferase (MST), and D-amino acid oxidase (DAO), which are also involved in tissue-specific biochemical pathways for H2S production in the human body. H2S exerts a wide range of pathological and physiological functions in the human body, from endocrine system and cellular longevity to hepatic protection and kidney function. Previous studies have shown that H2S plays important roles in peripheral nerve regeneration and degeneration and has significant value during Schwann cell dedifferentiation and proliferation but it is also associated with axonal degradation and the remyelination of Schwann cells. To date, physiological and toxic levels of H2S in the human body remain unclear and most of the mechanisms of action underlying the effects of H2S have yet to be fully elucidated. The primary purpose of this review was to provide an overview of the role of H2S in the human body and to describe its beneficial effects. PMID:27413423
Microbiota, immunity and the liver.
Vaikunthanathan, T; Safinia, N; Lombardi, G; Lechler, R I
2016-03-01
The gut harbors a complex community of over 100 trillion microbial cells known to exist in symbiotic harmony with the host influencing human physiology, metabolism, nutrition and immune function. It is now widely accepted that perturbations of this close partnership results in the pathogenesis of several major diseases with increasing evidence highlighting their role outside of the intestinal tract. The intimate proximity and circulatory loop of the liver and the gut has attracted significant attention regarding the role of the microbiota in the development and progression of liver disease. Here we give an overview of the interaction between the microbiota and the immune system and focus on their convincing role in both the propagation and treatment of liver disease. Copyright © 2016. Published by Elsevier B.V.
Endogenous Pyrogen Physiology.
ERIC Educational Resources Information Center
Beisel, William R.
1980-01-01
Discusses the physiology of endogenous pyrogen (EP), the fever-producing factor of cellular origin. Included are: its hormone-like role, its molecular nature, bioassay procedures, cellular production and mechanisms of EP action. (SA)
Todd, Jocelyn N; Maak, Travis G; Ateshian, Gerard A; Maas, Steve A; Weiss, Jeffrey A
2018-03-01
Osteoarthritis of the hip can result from mechanical factors, which can be studied using finite element (FE) analysis. FE studies of the hip often assume there is no significant loss of fluid pressurization in the articular cartilage during simulated activities and approximate the material as incompressible and elastic. This study examined the conditions under which interstitial fluid load support remains sustained during physiological motions, as well as the role of the labrum in maintaining fluid load support and the effect of its presence on the solid phase of the surrounding cartilage. We found that dynamic motions of gait and squatting maintained consistent fluid load support between cycles, while static single-leg stance experienced slight fluid depressurization with significant reduction of solid phase stress and strain. Presence of the labrum did not significantly influence fluid load support within the articular cartilage, but prevented deformation at the cartilage edge, leading to lower stress and strain conditions in the cartilage. A morphologically accurate representation of collagen fibril orientation through the thickness of the articular cartilage was not necessary to predict fluid load support. However, comparison with simplified fibril reinforcement underscored the physiological importance. The results of this study demonstrate that an elastic incompressible material approximation is reasonable for modeling a limited number of cyclic motions of gait and squatting without significant loss of accuracy, but is not appropriate for static motions or numerous repeated motions. Additionally, effects seen from removal of the labrum motivate evaluation of labral reattachment strategies in the context of labral repair. Copyright © 2018 Elsevier Ltd. All rights reserved.
Drug Sensitivity in Older Adults: The Role of Physiologic and Pharmacokinetic Factors.
ERIC Educational Resources Information Center
Cherry, Katie E.; Morton, Mark R.
1989-01-01
Notes that age-related changes in physiology and pharmacokinetics (how drugs are used in the body) lead to increased drug sensitivity and potentially harmful drug effects. Addresses heightened sensitivity to drug effects seen in older adults. Presents three examples of physiologic decline and discusses some broad considerations for geriatric…
From Tusko to Titin: the role for comparative physiology in an era of molecular discovery.
Lindstedt, S L; Nishikawa, K C
2015-06-15
As we approach the centenary of the term "comparative physiology," we reexamine its role in modern biology. Finding inspiration in Krogh's classic 1929 paper, we first look back to some timeless contributions to the field. The obvious and fascinating variation among animals is much more evident than is their shared physiological unity, which transcends both body size and specific adaptations. The "unity in diversity" reveals general patterns and principles of physiology that are invisible when examining only one species. Next, we examine selected contemporary contributions to comparative physiology, which provides the context in which reductionist experiments are best interpreted. We discuss the sometimes surprising insights provided by two comparative "athletes" (pronghorn and rattlesnakes), which demonstrate 1) animals are not isolated molecular mechanisms but highly integrated physiological machines, a single "rate-limiting" step may be exceptional; and 2) extremes in nature are rarely the result of novel mechanisms, but rather employ existing solutions in novel ways. Furthermore, rattlesnake tailshaker muscle effectively abolished the conventional view of incompatibility of simultaneous sustained anaerobic glycolysis and oxidative ATP production. We end this review by looking forward, much as Krogh did, to suggest that a comparative approach may best lend insights in unraveling how skeletal muscle stores and recovers mechanical energy when operating cyclically. We discuss and speculate on the role of the largest known protein, titin (the third muscle filament), as a dynamic spring capable of storing and recovering elastic recoil potential energy in skeletal muscle. Copyright © 2015 the American Physiological Society.
Lenoir, Magalie; Tang, Jeremy S.; Woods, Amina S.
2013-01-01
Repeated exposure to nicotine and other psychostimulant drugs produces persistent increases in their psychomotor and physiological effects (sensitization), a phenomenon related to the drugs' reinforcing properties and abuse potential. Here we examined the role of peripheral actions of nicotine in nicotine-induced sensitization of centrally mediated physiological parameters (brain, muscle, and skin temperatures), cortical and VTA EEG, neck EMG activity, and locomotion in freely moving rats. Repeated injections of intravenous nicotine (30 μg/kg) induced sensitization of the drug's effects on all these measures. In contrast, repeated injections of the peripherally acting analog of nicotine, nicotine pyrrolidine methiodide (nicotinePM, 30 μg/kg, i.v.) resulted in habituation (tolerance) of the same physiological, neuronal, and behavioral measures. However, after repeated nicotine exposure, acute nicotinePM injections induced nicotine-like physiological responses: powerful cortical and VTA EEG desynchronization, EMG activation, a large brain temperature increase, but weaker hyperlocomotion. Additionally, both the acute locomotor response to nicotine and nicotine-induced locomotor sensitization were attenuated by blockade of peripheral nicotinic receptors by hexamethonium (3 mg/kg, i.v.). These data suggest that the peripheral actions of nicotine, which precede its direct central actions, serve as a conditioned interoceptive cue capable of eliciting nicotine-like physiological and neural responses after repeated nicotine exposure. Thus, by providing a neural signal to the CNS that is repeatedly paired with the direct central effects of nicotine, the drug's peripheral actions play a critical role in the development of nicotine-induced physiological, neural, and behavioral sensitization. PMID:23761889
Lenoir, Magalie; Tang, Jeremy S; Woods, Amina S; Kiyatkin, Eugene A
2013-06-12
Repeated exposure to nicotine and other psychostimulant drugs produces persistent increases in their psychomotor and physiological effects (sensitization), a phenomenon related to the drugs' reinforcing properties and abuse potential. Here we examined the role of peripheral actions of nicotine in nicotine-induced sensitization of centrally mediated physiological parameters (brain, muscle, and skin temperatures), cortical and VTA EEG, neck EMG activity, and locomotion in freely moving rats. Repeated injections of intravenous nicotine (30 μg/kg) induced sensitization of the drug's effects on all these measures. In contrast, repeated injections of the peripherally acting analog of nicotine, nicotine pyrrolidine methiodide (nicotine(PM), 30 μg/kg, i.v.) resulted in habituation (tolerance) of the same physiological, neuronal, and behavioral measures. However, after repeated nicotine exposure, acute nicotine(PM) injections induced nicotine-like physiological responses: powerful cortical and VTA EEG desynchronization, EMG activation, a large brain temperature increase, but weaker hyperlocomotion. Additionally, both the acute locomotor response to nicotine and nicotine-induced locomotor sensitization were attenuated by blockade of peripheral nicotinic receptors by hexamethonium (3 mg/kg, i.v.). These data suggest that the peripheral actions of nicotine, which precede its direct central actions, serve as a conditioned interoceptive cue capable of eliciting nicotine-like physiological and neural responses after repeated nicotine exposure. Thus, by providing a neural signal to the CNS that is repeatedly paired with the direct central effects of nicotine, the drug's peripheral actions play a critical role in the development of nicotine-induced physiological, neural, and behavioral sensitization.
Anderson, Christopher J; Satkovich, John; Köseoğlu, Volkan K; Agaisse, Hervé; Kendall, Melissa M
2018-05-01
Ethanolamine is a ubiquitous and essential molecule within a host. Significantly, bacterial pathogens exploit ethanolamine during infection to promote growth and regulate virulence. The ethanolamine permease EutH is dispensable for growth in vitro under standard conditions, whereas EutH is required for ethanolamine utilization at low pH. These findings suggested a model in which EutH facilitates diffusion of ethanolamine into the bacterial cell in acidic environments. To date, the ecological significance of this model has not been thoroughly investigated, and the importance of EutH to bacterial growth under physiologically relevant conditions is not known. During infection, immune cells internalize invading bacteria within an acidic, nutrient-depleted vacuole called the phagosome. Here, we investigated the hypothesis that EutH promotes bacterial survival following phagocytosis. Our findings indicate that EutH is important for survival and replication of the facultative intracellular pathogens Salmonella enterica serovar Typhimurium and Listeria monocytogenes during prolonged or transient exposure to the phagosome, respectively. Furthermore, in agreement with EutH being important in the acidic environment, neutralization of the vacuole abolished the requirement for EutH. Significantly, consistent with a role for EutH in promoting intramacrophage survival, EutH was not required during S Typhimurium local intestinal infection but specifically conferred an advantage upon dissemination to peripheral organs. These findings reveal a physiologically relevant and conserved role for EutH in spatiotemporal niche adaptation during infection. Copyright © 2018 American Society for Microbiology.
Patil, Yuvraj N.; Dille, Kelly N.; Burk, David H.; Cortez, Cory C.; Gettys, Thomas W.
2015-01-01
Dietary methionine restriction (MR) produces a coordinated series of biochemical and physiological responses that improve biomarkers of metabolic health, increase energy expenditure, limit fat accretion, and improve overall insulin sensitivity. Inguinal white adipose tissue (IWAT) is a primary target and site of action where the diet initiates transcriptional programs linked to enhancing both synthesis and oxidation of lipid. Using a combination of ex vivo approaches to assess dietary effects on cell morphology and function, we report that dietary MR produced a 4-fold increase in multilocular, UCP1-expressing cells within this depot in conjunction with significant increases in mitochondrial content, size, and cristae density. Dietary MR increased expression of multiple enzymes within the citric acid cycle, as well as respiratory complexes I, II and III. The physiological significance of these responses, evaluated in isolated mitochondria by high resolution respirometry, was a significant increase in respiratory capacity measured using multiple substrates. The morphological, transcriptional, and biochemical remodeling of IWAT mitochondria enhances the synthetic and oxidative capacity of this tissue, and collectively underlie its expanded role as a significant contributor to the overall increase in metabolic flexibility and uncoupled respiration produced by the diet. PMID:26278039
Insulin: its Role in the Central Control of Reproduction
Sliwowska, Joanna H.; Fergani, Chrysanthi; Gawałek, Monika; Skowronska, Bogda; Fichna, Piotr; Lehman, Michael N.
2014-01-01
Insulin has long been recognized as a key regulator of energy homeostasis via its actions at the level of the brain, but in addition, plays a role in regulating neural control of reproduction. In this review, we consider and compare evidence from animal models demonstrating a role for insulin for physiological control of reproduction by effects on GnRH/LH secretion. We also review the role that insulin plays in prenatal programming of adult reproduction, and consider specific candidate neurons in the adult hypothalamus by which insulin may act to regulate reproductive function. Finally, we review clinical evidence of the role that insulin may play in adult human fertility and reproductive disorders. Overall, while insulin appears to have a significant impact on reproductive neuroendocrine function, there are many unanswered questions regarding its precise sites and mechanisms of action, and their impact on developing and adult reproductive neuroendocrine function. PMID:24874777
Insulin: its role in the central control of reproduction.
Sliwowska, Joanna H; Fergani, Chrysanthi; Gawałek, Monika; Skowronska, Bogda; Fichna, Piotr; Lehman, Michael N
2014-06-22
Insulin has long been recognized as a key regulator of energy homeostasis via its actions at the level of the brain, but in addition, plays a role in regulating neural control of reproduction. In this review, we consider and compare evidence from animal models demonstrating a role for insulin for physiological control of reproduction by effects on GnRH/LH secretion. We also review the role that insulin plays in prenatal programming of adult reproduction, and consider specific candidate neurons in the adult hypothalamus by which insulin may act to regulate reproductive function. Finally, we review clinical evidence of the role that insulin may play in adult human fertility and reproductive disorders. Overall, while insulin appears to have a significant impact on reproductive neuroendocrine function, there are many unanswered questions regarding its precise sites and mechanisms of action, and their impact on developing and adult reproductive neuroendocrine function. Copyright © 2014 Elsevier Inc. All rights reserved.
Cyclin D2 is a critical mediator of exercise-induced cardiac hypertrophy.
Luckey, Stephen W; Haines, Chris D; Konhilas, John P; Luczak, Elizabeth D; Messmer-Kratzsch, Antke; Leinwand, Leslie A
2017-12-01
A number of signaling pathways underlying pathological cardiac hypertrophy have been identified. However, few studies have probed the functional significance of these signaling pathways in the context of exercise or physiological pathways. Exercise studies were performed on females from six different genetic mouse models that have been shown to exhibit alterations in pathological cardiac adaptation and hypertrophy. These include mice expressing constitutively active glycogen synthase kinase-3β (GSK-3βS9A), an inhibitor of CaMK II (AC3-I), both GSK-3βS9A and AC3-I (GSK-3βS9A/AC3-I), constitutively active Akt (myrAkt), mice deficient in MAPK/ERK kinase kinase-1 (MEKK1 -/- ), and mice deficient in cyclin D2 (cyclin D2 -/- ). Voluntary wheel running performance was similar to NTG littermates for five of the mouse lines. Exercise induced significant cardiac growth in all mouse models except the cyclin D2 -/- mice. Cardiac function was not impacted in the cyclin D2 -/- mice and studies using a phospho-antibody array identified six proteins with increased phosphorylation (greater than 150%) and nine proteins with decreased phosphorylation (greater than 33% decrease) in the hearts of exercised cyclin D2 -/- mice compared to exercised NTG littermate controls. Our results demonstrate that unlike the other hypertrophic signaling molecules tested here, cyclin D2 is an important regulator of both pathologic and physiological hypertrophy. Impact statement This research is relevant as the hypertrophic signaling pathways tested here have only been characterized for their role in pathological hypertrophy, and not in the context of exercise or physiological hypertrophy. By using the same transgenic mouse lines utilized in previous studies, our findings provide a novel and important understanding for the role of these signaling pathways in physiological hypertrophy. We found that alterations in the signaling pathways tested here had no impact on exercise performance. Exercise induced cardiac growth in all of the transgenic mice except for the mice deficient in cyclin D2. In the cyclin D2 null mice, cardiac function was not impacted even though the hypertrophic response was blunted and a number of signaling pathways are differentially regulated by exercise. These data provide the field with an understanding that cyclin D2 is a key mediator of physiological hypertrophy.
Expression of regulatory proteins in choroid plexus changes in early stages of Alzheimer disease.
Krzyzanowska, Agnieszka; García-Consuegra, Inés; Pascual, Consuelo; Antequera, Desiree; Ferrer, Isidro; Carro, Eva
2015-04-01
Recent studies indicate that the choroid plexus has important physiologic and pathologic roles in Alzheimer disease (AD). To obtain additional insight on choroid plexus function, we performed a proteomic analysis of choroid plexus samples from patients with AD stages I to II (n = 16), III to IV (n = 16), and V to VI (n = 11) and 7 age-matched control subjects. We used 2-dimensional differential gel electrophoresis coupled with mass spectrometry to generate a complete picture of changes in choroid plexus protein expression occurring in AD patients. We identified 6 proteins: 14-3-3 β/α, 14-3-3 ε, moesin, proteasome activator complex subunit 1, annexin V, and aldehyde dehydrogenase, which were significantly regulated in AD patient samples (p < 0.05, >1.5-fold variation in expression vs control samples). These proteins are implicated in major physiologic functions including mitochondrial dysfunction and apoptosis regulation. These findings contribute additional significance to the emerging importance of molecular and functional changes of choroid plexus function in the pathophysiology of AD.
Effects of Caffeine on Olfactory Learning in Crickets.
Sugimachi, Seigo; Matsumoto, Yukihisa; Mizunami, Makoto; Okada, Jiro
2016-10-01
Caffeine is a plant-derived alkaloid that is generally known as a central nervous system (CNS) stimulant. In order to examine the effects of caffeine on higher CNS functions in insects, we used an appetitive olfactory learning paradigm for the cricket Gryllus bimaculatus. Crickets can form significant long-term memories (LTMs) after repetitive training sessions, during which they associate a conditioned stimulus (CS: odor) with an unconditioned stimulus (US: reward). Administration of hemolymphal injections of caffeine established LTM after only single-trial conditioning over a wide range of caffeine dosages (1.6 µµg/kg to 39 mg/kg). We investigated the physiological mechanisms underlying this enhancement of olfactory learning performance pharmacologically, focusing on three major physiological roles of caffeine: 1) inhibition of phosphodiesterase (PDE), 2) agonism of ryanodine receptors, and 3) antagonism of adenosine receptors. Application of drugs relevant to these actions resulted in significant effects on LTM formation. These results suggest that externally applied caffeine enhances LTM formation in insect olfactory learning via multiple cellular mechanisms.
Mechanical stress activates NMDA receptors in the absence of agonists.
Maneshi, Mohammad Mehdi; Maki, Bruce; Gnanasambandam, Radhakrishnan; Belin, Sophie; Popescu, Gabriela K; Sachs, Frederick; Hua, Susan Z
2017-01-03
While studying the physiological response of primary rat astrocytes to fluid shear stress in a model of traumatic brain injury (TBI), we found that shear stress induced Ca 2+ entry. The influx was inhibited by MK-801, a specific pore blocker of N-Methyl-D-aspartic acid receptor (NMDAR) channels, and this occurred in the absence of agonists. Other NMDA open channel blockers ketamine and memantine showed a similar effect. The competitive glutamate antagonists AP5 and GluN2B-selective inhibitor ifenprodil reduced NMDA-activated currents, but had no effect on the mechanically induced Ca 2+ influx. Extracellular Mg 2+ at 2 mM did not significantly affect the shear induced Ca 2+ influx, but at 10 mM it produced significant inhibition. Patch clamp experiments showed mechanical activation of NMDAR and inhibition by MK-801. The mechanical sensitivity of NMDARs may play a role in the normal physiology of fluid flow in the glymphatic system and it has obvious relevance to TBI.
Mechanical stress activates NMDA receptors in the absence of agonists
Maneshi, Mohammad Mehdi; Maki, Bruce; Gnanasambandam, Radhakrishnan; Belin, Sophie; Popescu, Gabriela K.; Sachs, Frederick; Hua, Susan Z.
2017-01-01
While studying the physiological response of primary rat astrocytes to fluid shear stress in a model of traumatic brain injury (TBI), we found that shear stress induced Ca2+ entry. The influx was inhibited by MK-801, a specific pore blocker of N-Methyl-D-aspartic acid receptor (NMDAR) channels, and this occurred in the absence of agonists. Other NMDA open channel blockers ketamine and memantine showed a similar effect. The competitive glutamate antagonists AP5 and GluN2B-selective inhibitor ifenprodil reduced NMDA-activated currents, but had no effect on the mechanically induced Ca2+ influx. Extracellular Mg2+ at 2 mM did not significantly affect the shear induced Ca2+ influx, but at 10 mM it produced significant inhibition. Patch clamp experiments showed mechanical activation of NMDAR and inhibition by MK-801. The mechanical sensitivity of NMDARs may play a role in the normal physiology of fluid flow in the glymphatic system and it has obvious relevance to TBI. PMID:28045032
Glucoweb: a case study of secure, remote biomonitoring and communication.
Nigrin, D J; Kohane, I S
2000-01-01
As the Internet begins to play a greater role in many healthcare processes, it is inevitable that remote monitoring of patients' physiological parameters over the Internet will become increasingly commonplace. Internet-based communication between patients and their healthcare providers has already become prevalent, and has gained significant attention in terms of confidentiality issues. However, transmission of data directly from patients' physiological biomonitoring devices over the Web has garnered significantly less focus, especially in the area of authentication and security. In this paper, we describe a prototype system called Glucoweb, which allows patients with diabetes mellitus to transmit their self-monitored blood glucose data directly from their personal glucometer device to their diabetes care provider over the Internet. No customized software is necessary on the patient's computer, only a Web browser and active Internet connection. We use this example to highlight key authentication and security measures that should be considered for devices that transmit healthcare data to remote locations.
Nitric oxide bioavailability in the microcirculation: insights from mathematical models.
Tsoukias, Nikolaos M
2008-11-01
Over the last 30 years nitric oxide (NO) has emerged as a key signaling molecule involved in a number of physiological functions, including in the regulation of microcirculatory tone. Despite significant scientific contributions, fundamental questions about NO's role in the microcirculation remain unanswered. Mathematical modeling can assist in investigations of microcirculatory NO physiology and address experimental limitations in quantifying vascular NO concentrations. The number of mathematical models investigating the fate of NO in the vasculature has increased over the last few years, and new models are continuously emerging, incorporating an increasing level of complexity and detail. Models investigate mechanisms that affect NO availability in health and disease. They examine the significance of NO release from nonendothelial sources, the effect of transient release, and the complex interaction of NO with other substances, such as heme-containing proteins and reactive oxygen species. Models are utilized to test and generate hypotheses for the mechanisms that regulate NO-dependent signaling in the microcirculation.
Tihanyi, B T; Köteles, F
2017-09-01
Body sensations play an essential role in the subjective evaluation of our physical health, illness, and healing. They are impacted by peripheral somatic and external processes, but they are also heavily modulated by mental processes, e.g., attention, motor control, and emotion. Body sensations, such as tingling, numbness, pulse, and warmth, can emerge due to simply focusing attention on a body part. It is however an open question, if these sensations are connected with actual peripheral changes or happen "only in the mind." Here, we first tested whether the intensity of such attention-related body sensations is related to autonomic and somatomotor physiological processes and to psychological traits. In this study, attention-related body sensations were not significantly connected to changes in physiology, except warmth sensation, which was linked to decrease in muscle tension. Overall intensity of tingling significantly correlated with body awareness and tendentiously with body-mind practice. This strengthened the hypothesis that attention-related body sensations are more the result of top-down functions, and the connection with peripheral processes is weak. Here, we suggested a novel protocol to examine the effect of manipulating attention on body sensations, which together with our results and discussion can inspire future researches.
Pearson, D T; Naughton, G A; Torode, M
2006-08-01
Entrepreneurial marketing of sport increases demands on sport development officers to identify talented individuals for specialist development at the youngest possible age. Talent identification results in the streamlining of resources to produce optimal returns from a sports investment. However, the process of talent identification for team sports is complex and success prediction is imperfect. The aim of this review is to describe existing practices in physiological tests used for talent identification in team sports and discuss the impact of maturity-related differences on the long term outcomes particularly for male participants. Maturation is a major confounding variable in talent identification during adolescence. A myriad of hormonal changes during puberty results in physical and physiological characteristics important for sporting performance. Significant changes during puberty make the prediction of adult performance difficult from adolescent data. Furthermore, for talent identification programs to succeed, valid and reliable testing procedures must be accepted and implemented in a range of performance-related categories. Limited success in scientifically based talent identification is evident in a range of team sports. Genetic advances challenge the ethics of talent identification in adolescent sport. However, the environment remains a significant component of success prediction in sport. Considerations for supporting talented young male athletes are discussed.
Cardiac torsion and electromagnetic fields: the cardiac bioinformation hypothesis.
Burleson, Katharine O; Schwartz, Gary E
2005-01-01
Although in physiology the heart is often referred to as a simple piston pump, there are in fact two additional features that are integral to cardiac physiology and function. First, the heart as it contracts in systole, also rotates and produces torsion due to the structure of the myocardium. Second, the heart produces a significant electromagnetic field with each contraction due to the coordinated depolarization of myocytes producing a current flow. Unlike the electrocardiogram, the magnetic field is not limited to volume conduction and extends outside the body. The therapeutic potential for interaction of this cardioelectromagnetic field both within and outside the body is largely unexplored. It is our hypothesis that the heart functions as a generator of bioinformation that is central to normative functioning of body. The source of this bioinformation is based on: (1) vortex blood flow in the left ventricle; (2) a cardiac electromagnetic field and both; (3) heart sounds; and (4) pulse pressure which produce frequency and amplitude information. Thus, there is a multidimensional role for the heart in physiology and biopsychosocial dynamics. Recognition of these cardiac properties may result in significant implications for new therapies for cardiovascular disease based on increasing cardiac energy efficiency (coherence) and bioinformation from the cardioelectromagnetic field. Research studies to test this hypothesis are suggested.
Friedman, W J; Dreyfus, C F; McEwen, B; Black, I B
1988-10-01
Recent evidence suggests that extracellular signals regulate neurotransmitter traits in brain catecholaminergic (CA) neurons as in the periphery. Development of the dopaminergic phenotype in the mouse substantia nigra (SN) was studied by monitoring tyrosine hydroxylase (TH), the rate-limiting enzyme in CA biosynthesis in vivo and in culture. Explants of SN were dissected from embryonic day 15 embryos and grown in culture for a week. To define the influence of depolarizing signals on central dopaminergic neurons, cultures were grown with the pharmacologic depolarizing agent veratridine. This treatment elicited a significant increase in TH enzyme activity, accompanied by elevated levels of enzyme protein. The increase in activity was prevented by TTX, suggesting that transmembrane Na+ influx was necessary for the rise in TH. A physiologic presynaptic agonist, substance P, also evoked a significant increase in TH activity; however, the coproduced tachykinin peptide, substance K (SK, neurokinin A) elicited a more dramatic rise. The SK effect was blocked by TTX, suggesting that the physiologic agonist was acting through the same mechanism as the pharmacologic agent veratridine. Immunoblot analysis revealed that SK elicited a parallel increase in TH enzyme protein. Our observations suggest that the novel peptide, SK, serves a physiological role in the regulation of TH in the striatonigral pathway.
Free fatty acid receptors and their role in regulation of energy metabolism.
Hara, Takafumi; Kimura, Ikuo; Inoue, Daisuke; Ichimura, Atsuhiko; Hirasawa, Akira
2013-01-01
The free fatty acid receptor (FFAR) is a G protein-coupled receptor (GPCR) activated by free fatty acids (FFAs), which play important roles not only as essential nutritional components but also as signaling molecules in numerous physiological processes. In the last decade, FFARs have been identified by the GPCR deorphanization strategy derived from the human genome database. To date, several FFARs have been identified and characterized as critical components in various physiological processes. FFARs are categorized according to the chain length of FFA ligands that activate each FFAR; FFA2 and FFA3 are activated by short chain FFAs, GPR84 is activated by medium-chain FFAs, whereas FFA1 and GPR120 are activated by medium- or long-chain FFAs. FFARs appear to act as physiological sensors for food-derived FFAs and digestion products in the gastrointestinal tract. Moreover, they are considered to be involved in the regulation of energy metabolism mediated by the secretion of insulin and incretin hormones and by the regulation of the sympathetic nerve systems, taste preferences, and inflammatory responses related to insulin resistance. Therefore, because FFARs can be considered to play important roles in physiological processes and various pathophysiological processes, FFARs have been targeted in therapeutic strategies for the treatment of metabolic disorders including type 2 diabetes and metabolic syndrome. In this review, we present a summary of recent progress regarding the understanding of their physiological roles in the regulation of energy metabolism and their potential as therapeutic targets.
Fei, Chen; Atterby, Christina; Edqvist, Per-Henrik; Pontén, Fredrik; Zhang, Wei Wei; Larsson, Erik; Ryan, Frank P
2014-01-01
There is growing evidence to suggest that human endogenous retroviruses (HERVs) have contributed to human evolution, being expressed in development, normal physiology and disease. A key difficulty in the scientific evaluation of this potential viral contribution is the accurate demonstration of virally expressed protein in specific human cells and tissues. In this study, we have adopted the endogenous retrovirus, ERV3, as our test model in developing a reliable high-capacity methodology for the expression of such endogenous retrovirus-coded protein. Two affinity-purified polyclonal antibodies to ERV3 Env-encoded protein were generated to detect the corresponding protein expression pattern in specific human cells, tissues and organs. Sampling included normal tissues from 144 individuals ranging from childhood to old age. This included more than forty different tissues and organs and some 216 different cancer tissues representing the twenty commonest forms of human cancer. The Rudbeck Laboratory, Uppsala University and Uppsala University Hospital, Uppsala, Sweden. The potential expression at likely physiological level of the ERV3Env encoded protein in a wide range of human cells, tissues and organs. We found that ERV3 encoded Env protein is expressed at substantive levels in placenta, testis, adrenal gland, corpus luteum, Fallopian tubes, sebaceous glands, astrocytes, bronchial epithelium and the ducts of the salivary glands. Substantive expression was also seen in a variety of epithelial cells as well as cells known to undergo fusion in inflammation and in normal physiology, including fused macrophages, myocardium and striated muscle. This contrasted strongly with the low levels expressed in other tissues types. These findings suggest that this virus plays a significant role in human physiology and may also play a possible role in disease. This technique can now be extended to the study of other HERV genomes within the human chromosomes that may have contributed to human evolution, physiology and disease.
Saeed, Sadia; Bech, Paul R; Hafeez, Tayyaba; Alam, Rabail; Falchi, Mario; Ghatei, Mohammad A; Bloom, Stephen R; Arslan, Muhammad; Froguel, Philippe
2014-04-01
Congenital leptin deficiency, a rare genetic disorder due to a homozygous mutation in the leptin gene (LEP), is accompanied by extreme obesity and hyperphagia. A number of gastrointestinal hormones have been shown to critically regulate food intake but their physiological role in hyperphagic response in congenital leptin deficiency has not been elucidated. This study is the first to evaluate the fasting and postprandial profiles of gut-derived hormones in homozygous and heterozygous carriers of LEP mutation. The study subjects from two consanguineous families consisted of five homozygous and eight heterozygous carriers of LEP mutation, c.398delG. Ten wild-type normal-weight subjects served as controls. Fasting and 1-h postprandial plasma ghrelin, glucagon-like peptide (GLP) 1, peptide YY (PYY), leptin and insulin levels were measured by immunoassays. Fasting plasma ghrelin levels in homozygotes remained remarkably unchanged following food consumption (P = 0.33) in contrast to a significant decline in heterozygous (P < 0.03) and normal (P < 0.02) subjects. A significant postprandial increase in PYY was observed in heterozygous (P < 0.02) and control subjects (P < 0.01), but not in the homozygous group (P = 0.22). A postprandial rise in GLP-1 levels was significant (P < 0.02) in all groups. Interestingly, fasting leptin levels in heterozygotes were not significantly different from controls and did not change significantly following meal. Our results demonstrate that gut hormones play little or no physiological role in driving the hyperphagic response of leptin-deficient subjects. In contrast, fasting and postprandial levels of gut hormones in heterozygous mutation carriers were comparable to those of normal-weight controls.
Ping, Jinglei; Vishnubhotla, Ramya; Xi, Jin; Ducos, Pedro; Saven, Jeffery G; Liu, Renyu; Johnson, Alan T Charlie
2018-05-22
Opioid neuropeptides play a significant role in pain perception, appetite regulation, sleep, memory, and learning. Advances in understanding of opioid peptide physiology are held back by the lack of methodologies for real-time quantification of affinities and kinetics of the opioid neuropeptide-receptor interaction at levels typical of endogenous secretion (<50 pM) in biosolutions with physiological ionic strength. To address this challenge, we developed all-electronic opioid-neuropeptide biosensors based on graphene microelectrodes functionalized with a computationally redesigned water-soluble μ-opioid receptor. We used the functionalized microelectrode in a bias-free charge measurement configuration to measure the binding kinetics and equilibrium binding properties of the engineered receptor with [d-Ala 2 , N-MePhe 4 , Gly-ol]-enkephalin and β-endorphin at picomolar levels in real time.
Spermine oxidase promotes bile canalicular lumen formation through acrolein production.
Uemura, Takeshi; Takasaka, Tomokazu; Igarashi, Kazuei; Ikegaya, Hiroshi
2017-11-01
Spermine oxidase (SMOX) catalyzes oxidation of spermine to generate spermidine, hydrogen peroxide (H 2 O 2 ) and 3-aminopropanal, which is spontaneously converted to acrolein. SMOX is induced by a variety of stimuli including bacterial infection, polyamine analogues and acetaldehyde exposure. However, the physiological functions of SMOX are not yet fully understood. We investigated the physiological role of SMOX in liver cells using human hepatocellular carcinoma cell line HepG2. SMOX localized to the bile canalicular lumen, as determined by F-actin staining. Knockdown of SMOX reduced the formation of bile canalicular lumen. We also found that phospho-Akt (phosphorylated protein kinase B) was localized to canalicular lumen. Treatment with Akt inhibitor significantly reduced the formation of bile canalicular lumen. Acrolein scavenger also inhibited the formation of bile canalicular lumen. PTEN, phosphatase and tensin homolog and an inhibitor of Akt, was alkylated in a SMOX-dependent manner. Our results suggest that SMOX plays a central role in the formation of bile canalicular lumen in liver cells by activating Akt pathway through acrolein production.
The Role of Stress Regulation on Neural Plasticity in Pain Chronification.
Li, Xiaoyun; Hu, Li
2016-01-01
Pain, especially chronic pain, is one of the most common clinical symptoms and has been considered as a worldwide healthcare problem. The transition from acute to chronic pain is accompanied by a chain of alterations in physiology, pathology, and psychology. Increasing clinical studies and complementary animal models have elucidated effects of stress regulation on the pain chronification via investigating activations of the hypothalamic-pituitary-adrenal (HPA) axis and changes in some crucial brain regions, including the amygdala, prefrontal cortex, and hippocampus. Although individuals suffer from acute pain benefit from such physiological alterations, chronic pain is commonly associated with maladaptive responses, like the HPA dysfunction and abnormal brain plasticity. However, the causal relationship among pain chronification, stress regulation, and brain alterations is rarely discussed. To call for more attention on this issue, we review recent findings obtained from clinical populations and animal models, propose an integrated stress model of pain chronification based on the existing models in perspectives of environmental influences and genetic predispositions, and discuss the significance of investigating the role of stress regulation on brain alteration in pain chronification for various clinical applications.
The Role of Stress Regulation on Neural Plasticity in Pain Chronification
Li, Xiaoyun
2016-01-01
Pain, especially chronic pain, is one of the most common clinical symptoms and has been considered as a worldwide healthcare problem. The transition from acute to chronic pain is accompanied by a chain of alterations in physiology, pathology, and psychology. Increasing clinical studies and complementary animal models have elucidated effects of stress regulation on the pain chronification via investigating activations of the hypothalamic-pituitary-adrenal (HPA) axis and changes in some crucial brain regions, including the amygdala, prefrontal cortex, and hippocampus. Although individuals suffer from acute pain benefit from such physiological alterations, chronic pain is commonly associated with maladaptive responses, like the HPA dysfunction and abnormal brain plasticity. However, the causal relationship among pain chronification, stress regulation, and brain alterations is rarely discussed. To call for more attention on this issue, we review recent findings obtained from clinical populations and animal models, propose an integrated stress model of pain chronification based on the existing models in perspectives of environmental influences and genetic predispositions, and discuss the significance of investigating the role of stress regulation on brain alteration in pain chronification for various clinical applications. PMID:28053788
Wong, Jen D; Shobo, Yetunde
2016-06-01
This study examines the influences of employment status and the moderating role of daily stressors on cortisol levels and responsivity in 182 workers and 253 retirees between 55 and 75 years old from the National Survey of Midlife Development in the United States (MIDUS-II). As a part of the Daily Diary Study, participants completed telephone interviews about their daily experiences across eight evenings and provided saliva samples across 4 days. Multilevel models showed that workers who experienced greater number of non-work related daily stressors significantly exhibited higher cortisol level at 30 min post awakening (b = 0.252, SE = 0.109, p < .05) and greater cortisol awakening response (b = 3.769, SE = 1.898, p < .05) the following morning as compared with retirees who experienced similar amount of daily stressors. Findings demonstrate the important consideration of daily stressors in identifying the ways in which social roles influence physiological functioning in midlife and late adulthood. © The Author(s) 2016.
The role of massage in sports performance and rehabilitation: current evidence and future direction.
Brummitt, Jason
2008-02-01
Massage is a popular treatment choice of athletes, coaches, and sports physical therapists. Despite its purported benefits and frequent use, evidence demonstrating its efficacy is scarce. To identify current literature relating to sports massage and its role in effecting an athlete's psychological readiness, in enhancing sports performance, in recovery from exercise and competition, and in the treatment of sports related musculoskeletal injuries. Electronic databases were used to identify papers relevant to this review. The following keywords were searched: massage, sports injuries, athletic injuries, physical therapy, rehabilitation, delayed onset muscle soreness, sports psychology, sports performance, sports massage, sports recovery, soft tissue mobilization, deep transverse friction massage, pre-event, and post exercise. RESEARCH STUDIES PERTAINING TO THE FOLLOWING GENERAL CATEGORIES WERE IDENTIFIED AND REVIEWED: pre-event (physiological and psychological variables), sports performance, recovery, and rehabilitation. Despite the fact clinical research has been performed, a poor appreciation exists for the appropriate clinical use of sports massage. Additional studies examining the physiological and psychological effects of sports massage are necessary in order to assist the sports physical therapist in developing and implementing clinically significant evidence based programs or treatments.
Gaucher, Matthieu; Dugé de Bernonville, Thomas; Lohou, David; Guyot, Sylvain; Guillemette, Thomas; Brisset, Marie-Noëlle; Dat, James F
2013-06-01
Flavonoids, like other metabolites synthesized via the phenylpropanoid pathway, possess a wide range of biological activities including functions in plant development and its interaction with the environment. Dihydrochalcones (mainly phloridzin, sieboldin, trilobatin, phloretin) represent the major flavonoid subgroup in apple green tissues. Although this class of phenolic compounds is found in very large amounts in some tissues (≈200mg/g of leaf DW), their physiological significance remains unclear. In the present study, we highlight their tissue-specific localization in young growing shoots suggesting a specific role in important physiological processes, most notably in response to biotic stress. Indeed, dihydrochalcones could constitute a basal defense, in particular phloretin which exhibits a strong broad-range bactericidal and fungicidal activity. Our results also indicate that sieboldin forms complexes with iron with strong affinity, reinforcing its antioxidant properties and conferring to this dihydrochalcone a potential for iron seclusion and/or storage. The importance of localization and biochemical properties of dihydrochalcones are discussed in view of the apple tree defense strategy against both biotic and abiotic stresses. Copyright © 2013 Elsevier Ltd. All rights reserved.
SiO2 nanoparticles change colour preference and cause Parkinson's-like behaviour in zebrafish
Li, Xiang; Liu, Bo; Li, Xin-Le; Li, Yi-Xiang; Sun, Ming-Zhu; Chen, Dong-Yan; Zhao, Xin; Feng, Xi-Zeng
2014-01-01
With advances in the development of various disciplines, there is a need to decipher bio-behavioural mechanisms via interdisciplinary means. Here, we present an interdisciplinary study of the role of silica nanoparticles (SiO2-NPs) in disturbing the neural behaviours of zebrafish and a possible physiological mechanism for this phenomenon. We used adult zebrafish as an animal model to evaluate the roles of size (15-nm and 50-nm) and concentration (300 μg/mL and 1000 μg/mL) in SiO2-NP neurotoxicity via behavioural and physiological analyses. With the aid of video tracking and data mining, we detected changes in behavioural phenotypes. We found that compared with 50-nm nanosilica, 15-nm SiO2-NPs produced greater significant changes in advanced cognitive neurobehavioural patterns (colour preference) and caused potentially Parkinson's disease-like behaviour. Analyses at the tissue, cell and molecular levels corroborated the behavioural results, demonstrating that nanosilica acted on the retina and dopaminergic (DA) neurons to change colour preference and to cause potentially Parkinson's disease-like behaviour. PMID:24448416
Dysfunction of pulmonary surfactant mediated by phospholipid oxidation is cholesterol-dependent.
Al-Saiedy, Mustafa; Pratt, Ryan; Lai, Patrick; Kerek, Evan; Joyce, Heidi; Prenner, Elmar; Green, Francis; Ling, Chang-Chun; Veldhuizen, Ruud; Ghandorah, Salim; Amrein, Matthias
2018-04-01
Pulmonary surfactant forms a cohesive film at the alveolar air-lung interface, lowering surface tension, and thus reducing the work of breathing and preventing atelectasis. Surfactant function becomes impaired during inflammation due to degradation of the surfactant lipids and proteins by free radicals. In this study, we examine the role of reactive nitrogen (RNS) and oxygen (ROS) species on surfactant function with and without physiological cholesterol levels (5-10%). Surface activity was assessed in vitro in a captive bubble surfactometer (CBS). Surfactant chemistry, monolayer fluidity and thermodynamic behavior were also recorded before and after oxidation. We report that physiologic amounts of cholesterol combined with oxidation results in severe impairment of surfactant function. We also show that surfactant polyunsaturated phospholipids are the most susceptible to oxidative alteration. Membrane thermodynamic experiments showed significant surfactant film stiffening after free radical exposure in the presence of cholesterol. These results point to a previously unappreciated role for cholesterol in amplifying defects in surface activity caused by oxidation of pulmonary surfactant, a finding that may have implications for treating several lung diseases. Copyright © 2018 Elsevier B.V. All rights reserved.
Docherty, Neil G; le Roux, Carel W
2016-03-01
Alterations in small intestinal physiology are proposed to play a causative role in the beneficial impact of Roux-en-Y gastric bypass on type 2 diabetes mellitus. The present article describes the key proposed mechanisms implicated with an emphasis on some of the newer findings in the field. Augmented incretin and diminished anti-incretin effects postsurgery are explored and a model proposed that reconciles the hindgut and foregut hypotheses of improved glycaemic control as being complementary rather than mutually exclusive. Synthesis of recent findings on postbypass changes in intestinal glucose handling then follows. Finally an updated view of the role of distal bile diversion and changes in the microbiota on enteroendocrine signalling is presented. A series of nonmutually exclusive changes in small intestinal physiology likely make a significant contribution to improved glycaemic control postgastric bypass. Longitudinal data indicate that these effects do not translate into a long-term cure. A number of surgery-induced changes, however, are amenable to device-based and pharmacology-based mimicry, and this is an area for prioritization of future research focus.
Roles of amino acids in preventing and treating intestinal diseases: recent studies with pig models.
Liu, Yulan; Wang, Xiuying; Hou, Yongqing; Yin, Yulong; Qiu, Yinsheng; Wu, Guoyao; Hu, Chien-An Andy
2017-08-01
Animal models are needed to study and understand a human complex disease. Because of their similarities in anatomy, structure, physiology, and pathophysiology, the pig has proven its usefulness in studying human gastrointestinal diseases, such as inflammatory bowel disease, ischemia/reperfusion injury, diarrhea, and cancer. To understand the pathogenesis of these diseases, a number of experimental models generated in pigs are available, for example, through surgical manipulation, chemical induction, microbial infection, and genetic engineering. Our interests have been using amino acids as therapeutics in pig and human disease models. Amino acids not only play an important role in protein biosynthesis, but also exert significant physiological effects in regulating immunity, anti-oxidation, redox regulation, energy metabolism, signal transduction, and animal behavior. Recent studies in pigs have shown that specific dietary amino acids can improve intestinal integrity and function under normal and pathological conditions that protect the host from different diseases. In this review, we summarize several pig models in intestinal diseases and how amino acids can be used as therapeutics in treating pig and human diseases.
Zinc oxide nanoflowers make new blood vessels
NASA Astrophysics Data System (ADS)
Barui, Ayan Kumar; Veeriah, Vimal; Mukherjee, Sudip; Manna, Joydeb; Patel, Ajay Kumar; Patra, Sujata; Pal, Krishnendu; Murali, Shruthi; Rana, Rohit K.; Chatterjee, Suvro; Patra, Chitta Ranjan
2012-11-01
It is well established that angiogenesis is the process of formation of new capillaries from pre-existing blood vessels. It is a complex process, involving both pro- and anti-angiogenic factors, and plays a significant role in physiological and pathophysiological processes such as embryonic development, atherosclerosis, post-ischemic vascularization of the myocardium, tumor growth and metastasis, rheumatoid arthritis etc. This is the first report of zinc oxide (ZnO) nanoflowers that show significant pro-angiogenic properties (formation of new capillaries from pre-existing blood vessels), observed by in vitro and in vivo angiogenesis assays. The egg yolk angiogenesis assay using ZnO nanoflowers indicates the presence of matured blood vessels formation. Additionally, it helps to promote endothelial cell (EA.hy926 cells) migration in wound healing assays. Formation of reactive oxygen species (ROS), especially hydrogen peroxide (H2O2)--a redox signaling molecule, might be the plausible mechanism for nanoflower-based angiogenesis. Angiogenesis by nanoflowers may provide the basis for the future development of new alternative therapeutic treatment strategies for cardiovascular and ischemic diseases, where angiogenesis plays a significant role.It is well established that angiogenesis is the process of formation of new capillaries from pre-existing blood vessels. It is a complex process, involving both pro- and anti-angiogenic factors, and plays a significant role in physiological and pathophysiological processes such as embryonic development, atherosclerosis, post-ischemic vascularization of the myocardium, tumor growth and metastasis, rheumatoid arthritis etc. This is the first report of zinc oxide (ZnO) nanoflowers that show significant pro-angiogenic properties (formation of new capillaries from pre-existing blood vessels), observed by in vitro and in vivo angiogenesis assays. The egg yolk angiogenesis assay using ZnO nanoflowers indicates the presence of matured blood vessels formation. Additionally, it helps to promote endothelial cell (EA.hy926 cells) migration in wound healing assays. Formation of reactive oxygen species (ROS), especially hydrogen peroxide (H2O2)--a redox signaling molecule, might be the plausible mechanism for nanoflower-based angiogenesis. Angiogenesis by nanoflowers may provide the basis for the future development of new alternative therapeutic treatment strategies for cardiovascular and ischemic diseases, where angiogenesis plays a significant role. Electronic supplementary information (ESI) available: See DOI: 10.1039/c2nr32369a
Tiede, L M; Cook, E A; Morsey, B; Fox, H S
2011-12-22
Mitochondrial dysfunction is implicated in a majority of neurodegenerative disorders and much study of neurodegenerative disease is done on cultured neurons. In traditional tissue culture, the oxygen level that cells experience is dramatically higher (21%) than in vivo conditions (1-11%). These differences can alter experimental results, especially, pertaining to mitochondria and oxidative metabolism. Our results show that primary neurons cultured at physiological oxygen levels found in the brain showed higher polarization, lower rates of ROS production, larger mitochondrial networks, greater cytoplasmic fractions of mitochondria and larger mitochondrial perimeters than those cultured at higher oxygen levels. Although neurons cultured in either physiological oxygen or atmospheric oxygen exhibit significant increases in mitochondrial reactive oxygen species (ROS) production when treated with the human immunodeficiency virus (HIV) virotoxin trans-activator of transcription, mitochondria of neurons cultured at physiological oxygen underwent depolarization with dramatically increased cell death, whereas those cultured at atmospheric oxygen became hyperpolarized with no increase in cell death. Studies with a second HIV virotoxin, negative regulation factor (Nef), revealed that Nef treatment also increased mitochondrial ROS production for both the oxygen conditions, but resulted in mitochondrial depolarization and increased death only in neurons cultured in physiological oxygen. These results indicate a role for oxidative metabolism in a mechanism of neurotoxicity during HIV infection and demonstrate the importance of choosing the correct, physiological, culture oxygen in mitochondrial studies performed in neurons.
Mechanisms of Chemical Carcinogenesis in the Kidneys
Radford, Robert; Frain, Helena; Ryan, Michael P.; Slattery, Craig; McMorrow, Tara
2013-01-01
Chemical carcinogens are substances which induce malignant tumours, increase their incidence or decrease the time taken for tumour formation. Often, exposure to chemical carcinogens results in tissue specific patterns of tumorigenicity. The very same anatomical, biochemical and physiological specialisations which permit the kidney to perform its vital roles in maintaining tissue homeostasis may in fact increase the risk of carcinogen exposure and contribute to the organ specific carcinogenicity observed with numerous kidney carcinogens. This review will address the numerous mechanisms which play a role in the concentration, bioactivation, and uptake of substances from both the urine and blood which significantly increase the risk of cancer in the kidney. PMID:24071941
Coronary atherosclerosis: Significance of autophagic armour.
Arora, Mansi; Kaul, Deepak
2012-09-26
Autophagy is a lysosomal degradation pathway of cellular components such as organelles and long-lived proteins. Though a protective role for autophagy has been established in various patho-physiologic conditions such as cancer, neurodegeneration, aging and heart failure, a growing body of evidence now reveals a protective role for autophagy in atherosclerosis, mainly by removing oxidatively damaged organelles and proteins and also by promoting cholesterol egress from the lipid-laden cells. Recent studies by Razani et al and Liao et al unravel novel pathways that might be involved in autophagic protection and in this commentary we highlight the importance of autophagy in atherosclerosis in the light of these two recent papers.
Lipid Rafts in Mast Cell Biology
Silveira e Souza, Adriana Maria Mariano; Mazucato, Vivian Marino; Jamur, Maria Célia; Oliver, Constance
2011-01-01
Mast cells have long been recognized to have a direct and critical role in allergic and inflammatory reactions. In allergic diseases, these cells exert both local and systemic responses, including allergic rhinitis and anaphylaxis. Mast cell mediators are also related to many chronic inflammatory conditions. Besides the roles in pathological conditions, the biological functions of mast cells include roles in innate immunity, involvement in host defense mechanisms against parasites, immunomodulation of the immune system, tissue repair, and angiogenesis. Despite their growing significance in physiological and pathological conditions, much still remains to be learned about mast cell biology. This paper presents evidence that lipid rafts or raft components modulate many of the biological processes in mast cells, such as degranulation and endocytosis, play a role in mast cell development and recruitment, and contribute to the overall preservation of mast cell structure and organization. PMID:21490812
At the crossroads of physiology and ecology: food supply and the timing of avian reproduction.
Davies, Scott; Deviche, Pierre
2014-06-01
This article is part of a Special Issue “Energy Balance”. The decision of when to breed is crucial to the reproductive success and fitness of seasonally breeding birds. The availability of food for adults prior to breeding has long been thought to play a critical role in timing the initiation of seasonal reproductive events, in particular laying. However, unequivocal evidence for such a role remains limited and the physiological mechanisms by which an increase in food availability results in seasonal activation of the reproductive system are largely speculative. This lack of mechanistic information partly reflects a lack of integration of ecological and physiological approaches to study seasonal reproduction. Indeed, most work pertaining to the role of food availability for adults on the timing of avian reproduction has been ecological and has focused almost exclusively on female traits associated with reproductive timing (e.g., lay date and clutch size). By contrast, most work on the physiological bases of the relationship between food availability and the timing of reproduction has investigated male traits associated with reproductive development (e.g., reproductive hormones and gonadal development). To advance our understanding of these topics, we review the role of proximate factors including food availability, social factors, and ambient temperature in the control of breeding decisions, and discuss the role of three potential candidates (leptin, glucocorticoids, and GnIH-neuropeptide Y) that may mediate the effects of food availability on these decisions. We emphasize that future progress in this area is heavily contingent upon the use of physiology-based approaches and their integration into current ecological frameworks. Published by Elsevier Inc.
Steinert, Robert E; Feinle-Bisset, Christine; Asarian, Lori; Horowitz, Michael; Beglinger, Christoph; Geary, Nori
2017-01-01
The efficacy of Roux-en-Y gastric-bypass (RYGB) and other bariatric surgeries in the management of obesity and type 2 diabetes mellitus and novel developments in gastrointestinal (GI) endocrinology have renewed interest in the roles of GI hormones in the control of eating, meal-related glycemia, and obesity. Here we review the nutrient-sensing mechanisms that control the secretion of four of these hormones, ghrelin, cholecystokinin (CCK), glucagon-like peptide-1 (GLP-1), and peptide tyrosine tyrosine [PYY(3-36)], and their contributions to the controls of GI motor function, food intake, and meal-related increases in glycemia in healthy-weight and obese persons, as well as in RYGB patients. Their physiological roles as classical endocrine and as locally acting signals are discussed. Gastric emptying, the detection of specific digestive products by small intestinal enteroendocrine cells, and synergistic interactions among different GI loci all contribute to the secretion of ghrelin, CCK, GLP-1, and PYY(3-36). While CCK has been fully established as an endogenous endocrine control of eating in healthy-weight persons, the roles of all four hormones in eating in obese persons and following RYGB are uncertain. Similarly, only GLP-1 clearly contributes to the endocrine control of meal-related glycemia. It is likely that local signaling is involved in these hormones' actions, but methods to determine the physiological status of local signaling effects are lacking. Further research and fresh approaches are required to better understand ghrelin, CCK, GLP-1, and PYY(3-36) physiology; their roles in obesity and bariatric surgery; and their therapeutic potentials. Copyright © 2017 the American Physiological Society.
Estrogen Biology: New Insights into GPER Function and Clinical Opportunities
Prossnitz, Eric R.; Barton, Matthias
2014-01-01
Estrogens play an important role in the regulation of normal physiology, aging and many disease states. Although the nuclear estrogen receptors have classically been described to function as ligand-activated transcription factors mediating genomic effects in hormonally regulated tissues, more recent studies reveal that estrogens also mediate rapid signaling events traditionally associated with G protein-coupled receptors. The G protein-coupled estrogen receptor GPER (formerly GPR30) has now become recognized as a major mediator of estrogen’s rapid cellular effects throughout the body. With the discovery of selective synthetic ligands for GPER, both agonists and antagonists, as well as the use of GPER knockout mice, significant advances have been made in our understanding of GPER function at the cellular, tissue and organismal levels. In many instances, the protective/beneficial effects of estrogen are mimicked by selective GPER agonism and are absent or reduced in GPER knockout mice, suggesting an essential or at least parallel role for GPER in the actions of estrogen. In this review, we will discuss recent advances and our current understanding of the role of GPER and certain drugs such as SERMs and SERDs in physiology and disease. We will also highlight novel opportunities for clinical development towards GPER-targeted therapeutics, for molecular imaging, as well as for theranostic approaches and personalized medicine. PMID:24530924
Anaerobic Threshold: Its Concept and Role in Endurance Sport
Ghosh, Asok Kumar
2004-01-01
aerobic to anaerobic transition intensity is one of the most significant physiological variable in endurance sports. Scientists have explained the term in various ways, like, Lactate Threshold, Ventilatory Anaerobic Threshold, Onset of Blood Lactate Accumulation, Onset of Plasma Lactate Accumulation, Heart Rate Deflection Point and Maximum Lactate Steady State. But all of these have great role both in monitoring training schedule and in determining sports performance. Individuals endowed with the possibility to obtain a high oxygen uptake need to complement with rigorous training program in order to achieve maximal performance. If they engage in endurance events, they must also develop the ability to sustain a high fractional utilization of their maximal oxygen uptake (%VO2 max) and become physiologically efficient in performing their activity. Anaerobic threshold is highly correlated to the distance running performance as compared to maximum aerobic capacity or VO2 max, because sustaining a high fractional utilization of the VO2 max for a long time delays the metabolic acidosis. Training at or little above the anaerobic threshold intensity improves both the aerobic capacity and anaerobic threshold level. Anaerobic Threshold can also be determined from the speed-heart rate relationship in the field situation, without undergoing sophisticated laboratory techniques. However, controversies also exist among scientists regarding its role in high performance sports. PMID:22977357
Anaerobic threshold: its concept and role in endurance sport.
Ghosh, Asok Kumar
2004-01-01
aerobic to anaerobic transition intensity is one of the most significant physiological variable in endurance sports. Scientists have explained the term in various ways, like, Lactate Threshold, Ventilatory Anaerobic Threshold, Onset of Blood Lactate Accumulation, Onset of Plasma Lactate Accumulation, Heart Rate Deflection Point and Maximum Lactate Steady State. But all of these have great role both in monitoring training schedule and in determining sports performance. Individuals endowed with the possibility to obtain a high oxygen uptake need to complement with rigorous training program in order to achieve maximal performance. If they engage in endurance events, they must also develop the ability to sustain a high fractional utilization of their maximal oxygen uptake (%VO(2) max) and become physiologically efficient in performing their activity. Anaerobic threshold is highly correlated to the distance running performance as compared to maximum aerobic capacity or VO(2) max, because sustaining a high fractional utilization of the VO(2) max for a long time delays the metabolic acidosis. Training at or little above the anaerobic threshold intensity improves both the aerobic capacity and anaerobic threshold level. Anaerobic Threshold can also be determined from the speed-heart rate relationship in the field situation, without undergoing sophisticated laboratory techniques. However, controversies also exist among scientists regarding its role in high performance sports.
Kobayashi, Yasuhiro; Jimenez-Krassel, Fermin; Ireland, James J; Smith, George W
2006-01-01
The ability of ovarian follicles to produce large amounts of estradiol is a hallmark of follicle health status. Estradiol producing capacity is lost in ovarian follicles before morphological signs of atresia. A prominent wave like pattern of growth of antral follicles is characteristic of monotocous species such as cattle, horses and humans. While our knowledge of the role of pituitary gonadotropins in support of antral follicle growth and development is well established, the intrinsic factors that suppress estradiol production and may help promote atresia during follicular waves are not well understood. Numerous growth factors and cytokines have been reported to suppress granulosa cell estradiol production in vitro, but the association of expression of many such factors in vivo with follicle health status and their physiological significance are not clear. The purpose of this review is to discuss the in vivo and in vitro evidence supporting a local physiological role for cocaine and amphetamine regulated transcript, inhibins and low molecular weight insulin like growth factor binding proteins in negative regulation of granulosa cell estradiol production, with emphasis on evidence from the bovine model system. PMID:16611367
Abbas, Ghulam; Murtaza, Behzad; Bibi, Irshad; Shahid, Muhammad; Khan, Muhammad Imran; Amjad, Muhammad; Hussain, Munawar; Natasha
2018-01-01
Environmental contamination with arsenic (As) is a global environmental, agricultural and health issue due to the highly toxic and carcinogenic nature of As. Exposure of plants to As, even at very low concentration, can cause many morphological, physiological, and biochemical changes. The recent research on As in the soil-plant system indicates that As toxicity to plants varies with its speciation in plants (e.g., arsenite, As(III); arsenate, As(V)), with the type of plant species, and with other soil factors controlling As accumulation in plants. Various plant species have different mechanisms of As(III) or As(V) uptake, toxicity, and detoxification. This review briefly describes the sources and global extent of As contamination and As speciation in soil. We discuss different mechanisms responsible for As(III) and As(V) uptake, toxicity, and detoxification in plants, at physiological, biochemical, and molecular levels. This review highlights the importance of the As-induced generation of reactive oxygen species (ROS), as well as their damaging impacts on plants at biochemical, genetic, and molecular levels. The role of different enzymatic (superoxide dismutase, catalase, glutathione reductase, and ascorbate peroxidase) and non-enzymatic (salicylic acid, proline, phytochelatins, glutathione, nitric oxide, and phosphorous) substances under As(III/V) stress have been delineated via conceptual models showing As translocation and toxicity pathways in plant species. Significantly, this review addresses the current, albeit partially understood, emerging aspects on (i) As-induced physiological, biochemical, and genotoxic mechanisms and responses in plants and (ii) the roles of different molecules in modulation of As-induced toxicities in plants. We also provide insight on some important research gaps that need to be filled to advance our scientific understanding in this area of research on As in soil-plant systems. PMID:29301332
Wu, James T.; Kral, John G.
2004-01-01
Objective: Ghrelin is a novel gastric hormone recognized in 1999 as a mediator of growth hormone release. Since growth hormone is anabolic, an important function of ghrelin may be to coordinate energy needs with the growth process. Newly discovered biologic roles of ghrelin imply that it may have other important physiological functions as well. This is a review of recent clinically relevant, yet less well-known, physiologic actions of ghrelin. Summary Background Data: Ghrelin has profound orexigenic, adipogenic, and somatotrophic properties, increasing food intake and body weight. Secreted predominantly from the stomach, ghrelin is the natural ligand for the growth hormone secretagogue receptor in the pituitary gland, thus fulfilling criteria of a brain-gut peptide. The brain-gut axis is the effector of anabolism by regulating growth, feeding, and metabolism via vagal afferents mediating ghrelin signaling. However, the wide tissue distribution of ghrelin suggests that it may have other functions as well. Methods: Systematic literature review of all PubMed citations between 1999 and August 2003 focusing on clinically relevant biochemical and physiological characteristics of ghrelin. Results: Ghrelin is an important component of an integrated regulatory system of growth and metabolism acting via the vagus nerve, and is implicated in a variety of altered energy states such as obesity, eating disorders, neoplasia, and cachexia. It also enhances immune responses and potentially down-regulates anti-inflammatory molecules. Ghrelin's role as a brain-gut peptide emphasizes the significance of afferent vagal fibers as a major pathway to the brain, serving the purpose of maintaining physiologic homeostasis. Conclusions: The discovery of ghrelin has increased our understanding of feeding regulation, nutritional homeostasis, and metabolic processes. Further characterization of ghrelin's functions will likely generate new pharmacological approaches to diagnose and treat different disease entities including those related to the over-nutrition of obesity and the catabolic response to surgical trauma. PMID:15024307
Imaging for lung physiology: What do we wish we could measure?
Buxton, Richard B.
2012-01-01
The role of imaging as a tool for investigating lung physiology is growing at an accelerating pace. Looking forward, we wished to identify unresolved issues in lung physiology that might realistically be addressed by imaging methods in development or imaging approaches that could be considered. The role of imaging is framed in terms of the importance of good spatial and temporal resolution and the types of questions that could be addressed as these technical capabilities improve. Recognizing that physiology is fundamentally a quantitative science, a recurring emphasis is on the need for imaging methods that provide reliable measurements of specific physiological parameters. The topics included necessarily reflect our perspective on what are interesting questions and are not meant to be a comprehensive review. Nevertheless, we hope that this essay will be a spur to physiologists to think about how imaging could usefully be applied in their research and to physical scientists developing new imaging methods to attack challenging questions imaging could potentially answer. PMID:22582217
Effects of Diets High in Unsaturated Fatty Acids on Socially Induced Stress Responses in Guinea Pigs
Nemeth, Matthias; Millesi, Eva; Wagner, Karl-Heinz; Wallner, Bernard
2014-01-01
Unsaturated fatty acids (UFAs), such as omega-3 and omega-6 poly- and omega-9 monounsaturated fatty acids are important nutrients and major components of neuronal cell membranes. They play a major role in modulating brain functions and physiology and may therefore diminish behavioral and physiological stress reactions in corroboration with decreased cortisol concentrations. Functionally, cortisol itself can modulate several behaviors and also the fatty acid metabolism in the long term. But only little is known about the behavioral and physiological influences of dietary UFAs in a social group, where individuals are regularly exposed to stressful situations. Therefore, the aim of this study was to determine the effects of dietary UFAs on saliva cortisol concentrations and behavioral responses in socially confronted guinea pigs. Three groups of animals were additionally supplemented with 500 mg chia seeds (high in omega-3), walnuts (high in omega-6), or peanuts (high in omega-9) per kg bodyweight each day and compared to a control group. During social confrontation saliva cortisol concentrations significantly increased in all groups, which was accompanied by a loss in bodyweight. However, cortisol levels remained lower in the chia and walnut groups compared to controls. Additionally, the walnut group displayed significantly increased locomotion, while no differences between groups were detected in socio-positive, sexual, or aggressive behaviors. Total plasma omega-3, omega-6, and omega-9 fatty acids were significantly increased in the corresponding groups, due to the dietary supplementations. However, a significant decrease in plasma omega-3 and an increase in plasma n-6 fatty acids were detected in the chia group when comparing the measurements before and after social confrontation. We conclude that both omega-3 and omega-6 polyunsaturated fatty acids can diminish behavioral and physiological stress responses to the social environment, enabling individuals to cope with social stressors, but at the expense of plasma derived omega-3 fatty acids. PMID:25551380
Samma, Muhammad Kaleem; Zhou, Heng; Cui, Weiti; Zhu, Kaikai; Zhang, Jing; Shen, Wenbiao
2017-02-01
Recent results discovered the protective roles of methane (CH 4 ) against oxidative stress in animals. However, the possible physiological roles of CH 4 in plants are still unknown. By using physiological, histochemical and molecular approaches, the beneficial role of CH 4 in germinating alfalfa seeds upon copper (Cu) stress was evaluated. Endogenous production of CH 4 was significantly increased in Cu-stressed alfalfa seeds, which was mimicked by 0.39 mM CH 4 . The pretreatment with CH 4 significantly alleviated the inhibition of seed germination and seedling growth induced by Cu stress. Cu accumulation was obviously blocked as well. Meanwhile, α/β amylase activities and sugar contents were increased, all of which were consistent with the alleviation of seed germination inhibition triggered by CH 4 . The Cu-triggered oxidative stress was also mitigated, which was confirmed by the decrease of lipid peroxidation and reduction of Cu-induced loss of plasma membrane integrity in CH 4 -pretreated alfalfa seedlings. The results of antioxidant enzymes, including ascorbate peroxidase (APX), superoxide dismutase (SOD), catalase (CAT), and guaiacol peroxidase (POD) total or isozymatic activities, and corresponding transcripts (APX1/2, Cu/Zn SOD and Mn-SOD), indicated that CH 4 reestablished cellular redox homeostasis. Further, Cu-induced proline accumulation was partly impaired by CH 4 , which was supported by the alternation of proline metabolism. Together, these results indicated that CH 4 performs an advantageous effect on the alleviation of seed germination inhibition caused by Cu stress, and reestablishment of redox homeostasis mainly via increasing antioxidant defence.
The Potential Role of Nitric Oxide in Halting Cancer Progression Through Chemoprevention.
Vahora, Huzefa; Khan, Munawwar Ali; Alalami, Usama; Hussain, Arif
2016-03-01
Nitric oxide (NO) in general plays a beneficial physiological role as a vasorelaxant and the role of NO is decided by its concentration present in physiological environments. NO either facilitates cancer-promoting characters or act as an anti-cancer agent. The dilemma in this regard still remains unanswered. This review summarizes the recent information on NO and its role in carcinogenesis and tumor progression, as well as dietary chemopreventive agents which have NO-modulating properties with safe cytotoxic profile. Understanding the molecular mechanisms and cross-talk modulating NO effect by these chemopreventive agents can allow us to develop better therapeutic strategies for cancer treatment.
Functional metabolite assemblies—a review
NASA Astrophysics Data System (ADS)
Aizen, Ruth; Tao, Kai; Rencus-Lazar, Sigal; Gazit, Ehud
2018-05-01
Metabolites are essential for the normal operation of cells and fulfill various physiological functions. It was recently found that in several metabolic disorders, the associated metabolites could self-assemble to generate amyloid-like structures, similar to canonical protein amyloids that have a role in neurodegenerative disorders. Yet, assemblies with typical amyloid characteristics are also known to have physiological function. In addition, many non-natural proteins and peptides presenting amyloidal properties have been used for the fabrication of functional nanomaterials. Similarly, functional metabolite assemblies are also found in nature, demonstrating various physiological roles. A notable example is the structural color formed by guanine crystals or fluorescent crystals in feline eyes responsible for enhanced night vision. Moreover, some metabolites have been used for the in vitro fabrication of functional materials, such as glycine crystals presenting remarkable piezoelectric properties or indigo films used to assemble organic semi-conductive electronic devices. Therefore, we believe that the study of metabolite assemblies is not only important in order to understand their role in normal physiology and in pathology, but also paves a new route in exploring the fabrication of organic, bio-compatible materials.
The Integrative Role of the Sigh in Psychology, Physiology, Pathology, and Neurobiology
Ramirez, Jan-Marino
2015-01-01
“Sighs, tears, grief, distress” expresses Johann Sebastian Bach in a musical example for the relationship between sighs and deep emotions. This review explores the neurobiological basis of the sigh and its relationship with psychology, physiology, and pathology. Sighs monitor changes in brain states, induce arousal, and reset breathing variability. These behavioral roles homeostatically regulate breathing stability under physiological and pathological conditions. Sighs evoked in hypoxia evoke arousal and thereby become critical for survival. Hypoarousal and failure to sigh have been associated with sudden infant death syndrome. Increased breathing irregularity may provoke excessive sighing and hyperarousal, a behavioral sequence that may play a role in panic disorders. Essential for generating sighs and breathing is the pre-Bötzinger complex. Modulatory and synaptic interactions within this local network and between networks located in the brainstem, cerebellum, cortex, hypothalamus, amygdala, and the periaqueductal gray may govern the relationships between physiology, psychology, and pathology. Unraveling these circuits will lead to a better understanding of how we balance emotions and how emotions become pathological. PMID:24746045
The Role of Flipped Learning in Managing the Cognitive Load of a Threshold Concept in Physiology
ERIC Educational Resources Information Center
Akkaraju, Shylaja
2016-01-01
To help students master challenging, threshold concepts in physiology, I used the flipped learning model in a human anatomy and physiology course with very encouraging results in terms of student motivation, preparedness, engagement, and performance. The flipped learning model was enhanced by pre-training and formative assessments that provided…
Comparative physiology of a central hardwood old-growth forest canopy and forest gap
A. R. Gillespie; J. Waterman; K. Saylors
1993-01-01
Concerns of poor oak regeneration, changing climate, biodiversity patterns, and carbon cycling in the Central Hardwoods have prompted ecological and physiological studies of old-growth forests and their role in maintaining the landscape. To examine the effects of old-growth canopy structure on the physiological productivity of overstory and understory species, we...
Case Study Analysis and the Remediation of Misconceptions about Respiratory Physiology
ERIC Educational Resources Information Center
Cliff, William H.
2006-01-01
Most students enter the physiology classroom with one or more fundamental misconceptions about respiratory physiology. This study examined the prevalence of four respiratory misconceptions and determined the role of case analysis in the remediation of one of them. A case study was used to help students learn about oxygen transport in the blood and…
ERIC Educational Resources Information Center
Mavritsaki, Eirini; Heinke, Dietmar; Allen, Harriet; Deco, Gustavo; Humphreys, Glyn W.
2011-01-01
We present the case for a role of biologically plausible neural network modeling in bridging the gap between physiology and behavior. We argue that spiking-level networks can allow "vertical" translation between physiological properties of neural systems and emergent "whole-system" performance--enabling psychological results to be simulated from…
Physiological functioning of the ear and masking
NASA Technical Reports Server (NTRS)
1984-01-01
The physiological functions of the ear and the role masking plays in speech communication are examined. Topics under investigation include sound analysis of the ear, the aural reflex, and various types of noise masking.
Hematological shift in goat kids naturally devoid of prion protein.
Reiten, Malin R; Bakkebø, Maren K; Brun-Hansen, Hege; Lewandowska-Sabat, Anna M; Olsaker, Ingrid; Tranulis, Michael A; Espenes, Arild; Boysen, Preben
2015-01-01
The physiological role of the cellular prion protein (PrP(C)) is incompletely understood. The expression of PrP(C) in hematopoietic stem cells and immune cells suggests a role in the development of these cells, and in PrP(C) knockout animals altered immune cell proliferation and phagocytic function have been observed. Recently, a spontaneous nonsense mutation at codon 32 in the PRNP gene in goats of the Norwegian Dairy breed was discovered, rendering homozygous animals devoid of PrP(C). Here we report hematological and immunological analyses of homozygous goat kids lacking PrP(C) (PRNP(Ter/Ter) ) compared to heterozygous (PRNP (+/Ter)) and normal (PRNP (+/+)) kids. Levels of cell surface PrP(C) and PRNP mRNA in peripheral blood mononuclear cells (PBMCs) correlated well and were very low in PRNP (Ter/Ter), intermediate in PRNP (+/Ter) and high in PRNP (+/+) kids. The PRNP (Ter/Ter) animals had a shift in blood cell composition with an elevated number of red blood cells (RBCs) and a tendency toward a smaller mean RBC volume (P = 0.08) and an increased number of neutrophils (P = 0.068), all values within the reference ranges. Morphological investigations of blood smears and bone marrow imprints did not reveal irregularities. Studies of relative composition of PBMCs, phagocytic ability of monocytes and T-cell proliferation revealed no significant differences between the genotypes. Our data suggest that PrP(C) has a role in bone marrow physiology and warrant further studies of PrP(C) in erythroid and immune cell progenitors as well as differentiated effector cells also under stressful conditions. Altogether, this genetically unmanipulated PrP(C)-free animal model represents a unique opportunity to unveil the enigmatic physiology and function of PrP(C).
Takano, Yoko; Echizen, Honami
2017-01-01
Abstract Significance: Hydrogen sulfide (H2S) plays roles in many physiological processes, including relaxation of vascular smooth muscles, mediation of neurotransmission, inhibition of insulin signaling, and regulation of inflammation. Also, hydropersulfide (R−S−SH) and polysulfide (−S−Sn−S−) have recently been identified as reactive sulfur species (RSS) that regulate the bioactivities of multiple proteins via S-sulfhydration of cysteine residues (protein Cys−SSH) and show cytoprotection. Chemical tools such as fluorescent probes and selective inhibitors are needed to establish in detail the physiological roles of H2S and polysulfide. Recent Advances: Although many fluorescent probes for H2S are available, fluorescent probes for hydropersulfide and polysulfide have only recently been developed and used to detect these sulfur species in living cells. Critical Issues: In this review, we summarize recent progress in developing chemical tools for the study of H2S, hydropersulfide, and polysulfide, covering fluorescent probes based on various design strategies and selective inhibitors of H2S- and polysulfide-producing enzymes (cystathionine γ-lyase, cystathionine β-synthase, and 3-mercaptopyruvate sulfurtransferase), and we summarize their applications in biological studies. Future Directions: Despite recent progress, the precise biological functions of H2S, hydropersulfide, and polysulfide remain to be fully established. Fluorescent probes and selective inhibitors are effective chemical tools to study the physiological roles of these sulfur molecules in living cells and tissues. Therefore, further development of a broad range of practical fluorescent probes and selective inhibitors as tools for studies of RSS biology is currently attracting great interest. Antioxid. Redox Signal. 27, 669–683. PMID:28443673
Zhou, Gao; Zhou, Wenyu; Schüssler-Fiorenza Rose, Sophia Miryam; Perelman, Dalia; Colbert, Elizabeth; Runge, Ryan; Rego, Shannon; Sonecha, Ria; Datta, Somalee; McLaughlin, Tracey; Snyder, Michael P.
2017-01-01
A new wave of portable biosensors allows frequent measurement of health-related physiology. We investigated the use of these devices to monitor human physiological changes during various activities and their role in managing health and diagnosing and analyzing disease. By recording over 250,000 daily measurements for up to 43 individuals, we found personalized circadian differences in physiological parameters, replicating previous physiological findings. Interestingly, we found striking changes in particular environments, such as airline flights (decreased peripheral capillary oxygen saturation [SpO2] and increased radiation exposure). These events are associated with physiological macro-phenotypes such as fatigue, providing a strong association between reduced pressure/oxygen and fatigue on high-altitude flights. Importantly, we combined biosensor information with frequent medical measurements and made two important observations: First, wearable devices were useful in identification of early signs of Lyme disease and inflammatory responses; we used this information to develop a personalized, activity-based normalization framework to identify abnormal physiological signals from longitudinal data for facile disease detection. Second, wearables distinguish physiological differences between insulin-sensitive and -resistant individuals. Overall, these results indicate that portable biosensors provide useful information for monitoring personal activities and physiology and are likely to play an important role in managing health and enabling affordable health care access to groups traditionally limited by socioeconomic class or remote geography. PMID:28081144
Rudnicki, Jacek; Boberski, Marek; Butrymowicz, Ewa; Niedbalski, Paweł; Ogniewski, Paweł; Niedbalski, Marek; Niedbalski, Zbigniew; Podraza, Wojciech; Podraza, Hanna
2012-08-01
Stimulation of the nervous system plays an important role in brain function and psychomotor development of children. Massage can benefit premature infants, but has limitations. The authors conducted a study to verify the direct effects of massage on amplitude-integrated electroencephalography (aEEG), oxygen saturation (SaO(2)), and pulse analyzed by color cerebral function monitor (CCFM) and cerebral blood flow assessed by the Doppler technique. The amplitude of the aEEG trend during massage significantly increased. Massage also impacted the dominant frequency δ waves. Frequency significantly increased during the massage and return to baseline after treatment. SaO(2) significantly decreased during massage. In four premature infants, massage was discontinued due to desaturation below 85%. Pulse frequency during the massage decreased but remained within physiological limits of greater than 100 beats per minute in all infants. Doppler flow values in the anterior cerebral artery measured before and after massage did not show statistically significant changes. Resistance index after massage decreased, which might provide greater perfusion of the brain, but this difference was not statistically significant. Use of the CCFM device allows for monitoring of three basic physiologic functions, namely aEEG, SaO(2), and pulse, and increases the safety of massage in preterm infants. Copyright © 2012 by Thieme Medical Publishers
Lack of Day/Night variation in fibroblast growth factor 21 levels in young healthy men.
Foo, J-P; Aronis, K N; Chamberland, J P; Mantzoros, C S
2015-06-01
Fibroblast growth factor (FGF) 21 is an endocrine factor with an emerging role as a metabolic regulator. We previously reported the presence of a significant day/night variation of FGF-21 in energy-replete, healthy female subjects. However the day/night patterns of secretion in male subjects remain to be fully elucidated. To elucidate day/night pattern of FGF-21 levels in male subjects in the energy-replete state, its relationship to FFA and to investigate whether a sexual dimorphism exists in FGF-21 physiology. Eight healthy lean male subjects were studied for up to 5 days while on an isocaloric diet. Blood samples were obtained for measurement of FGF-21 and free fatty acids (FFA) hourly from 0800 AM on day 4 till 0800AM on day 5. FGF-21 did not exhibit any statistically significant day/night variation pattern of circulating FGF-21 levels during the isocaloric fed state in male subjects. FGF-21 levels in male subjects are closely cross-correlated with FFA levels, similar to female subjects. A sexual dimorphism exists in FGF-21 physiology; that as opposed to female subjects, no significant day/night variation exists in FGF-21 rhythm in male subjects in the energy-replete state. Circulating pattern of FGF-21, similar to the female subjects, was highly cross-correlated to the FFA levels in the male subjects, signifying that the sexual dimorphism in FGF-21 physiology may be related to the differing lipid metabolism in both the genders.
Drake, Madeline J; Miller, Nathan A; Todgham, Anne E
2017-09-01
Much of our understanding of the thermal physiology of intertidal organisms comes from experiments with animals acclimated under constant conditions and exposed to a single heat stress. In nature, however, the thermal environment is more complex. Aerial exposure and the unpredictable nature of thermal stress during low tides may be critical factors in defining the thermal physiology of intertidal organisms. In the fingered limpet, Lottia digitalis , we investigated whether upper temperature tolerance and thermal sensitivity were influenced by the pattern of fluctuation with which thermal stress was applied. Specifically, we examined whether there was a differential response (measured as cardiac performance) to repeated heat stress of a constant and predictable magnitude compared with heat stress applied in a stochastic and unpredictable nature. We also investigated differences in cellular metabolism and damage following immersion for insights into biochemical mechanisms of tolerance. Upper temperature tolerance increased with aerial exposure, but no significant differences were found between predictable treatments of varying magnitudes (13°C versus 24°C versus 32°C). Significant differences in thermal tolerance were found between unpredictable trials with different heating patterns. There were no significant differences among treatments in basal citrate synthase activity, glycogen content, oxidative stress or antioxidants. Our results suggest that aerial exposure and recent thermal history, paired with relief from high low-tide temperatures, are important factors modulating the capacity of limpets to deal with thermal stress. © 2017. Published by The Company of Biologists Ltd.
Ramprasath, Tharmarajan; Kalpana, Krishnan
2015-01-01
Physiological cardiac hypertrophy is an adaptive mechanism, induced during chronic exercise. As it is reversible and not associated with cardiomyocyte death, it is considered as a natural tactic to prevent cardiac dysfunction and failure. Though, different studies revealed the importance of microRNAs (miRNAs) in pathological hypertrophy, their role during physiological hypertrophy is largely unexplored. Hence, this study is aimed at revealing the global expression profile of miRNAs during physiological cardiac hypertrophy. Chronic swimming protocol continuously for eight weeks resulted in induction of physiological hypertrophy in rats and histopathology revealed the absence of tissue damage, apoptosis or fibrosis. Subsequently, the total RNA was isolated and small RNA sequencing was executed. Analysis of small RNA reads revealed the differential expression of a large set of miRNAs during physiological hypertrophy. The expression profile of the significantly differentially expressed miRNAs was validated by qPCR. In silico prediction of target genes by miRanda, miRdB and TargetScan and subsequent qPCR analysis unraveled that miRNAs including miR-99b, miR-100, miR-19b, miR-10, miR-208a, miR-133, miR-191a, miR-22, miR-30e and miR-181a are targeting the genes that primarily regulate cell proliferation and cell death. Gene ontology and pathway mapping showed that the differentially expressed miRNAs and their target genes were mapped to apoptosis and cell death pathways principally via PI3K/Akt/mTOR and MAPK signaling. In summary, our data indicates that regulation of these miRNAs with apoptosis regulating potential can be one of the major key factors in determining pathological or physiological hypertrophy by controlling fibrosis, apoptosis and cell death mechanisms. PMID:25793527
Syndecan-4 Signaling Is Required for Exercise-Induced Cardiac Hypertrophy
Xie, Jun; He, Guixin; Chen, Qinhua; Sun, Jiayin; Dai, Qin; Lu, Jianrong; Li, Guannan; Wu, Han; Li, Ran; Chen, Jianzhou; Xu, Wei; Xu, Biao
2016-01-01
Cardiac hypertrophy can be broadly classified as either physiological or pathological. Physiological stimuli such as exercise cause adaptive cardiac hypertrophy and normal heart function. Pathological stimuli including hypertension and aortic valvular stenosis cause maladaptive cardiac remodeling and ultimately heart failure. Syndecan-4 (synd4) is a transmembrane proteoglycan identified as being involved in cardiac adaptation after injury, but whether it takes part in physiological cardiac hypertrophy is unclear. We observed upregulation of synd4 in exercise-induced hypertrophic myocardium. To evaluate the role of synd4 in the physiological form of cardiac hypertrophy, mice lacking synd4 (synd4–/–) were exercised by swimming for 4 wks. Ultrasonic cardiogram (UCG) and histological analysis revealed that swimming induced the hypertrophic phenotype but was blunted in synd4–/– compared with wild-type (WT) mice. The swimming-induced activation of Akt, a key molecule in physiological hypertrophy was also more decreased than in WT controls. In cultured cardiomyocytes, synd4 overexpression could induce cell enlargement, protein synthesis and distinct physiological molecular alternation. Akt activation also was observed in synd4-overexpressed cardiomyocytes. Furthermore, inhibition of protein kinase C (PKC) prevented the synd4-induced hypertrophic phenotype and Akt phosphorylation. This study identified an essential role of synd4 in mediation of physiological cardiac hypertrophy. PMID:26835698
Brown Adipose Tissue Improves Whole-Body Glucose Homeostasis and Insulin Sensitivity in Humans
Chondronikola, Maria; Volpi, Elena; Børsheim, Elisabet; Porter, Craig; Annamalai, Palam; Enerbäck, Sven; Lidell, Martin E.; Saraf, Manish K.; Labbe, Sebastien M.; Hurren, Nicholas M.; Yfanti, Christina; Chao, Tony; Andersen, Clark R.; Cesani, Fernando; Hawkins, Hal
2014-01-01
Brown adipose tissue (BAT) has attracted scientific interest as an antidiabetic tissue owing to its ability to dissipate energy as heat. Despite a plethora of data concerning the role of BAT in glucose metabolism in rodents, the role of BAT (if any) in glucose metabolism in humans remains unclear. To investigate whether BAT activation alters whole-body glucose homeostasis and insulin sensitivity in humans, we studied seven BAT-positive (BAT+) men and five BAT-negative (BAT−) men under thermoneutral conditions and after prolonged (5–8 h) cold exposure (CE). The two groups were similar in age, BMI, and adiposity. CE significantly increased resting energy expenditure, whole-body glucose disposal, plasma glucose oxidation, and insulin sensitivity in the BAT+ group only. These results demonstrate a physiologically significant role of BAT in whole-body energy expenditure, glucose homeostasis, and insulin sensitivity in humans, and support the notion that BAT may function as an antidiabetic tissue in humans. PMID:25056438
Regulation of the Cardiovascular System by Histamine.
Hattori, Yuichi; Hattori, Kohshi; Matsuda, Naoyuki
2017-01-01
Histamine mediates a wide range of cellular responses, including allergic and inflammatory reactions, gastric acid secretion, and neurotransmission in the central nervous system. Histamine also exerts a series of actions upon the cardiovascular system but may not normally play a significant role in regulating cardiovascular function. During tissue injury, inflammation, and allergic responses, mast cells (or non-mast cells) within the tissues can release large amounts of histamine that leads to noticeable cardiovascular effects. Owing to intensive research during several decades, the distribution, function, and pathophysiological role of cardiovascular H 1 - and H 2 -receptors has become recognized adequately. Besides the recognized H 1 - and H 2 -receptor-mediated cardiovascular responses, novel roles of H 3 - and H 4 -receptors in cardiovascular physiology and pathophysiology have been identified over the last decade. In this review, we describe recent advances in our understanding of cardiovascular function and dysfunction mediated by histamine receptors, including H 3 - and H 4 -receptors, their potential mechanisms of action, and their pathological significance.
PHOTOPERIODISM, REPRODUCTION(PHYSIOLOGY)), (*ENDOCRINE GLANDS , REPRODUCTION(PHYSIOLOGY)), RODENTS, REPRODUCTIVE SYSTEM, EYE, EXCISION, TESTES, OVARIES, ADRENAL GLANDS , THYROID GLAND , IODINE, THIOUREA, RATS, HAMSTERS
Hu, Wen-Jun; Wu, Qian; Liu, Xiang; Shen, Zhi-Jun; Chen, Juan; Liu, Ting-Wu; Chen, Juan; Zhu, Chun-Quan; Wu, Fei-Hua; Chen, Lin; Wei, Jia; Qiu, Xiao-Yun; Shen, Guo-Xin; Zheng, Hai-Lei
2016-01-04
Acid rain (AR) impacts forest health by leaching calcium (Ca) away from soils and plants. Ca is an essential element and participates in various plant physiological responses. In the present study, the protective role of exogenous Ca in alleviating AR stress in Liquidambar formosana Hance at the physiological and proteomic levels was examined. Our results showed that low Ca condition resulted in the chlorophyll content and photosynthesis decreasing significantly in L. formosana leaves; however, these effects could be reversed by high Ca supplementation. Further proteomic analyses successfully identified 81 differentially expressed proteins in AR-treated L. formosana under different Ca levels. In particular, some of the proteins are involved in primary metabolism, photosynthesis, energy production, antioxidant defense, transcription, and translation. Moreover, quantitative real time polymerase chain reaction (qRT-PCR) results indicated that low Ca significantly increased the expression level of the investigated Ca-related genes, which can be reversed by high Ca supplementation under AR stress. Further, Western blotting analysis revealed that exogenous Ca supply reduced AR damage by elevating the expression of proteins involved in the Calvin cycle, reactive oxygen species (ROS) scavenging system. These findings allowed us to better understand how woody plants respond to AR stress at various Ca levels and the protective role of exogenous Ca against AR stress in forest tree species.
Vail, Graham; Cheng, Aifang; Han, Yu Ray; Zhao, Teng; Du, Shengwang; Loy, Michael M T; Herrup, Karl; Plummer, Mark R
2016-07-01
Ataxia telangiectasia is a multisystemic disorder that includes a devastating neurodegeneration phenotype. The ATM (ataxia-telangiectasia mutated) protein is well-known for its role in the DNA damage response, yet ATM is also found in association with cytoplasmic vesicular structures: endosomes and lysosomes, as well as neuronal synaptic vesicles. In keeping with this latter association, electrical stimulation of the Schaffer collateral pathway in hippocampal slices from ATM-deficient mice does not elicit normal long-term potentiation (LTP). The current study was undertaken to assess the nature of this deficit. Theta burst-induced LTP was reduced in Atm(-/-) animals, with the reduction most pronounced at burst stimuli that included 6 or greater trains. To assess whether the deficit was associated with a pre- or postsynaptic failure, we analyzed paired-pulse facilitation and found that it too was significantly reduced in Atm(-/-) mice. This indicates a deficit in presynaptic function. As further evidence that these synaptic effects of ATM deficiency were presynaptic, we used stochastic optical reconstruction microscopy. Three-dimensional reconstruction revealed that ATM is significantly more closely associated with Piccolo (a presynaptic marker) than with Homer1 (a postsynaptic marker). These results underline how, in addition to its nuclear functions, ATM plays an important functional role in the neuronal synapse where it participates in the regulation of presynaptic vesicle physiology. Copyright © 2016 the American Physiological Society.
Feng, Mao; Ramadan, Haitham; Han, Bin; Fang, Yu; Li, Jianke
2014-07-05
Hemolymph plays key roles in honey bee molecule transport, immune defense, and in monitoring the physiological condition. There is a lack of knowledge regarding how the proteome achieves these biological missions for both the western and eastern honey bees (Apis mellifera and Apis cerana). A time-resolved proteome was compared using two-dimensional electrophoresis-based proteomics to reveal the mechanistic differences by analysis of hemolymph proteome changes between the worker bees of two bee species during the larval to pupal stages. The brood body weight of Apis mellifera was significantly heavier than that of Apis cerana at each developmental stage. Significantly, different protein expression patterns and metabolic pathways were observed in 74 proteins (166 spots) that were differentially abundant between the two bee species. The function of hemolymph in energy storage, odor communication, and antioxidation is of equal importance for the western and eastern bees, indicated by the enhanced expression of different protein species. However, stronger expression of protein folding, cytoskeletal and developmental proteins, and more highly activated energy producing pathways in western bees suggests that the different bee species have developed unique strategies to match their specific physiology using hemolymph to deliver nutrients and in immune defense. Our disparate findings constitute a proof-of-concept of molecular details that the ecologically shaped different physiological conditions of different bee species match with the hemolymph proteome during the brood stage. This also provides a starting point for future research on the specific hemolymph proteins or pathways related to the differential phenotypes or physiology.
Harrison-Bernard, Lisa M; Naljayan, Mihran V; Eason, Jane M; Mercante, Donald E; Gunaldo, Tina P
2017-12-01
The primary purpose of conducting an interprofessional education (IPE) experience during the renal physiology block of a graduate-level course was to provide basic science, physical therapy, and physician assistant graduate students with an opportunity to work as a team in the diagnosis, treatment, and collaborative care of a patient with acute kidney injury. The secondary purpose was to enhance the understanding of basic renal physiology principles with a patient case presentation of renal pathophysiology. The overall purpose was to assess the value of IPE integration within a basic science course by examining student perceptions and program evaluation. Graduate-level students operated in interprofessional teams while working through an acute kidney injury patient case. The following Interprofessional Education Collaborative subcompetencies were targeted: Roles/Responsibilities (RR) Behavioral Expectations (RR1, RR4) and Interprofessional Communication (CC) Behavioral Expectations (CC4). Clinical and IPE stimulus questions were discussed both within and between teams with assistance provided by faculty facilitators. Students were given a pre- and postsurvey to determine their knowledge of IPE. There were statistically significant increases from pre- to postsurvey scores for all six IPE questions for all students. Physical therapy and physician assistant students had a statistically significant increase in pre- to postsurvey scores, indicating a more favorable perception of their interprofessional competence for RR1, RR4, and CC4. No changes were noted in pre- to postsurvey scores for basic science graduate students. Incorporating planned IPE experiences into multidisciplinary health science courses represents an appropriate venue to have students learn and apply interprofessional competencies. Copyright © 2017 the American Physiological Society.
Taylor, S.B.; Watterson, L.R.; Kufahl, P.R.; Nemirovsky, N.E.; Tomek, S.E.; Conrad, C.D.; Olive, M.F.
2016-01-01
Stress is a contributing factor to the development and maintenance of addiction in humans. However, few studies have shown that stress potentiates the rewarding and/or reinforcing effects of methamphetamine in rodent models of addiction. The present study assessed the effects of exposure to 14 days of chronic variable stress (CVS), or no stress as a control (CON), on the rewarding and reinforcing effects of methamphetamine in adult rats using the conditioned place preference (Experiment 1) and intravenous self-administration (Experiment 2) paradigms. In Experiment 2, we also assessed individual differences in open field locomotor activity, anxiety-like behavior in the elevated plus maze (EPM), and physiological responses to a novel environment as possible predictors of methamphetamine intake patterns. Exposure to CVS for 14 days did not affect overall measures of methamphetamine conditioned reward or reinforcement. However, analyses of individual differences and direct vs. indirect effects revealed that rats exhibiting high physiological reactivity and locomotor activity in the EPM and open field tests self-administered more methamphetamine and reached higher breakpoints for drug reinforcement than rats exhibiting low reactivity. In addition, CVS exposure significantly increased the proportion of rats that exhibited high reactivity, and high reactivity was significantly correlated with increased levels of methamphetamine intake. These findings suggest that individual differences in physiological and locomotor reactivity to novel environments, as well as their interactions with stress history, predict patterns of drug intake in rodent models of methamphetamine addiction. Such predictors may eventually inform future strategies for implementing individualized treatment strategies for amphetamine use disorders. PMID:27163191
Serum Ferritin: Past, Present and Future
Wang, Wei; Knovich, Mary Ann; Coffman, Lan G.; Torti, Frank M.; Torti, Suzy V.
2010-01-01
Background Serum ferritin was discovered in the 1930’s, and was developed as a clinical test in the 1970’s. Many diseases are associated with iron overload or iron deficiency. Serum ferritin is widely used in diagnosing and monitoring these diseases. Scope of Review In this chapter, we discuss the role of serum ferritin in physiological and pathological processes and its use as a clinical tool. Major Conclusions Although many aspects of the fundamental biology of serum ferritin remain surprisingly unclear, a growing number of roles have been attributed to extracellular ferritin, including newly described roles in iron delivery, angiogenesis, inflammation, immunity, signaling and cancer. General Significance Serum ferritin remains a clinically useful tool. Further studies on the biology of this protein may provide new biological insights. PMID:20304033
Brown adipose tissue: The heat is on the heart.
Thoonen, Robrecht; Hindle, Allyson G; Scherrer-Crosbie, Marielle
2016-06-01
The study of brown adipose tissue (BAT) has gained significant scientific interest since the discovery of functional BAT in adult humans. The thermogenic properties of BAT are well recognized; however, data generated in the last decade in both rodents and humans reveal therapeutic potential for BAT against metabolic disorders and obesity. Here we review the current literature in light of a potential role for BAT in beneficially mediating cardiovascular health. We focus mainly on BAT's actions in obesity, vascular tone, and glucose and lipid metabolism. Furthermore, we discuss the recently discovered endocrine factors that have a potential beneficial role in cardiovascular health. These BAT-secreted factors may have a favorable effect against cardiovascular risk either through their metabolic role or by directly affecting the heart. Copyright © 2016 the American Physiological Society.
ERIC Educational Resources Information Center
Singh, Satendra
2013-01-01
The Undergraduate Medical Program (Bachelor of Medicine and Bachelor of Surgery) at University College of Medical Sciences (Delhi, India) is a 4.5-yr, intense academic program where physiology is taught in the first year. To make the learning experience enriching, the Department of Physiology organizes four student seminars (two seminars/semester)…
Miyadera, Hiroko; Shiomi, Kazuro; Ui, Hideaki; Yamaguchi, Yuichi; Masuma, Rokuro; Tomoda, Hiroshi; Miyoshi, Hideto; Osanai, Arihiro; Kita, Kiyoshi; Ōmura, Satoshi
2003-01-01
Enzymes in the mitochondrial respiratory chain are involved in various physiological events in addition to their essential role in the production of ATP by oxidative phosphorylation. The use of specific and potent inhibitors of complex I (NADH-ubiquinone reductase) and complex III (ubiquinol-cytochrome c reductase), such as rotenone and antimycin, respectively, has allowed determination of the role of these enzymes in physiological processes. However, unlike complexes I, III, and IV (cytochrome c oxidase), there are few potent and specific inhibitors of complex II (succinate-ubiquinone reductase) that have been described. In this article, we report that atpenins potently and specifically inhibit the succinate-ubiquinone reductase activity of mitochondrial complex II. Therefore, atpenins may be useful tools for clarifying the biochemical and structural properties of complex II, as well as for determining its physiological roles in mammalian tissues. PMID:12515859
Role of sugars under abiotic stress.
Sami, Fareen; Yusuf, Mohammad; Faizan, Mohammad; Faraz, Ahmad; Hayat, Shamsul
2016-12-01
Sugars are the most important regulators that facilitate many physiological processes, such as photosynthesis, seed germination, flowering, senescence, and many more under various abiotic stresses. Exogenous application of sugars in low concentration promote seed germination, up regulates photosynthesis, promotes flowering, delayed senescence under various unfavorable environmental conditions. However, high concentration of sugars reverses all these physiological process in a concentration dependent manner. Thus, this review focuses the correlation between sugars and their protective functions in several physiological processes against various abiotic stresses. Keeping in mind the multifaceted role of sugars, an attempt has been made to cover the role of sugar-regulated genes associated with photosynthesis, seed germination and senescence. The concentration of sugars determines the expression of these sugar-regulated genes. This review also enlightens the interaction of sugars with several phytohormones, such as abscisic acid, ethylene, cytokinins and gibberellins and its effect on their biosynthesis under abiotic stress conditions. Copyright © 2016 Elsevier Masson SAS. All rights reserved.
Grossi, Giorgio; Perski, Aleksander; Osika, Walter; Savic, Ivanka
2015-12-01
The aim of this paper was to provide an overview of the literature on clinically significant burnout, focusing on its assessment, associations with sleep disturbances, cognitive impairments, as well as neurobiological and physiological correlates. Fifty-nine English language articles and six book chapters were included. The results indicate that exhaustion disorder (ED), as described in the Swedish version of the International Classification of Diseases, seems to be the most valid clinical equivalent of burnout. The data supports the notion that sleep impairments are causative and maintaining factors for this condition. Patients with clinical burnout/ED suffer from cognitive impairments in the areas of memory and executive functioning. The studies on neuro-biological mechanisms have reported functional uncoupling of networks relating the limbic system to the pre-frontal cortex, and decreased volumes of structures within the basal ganglia. Although there is a growing body of literature on the physiological correlates of clinical burnout/ED, there is to date no biomarker for this condition. More studies on the role of sleep disturbances, cognitive impairments, and neurobiological and physiological correlates in clinical burnout/ED are warranted. © 2015 Scandinavian Psychological Associations and John Wiley & Sons Ltd.
A Randomized Crossover Trial on Acute Stress-Related Physiological Responses to Mountain Hiking
Grafetstätter, Carina; Hartl, Arnulf; Kopp, Martin
2017-01-01
Green exercise, defined as physical activity in natural environments, might have positive effects on stress-related physiological measures. Little is known about the acute effects of green exercise bouts lasting longer than 60 min. Therefore, the aim of the present study was to analyze the acute effects of a three-hour green exercise intervention (mountain hiking) on stress-related physiological responses. Using a randomized crossover design, 42 healthy participants were exposed to three different conditions in a field-based experiment: outdoor mountain hiking, indoor treadmill walking, and sedentary control condition (three hours each). At baseline and at follow-up (five minutes after the condition), stress-related physiological responses (salivary cortisol, blood pressure, and heart rate variability) were measured. Salivary cortisol decreased in all conditions, but showed a larger decrease after both mountain hiking and treadmill walking compared to the sedentary control situation (partial η2 = 0.10). No differences were found between mountain hiking and treadmill walking in salivary cortisol. In heart rate variability and blood pressure, changes from baseline to follow-up did not significantly differ between the three conditions. The results indicate that three hours of hiking indoors or outdoors elicits positive effects on salivary cortisol concentration. Environmental effects seem to play a minor role in salivary cortisol, blood pressure, and heart rate variability. PMID:28800067
Donato, Jose; Lee, Charlotte; Ratra, Dhirender; Franci, Celso R.; Canteras, Newton S.; Elias, Carol F.
2013-01-01
We have recently demonstrated that the ventral premammillary nucleus (PMV) plays a key role in the metabolic control of the female reproductive axis. However, whether PMV neurons modulate the reproductive neural circuitry and/or the expression of sexual behaviors has not been determined. Here, we showed that the expression of estrogen and progesterone receptors in the PMV is modulated by changing levels of sex steroids across the estrous cycle. We also showed that sexual behavior, not the high physiologic levels of sex steroids, induces Fos in PMV neurons. Bilateral lesions of the PMV caused no significant changes in proceptive behavior but a high percentage of PMV-lesioned rats failed to exhibit lordosis behavior when exposed to a sexually-experienced male rat (50% vs. 18% in the control group). Notably, lesions of the PMV disrupted the physiologic fluctuations of Kiss1 and GnRH mRNA expression characteristic of the proestrus-to-estrus transition. This neurochemical imbalance may ultimately alter female reproductive behavior. Our findings suggest that the PMV is a component of the neural circuitry that modulates the physiologic fluctuations of key neuroendocrine players (i.e., Kiss1 and GnRH) in the control of the female reproductive physiology. PMID:23518222
The Adaptive Brain: Glenn Hatton and the Supraoptic Nucleus
Leng, G.; Moos, F. C.; Armstrong, W. E.
2017-01-01
In December 2009, Glenn Hatton died, and neuroendocrinology lost a pioneer who had done much to forge our present understanding of the hypothalamus and whose productivity had not faded with the passing years. Glenn, an expert in both functional morphology and electrophysiology, was driven by a will to understand the significance of his observations in the context of the living, behaving organism. He also had the wit to generate bold and challenging hypotheses, the wherewithal to expose them to critical and elegant experimental testing, and a way with words that gave his papers and lectures clarity and eloquence. The hypothalamo-neurohypophysial system offered a host of opportunities for understanding how physiological functions are fulfilled by the electrical activity of neurones, how neuronal behaviour changes with changing physiological states, and how morphological changes contribute to the physiological response. In the vision that Glenn developed over 35 years, the neuroendocrine brain is as dynamic in structure as it is adaptable in function. Its adaptability is reflected not only by mere synaptic plasticity, but also by changes in neuronal morphology and in the morphology of the glial cells. Astrocytes, in Glenn’s view, were intimate partners of the neurones, partners with an essential role in adaptation to changing physiological demands. PMID:20298459
Behavioral and Physiological Consequences of Sleep Restriction
Banks, Siobhan; Dinges, David F.
2007-01-01
Adequate sleep is essential for general healthy functioning. This paper reviews recent research on the effects of chronic sleep restriction on neurobehavioral and physiological functioning and discusses implications for health and lifestyle. Restricting sleep below an individual's optimal time in bed (TIB) can cause a range of neurobehavioral deficits, including lapses of attention, slowed working memory, reduced cognitive throughput, depressed mood, and perseveration of thought. Neurobehavioral deficits accumulate across days of partial sleep loss to levels equivalent to those found after 1 to 3 nights of total sleep loss. Recent experiments reveal that following days of chronic restriction of sleep duration below 7 hours per night, significant daytime cognitive dysfunction accumulates to levels comparable to that found after severe acute total sleep deprivation. Additionally, individual variability in neurobehavioral responses to sleep restriction appears to be stable, suggesting a traitlike (possibly genetic) differential vulnerability or compensatory changes in the neurobiological systems involved in cognition. A causal role for reduced sleep duration in adverse health outcomes remains unclear, but laboratory studies of healthy adults subjected to sleep restriction have found adverse effects on endocrine functions, metabolic and inflammatory responses, suggesting that sleep restriction produces physiological consequences that may be unhealthy. Citation: Banks S; Dinges DF. Behavioral and physiological consequences of sleep restriction. J Clin Sleep Med 2007;3(5):519-528. PMID:17803017
Arousal and affective differences between student gamblers and non-gamblers during a card game.
Pascual-Leone, Antonio; Campeau, Jennifer L; Harrington, Shawn J
2012-12-01
The current study examined the differences in arousal (physiologically and subjectively) between gamblers and non-gamblers. Thirty students from a mid-sized university took part in the study for a chance to win money in a gambling task. Nearly half of the participants identified themselves as non-gamblers and slightly more than half of the participants considered themselves gamblers. Findings indicated that gamblers experienced a significantly higher increase in physiological arousal (heart rate) compared to non-gamblers during the gambling experience. The results suggests the possibility that physiological arousal may play a role in the appeal of gambling to certain types of people. Furthermore, when gamblers suffered a loss at the end of the game, they reported feeling worse as compared to the non-gamblers and relative to their state before playing. Moreover, this affective change explained 28.6% of the variance in gambling behavior according to self-reports. Findings suggest that gamblers in our study may have been more personally invested in the gambling tasks, such that losing was more disappointing to the habitual gamblers than the non-gamblers.
Adrenocortical stress responses influence an invasive vertebrate's fitness in an extreme environment
Jessop, Tim S.; Letnic, Mike; Webb, Jonathan K.; Dempster, Tim
2013-01-01
Continued range expansion into physiologically challenging environments requires invasive species to maintain adaptive phenotypic performance. The adrenocortical stress response, governed in part by glucocorticoid hormones, influences physiological and behavioural responses of vertebrates to environmental stressors. However, any adaptive role of this response in invasive populations that are expanding into extreme environments is currently unclear. We experimentally manipulated the adrenocortical stress response of invasive cane toads (Rhinella marina) to investigate its effect on phenotypic performance and fitness at the species' range front in the Tanami Desert, Australia. Here, toads are vulnerable to overheating and dehydration during the annual hot–dry season and display elevated plasma corticosterone levels indicative of severe environmental stress. By comparing unmanipulated control toads with toads whose adrenocortical stress response was manipulated to increase acute physiological stress responsiveness, we found that control toads had significantly reduced daily evaporative water loss and higher survival relative to the experimental animals. The adrenocortical stress response hence appears essential in facilitating complex phenotypic performance and setting fitness trajectories of individuals from invasive species during range expansion. PMID:23945686
[The role of environmental factors in managing labour stress].
Rados, Melinda; Mészáros, Judit
2017-07-01
Emotional, cognitive and behavioural aspects of birth and labour stress are strongly associated with the underlying physiological processes. To study the factors of physical security and social support, the administration of synthetic oxytocin, and how they relate to perceived stress during childbirth. Women's experienced physical security, social support and oxytocin administration was measured with targeted questions, and their perceived stress with the short and modified version of the Perceived Stress Scale. A strong negative association was found between perceived stress and physical and social security. The group of women experiencing low physical and social security perceived significantly higher stress, while those given synthetic oxytocin perceived higher stress, and lower physical and social security. Since physiological, psychological processes and behaviours are strongly intertwined, the support of natural physiological birth without interventions is recommended, which considers not only short-term but long-term health consequences for mother and child. The contribution of calming physical surroundings, minimal interventions and empowering support of caregivers to safe and satisfying birth is demonstrated in a model. Orv Hetil. 2017; 158(29): 1149-1156.
Taylor, Zoe E.; Eisenberg, Nancy; Spinrad, Tracy L.
2015-01-01
The goal of this study was to examine physiological and environmental predictors of children’s sympathy (an emotional response consisting of feelings of concern or sorrow for others who are distressed or in need) and whether temperamental effortful control mediated these relations. Specifically, in a study of 192 children (23% Hispanic; 54% male), respiratory sinus arrhythmia (RSA), a measure thought to reflect physiological regulation, and observed authoritative parenting (both at 42 months) were examined as predictors of children’s effortful control (at 54 months) and, in turn, children’s sympathy (at 72 and 84 months). Measures of both baseline RSA and RSA suppression were examined. In a structural equation model, observed parenting was positively related to children’s subsequent sympathy through its positive relation to effortful control. Furthermore, the indirect path from baseline RSA to higher sympathy through effortful control was marginally significant. Authoritative parenting and baseline RSA uniquely predicted individual differences in children’s effortful control. Findings highlight the potential role of both authoritative parenting and physiological regulation in the development of children’s sympathy. PMID:25329555
Taylor, Zoe E; Eisenberg, Nancy; Spinrad, Tracy L
2015-01-01
The goal of this study was to examine physiological and environmental predictors of children's sympathy (an emotional response consisting of feelings of concern or sorrow for others who are distressed or in need) and whether temperamental effortful control mediated these relations. Specifically, in a study of 192 children (23% Hispanic; 54% male), respiratory sinus arrhythmia (RSA), a measure thought to reflect physiological regulation, and observed authoritative parenting (both at 42 months) were examined as predictors of children's effortful control (at 54 months) and, in turn, children's sympathy (at 72 and 84 months). Measures of both baseline RSA and RSA suppression were examined. In a structural equation model, observed parenting was positively related to children's subsequent sympathy through its positive relation to effortful control. Furthermore, the indirect path from baseline RSA to higher sympathy through effortful control was marginally significant. Authoritative parenting and baseline RSA uniquely predicted individual differences in children's effortful control. Findings highlight the potential role of both authoritative parenting and physiological regulation in the development of children's sympathy.
Seebacher, Frank
2005-10-01
Biological functions are dependent on the temperature of the organism. Animals may respond to fluctuation in the thermal environment by regulating their body temperature and by modifying physiological and biochemical rates. Phenotypic flexibility (reversible phenotypic plasticity, acclimation, or acclimatisation in rate functions occurs in all major taxonomic groups and may be considered as an ancestral condition. Within the Reptilia, representatives from all major groups show phenotypic flexibility in response to long-term or chronic changes in the thermal environment. Acclimation or acclimatisation in reptiles are most commonly assessed by measuring whole animal responses such as oxygen consumption, but whole animal responses are comprised of variation in individual traits such as enzyme activities, hormone expression, and cardiovascular functions. The challenge now lies in connecting the changes in the components to the functioning of the whole animal and its fitness. Experimental designs in research on reptilian thermal physiology should incorporate the capacity for reversible phenotypic plasticity as a null-hypothesis, because the significance of differential body temperature-performance relationships (thermal reaction norms) between individuals, populations, or species cannot be assessed without testing that null-hypothesis.
International collaboration on Russian spacecraft and the case for free flyer biosatellites
NASA Technical Reports Server (NTRS)
Grindeland, Richard E.; Ilyin, Eugene A.; Holley, Daniel C.; Skidmore, Michael G.
2005-01-01
Animal research has been critical to the initiation and progress of space exploration. Animals were the original explorers of "space" two centuries ago and have played a crucial role by demonstrating that the space environment, with precautions, is compatible with human survival. Studies of mammals have yielded much of our knowledge of space physiology. As spaceflights to other planets are anticipated, animal research will continue to be essential to further reveal space physiology and to enable the longer missions. Much of the physiology data collected from space was obtained from the Cosmos (Bion) spaceflights, a series of Russian (Soviet)-International collaborative flights, over a 22 year period, which employed unmanned, free flyer biosatellites. Begun as a Soviet-only program, after the second flight the Russians invited American and other foreign scientists to participate. This program filled the 10 year hiatus between the last US biosatellite and the first animal experiments on the shuttles. Of the 11 flights in the Cosmos program nine of them were international; the flights continued over the years regardless of political differences between the Soviet Union and the Western world. The science evolved from sharing tissues to joint international planning and development, and from rat postmortem tissue analysis to in vivo measurements of a host of monkey physiological parameters during flight. Many types of biological specimens were carried on the modified Vostok spacecraft, but only the mammalian studies are discussed herein. The types of studies done encompass the full range of physiology and have begun to answer "critical" questions of space physiology posed by various ad hoc committees. The studies have not only yielded a prodigious and significant body of data, they have also introduced some new perspectives in physiology. A number of the physiological insights gained are relevant to physiology on Earth. The Cosmos flights also added significantly to flight-related technology, some of which also has application on our planet. In summary, the Cosmos biosatellite flights were extremely productive and of low cost. The Bion vehicles are versatile in that they can be placed into a variety of orbits and altitudes, and can carry radiation sources or other hazardous material which cannot be carried on manned vehicles. With recent advances in sensor, robotic, and data processing technology, future free flyers will be even more productive, and will largely preclude the need to fly animal experiments on manned vehicles. Currently, mammalian researchers do not have access to space for an unknown time, seriously impeding the advancement and understanding of space physiology during long duration missions. Initiation of a new, international program of free flyer biosatellites is critical to our further understanding of space physiology, and essential to continued human exploration of space.
Czarzasta, Katarzyna; Cudnoch-Jedrzejewska, Agnieszka
2014-01-01
Research studies indicate a role of the apelinergic and vasopressinergic systems both in the regulation of the cardiovascular system and the pathogenesis of CVD, including in such settings as obesity and stress. Based on these data, it may be suggested that interactions between these systems underlie numerous physiological and pathophysiological processes, some of them related to the cardiovascular system. Better understanding of the role of these systems and their interactions, both physiological and related to the pathogenesis of CVD, will allow further advances in prevention and drug therapy.
Cerebellar neurodegeneration in the absence of microRNAs
Schaefer, Anne; O'Carroll, Dónal; Tan, Chan Lek; Hillman, Dean; Sugimori, Mutsuyuki; Llinas, Rodolfo; Greengard, Paul
2007-01-01
Genome-encoded microRNAs (miRNAs) are potent regulators of gene expression. The significance of miRNAs in various biological processes has been suggested by studies showing an important role of these small RNAs in regulation of cell differentiation. However, the role of miRNAs in regulation of differentiated cell physiology is not well established. Mature neurons express a large number of distinct miRNAs, but the role of miRNAs in postmitotic neurons has not been examined. Here, we provide evidence for an essential role of miRNAs in survival of differentiated neurons. We show that conditional Purkinje cell–specific ablation of the key miRNA-generating enzyme Dicer leads to Purkinje cell death. Deficiency in Dicer is associated with progressive loss of miRNAs, followed by cerebellar degeneration and development of ataxia. The progressive neurodegeneration in the absence of Dicer raises the possibility of an involvement of miRNAs in neurodegenerative disorders. PMID:17606634
Chai, Sam; Wan, Xiaoping; Nassal, Drew M; Liu, Haiyan; Moravec, Christine S; Ramirez-Navarro, Angelina; Deschênes, Isabelle
2017-06-01
Two-pore K + (K 2p ) channels have been described in modulating background conductance as leak channels in different physiological systems. In the heart, the expression of K 2p channels is heterogeneous with equivocation regarding their functional role. Our objective was to determine the K 2p expression profile and their physiological and pathophysiological contribution to cardiac electrophysiology. Induced pluripotent stem cells (iPSCs) generated from humans were differentiated into cardiomyocytes (iPSC-CMs). mRNA was isolated from these cells, commercial iPSC-CM (iCells), control human heart ventricular tissue (cHVT), and ischemic (iHF) and nonischemic heart failure tissues (niHF). We detected 10 K 2p channels in the heart. Comparing quantitative PCR expression of K 2p channels between human heart tissue and iPSC-CMs revealed K 2p 1.1, K 2p 2.1, K 2p 5.1, and K 2p 17.1 to be higher expressed in cHVT, whereas K 2p 3.1 and K 2p 13.1 were higher in iPSC-CMs. Notably, K 2p 17.1 was significantly lower in niHF tissues compared with cHVT. Action potential recordings in iCells after K 2p small interfering RNA knockdown revealed prolongations in action potential depolarization at 90% repolarization for K 2p 2.1, K 2p 3.1, K 2p 6.1, and K 2p 17.1. Here, we report the expression level of 10 human K 2p channels in iPSC-CMs and how they compared with cHVT. Importantly, our functional electrophysiological data in human iPSC-CMs revealed a prominent role in cardiac ventricular repolarization for four of these channels. Finally, we also identified K 2p 17.1 as significantly reduced in niHF tissues and K 2p 4.1 as reduced in niHF compared with iHF. Thus, we advance the notion that K 2p channels are emerging as novel players in cardiac ventricular electrophysiology that could also be remodeled in cardiac pathology and therefore contribute to arrhythmias. NEW & NOTEWORTHY Two-pore K + (K 2p ) channels are traditionally regarded as merely background leak channels in myriad physiological systems. Here, we describe the expression profile of K 2p channels in human-induced pluripotent stem cell-derived cardiomyocytes and outline a salient role in cardiac repolarization and pathology for multiple K 2p channels. Copyright © 2017 the American Physiological Society.
5-Fluorouracil sensitivity varies among oral micro-organisms.
Vanlancker, Eline; Vanhoecke, Barbara; Smet, Rozel; Props, Ruben; Van de Wiele, Tom
2016-08-01
5-Fluorouracil (5-FU), a commonly used chemotherapeutic agent, often causes oral mucositis, an inflammation and ulceration of the oral mucosa. Micro-organisms in the oral cavity are thought to play an important role in the aggravation and severity of mucositis, but the mechanisms behind this remain unclear. Although 5-FU has been shown to elicit antibacterial effects at high concentrations (>100 µM), its antibacterial effect at physiologically relevant concentrations in the oral cavity is unknown. This study reports the effect of different concentrations of 5-FU (range 0.1-50 µM) on the growth and viability of bacterial monocultures that are present in the oral cavity and the possible role in the activity of dihydropyrimidine dehydrogenase (DPD), an enzyme involved in 5-FU resistance. Our data showed a differential sensitivity among the tested oral species towards physiological concentrations of 5-FU. Klebsiellaoxytoca, Streptococcus salivarius, Streptococcus mitis, Streptococcus oralis, Pseudomonas aeruginosa and Lactobacillus salivarius appeared to be highly resistant to all tested concentrations. In contrast, Lactobacillusoris, Lactobacillus plantarum, Streptococcus pyogenes, Fusobacterium nucleatum and Neisseria mucosa showed a significant reduction in growth and viability starting from very low concentrations (0.2-3.1 µM). We can also provide evidence that DPD is not involved in the 5-FU resistance of the selected species. The observed variability in response to physiological 5-FU concentrations may explain why certain microbiota lead to a community dysbiosis and/or an overgrowth of certain resistant micro-organisms in the oral cavity following cancer treatment.
Lillie, M A; Armstrong, T E; Gérard, S G; Shadwick, R E; Gosline, J M
2012-08-09
This study was undertaken to understand elastin's role in the mechanical homeostasis of the arterial wall. The mechanical properties of elastin vary along the aorta, and we hypothesized this maintained a uniform mechanical environment for the elastin, despite regional variation in loading. Elastin's physiological loading was determined by comparing the inflation response of intact and autoclave purified elastin aortas from the proximal and distal thoracic aorta. Elastin's stretch and stress depend on collagen recruitment. Collagen recruitment started in the proximal aorta at systolic pressures (13.3 to 14.6 kPa) and in the distal at sub-diastolic pressures (9.3 to 10.6 kPa). In the proximal aorta collagen did not contribute significantly to the stress or stiffness, indicating that elastin determined the vessel properties. In the distal aorta, the circumferential incremental modulus was 70% higher than in the proximal aorta, half of which (37%) was due to a stiffening of the elastin. Compared to the elastin tissue in the proximal aorta, the distal elastin suffered higher physiological circumferential stretch (29%, P=0.03), circumferential stress (39%, P=0.02), and circumferential stiffness (37%, P=0.006). Elastin's physiological axial stresses were also higher (67%, P=0.003). These findings do not support the hypothesis that the loading on elastin is constant along the aorta as we expected from homeostasis. Copyright © 2012 Elsevier Ltd. All rights reserved.
Cardiac Physiology of Aging: Extracellular Considerations.
Horn, Margaux A
2015-07-01
Aging is a major risk factor for the development of cardiovascular disease, with the majority of affected patients being elderly. Progressive changes to myocardial structure and function occur with aging, often in concert with underlying pathologies. However, whether chronological aging results in a remodeled "aged substrate" has yet to be established. In addition to myocyte contractility, myocardial performance relies heavily on the cardiac extracellular matrix (ECM), the roles of which are as dynamic as they are significant; including providing structural integrity, assisting in force transmission throughout the cardiac cycle and acting as a signaling medium for communication between cells and the extracellular environment. In the healthy heart, ECM homeostasis must be maintained, and matrix deposition is in balance with degradation. Consequently, alterations to, or misregulation of the cardiac ECM has been shown to occur in both aging and in pathological remodeling with disease. Mounting evidence suggests that age-induced matrix remodeling may occur at the level of ECM control; including collagen synthesis, deposition, maturation, and degradation. Furthermore, experimental studies using aged animal models not only suggest that the aged heart may respond differently to insult than the young, but the identification of key players specific to remodeling with age may hold future therapeutic potential for the treatment of cardiac dysfunction in the elderly. This review will focus on the role of the cardiac interstitium in the physiology of the aging myocardium, with particular emphasis on the implications to age-related remodeling in disease. © 2015 American Physiological Society.
Fatisson, Julien; Quevedo, Ivan R; Wilkinson, Kevin J; Tufenkji, Nathalie
2012-03-01
The use of engineered nanoparticles (ENPs) in commercial products has increased substantially over the last few years. Some research has been conducted in order to determine whether or not such materials are cytotoxic, but questions remain regarding the role that physiological media and sera constituents play in ENP aggregation or stabilization. In this study, several characterization methods were used to evaluate the particle size and surface potential of 6 ENPs suspended in a number of culture media and in the presence of different culture media constituents. Dynamic light scattering (DLS) and fluorescence correlation spectroscopy (FCS) were employed for size determinations. Results were interpreted on the basis of ENP surface potentials evaluated from particle electrophoretic mobilities (EPM). Measurements made after 24h of incubation at 37°C showed that the cell culture medium constituents had only moderate impact on the physicochemical properties of the ENP, although incubation in bovine serum albumin destabilized the colloidal system. In contrast, most of the serum proteins increased colloidal stabilization. Moreover, the type of ENP surface modification played a significant role in ENP behavior whereby the complexity of interactions between the ENPs and the medium components generally decreased with increasing complexity of the particle surface. This investigation emphasizes the importance of ENP characterization under conditions that are representative of cell culture media or physiological conditions for improved assessments of nanoparticle cytotoxicity. Copyright © 2011 Elsevier B.V. All rights reserved.
El Bissati, Kamal; Downie, Megan J; Kim, Seong-Kyoun; Horowitz, Michael; Carter, Nicola; Ullman, Buddy; Ben Mamoun, Choukri
2008-10-01
The malaria parasite, Plasmodium falciparum, is unable to synthesize the purine ring de novo and is therefore wholly dependent upon purine salvage from the host for survival. Previous studies have indicated that a P. falciparum strain in which the purine transporter PfNT1 had been disrupted was unable to grow on physiological concentrations of adenosine, inosine and hypoxanthine. We have now used an episomally complemented pfnt1Delta knockout parasite strain to confirm genetically the functional role of PfNT1 in P. falciparum purine uptake and utilization. Episomal complementation by PfNT1 restored the ability of pfnt1Delta parasites to transport and utilize adenosine, inosine and hypoxanthine as purine sources. The ability of wild-type and pfnt1Delta knockout parasites to transport and utilize the other physiologically relevant purines adenine, guanine, guanosine and xanthine was also examined. Unlike wild-type and complemented P. falciparum parasites, pfnt1Delta parasites could not proliferate on guanine, guanosine or xanthine as purine sources, and no significant transport of these substrates could be detected in isolated parasites. Interestingly, whereas isolated pfnt1Delta parasites were still capable of adenine transport, these parasites grew only when adenine was provided at high, non-physiological concentrations. Taken together these results demonstrate that, in addition to hypoxanthine, inosine and adenosine, PfNT1 is essential for the transport and utilization of xanthine, guanine and guanosine.
Krizbai, I A; Bauer, H; Amberger, A; Hennig, B; Szabó, H; Fuchs, R; Bauer, H C
2000-09-01
The capacity of vascular endothelial cells to modulate their phenotype in response to changes in environmental conditions is one of the most important characteristics of this cell type. Since different growth factors may play an important signalling role in this adaptive process we have investigated the effect of endothelial cell growth factor (ECGF) on morphological, physiological and molecular characteristics of cerebral endothelial cells (CECs). CECs grown in the presence of ECGF and its cofactor heparin exhibit an epithelial-like morphology (type I CECs). Upon removal of growth factors, CECs develop an elongated spindle-like shape (type II CECs) which is accompanied by the reorganization of actin filaments and the induction of alpha-actin expression. Since one of the most important functions of CECs is the creation of a selective diffusion barrier between the blood and the central nervous system (CNS), we have studied the expression of junction-related proteins in both cell types. We have found that removal of growth factors from endothelial cultures leads to the downregulation of cadherin and occludin protein levels. The loss of junctional proteins was accompanied by a significant increase in the migratory activity and an altered protease activity profile of the cells. TGF-beta1 suppressed endothelial migration in all experiments. Our data provide evidence to suggest that particular endothelial functions are largely controlled by the presence of growth factors. The differences in adhesiveness and migration may play a role in important physiological and pathological processes of endothelial cells such as vasculogenesis or tumor progression.
Schafer, Ellen J; Campo, Shelly; Colaizy, Tarah T; Mulder, Pamela J; Breheny, Patrick; Ashida, Sato
2017-12-01
Breast-feeding initiation rates have increased in the USA; however, maintenance of breast-feeding for recommended durations is low. The objective of the present study was to identify factors that may facilitate breast-feeding for longer durations among first-time mothers, including physiological and social experiences and changes in maternal perceptions. Survival analysis and linear regression methods were used to explore the relationship between experiences and breast-feeding duration, and the possible mediating effect of changes in maternal perceptions. Secondary data from the Infant Feeding Practices Study II, conducted in the USA between 2005 and 2007. Data from 762 first-time mothers who ever breast-fed were analysed. Experiencing trouble with baby's latch, problems with milk flow/supply and painful breast-feeding were significantly associated with breast-feeding duration (64, 26 and 36 % shorter duration, respectively). Meanwhile, positive changes in perception with respect to breast-feeding self-efficacy, opinion about infant feeding and belief about breast milk were associated with 16-27 % longer duration. Furthermore, changes in perception were observed to partially mediate the impact of physiological experiences on breast-feeding duration. Perceptions of breast-feeding self-efficacy, beliefs and opinions can change over time and are influenced by breast-feeding experiences. The combined effect of experience and perception plays a key role in influencing breast-feeding duration. Future research should explore interventions to maintain or improve these perceptions while accounting for physiological experiences to support breast-feeding for recommended durations among first-time mothers.
Sex Differences in Androgen Regulation of Metabolism in Nonhuman Primates.
True, Cadence; Abbott, David H; Roberts, Charles T; Varlamov, Oleg
2017-01-01
The in-depth characterization of sex differences relevant to human physiology requires the judicious use of a variety of animal models and human clinical data. Nonhuman primates (NHPs) represent an important experimental system that bridges rodent studies and clinical investigations. NHP studies have been especially useful in understanding the role of sex hormones in development and metabolism and also allow the elucidation of the effects of pertinent dietary influences on physiology pertinent to disease states such as obesity and diabetes. This chapter summarizes the current state of our understanding of androgen effects on male and female NHP metabolism relevant to hypogonadism in human males and polycystic ovary syndrome in human females. This review will also focus on the interaction between altered androgen levels and dietary restriction and excess, in particular the Western-style diet that underlies significant human pathophysiology.
SEX DIFFERENCES IN ANDROGEN REGULATION OF METABOLISM IN NONHUMAN PRIMATES
True, Cadence; Abbott, David H.; Roberts, Charles T.; Varlamov, Oleg
2018-01-01
The in-depth characterization of sex differences relevant to human physiology requires the judicious use of a variety of animal models and human clinical data. Nonhuman primates (NHPs) represent an important experimental system that bridges rodent studies and clinical investigations. NHP studies have been especially useful in understanding the role of sex hormones in development and metabolism and also allow the elucidation of the effects of pertinent dietary influences on physiology pertinent to disease states such as obesity and diabetes. This chapter summarizes the current state of our understanding of androgen effects on male and female NHP metabolism relevant to hypogonadism in human males and polycystic ovary syndrome in human females, as well as the interaction between altered androgen levels and dietary restriction and excess, in particular the western-style diet that underlies significant human pathophysiology. PMID:29224110
Proceedings of the 1973 Lyndon B. Johnson Space Center Endocrine Program Conference
NASA Technical Reports Server (NTRS)
1975-01-01
Papers given at the conference are presented. Subjects covered include the following: biochemical changes during 28 days of space flight, modulating the pituitary-adrenal response to stress, the significance of biorhythms in space flight, the importance of the rein-angiotensin system in normal cardiovascular homeostasis, a progress report of stress-induced changes in corticosteroid metabolism, recent studies of physiological factors involved in the regulation of serotonin content and turnover in the brain, the role of brain biogenic amines in the control of pituitary-adrenocortical activity, application of the water immersion model to man by studies of acid-base homeostasis during simulated weightlessness, the present status of physiological studies and analysis of calcium homeostasis in the Apollo and Skylab programs, and endocrine considerations in the red-cell-mass and plasma-volume changes of Skylab 2 and 3 crews.
Anthropometric and physiological predispositions for elite soccer.
Reilly, T; Bangsbo, J; Franks, A
2000-09-01
This review is focused on anthropometric and physiological characteristics of soccer players with a view to establishing their roles within talent detection, identification and development programmes. Top-class soccer players have to adapt to the physical demands of the game, which are multifactorial. Players may not need to have an extraordinary capacity within any of the areas of physical performance but must possess a reasonably high level within all areas. This explains why there are marked individual differences in anthropometric and physiological characteristics among top players. Various measurements have been used to evaluate specific aspects of the physical performance of both youth and adult soccer players. The positional role of a player is related to his or her physiological capacity. Thus, midfield players and full-backs have the highest maximal oxygen intakes ( > 60 ml x kg(-1) x min(-1)) and perform best in intermittent exercise tests. On the other hand, midfield players tend to have the lowest muscle strength. Although these distinctions are evident in adult and elite youth players, their existence must be interpreted circumspectly in talent identification and development programmes. A range of relevant anthropometric and physiological factors can be considered which are subject to strong genetic influences (e.g. stature and maximal oxygen intake) or are largely environmentally determined and susceptible to training effects. Consequently, fitness profiling can generate a useful database against which talented groups may be compared. No single method allows for a representative assessment of a player's physical capabilities for soccer. We conclude that anthropometric and physiological criteria do have a role as part of a holistic monitoring of talented young players.
Lozano-Soldevilla, Diego
2018-01-01
The parieto-occipital alpha (8–13 Hz) rhythm is by far the strongest spectral fingerprint in the human brain. Almost 90 years later, its physiological origin is still far from clear. In this Research Topic I review human pharmacological studies using electroencephalography (EEG) and magnetoencephalography (MEG) that investigated the physiological mechanisms behind posterior alpha. Based on results from classical and recent experimental studies, I find a wide spectrum of drugs that modulate parieto-occipital alpha power. Alpha frequency is rarely affected, but this might be due to the range of drug dosages employed. Animal and human pharmacological findings suggest that both GABA enhancers and NMDA blockers systematically decrease posterior alpha power. Surprisingly, most of the theoretical frameworks do not seem to embrace these empirical findings and the debate on the functional role of alpha oscillations has been polarized between the inhibition vs. active poles hypotheses. Here, I speculate that the functional role of alpha might depend on physiological excitation as much as on physiological inhibition. This is supported by animal and human pharmacological work showing that GABAergic, glutamatergic, cholinergic, and serotonergic receptors in the thalamus and the cortex play a key role in the regulation of alpha power and frequency. This myriad of physiological modulations fit with the view that the alpha rhythm is a complex rhythm with multiple sources supported by both thalamo-cortical and cortico-cortical loops. Finally, I briefly discuss how future research combining experimental measurements derived from theoretical predictions based of biophysically realistic computational models will be crucial to the reconciliation of these disparate findings. PMID:29670518
Rubel, Carrie E.; Schisler, Jonathan C.; Hamlett, Eric D.; DeKroon, Robert M.; Gautel, Mathias; Alzate, Oscar; Patterson, Cam
2013-01-01
The ubiquitin-proteasome system (UPS) plays a central role in maintaining protein homeostasis, emphasized by a myriad of diseases that are associated with altered UPS function such as cancer, muscle-wasting, and neurodegeneration. Protein ubiquitination plays a central role in both the promotion of proteasomal degradation as well as cellular signaling through regulation of the stability of transcription factors and other signaling molecules. Substrate specificity is a critical regulatory step of ubiquitination and is mediated by ubiquitin ligases. Recent studies implicate ubiquitin ligases in multiple models of cardiac diseases such as cardiac hypertrophy, atrophy, and ischemia/reperfusion injury, both in a cardioprotective and maladaptive role. Therefore, identifying physiological substrates of cardiac ubiquitin ligases provides both mechanistic insights into heart disease as well as possible therapeutic targets. Current methods identifying substrates for ubiquitin ligases rely heavily upon non-physiologic in vitro methods, impeding the unbiased discovery of physiological substrates in relevant model systems. Here we describe a novel method for identifying ubiquitin ligase substrates utilizing Tandem Ubiquitin Binding Entities (TUBE) technology, two-dimensional differential in gel electrophoresis (2-D DIGE), and mass spectrometry, validated by the identification of both known and novel physiological substrates of the ubiquitin ligase MuRF1 in primary cardiomyocytes. This method can be applied to any ubiquitin ligase, both in normal and disease model systems, in order to identify relevant physiological substrates under various biological conditions, opening the door to a clearer mechanistic understanding of ubiquitin ligase function and broadening their potential as therapeutic targets. PMID:23695782
DOE Office of Scientific and Technical Information (OSTI.GOV)
Miyazaki, Masaya; Nishihara, Hiroshi, E-mail: hnishihara@med.hokudai.ac.jp; Hasegawa, Hideki
Highlights: •NS1 induced excessive phosphorylation of ERK and elevated cell viability. •NS1-BP expression and CRKL knockdown abolished survival effect of NS1. •NS1-BP and NS1 formed the complex through the interaction with CRKL-SH3(N). -- Abstract: The influenza A virus non-structural protein 1 (NS1) is a multifunctional virulence factor consisting of an RNA binding domain and several Src-homology (SH) 2 and SH3 binding motifs, which promotes virus replication in the host cell and helps to evade antiviral immunity. NS1 modulates general host cell physiology in association with various cellular molecules including NS1-binding protein (NS1-BP) and signaling adapter protein CRK-like (CRKL), while themore » physiological role of NS1-BP during influenza A virus infection especially in association with NS1 remains unclear. In this study, we analyzed the intracellular association of NS1-BP, NS1 and CRKL to elucidate the physiological roles of these molecules in the host cell. In HEK293T cells, enforced expression of NS1 of A/Beijing (H1N1) and A/Indonesia (H5N1) significantly induced excessive phosphorylation of ERK and elevated cell viability, while the over-expression of NS1-BP and the abrogation of CRKL using siRNA abolished such survival effect of NS1. The pull-down assay using GST-fusion CRKL revealed the formation of intracellular complexes of NS1-BP, NS1 and CRKL. In addition, we identified that the N-terminus SH3 domain of CRKL was essential for binding to NS1-BP using GST-fusion CRKL-truncate mutants. This is the first report to elucidate the novel function of NS1-BP collaborating with viral protein NS1 in modulation of host cell physiology. In addition, an alternative role of adaptor protein CRKL in association with NS1 and NS1-BP during influenza A virus infection is demonstrated.« less
Jo, Young Goun; Choi, Hyun Jung; Kim, Jung Chul; Cho, Young Nan; Kang, Jeong Hwa; Jin, Hye Mi; Kee, Seung Jung; Park, Yong Wook
2017-05-01
Mucosal-associated invariant T (MAIT) cells and natural killer T (NKT) cells are known to play important roles in autoimmunity, infectious diseases and cancers. However, little is known about the roles of these invariant T cells in multiple trauma. The purposes of this study were to examine MAIT and NKT cell levels in patients with multiple trauma and to investigate potential relationships between these cell levels and clinical parameters. The study cohort was composed of 14 patients with multiple trauma and 22 non-injured healthy controls (HCs). Circulating MAIT and NKT cell levels in the peripheral blood were measured by flow cytometry. The severity of injury was categorised according to the scoring systems, such as Acute Physiology and Chronic Health Evaluation (APACHE) II score, Simplified Acute Physiology Score (SAPS) II, and Injury Severity Score (ISS). Circulating MAIT and NKT cell numbers were significantly lower in multiple trauma patients than in HCs. Linear regression analysis showed that circulating MAIT cell numbers were significantly correlated with age, APACHE II, SAPS II, ISS category, hemoglobin, and platelet count. NKT cell numbers in the peripheral blood were found to be significantly correlated with APACHE II, SAPS II, and ISS category. This study shows numerical deficiencies of circulating MAIT cells and NKT cells in multiple trauma. In addition, these invariant T cell deficiencies were found to be associated with disease severity. These findings provide important information for predicting the prognosis of multiple trauma. © 2017 The Korean Academy of Medical Sciences.
RESPONSE OF THE THERMOREGULATORY SYSTEM TO TOXIC CHEMICALS
The thermoregulatory system plays a crucial role in the physiological response to pesticides, airborne pollutants, and other toxic agents. The exposure to toxicants via inhalation, cutaneous absorption, or ingestion, their clearance from the body, the physiological responses, del...
Response of the Thermoregulatory System to Toxic Chemicals
The thermoregulatory system plays a crucial role in the physiological response to pesticides, airborne pollutants, and other toxic agents. The exposure to toxicants via inhalation, cutaneous absorption, or ingestion, their clearance from the body, the physiological responses, del...
Lopes de Carvalho, Renata; McCallum, Hamish; Pereira, Marcos Horácio
2002-01-01
Zoonotic visceral leishmaniasis (ZVL) is a serious public health problem in several Brazilian cities. Although the proximity of chicken houses is often cited as a risk factor in studies of urban ZVL, the role chickens play in the epidemiology of the disease has not been defined. Chickens attract both male and female sand flies (Lutzomyia longipalpis), but are unable to sustain Leishmania infections, and their presence may exert a zooprophylactic effect. We discuss environmental, physiologic, socioeconomic, and cultural factors related to chicken raising that could influence Le. infantum transmission in Brazilian cities and evaluate whether this practice significantly affects the risk of acquiring ZVL. PMID:12498667
Grandma's TUM-my Trouble: A Case Study in Renal Physiology and Acid-Base Balance
ERIC Educational Resources Information Center
Massey, Ann T.
2015-01-01
This case study involves the role of the kidneys in regulating blood pH and electrolytes. The case was used near the end of a two-semester Human Anatomy and Physiology course sequence, during the time when renal physiology was under study. Groups of two to three students were given the case and associated information (lab values, etc.). Students…
He, Jiali; Li, Hong; Luo, Jie; Ma, Chaofeng; Li, Shaojun; Qu, Long; Gai, Ying; Jiang, Xiangning; Janz, Dennis; Polle, Andrea; Tyree, Melvin; Luo, Zhi-Bin
2013-01-01
Bark tissue of Populus × canescens can hyperaccumulate cadmium, but microstructural, transcriptomic, and physiological response mechanisms are poorly understood. Histochemical assays, transmission electron microscopic observations, energy-dispersive x-ray microanalysis, and transcriptomic and physiological analyses have been performed to enhance our understanding of cadmium accumulation and detoxification in P. × canescens. Cadmium was allocated to the phloem of the bark, and subcellular cadmium compartmentalization occurred mainly in vacuoles of phloem cells. Transcripts involved in microstructural alteration, changes in nutrition and primary metabolism, and stimulation of stress responses showed significantly differential expression in the bark of P. × canescens exposed to cadmium. About 48% of the differentially regulated transcripts formed a coregulation network in which 43 hub genes played a central role both in cross talk among distinct biological processes and in coordinating the transcriptomic regulation in the bark of P. × canescens in response to cadmium. The cadmium transcriptome in the bark of P. × canescens was mirrored by physiological readouts. Cadmium accumulation led to decreased total nitrogen, phosphorus, and calcium and increased sulfur in the bark. Cadmium inhibited photosynthesis, resulting in decreased carbohydrate levels. Cadmium induced oxidative stress and antioxidants, including free proline, soluble phenolics, ascorbate, and thiol compounds. These results suggest that orchestrated microstructural, transcriptomic, and physiological regulation may sustain cadmium hyperaccumulation in P. × canescens bark and provide new insights into engineering woody plants for phytoremediation. PMID:23530184
Tiede, L M; Cook, E A; Morsey, B; Fox, H S
2011-01-01
Mitochondrial dysfunction is implicated in a majority of neurodegenerative disorders and much study of neurodegenerative disease is done on cultured neurons. In traditional tissue culture, the oxygen level that cells experience is dramatically higher (21%) than in vivo conditions (1–11%). These differences can alter experimental results, especially, pertaining to mitochondria and oxidative metabolism. Our results show that primary neurons cultured at physiological oxygen levels found in the brain showed higher polarization, lower rates of ROS production, larger mitochondrial networks, greater cytoplasmic fractions of mitochondria and larger mitochondrial perimeters than those cultured at higher oxygen levels. Although neurons cultured in either physiological oxygen or atmospheric oxygen exhibit significant increases in mitochondrial reactive oxygen species (ROS) production when treated with the human immunodeficiency virus (HIV) virotoxin trans-activator of transcription, mitochondria of neurons cultured at physiological oxygen underwent depolarization with dramatically increased cell death, whereas those cultured at atmospheric oxygen became hyperpolarized with no increase in cell death. Studies with a second HIV virotoxin, negative regulation factor (Nef), revealed that Nef treatment also increased mitochondrial ROS production for both the oxygen conditions, but resulted in mitochondrial depolarization and increased death only in neurons cultured in physiological oxygen. These results indicate a role for oxidative metabolism in a mechanism of neurotoxicity during HIV infection and demonstrate the importance of choosing the correct, physiological, culture oxygen in mitochondrial studies performed in neurons. PMID:22190005
ERIC Educational Resources Information Center
Tipton, Charles M.
2013-01-01
Society members whose research publication during the past 125 yr had an important impact on the discipline of physiology were featured at the American Physiological Society (APS)'s 125th Anniversary symposium. The daunting and challenging task of identifying and selecting significant publications was assumed by the Steering Committee of the…
Modulation of tyrosine hydroxylase expression by melatonin in human SH-SY5Y neuroblastoma cells.
McMillan, Catherine R; Sharma, Rohita; Ottenhof, Tom; Niles, Lennard P
2007-06-04
We have previously reported in vivo preservation of tyrosine hydroxylase (TH), the rate-limiting enzyme in dopamine synthesis, following treatment with physiological doses of melatonin, in a 6-hydroxydopamine model of Parkinson's disease. Based on these findings, we postulated that melatonin would similarly modulate the expression of TH in vitro. Therefore, using human SH-SY5Y neuroblastoma cells which can differentiate into dopaminergic neurons following treatment with retinoic acid, we first examined whether these cells express melatonin receptors. Subsequently, the physiological dose-dependent effects of melatonin on TH expression were examined in both undifferentiated and differentiated cells. The novel detection of the G protein-coupled melatonin MT(1) receptor in SH-SY5Y cells by RT-PCR was confirmed by sequencing and Western blotting. In addition, following treatment of SH-SY5Y cells with melatonin (0.1-100 nM) for 24h, Western analysis revealed a significant increase in TH protein levels. A biphasic response, with significant increases in TH protein at 0.5 and 1 nM melatonin and a reversal at higher doses was seen in undifferentiated cells; whereas in differentiated cells, melatonin was effective at doses of 1 and 100 nM. These findings suggest a physiological role for melatonin in modulating TH expression, possibly via the MT(1) receptor.
Intestinal adaptations in chronic kidney disease and the influence of gastric bypass surgery.
Hatch, Marguerite
2014-09-01
Studies have shown that compensatory adaptations in gastrointestinal oxalate transport can impact the amount of oxalate excreted by the kidney. Hyperoxaluria is a major risk factor in the formation of kidney stones, and oxalate is derived from both the diet and the liver metabolism of glyoxylate. Although the intestine generally absorbs oxalate from dietary sources and can contribute as much as 50% of urinary oxalate, enteric oxalate elimination plays a significant role when renal function is compromised. While the mechanistic basis for these changes in the direction of intestinal oxalate movements in chronic renal failure involves an upregulation of angiotensin II receptors in the large intestine, enteric secretion/excretion of oxalate can also occur by mechanisms that are independent of angiotensin II. Most notably, the commensal bacterium Oxalobacter sp. interacts with the host enterocyte and promotes the movement of oxalate from the blood into the lumen, resulting in the beneficial effect of significantly lowering urinary oxalate excretion. Changes in the passive permeability of the intestine, such as in steatorrhoea and following gastric bypass, also promote oxalate absorption and hyperoxaluria. In summary, this report highlights the two-way physiological signalling between the gut and the kidney, which may help to alleviate the consequences of certain kidney diseases. © 2014 The Author. Experimental Physiology © 2014 The Physiological Society.
Susceptibility and tolerance of rice crop to salt threat: Physiological and metabolic inspections
Che Lah, Wan Afifudeen; Abd. Kadir, Nisrin; Mustaqim, Mohamad; Rahmat, Zaidah; Ahmad, Aziz; Ismail, Mohd Razi
2018-01-01
Salinity threat is estimated to reduce global rice production by 50%. Comprehensive analysis of the physiological and metabolite changes in rice plants from salinity stress (i.e. tolerant versus susceptible plants) is important to combat higher salinity conditions. In this study, we screened a total of 92 genotypes and selected the most salinity tolerant line (SS1-14) and most susceptible line (SS2-18) to conduct comparative physiological and metabolome inspections. We demonstrated that the tolerant line managed to maintain their water and chlorophyll content with lower incidence of sodium ion accumulation. We also examined the antioxidant activities of these lines: production of ascorbate peroxidase (APX) and catalase (CAT) were significantly higher in the sensitive line while superoxide dismutase (SOD) was higher in the tolerant line. Partial least squares discriminant analysis (PLS-DA) score plots show significantly different response for both lines after the exposure to salinity stress. In the tolerant line, there was an upregulation of non-polar metabolites and production of sucrose, GABA and acetic acid, suggesting an important role in salinity adaptation. In contrast, glutamine and putrescine were noticeably high in the susceptible rice. Coordination of different strategies in tolerant and susceptible lines show that they responded differently after exposure to salt stress. These findings can assist crop development in terms of developing tolerance mechanisms for rice crops. PMID:29489838
Corticosterone predicts foraging behavior and parental care in macaroni penguins.
Crossin, Glenn T; Trathan, Phil N; Phillips, Richard A; Gorman, Kristen B; Dawson, Alistair; Sakamoto, Kentaro Q; Williams, Tony D
2012-07-01
Corticosterone has received considerable attention as the principal hormonal mediator of allostasis or physiological stress in wild animals. More recently, it has also been implicated in the regulation of parental care in breeding birds, particularly with respect to individual variation in foraging behavior and provisioning effort. There is also evidence that prolactin can work either inversely or additively with corticosterone to achieve this. Here we test the hypothesis that endogenous corticosterone plays a key physiological role in the control of foraging behavior and parental care, using a combination of exogenous corticosterone treatment, time-depth telemetry, and physiological sampling of female macaroni penguins (Eudyptes chrysolophus) during the brood-guard period of chick rearing, while simultaneously monitoring patterns of prolactin secretion. Plasma corticosterone levels were significantly higher in females given exogenous implants relative to those receiving sham implants. Increased corticosterone levels were associated with significantly higher levels of foraging and diving activity and greater mass gain in implanted females. Elevated plasma corticosterone was also associated with an apparent fitness benefit in the form of increased chick mass. Plasma prolactin levels did not correlate with corticosterone levels at any time, nor was prolactin correlated with any measure of foraging behavior or parental care. Our results provide support for the corticosterone-adaptation hypothesis, which predicts that higher corticosterone levels support increased foraging activity and parental effort.
Ecological and physiological aspects of transit work.
Krivoschekov, S G
1991-01-01
The organism of transit workers is overloaded after repeated translocation on long distances. Power work capacity (PWC), biological rhythms and psycho-emotional tension were studied in 240 transit workers flying to work from the Ukraine to West Siberia. Decreased PWC, disturbed diurnal rhythm, and increased emotional tension were found to be related to the increase in transit work service. The role of seasonal differences and functional activity, reflected in increased sympathetic activity in summer and parasympathetic in winter, was found to be significant.
MicroRNA Regulation of Lipid Metabolism
Flowers, Elena; Froelicher, Erika Sivarajan; Aouizerat, Bradley E.
2012-01-01
MicroRNA are structural components of an epigenetic mechanism of post-transcriptional regulation of messenger RNA translation. Recently, there is significant interest in the application of microRNA as a blood-based biomarker of underlying physiologic conditions, and the therapeutic administration of microRNA inhibitors and mimics. The purpose of this review is to describe the current body of knowledge on microRNA regulation of genes involved in lipid metabolism, and to introduce the role of microRNA in development and progression of atherosclerosis. PMID:22607769
[Novel concepts in biology of diffuse endocrine system: results and future investigations].
Iaglov, V V; Iaglova, N V
2012-01-01
Diffuse endocrine system is a largest part of endocrine system of vertebrates. Recend findings showed that DES-cells are not neuroectodermal but have ectodermal, mesodermal, and entodermal ontogeny. The article reviews novel concept of diffuse endocrine system anatomy and physiology, functional role of DES hormones and poorly investigated aspects like DES-cell morphology, hormones secretion in normal and pathologic conditions. Further research of diffuse endocrine system has a great significance for biochemistry, morphology, and clinical medicine.
The role of physiological traits in assortment among and within fish shoals
Marras, Stefano
2017-01-01
Individuals of gregarious species often group with conspecifics to which they are phenotypically similar. This among-group assortment has been studied for body size, sex and relatedness. However, the role of physiological traits has been largely overlooked. Here, we discuss mechanisms by which physiological traits—particularly those related to metabolism and locomotor performance—may result in phenotypic assortment not only among but also within animal groups. At the among-group level, varying combinations of passive assortment, active assortment, phenotypic plasticity and selective mortality may generate phenotypic differences among groups. Even within groups, however, individual variation in energy requirements, aerobic and anaerobic capacity, neurological lateralization and tolerance to environmental stressors are likely to produce differences in the spatial location of individuals or associations between group-mates with specific physiological phenotypes. Owing to the greater availability of empirical research, we focus on groups of fishes (i.e. shoals and schools). Increased knowledge of physiological mechanisms influencing among- and within-group assortment will enhance our understanding of fundamental concepts regarding optimal group size, predator avoidance, group cohesion, information transfer, life-history strategies and the evolutionary effects of group membership. In a broader perspective, predicting animal responses to environmental change will be impossible without a comprehensive understanding of the physiological basis of the formation and functioning of animal social groups. This article is part of the themed issue ‘Physiological determinants of social behaviour in animals’. PMID:28673911
Neutrophil-derived cytokines involved in physiological and pathological angiogenesis.
Tecchio, Cristina; Cassatella, Marco Antonio
2014-01-01
Increasing data from the literature point to a neutrophil-mediated role via cytokine production in several aspects of mammalian biology, including angiogenesis. In such regard, neutrophils have been shown to synthetize and release a number of molecules able to promote, directly or indirectly, the growth and migration of endothelial cells, in turn inducing the formation of new blood vessels from preexisting ones. Interestingly, neutrophil-derived cytokines can be involved either in physiological or in pathological angiogenesis, depending on either the functioning or dysregulation of sophisticated interplays among different cell types, extracellular matrix and soluble mediators within the microenvironment. Our review resumes the most interesting studies elucidating the role of neutrophil-derived cytokines in human physiological and pathological angiogenesis. When appropriate, supporting observations generated in animal models will be also mentioned. Particular emphasis will be given to VEGF and PK2/Bv8, rather than CXCL8/IL-8 and OSM. We will also discuss the potential role of neutrophil-derived cytokines such as FGF2, Ang1 and IL-17, whose roles in angiogenesis - albeit anticipated - remain to be elucidated. Copyright © 2014 S. Karger AG, Basel.
Boswell, C. Andrew; Ferl, Gregory Z.; Mundo, Eduardo E.; Bumbaca, Daniela; Schweiger, Michelle G.; Theil, Frank-Peter; Fielder, Paul J.; Khawli, Leslie A.
2011-01-01
Background The identification of clinically meaningful and predictive models of disposition kinetics for cancer therapeutics is an ongoing pursuit in drug development. In particular, the growing interest in preclinical evaluation of anti-angiogenic agents alone or in combination with other drugs requires a complete understanding of the associated physiological consequences. Methodology/Principal Findings Technescan™ PYP™, a clinically utilized radiopharmaceutical, was used to measure tissue vascular volumes in beige nude mice that were naïve or administered a single intravenous bolus dose of a murine anti-vascular endothelial growth factor (anti-VEGF) antibody (10 mg/kg) 24 h prior to assay. Anti-VEGF had no significant effect (p>0.05) on the fractional vascular volumes of any tissues studied; these findings were further supported by single photon emission computed tomographic imaging. In addition, apart from a borderline significant increase (p = 0.048) in mean hepatic blood flow, no significant anti-VEGF-induced differences were observed (p>0.05) in two additional physiological parameters, interstitial fluid volume and the organ blood flow rate, measured using indium-111-pentetate and rubidium-86 chloride, respectively. Areas under the concentration-time curves generated by a physiologically-based pharmacokinetic model changed substantially (>25%) in several tissues when model parameters describing compartmental volumes and blood flow rates were switched from literature to our experimentally derived values. However, negligible changes in predicted tissue exposure were observed when comparing simulations based on parameters measured in naïve versus anti-VEGF-administered mice. Conclusions/Significance These observations may foster an enhanced understanding of anti-VEGF effects in murine tissues and, in particular, may be useful in modeling antibody uptake alone or in combination with anti-VEGF. PMID:21436893
Zhang, Huixian; Qin, Geng; Zhang, Yanhong; Li, Shuisheng; Lin, Qiang
2016-10-15
Leptin is an essential hormone for the regulation of energy metabolism and food intake in vertebrate animals. To better understand the physiological roles of leptin in nutrient regulation in paternal ovoviviparous fish (family Syngnathidae), the present study cloned the full-length of leptin-a and leptin receptor (lepr) genes in lined seahorse (Hippocampus erectus). Results showed that there was a 576-bp intron between two exons in leptin-a gene but no leptin-b gene in seahorse. Although the primary amino acid sequence conservation of seahorse leptin-a was very low, the 3-D structure modeling of seahorse leptin-a revealed strong conservation of tertiary structure with other vertebrates. Seahorse leptin-a mRNA was highly expressed in brain, whereas lepr mRNA was mainly expressed in ovary and gill. Interestingly, both leptin-a and lepr mRNA were expressed in the brood pouch of male seahorse, suggesting the leptin system plays a role during the male pregnancy. Physiological experiments showed that the expression of hepatic leptin-a and lepr mRNA in unfed seahorses was significantly higher than that in those fed 100%, as well as 60%, of their food during the fasting stage, showing that seahorse might initiate the leptin system to regulate its energy metabolism while starving. Moreover, the expression of leptin-a in the brood pouch of pregnant seahorse was significantly upregulated compared with non-pregnant seahorse, whereas the expression of lepr was downregulated, suggesting that the leptin system might be involved in the male pregnancy. In conclusion, the leptin system plays a role in the energy metabolism and food intake, and might provide new insights into molecular regulation of male pregnancy in seahorse. © 2016. Published by The Company of Biologists Ltd.
Adiponectin regulates thermal nociception in a mouse model of neuropathic pain.
Sun, L; Li, H; Tai, L W; Gu, P; Cheung, C W
2018-06-01
Adiponectin, a cytokine secreted by adipocytes, plays an important role in regulating glucose and lipid metabolism. However, the role of adiponectin in pain conditions is largely unknown. This study aimed to identify the role and mechanism of adiponectin in nociceptive sensitivity under physiological and pathological states utilising adiponectin knockout (KO) mice. Wild type (WT) and adiponectin KO mice were subjected to partial sciatic nerve ligation (pSNL) or sham operation. Pain-like behavioural tests, including thermal allodynia, hyperalgesia, and mechanical allodynia, were performed before and after pSNL from Day 3-21. Dorsal root ganglions (DRGs), lumbar spinal segments at L3-5, and somatosensory cortex were collected for protein measurement via western blotting and immunofluorescence staining. Compared with WT mice, KO mice had significantly lower (40-50%) paw withdrawal latency to innocuous and noxious stimuli before and after pSNL. In DRG neurones from KO mice, where adiponectin receptor (AdipoR) 2 is located, phosphorylated p38 mitogen-activated protein kinase (p-p38 MAPK) and heat-sensitive transient receptor potential cation channel subfamily V member 1 (TRPV1) were significantly higher (by two- to three-fold) than from WT mice. In spinal microglia and somatosensory cortical neurones, where AdipoR1 is mainly located, p-p38 MAPK and TRPV1 were also higher (by two- to three-fold) in KO compared with WT mice, and altered signalling of these molecules was exacerbated (1.2- to 1.3-fold) by pSNL. Our results show that adiponectin regulates thermal nociceptive sensitivity by inhibiting activation of DRG neurones, spinal microglia, and somatosensory cortical neurones in physiological and neuropathic pain states. This study has relevance for patients with adiponectin disorders, such as obesity and diabetes. Copyright © 2018 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.
Zhang, Huixian; Qin, Geng; Zhang, Yanhong; Li, Shuisheng
2016-01-01
ABSTRACT Leptin is an essential hormone for the regulation of energy metabolism and food intake in vertebrate animals. To better understand the physiological roles of leptin in nutrient regulation in paternal ovoviviparous fish (family Syngnathidae), the present study cloned the full-length of leptin-a and leptin receptor (lepr) genes in lined seahorse (Hippocampus erectus). Results showed that there was a 576-bp intron between two exons in leptin-a gene but no leptin-b gene in seahorse. Although the primary amino acid sequence conservation of seahorse leptin-a was very low, the 3-D structure modeling of seahorse leptin-a revealed strong conservation of tertiary structure with other vertebrates. Seahorse leptin-a mRNA was highly expressed in brain, whereas lepr mRNA was mainly expressed in ovary and gill. Interestingly, both leptin-a and lepr mRNA were expressed in the brood pouch of male seahorse, suggesting the leptin system plays a role during the male pregnancy. Physiological experiments showed that the expression of hepatic leptin-a and lepr mRNA in unfed seahorses was significantly higher than that in those fed 100%, as well as 60%, of their food during the fasting stage, showing that seahorse might initiate the leptin system to regulate its energy metabolism while starving. Moreover, the expression of leptin-a in the brood pouch of pregnant seahorse was significantly upregulated compared with non-pregnant seahorse, whereas the expression of lepr was downregulated, suggesting that the leptin system might be involved in the male pregnancy. In conclusion, the leptin system plays a role in the energy metabolism and food intake, and might provide new insights into molecular regulation of male pregnancy in seahorse. PMID:27628034
Dynamical analysis of Parkinsonian state emulated by hybrid Izhikevich neuron models
NASA Astrophysics Data System (ADS)
Liu, Chen; Wang, Jiang; Yu, Haitao; Deng, Bin; Wei, Xile; Li, Huiyan; Loparo, Kenneth A.; Fietkiewicz, Chris
2015-11-01
Computational models play a significant role in exploring novel theories to complement the findings of physiological experiments. Various computational models have been developed to reveal the mechanisms underlying brain functions. Particularly, in the development of therapies to modulate behavioral and pathological abnormalities, computational models provide the basic foundations to exhibit transitions between physiological and pathological conditions. Considering the significant roles of the intrinsic properties of the globus pallidus and the coupling connections between neurons in determining the firing patterns and the dynamical activities of the basal ganglia neuronal network, we propose a hypothesis that pathological behaviors under the Parkinsonian state may originate from combined effects of intrinsic properties of globus pallidus neurons and synaptic conductances in the whole neuronal network. In order to establish a computational efficient network model, hybrid Izhikevich neuron model is used due to its capacity of capturing the dynamical characteristics of the biological neuronal activities. Detailed analysis of the individual Izhikevich neuron model can assist in understanding the roles of model parameters, which then facilitates the establishment of the basal ganglia-thalamic network model, and contributes to a further exploration of the underlying mechanisms of the Parkinsonian state. Simulation results show that the hybrid Izhikevich neuron model is capable of capturing many of the dynamical properties of the basal ganglia-thalamic neuronal network, such as variations of the firing rates and emergence of synchronous oscillations under the Parkinsonian condition, despite the simplicity of the two-dimensional neuronal model. It may suggest that the computational efficient hybrid Izhikevich neuron model can be used to explore basal ganglia normal and abnormal functions. Especially it provides an efficient way of emulating the large-scale neuron network and potentially contributes to development of improved therapy for neurological disorders such as Parkinson's disease.
Hristov, Kiril L.; Smith, Amy C.; Parajuli, Shankar P.; Malysz, John; Rovner, Eric S.
2016-01-01
Transient receptor potential melastatin 4 (TRPM4) channels are Ca2+-activated nonselective cation channels that have been recently identified as regulators of detrusor smooth muscle (DSM) function in rodents. However, their expression and function in human DSM remain unexplored. We provide insights into the functional role of TRPM4 channels in human DSM under physiological conditions. We used a multidisciplinary experimental approach, including RT-PCR, Western blotting, immunohistochemistry and immunocytochemistry, patch-clamp electrophysiology, and functional studies of DSM contractility. DSM samples were obtained from patients without preoperative overactive bladder symptoms. RT-PCR detected mRNA transcripts for TRPM4 channels in human DSM whole tissue and freshly isolated single cells. Western blotting and immunohistochemistry with confocal microscopy revealed TRPM4 protein expression in human DSM. Immunocytochemistry further detected TRPM4 protein expression in DSM single cells. Patch-clamp experiments showed that 9-phenanthrol, a selective TRPM4 channel inhibitor, significantly decreased the transient inward cation currents and voltage step-induced whole cell currents in freshly isolated human DSM cells. In current-clamp mode, 9-phenanthrol hyperpolarized the human DSM cell membrane potential. Furthermore, 9-phenanthrol attenuated the spontaneous phasic, carbachol-induced and nerve-evoked contractions in human DSM isolated strips. Significant species-related differences in TRPM4 channel activity between human, rat, and guinea pig DSM were revealed, suggesting a more prominent physiological role for the TRPM4 channel in the regulation of DSM function in humans than in rodents. In conclusion, TRPM4 channels regulate human DSM excitability and contractility and are critical determinants of human urinary bladder function. Thus, TRPM4 channels could represent promising novel targets for the pharmacological or genetic control of overactive bladder. PMID:26791488
Role of naturally occurring osmolytes in protein folding and stability.
Kumar, Raj
2009-11-01
Osmolytes are typically accumulated in the intracellular environment at relatively high concentrations when cells/tissues are subjected to stress conditions. Osmolytes are common in a variety of organisms, including microorganisms, plants, and animals. They enhance thermodynamic stability of proteins by providing natively folded conformations without perturbing other cellular processes. By burying the backbone into the core of folded proteins, osmolytes can provide significant stability to proteins. Two properties of osmolytes are particularly important: (i) their ability to impart increased thermodynamic stability to folded proteins; and (ii) their compatibility in the intracellular environment at high concentrations. Under physiological conditions, the cellular compositions of osmolytes may vary significantly. This may lead to different protein folding pathways utilized in cells depending upon the intracellular environment. Proper understanding of the role of osmolytes in cell regulation should allow predicting the action of osmolytes on macromolecular interactions in stressed and crowded environments typical of cellular conditions.
Camilleri, Michael; Oduyebo, Ibironke; Halawi, Houssam
2016-11-01
Several chemical and molecular factors in the intestine are reported to be altered and to have a potentially significant role in irritable bowel syndrome (IBS), particularly in IBS with diarrhea. These include bile acids; short-chain fatty acids; mucosal barrier proteins; mast cell products such as histamine, proteases, and tryptase; enteroendocrine cell products; and mucosal mRNAs, proteins, and microRNAs. This article reviews the current knowledge and unanswered questions in the pathobiology of the chemical and molecular factors in IBS. Evidence continues to point to significant roles in pathogenesis of these chemical and molecular mechanisms, which may therefore constitute potential targets for future research and therapy. However, it is still necessary to address the interaction between these factors in the gut and to appraise how they may influence hypervigilance in the central nervous system in patients with IBS. Copyright © 2016 the American Physiological Society.
Fructose metabolism in the cerebellum.
Funari, Vincent A; Crandall, James E; Tolan, Dean R
2007-01-01
Under normal physiological conditions, the brain utilizes only a small number of carbon sources for energy. Recently, there is growing molecular and biochemical evidence that other carbon sources, including fructose, may play a role in neuro-energetics. Fructose is the number one commercial sweetener in Western civilization with large amounts of fructose being toxic, yet fructose metabolism remains relatively poorly characterized. Fructose is purportedly metabolized via either of two pathways, the fructose-1-phosphate pathway and/or the fructose-6-phosphate pathway. Many early metabolic studies could not clearly discriminate which of these two pathways predominates, nor could they distinguish which cell types in various tissues are capable of fructose metabolism. In addition, the lack of good physiological models, the diet-induced changes in gene expression in many tissues, the involvement of multiple genes in multiple pathways involved in fructose metabolism, and the lack of characterization of some genes involved in fructose metabolism have complicated our understanding of the physiological role of fructose in neuro-energetics. A recent neuro-metabolism study of the cerebellum demonstrated fructose metabolism and co-expression of the genes specific for the fructose 1-phosphate pathway, GLUT5 (glut5) and ketohexokinase (khk), in Purkinje cells suggesting this as an active pathway in specific neurons? Meanwhile, concern over the rapid increase in dietary fructose, particularly among children, has increased awareness about how fructose is metabolized in vivo and what effects a high fructose diet might have. In this regard, establishment of cellular and molecular studies and physiological characterization of the important and/or deleterious roles fructose plays in the brain is critical. This review will discuss the status of fructose metabolism in the brain with special reference to the cerebellum and the physiological roles of the different pathways.
Lavender fragrance cleansing gel effects on relaxation.
Field, Tiffany; Diego, Miguel; Hernandez-Reif, Maria; Cisneros, Wendy; Feijo, Larissa; Vera, Yanexy; Gil, Karla; Grina, Diana; Claire He, Qing
2005-02-01
Alertness, mood, and math computations were assessed in 11 healthy adults who sniffed a cosmetic cleansing gel with lavender floral blend aroma, developed to be relaxing using Mood Mapping. EEG patterns and heart rate were also recorded before, during, and after the aroma session. The lavender fragrance blend had a significant transient effect of improving mood, making people feel more relaxed, and performing the math computation faster. The self-report and physiological data are consistent with relaxation profiles during other sensory stimuli such as massage and music, as reported in the literature. The data suggest that a specific cosmetic fragrance can have a significant role in enhancing relaxation.
Prolactin, thyrotropin, and growth hormone release during stress associated with parachute jumping.
Noel, G L; Dimond, R C; Earll, J M; Frantz, A G
1976-05-01
Prolactin, growth hormone, and thyrotropin (TSH) release during the stress of parachute jumping has been evaluated in 14 male subjects. Subjects were studied at several times before and immediately after their first military parachute jump. All three hormones had risen significantly 1 to 14 min after the jump, compared to mean levels measured immediately beforehand. Earlier studies of physical exercise by ourselves and others would suggest that emotional stress played a role in producing changes of this magnitude. We conclude that prolactin, TSH, and growth hormone are released in physiologically significant amounts in association with the stress of parachute jumping.
Zcchc11 Uridylates Mature miRNAs to Enhance Neonatal IGF-1 Expression, Growth, and Survival
Kozlowski, Elyse; Matsuura, Kori Y.; Ferrari, Joseph D.; Morris, Samantha A.; Powers, John T.; Daley, George Q.; Quinton, Lee J.; Mizgerd, Joseph P.
2012-01-01
The Zcchc11 enzyme is implicated in microRNA (miRNA) regulation. It can uridylate let-7 precursors to decrease quantities of the mature miRNA in embryonic stem cell lines, suggested to mediate stem cell maintenance. It can uridylate mature miR-26 to relieve silencing activity without impacting miRNA content in cancer cell lines, suggested to mediate cytokine and growth factor expression. Broader roles of Zcchc11 in shaping or remodeling the miRNome or in directing biological or physiological processes remain entirely speculative. We generated Zcchc11-deficient mice to address these knowledge gaps. Zcchc11 deficiency had no impact on embryogenesis or fetal development, but it significantly decreased survival and growth immediately following birth, indicating a role for this enzyme in early postnatal fitness. Deep sequencing of small RNAs from neonatal livers revealed roles of this enzyme in miRNA sequence diversity. Zcchc11 deficiency diminished the lengths and terminal uridine frequencies for diverse mature miRNAs, but it had no influence on the quantities of any miRNAs. The expression of IGF-1, a liver-derived protein essential to early growth and survival, was enhanced by Zcchc11 expression in vitro, and miRNA silencing of IGF-1 was alleviated by uridylation events observed to be Zcchc11-dependent in the neonatal liver. In neonatal mice, Zcchc11 deficiency significantly decreased IGF-1 mRNA in the liver and IGF-1 protein in the blood. We conclude that the Zcchc11-mediated terminal uridylation of mature miRNAs is pervasive and physiologically significant, especially important in the neonatal period for fostering IGF-1 expression and enhancing postnatal growth and survival. We propose that the miRNA 3′ terminus is a regulatory node upon which multiple enzymes converge to direct silencing activity and tune gene expression. PMID:23209448
Nahar, Kamrun; Hasanuzzaman, Mirza; Alam, Md. Mahabub; Fujita, Masayuki
2015-01-01
Drought is considered one of the most acute environmental stresses presently affecting agriculture. We studied the role of exogenous glutathione (GSH) in conferring drought stress tolerance in mung bean (Vigna radiata L. cv. Binamoog-1) seedlings by examining the antioxidant defence and methylglyoxal (MG) detoxification systems and physiological features. Six-day-old seedlings were exposed to drought stress (−0.7 MPa), induced by polyethylene glycol alone and in combination with GSH (1 mM) for 24 and 48 h. Drought stress decreased seedling dry weight and leaf area; resulted in oxidative stress as evidenced by histochemical detection of hydrogen peroxide (H2O2) and O2⋅− in the leaves; increased lipid peroxidation (malondialdehyde), reactive oxygen species like H2O2 content and O2⋅− generation rate and lipoxygenase activity; and increased the MG level. Drought decreased leaf succulence, leaf chlorophyll and relative water content (RWC); increased proline (Pro); decreased ascorbate (AsA); increased endogenous GSH and glutathione disulfide (GSSG) content; decreased the GSH/GSSG ratio; increased ascorbate peroxidase and glutathione S-transferase activities; and decreased the activities of monodehydroascorbate reductase (MDHAR), dehydroascorbate reductase (DHAR) and catalase. The activities of glyoxalase I (Gly I) and glyoxalase II (Gly II) increased due to drought stress. In contrast to drought stress alone, exogenous GSH enhanced most of the components of the antioxidant and glyoxalase systems in drought-affected mung bean seedlings at 24 h, but GSH did not significantly affect AsA, Pro, RWC, leaf succulence and the activities of Gly I and DHAR after 48 h of stress. Thus, exogenous GSH supplementation with drought significantly enhanced the antioxidant components and successively reduced oxidative damage, and GSH up-regulated the glyoxalase system and reduced MG toxicity, which played a significant role in improving the physiological features and drought tolerance. PMID:26134121
Nishiyama, Keiji; Suzuki, Hirobumi; Maruyama, Minoru; Yoshihara, Tomoki; Ohta, Hiroyuki
2017-09-01
G protein-coupled receptor 52 (GPR52) is largely co-expressed with dopamine D 2 receptor (DRD2) in the striatum and nucleus accumbens, and this expression pattern is similar to that of adenosine A 2A receptor (ADORA2A). GPR52 has been proposed as a therapeutic target for positive symptoms of schizophrenia, based on observations from pharmacological and transgenic mouse studies. However, the physiological role of GPR52 in dopaminergic functions in the basal ganglia remains unclear. Here, we used GPR52 knockout (KO) mice to examine the role of GPR52 in dopamine receptor-mediated and ADORA2A-mediated locomotor activity and dopamine receptor signaling. High expression of GPR52 protein in the striatum, nucleus accumbens, and lateral globus pallidus of wild type (WT) littermates was confirmed by immunohistochemical analysis. GPR52 KO and WT mice exhibited almost identical locomotor responses to the dopamine releaser methamphetamine and the N-methyl-d-aspartate antagonist MK-801. In contrast, the locomotor response to the ADORA2A antagonist istradefylline was significantly augmented in GPR52 KO mice compared to WT mice. Gene expression analysis revealed that striatal expression of DRD2, but not of dopamine D 1 receptor and ADORA2A, was significantly decreased in GPR52 KO mice. Moreover, a significant reduction in the mRNA expression of enkephalin, a marker of the activity of striatopallidal neurons, was observed in the striatum of GPR52 KO mice, suggesting that GPR52 deletion could enhance DRD2 signaling. Taken together, these results imply the physiological relevance of GPR52 in modulating the function of striatopallidal neurons, possibly by interaction of GPR52 with ADORA2A and DRD2. Copyright © 2017 Elsevier B.V. All rights reserved.
Concurrent and robust regulation of feeding behaviors and metabolism by orexin neurons.
Inutsuka, Ayumu; Inui, Azusa; Tabuchi, Sawako; Tsunematsu, Tomomi; Lazarus, Michael; Yamanaka, Akihiro
2014-10-01
Orexin neurons in the hypothalamus regulate energy homeostasis by coordinating various physiological responses. Past studies have shown the role of the orexin peptide itself; however, orexin neurons contain not only orexin but also other neurotransmitters such as glutamate and dynorphin. In this study, we examined the physiological role of orexin neurons in feeding behavior and metabolism by pharmacogenetic activation and chronic ablation. We generated novel orexin-Cre mice and utilized Cre-dependent adeno-associated virus vectors to express Gq-coupled modified GPCR, hM3Dq or diphtheria toxin fragment A in orexin neurons. By intraperitoneal injection of clozapine-N oxide in orexin-Cre mice expressing hM3Dq in orexin neurons, we could selectively manipulate the activity of orexin neurons. Pharmacogenetic stimulation of orexin neurons simultaneously increased locomotive activity, food intake, water intake and the respiratory exchange ratio (RER). Elevation of blood glucose levels and RER persisted even after locomotion and feeding behaviors returned to basal levels. Accordantly, 83% ablation of orexin neurons resulted in decreased food and water intake, while 70% ablation had almost no effect on these parameters. Our results indicate that orexin neurons play an integral role in regulation of both feeding behavior and metabolism. This regulation is so robust that greater than 80% of orexin neurons were ablated before significant changes in feeding behavior emerged. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.
Estrogen biology: new insights into GPER function and clinical opportunities.
Prossnitz, Eric R; Barton, Matthias
2014-05-25
Estrogens play an important role in the regulation of normal physiology, aging and many disease states. Although the nuclear estrogen receptors have classically been described to function as ligand-activated transcription factors mediating genomic effects in hormonally regulated tissues, more recent studies reveal that estrogens also mediate rapid signaling events traditionally associated with G protein-coupled receptors. The G protein-coupled estrogen receptor GPER (formerly GPR30) has now become recognized as a major mediator of estrogen's rapid cellular effects throughout the body. With the discovery of selective synthetic ligands for GPER, both agonists and antagonists, as well as the use of GPER knockout mice, significant advances have been made in our understanding of GPER function at the cellular, tissue and organismal levels. In many instances, the protective/beneficial effects of estrogen are mimicked by selective GPER agonism and are absent or reduced in GPER knockout mice, suggesting an essential or at least parallel role for GPER in the actions of estrogen. In this review, we will discuss recent advances and our current understanding of the role of GPER and the activity of clinically used drugs, such as SERMs and SERDs, in physiology and disease. We will also highlight novel opportunities for clinical development towards GPER-targeted therapeutics, for molecular imaging, as well as for theranostic approaches and personalized medicine. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.
[Diet and civilization diseases--carbohydrate aspects].
Haslbeck, M
1990-01-01
Carbohydrates are a major component of our food, they are important as body energy stores and they play an important role in cellular structures. In the present paper a classification of food carbohydrates, of dietary fibers and sweeteners is presented and the major physiological effects are discussed. Furthermore, the significance of carbohydrates for the etiology and the treatment of nutrition related diseases which are closely related to the development of arteriosclerosis is outlined. Carbohydrates are beside fat the major determinants of the daily caloric intake. This illustrates their impact on the development of obesity with its predominant role as a risk factor for the development of cardiovascular disease. Furthermore, the role of sugar consumption in the relation to dental caries is stressed. Also the central role of carbohydrate consumption for the treatment of diabetes mellitus is described. Problems of the diabetes diet, the role of the dietary fiber in the treatment of different diseases and the necessity of sweetness in nutrition are discussed in greater detail.
Physiological regulation and metabolic role of browning in white adipose tissue.
Jankovic, Aleksandra; Otasevic, Vesna; Stancic, Ana; Buzadzic, Biljana; Korac, Aleksandra; Korac, Bato
2017-09-01
Great progress has been made in our understanding of the browning process in white adipose tissue (WAT) in rodents. The recognition that i) adult humans have physiologically inducible brown adipose tissue (BAT) that may facilitate resistance to obesity and ii) that adult human BAT molecularly and functionally resembles beige adipose tissue in rodents, reignited optimism that obesity and obesity-related diabetes type 2 can be battled by controlling the browning of WAT. In this review the main cellular mechanisms and molecular mediators of browning of WAT in different physiological states are summarized. The relevance of browning of WAT in metabolic health is considered primarily through a modulation of biological role of fat tissue in overall metabolic homeostasis.
Rozier, Kelvin; Bondarenko, Vladimir E
2017-05-01
The β 1 - and β 2 -adrenergic signaling systems play different roles in the functioning of cardiac cells. Experimental data show that the activation of the β 1 -adrenergic signaling system produces significant inotropic, lusitropic, and chronotropic effects in the heart, whereas the effects of the β 2 -adrenergic signaling system is less apparent. In this paper, a comprehensive compartmentalized experimentally based mathematical model of the combined β 1 - and β 2 -adrenergic signaling systems in mouse ventricular myocytes is developed to simulate the experimental findings and make testable predictions of the behavior of the cardiac cells under different physiological conditions. Simulations describe the dynamics of major signaling molecules in different subcellular compartments; kinetics and magnitudes of phosphorylation of ion channels, transporters, and Ca 2+ handling proteins; modifications of action potential shape and duration; and [Ca 2+ ] i and [Na + ] i dynamics upon stimulation of β 1 - and β 2 -adrenergic receptors (β 1 - and β 2 -ARs). The model reveals physiological conditions when β 2 -ARs do not produce significant physiological effects and when their effects can be measured experimentally. Simulations demonstrated that stimulation of β 2 -ARs with isoproterenol caused a marked increase in the magnitude of the L-type Ca 2+ current, [Ca 2+ ] i transient, and phosphorylation of phospholamban only upon additional application of pertussis toxin or inhibition of phosphodiesterases of type 3 and 4. The model also made testable predictions of the changes in magnitudes of [Ca 2+ ] i and [Na + ] i fluxes, the rate of decay of [Na + ] i concentration upon both combined and separate stimulation of β 1 - and β 2 -ARs, and the contribution of phosphorylation of PKA targets to the changes in the action potential and [Ca 2+ ] i transient. Copyright © 2017 the American Physiological Society.
Vaish, Manisha; Price-Whelan, Alexa; Reyes-Robles, Tamara; Liu, Jun; Jereen, Amyeo; Christie, Stephanie; Alonzo, Francis; Benson, Meredith A; Torres, Victor J; Krulwich, Terry A
2018-03-01
Staphylococcus aureus has three types of cation/proton antiporters. The type 3 family includes two m ultisubunit N a + / H + (Mnh) antiporters, Mnh1 and Mnh2. These antiporters are clusters of seven hydrophobic membrane-bound protein subunits. Mnh antiporters play important roles in maintaining cytoplasmic pH in prokaryotes, enabling their survival under extreme environmental stress. In this study, we investigated the physiological roles and catalytic properties of Mnh1 and Mnh2 in S. aureus Both Mnh1 and Mnh2 were cloned separately into a pGEM3Z+ vector in the antiporter-deficient KNabc Escherichia coli strain. The catalytic properties of the antiporters were measured in everted (inside out) vesicles. The Mnh1 antiporter exhibited a significant exchange of Na + /H + cations at pH 7.5. Mnh2 showed a significant exchange of both Na + /H + and K + /H + cations, especially at pH 8.5. Under elevated salt conditions, deletion of the mnhA1 gene resulted in a significant reduction in the growth rate of S. aureus in the range of pH 7.5 to 9. Deletion of mnhA2 had similar effects but mainly in the range of pH 8.5 to 9.5. Double deletion of mnhA1 and mnhA2 led to a severe reduction in the S. aureus growth rate mainly at pH values above 8.5. The effects of functional losses of both antiporters in S. aureus were also assessed via their support of virulence in a mouse in vivo infection model. Deletion of the mnhA1 gene led to a major loss of S. aureus virulence in mice, while deletion of mnh2 led to no change in virulence. IMPORTANCE This study focuses on the catalytic properties and physiological roles of Mnh1 and Mnh2 cation/proton antiporters in S. aureus and their contributions under different stress conditions. The Mnh1 antiporter was found to have catalytic activity for Na + /H + antiport, and it plays a significant role in maintaining halotolerance at pH 7.5 while the Mnh2 antiporter has catalytic antiporter activities for Na + /H + and K + /H + that have roles in both osmotolerance and halotolerance in S. aureus Study of S. aureus with a single deletion of either mnhA1 or mnhA2 was assessed in an infection model of mice. The result shows that mnhA1 , but not mnhA2 , plays a major role in S. aureus virulence. Copyright © 2018 Vaish et al.
Shimada, Takashi; Kakitani, Makoto; Yamazaki, Yuji; Hasegawa, Hisashi; Takeuchi, Yasuhiro; Fujita, Toshiro; Fukumoto, Seiji; Tomizuka, Kazuma; Yamashita, Takeyoshi
2004-01-01
Inorganic phosphate is essential for ECM mineralization and also as a constituent of important molecules in cellular metabolism. Investigations of several hypophosphatemic diseases indicated that a hormone-like molecule probably regulates serum phosphate concentration. FGF23 has recently been recognized as playing important pathophysiological roles in several hypophosphatemic diseases. We present here the evidence that FGF23 is a physiological regulator of serum phosphate and 1,25-dihydroxyvitamin D (1,25[OH]2D) by generating FGF23-null mice. Disruption of the Fgf23 gene did not result in embryonic lethality, although homozygous mice showed severe growth retardation with abnormal bone phenotype and markedly short life span. The Fgf23–/– mice displayed significantly high serum phosphate with increased renal phosphate reabsorption. They also showed an elevation in serum 1,25(OH)2D that was due to the enhanced expression of renal 25-hydroxyvitamin D-1α-hydroxylase (1α-OHase) from 10 days of age. These phenotypes could not be explained by currently known regulators of mineral homeostasis, indicating that FGF23 is essential for normal phosphate and vitamin D metabolism. PMID:14966565
Shimada, Takashi; Kakitani, Makoto; Yamazaki, Yuji; Hasegawa, Hisashi; Takeuchi, Yasuhiro; Fujita, Toshiro; Fukumoto, Seiji; Tomizuka, Kazuma; Yamashita, Takeyoshi
2004-02-01
Inorganic phosphate is essential for ECM mineralization and also as a constituent of important molecules in cellular metabolism. Investigations of several hypophosphatemic diseases indicated that a hormone-like molecule probably regulates serum phosphate concentration. FGF23 has recently been recognized as playing important pathophysiological roles in several hypophosphatemic diseases. We present here the evidence that FGF23 is a physiological regulator of serum phosphate and 1,25-dihydroxyvitamin D (1,25[OH]2D) by generating FGF23-null mice. Disruption of the Fgf23 gene did not result in embryonic lethality, although homozygous mice showed severe growth retardation with abnormal bone phenotype and markedly short life span. The Fgf23(-/-) mice displayed significantly high serum phosphate with increased renal phosphate reabsorption. They also showed an elevation in serum 1,25(OH)2D that was due to the enhanced expression of renal 25-hydroxyvitamin D-1alpha-hydroxylase (1alpha-OHase) from 10 days of age. These phenotypes could not be explained by currently known regulators of mineral homeostasis, indicating that FGF23 is essential for normal phosphate and vitamin D metabolism.
Physiology and pathophysiology of renal erythropoietin-producing cells.
Shih, Hong-Mou; Wu, Chih-Jen; Lin, Shuei-Liong
2018-04-11
Anemia is a common complication and contributes to increased morbidity and mortality in chronic kidney disease (CKD) patients. Whereas there has been a significant improvement of understanding the underlying mechanism of erythropoiesis, the treatment of renal anemia is still restricted to erythropoietin (EPO)-stimulating agents. The purpose of this article is to review the physiology of erythropoiesis, functional role of EPO and underlying molecular and cellular basis that regulate EPO production. Regulation of EPO production is at mRNA level. When anemia or hypoxia occurs, transcriptional factor, hypoxia-inducible factor (HIF), binds to EPO 5' hypoxic response element and EPO gene transcription increases. The renal EPO is mainly produced by pericytes. In CKD, pericytes transdifferentiate to myofibroblasts, and subsequently the ability of EPO production decreases, leading to renal anemia. Recent experimental and clinical studies show the promising efficacy of prolyl hydroxylase inhibitors in renal anemia through increasing EPO production by stabilizing HIF. Recent advances on epigenetics create a new field to study EPO gene expression at chromatin level. We will discuss the role of demethylating agent on restoring EPO expression, providing a novel approach to the treatment of renal anemia. Copyright © 2018. Published by Elsevier B.V.
Shabala, Sergey
2011-04-01
Waterlogging affects large areas of agricultural land, resulting in severe economic penalties because of massive losses in crop production. Traditionally, plant breeding for waterlogging tolerance has been based on the field assessment of a range of agronomic and morphological characteristics. This review argues for a need to move towards more physiologically based approaches by targeting specific cellular mechanisms underling key components of waterlogging tolerance in plants. Also, while the main focus of researchers was predominantly on plant anoxia tolerance, less attention was given to plant tolerance to phytotoxins under waterlogged conditions. This paper reviews the production of major elemental and organic phytotoxins in waterlogged soils and describes their adverse effects on plant performance. The critical role of plasma membrane transporters in plant tolerance to secondary metabolite toxicity is highlighted, and ionic mechanisms mediating the this tolerance are discussed. A causal link between the secondary metabolite-induced disturbances to cell ionic homeostasis and programmed cell death is discussed, and a new ethylene-independent pathway for aerenchyma formation is put forward. It is concluded that plant breeding for waterlogging tolerance may significantly benefit from targeting mechanisms of tolerance to phytotoxins.
The Role of Massage in Sports Performance and Rehabilitation: Current Evidence and Future Direction
2008-01-01
Background Massage is a popular treatment choice of athletes, coaches, and sports physical therapists. Despite its purported benefits and frequent use, evidence demonstrating its efficacy is scarce. Purpose To identify current literature relating to sports massage and its role in effecting an athlete's psychological readiness, in enhancing sports performance, in recovery from exercise and competition, and in the treatment of sports related musculoskeletal injuries. Methods Electronic databases were used to identify papers relevant to this review. The following keywords were searched: massage, sports injuries, athletic injuries, physical therapy, rehabilitation, delayed onset muscle soreness, sports psychology, sports performance, sports massage, sports recovery, soft tissue mobilization, deep transverse friction massage, pre-event, and post exercise. Results Research studies pertaining to the following general categories were identified and reviewed: pre-event (physiological and psychological variables), sports performance, recovery, and rehabilitation. Discussion Despite the fact clinical research has been performed, a poor appreciation exists for the appropriate clinical use of sports massage. Conclusion Additional studies examining the physiological and psychological effects of sports massage are necessary in order to assist the sports physical therapist in developing and implementing clinically significant evidence based programs or treatments. PMID:21509135
Circulatory shear flow alters the viability and proliferation of circulating colon cancer cells
NASA Astrophysics Data System (ADS)
Fan, Rong; Emery, Travis; Zhang, Yongguo; Xia, Yuxuan; Sun, Jun; Wan, Jiandi
2016-06-01
During cancer metastasis, circulating tumor cells constantly experience hemodynamic shear stress in the circulation. Cellular responses to shear stress including cell viability and proliferation thus play critical roles in cancer metastasis. Here, we developed a microfluidic approach to establish a circulatory microenvironment and studied circulating human colon cancer HCT116 cells in response to a variety of magnitude of shear stress and circulating time. Our results showed that cell viability decreased with the increase of circulating time, but increased with the magnitude of wall shear stress. Proliferation of cells survived from circulation could be maintained when physiologically relevant wall shear stresses were applied. High wall shear stress (60.5 dyne/cm2), however, led to decreased cell proliferation at long circulating time (1 h). We further showed that the expression levels of β-catenin and c-myc, proliferation regulators, were significantly enhanced by increasing wall shear stress. The presented study provides a new insight to the roles of circulatory shear stress in cellular responses of circulating tumor cells in a physiologically relevant model, and thus will be of interest for the study of cancer cell mechanosensing and cancer metastasis.
Pulsed magnetic field induced fast drug release from magneto liposomes via ultrasound generation.
Podaru, George; Ogden, Saralyn; Baxter, Amanda; Shrestha, Tej; Ren, Shenqiang; Thapa, Prem; Dani, Raj Kumar; Wang, Hongwang; Basel, Matthew T; Prakash, Punit; Bossmann, Stefan H; Chikan, Viktor
2014-10-09
Fast drug delivery is very important to utilize drug molecules that are short-lived under physiological conditions. Techniques that can release model molecules under physiological conditions could play an important role to discover the pharmacokinetics of short-lived substances in the body. Here an experimental method is developed for the fast release of the liposomes' payload without a significant increase in (local) temperatures. This goal is achieved by using short magnetic pulses to disrupt the lipid bilayer of liposomes loaded with magnetic nanoparticles. The drug release has been tested by two independent assays. The first assay relies on the AC impedance measurements of MgSO4 released from the magnetic liposomes. The second standard release assay is based on the increase of the fluorescence signal from 5(6)-carboxyfluorescein dye when the dye is released from the magneto liposomes. The efficiency of drug release ranges from a few percent to up to 40% in the case of the MgSO4. The experiments also indicate that the magnetic nanoparticles generate ultrasound, which is assumed to have a role in the release of the model drugs from the magneto liposomes.
Human Adaptation to Isolated and Confined Environments
NASA Technical Reports Server (NTRS)
Evans, Gary W.; Stokols, Daniel; Carrere, Sybil
1987-01-01
A study was conducted over seven months in a winter Antarctic isolated and confined environment (ICE). Physiological and psychological data was collected several times a week. Information was collected on a monthly basis on behavior and the use of physical facilities. Adaptation and information indicated that there was a significant decrease in epinephrine and norepinephrine during the middle trimester of the winter. No vital changes were found for blood pressure. Self reports of hostility and anxiety show a linear increase. There were no significant changes in depression during ICE. The physiological and psychological data do not move in a synchronous fashion over time. The data also suggest that both ambient qualities of an ICE and discrete social environmental events, such as the arrival of the summer crew, have an impact on the outcome measures used. It may be most appropiate to develop a model for ICE's that incorporates not only global chronic stressors common to all ICE's but also the role of discrete environmental effects which can minimize or enhance the influence of more chronic stressors. Behavioral adjustment information highlight the importance of developing schedules which balance work and recreational activities.
Direct manipulation of physiological arousal in induced anxiety therapy - biofeedback approach.
Sappington, A A
1977-10-01
This study investigated the role of physiological arousal in the affect induction phase of Induced Anxiety therapy by using biofeedback to facilitate arousal. Twenty-one college students who were suffering from free-floating anxiety were assigned randomly to one of three groups: (1) a no-treatment control group simply completed the measures before and after therapy; (2) a conventional Induced Anxiety group went through five standard Induced Anxiety sessions; and (3) biofeedback Induced Anxiety group went through a similar procedure except that biofeedback was used in the affect induction phase to facilitate heart rate increase. It was found that the biofeedback procedure did result in a greater heart rate increase during the affect induction phase arousal than did the conventional procedure (.01 level of significance), but did not facilitate subjective emotional arousal. Biofeedback Induced Anxiety resulted in a greater reduction of trait anxiety as measured by the Multiple Affect Adjective Check List than did the no-treatment group or the conventonal Induced Anxiety group. The conventional Induced Anxiety group did not differ significantly from the no-treatment control group.
Aquaporins in the eye: Expression, function, and roles in ocular disease☆
Schey, Kevin L.; Wang, Zhen; Wenke, Jamie L.; Qi, Ying
2015-01-01
Background All thirteen known mammalian aquaporins have been detected in the eye. Moreover, aquaporins have been identified as playing essential roles in ocular functions ranging from maintenance of lens and corneal transparency to production of aqueous humor to maintenance of cellular homeostasis and regulation of signal transduction in the retina. Scope of review This review summarizes the expression and known functions of ocular aquaporins and discusses their known and potential roles in ocular diseases. Major conclusions Aquaporins play essential roles in all ocular tissues. Remarkably, not all aquaporin function as a water permeable channel and the functions of many aquaporins in ocular tissues remain unknown. Given their vital roles in maintaining ocular function and their roles in disease, aquaporins represent potential targets for future therapeutic development. General significance Since aquaporins play key roles in ocular physiology, an understanding of these functions is important to improving ocular health and treating diseases of the eye. It is likely that future therapies for ocular diseases will rely on modulation of aquaporin expression and/or function. This article is part of a Special Issue entitled Aquaporins. PMID:24184915
The role of food in the functional gastrointestinal disorders: introduction to a manuscript series.
Chey, William D
2013-05-01
Functional gastrointestinal disorders (FGIDs) are characterized by the presence of chronic or recurrent symptoms that are felt to originate from the gastrointestinal (GI) tract, which cannot be attributed to an identifiable structural or biochemical cause. Food is associated with symptom onset or exacerbation in a significant proportion of FGID patients. Despite this, the role of food in the pathogenesis of the FGIDs has remained poorly understood. For this reason, diet has largely played an adjunctive rather than a primary role in the management of FGID patients. In recent years, there has been a rapid expansion in our understanding of the role of food in GI function and sensation and how food relates to GI symptoms in FGID patients. In a series of evidence-based manuscripts produced by the Rome Foundation Working Group on the role of food in FGIDs, comprehensive reviews of the physiological changes associated with nutrient intake, and the respective roles of carbohydrates, fiber, protein, and fats are provided. The series concludes with a manuscript that provides guidance on proper clinical trial design when considering the role of food in FGIDs.
Glucocorticoid programming of neuroimmune function.
Walker, David J; Spencer, Karen A
2018-01-15
Throughout life physiological systems strive to maintain homeostasis and these systems are susceptible to exposure to maternal or environmental perturbations, particularly during embryonic development. In some cases, these perturbations may influence genetic and physiological processes that permanently alter the functioning of these physiological systems; a process known as developmental programming. In recent years, the neuroimmune system has garnered attention for its fundamental interactions with key hormonal systems, such as the hypothalamic pituitary adrenal (HPA) axis. The ultimate product of this axis, the glucocorticoid hormones, play a key role in modulating immune responses within the periphery and the CNS as part of the physiological stress response. It is well-established that elevated glucocorticoids induced by developmental stress exert profound short and long-term physiological effects, yet there is relatively little information of how these effects are manifested within the neuroimmune system. Pre and post-natal periods are prime candidates for manipulation in order to uncover the physiological mechanisms that underlie glucocorticoid programming of neuroimmune responses. Understanding the potential programming role of glucocorticoids may be key in uncovering vulnerable windows of CNS susceptibility to stressful experiences during embryonic development and improve our use of glucocorticoids as therapeutics in the treatment of neurodegenerative diseases. Crown Copyright © 2017. Published by Elsevier Inc. All rights reserved.
Renal nerves dynamically regulate renal blood flow in conscious, healthy rabbits.
Schiller, Alicia M; Pellegrino, Peter R; Zucker, Irving H
2016-01-15
Despite significant clinical interest in renal denervation as a therapy, the role of the renal nerves in the physiological regulation of renal blood flow (RBF) remains debated. We hypothesized that the renal nerves physiologically regulate beat-to-beat RBF variability (RBFV). This was tested in chronically instrumented, healthy rabbits that underwent either bilateral surgical renal denervation (DDNx) or a sham denervation procedure (INV). Artifact-free segments of RBF and arterial pressure (AP) from calmly resting, conscious rabbits were used to extract RBFV and AP variability for time-domain, frequency-domain, and nonlinear analysis. Whereas steady-state measures of RBF, AP, and heart rate did not statistically differ between groups, DDNx rabbits had greater RBFV than INV rabbits. AP-RBF transfer function analysis showed greater admittance gain in DDNx rabbits than in INV rabbits, particularly in the low-frequency (LF) range where systemic sympathetic vasomotion gives rise to AP oscillations. In the LF range, INV rabbits exhibited a negative AP-RBF phase shift and low coherence, consistent with the presence of an active control system. Neither of these features were present in the LF range of DDNx rabbits, which showed no phase shift and high coherence, consistent with a passive, Ohm's law pressure-flow relationship. Renal denervation did not significantly affect nonlinear RBFV measures of chaos, self-affinity, or complexity, nor did it significantly affect glomerular filtration rate or extracellular fluid volume. Cumulatively, these data suggest that the renal nerves mediate LF renal sympathetic vasomotion, which buffers RBF from LF AP oscillations in conscious, healthy rabbits. Copyright © 2016 the American Physiological Society.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Tabita, F. Robert
2008-12-04
During the past years of this project we have made progress relative to the two major goals of the proposal: (1) to study the biochemistry and regulation of the reductive TCA cycle of CO 2 fixation and (2) to probe the physiological role of a RubisCO-like protein (RLP). Both studies primarily employ the green sulfur bacterium Chlorobium tepidum as well as other photosynthetic bacteria including Rhodospirillum rubrum and Rhodopseudomonas palustris.
Role of Neuroactive Steroids in the Peripheral Nervous System
Melcangi, Roberto Cosimo; Giatti, Silvia; Pesaresi, Marzia; Calabrese, Donato; Mitro, Nico; Caruso, Donatella; Garcia-Segura, Luis Miguel
2011-01-01
Several reviews have so far pointed out on the relevant physiological and pharmacological role exerted by neuroactive steroids in the central nervous system. In the present review we summarize observations indicating that synthesis and metabolism of neuroactive steroids also occur in the peripheral nerves. Interestingly, peripheral nervous system is also a target of their action. Indeed, as here reported neuroactive steroids are physiological regulators of peripheral nerve functions and they may also represent interesting therapeutic tools for different types of peripheral neuropathy. PMID:22654839
[Beta-endorphin--physiologic role and menstrual cycle disorders].
Meczekalski, B; Warenik-Szymankiewicz, A
1995-10-01
There are three classes of endogenous opioid peptides: endorphins, enkephalins, dynorphins. Beta-endorphin is the main representative of endogenous opioid peptides. Beta-endorphin plays a role in the regulation of the normal menstrual cycle and possibly in the onset of puberty. This peptide is also involved in the pathophysiology of such menstrual disorders as: exercise-associated amenorrhoea, stress-induced amenorrhoea, weight loss related amenorrhoea and premenstrual syndrome. Probable mechanism is that alterations in the levels of beta-endorphin may change the pulsatile release of GnRH. This article reviews contemporary views on the role of beta-endorphin in the physiology and disorders of the menstrual cycle.
Update in TSH Receptor Agonists and Antagonists
Neumann, Susanne
2012-01-01
The physiological role of the TSH receptor (TSHR) as a major regulator of thyroid function is well understood, but TSHRs are also expressed in multiple normal extrathyroidal tissues, and the physiological roles of TSHRs in these tissues are unclear. Moreover, TSHRs play a major role in several pathological conditions including hyperthyroidism, hypothyroidism, and thyroid tumors. Small molecule, “drug-like” TSHR agonists, neutral antagonists, and inverse agonists may be useful as probes of TSHR function in extrathyroidal tissues and as leads to develop drugs for several diseases of the thyroid. In this Update, we review the most recent findings regarding the development and use of these small molecule TSHR ligands. PMID:23019348
The role of adult hippocampal neurogenesis in brain health and disease.
Toda, Tomohisa; Parylak, Sarah L; Linker, Sara B; Gage, Fred H
2018-04-20
Adult neurogenesis in the dentate gyrus of the hippocampus is highly regulated by a number of environmental and cell-intrinsic factors to adapt to environmental changes. Accumulating evidence suggests that adult-born neurons may play distinct physiological roles in hippocampus-dependent functions, such as memory encoding and mood regulation. In addition, several brain diseases, such as neurological diseases and mood disorders, have deleterious effects on adult hippocampal neurogenesis, and some symptoms of those diseases can be partially explained by the dysregulation of adult hippocampal neurogenesis. Here we review a possible link between the physiological functions of adult-born neurons and their roles in pathological conditions.
Ohnuki, Yoshiki; Umeki, Daisuke; Mototani, Yasumasa; Jin, Huiling; Cai, Wenqian; Shiozawa, Kouichi; Suita, Kenji; Saeki, Yasutake; Fujita, Takayuki; Ishikawa, Yoshihiro; Okumura, Satoshi
2014-12-15
The predominant isoform of β-adrenoceptor (β-AR) in skeletal muscle is β2-AR and that in the cardiac muscle is β1-AR. We have reported that Epac1 (exchange protein directly activated by cAMP 1), a new protein kinase A-independent cAMP sensor, does not affect cardiac hypertrophy in response to pressure overload or chronic isoproterenol (isoprenaline) infusion. However, the role of Epac1 in skeletal muscle hypertrophy remains poorly understood. We thus examined the effect of disruption of Epac1, the major Epac isoform in skeletal muscle, on masseter muscle hypertrophy induced by chronic β2-AR stimulation with clenbuterol (CB) in Epac1-null mice (Epac1KO). The masseter muscle weight/tibial length ratio was similar in wild-type (WT) and Epac1KO at baseline and was significantly increased in WT after CB infusion, but this increase was suppressed in Epac1KO. CB treatment significantly increased the proportion of myosin heavy chain (MHC) IIb at the expense of that of MHC IId/x in both WT and Epac1KO, indicating that Epac1 did not mediate the CB-induced MHC isoform transition towards the faster isoform. The mechanism of suppression of CB-mediated hypertrophy in Epac1KO is considered to involve decreased activation of Akt signalling. In addition, CB-induced histone deacetylase 4 (HDAC4) phosphorylation on serine 246 mediated by calmodulin kinase II (CaMKII), which plays a role in skeletal muscle hypertrophy, was suppressed in Epac1KO. Our findings suggest that Epac1 plays a role in β2-AR-mediated masseter muscle hypertrophy, probably through activation of both Akt signalling and CaMKII/HDAC4 signalling. © 2014 The Authors. The Journal of Physiology © 2014 The Physiological Society.
Physiologically-based kinetic modelling in risk assessment
The European Union Reference Laboratory for Alternatives to Animal Testing (EURL ECVAM) hosted a two-day workshop with an aim to discuss the role and application of Physiologically Based Kinetic (PBK) models in regulatory decision making. The EURL ECVAM strategy document on Toxic...
Chen, Shulian; Peng, Chuandu; Wei, Xin; Luo, Deyi; Lin, Yifei; Yang, Tongxin; Jin, Xi; Gong, Lina; Li, Hong; Wang, Kunjie
2017-08-01
To investigate the effect of simulated physiological stretch on the expression of extracellular matrix (ECM) proteins and the role of integrin α4/αv, focal adhesion kinase (FAK), extracellular regulated protein kinases 1/2 (ERK1/2) in the stretch-induced ECM protein expression of human bladder smooth muscle cells (HBSMCs). HBSMCs were seeded onto silicone membrane and subjected to simulated physiological stretch at the range of 5, 10, and 15% elongation. Expression of primary ECM proteins in HBSMCs was analyzed by real-time polymerase chain reaction and Western blot. Specificity of the FAK and ERK1/2 was determined by Western blot with FAK inhibitor and ERK1/2 inhibitor (PD98059). Specificity of integrin α4 and integrin αv was determined with small interfering ribonucleic acid (siRNA) transfection. The expression of collagen I (Col1), collagen III (Col3), and fibronectin (Fn) was increased significantly under the simulated physiological stretch of 10 and 15%. Integrin α4 and αv, FAK, ERK1/2 were activated by 10% simulated physiological stretch compared with the static condition. Pretreatment of ERK1/2 inhibitor, FAK inhibitor, integrin α4 siRNA, or integrin αv siRNA reduced the stretch-induced expression of ECM proteins. And FAK inhibitor decreased the stretch-induced ERK1/2 activity and ECM protein expression. Integrin α4 siRNA or integrin αv siRNA inhibited the stretch-induced activity of FAK. Simulated physiological stretch increases the expression of ECM proteins in HBSMCs, and integrin α4/αv-FAK-ERK1/2 signaling pathway partly modulates the mechano-transducing process.
Woody, Mary L.; Feurer, Cope; Sosoo, Effua E.; Hastings, Paul D.; Gibb, Brandon E.
2017-01-01
Background The family environment plays an important role in the intergenerational transmission of MDD, but less is known about how day-to-day mother-child interactions may be disrupted in families with a history of MDD. Disruptions in mother-child synchrony, the dynamic and convergent exchange of physiological and behavioral cues during interactions, may be one important risk factor. Although maternal MDD is associated with a lack of mother-child synchrony at the behavioral level, no studies have examined the impact of maternal MDD on physiological synchrony. Therefore, the current study examined whether maternal history of MDD moderates mother-child physiological synchrony (measured via RSA) during positive and negative discussions. Method Children ages 7–11 and mothers with either a history of MDD during the child’s lifetime (n=44) or no lifetime diagnosis of any mood disorder (n=50) completed positive and negative discussion tasks while RSA was continuously recorded for both child and mother. Results Results indicated significant between-dyad and within-dyad group differences in physiological synchrony during positive and negative discussions. Between-dyad analyses revealed evidence of synchrony only among never depressed dyads, among whom higher average mother RSA during both discussions was associated with higher average child RSA. Within-dyad analyses revealed that never depressed dyads displayed positive synchrony (RSA concordance) whereas dyads with a history of maternal MDD displayed negative synchrony (RSA discordance) during the negative discussion and that the degree of negative synchrony exhibited during the negative discussion was associated with mothers’ and children’s levels of sadness. Conclusions These results provide preliminary evidence that physiological synchrony is disrupted in families with a history of maternal MDD and may be a potential risk factor for the intergenerational transmission of depression. PMID:27090774
Stable isotope tracers and exercise physiology: past, present and future.
Wilkinson, Daniel J; Brook, Matthew S; Smith, Kenneth; Atherton, Philip J
2017-05-01
Stable isotope tracers have been invaluable assets in physiological research for over 80 years. The application of substrate-specific stable isotope tracers has permitted exquisite insight into amino acid, fatty-acid and carbohydrate metabolic regulation (i.e. incorporation, flux, and oxidation, in a tissue-specific and whole-body fashion) in health, disease and response to acute and chronic exercise. Yet, despite many breakthroughs, there are limitations to 'substrate-specific' stable isotope tracers, which limit physiological insight, e.g. the need for intravenous infusions and restriction to short-term studies (hours) in controlled laboratory settings. In recent years significant interest has developed in alternative stable isotope tracer techniques that overcome these limitations, in particular deuterium oxide (D 2 O or heavy water). The unique properties of this tracer mean that through oral administration, the turnover and flux through a number of different substrates (muscle proteins, lipids, glucose, DNA (satellite cells)) can be monitored simultaneously and flexibly (hours/weeks/months) without the need for restrictive experimental control. This makes it uniquely suited for the study of 'real world' human exercise physiology (amongst many other applications). Moreover, using D 2 O permits evaluation of turnover of plasma and muscle proteins (e.g. dynamic proteomics) in addition to metabolomics (e.g. fluxomics) to seek molecular underpinnings, e.g. of exercise adaptation. Here, we provide insight into the role of stable isotope tracers, from substrate-specific to novel D 2 O approaches, in facilitating our understanding of metabolism. Further novel potential applications of stable isotope tracers are also discussed in the context of integration with the snowballing field of 'omic' technologies. © 2016 The Authors. The Journal of Physiology © 2016 The Physiological Society.
Taylor, S B; Watterson, L R; Kufahl, P R; Nemirovsky, N E; Tomek, S E; Conrad, C D; Olive, M F
2016-09-01
Stress is a contributing factor to the development and maintenance of addiction in humans. However, few studies have shown that stress potentiates the rewarding and/or reinforcing effects of methamphetamine in rodent models of addiction. The present study assessed the effects of exposure to 14 days of chronic variable stress (CVS), or no stress as a control (CON), on the rewarding and reinforcing effects of methamphetamine in adult rats using the conditioned place preference (Experiment 1) and intravenous self-administration (Experiment 2) paradigms. In Experiment 2, we also assessed individual differences in open field locomotor activity, anxiety-like behavior in the elevated plus maze (EPM), and physiological responses to a novel environment as possible predictors of methamphetamine intake patterns. Exposure to CVS for 14 days did not affect overall measures of methamphetamine conditioned reward or reinforcement. However, analyses of individual differences and direct vs. indirect effects revealed that rats exhibiting high physiological reactivity and locomotor activity in the EPM and open field tests self-administered more methamphetamine and reached higher breakpoints for drug reinforcement than rats exhibiting low reactivity. In addition, CVS exposure significantly increased the proportion of rats that exhibited high reactivity, and high reactivity was significantly correlated with increased levels of methamphetamine intake. These findings suggest that individual differences in physiological and locomotor reactivity to novel environments, as well as their interactions with stress history, predict patterns of drug intake in rodent models of methamphetamine addiction. Such predictors may eventually inform future strategies for implementing individualized treatment strategies for amphetamine use disorders. Copyright © 2016 Elsevier Ltd. All rights reserved.
Guo, Xinwei; Ma, Zeyang; Zhang, Zhonghui; Cheng, Lailiang; Zhang, Xiuren; Li, Tianhong
2017-01-01
Transition from vegetative to floral buds is a critical physiological change during flower induction that determines fruit productivity. Small non-coding RNAs (sRNAs) including microRNAs (miRNAs) and small interfering RNAs (siRNAs) are pivotal regulators of plant growth and development. Although the key role of sRNAs in flowering regulation has been well-described in Arabidopsis and some other annual plants, their relevance to vegetative-to-floral transition (hereafter, referred to floral transition) in perennial woody trees remains under defined. Here, we performed Illumina sequencing of sRNA libraries prepared from vegetative and floral bud during flower induction of the apple trees. A large number of sRNAs exemplified by 33 previously annotated miRNAs and six novel members display significant differential expression (DE) patterns. Notably, most of these DE-miRNAs in floral transition displayed opposite expression changes in reported phase transition in apple trees. Bioinformatics analysis suggests most of the DE-miRNAs targeted transcripts involved in SQUAMOSA PROMOTER BINDING PROTEIN-LIKE ( SPL ) gene regulation, stress responses, and auxin and gibberellin (GA) pathways, with further suggestion that there is an inherent link between physiological stress response and metabolism reprogramming during floral transition. We also observed significant changes in 24 nucleotide (nt) sRNAs that are hallmarks for RNA-dependent DNA methylation (RdDM) pathway, suggestive of the correlation between epigenetic modifications and the floral transition. The study not only provides new insight into our understanding of fundamental mechanism of poorly studied floral transition in apple and other woody plants, but also presents important sRNA resource for future in-depth research in the apple flowering physiology.
Guo, Xinwei; Ma, Zeyang; Zhang, Zhonghui; Cheng, Lailiang; Zhang, Xiuren; Li, Tianhong
2017-01-01
Transition from vegetative to floral buds is a critical physiological change during flower induction that determines fruit productivity. Small non-coding RNAs (sRNAs) including microRNAs (miRNAs) and small interfering RNAs (siRNAs) are pivotal regulators of plant growth and development. Although the key role of sRNAs in flowering regulation has been well-described in Arabidopsis and some other annual plants, their relevance to vegetative-to-floral transition (hereafter, referred to floral transition) in perennial woody trees remains under defined. Here, we performed Illumina sequencing of sRNA libraries prepared from vegetative and floral bud during flower induction of the apple trees. A large number of sRNAs exemplified by 33 previously annotated miRNAs and six novel members display significant differential expression (DE) patterns. Notably, most of these DE-miRNAs in floral transition displayed opposite expression changes in reported phase transition in apple trees. Bioinformatics analysis suggests most of the DE-miRNAs targeted transcripts involved in SQUAMOSA PROMOTER BINDING PROTEIN-LIKE (SPL) gene regulation, stress responses, and auxin and gibberellin (GA) pathways, with further suggestion that there is an inherent link between physiological stress response and metabolism reprogramming during floral transition. We also observed significant changes in 24 nucleotide (nt) sRNAs that are hallmarks for RNA-dependent DNA methylation (RdDM) pathway, suggestive of the correlation between epigenetic modifications and the floral transition. The study not only provides new insight into our understanding of fundamental mechanism of poorly studied floral transition in apple and other woody plants, but also presents important sRNA resource for future in-depth research in the apple flowering physiology. PMID:28611800
Ishiguro, Tomohito; Takeda, Jun; Fang, Xin; Bronson, Heather; Olson, David M
2016-07-01
The role of interleukin-1 (IL-1), a pro-inflammatory cytokine, in parturition is typically noted by changes in its concentrations. Studying the expression of its receptor family, IL-1 receptor (IL-1R) 1, IL-1R2, IL-1R accessory protein (IL-1RAcP), and its predominantly brain isoform, IL-1RAcPb, during late gestation in the uterus in the Long-Evans rat is another. We assessed changes in their mRNA and protein relative abundance in the uterus and compared IL-1RAcP and IL-1RAcPb mRNA abundance in uterus, cervix, ovaries, placenta, and whole blood of Long-Evans rats during late gestation or in RU486 and progesterone-treated dams using quantitative real-time PCR and western immunoblotting. IL-1R1, IL-1RAcP, and IL-1RAcPb mRNA abundance significantly increased in the uterus at delivery whereas IL-1R2 mRNA abundance significantly decreased. IL-1R1 protein increased at term and IL-1R2 protein decreased at term compared to nonpregnant uteri. IL1-RAcPb mRNA abundance was less than IL-1RAcP, but in the lower uterine segment it was the highest of all tissues examined. RU486 stimulated preterm delivery and an increase in IL-1R1 mRNA abundance whereas progesterone administration extended pregnancy and suppressed the increase in IL-1R1. These data suggest that changes in uterine sensitivity to IL-1 occur during late gestation and suggest another level of regulation for the control of delivery. The roles for IL-1RAcP and IL-1RAcPb need to be determined, but may relate to different intracellular signaling pathways. © 2016 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.
Warnhoff, Kurt; Murphy, John T.; Kumar, Sandeep; Schneider, Daniel L.; Peterson, Michelle; Hsu, Simon; Guthrie, James; Robertson, J. David; Kornfeld, Kerry
2014-01-01
The insulin/IGF-1 signaling pathway plays a critical role in stress resistance and longevity, but the mechanisms are not fully characterized. To identify genes that mediate stress resistance, we screened for C. elegans mutants that can tolerate high levels of dietary zinc. We identified natc-1, which encodes an evolutionarily conserved subunit of the N-terminal acetyltransferase C (NAT) complex. N-terminal acetylation is a widespread modification of eukaryotic proteins; however, relatively little is known about the biological functions of NATs. We demonstrated that loss-of-function mutations in natc-1 cause resistance to a broad-spectrum of physiologic stressors, including multiple metals, heat, and oxidation. The C. elegans FOXO transcription factor DAF-16 is a critical target of the insulin/IGF-1 signaling pathway that mediates stress resistance, and DAF-16 is predicted to directly bind the natc-1 promoter. To characterize the regulation of natc-1 by DAF-16 and the function of natc-1 in insulin/IGF-1 signaling, we analyzed molecular and genetic interactions with key components of the insulin/IGF-1 pathway. natc-1 mRNA levels were repressed by DAF-16 activity, indicating natc-1 is a physiological target of DAF-16. Genetic studies suggested that natc-1 functions downstream of daf-16 to mediate stress resistance and dauer formation. Based on these findings, we hypothesize that natc-1 is directly regulated by the DAF-16 transcription factor, and natc-1 is a physiologically significant effector of the insulin/IGF-1 signaling pathway that mediates stress resistance and dauer formation. These studies identify a novel biological function for natc-1 as a modulator of stress resistance and dauer formation and define a functionally significant downstream effector of the insulin/IGF-1 signaling pathway. Protein N-terminal acetylation mediated by the NatC complex may play an evolutionarily conserved role in regulating stress resistance. PMID:25330323
The short history of gastroenterology.
Sródka, A
2003-12-01
In this paper research on the stomach and bowel physiology is presented in a historical perspective. The author tries to show how digestive processes were interpreted by the ancients and how they tried to adjust them to the dominating humoral theory of disease. It is pointed out that the breakthrough which created a new way of understanding of the function of the digestive system was made by Andreas Vesalius and his modern model of anatomy. The meaning of acceptance of chemical processes in digestion by iatrochemics representatives in XVII century is shown. Physiological research in XIX century, which decided about a rapid development of physiology, especially the physiology of the gastrointestinal tract, is discussed. Experiments were performed by all main representatives of this discipline: Claude Bernard, Jan Ewangelista Purkyne, Rudolph Heidenhain and especially Ivan Pavlov, who, thanks to the discoveries in the secretion physiology, explained basic functions of the central nervous system. The XX century was dominated by the research showing the important role of the endocrine system and biological agents in the regulation of secretion and motility of the digestive system. The following discoveries are discussed: Ernest Sterling (secretin), John Edkins (gastrin) and André Latarjet and Lester Dragstedt (acetylcholine). It is underlined that Polish scientists play an important role in the development of the gastroenterological science--among others, Walery Jaworski, who made a historical suggestion about the role of the spiral bacteria in etiopathogenesis of the peptic ulcer, Leon Popielski, who stated the stimulating influence of histamine on the stomach acid secretion, Julian Walawski, who discovered enterogastrons--hormones decreasing secretion. As a supplement, there is the list of achievements in the field of the physiology and pathology of the gastrointestinal tract awarded with Nobel Prize and the list of most important Polish papers in this field.
Physiological adaptations to interval training and the role of exercise intensity.
MacInnis, Martin J; Gibala, Martin J
2017-05-01
Interval exercise typically involves repeated bouts of relatively intense exercise interspersed by short periods of recovery. A common classification scheme subdivides this method into high-intensity interval training (HIIT; 'near maximal' efforts) and sprint interval training (SIT; 'supramaximal' efforts). Both forms of interval training induce the classic physiological adaptations characteristic of moderate-intensity continuous training (MICT) such as increased aerobic capacity (V̇O2 max ) and mitochondrial content. This brief review considers the role of exercise intensity in mediating physiological adaptations to training, with a focus on the capacity for aerobic energy metabolism. With respect to skeletal muscle adaptations, cellular stress and the resultant metabolic signals for mitochondrial biogenesis depend largely on exercise intensity, with limited work suggesting that increases in mitochondrial content are superior after HIIT compared to MICT, at least when matched-work comparisons are made within the same individual. It is well established that SIT increases mitochondrial content to a similar extent to MICT despite a reduced exercise volume. At the whole-body level, V̇O2 max is generally increased more by HIIT than MICT for a given training volume, whereas SIT and MICT similarly improve V̇O2 max despite differences in training volume. There is less evidence available regarding the role of exercise intensity in mediating changes in skeletal muscle capillary density, maximum stroke volume and cardiac output, and blood volume. Furthermore, the interactions between intensity and duration and frequency have not been thoroughly explored. While interval training is clearly a potent stimulus for physiological remodelling in humans, the integrative response to this type of exercise warrants further attention, especially in comparison to traditional endurance training. © 2016 The Authors. The Journal of Physiology © 2016 The Physiological Society.
NASA Astrophysics Data System (ADS)
Wang, Jie; Russell, Bayden D.; Ding, Meng-Wen; Dong, Yun-Wei
2018-05-01
Understanding physiological responses of organisms to warming and ocean acidification is the first step towards predicting the potential population- and community-level ecological impacts of these stressors. Increasingly, physiological plasticity is being recognized as important for organisms to adapt to the changing microclimates. Here, we evaluate the importance of physiological plasticity for coping with ocean acidification and elevated temperature, and its variability among individuals, of the intertidal limpet Cellana toreuma from the same population in Xiamen. Limpets were collected from shaded mid-intertidal rock surfaces. They were acclimated under combinations of different pCO2 concentrations (400 and 1000 ppm, corresponding to a pH of 8.1 and 7.8) and temperatures (20 and 24 °C) in a short-term period (7 days), with the control conditions (20 °C and 400 ppm) representing the average annual temperature and present-day pCO2 level at the collection site. Heart rates (as a proxy for metabolic performance) and expression of genes encoding inducible and constitutive heat-shock proteins (hsp70 and hsc70) at different heat-shock temperatures (26, 30, 34, and 38 °C) were measured. Hsp70 and Hsc70 play important roles in protecting cells from heat stresses, but have different expression patterns, with Hsp70 significantly increased in expression during stress and Hsc70 constitutively expressed and only mildly induced during stress. Analysis of heart rate showed significantly higher temperature coefficients (Q10 rates) for limpets at 20 °C than at 24 °C and post-acclimation thermal sensitivity of limpets at 400 ppm was lower than at 1000 ppm. Expression of hsp70 linearly increased with the increasing heat-shock temperatures, with the largest slope occurring in limpets acclimated under a future scenario (24 °C and 1000 ppm pCO2). These results suggested that limpets showed increased sensitivity and stress response under future conditions. Furthermore, the increased variation in physiological response under the future scenario indicated that some individuals have higher physiological plasticity to cope with these conditions. While short-term acclimation to reduced pH seawater decreases the ability of partial individuals against thermal stress, physiological plasticity and variability seem to be crucial in allowing some intertidal animals to survive in a rapidly changing environment.
NASA Astrophysics Data System (ADS)
Fowler, M. D.; Kooperman, G. J.; Pritchard, M. S.; Randerson, J. T.
2017-12-01
River flooding events, which are the most frequently occurring natural disaster today, are expected to become more frequent and intense in response to climate change. However, the magnitude of these changes remains debated, in part due to uncertainty in our understanding of the physical processes that contribute to these events and their representation in global climate models. While the intensification of precipitation has been shown to be a primary driver of increased flooding, plant physiological responses to increasing CO2 may also play an important role. As the atmospheric concentration of CO2 increases, plants may respond by reducing the width of their stomata (i.e. stomatal conductance), which can decrease water lost through transpiration and in turn maintain higher soil moisture levels. On long timescales, reduced transpiration has been shown to increase average runoff, but on short timescales elevated soil moisture can also increase instantaneous runoff by limiting the rate at which water is able to infiltrate the soil surface. Here, through hydrodynamic downscaling, we isolate the portion of flooding amplification that can be attributed to the physiological response to increasing CO2. This builds on a new analysis that has revealed such physiological effects can rival changes caused by the atmospheric response alone in the tails of the runoff distribution. We use a set of four simulations run with the Community Earth System Model: one pre-industrial control simulation and three others that are forced with four times CO2. In the three climate change simulations, the increased CO2 is applied only to the land-surface, only to the atmosphere, and to both, respectively. Thirty years of daily runoff from these experiments are used as input for the hydrodynamic CaMa-Flood model. Our results reveal that both the radiative and physiological responses to climate change contribute significantly to future changes in flood return period and inundated area. This implies that better constraining the sensitivity of stomatal conductance to CO2 is of first order importance to reducing uncertainty for potential flood frequency and associated risk in a changing climate.
The role of open stone surgery
El-Husseiny, Tamer; Buchholz, Noor
2012-01-01
Objective To highlight the role of open stone surgery in the management of urolithiasis in the current era of minimally invasive therapies. The introduction and continuous development of extracorporeal shockwave lithotripsy (ESWL), ureterorenoscopy and percutaneous nephrolithotomy (PCNL) over the past 30 years have led to a significant change in the current management of urolithiasis, where the indications for open stone surgery have been narrowed significantly, making it a second- or third-line treatment option. Methods We reviewed the most recent guidelines published by the European Association of Urology and the American Urological Association, and reviewed reports through a MEDLINE search to identify the indications and current role of open stone surgery. Results From the MEDLINE search, it was obvious that the number of papers published on open renal stone surgery has decreased during the last three decades, soon after the introduction of ESWL and PCNL. Conclusion Although currently most patients with stones can be managed by minimally invasive therapy, we believe that open surgery still has a role, and therefore it is of great importance to recognise that a small group of patients with complex stone disease, and those with anatomical and physiological anomalies, will benefit from this treatment option. PMID:26558038
Hernandez, L L
2018-04-25
Lactation is a physiological event that is exclusive to mammals. Lactation evolved as a strategy to improve the survival of the young by providing them with the complete nutrition that is required for survival upon birth as well as maternal-offspring bonding. Typically, milk production by the dam matches the demand of the young. The dairy cow is a unique exception in which the discoveries and genetic selection related to lactation physiology have been applied and resulted in a dramatic increase in milk yield of dairy cows. Studies on the role of mammary-derived serotonin and the coordination of various aspects of milk production and maternal metabolism have revealed novel mechanisms by which milk production and maternal metabolism can be improved. Furthermore, the investigation into molecular and cellular mechanisms regulating mammary gland function has revealed the importance of epigenetics on mammary gland function. Understanding mammary gland function at the cellular and physiological levels will be important for improving mammary gland control of maternal metabolism during early lactation. The early lactation period is a critical time for a dairy cow as that is when she is most susceptible to disease and metabolic disorders that can lead to negative effects on her productive capacity and overall health. Our research in the area of serotonin physiology has illustrated the importance of serotonin on the regulation of lactation and maternal homeostasis. Future research in the area of lactation physiology should be targeted at improving maternal health and longevity in the herd through manipulation of the signals the mammary gland sends to coordinate maternal metabolism and synthesize milk. Specifically, we believe that serotonin will play a central role in understanding the communication between the mammary gland and the maternal physiology during lactation. Copyright © 2018 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.
Physiological modeling for detecting degree of perception of a color-deficient person.
Rajalakshmi, T; Prince, Shanthi
2017-04-01
Physiological modeling of retina plays a vital role in the development of high-performance image processing methods to produce better visual perception. People with normal vision have an ability to discern different colors. The situation is different in the case of people with color blindness. The aim of this work is to develop a human visual system model for detecting the level of perception of people with red, green and blue deficiency by considering properties like luminance, spatial and temporal frequencies. Simulation results show that in the photoreceptor, outer plexiform and inner plexiform layers, the energy and intensity level of the red, green and blue component for a normal person is proved to be significantly higher than for dichromats. The proposed method explains with appropriate results that red and blue color blindness people could not perceive red and blue color completely.
Effect of spatial coherence of light on the photoregulation processes in cells
NASA Astrophysics Data System (ADS)
Budagovsky, A. V.; Solovykh, N. V.; Yankovskaya, M. B.; Maslova, M. V.; Budagovskaya, O. N.; Budagovsky, I. A.
2016-07-01
The effect of the statistical properties of light on the value of the photoinduced reaction of the biological objects, which differ in the morphological and physiological characteristics, the optical properties, and the size of cells, was studied. The fruit of apple trees, the pollen of cherries, the microcuttings of blackberries in vitro, and the spores and the mycelium of fungi were irradiated by quasimonochromatic light fluxes with identical energy parameters but different values of coherence length and radius of correlation. In all cases, the greatest stimulation effect occurred when the cells completely fit in the volume of the coherence of the field, while both temporal and spatial coherence have a significant and mathematically certain impact on the physiological activity of cells. It was concluded that not only the spectral, but also the statistical (coherent) properties of the acting light play an important role in the photoregulation process.
Social Disadvantage, Severe Child Abuse, and Biological Profiles in Adulthood.
Lee, Chioun; Coe, Christopher L; Ryff, Carol D
2017-09-01
Guided by the stress process model and the life course perspective, we hypothesize: (1) that childhood abuse is concentrated, in terms of type and intensity, among socially disadvantaged individuals, and (2) that experiencing serious abuse contributes to poor biological profiles in multiple body systems in adulthood. Data came from the Biomarker subsample of Midlife in the United States (2004-2006). We used latent class analysis to identify distinct profiles of childhood abuse, each reflecting a combination of type and severity. Results indicate that disadvantaged groups, women, and those from disadvantaged families are at greater risk of experiencing more severe and multiple types of abuse. Those with more severe and multifaceted childhood abuse show greater physiological dysregulation. Childhood abuse experiences partially accounted for the social status differences in physiological profiles. Our findings underscore that differential exposure to serious childhood stressors plays a significant role in gender and class inequalities in adult health.
Abnormal cardiac response to exercise in a murine model of familial hypertrophic cardiomyopathy.
Nguyen, Lan; Chung, Jessica; Lam, Lien; Tsoutsman, Tatiana; Semsarian, Christopher
2007-07-10
Clinical outcome in familial hypertrophic cardiomyopathy (FHC) may be influenced by modifying factors such as exercise. Transgenic mice which overexpress the human disease-causing cTnI gene mutation, Gly203Ser (designated cTnI-G203S), develop all the characteristic phenotypic features of FHC. To study the modifying effect of exercise in early disease, mice underwent swimming exercise at an early age prior to the development of the FHC phenotype. In non-transgenic and cTnI-wt mice, swimming resulted in a significant increase in left ventricular wall thickness and contractility on echocardiography, consistent with a physiological hypertrophic response to exercise. In contrast, cTnI-G203S mice showed no increase in these parameters, indicating an abnormal response to exercise. The lack of a physiological response to exercise may indicate an important novel mechanistic insight into the role of exercise in triggering adverse events in FHC.
MiRNAs of peripheral blood as the biomarker of schizophrenia.
He, Kuanjun; Guo, Chuang; He, Lin; Shi, Yongyong
2018-01-01
The diagnosis of schizophrenia is currently based on the symptoms and bodily signs rather than on the pathological and physiological markers of the patient. In the search for new molecular targeted therapy medicines, and recurrence of early-warning indicators have become the major focus of contemporary research, because they improve diagnostic accuracy. Biomarkers reflect the physiological, physical and biochemical status of the body, and so have extensive applicability and practical significance. The ascertainment of schizophrenia biomarkers will help diagnose, stratify of disease, and treat of schizophrenia patients. The detection of biomarkers from blood has become a promising area of schizophrenia research. Recently, a series of studies revealed that, MiRNAs play an important role in the genesis of schizophrenia, and their abnormal expressions have the potential to be used as biomarkers of schizophrenia. This article presents and summarizes the value of peripheral blood miRNAs with abnormal expression as the biomarker of schizophrenia.
[The historical background of the pineal gland: I. From a spiritual valve to the seat of the soul].
López-Muñoz, Francisco; Marín, Fernando; Alamo, Cecilio
Throughout history, the special anatomical location of the pineal gland in the central nervous system has given rise to a number of physiological hypotheses regarding the functional role of this organ. In classical ancient times, the pineal body (conarium) was considered to be a sort of valve-like sphincter that regulated the flow of the spiritus animalis at the ventricular level. But it was not until the 17th century that the pineal gland finally reached its highest levels of physiological significance, when Rene Descartes considered it to be the anatomical structure that housed the seat of the soul. The Cartesian hypotheses regarding the pineal gland did not arouse much interest in the scientific community of the time, and attention to this organ dwindled from then until the 20th century, when its neuroendocrinological nature was finally confirmed.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Penry, D.L.; Weston, D.P.
1998-11-01
The uptake of hydrophobic contaminants from ingested sediment can contribute significantly to body burdens of deposit feeders, and feeding behavior and digestive physiology can play important roles in bioaccumulation. The authors examined the uptake of polycyclic aromatic hydrocarbons (PAHs) by the deposit-feeding polychaete Abarenicola pacifica in experiments in which worms were first acclimated to low or high organic carbon sediments with 0.08 or 0.45% total organic carbon, respectively and then transferred to low or high organic carbon test sediments contaminated with radiolabeled phenanthrene or benzo[a]pyrene. Ingestion rate was measurements are essential in many types of bioaccumulation studies because differences inmore » ingestion rates between sediment types may confound some traditional measures of bioavailability. Physiological acclimation to the low or high organic carbon sediments did not appear to affect PAH uptake from the test sediments, but acclimation did affect biotransformation capabilities, particularly for phenanthrene.« less
Role of melanocortins in the central control of feeding.
Vergoni, A V; Bertolini, A
2000-09-29
The injection of a melanocortin peptide or of melanocortin peptide analogues into the cerebrospinal fluid or into the ventromedial hypothalamus in nanomolar or subnanomolar doses induces a long-lasting inhibition of food intake. The effect keeps significant for up to 9 h and has been observed in all animal species so far tested, the most susceptible being the rabbit. The anorectic effect of these peptides is a primary one, not secondary to the shift towards other components of the complex melanocortin-induced behavioral syndrome, in particular grooming. The site of action is in the brain, and the effect is not adrenal-mediated because it is fully exhibited also by adrenalectomized animals. It is a very strong effect, because the degree of feeding inhibition is not reduced in conditions of hunger, either induced by 24 h starvation, or by insulin-induced hypoglycemia, or by stimulation of gamma-aminobutyric acid (GABA), noradrenergic or opioid systems. The microstructural analysis of feeding behavior suggests that melanocortins act as satiety-inducing agents, because they do not significantly modify the latencies to start eating, but shorten the latencies to stop eating. The mechanism of action involves the activation of melanocortin MC(4) receptors, because selective melanocortin MC(4) receptor antagonists inhibit the anorectic effect of melanocortins, while inducing per se a strong stimulation of food intake and a significant increase in body weight. Melanocortins seem to play an important role in stress-induced anorexia, because such condition, in rats, is significantly attenuated by the blockage of melanocortin MC(4) receptors; such a role is not secondary to an increased release of corticotropin-releasing factor (CRF), because, on the other hand, the CRF-induced anorexia is not affected at all by the blockage of melanocortin MC(4) receptors. The physiological meaning of the feeding inhibitory effect of melanocortins, and, by consequence, the physiological role of melanocortins in the complex machinery responsible for body weight homeostasis, is testified by the hyperphagia/obesity syndromes caused by mutations in the pro-opiomelanocortin (POMC) gene, or in the melanocortin MC(4) receptor gene, or in the agouti locus. Finally, recent evidences suggest that melanocortins could be involved in mediating the effects of leptin, and in controlling the expression of neuropeptide Y (NPY).
Chung, Ki Wung; Kim, Kyung Mok; Choi, Yeon Ja; An, Hye Jin; Lee, Bonggi; Kim, Dae Hyun; Lee, Eun Kyeong; Im, Eunok; Lee, Jaewon; Im, Dong Soon; Yu, Byung Pal; Chung, Hae Young
2017-07-03
Macroautophagy/autophagy is a central mechanism by which cells maintain integrity and homeostasis, and endotoxin-induced autophagy plays important roles in innate immunity. Although TLR4 stimulation mediated by lipopolysaccharide (LPS) also upregulates autophagy in hepatocytes and liver, its physiological role remains elusive. The objective of this study was to determine the role of LPS-induced autophagy in the regulation of liver lipid metabolism. LPS treatment (5 mg/kg) increased autophagy, as detected by LC3 conversion and transmission electron microscopy (TEM) analysis in C57BL6 mouse livers. AC2F hepatocytes also showed increased autophagic flux after LPS treatment (1 μg/ml). To investigate the role of LPS-induced autophagy further, liver lipid metabolism changes in LPS-treated mice and fasted controls were compared. Interestingly, LPS-treated mice showed less lipid accumulation in liver than fasted mice despite increased fatty acid uptake and lipid synthesis-associated genes. In vitro analysis using AC2F hepatocytes demonstrated LPS-induced autophagy influenced the degradation of lipid droplets. Inhibition of LPS-induced autophagy using bafilomycin A 1 or Atg7 knockdown significantly increased lipid accumulation in AC2F hepatocytes. In addition, pretreatment with chloroquine aggravated LPS-induced lipid accumulation and inflammation in C57BL6 mouse livers. The physiological importance of autophagy was verified in LPS-treated young and aged rats. Autophagic response was diminished in LPS-treated aged rats and lipid metabolism was impaired during sepsis, indicating autophagy response is important for regulating lipid metabolism after endotoxin challenge. Our findings demonstrate endotoxin-induced autophagy is important for the regulation of lipid metabolism, and suggest that autophagy helps maintain lipid metabolism homeostasis during sepsis.
The Central Role of PhEIN2 in Ethylene Responses throughout Plant Development in Petunia1
Shibuya, Kenichi; Barry, Kristin G.; Ciardi, Joseph A.; Loucas, Holly M.; Underwood, Beverly A.; Nourizadeh, Saeid; Ecker, Joseph R.; Klee, Harry J.; Clark, David G.
2004-01-01
The plant hormone ethylene regulates many aspects of growth and development. Loss-of-function mutations in ETHYLENE INSENSITIVE2 (EIN2) result in ethylene insensitivity in Arabidopsis, indicating an essential role of EIN2 in ethylene signaling. However, little is known about the role of EIN2 in species other than Arabidopsis. To gain a better understanding of EIN2, a petunia (Petunia × hybrida cv Mitchell Diploid [MD]) homolog of the Arabidopsis EIN2 gene (PhEIN2) was isolated, and the role of PhEIN2 was analyzed in a wide range of plant responses to ethylene, many that do not occur in Arabidopsis. PhEIN2 mRNA was present at varying levels in tissues examined, and the PhEIN2 expression decreased after ethylene treatment in petals. These results indicate that expression of PhEIN2 mRNA is spatially and temporally regulated in petunia during plant development. Transgenic petunia plants with reduced PhEIN2 expression were compared to wild-type MD and ethylene-insensitive petunia plants expressing the Arabidopsis etr1-1 gene for several physiological processes. Both PhEIN2 and etr1-1 transgenic plants exhibited significant delays in flower senescence and fruit ripening, inhibited adventitious root and seedling root hair formation, premature death, and increased hypocotyl length in seedling ethylene response assays compared to MD. Moderate or strong levels of reduction in ethylene sensitivity were achieved with expression of both etr1-1 and PhEIN2 transgenes, as measured by downstream expression of PhEIL1. These results demonstrate that PhEIN2 mediates ethylene signals in a wide range of physiological processes and also indicate the central role of EIN2 in ethylene signal transduction. PMID:15466231
Aquaporins in the kidney: emerging new aspects.
Yamamoto, T; Sasaki, S
1998-10-01
Since 1992 and the discovery of an MIP (major intrinsic protein of lens fiber cell) homologue protein that selectively permeates water, aquaporin (AQP), there has been an explosion of research in this field. Early research speculated that aquaporins played indispensible physiological roles in bacteria and plants, as well as in mammalian organs such as red blood cells, kidney, eye, brain and lung, where water transport rapidly takes place. Yet human subjects were identified who lacked AQP1 and yet had no apparent phenotypical changes clinically. To date 10 aquaporins have been discovered and a plethora of MIP members, and their prevalance in almost all organisms is a testament to their indispensible roles in the body, possibly as water and small neutral solute transporting channels. The recent localization of many different aquaporins in the same organ indicates that they may work cooperatively, which may partially explain the mystery of their physiological mechanism. Because the physiological roles of most aquaporins are currently only speculation, more extensive research is necessary to understand the exact function of each aquaporin.
Frank, G R
1995-06-01
The year 1994 is likely to be remembered by many endocrinologists as the year in which dramatic new light was shed on the role played by estrogen in human skeletal physiology. It was in 1994 that two new syndromes were described, each representing a human model in which estrogen action was lacking. The first case was a female with an aromatase defect and a resultant inability to synthesize estrogen, and the second case was a man with an estrogen receptor gene defect that resulted in a non-functioning estrogen receptor and complete estrogen resistance. By examining the phenotypes of these two individuals, we were able, for the first time, to see what pubertal skeletal changes occur in the absence of estrogen action and directly extrapolate the role of estrogen in skeletal physiology. What has become abundantly clear is that it is estrogen and not androgen that is responsible for pubertal epiphyseal maturation and skeletal mineralization.
Nitric Oxide-Dependent Posttranslational Modification in Plants: An Update
Astier, Jeremy; Lindermayr, Christian
2012-01-01
Nitric oxide (NO) has been demonstrated as an essential regulator of several physiological processes in plants. The understanding of the molecular mechanism underlying its critical role constitutes a major field of research. NO can exert its biological function through different ways, such as the modulation of gene expression, the mobilization of second messengers, or interplays with protein kinases. Besides this signaling events, NO can be responsible of the posttranslational modifications (PTM) of target proteins. Several modifications have been identified so far, whereas metal nitrosylation, the tyrosine nitration and the S-nitrosylation can be considered as the main ones. Recent data demonstrate that these PTM are involved in the control of a wide range of physiological processes in plants, such as the plant immune system. However, a great deal of effort is still necessary to pinpoint the role of each PTM in plant physiology. Taken together, these new advances in proteomic research provide a better comprehension of the role of NO in plant signaling. PMID:23203119
Oxidant/Antioxidant Balance in Animal Nutrition and Health: The Role of Protein Oxidation
Celi, Pietro; Gabai, Gianfranco
2015-01-01
This review examines the role that oxidative stress (OS), and protein oxidation in particular, plays in nutrition, metabolism, and health of farm animals. The route by which redox homeostasis is involved in some important physiological functions and the implications of the impairment of oxidative status on animal health and diseases is also examined. Proteins have various and, at the same time, unique biological functions and their oxidation can result in structural changes and various functional modifications. Protein oxidation seems to be involved in pathological conditions, such as respiratory diseases and parasitic infection; however, some studies also suggest that protein oxidation plays a crucial role in the regulation of important physiological functions, such as reproduction, nutrition, metabolism, lactation, gut health, and neonatal physiology. As the characterization of the mechanisms by which OS may influence metabolism and health is attracting considerable scientific interest, the aim of this review is to present veterinary scientists and clinicians with various aspects of oxidative damage to proteins. PMID:26664975
Morphological and Physiological Alteration of Maize Root Architectures on Drought Stress.
USDA-ARS?s Scientific Manuscript database
Drought tolerance is a complex agronomic trait and root characteristics logically play an important role in determining the response of plants to drought stress. Research experiments were conducted to investigate genotypic variations in morphological and physiological responses of roots to drought s...
Pu, Jun; Yuan, Ancai; Shan, Peiren; Gao, Erhe; Wang, Xiaoliang; Wang, Yajing; Lau, Wayne Bond; Koch, Walter; Ma, Xin-Liang; He, Ben
2013-01-01
Aims Emerging evidence indicates that nuclear receptors play a critical regulatory role in cardiovascular physiology/pathology. Recently, farnesoid-X-receptor (FXR), a member of the metabolic nuclear receptor superfamily, has been demonstrated to be expressed in vascular cells, with important roles in vascular physiology/pathology. However, the potential cardiac function of FXR remains unclear. We investigated the cardiac expression and biological function of FXR. Methods and results Farnesoid-X-receptor was detected in both isolated neonatal rat cardiac myocytes and fibroblasts. Natural and synthetic FXR agonists upregulated cardiac FXR expression, stimulated myocyte apoptosis, and reduced myocyte viability dose- and time-dependently. Mechanistic studies demonstrated that FXR agonists disrupted mitochondria, characterized by mitochondrial permeability transition pores activation, mitochondrial potential dissipation, cytochrome c release, and both caspase-9 and -3 activation. Such mitochondrial apoptotic responses were abolished by siRNA-mediated silencing of endogenous FXR or pharmacological inhibition of mitochondrial death signalling. Furthermore, low levels of FXR were detected in the adult mouse heart, with significant (∼2.0-fold) upregulation after myocardial ischaemia/reperfusion (MI/R). Pharmacological inhibition or genetic ablation of FXR significantly reduced myocardial apoptosis by 29.0–53.4%, decreased infarct size by 23.4–49.7%, and improved cardiac function in ischaemic/reperfused myocardium. Conclusion These results demonstrate that nuclear receptor FXR acts as a novel functional receptor in cardiac tissue, regulates apoptosis in cardiomyocytes, and contributes to MI/R injury. PMID:22307460
Rad GTPase is essential for the regulation of bone density and bone marrow adipose tissue in mice.
Withers, Catherine N; Brown, Drew M; Byiringiro, Innocent; Allen, Matthew R; Condon, Keith W; Satin, Jonathan; Andres, Douglas A
2017-10-01
The small GTP-binding protein Rad (RRAD, Ras associated with diabetes) is the founding member of the RGK (Rad, Rem, Rem2, and Gem/Kir) family that regulates cardiac voltage-gated Ca 2+ channel function. However, its cellular and physiological functions outside of the heart remain to be elucidated. Here we report that Rad GTPase function is required for normal bone homeostasis in mice, as Rad deletion results in significantly lower bone mass and higher bone marrow adipose tissue (BMAT) levels. Dynamic histomorphometry in vivo and primary calvarial osteoblast assays in vitro demonstrate that bone formation and osteoblast mineralization rates are depressed, while in vitro osteoclast differentiation is increased, in the absence of Rad. Microarray analysis revealed that canonical osteogenic gene expression (Runx2, osterix, etc.) is not altered in Rad -/- calvarial osteoblasts; instead robust up-regulation of matrix Gla protein (MGP, +11-fold), an inhibitor of extracellular matrix mineralization and a protein secreted during adipocyte differentiation, was observed. Strikingly, Rad deficiency also resulted in significantly higher marrow adipose tissue levels in vivo and promoted spontaneous in vitro adipogenesis of primary calvarial osteoblasts. Adipogenic differentiation of wildtype calvarial osteoblasts resulted in the loss of endogenous Rad protein, further supporting a role for Rad in the control of BMAT levels. These findings reveal a novel in vivo function for Rad and establish a role for Rad signaling in the complex physiological control of skeletal homeostasis and bone marrow adiposity. Copyright © 2017 Elsevier Inc. All rights reserved.
In-cell thermodynamics and a new role for protein surfaces.
Smith, Austin E; Zhou, Larry Z; Gorensek, Annelise H; Senske, Michael; Pielak, Gary J
2016-02-16
There is abundant, physiologically relevant knowledge about protein cores; they are hydrophobic, exquisitely well packed, and nearly all hydrogen bonds are satisfied. An equivalent understanding of protein surfaces has remained elusive because proteins are almost exclusively studied in vitro in simple aqueous solutions. Here, we establish the essential physiological roles played by protein surfaces by measuring the equilibrium thermodynamics and kinetics of protein folding in the complex environment of living Escherichia coli cells, and under physiologically relevant in vitro conditions. Fluorine NMR data on the 7-kDa globular N-terminal SH3 domain of Drosophila signal transduction protein drk (SH3) show that charge-charge interactions are fundamental to protein stability and folding kinetics in cells. Our results contradict predictions from accepted theories of macromolecular crowding and show that cosolutes commonly used to mimic the cellular interior do not yield physiologically relevant information. As such, we provide the foundation for a complete picture of protein chemistry in cells.
NASA Astrophysics Data System (ADS)
Huber, Martin; Braun, Hans; Krieg, J.\\:Urgen-Christian
2004-03-01
Sensitization is discussed as an important phenomenon playing a role in normal physiology but also with respect to the initiation and progression of a variety of neuropsychiatric disorders such as epilepsia, substance-related disorders or recurrent affective disorders. The relevance to understand the dynamics of sensitization phenomena is emphasized by recent findings that even single stimulations can induce longlasting changes in biological systems. To address specific questions associated with the sensitization dynamics, we use a computational approach and develop simple but physiologically-plausible models. In the present study we examine the effect of noisy stimulation on sensitization development in the model. We consider sub- and suprathresold stimulations with varying noise intensities and determine as response measures the (i) absolute number of stimulus-induced sensitzations and (ii) the temporal relsation of stimulus-sensitization coupling. The findings indicate that stochastic effects including stochastic resonance might well contribute to the physiology of sensitization mechanisms under both nomal and pathological conditions.
von Zastrow, Mark; Svingos, Adena; Haberstock-Debic, Helena; Evans, Chris
2003-06-01
Opiate drugs such as morphine and heroin are among the most effective analgesics known. Prolonged or repeated administration of opiates produces adaptive changes in the nervous system that lead to reduced drug potency or efficacy (tolerance), as well as physiological withdrawal symptoms and behavioral manifestations such as craving when drug use is terminated (dependence). These adaptations limit the therapeutic utility of opiate drugs, particularly in the treatment of chronically painful conditions, and are thought to contribute to the highly addictive nature of opiates. For many years it has been proposed that physiological tolerance to opiate drugs is associated with a modification of the number or functional activity of opioid receptors in specific neurons. We now understand certain mechanisms of opioid receptor desensitization and endocytosis in considerable detail. However, the functional roles that these mechanisms play in the complex physiological adaptation of the intact nervous system to opiates are only beginning to be explored.
Integration of the response to a dietary potassium load: a paleolithic perspective.
Kamel, Kamel S; Schreiber, Martin; Halperin, Mitchell L
2014-05-01
Our purpose is to integrate new insights in potassium (K(+)) physiology to understand K(+) homeostasis and illustrate some of their clinical implications. Since control mechanisms that are essential for survival were likely developed in Paleolithic times, we think the physiology of K(+) homeostasis can be better revealed when viewed from what was required to avoid threats and achieve balance in Paleolithic times. Three issues will be highlighted. First, we shall consider the integrative physiology of the gastrointestinal tract and the role of lactic acid released from enterocytes following absorption of sugars (fruit and berries) to cause a shift of this K(+) load into the liver. Second, we shall discuss the integrative physiology of WNK kinases and modulation of delivery of bicarbonate to the distal nephron to switch the aldosterone response from sodium chloride retention to K(+) secretion when faced with a K(+) load. Third, we shall emphasize the role of intra-renal recycling of urea in achieving K(+) homeostasis when the diet contains protein and K(+).
Physiological Roles of Adipokines, Hepatokines, and Myokines in Ruminants.
Roh, Sang-Gun; Suzuki, Yutaka; Gotoh, Takafumi; Tatsumi, Ryuichi; Katoh, Kazuo
2016-01-01
Since the discovery of leptin secreted from adipocytes, specialized tissues and cells have been found that secrete the several peptides (or cytokines) that are characterized to negatively and positively regulate the metabolic process. Different types of adipokines, hepatokines, and myokines, which act as cytokines, are secreted from adipose, liver, and muscle tissue, respectively, and have been identified and examined for their physiological roles in humans and disease in animal models. Recently, various studies of these cytokines have been conducted in ruminants, including dairy cattle, beef cattle, sheep, and goat. Interestingly, a few cytokines from these tissues in ruminants play an important role in the post-parturition, lactation, and fattening (marbling) periods. Thus, understanding these hormones is important for improving nutritional management in dairy cows and beef cattle. However, to our knowledge, there have been no reviews of the characteristics of these cytokines in beef and dairy products in ruminants. In particular, lipid and glucose metabolism in adipose tissue, liver tissue, and muscle tissue are very important for energy storage, production, and synthesis, which are regulated by these cytokines in ruminant production. In this review, we summarize the physiological roles of adipokines, hepatokines, and myokines in ruminants. This discussion provides a foundation for understanding the role of cytokines in animal production of ruminants.
Anxiety as a factor influencing physiological effects of acupuncture.
Vickland, Victor; Rogers, Carole; Craig, Ashley; Tran, Yvonne
2009-08-01
This study investigated the influence of manual acupuncture on heart rate variability and the role which anxiety can play in modifying physiological outcomes. Analysis of heart rate variability (HRV) was used as a sensitive and a reliable indicator of the balance between sympathetic and parasympathetic regulation of the heartbeat. Two groups of healthy female subjects were recruited into the study. The control group (n=30) attended one experimental session where no acupuncture treatment was used. The experimental group (n=30) attended three sessions in which unilateral manual stimulation of acupuncture points LU7 and KD6 was performed. The stimulation of the acupuncture points LU7 and KD6 was not associated with significant changes in HRV. Previous familiarity with acupuncture did not influence the outcomes but level of anxiety had a strong impact on physiological outcomes. Stimulation of LU7 acupuncture point counterbalanced naturally occurring sympathetic increase over time and had relaxing and harmonizing effect on the heart rhythm without influencing subjective perception of increased anxiety. Stimulation of KD6 acupuncture point had sympathetic influence on HRV in subjects with low "trait" anxiety and this influence was nullified by simultaneous stimulation of LU7 acupuncture point. It seems likely that the level of anxiety can modify HRV during acupuncture treatment and up to 40 min after the treatment. Psychological factors such as anxiety level should be considered as having important influence on physiological response to acupuncture.
Reddy, Srirama Krishna; Liu, Shuyu; Rudd, Jackie C; Xue, Qingwu; Payton, Paxton; Finlayson, Scott A; Mahan, James; Akhunova, Alina; Holalu, Srinidhi V; Lu, Nanyan
2014-09-01
Hard red winter wheat crops on the U.S. Southern Great Plains often experience moderate to severe drought stress, especially during the grain filling stage, resulting in significant yield losses. Cultivars TAM 111 and TAM 112 are widely cultivated in the region, share parentage and showed superior but distinct adaption mechanisms under water-deficit (WD) conditions. Nevertheless, the physiological and molecular basis of their adaptation remains unknown. A greenhouse study was conducted to understand the differences in the physiological and transcriptomic responses of TAM 111 and TAM 112 to WD stress. Whole-plant data indicated that TAM 112 used more water, produced more biomass and grain yield under WD compared to TAM 111. Leaf-level data at the grain filling stage indicated that TAM 112 had elevated abscisic acid (ABA) content and reduced stomatal conductance and photosynthesis as compared to TAM 111. Sustained WD during the grain filling stage also resulted in greater flag leaf transcriptome changes in TAM 112 than TAM 111. Transcripts associated with photosynthesis, carbohydrate metabolism, phytohormone metabolism, and other dehydration responses were uniquely regulated between cultivars. These results suggested a differential role for ABA in regulating physiological and transcriptomic changes associated with WD stress and potential involvement in the superior adaptation and yield of TAM 112. Copyright © 2014 Elsevier GmbH. All rights reserved.
A Review of the Internal and External Physiological Demands Associated With Batting in Cricket.
Scanlan, Aaron T; Berkelmans, Daniel M; Vickery, William M; Kean, Crystal O
2016-11-01
Cricket is a popular international team sport with various game formats ranging from long-duration multiday tests to short-duration Twenty20 game play. The role of batsmen is critical to all game formats, with differing physiological demands imposed during each format. Investigation of the physiological demands imposed during cricket batting has historically been neglected, with much of the research focusing on bowling responses and batting technique. A greater understanding of the physiological demands of the batting role in cricket is required to assist strength and conditioning professionals and coaches with the design of training plans, recovery protocols, and player-management strategies. This brief review provides an updated synthesis of the literature examining the internal (eg, metabolic demands and heart rate) and external (eg, activity work rates) physiological responses to batting in the various game formats, as well as simulated play and small-sided-games training. Although few studies have been done in this area, the summary of data provides important insight regarding physiological responses to batting and highlights that more research on this topic is required. Future research is recommended to combine internal and external measures during actual game play, as well as comparing different game formats and playing levels. In addition, understanding the relationship between batting technique and physiological responses is warranted to gain a more holistic understanding of batting in cricket, as well as to develop appropriate coaching and training strategies.
Genetic Alterations Affecting Cholesterol Metabolism and Human Fertility1
DeAngelis, Anthony M.; Roy-O'Reilly, Meaghan; Rodriguez, Annabelle
2014-01-01
ABSTRACT Single nucleotide polymorphisms (SNPs) represent genetic variations among individuals in a population. In medicine, these small variations in the DNA sequence may significantly impact an individual's response to certain drugs or influence the risk of developing certain diseases. In the field of reproductive medicine, a significant amount of research has been devoted to identifying polymorphisms which may impact steroidogenesis and fertility. This review discusses current understanding of the effects of genetic variations in cholesterol metabolic pathways on human fertility that bridge novel linkages between cholesterol metabolism and reproductive health. For example, the role of the low-density lipoprotein receptor (LDLR) in cellular metabolism and human reproduction has been well studied, whereas there is now an emerging body of research on the role of the high-density lipoprotein (HDL) receptor scavenger receptor class B type I (SR-BI) in human lipid metabolism and female reproduction. Identifying and understanding how polymorphisms in the SCARB1 gene or other genes related to lipid metabolism impact human physiology is essential and will play a major role in the development of personalized medicine for improved diagnosis and treatment of infertility. PMID:25122065
Role of Endogenous Sulfur Dioxide in Regulating Vascular Structural Remodeling in Hypertension
Chen, Selena; Tang, Chaoshu
2016-01-01
Sulfur dioxide (SO2), an emerging gasotransmitter, was discovered to be endogenously generated in the cardiovascular system. Recently, the physiological effects of endogenous SO2 were confirmed. Vascular structural remodeling (VSR), an important pathological change in many cardiovascular diseases, plays a crucial role in the pathogenesis of the diseases. Here, the authors reviewed the research progress of endogenous SO2 in regulating VSR by searching the relevant data from PubMed and Medline. In spontaneously hypertensive rats (SHRs) and pulmonary hypertensive rats, SO2/aspartate aminotransferase (AAT) pathway was significantly altered. SO2 inhibited vascular smooth muscle cell (VSMC) proliferation, promoted apoptosis, inhibited the synthesis of extracellular collagen but promoted its degradation, and enhanced antioxidative capacity, thereby playing a significant role in attenuating VSR. However, the detailed mechanisms needed to be further explored. Further studies in this field would be important for the better understanding of the pathogenesis of systemic hypertension and pulmonary hypertension. Also, clinical trials are needed to demonstrate if SO2 would be a potential therapeutic target in cardiovascular diseases. PMID:27721913
Leptin in pediatrics: A hormone from adipocyte that wheels several functions in children
Soliman, Ashraf T.; Yasin, Mohamed; Kassem, Ahmed
2012-01-01
The protein leptin, a pleiotropic hormone regulates appetite and energy balance of the body and plays important roles in controlling linear growth, pubertal development, cardiovascular function, and immunity. Recent findings in the understanding of the structure, functional roles, and clinical significance of conditions with increased and decreased leptin secretion are summarized. Balance between leptin and other hormones is significantly regulated by nutritional status. This balance influences many organ systems, including the brain, liver, and skeletal muscle, to mediate the essential adaptation process. The aim of this review is to summarize the possible physiological functions of leptin and its signaling pathways during childhood and adolescence including control of food intake, energy regulation, growth and puberty, and immunity. Moreover, its secretion and possible roles in the adaptation process during different disease states (obesity, malnutrition, eating disorders, delayed puberty, congenital heart diseases and hepatic disorders) are discussed. The clinical manifestations and the successful management of patients with genetic leptin deficiency and the application of leptin therapy in other diseases including lipodystrophy, states with severe insulin resistance, and diabetes mellitus are discussed. PMID:23565493
Biological properties of extracellular vesicles and their physiological functions
Yáñez-Mó, María; Siljander, Pia R.-M.; Andreu, Zoraida; Zavec, Apolonija Bedina; Borràs, Francesc E.; Buzas, Edit I.; Buzas, Krisztina; Casal, Enriqueta; Cappello, Francesco; Carvalho, Joana; Colás, Eva; Silva, Anabela Cordeiro-da; Fais, Stefano; Falcon-Perez, Juan M.; Ghobrial, Irene M.; Giebel, Bernd; Gimona, Mario; Graner, Michael; Gursel, Ihsan; Gursel, Mayda; Heegaard, Niels H. H.; Hendrix, An; Kierulf, Peter; Kokubun, Katsutoshi; Kosanovic, Maja; Kralj-Iglic, Veronika; Krämer-Albers, Eva-Maria; Laitinen, Saara; Lässer, Cecilia; Lener, Thomas; Ligeti, Erzsébet; Linē, Aija; Lipps, Georg; Llorente, Alicia; Lötvall, Jan; Manček-Keber, Mateja; Marcilla, Antonio; Mittelbrunn, Maria; Nazarenko, Irina; Hoen, Esther N.M. Nolte-‘t; Nyman, Tuula A.; O'Driscoll, Lorraine; Olivan, Mireia; Oliveira, Carla; Pállinger, Éva; del Portillo, Hernando A.; Reventós, Jaume; Rigau, Marina; Rohde, Eva; Sammar, Marei; Sánchez-Madrid, Francisco; Santarém, N.; Schallmoser, Katharina; Ostenfeld, Marie Stampe; Stoorvogel, Willem; Stukelj, Roman; Van der Grein, Susanne G.; Vasconcelos, M. Helena; Wauben, Marca H. M.; De Wever, Olivier
2015-01-01
In the past decade, extracellular vesicles (EVs) have been recognized as potent vehicles of intercellular communication, both in prokaryotes and eukaryotes. This is due to their capacity to transfer proteins, lipids and nucleic acids, thereby influencing various physiological and pathological functions of both recipient and parent cells. While intensive investigation has targeted the role of EVs in different pathological processes, for example, in cancer and autoimmune diseases, the EV-mediated maintenance of homeostasis and the regulation of physiological functions have remained less explored. Here, we provide a comprehensive overview of the current understanding of the physiological roles of EVs, which has been written by crowd-sourcing, drawing on the unique EV expertise of academia-based scientists, clinicians and industry based in 27 European countries, the United States and Australia. This review is intended to be of relevance to both researchers already working on EV biology and to newcomers who will encounter this universal cell biological system. Therefore, here we address the molecular contents and functions of EVs in various tissues and body fluids from cell systems to organs. We also review the physiological mechanisms of EVs in bacteria, lower eukaryotes and plants to highlight the functional uniformity of this emerging communication system. PMID:25979354
Biological properties of extracellular vesicles and their physiological functions.
Yáñez-Mó, María; Siljander, Pia R-M; Andreu, Zoraida; Zavec, Apolonija Bedina; Borràs, Francesc E; Buzas, Edit I; Buzas, Krisztina; Casal, Enriqueta; Cappello, Francesco; Carvalho, Joana; Colás, Eva; Cordeiro-da Silva, Anabela; Fais, Stefano; Falcon-Perez, Juan M; Ghobrial, Irene M; Giebel, Bernd; Gimona, Mario; Graner, Michael; Gursel, Ihsan; Gursel, Mayda; Heegaard, Niels H H; Hendrix, An; Kierulf, Peter; Kokubun, Katsutoshi; Kosanovic, Maja; Kralj-Iglic, Veronika; Krämer-Albers, Eva-Maria; Laitinen, Saara; Lässer, Cecilia; Lener, Thomas; Ligeti, Erzsébet; Linē, Aija; Lipps, Georg; Llorente, Alicia; Lötvall, Jan; Manček-Keber, Mateja; Marcilla, Antonio; Mittelbrunn, Maria; Nazarenko, Irina; Nolte-'t Hoen, Esther N M; Nyman, Tuula A; O'Driscoll, Lorraine; Olivan, Mireia; Oliveira, Carla; Pállinger, Éva; Del Portillo, Hernando A; Reventós, Jaume; Rigau, Marina; Rohde, Eva; Sammar, Marei; Sánchez-Madrid, Francisco; Santarém, N; Schallmoser, Katharina; Ostenfeld, Marie Stampe; Stoorvogel, Willem; Stukelj, Roman; Van der Grein, Susanne G; Vasconcelos, M Helena; Wauben, Marca H M; De Wever, Olivier
2015-01-01
In the past decade, extracellular vesicles (EVs) have been recognized as potent vehicles of intercellular communication, both in prokaryotes and eukaryotes. This is due to their capacity to transfer proteins, lipids and nucleic acids, thereby influencing various physiological and pathological functions of both recipient and parent cells. While intensive investigation has targeted the role of EVs in different pathological processes, for example, in cancer and autoimmune diseases, the EV-mediated maintenance of homeostasis and the regulation of physiological functions have remained less explored. Here, we provide a comprehensive overview of the current understanding of the physiological roles of EVs, which has been written by crowd-sourcing, drawing on the unique EV expertise of academia-based scientists, clinicians and industry based in 27 European countries, the United States and Australia. This review is intended to be of relevance to both researchers already working on EV biology and to newcomers who will encounter this universal cell biological system. Therefore, here we address the molecular contents and functions of EVs in various tissues and body fluids from cell systems to organs. We also review the physiological mechanisms of EVs in bacteria, lower eukaryotes and plants to highlight the functional uniformity of this emerging communication system.
Cholinergic modulation of cognitive processing: insights drawn from computational models
Newman, Ehren L.; Gupta, Kishan; Climer, Jason R.; Monaghan, Caitlin K.; Hasselmo, Michael E.
2012-01-01
Acetylcholine plays an important role in cognitive function, as shown by pharmacological manipulations that impact working memory, attention, episodic memory, and spatial memory function. Acetylcholine also shows striking modulatory influences on the cellular physiology of hippocampal and cortical neurons. Modeling of neural circuits provides a framework for understanding how the cognitive functions may arise from the influence of acetylcholine on neural and network dynamics. We review the influences of cholinergic manipulations on behavioral performance in working memory, attention, episodic memory, and spatial memory tasks, the physiological effects of acetylcholine on neural and circuit dynamics, and the computational models that provide insight into the functional relationships between the physiology and behavior. Specifically, we discuss the important role of acetylcholine in governing mechanisms of active maintenance in working memory tasks and in regulating network dynamics important for effective processing of stimuli in attention and episodic memory tasks. We also propose that theta rhythm plays a crucial role as an intermediary between the physiological influences of acetylcholine and behavior in episodic and spatial memory tasks. We conclude with a synthesis of the existing modeling work and highlight future directions that are likely to be rewarding given the existing state of the literature for both empiricists and modelers. PMID:22707936
Chavez-Solano, Marbella; Ibarra-Sanchez, Alfredo; Treviño, Mario; Gonzalez-Espinosa, Claudia; Lamas, Monica
2016-04-01
Fyn kinase is widely expressed in neuronal and glial cells of the brain, where it exerts multiple functional roles that affect fundamental physiological processes. The aim of our study was to investigate the, so far unknown, functional role of Fyn in the retina. We report that Fyn is expressed, in vivo, in a subpopulation of Müller glia. We used a mouse model of Fyn genetic ablation and Müller-enriched primary cultures to demonstrate that Fyn deficiency induces morphological alterations in the mature retina, a reduction in the thickness of the outer and inner nuclear layers and alterations in postnatal Müller cell physiology. These include shortening of Müller cell processes, a decrease in cell proliferation, inactivation of the Akt signal transduction pathway, a reduced number of focal adhesions points and decreased adhesion of these cells to the ECM. As abnormalities in Müller cell physiology have been previously associated to a compromised retinal function we evaluated behavioral responses to visual stimulation. Our results associate Fyn deficiency with impaired visual optokinetic responses under scotopic and photopic light conditions. Our study reveals novel roles for Fyn kinase in retinal morphology and Müller cell physiology and suggests that Fyn is required for optimal visual processing. Copyright © 2016 Elsevier Inc. All rights reserved.
Ouedraogo, Zangbéwendé Guy; Fouache, Allan; Trousson, Amalia; Baron, Silvère; Lobaccaro, Jean-Marc A
2017-10-01
Liver X receptors (LXRs) are members of the nuclear receptor superfamily that have been shown to regulate various physiological functions such as lipid metabolism and cholesterol homeostasis. Concordant reports have elicited the possibility to target them to cure many human diseases including arteriosclerosis, cancer, arthritis, and diabetes. The high relevance of modulating LXR activities to treat numerous skin diseases, mainly those with exacerbated inflammation processes, contrasts with the lack of approved therapeutic use. This review makes an assessment to sum up the findings regarding the physiological roles of LXRs in skin and help progress towards the therapeutic and safe management of their activities. It focuses on the possible pharmacological targeting of LXRs to cure or prevent selected skin diseases. Copyright © 2017 Elsevier B.V. All rights reserved.
Zinc and Wound Healing: A Review of Zinc Physiology and Clinical Applications.
Kogan, Samuel; Sood, Aditya; Garnick, Mark S
2017-04-01
Our understanding of the role of zinc in normal human physiology is constantly expanding, yet there are major gaps in our knowledge with regard to the function of zinc in wound healing. This review aims to provide the clinician with sufficient understanding of zinc biology and an up-to-date perspective on the role of zinc in wound healing. Zinc is an essential ion that is crucial for maintenance of normal physiology, and zinc deficiency has many manifestations ranging from delayed wound healing to immune dysfunction and impairment of multiple sensory systems. While consensus has been reached regarding the detrimental effects of zinc deficiency on wound healing, there is considerable discord in the literature on the optimal methods and true benefits of zinc supplementation.
Koba, Satoshi; Inoue, Ryo; Watanabe, Tatsuo
2016-06-01
Freezing, a characteristic pattern of defensive behavior elicited by fear, is associated with a decrease in the heart rate. Central mechanisms underlying fear bradycardia are poorly understood. The periaqueductal gray (PAG) in the midbrain is known to contribute to autonomic cardiovascular adjustments associated with various emotional behaviors observed during active or passive defense reactions. The purpose of this study was to elucidate the role played by PAG neurons in eliciting fear bradycardia. White noise sound (WNS) exposure at 90 dB induced freezing behavior and elicited bradycardia in conscious rats. The WNS exposure-elicited bradycardia was mediated parasympathetically because intravenous administration of atropine abolished the bradycardia (P < 0.05). Moreover, WNS exposure-elicited bradycardia was mediated by neuronal activation of the lateral/ventrolateral PAG (l/vlPAG) because bilateral microinjection of muscimol, a GABAA agonist, into the l/vlPAG significantly suppressed the bradycardia. It is noted that muscimol microinjected bilaterally into the dorsolateral PAG had no effect on WNS exposure-elicited bradycardia. Furthermore, retrograde neuronal tracing experiments combined with immunohistochemistry demonstrated that a number of l/vlPAG neurons that send direct projections to the nucleus ambiguus (NA) in the medulla, a major origin of parasympathetic preganglionic neurons to the heart, were activated by WNS exposure. Based on these findings, we propose that the l/vlPAG-NA monosynaptic pathway transmits fear-driven central signals, which elicit bradycardia through parasympathetic outflow. © 2016 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.
Pharmacology, signaling and physiological relevance of the G protein-coupled receptor 55.
Balenga, Nariman A B; Henstridge, Christopher M; Kargl, Julia; Waldhoer, Maria
2011-01-01
According to The European Monitoring Centre for Drugs and Drug Addiction (EMCDDA), ∼70 million European adults have consumed cannabis on at least one occasion. Cannabis consumption leads to a variety of psychoactive effects due to the presence of the constituent Δ(9)-tetrahydrocannabinol (Δ(9)-THC). Δ(9)-THC interacts with the endocannabinoid system (ECS), which consists of the seven transmembrane spanning (7TM)/G protein-coupled receptors (GPCRs) CB(1) and CB(2), their respective ligands (endocannabinoids), and enzymes involved in their biosynthesis and degradation. This system plays a critical role in many physiological processes such as learning and memory, appetite control, pain sensation, motor coordination, lipogenesis, modulation of immune response, and the regulation of bone mass. Therefore, a huge effort has been spent trying to fully elucidate the composition and function of the ECS. The G protein-coupled receptor 55 (GPR55) was recently proposed as a novel component of this system; however, its classification as a cannabinoid receptor has been significantly hampered by its complex pharmacology, signaling, and cellular function. GPR55 is phylogenetically distinct from the traditional cannabinoid receptors, but in some experimental paradigms, it is activated by endocannabinoids, phytocannabinoids, and synthetic cannabinoid ligands. However, the most potent compound appears to be a lysophospholipid known as lysophosphatidylinositol (LPI). Here, we provide a comprehensive evaluation of the current pharmacology and signaling of GPR55 and review the proposed role of this receptor in a number of physiological and pathophysiological processes. Copyright © 2011 Elsevier Inc. All rights reserved.
The complementary and divergent roles of uncoupling proteins 1 and 3 in thermoregulation
Riley, Christopher L.; Dao, Christine; Kenaston, M. Alexander; Muto, Luigina; Kohno, Shohei; Nowinski, Sara M.; Solmonson, Ashley D.; Pfeiffer, Matthew; Sack, Michael N.; Lu, Zhongping; Fiermonte, Giuseppe; Sprague, Jon E.
2016-01-01
Key points Both uncoupling protein 1 (UCP1) and UCP3 are important for mammalian thermoregulation.UCP1 and UCP3 in brown adipose tissue mediate early and late phases of sympathomimetic thermogenesis, respectively.Lipopolysaccharide thermogenesis requires skeletal muscle UCP3 but not UCP1.Acute noradrenaline‐induced hyperthermia requires UCP1 but not UCP3.Loss of both UCP1 and UCP3 accelerate the loss of body temperature compared to UCP1KO alone during acute cold exposure. Abstract Uncoupling protein 1 (UCP1) is the established mediator of brown adipose tissue‐dependent thermogenesis. In contrast, the role of UCP3, expressed in both skeletal muscle and brown adipose tissue, in thermoregulatory physiology is less well understood. Here, we show that mice lacking UCP3 (UCP3KO) have impaired sympathomimetic (methamphetamine) and completely abrogated lipopolysaccharide (LPS) thermogenesis, but a normal response to noradrenaline. By comparison, UCP1 knockout (UCP1KO) mice exhibit blunted methamphetamine and fully inhibited noradrenaline thermogenesis, but an increased febrile response to LPS. We further establish that mice lacking both UCP1 and 3 (UCPDK) fail to show methamphetamine‐induced hyperthermia, and have a markedly accelerated loss of body temperature and survival after cold exposure compared to UCP1KO mice. Finally, we show that skeletal muscle‐specific human UCP3 expression is able to significantly rescue LPS, but not sympathomimetic thermogenesis blunted in UCP3KO mice. These studies identify UCP3 as an important mediator of physiological thermogenesis and support a renewed focus on targeting UCP3 in metabolic physiology. PMID:27647490
Oxytocin receptor dynamics in the brain across development and species.
Vaidyanathan, Radhika; Hammock, Elizabeth A D
2017-02-01
Oxytocin (OXT) signaling through the OXT receptor plays a significant role in a variety of physiological processes throughout the lifespan. OXT's effects depend on the tissue distribution of the receptor. This tissue specificity is dynamic and changes across development, and also varies with sex, experience, and species. The purpose of this review is to highlight these themes with examples from several life stages and several species. Important knowledge gaps will also be emphasized. Understanding the effective sites of action for OXT via its receptor will help refine hypotheses about the roles of this important neuropeptide in the experience-dependent development and expression of species-typical social behavior. © 2016 Wiley Periodicals, Inc. Develop Neurobiol 77: 143-157, 2017. © 2016 Wiley Periodicals, Inc.
Fatigue Factors in Regional Airline Operations
NASA Technical Reports Server (NTRS)
Rosekind, Mark R.; Weldon, Keri J.; Co, Elizabeth L.; Miller, Donna L.; Gregory, Kevin B.; Smith, Roy M.; Johnson, Julie M.; Gander, Philippa H.; Lebacqz, J. Victor
1994-01-01
This paper describes human sleep and circadian physiology regarding their role as contributors to fatigue engendered by flight operations. The demands of regional airline operations are then examined for potential areas where these physiological factors will be affected. Finally, approaches to systematically investigate these issues scientifically will be described.
Ventricular Assist Devices: Physiology Meets Technology
1993-01-01
nmuse’s primary responsbility focuses on the patient . Expert clinical skills plus a thorugh - of the physiology behind VADs are necessary for a nurse...five roles of the CNS to effectively and efficiently manage VAD patients . Expert clinical skills and in-depth knowledge enables the CNS to anticipate
Prostaglandins in reproductive physiology*
Craig, Gillian M.
1975-01-01
The role of prostaglandins in reproductive physiology is reviewed with particular emphasis on their possible importance in ovulation in humans. A possible interaction between gonadal steroids, biogenic amines and prostaglandins at hypothalamic-pituitary level, in relation to the release of luteinizing hormone releasing factor, and LH, is discussed. Anomalies regarding the role of oestrogens in LH release are noted, and it is suggested that high oestrogen levels may release prostaglandins from the uterus and/or centrally in humans, in connection with the mid-cycle LH surge and ovulation. A hypothetical role for prostaglandins in sexual behaviour and premenstrual changes is discussed. The hypotheses open up new areas for clinical research to establish the role of prostaglandins in human endocrinology. The need for measurement of prostaglandin metabolites in blood and urine is emphasized. PMID:1089972
NASA Astrophysics Data System (ADS)
Siegwolf, R. T. W.; Buchmann, N.; Frank, D.; Joos, F.; Kahmen, A.; Treydte, K.; Leuenberger, M.; Saurer, M.
2012-04-01
Trees play are a critical role in the carbon cycle - their photosynthetic assimilation is one of the largest terrestrial carbon fluxes and their standing biomass represents the largest carbon pool of the terrestrial biosphere. Understanding how tree physiology and growth respond to long-term environmental change is pivotal to predict the magnitude and direction of the terrestrial carbon sink. iTREE is an interdisciplinary research framework to capitalize on synergies among leading dendroclimatologists, plant physiologists, isotope specialists, and global carbon cycle modelers with the objectives of reducing uncertainties related to tree/forest growth in the context of changing natural environments. Cross-cutting themes in our project are tree rings, stable isotopes, and mechanistic modelling. We will (i) establish a European network of tree-ring based isotope time-series to retrodict interannual to long-term tree physiological changes, (ii) conduct laboratory and field experiments to adapt a mechanistic isotope model to derive plant physiological variables from tree-ring isotopes, (iii) implement this model into a dynamic global vegetation model, and perform subsequent model-data validation exercises to refine model representation of plant physiological processes and (iv) attribute long-term variation in tree growth to plant physiological and environmental drivers, and identify how our refined knowledge revises predictions of the coupled carbon-cycle climate system. We will contribute to i) advanced quantifications of long-term variation in tree growth across Central Europe, ii) novel long-term information on key physiological processes that underlie variations in tree growth, and iii) improved carbon cycle models that can be employed to revise predictions of the coupled carbon-cycle climate system. Hence iTREE will significantly contribute towards a seamless understanding of the responses of terrestrial ecosystems to long-term environmental change, and ultimately help reduce uncertainties of the magnitude and direction of the past and future terrestrial carbon sink.
Soares, Juliana B. R. Correa; Gaviraghi, Alessandro; Oliveira, Marcus F.
2015-01-01
Adult females of Aedes aegypti are facultative blood sucking insects and vectors of Dengue and yellow fever viruses. Insect dispersal plays a central role in disease transmission and the extremely high energy demand posed by flight is accomplished by a very efficient oxidative phosphorylation process, which take place within flight muscle mitochondria. These organelles play a central role in energy metabolism, interconnecting nutrient oxidation to ATP synthesis, but also represent an important site of cellular superoxide production. Given the importance of mitochondria to cell physiology, and the potential contributions of this organelle for A. aegypti biology and vectorial capacity, here, we conducted a systematic assessment of mitochondrial physiology in flight muscle of young adult A. aegypti fed exclusively with sugar. This was carried out by determining the activities of mitochondrial enzymes, the substrate preferences to sustain respiration, the mitochondrial bioenergetic efficiency and capacity, in both mitochondria-enriched preparations and mechanically permeabilized flight muscle in both sexes. We also determined the substrates preferences to promote mitochondrial superoxide generation and the main sites where it is produced within this organelle. We observed that respiration in A. aegypti mitochondria was essentially driven by complex I and glycerol 3 phosphate dehydrogenase substrates, which promoted distinct mitochondrial bioenergetic capacities, but with preserved efficiencies. Respiration mediated by proline oxidation in female mitochondria was strikingly higher than in males. Mitochondrial superoxide production was essentially mediated through proline and glycerol 3 phosphate oxidation, which took place at sites other than complex I. Finally, differences in mitochondrial superoxide production among sexes were only observed in male oxidizing glycerol 3 phosphate, exhibiting higher rates than in female. Together, these data represent a significant step towards the understanding of fundamental mitochondrial processes in A. aegypti, with potential implications for its physiology and vectorial capacity. PMID:25803027
Grodzki, Ana Cristina G.; Giulivi, Cecilia; Lein, Pamela J.
2013-01-01
The human THP-1 cell line is widely used as an in vitro model system for studying macrophage differentiation and function. Conventional culture conditions for these cells consist of ambient oxygen pressure (∼20% v/v) and medium supplemented with the thiol 2-mercaptoethanol (2-ME) and serum. In consideration of the redox activities of O2 and 2-ME, and the extensive experimental evidence supporting a role for reactive oxygen species (ROS) in the differentiation and function of macrophages, we addressed the question of whether culturing THP-1 cells under a more physiologically relevant oxygen tension (5% O2) in the absence of 2-ME and serum would alter THP-1 cell physiology. Comparisons of cultures maintained in 18% O2 versus 5% O2 indicated that reducing oxygen tension had no effect on the proliferation of undifferentiated THP-1 cells. However, decreasing the oxygen tension to 5% O2 significantly increased the rate of phorbol ester-induced differentiation of THP-1 cells into macrophage-like cells as well as the metabolic activity of both undifferentiated and PMA-differentiated THP-1 cells. Removal of both 2-ME and serum from the medium decreased the proliferation of undifferentiated THP-1 cells but increased metabolic activity and the rate of differentiation under either oxygen tension. In differentiated THP-1 cells, lowering the oxygen tension to 5% O2 decreased phagocytic activity, the constitutive release of β-hexosaminidase and LPS-induced NF-κB activation but enhanced LPS-stimulated release of cytokines. Collectively, these data demonstrate that oxygen tension influences THP-1 cell differentiation and primary macrophage functions, and suggest that culturing these cells under tightly regulated oxygen tension in the absence of exogenous reducing agent and serum is likely to provide a physiologically relevant baseline from which to study the role of the local redox environment in regulating THP-1 cell physiology. PMID:23355903
Du, Jing; Guo, Shirong; Sun, Jin; Shu, Sheng
2018-05-01
The mechanism of exogenous Spd-induced Ca(NO 3 ) 2 stress tolerance in cucumber was studied by proteomics and physiological analyses. Protein-protein interaction network revealed 13 key proteins involved in Spd-induced Ca(NO 3 ) 2 stress resistance. Ca(NO 3 ) 2 stress is one of the major reasons for secondary salinization that limits cucumber plant development in greenhouse. The conferred protective role of exogenous Spd on cucumber in response to Ca(NO 3 ) 2 stress cues involves changes at the cellular and physiological levels. To investigate the molecular foundation of exogenous Spd in Ca(NO 3 ) 2 stress tolerance, a proteomic approach was performed in our work. After a 9 days period of Ca(NO 3 ) 2 stress and/or exogenous Spd, 71 differential protein spots were confidently identified. The resulting proteins were enriched in seven different categories of biological processes, including protein metabolism, carbohydrate and energy metabolism, ROS homeostasis and stress defense, cell wall related, transcription, others and unknown. Protein metabolism (31.2%), carbohydrate and energy metabolism (15.6%), ROS homeostasis and stress defense (32.5%) were the three largest functional categories in cucumber root and most of them were significantly increased by exogenous Spd. The Spd-responsive protein interaction network revealed 13 key proteins, whose accumulation changes could be critical for Spd-induced resistance; all 13 proteins were upregulated by Spd at transcriptional and protein levels in response to Ca(NO 3 ) 2 stress. Furthermore, accumulation of antioxidant enzymes, non-enzymatic antioxidant and polyamines, along with reduction of H 2 O 2 and MDA, were detected after exogenous Spd application during Ca(NO 3 ) 2 stress. The results of these proteomic and physiological analyses in cucumber root may facilitate a better understanding of the underlying mechanism of Ca(NO 3 ) 2 stress tolerance mediated by exogenous Spd.
Grimbuhler, Sonia; Viel, Jean-François
2018-06-19
The proper use of personal protective equipment (PPE) plays an important role in reducing exposure to pesticides in vineyard farming activities, including re-entry tasks. However, discomfort from clothing systems may increase the physiological burden on workers. We compared the physiological burdens of vineyard workers wearing three different types of PPE during canopy management in field humid conditions while accounting for occupational, climatic, and geographical environments. The study was conducted in the Bordeaux vineyards of southern France during June 2012. A total of 42 workers from seven vineyards consented to field observations. The following PPE garments were randomly allocated: HF Estufa polyamide (Brisa®), Tyvek® Classic Plus, and Tychem® C Standard. Participant sociodemographic characteristics were collected using a structured questionnaire. Skin temperature and heart rate were monitored continuously using portable devices. Multivariate multilevel linear regression models were performed to account for the hierarchical structure of data. No significant difference was found for mean skin temperature during work. Regardless of the cardiac strain parameter considered, the Tyvek® Classic Plus garment produced the poorest results (P ≤ 0.03). Under the very humid conditions encountered during the field study, the thinness and breathability of the Tyvek® Classic Plus garment resulted in undergarment humidity, imposing additional physiological burden on vineyard workers. These results confirm that the idea of using generic coveralls in any farming activity is unsuitable. Compromises should be created between physiological costs and protection, depending on the agricultural task performed, the crop grown, and the environmental conditions encountered.
Oken, Barry S.
2016-01-01
Abstract Objective: Aromas may improve physiologic and cognitive function after stress, but associated mechanisms remain unknown. This study evaluated the effects of lavender aroma, which is commonly used for stress reduction, on physiologic and cognitive functions. The contribution of pharmacologic, hedonic, and expectancy-related mechanisms of the aromatherapy effects was evaluated. Methods: Ninety-two healthy adults (mean age, 58.0 years; 79.3% women) were randomly assigned to three aroma groups (lavender, perceptible placebo [coconut], and nonperceptible placebo [water] and to two prime subgroups (primed, with a suggestion of inhaling a powerful stress-reducing aroma, or no prime). Participants' performance on a battery of cognitive tests, physiologic responses, and subjective stress were evaluated at baseline and after exposure to a stress battery during which aromatherapy was present. Participants also rated the intensity and pleasantness of their assigned aroma. Results: Pharmacologic effects of lavender but not placebo aromas significantly benefited post-stress performance on the working memory task (F(2, 86) = 5.41; p = 0.006). Increased expectancy due to positive prime, regardless of aroma type, facilitated post-stress performance on the processing speed task (F(1, 87) = 8.31; p = 0.005). Aroma hedonics (pleasantness and intensity) played a role in the beneficial lavender effect on working memory and physiologic function. Conclusions: The observable aroma effects were produced by a combination of mechanisms involving aroma-specific pharmacologic properties, aroma hedonic properties, and participant expectations. In the future, each of these mechanisms could be manipulated to produce optimal functioning. PMID:27355279
Lebedev, Valery P; Malygin, A V; Kovalevski, A V; Rychkova, S V; Sisoev, V N; Kropotov, S P; Krupitski, E M; Gerasimova, L I; Glukhov, D V; Kozlowski, G P
2002-03-01
It is well known that deficit of endorphins plays an important role in disturbances of human psycho-physiological status. Previously, we revealed that brain endorphinergic structures have quasiresonance characteristics. On the basis of these data, a method of activation of the brain endorphinergic structures by means of noninvasive and rather selective transcranial electrostimulation (TES) as a kind of functional electrical stimulation (FES) was elaborated. New models of TES devices (TRANSAIR) were developed for indoor and outdoor usage. To increase the efficacy of TES, the frequency modulation according to normal distribution in the limits of the quasiresonance characteristics was put into operation. The blind and placebo-controlled (passive and active placebo) study was produced to estimate the TES effects on stress events and accompanied psycho-physiological and autonomic disturbances of different intensities on volunteers and patients in the following groups: everyday stress and fatigue; stress in regular military service and in field conditions; stress in the relatives of those lost in mass disaster; posttraumatic stress (thermal burns); and affective disorders in a postabstinence period. Some subjective verbal and nonverbal tests and objective tests (including heart rate variability) were used for estimation of the initial level of psycho-physiological status, which changes after TES sessions. It was demonstrated that fatigue, stress, and other accompanied psycho-physiological disturbances were significantly improved or abolished after 2-5 TES sessions. The TES effects were more pronounced in cases of heavier disturbances. In conclusion, activation of the brain endorphinergic structures by TES is an effective homeostatic method of FES that sufficiently improves quality of life.
Aremu, Adeyemi O; Masondo, Nqobile A; Rengasamy, Kannan R R; Amoo, Stephen O; Gruz, Jiří; Bíba, Ondřej; Šubrtová, Michaela; Pěnčík, Aleš; Novák, Ondřej; Doležal, Karel; Van Staden, Johannes
2015-06-01
Eckol, a major phenolic compound isolated from brown seaweed significantly enhanced the bulb size and bioactive compounds in greenhouse-grown Eucomis autumnalis. We investigated the effect of eckol and phloroglucinol (PG) (phenolic compounds) isolated from the brown seaweed, Ecklonia maxima (Osbeck) Papenfuss on the growth, phytochemical and auxin content in Eucomis autumnalis (Mill.) Chitt. The model plant is a popular medicinal species with increasing conservation concern. Eckol and PG were tested at 10(-5), 10(-6) and 10(-7) M using soil drench applications. After 4 months, growth parameters, phytochemical and auxin content were recorded. When compared to the control, eckol (10(-6) M) significantly improved bulb size, fresh weight and root production while the application of PG (10(-6) M) significantly increased the bulb numbers. However, both compounds had no significant stimulatory effect on aerial organs. Bioactive phytochemicals such as p-hydroxybenzoic and ferulic acids were significantly increased in eckol (10(-5) M) and PG (10(-6) M) treatments, compared to the control. Aerial (1,357 pmol/g DW) and underground (1,474 pmol/g DW) parts of eckol-treated (10(-5) M) plants yielded the highest concentration of indole-3-acetic acid. Overall, eckol and PG elicited a significant influence on the growth and physiological response in E. autumnalis. Considering the medicinal importance of E. autumnalis and the increasing strains on its wild populations, these compounds are potential tools to enhance their cultivation and growth.
Oh, Minyoung; Elvitigala, Don Anushka Sandaruwan; Bathige, S D N K; Lee, Seongdo; Kim, Myoung-Jin; Lee, Jehee
2016-11-01
Apoptosis is a physiological process that can also participate in host immune defense mechanisms, including tumor growth suppression along with homeostasis and maturation of immune cells. Caspases are known to be involved in cellular apoptotic signaling; among them, caspase-8 plays an important role in the initiation phase of the apoptotic death cascade. In the current study, we molecularly characterized a caspase-8 homolog (designated as HaCasp-8) from Hippocampus abdominalis. The HaCasp-8 gene harbors a 1476 bp open reading frame (ORF) that codes for a protein of 492 amino acids (aa) with a predicted molecular mass of 55 kDa. HaCasp-8 houses the typical domain architecture of known initiator caspases, including the death effector domain and the carboxyl-terminal catalytic domain. As expected, phylogenetic analysis reflected a closer evolutionary relationship of HaCasp-8 with its teleostean similitudes. The results of our qPCR assays confirmed the ubiquitous expression of HaCasp-8 in physiologically important tissues examined, with pronounced expression levels in ovary tissues, followed by blood cells. HaCasp-8 expression at the mRNA level was found to be significantly modulated by lipopolysaccharide, polyinosinic:polycytidylic acid, Streptococcus iniae, and Edwardsiella tarda injection. Overexpression of HaCasp-8 could trigger a significant level of cell death in HEK293T cells, suggesting its putative role in cell death. Taken together, our findings suggest that HaCasp-8 is an important component in the caspase cascade, and its expression can be significantly modulated under pathogen stress conditions in the big-belly seahorse. Copyright © 2016 Elsevier Ltd. All rights reserved.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Wang, Chaoyun; He, Yanhao; Department of Pharmacology, Xi'an Jiaotong University School of Medicine, Key Laboratory of Environment and Genes Related to Disease, Ministry of Education, Xi'an, Shaanxi 710061
Intracellular reactive oxygen species (ROS) are derived from nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. Angiotensin II (Ang II) can cause endothelial dysfunction by promoting intracellular ROS generation. Safflor yellow B (SYB) effectively inhibits ROS generation by upregulating Bcl-2 expression. In this study, we examined the effects of SYB on Ang II-induced injury to human umbilical vein endothelial cells (HUVECs), and elucidated the roles of NADPH oxidase and Bcl-2. We treated cultured HUVECs with Ang II, SYB, and Bcl-2 siRNA, and determined NADPH oxidase activity and ROS levels. Furthermore, cellular and mitochondrial physiological states were evaluated, and the expression levels ofmore » target proteins were analyzed. Ang II significantly enhanced intracellular ROS levels, caused mitochondrial membrane dysfunction, and decreased cell viability, leading to apoptosis. This was associated with increased expression of AT1R and p22{sup phox}, increased NADPH oxidase activity, and an increased ratio of Bax/Bcl-2, leading to decreases in antioxidant enzyme activities, which were further strengthened after blocking Bcl-2. Compared to Ang II treatment alone, co-treatment with SYB significantly reversed HUVEC injury. Taken together, these results demonstrate that SYB could significantly protect endothelial cells from Ang II-induced cell damage, and that it does so by upregulating Bcl-2 expression and inhibiting ROS generation. - Highlights: • Angiotensin II depresses mitochondria physiological function. • Angiotensin II activates NADPH oxidase via up-regulating expresion of p22{sup phox}. • Bcl-2 plays a pivotal role in improving mitochondria function and regulates ROS level. • Inhibitor of Bcl-2 promotes angiotensin II mediated HUVEC injury. • SYB attenuates angiotensin II mediated HUVEC injury via up regulating Bcl-2 expression.« less
Dietary inorganic nitrate: From villain to hero in metabolic disease?
McNally, Ben; Griffin, Julian L.
2015-01-01
Historically, inorganic nitrate was believed to be an inert by‐product of nitric oxide (NO) metabolism that was readily excreted by the body. Studies utilising doses of nitrate far in excess of dietary and physiological sources reported potentially toxic and carcinogenic effects of the anion. However, nitrate is a significant component of our diets, with the majority of the anion coming from green leafy vegetables, which have been consistently shown to offer protection against obesity, type 2 diabetes and metabolic diseases. The discovery of a metabolic pathway in mammals, in which nitrate is reduced to NO, via nitrite, has warranted a re‐examination of the physiological role of this small molecule. Obesity, type 2 diabetes and the metabolic syndrome are associated with a decrease in NO bioavailability. Recent research suggests that the nitrate‐nitrite‐NO pathway may be harnessed as a therapeutic to supplement circulating NO concentrations, with both anti‐obesity and anti‐diabetic effects, as well as improving vascular function. In this review, we examine the key studies that have led to the re‐evaluation of the physiological function of inorganic nitrate, from toxic and carcinogenic metabolite, to a potentially important and beneficial agent in the treatment of metabolic disease. PMID:26227946
Tanaka, Ryo; Umemura, Masanari; Narikawa, Masatoshi; Fujita, Takayuki; Yokoyama, Utako; Ishigami, Tomoaki; Kimura, Kazuo; Tamura, Kouichi; Ishikawa, Yoshihiro
2018-05-01
Mechanical stresses play important roles in the process of constructing and modifying heart structure. It has been well established that stretch force acting on cardiac fibroblasts induces fibrosis. However, the effects of compressive force, that is, hydrostatic pressure (HP), have not been well elucidated. We thus evaluated the effects of HP using a pressure-loading apparatus in human cardiac fibroblasts (HCFs) in vitro. In this study, high HP (200 mmHg) resulted in significant phosphorylation of Akt in HCFs. HP then greatly inhibited glycogen synthase kinase 3 (GSK-3)α, which acts downstream of the PI3K/Akt pathway. Similarly, HP suppressed mRNA transcription of inflammatory cytokine-6, collagen I and III, and matrix metalloproteinase 1, compared with an atmospheric pressure condition. Furthermore, HP inhibited collagen matrix production in a three-dimensional HCF culture. Taken together, high HP suppressed the differentiation of fibroblasts into the myofibroblast phenotype. HP under certain conditions suppressed cardiac fibrosis via Akt/GSK-3 signaling in HCFs. These results might help to elucidate the pathology of some types of heart disease. © 2018 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.
Manipulating neural activity in physiologically classified neurons: triumphs and challenges
Gore, Felicity; Schwartz, Edmund C.; Salzman, C. Daniel
2015-01-01
Understanding brain function requires knowing both how neural activity encodes information and how this activity generates appropriate responses. Electrophysiological, imaging and immediate early gene immunostaining studies have been instrumental in identifying and characterizing neurons that respond to different sensory stimuli, events and motor actions. Here we highlight approaches that have manipulated the activity of physiologically classified neurons to determine their role in the generation of behavioural responses. Previous experiments have often exploited the functional architecture observed in many cortical areas, where clusters of neurons share response properties. However, many brain structures do not exhibit such functional architecture. Instead, neurons with different response properties are anatomically intermingled. Emerging genetic approaches have enabled the identification and manipulation of neurons that respond to specific stimuli despite the lack of discernable anatomical organization. These approaches have advanced understanding of the circuits mediating sensory perception, learning and memory, and the generation of behavioural responses by providing causal evidence linking neural response properties to appropriate behavioural output. However, significant challenges remain for understanding cognitive processes that are probably mediated by neurons with more complex physiological response properties. Currently available strategies may prove inadequate for determining how activity in these neurons is causally related to cognitive behaviour. PMID:26240431
Light during darkness and cancer: relationships in circadian photoreception and tumor biology.
Jasser, Samar A; Blask, David E; Brainard, George C
2006-05-01
The relationship between circadian phototransduction and circadian-regulated processes is poorly understood. Melatonin, commonly a circadian phase marker, may play a direct role in a myriad of physiologic processes. The circadian rhythm for pineal melatonin secretion is regulated by the hypothalamic suprachiasmatic nucleus (SCN). Its neural source of light input is a unique subset of intrinsically photosensitive retinal ganglion cells expressing melanopsin, the primary circadian photopigment in rodents and primates. Action spectra of melatonin suppression by light have shown that light in the 446-477 nm range, distinct from the visual system's peak sensitivity, is optimal for stimulating the human circadian system. Breast cancer is the oncological disease entity whose relationship to circadian rhythm fluctuations has perhaps been most extensively studied. Empirical data has increasingly supported the hypothesis that higher risk of breast cancer in industrialized countries is partly due to increased exposure to light at night. Studies of tumor biology implicate melatonin as a potential mediator of this effect. Yet, causality between lifestyle factors and circadian tumor biology remains elusive and likely reflects significant variability with physiologic context. Continued rigorous empirical inquiry into the physiology and clinical implications of these habitual, integrated aspects of life is highly warranted at this time.
Sulovic, Ljiljana S; Mahmutovic, Meho; Lazic, Snezana; Sulovic, Nenad
2017-05-01
Aims "Athlete's heart" is a cardiac adaptation to long-term intensive training. The aims of this study were to show the prevalence of left ventricular hypertrophy in teenagers who participate in sports, to define the different types of cardiac re-modelling, and to differentiate between physiological and pathological hypertrophy. Echocardiographic measurements were obtained by M-mode, two dimensional, and Doppler techniques of participants from sports and control groups. The echocardiographic examinations included 100 healthy teenagers taking part in dynamic sports such as football and basketball and 100 healthy teenagers taking part in static sports such as karate and judo. The control group (n=100) included healthy, sedentary teenagers. Sports participants had significantly higher left ventricular mass when compared with the control group, (p0.05). Respondents from both groups had E/A ratios (transmitral flow velocity ratio)>1, preserved diastolic function, and statistically they did not differ from the control group. Echocardiographic parameters show that physiological hypertrophy and cardiac re-modelling are present in teenagers who play sports. Unexpectedly, the prevalence of concentric and eccentric types of re-modelling is equally possible in the group of static sports participants.
Metabolic Adaptation to Muscle Ischemia
NASA Technical Reports Server (NTRS)
Cabrera, Marco E.; Coon, Jennifer E.; Kalhan, Satish C.; Radhakrishnan, Krishnan; Saidel, Gerald M.; Stanley, William C.
2000-01-01
Although all tissues in the body can adapt to varying physiological/pathological conditions, muscle is the most adaptable. To understand the significance of cellular events and their role in controlling metabolic adaptations in complex physiological systems, it is necessary to link cellular and system levels by means of mechanistic computational models. The main objective of this work is to improve understanding of the regulation of energy metabolism during skeletal/cardiac muscle ischemia by combining in vivo experiments and quantitative models of metabolism. Our main focus is to investigate factors affecting lactate metabolism (e.g., NADH/NAD) and the inter-regulation between carbohydrate and fatty acid metabolism during a reduction in regional blood flow. A mechanistic mathematical model of energy metabolism has been developed to link cellular metabolic processes and their control mechanisms to tissue (skeletal muscle) and organ (heart) physiological responses. We applied this model to simulate the relationship between tissue oxygenation, redox state, and lactate metabolism in skeletal muscle. The model was validated using human data from published occlusion studies. Currently, we are investigating the difference in the responses to sudden vs. gradual onset ischemia in swine by combining in vivo experimental studies with computational models of myocardial energy metabolism during normal and ischemic conditions.
AKAP-scaffolding proteins and regulation of cardiac physiology
Mauban, JRH; O'Donnell, M; Warrier, S; Manni, S; Bond, M
2009-01-01
A kinase anchoring proteins (AKAPs) compose a growing list of diverse but functionally related proteins defined by their ability to bind to the regulatory subunit of protein kinase A. AKAPs perform an integral role in the spatiotemporal modulation of a multitude of cellular signaling pathways. This review highlights the extensive role of AKAPs in cardiac excitation/contraction coupling and cardiac physiology. The literature shows that particular AKAPs are involved in cardiac Ca2+ influx, release, re-uptake, and myocyte repolarization. Studies have also suggested roles for AKAPs in cardiac remodeling. Transgenic studies show functional effects of AKAPs, not only in the cardiovascular system, but in other organ systems as well. PMID:19364910
The Contribution of L-Type Cav1.3 Channels to Retinal Light Responses
Shi, Liheng; Chang, Janet Ya-An; Yu, Fei; Ko, Michael L.; Ko, Gladys Y.-P.
2017-01-01
L-type voltage-gated calcium channels (LTCCs) regulate tonic neurotransmitter release from sensory neurons including retinal photoreceptors. There are three types of LTCCs (Cav1.2, Cav1.3, and Cav1.4) expressed in the retina. While Cav1.2 is expressed in all retinal cells including the Müller glia and neurons, Cav1.3 and Cav1.4 are expressed in the retinal neurons with Cav1.4 exclusively expressed in the photoreceptor synaptic terminals. Mutations in the gene encoding Cav1.4 cause incomplete X-linked congenital stationary night blindness in humans. Even though Cav1.3 is present in the photoreceptor inner segments and the synaptic terminals in various vertebrate species, its role in vision is unclear, since genetic alterations in Cav1.3 are not associated with severe vision impairment in humans or in Cav1.3-null (Cav1.3−/−) mice. However, a failure to regulate Cav1.3 was found in a mouse model of Usher syndrome, the most common cause of combined deafness and blindness in humans, indicating that Cav1.3 may contribute to retinal function. In this report, we combined physiological and morphological data to demonstrate the role of Cav1.3 in retinal physiology and function that has been undervalued thus far. Through ex vivo and in vivo electroretinogram (ERG) recordings and immunohistochemical staining, we found that Cav1.3 plays a role in retinal light responses and synaptic plasticity. Pharmacological inhibition of Cav1.3 decreased ex vivo ERG a- and b-wave amplitudes. In Cav1.3−/− mice, their dark-adapted ERG a-, b-wave, and oscillatory potential amplitudes were significantly dampened, and implicit times were delayed compared to the wild type (WT). Furthermore, the density of ribbon synapses was reduced in the outer plexiform layer of Cav1.3−/− mice retinas. Hence, Cav1.3 plays a more prominent role in retinal physiology and function than previously reported. PMID:29259539
Chang, Ji Suk; Jun, Hee-Jin; Park, Minsung
2016-10-01
The transcriptional coactivator PGC-1α plays a central role in hepatic gluconeogenesis. We previously reported that alternative splicing of the PGC-1α gene produces an additional transcript encoding the truncated protein NT-PGC-1α NT-PGC-1α is co-expressed with PGC-1α and highly induced by fasting in the liver. NT-PGC-1α regulates tissue-specific metabolism, but its role in the liver has not been investigated. Thus, the objective of this study was to determine the role of hepatic NT-PGC-1α in the regulation of gluconeogenesis. Adenovirus-mediated expression of NT-PGC-1α in primary hepatocytes strongly stimulated the expression of key gluconeogenic enzyme genes (PEPCK and G6Pase), leading to increased glucose production. To further understand NT-PGC-1α function in hepatic gluconeogenesis in vivo, we took advantage of a previously reported FL-PGC-1α -/- mouse line that lacks full-length PGC-1α (FL-PGC-1α) but retains a slightly shorter and functionally equivalent form of NT-PGC-1α (NT-PGC-1α 254 ). In FL-PGC-1α -/- mice, NT-PGC-1α 254 was induced by fasting in the liver and recruited to the promoters of PEPCK and G6Pase genes. The enrichment of NT-PGC-1α 254 at the promoters was closely associated with fasting-induced increase in PEPCK and G6Pase gene expression and efficient production of glucose from pyruvate during a pyruvate tolerance test in FL-PGC-1α -/- mice. Moreover, FL-PGC-1α -/- primary hepatocytes showed a significant increase in gluconeogenic gene expression and glucose production after treatment with dexamethasone and forskolin, suggesting that NT-PGC-1α 254 is sufficient to stimulate the gluconeogenic program in the absence of FL-PGC-1α Collectively, our findings highlight the role of hepatic NT-PGC-1α in stimulating gluconeogenic gene expression and glucose production. © 2016 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.
The Contribution of L-Type Cav1.3 Channels to Retinal Light Responses.
Shi, Liheng; Chang, Janet Ya-An; Yu, Fei; Ko, Michael L; Ko, Gladys Y-P
2017-01-01
L-type voltage-gated calcium channels (LTCCs) regulate tonic neurotransmitter release from sensory neurons including retinal photoreceptors. There are three types of LTCCs (Ca v 1.2, Ca v 1.3, and Ca v 1.4) expressed in the retina. While Ca v 1.2 is expressed in all retinal cells including the Müller glia and neurons, Ca v 1.3 and Ca v 1.4 are expressed in the retinal neurons with Ca v 1.4 exclusively expressed in the photoreceptor synaptic terminals. Mutations in the gene encoding Ca v 1.4 cause incomplete X-linked congenital stationary night blindness in humans. Even though Ca v 1.3 is present in the photoreceptor inner segments and the synaptic terminals in various vertebrate species, its role in vision is unclear, since genetic alterations in Ca v 1.3 are not associated with severe vision impairment in humans or in Ca v 1.3-null (Ca v 1.3 -/- ) mice. However, a failure to regulate Ca v 1.3 was found in a mouse model of Usher syndrome, the most common cause of combined deafness and blindness in humans, indicating that Ca v 1.3 may contribute to retinal function. In this report, we combined physiological and morphological data to demonstrate the role of Ca v 1.3 in retinal physiology and function that has been undervalued thus far. Through ex vivo and in vivo electroretinogram (ERG) recordings and immunohistochemical staining, we found that Ca v 1.3 plays a role in retinal light responses and synaptic plasticity. Pharmacological inhibition of Ca v 1.3 decreased ex vivo ERG a- and b-wave amplitudes. In Ca v 1.3 -/- mice, their dark-adapted ERG a-, b-wave, and oscillatory potential amplitudes were significantly dampened, and implicit times were delayed compared to the wild type (WT). Furthermore, the density of ribbon synapses was reduced in the outer plexiform layer of Ca v 1.3 -/- mice retinas. Hence, Ca v 1.3 plays a more prominent role in retinal physiology and function than previously reported.
Role of Proangiogenic Factors in Immunopathogenesis of Multiple Sclerosis.
Hamid, Kabir Magaji; Mirshafiey, Abbas
2016-02-01
Angiogenesis is a complex and balanced process in which new blood vessels form from preexisting ones by sprouting, splitting, growth and remodeling. This phenomenon plays a vital role in many physiological and pathological processes. However, the disturbance in physiological process can play a role in pathogenesis of some chronic inflammatory diseases, including multiple sclerosis (MS) in human and its animal model. Although the relation between abnormal blood vessels and MS lesions was established in previous studies, but the role of pathological angiogenesis remains unclear. In this study, the link between proangiogenic factors and multiple sclerosis pathogenesis was examined by conducting a systemic review. Thus we searched the English medical literature via PubMed, ISI web of knowledge, Medline and virtual health library (VHL) databases. In this review, we describe direct and indirect roles of some proangiogenic factors in MS pathogenesis and report the association of these factors with pathological and inflammatory angiogenesis.
Revisiting the role of erythropoietin for treatment of ocular disorders
Shirley Ding, S L; Leow, S N; Munisvaradass, R; Koh, E H; Bastion, M L C; Then, K Y; Kumar, S; Mok, P L
2016-01-01
Erythropoietin (EPO) is a glycoprotein hormone conventionally thought to be responsible only in producing red blood cells in our body. However, with the discovery of the presence of EPO and EPO receptors in the retinal layers, the EPO seems to have physiological roles in the eye. In this review, we revisit the role of EPO in the eye. We look into the biological role of EPO in the development of the eye and the physiologic roles that it has. Apart from that, we seek to understand the mechanisms and pathways of EPO that contributes to the therapeutic and pathological conditions of the various ocular disorders such as diabetic retinopathy, retinopathy of prematurity, glaucoma, age-related macular degeneration, optic neuritis, and retinal detachment. With these understandings, we discuss the clinical applications of EPO for treatment of ocular disorders, modes of administration, EPO formulations, current clinical trials, and its future directions. PMID:27285322
Qiao, Hui; Jiang, Fengwei; Xiong, Yiwei; Jiang, Sufei; Fu, Hongtuo; Li, Fei; Zhang, Wenyi; Sun, Shengming; Jin, Shubo; Gong, Yongsheng; Wu, Yan
2018-01-01
The oriental river prawn, Macrobrachium nipponense, is an important commercial aquaculture resource in China. In order to overwinter, M. nipponense displays decreased physiological activity and less consumption of energy. Sudden warming would trigger molting and cause an extensive death, resulting in huge economic losses. Therefore, it is of great practical significance to study the molting mechanism of oriental river prawns. Molt-inhibiting hormone gene (MIH) plays a major role in regulating molting in crustaceans. In this study, a full length MIH cDNA of M. nipponense (Mn-MIH) was cloned from the eyestalk. The total length of the Mn-MIH was 925 bp, encoding a protein of 119 amino acids. Tissue distribution analysis showed that Mn-MIH was highly expressed in the eyestalk, and that it had relatively low expression in gill, ovary, and abdominal ganglion. Mn-MIH was detected in all developmental stages, and changed regularly in line with the molting cycle of the embryo and larva. Mn-MIH varied in response to the molting cycle, suggesting that Mn-MIH negatively regulates ecdysteroidogenesis. Mn-MIH inhibition by RNAi resulted in a significant acceleration of molting cycles in both males and females, confirming the inhibitory role of MIH in molting. After long-term RNAi males, but not females had significant weight gain, confirming that Mn-MIH plays an important role in growth of M. nipponense. Our work contributes to a better understanding of the role of Mn-MIH in crustacean molting and growth.
Jiang, Fengwei; Xiong, Yiwei; Jiang, Sufei; Fu, Hongtuo; Li, Fei; Zhang, Wenyi; Sun, Shengming; Jin, Shubo; Gong, Yongsheng; Wu, Yan
2018-01-01
The oriental river prawn, Macrobrachium nipponense, is an important commercial aquaculture resource in China. In order to overwinter, M. nipponense displays decreased physiological activity and less consumption of energy. Sudden warming would trigger molting and cause an extensive death, resulting in huge economic losses. Therefore, it is of great practical significance to study the molting mechanism of oriental river prawns. Molt-inhibiting hormone gene (MIH) plays a major role in regulating molting in crustaceans. In this study, a full length MIH cDNA of M. nipponense (Mn-MIH) was cloned from the eyestalk. The total length of the Mn-MIH was 925 bp, encoding a protein of 119 amino acids. Tissue distribution analysis showed that Mn-MIH was highly expressed in the eyestalk, and that it had relatively low expression in gill, ovary, and abdominal ganglion. Mn-MIH was detected in all developmental stages, and changed regularly in line with the molting cycle of the embryo and larva. Mn-MIH varied in response to the molting cycle, suggesting that Mn-MIH negatively regulates ecdysteroidogenesis. Mn-MIH inhibition by RNAi resulted in a significant acceleration of molting cycles in both males and females, confirming the inhibitory role of MIH in molting. After long-term RNAi males, but not females had significant weight gain, confirming that Mn-MIH plays an important role in growth of M. nipponense. Our work contributes to a better understanding of the role of Mn-MIH in crustacean molting and growth. PMID:29889902
2011-01-01
can have a significant impact on normal physiological functioning if precipitous increases in core temperature are not adequately controlled with...anterior hypothalamusIntroduction Thermal stress can have a significant impact on normal physiological functioning if precipitous increases in core...fat and skin). The regulation of a relatively constant internal temperature is critical for normal physiological functioning of tissues and cells, as
Fruit Calcium: Transport and Physiology
Hocking, Bradleigh; Tyerman, Stephen D.; Burton, Rachel A.; Gilliham, Matthew
2016-01-01
Calcium has well-documented roles in plant signaling, water relations and cell wall interactions. Significant research into how calcium impacts these individual processes in various tissues has been carried out; however, the influence of calcium on fruit ripening has not been thoroughly explored. Here, we review the current state of knowledge on how calcium may impact the development, physical traits and disease susceptibility of fruit through facilitating developmental and stress response signaling, stabilizing membranes, influencing water relations and modifying cell wall properties through cross-linking of de-esterified pectins. We explore the involvement of calcium in hormone signaling integral to the physiological mechanisms behind common disorders that have been associated with fruit calcium deficiency (e.g., blossom end rot in tomatoes or bitter pit in apples). This review works toward an improved understanding of how the many roles of calcium interact to influence fruit ripening, and proposes future research directions to fill knowledge gaps. Specifically, we focus mostly on grapes and present a model that integrates existing knowledge around these various functions of calcium in fruit, which provides a basis for understanding the physiological impacts of sub-optimal calcium nutrition in grapes. Calcium accumulation and distribution in fruit is shown to be highly dependent on water delivery and cell wall interactions in the apoplasm. Localized calcium deficiencies observed in particular species or varieties can result from differences in xylem morphology, fruit water relations and pectin composition, and can cause leaky membranes, irregular cell wall softening, impaired hormonal signaling and aberrant fruit development. We propose that the role of apoplasmic calcium-pectin crosslinking, particularly in the xylem, is an understudied area that may have a key influence on fruit water relations. Furthermore, we believe that improved knowledge of the calcium-regulated signaling pathways that control ripening would assist in addressing calcium deficiency disorders and improving fruit pathogen resistance. PMID:27200042
Physiological role of short peptides in nutrition.
Tutel'yan, V A; Khavinson, V Kh; Malinin, V V
2003-01-01
Here we review new data about the physiological role of short peptides and their use as biologically active food additives (parapharmaceutics). Some approaches to the development of peptide preparations for peroral administration are considered and the mechanisms of nonspecific and tissue-specific effects produced by peroral peptide parapharmaceutics are discussed. Particular attention is given to biological properties of short peptides synthesized at the St. Petersburg Institute of Bioregulation and Gerontology. These peptides hold much promise for the synthesis of parapharmaceutics increasing organism's resistance to extreme factors and preventing accelerated aging and age-related diseases.
Proteorhodopsins: an array of physiological roles?
Fuhrman, Jed A; Schwalbach, Michael S; Stingl, Ulrich
2008-06-01
Metagenomic analyses have revealed widespread and diverse retinal-binding rhodopsin proteins (named proteorhodopsins) among numerous marine bacteria and archaea, which has challenged the notion that solar energy can only enter marine ecosystems by chlorophyll-based photosynthesis. Most marine proteorhodopsins share structural and functional similarities with archaeal bacteriorhodopsins, which generate proton motive force via light-activated proton pumping, thereby ultimately powering ATP production. This suggests an energetic role for proteorhodopsins. However, results from a growing number of investigations do not readily fit this model, which indicates that proteorhodopsins could have a range of physiological functions.
Analysis of Extracellular Vesicles in the Tumor Microenvironment.
Al-Nedawi, Khalid; Read, Jolene
2016-01-01
Extracellular vesicles (ECV) are membrane compartments shed from all types of cells in various physiological and pathological states. In recent years, ECV have gained an increasing interest from the scientific community for their role as an intercellular communicator that plays important roles in modifying the tumor microenvironment. Multiple techniques have been established to collect ECV from conditioned media of cell culture or physiological fluids. The gold standard methodology is differential centrifugation. Although alternative techniques exist to collect ECV, these techniques have not proven suitable as a substitution for the ultracentrifugation procedure.
Protein disulfide isomerase a multifunctional protein with multiple physiological roles
NASA Astrophysics Data System (ADS)
Ali Khan, Hyder; Mutus, Bulent
2014-08-01
Protein disulfide isomerase (PDI), is a member of the thioredoxin superfamily of redox proteins. PDI has three catalytic activities including, thiol-disulfide oxireductase, disulfide isomerase and redox-dependent chaperone. Originally, PDI was identified in the lumen of the endoplasmic reticulum and subsequently detected at additional locations, such as cell surfaces and the cytosol. This review will provide an overview of the recent advances in relating the structural features of PDI to its multiple catalytic roles as well as its physiological and pathophysiological functions related to redox regulation and protein folding.
Exercise and Children's Health.
ERIC Educational Resources Information Center
Rowland, Thomas W.
This book paints a broad picture of the role of exercise in children's health and provides information for the physician and other health care providers on healthful forms of physical activity for children. The book is divided into three parts: (1) "Developmental Exercise Physiology: The Physiological Basis of Physical Fitness in Children"; (2)…
Direct Manipulation of Physiological Arousal in Induced Anxiety Therapy-Biofeedback Approach
ERIC Educational Resources Information Center
Sappington, A. A.
1977-01-01
Induced Anxiety is a brief psychotherapy procedure that teaches individuals to cope with negative effect by using relaxation techniques. This research investigated the role of physiological arousal in the affect induction phase of Induced Anxiety therapy by using biofeedback to facilitate arousal. Twenty-one college students suffering from…
Handy, Ariel B; Stanton, Amelia M; Pulverman, Carey S; Meston, Cindy M
2018-01-01
Many sexual psychophysiologic studies have failed to find differences in physiologic genital arousal between women with and those without sexual dysfunction. However, differences in self-reported (ie, perceived) measures of genital responses between these 2 groups of women have been noted. To determine whether women with and without sexual dysfunction differ on measures of physiologic and perceived genital arousal based on type of analytic technique used, to explore differences in perceived genital arousal, and to assess the relation between physiologic and perceived genital arousal. Data from 5 studies (N = 214) were used in this analysis. Women were categorized into 3 groups: women with arousal-specific sexual dysfunction (n = 40), women with decreased sexual function (n = 72), and women who were sexually functional (n = 102). Women viewed an erotic film while their physiologic genital arousal was measured using a vaginal photoplethysmograph. After watching the film, women completed a self-report measure of perceived genital arousal. There were differences in vaginal pulse amplitude (VPA) levels and association of VPA with perceived genital sensations based on level of sexual function. Commonly used methods of analysis failed to identify significant differences in VPA among these groups of women. When VPA data were analyzed with hierarchical linear modeling, significant differences emerged. Notably, women with arousal-specific dysfunction exhibited lower VPA than sexually functional women at the beginning of the assessment. As the erotic film progressed, women with arousal-specific dysfunction became aroused at a faster rate than sexually functional women, and these 2 groups ultimately reached a similar level of VPA. Sexually functional women reported the highest levels of perceived genital responses among the 3 groups of women. No significant relation between VPA and perceived genital arousal emerged. Women's perception of their genital responses could play a role in women's experience of sexual dysfunction and might be more clinically relevant for women with sexual dysfunction than genital blood flow. This study's large sample is unique in sexual psychophysiology, and it strengthens the credibility of the findings. However, this study is limited in that arousal-specific dysfunction was determined with self-report measures, not by a clinician-administered assessment. These findings suggest distinct response trajectories in women with and without sexual dysfunction, and although perceived genital responses are important for women who are experiencing problems with arousal, they do not seem to be related to objective measures of physiologic arousal. Handy AB, Stanton AM, Pulverman CS, Meston CM. Differences in Perceived and Physiologic Genital Arousal Between Women With and Without Sexual Dysfunction. J Sex Med 2018;15:52-63. Copyright © 2017 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.