Physiological Mechanisms Only Tell Half Story: Multiple Biological Processes are involved in Regulating Freezing Tolerance of Imbibed Lactuca sativa Seeds

PubMed Central

Jaganathan, Ganesh K.; Han, Yingying; Li, Weijie; Song, Danping; Song, Xiaoyan; Shen, Mengqi; Zhou, Qiang; Zhang, Chenxue; Liu, Baolin

2017-01-01

The physiological mechanisms by which imbibed seeds survive freezing temperatures in their natural environment have been categorized as freezing avoidance by supercooling and freezing tolerance by extracellular freeze-desiccation, but the biochemical and molecular mechanisms conferring seed freezing tolerance is unexplored. In this study, using imbibed Lactuca sativa seeds we show that fast cooled seeds (60 °C h−1) suffered significantly higher membrane damage at temperature between −20 °C and −10 °C than slow cooled (3 °Ch−1) seeds (P < 0.05), presumably explaining viability loss during fast cooling when temperature approaches −20 °C. Total soluble sugars increase in low temperature environment, but did not differ significantly between two cooling rates (P > 0.05). However, both SOD activity and accumulation of free proline were induced significantly after slow cooling to −20 °C compared with fast cooling. RNA-seq demonstrated that multiple pathways were differentially regulated between slow and fast cooling. Real-time verification of some differentially expressed genes (DEGs) revealed that fast cooling caused mRNA level changes of plant hormone and ubiquitionation pathways at higher sub-zero temperature, whilst slow cooling caused mRNA level change of those pathways at lower sub-zero ttemperatures. Thus, we conclude that imbibed seed tolerate low temperature not only by physiological mechanisms but also by biochemical and molecular changes. PMID:28287125

Physiological Mechanisms Only Tell Half Story: Multiple Biological Processes are involved in Regulating Freezing Tolerance of Imbibed Lactuca sativa Seeds.

PubMed

Jaganathan, Ganesh K; Han, Yingying; Li, Weijie; Song, Danping; Song, Xiaoyan; Shen, Mengqi; Zhou, Qiang; Zhang, Chenxue; Liu, Baolin

2017-03-13

The physiological mechanisms by which imbibed seeds survive freezing temperatures in their natural environment have been categorized as freezing avoidance by supercooling and freezing tolerance by extracellular freeze-desiccation, but the biochemical and molecular mechanisms conferring seed freezing tolerance is unexplored. In this study, using imbibed Lactuca sativa seeds we show that fast cooled seeds (60 °C h -1 ) suffered significantly higher membrane damage at temperature between -20 °C and -10 °C than slow cooled (3 °Ch -1 ) seeds (P < 0.05), presumably explaining viability loss during fast cooling when temperature approaches -20 °C. Total soluble sugars increase in low temperature environment, but did not differ significantly between two cooling rates (P > 0.05). However, both SOD activity and accumulation of free proline were induced significantly after slow cooling to -20 °C compared with fast cooling. RNA-seq demonstrated that multiple pathways were differentially regulated between slow and fast cooling. Real-time verification of some differentially expressed genes (DEGs) revealed that fast cooling caused mRNA level changes of plant hormone and ubiquitionation pathways at higher sub-zero temperature, whilst slow cooling caused mRNA level change of those pathways at lower sub-zero ttemperatures. Thus, we conclude that imbibed seed tolerate low temperature not only by physiological mechanisms but also by biochemical and molecular changes.

Metabolic and physiological adjustment of Suaeda maritima to combined salinity and hypoxia

PubMed Central

Behr, Jan H.; Bouchereau, Alain; Berardocco, Solenne; Seal, Charlotte E.; Flowers, Timothy J.

2017-01-01

Background and Aims Suaeda maritima is a halophyte commonly found on coastal wetlands in the intertidal zone. Due to its habitat S. maritima has evolved tolerance to high salt concentrations and hypoxic conditions in the soil caused by periodic flooding. In the present work, the adaptive mechanisms of S. maritima to salinity combined with hypoxia were investigated on a physiological and metabolic level. Methods To compare the adaptive mechanisms to deficient, optimal and stressful salt concentrations, S. maritima plants were grown in a hydroponic culture under low, medium and high salt concentrations. Additionally, hypoxic conditions were applied to investigate the impact of hypoxia combined with different salt concentrations. A non-targeted metabolic approach was used to clarify the biochemical pathways underlying the metabolic and physiological adaptation mechanisms of S. maritima. Key Results Roots exposed to hypoxic conditions showed an increased level of tricarboxylic acid (TCA)-cycle intermediates such as succinate, malate and citrate. During hypoxia, the concentration of free amino acids increased in shoots and roots. Osmoprotectants such as proline and glycine betaine increased in concentrations as the external salinity was increased under hypoxic conditions. Conclusions The combination of high salinity and hypoxia caused an ionic imbalance and an increase of metabolites associated with osmotic stress and photorespiration, indicating a severe physiological and metabolic response under these conditions. Disturbed proline degradation in the roots induced an enhanced proline accumulation under hypoxia. The enhanced alanine fermentation combined with a partial flux of the TCA cycle might contribute to the tolerance of S. maritima to hypoxic conditions. PMID:28110268

Role of the decreased nitric oxide bioavailability in the vascular complications of diabetes mellitus.

PubMed

Masha, Andi; Dinatale, Stefano; Allasia, Stefano; Martina, Valentino

2011-09-01

This mini-review takes into consideration the physiology, synthesis and mechanisms of action of the nitric oxide (NO) and, subsequently, the causes and effects of the NO bioavailability impairment. In diabetes mellitus the reduced NO bioavailability is caused by the increased free radicals production, secondary to hyperglycemia. The reactive oxygen species oxidize the cofactors of the nitric oxide synthase, diminishing their active forms and consequently leading to a decreased NO production. Furthermore the decreased concentration of reduced glutathione results in a diminished production of nitrosoglutathione. These molecules are important intermediates of the NO pathway and physiologically activate the soluble guanylate cyclase. Their decrease in oxidative states of the cell, therefore, leads to a reduced cGMP production which represents the principal molecule that carries out NO's major effects. Finally we considered the eventual therapeutic strategies to improve NO bioavailability by acting on the causes of its decrease. Therefore the treatments proposed are based on the possibility to counteract the oxidation and, in this context, the physiopathological mechanisms strongly support the treatment with thiols.

SiO2 nanoparticles change colour preference and cause Parkinson's-like behaviour in zebrafish

PubMed Central

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

DigitalHuman (DH): An Integrative Mathematical Model ofHuman Physiology

NASA Technical Reports Server (NTRS)

Hester, Robert L.; Summers, Richard L.; lIescu, Radu; Esters, Joyee; Coleman, Thomas G.

2010-01-01

Mathematical models and simulation are important tools in discovering the key causal relationships governing physiological processes and improving medical intervention when physiological complexity is a central issue. We have developed a model of integrative human physiology called DigitalHuman (DH) consisting of -5000 variables modeling human physiology describing cardiovascular, renal, respiratory, endocrine, neural and metabolic physiology. Users can view time-dependent solutions and interactively introduce perturbations by altering numerical parameters to investigate new hypotheses. The variables, parameters and quantitative relationships as well as all other model details are described in XML text files. All aspects of the model, including the mathematical equations describing the physiological processes are written in XML open source, text-readable files. Model structure is based upon empirical data of physiological responses documented within the peer-reviewed literature. The model can be used to understand proposed physiological mechanisms and physiological interactions that may not be otherwise intUitively evident. Some of the current uses of this model include the analyses of renal control of blood pressure, the central role of the liver in creating and maintaining insulin resistance, and the mechanisms causing orthostatic hypotension in astronauts. Additionally the open source aspect of the modeling environment allows any investigator to add detailed descriptions of human physiology to test new concepts. The model accurately predicts both qualitative and more importantly quantitative changes in clinically and experimentally observed responses. DigitalHuman provides scientists a modeling environment to understand the complex interactions of integrative physiology. This research was supported by.NIH HL 51971, NSF EPSCoR, and NASA

[The mechanism of phenoptosis: 2. Hayflick limit is caused by the programmed attenuation of bioenergetics].

PubMed

Trubitsin, A G

2010-01-01

This article continues earlier started theme on a substantiation of the programmed aging mechanism (phenoptosis). The concept underlying this mechanism is that the life represents a lot of the interconnected physical and chemical processes moving by the bioenergetics. The gradual programmed decrease of the level of bioenergetics causes the slow and coordinated attenuation of all physiological functions, i.e. aging. For a convincing substantiation of such mechanism it is necessary to show, how attenuation of bioenergetics causes the basic nocuous processes accompanying aging. It is shown earlier that the age dependent decrease in level of bioenergetics causes increase in production of reactive oxygen species by mitochondria and decrease in overall level of protein synthesis. The proof that Hayflick limit is also caused by the decrease in level of bioenergetics is presented in this article. Decrease in level of bioenergetics below certain critical level deprives a cell the ability to pass the restriction point of G1-phase of proliferative cycle. The inhibitor of cyclin-dependent kinase, p27, prevents the passage through this critical point in all normal cells. During division of normal somatic cells p27 is removed by cyclin E-Cdk2 complex. Interaction p27 with cyclin E-Cdk2 complex can have two consequences. At the normal physiological level of bioenergetics the cyclin E-Cdk2 phosphorylates p27, then the latter is destroyed by proteolytic enzymes--the cell enters in S-phase. When the programme decreases the bioenergetics level below certain value the cyclin E-Cdk2 becomes the target for p27. As a result the inhibitor evacuation stops and restriction point becomes closed--a cell enters irreversible proliferative rest.

Gynecomastia.

PubMed

Leung, A K

1989-04-01

Gynecomastia may be physiologic, familial, pathologic, drug-induced or, in many cases, of unknown etiology. Breast enlargement is usually unilateral and asymptomatic. Mechanisms of gynecomastia involve increased estrogen stimulation, decreased testosterone levels or a decreased androgen/estrogen ratio. Hyperprolactinemia is not a cause. Treatment of gynecomastia should be directed at the underlying cause when one can be identified. Most cases are benign and can be managed by explanation, reassurance and observation.

Piezo2 senses airway stretch and mediates lung inflation-induced apnoea

PubMed Central

Nonomura, Keiko; Woo, Seung-Hyun; Chang, Rui B.; Gillich, Astrid; Qiu, Zhaozhu; Francisco, Allain G.; Ranade, Sanjeev S.; Liberles, Stephen D.; Patapoutian, Ardem

2017-01-01

Respiratory dysfunction is a notorious cause of perinatal mortality in infants and sleep apnoea in adults, but the mechanisms of respiratory control are not clearly understood. Mechanical signals transduced by airway-innervating sensory neurons control respiration; however, the physiological significance and molecular mechanisms of these signals remain obscured. Here we show that global and sensory neuron-specific ablation of the mechanically activated ion channel Piezo2 causes respiratory distress and death in newborn mice. Optogenetic activation of Piezo2+ vagal sensory neurons causes apnoea in adult mice. Moreover, induced ablation of Piezo2 in sensory neurons of adult mice causes decreased neuronal responses to lung inflation, an impaired Hering–Breuer mechanoreflex, and increased tidal volume under normal conditions. These phenotypes are reproduced in mice lacking Piezo2 in the nodose ganglion. Our data suggest that Piezo2 is an airway stretch sensor and that Piezo2-mediated mechanotransduction within various airway-innervating sensory neurons is critical for establishing efficient respiration at birth and maintaining normal breathing in adults. PMID:28002412

Intravital imaging of mouse urothelium reveals activation of extracellular signal-regulated kinase by stretch-induced intravesical release of ATP.

PubMed

Sano, Takeshi; Kobayashi, Takashi; Negoro, Hiromitsu; Sengiku, Atsushi; Hiratsuka, Takuya; Kamioka, Yuji; Liou, Louis S; Ogawa, Osamu; Matsuda, Michiyuki

2016-11-01

To better understand the roles played by signaling molecules in the bladder, we established a protocol of intravital imaging of the bladder of mice expressing a Förster/fluorescence resonance energy transfer (FRET) biosensor for extracellular signal-regulated kinase (ERK), which plays critical roles not only in cell growth but also stress responses. With an upright two-photon excitation microscope and a vacuum-stabilized imaging window, cellular ERK activity was visualized in the whole bladder wall, from adventitia to urothelium. We found that bladder distention caused by elevated intravesical pressure (IVP) activated ERK in the urothelium, but not in the detrusor smooth muscle. When bladder distension was prevented, high IVP failed to activate ERK, suggesting that mechanical stretch, but not the high IVP, caused ERK activation. To delineate its molecular mechanism, the stretch-induced ERK activation was reproduced in an hTERT-immortalized human urothelial cell line (TRT-HU1) in vitro. We found that uniaxial stretch raised the ATP concentration in the culture medium and that inhibition of ATP signaling by apyrase or suramin suppressed the stretch-induced ERK activation in TRT-HU1 cells. In agreement with this in vitro observation, pretreatment with apyrase or suramin suppressed the high IVP-induced urothelial ERK activation in vivo. Thus, we propose that mechanical stretch induces intravesical secretion of ATP and thereby activates ERK in the urothelium. Our method of intravital imaging of the bladder of FRET biosensor-expressing mice should open a pathway for the future association of physiological stimuli with the activities of intracellular signaling networks. © 2016 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

Physiological Reactivity in a Community Sample of Sexually Aggressive Young Men: A Test of Competing Hypotheses

PubMed Central

Peterson, Zoë D.; Janssen, Erick; Goodrich, David; Heiman, Julia R.

2015-01-01

Men’s sexually aggressive behavior potentially could relate to either physiological hyporeactivity or hyperreactivity, and these two different physiological profiles could be associated with different underlying causes of sexual aggression. Thus, measurement of physiological reactivity could provide insight into mechanisms relevant to the etiology of sexual aggression. The relationship between sexual aggression and physiological reactivity was investigated in 78 community men (38 sexually aggressive and 40 non-aggressive men). In a laboratory protocol, the men were exposed to neutral, negative-affect-inducing, and positive-affect-inducing stimuli. Men’s salivary cortisol concentrations and electrodermal activity (EDA) were measured throughout the laboratory procedure. Sexually aggressive men demonstrated (1) lower overall cortisol levels and (2) lower EDA reactivity in some conditions as compared to non-aggressive men. Results of this study were consistent with the idea that men’s sexual aggression is associated with physiological hyporeactivity, a physiological profile that has been found to be associated with externalizing behaviors and psychopathic traits. PMID:24310818

Physiological reactivity in a community sample of sexually aggressive young men: a test of competing hypotheses.

PubMed

Peterson, Zoë D; Janssen, Erick; Goodrich, David; Heiman, Julia R

2014-01-01

Men's sexually aggressive behavior potentially could relate to either physiological hyporeactivity or hyperreactivity, and these two different physiological profiles could be associated with different underlying causes of sexual aggression. Thus, measurement of physiological reactivity could provide insight into mechanisms relevant to the etiology of sexual aggression. The relationship between sexual aggression and physiological reactivity was investigated in 78 community men (38 sexually aggressive and 40 non-aggressive men). In a laboratory protocol, the men were exposed to neutral, negative-affect-inducing, and positive-affect-inducing stimuli. Men's salivary cortisol concentrations and electrodermal activity (EDA) were measured throughout the laboratory procedure. Sexually aggressive men demonstrated (1) lower overall cortisol levels and (2) lower EDA reactivity in some conditions as compared to non-aggressive men. Results of this study were consistent with the idea that men's sexual aggression is associated with physiological hyporeactivity, a physiological profile that has been found to be associated with externalizing behaviors and psychopathic traits. © 2013 Wiley Periodicals, Inc.

Epigenetics of reproductive infertility.

PubMed

Das, Laxmidhar; Parbin, Sabnam; Pradhan, Nibedita; Kausar, Chahat; Patra, Samir K

2017-06-01

Infertility is a complex pathophysiological condition. It may caused by specific or multiple physical and physiological factors, including abnormalities in homeostasis, hormonal imbalances and genetic alterations. In recent times various studies implicated that, aberrant epigenetic mechanisms are associated with reproductive infertility. There might be transgenerational effects associated with epigenetic modifications of gametes and studies suggest the importance of alterations in epigenetic modification at early and late stages of gametogenesis. To determine the causes of infertility it is necessary to understand the altered epigenetic modifications of associated gene and mechanisms involved therein. This review is devoted to elucidate the recent mechanistic advances in regulation of genes by epigenetic modification and emphasizes their possible role related to reproductive infertility. It includes environmental, nutritional, hormonal and physiological factors and influence of internal structural architecture of chromatin nucleosomes affecting DNA and histone modifications in both male and female gametes, early embryogenesis and offspring. Finally, we would like to emphasize that research on human infertility by gene knock out of epigenetic modifiers genes must be relied upon animal models.

Heavy Metal Pollution from Gold Mines: Environmental Effects and Bacterial Strategies for Resistance.

PubMed

Fashola, Muibat Omotola; Ngole-Jeme, Veronica Mpode; Babalola, Olubukola Oluranti

2016-10-26

Mining activities can lead to the generation of large quantities of heavy metal laden wastes which are released in an uncontrolled manner, causing widespread contamination of the ecosystem. Though some heavy metals classified as essential are important for normal life physiological processes, higher concentrations above stipulated levels have deleterious effects on human health and biota. Bacteria able to withstand high concentrations of these heavy metals are found in the environment as a result of various inherent biochemical, physiological, and/or genetic mechanisms. These mechanisms can serve as potential tools for bioremediation of heavy metal polluted sites. This review focuses on the effects of heavy metal wastes generated from gold mining activities on the environment and the various mechanisms used by bacteria to counteract the effect of these heavy metals in their immediate environment.

Heavy Metal Pollution from Gold Mines: Environmental Effects and Bacterial Strategies for Resistance

PubMed Central

Fashola, Muibat Omotola; Ngole-Jeme, Veronica Mpode; Babalola, Olubukola Oluranti

2016-01-01

Mining activities can lead to the generation of large quantities of heavy metal laden wastes which are released in an uncontrolled manner, causing widespread contamination of the ecosystem. Though some heavy metals classified as essential are important for normal life physiological processes, higher concentrations above stipulated levels have deleterious effects on human health and biota. Bacteria able to withstand high concentrations of these heavy metals are found in the environment as a result of various inherent biochemical, physiological, and/or genetic mechanisms. These mechanisms can serve as potential tools for bioremediation of heavy metal polluted sites. This review focuses on the effects of heavy metal wastes generated from gold mining activities on the environment and the various mechanisms used by bacteria to counteract the effect of these heavy metals in their immediate environment. PMID:27792205

Recent Advances in Particulate Matter and Nanoparticle Toxicology: A Review of the In Vivo and In Vitro Studies

PubMed Central

Nemmar, Abderrahim; Holme, Jørn A.; Rosas, Irma; Schwarze, Per E.

2013-01-01

Epidemiological and clinical studies have linked exposure to particulate matter (PM) to adverse health effects, which may be registered as increased mortality and morbidity from various cardiopulmonary diseases. Despite the evidence relating PM to health effects, the physiological, cellular, and molecular mechanisms causing such effects are still not fully characterized. Two main approaches are used to elucidate the mechanisms of toxicity. One is the use of in vivo experimental models, where various effects of PM on respiratory, cardiovascular, and nervous systems can be evaluated. To more closely examine the molecular and cellular mechanisms behind the different physiological effects, the use of various in vitro models has proven to be valuable. In the present review, we discuss the current advances on the toxicology of particulate matter and nanoparticles based on these techniques. PMID:23865044

Molecular bases of circadian rhythmicity in renal physiology and pathology

PubMed Central

Bonny, Olivier; Vinciguerra, Manlio; Gumz, Michelle L.; Mazzoccoli, Gianluigi

2013-01-01

The physiological processes that maintain body homeostasis oscillate during the day. Diurnal changes characterize kidney functions, comprising regulation of hydro-electrolytic and acid-base balance, reabsorption of small solutes and hormone production. Renal physiology is characterized by 24-h periodicity and contributes to circadian variability of blood pressure levels, related as well to nychthemeral changes of sodium sensitivity, physical activity, vascular tone, autonomic function and neurotransmitter release from sympathetic innervations. The circadian rhythmicity of body physiology is driven by central and peripheral biological clockworks and entrained by the geophysical light/dark cycle. Chronodisruption, defined as the mismatch between environmental–social cues and physiological–behavioral patterns, causes internal desynchronization of periodic functions, leading to pathophysiological mechanisms underlying degenerative, immune related, metabolic and neoplastic diseases. In this review we will address the genetic, molecular and anatomical elements that hardwire circadian rhythmicity in renal physiology and subtend disarray of time–dependent changes in renal pathology. PMID:23901050

Strain-level genomic and physiological variation in four Microbacterium spp.chromate reducers

EPA Science Inventory

Hexavalent chromium [Cr(VI)], a soluble carcinogen, has caused widespread contamination of soil and water in many industrial nations. Bacteria have been shown to be an active component in the geochemical cycling of chromium, but the mechanisms governing Cr(VI) reduction are poor...

Transcriptional profiling of mechanically and genetically sink-limited soybeans

USDA-ARS?s Scientific Manuscript database

The absence of a reproductive sink causes physiological and morphological changes in soybean plants. These include increased accumulation of nitrogen and starch in the leaves and delayed leaf senescence. To identify transcriptional changes that occur in leaves of these sink-limited plants, we used R...

Molecular mechanism of a COOH-terminal gating determinant in the ROMK channel revealed by a Bartter's disease mutation

PubMed Central

Flagg, Thomas P; Yoo, Dana; Sciortino, Christopher M; Tate, Margaret; Romero, Michael F; Welling, Paul A

2002-01-01

The ROMK subtypes of inward-rectifier K+ channels mediate potassium secretion and regulate NaCl reabsorption in the kidney. Loss-of-function mutations in this pH-sensitive K+ channel cause Bartter's disease, a familial salt wasting nephropathy. One disease-causing mutation truncates the extreme COOH-terminus and induces a closed gating conformation. Here we identify a region within the deleted domain that plays an important role in pH-dependent gating. The domain contains a structural element that functionally interacts with the pH sensor in the cytoplasmic NH2-terminus to set a physiological range of pH sensitivity. Removal of the domain shifts the pKa towards alkaline pH values, causing channel inactivation under physiological conditions. Suppressor mutations within the pH sensor rescued channel gating and trans addition of the cognate peptide restored pH sensitivity. A specific interdomain interaction was revealed in an in vitro protein-protein binding assay between the NH2- and COOH-terminal cytoplasmic domains expressed as bacterial fusion proteins. These results provide new insights into the molecular mechanisms underlying Kir channel regulation and channel gating defects that are associated with Bartter's disease. PMID:12381810

Research frontiers in drought-induced tree mortality: Crossing scales and disciplines

DOE PAGES

Hartmann, Henrik; Adams, Henry D.; Anderegg, William R. L.; ...

2015-01-12

Sudden and widespread forest die-back and die-off (e.g., Huang & Anderegg, 2012) and increased mortality rates (e.g., Peng et al., 2011) in many forest ecosystems across the globe have been linked to drought and elevated temperatures (Allen et al., 2010, Fig. 1). Furthermore, these observations have caused a focus on the physiological mechanisms of drought-induced tree mortality (e.g. McDowell et al., 2008) and many studies, both observational and manipulative, have been carried out to explain tree death during drought from a physiological perspective.

Interruption to cutaneous gas exchange is not a likely mechanism of WNS-associated death in bats.

PubMed

Carey, Charleve S; Boyles, Justin G

2015-07-01

Pseudogymnoascus destructans is the causative fungal agent of white-nose syndrome (WNS), an emerging fungal-borne epizootic. WNS is responsible for a catastrophic decline of hibernating bats in North America, yet we have limited understanding of the physiological interactions between pathogen and host. Pseudogymnoascus destructans severely damages wings and tail membranes, by causing dryness that leads to whole sections crumbling off. Four possible mechanisms have been proposed by which infection could lead to dehydration; in this study, we tested one: P. destructans infection could cause disruption to passive gas-exchange pathways across the wing membranes, thereby causing a compensatory increase in water-intensive pulmonary respiration. We hypothesized that total evaporative water loss would be greater when passive gas exchange was inhibited. We found that bats did not lose more water when passive pathways were blocked. This study provides evidence against the proposed proximal mechanism that disruption to passive gas exchange causes dehydration and death to WNS-infected bats. © 2015. Published by The Company of Biologists Ltd.

A mechano-acoustic model of the effect of superior canal dehiscence on hearing in chinchilla

PubMed Central

Songer, Jocelyn E.; Rosowski, John J.

2008-01-01

Superior canal dehiscence (SCD) is a pathological condition of the ear that can cause a conductive hearing loss. The effect of SCD (a hole in the bony wall of the superior semicircular canal) on chinchilla middle- and inner-ear mechanics is analyzed with a circuit model of the dehiscence. The model is used to predict the effect of dehiscence on auditory sensitivity and mechanics. These predictions are compared to previously published measurements of dehiscence related changes in chinchilla cochlear potential, middle-ear input admittance and stapes velocity. The comparisons show that the model predictions are both qualitatively and quantitatively similar to the physiological results for frequencies where physiologic data are available. The similarity supports the third-window hypothesis of the effect of superior canal dehiscence on auditory sensitivity and mechanics and provides the groundwork for the development of a model that predicts the effect of superior canal dehiscence syndrome on auditory sensitivity and mechanics in humans. PMID:17672643

Mechanisms of vascular aging: What can we learn from Hutchinson-Gilford progeria syndrome?

PubMed

Del Campo, Lara; Hamczyk, Magda R; Andrés, Vicente; Martínez-González, José; Rodríguez, Cristina

Aging is the main risk factor for cardiovascular disease (CVD). The increased prevalence of CVD is partly due to the global increase in life expectancy. In this context, it is essential to identify the mechanisms by which aging induces CVD, with the ultimate aim of reducing its incidence. Both atherosclerosis and heart failure significantly contribute to age-associated CVD morbidity and mortality. Hutchinson-Gilford progeria syndrome (HGPS) is a rare genetic disorder caused by the synthesis of progerin, which is noted for accelerated aging and CVD. This mutant form of prelamin A induces generalised atherosclerosis, vascular calcification, and cardiac electrophysiological abnormalities, leading to premature aging and death, mainly due to myocardial infarction and stroke. This review discusses the main vascular structural and functional abnormalities during physiological and premature aging, as well as the mechanisms involved in the exacerbated CVD and accelerated aging induced by the accumulation of progerin and prelamin A. Both proteins are expressed in non-HGPS individuals, and physiological aging shares many features of progeria. Research into HGPS could therefore shed light on novel mechanisms involved in the physiological aging of the cardiovascular system. Copyright © 2018 Sociedad Española de Arteriosclerosis. Publicado por Elsevier España, S.L.U. All rights reserved.

Does Conspecific Fighting Yield Conditioned Taste Aversion in Rats?

ERIC Educational Resources Information Center

Nakajima, Sadahiko; Kumazawa, Gaku; Ieki, Hayato; Hashimoto, Aya

2012-01-01

Running in an activity wheel yields conditioned aversion to a taste solution consumed before the running, but its underlying physiological mechanism is unknown. According to the claim that energy expenditure or general stress caused by physical exercise is a critical factor for this taste-aversion learning, not only running but also other…

Acid-base physiology, neurobiology and behaviour in relation to CO2-induced ocean acidification.

PubMed

Tresguerres, Martin; Hamilton, Trevor J

2017-06-15

Experimental exposure to ocean and freshwater acidification affects the behaviour of multiple aquatic organisms in laboratory tests. One proposed cause involves an imbalance in plasma chloride and bicarbonate ion concentrations as a result of acid-base regulation, causing the reversal of ionic fluxes through GABA A receptors, which leads to altered neuronal function. This model is exclusively based on differential effects of the GABA A receptor antagonist gabazine on control animals and those exposed to elevated CO 2 However, direct measurements of actual chloride and bicarbonate concentrations in neurons and their extracellular fluids and of GABA A receptor properties in aquatic organisms are largely lacking. Similarly, very little is known about potential compensatory mechanisms, and about alternative mechanisms that might lead to ocean acidification-induced behavioural changes. This article reviews the current knowledge on acid-base physiology, neurobiology, pharmacology and behaviour in relation to marine CO 2 -induced acidification, and identifies important topics for future research that will help us to understand the potential effects of predicted levels of aquatic acidification on organisms. © 2017. Published by The Company of Biologists Ltd.

Exertional Dyspnoea in Chronic Respiratory Diseases: From Physiology to Clinical Application.

PubMed

Dubé, Bruno-Pierre; Vermeulen, François; Laveneziana, Pierantonio

2017-02-01

Dyspnoea is a complex, highly personalized and multidimensional sensory experience, and its underlying cause and mechanisms are still being investigated. Exertional dyspnoea is one of the most frequently encountered symptoms of patients with cardiopulmonary diseases, and is a common reason for seeking medical help. As the symptom usually progresses with the underlying disease, it can lead to an avoidance of physical activity, peripheral muscle deconditioning and decreased quality of life. Dyspnoea is closely associated with quality of life, exercise (in)tolerance and prognosis in various conditions, including chronic obstructive pulmonary disease, heart failure, interstitial lung disease and pulmonary hypertension, and is therefore an important therapeutic target. Effective management and treatment of dyspnoea is an important challenge for caregivers, and therapeutic options that attempt to reverse its underlying cause have been only partially successful This "review" will attempt to shed light on the physiological mechanisms underlying dyspnoea during exercise and to translate/apply them to a broad clinical spectrum of cardio-respiratory disorders. Copyright © 2016 SEPAR. Publicado por Elsevier España, S.L.U. All rights reserved.

Evolutionary considerations in the development of chronic pelvic pain.

PubMed

Jarrell, John; Arendt-Nielsen, Lars

2016-08-01

Chronic pelvic pain is common among women of reproductive age and is associated with significant morbidity and comorbidities. In this Viewpoint, we explore the evolutionary cause of pelvic pain and summarize evidence that supports a menstruation-related evolutionary cause of chronic visceral pelvic pain: (1) lifetime menstruation has increased; (2) severe dysmenorrhea is common in the chronic pelvic pain population, particularly among those with pain sensitization; and (3) a potential biological mechanism can be identified. Thus, chronic pelvic pain may arise from the mismatch between the slow pace of biological evolution in our bodies and the relatively rapid pace of cultural changes that have resulted in increased menstrual frequency due to earlier menarche, later mortality, and lower fecundity. One possible mechanism that explains the development of persistent pain from repeated episodes of intermittent pain is hyperalgesic priming, a physiological process defined as a long-lasting latent hyperresponsiveness of nociceptors to inflammatory mediators after an inflammatory or neuropathic insult. The repetitive severely painful menstrual episodes may play such a role. From an evolutionary perspective the relatively rapid increase in lifetime menstruation experience in contemporary society may contribute to a mismatch between lifetime menstruation and the physiological pain processes, leading to a maladaptive state of chronic visceral pelvic pain. Our current physiology does not conform to current human needs. Copyright © 2016 Elsevier Inc. All rights reserved.

Human physiological responses to cold exposure: Acute responses and acclimatization to prolonged exposure.

PubMed

Castellani, John W; Young, Andrew J

2016-04-01

Cold exposure in humans causes specific acute and chronic physiological responses. This paper will review both the acute and long-term physiological responses and external factors that impact these physiological responses. Acute physiological responses to cold exposure include cutaneous vasoconstriction and shivering thermogenesis which, respectively, decrease heat loss and increase metabolic heat production. Vasoconstriction is elicited through reflex and local cooling. In combination, vasoconstriction and shivering operate to maintain thermal balance when the body is losing heat. Factors (anthropometry, sex, race, fitness, thermoregulatory fatigue) that influence the acute physiological responses to cold exposure are also reviewed. The physiological responses to chronic cold exposure, also known as cold acclimation/acclimatization, are also presented. Three primary patterns of cold acclimatization have been observed, a) habituation, b) metabolic adjustment, and c) insulative adjustment. Habituation is characterized by physiological adjustments in which the response is attenuated compared to an unacclimatized state. Metabolic acclimatization is characterized by an increased thermogenesis, whereas insulative acclimatization is characterized by enhancing the mechanisms that conserve body heat. The pattern of acclimatization is dependent on changes in skin and core temperature and the exposure duration. Published by Elsevier B.V.

A short pulse of mechanical force induces gene expression and growth in MC3T3-E1 osteoblasts via an ERK 1/2 pathway

NASA Technical Reports Server (NTRS)

Hatton, Jason P.; Pooran, Milad; Li, Chai-Fei; Luzzio, Chris; Hughes-Fulford, Millie

2003-01-01

Physiological mechanical loading is crucial for maintenance of bone integrity and architecture. We have calculated the strain caused by gravity stress on osteoblasts and found that 4-30g corresponds to physiological levels of 40-300 microstrain. Short-term gravity loading (15 minutes) induced a 15-fold increase in expression of growth-related immediate early gene c-fos, a 5-fold increase in egr-1, and a 3-fold increase in autocrine bFGF. The non-growth-related genes EP-1, TGF-beta, and 18s were unaffected by gravity loading. Short-term physiological loading induced extracellular signal-regulated kinase (ERK 1/2) phosphorylation in a dose-dependent manner with maximum phosphorylation saturating at mechanical loading levels of 12g (p < 0.001) with no effect on total ERK. The phosphorylation of focal adhesion kinase (FAK) was unaffected by mechanical force. g-Loading did not activate P38 MAPK or c-jun N-terminal kinase (JNK). Additionally, a gravity pulse resulted in the localization of phosphorylated ERK 1/2 to the nucleus; this did not occur in unloaded cells. The induction of c-fos was inhibited 74% by the MEK1/2 inhibitor U0126 (p < 0.001) but was not affected by MEK1 or p38 MAPK-specific inhibitors. The long-term consequence of a single 15-minute gravity pulse was a 64% increase in cell growth (p < 0.001). U0126 significantly inhibited gravity-induced growth by 50% (p < 0.001). These studies suggest that short periods of physiological mechanical stress induce immediate early gene expression and growth in MC3T3-E1 osteoblasts primarily through an ERK 1/2-mediated pathway.

Developmental Ethanol Exposure Leads to Dysregulation of Lipid Metabolism and Oxidative Stress in Drosophila

PubMed Central

Logan-Garbisch, Theresa; Bortolazzo, Anthony; Luu, Peter; Ford, Audrey; Do, David; Khodabakhshi, Payam; French, Rachael L.

2014-01-01

Ethanol exposure during development causes an array of developmental abnormalities, both physiological and behavioral. In mammals, these abnormalities are collectively known as fetal alcohol effects (FAE) or fetal alcohol spectrum disorder (FASD). We have established a Drosophila melanogaster model of FASD and have previously shown that developmental ethanol exposure in flies leads to reduced expression of insulin-like peptides (dILPs) and their receptor. In this work, we link that observation to dysregulation of fatty acid metabolism and lipid accumulation. Further, we show that developmental ethanol exposure in Drosophila causes oxidative stress, that this stress is a primary cause of the developmental lethality and delay associated with ethanol exposure, and, finally, that one of the mechanisms by which ethanol increases oxidative stress is through abnormal fatty acid metabolism. These data suggest a previously uncharacterized mechanism by which ethanol causes the symptoms associated with FASD. PMID:25387828

Ageing and moisture uptake in polymethyl methacrylate (PMMA) bone cements☆

PubMed Central

Ayre, Wayne Nishio; Denyer, Stephen P.; Evans, Samuel L.

2014-01-01

Bone cements are extensively employed in orthopaedics for joint arthroplasty, however implant failure in the form of aseptic loosening is known to occur after long-term use. The exact mechanism causing this is not well understood, however it is thought to arise from a combination of fatigue and chemical degradation resulting from the hostile in vivo environment. In this study, two commercial bone cements were aged in an isotonic fluid at physiological temperatures and changes in moisture uptake, microstructure and mechanical and fatigue properties were studied. Initial penetration of water into the cement followed Fickian diffusion and was thought to be caused by vacancies created by leaching monomer. An increase in weight of approximately 2% was experienced after 30 days ageing and was accompanied by hydrolysis of poly(methyl methacrylate) (PMMA) in the outermost layers of the cement. This molecular change and the plasticising effect of water resulted in reduced mechanical and fatigue properties over time. Cement ageing is therefore thought to be a key contributor in the long-term failure of cemented joint replacements. The results from this study have highlighted the need to develop cements capable of withstanding long-term degradation and for more accurate test methods, which fully account for physiological ageing. PMID:24445003

Ageing and moisture uptake in polymethyl methacrylate (PMMA) bone cements.

PubMed

Ayre, Wayne Nishio; Denyer, Stephen P; Evans, Samuel L

2014-04-01

Bone cements are extensively employed in orthopaedics for joint arthroplasty, however implant failure in the form of aseptic loosening is known to occur after long-term use. The exact mechanism causing this is not well understood, however it is thought to arise from a combination of fatigue and chemical degradation resulting from the hostile in vivo environment. In this study, two commercial bone cements were aged in an isotonic fluid at physiological temperatures and changes in moisture uptake, microstructure and mechanical and fatigue properties were studied. Initial penetration of water into the cement followed Fickian diffusion and was thought to be caused by vacancies created by leaching monomer. An increase in weight of approximately 2% was experienced after 30 days ageing and was accompanied by hydrolysis of poly(methyl methacrylate) (PMMA) in the outermost layers of the cement. This molecular change and the plasticising effect of water resulted in reduced mechanical and fatigue properties over time. Cement ageing is therefore thought to be a key contributor in the long-term failure of cemented joint replacements. The results from this study have highlighted the need to develop cements capable of withstanding long-term degradation and for more accurate test methods, which fully account for physiological ageing. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.

A novel initiation mechanism of death in Streptococcus pneumoniae induced by the human milk protein-lipid complex HAMLET and activated during physiological death.

PubMed

Clementi, Emily A; Marks, Laura R; Duffey, Michael E; Hakansson, Anders P

2012-08-03

To cause colonization or infection, most bacteria grow in biofilms where differentiation and death of subpopulations is critical for optimal survival of the whole population. However, little is known about initiation of bacterial death under physiological conditions. Membrane depolarization has been suggested, but never shown to be involved, due to the difficulty of performing such studies in bacteria and the paucity of information that exists regarding ion transport mechanisms in prokaryotes. In this study, we performed the first extensive investigation of ion transport and membrane depolarization in a bacterial system. We found that HAMLET, a human milk protein-lipid complex, kills Streptococcus pneumoniae (the pneumococcus) in a manner that shares features with activation of physiological death from starvation. Addition of HAMLET to pneumococci dissipated membrane polarity, but depolarization per se was not enough to trigger death. Rather, both HAMLET- and starvation-induced death of pneumococci specifically required a sodium-dependent calcium influx, as shown using calcium and sodium transport inhibitors. This mechanism was verified under low sodium conditions, and in the presence of ionomycin or monensin, which enhanced pneumococcal sensitivity to HAMLET- and starvation-induced death. Pneumococcal death was also inhibited by kinase inhibitors, and indicated the involvement of Ser/Thr kinases in these processes. The importance of this activation mechanism was made evident, as dysregulation and manipulation of physiological death was detrimental to biofilm formation, a hallmark of bacterial colonization. Overall, our findings provide novel information on the role of ion transport during bacterial death, with the potential to uncover future antimicrobial targets.

A Novel Initiation Mechanism of Death in Streptococcus pneumoniae Induced by the Human Milk Protein-Lipid Complex HAMLET and Activated during Physiological Death*

PubMed Central

Clementi, Emily A.; Marks, Laura R.; Duffey, Michael E.; Hakansson, Anders P.

2012-01-01

To cause colonization or infection, most bacteria grow in biofilms where differentiation and death of subpopulations is critical for optimal survival of the whole population. However, little is known about initiation of bacterial death under physiological conditions. Membrane depolarization has been suggested, but never shown to be involved, due to the difficulty of performing such studies in bacteria and the paucity of information that exists regarding ion transport mechanisms in prokaryotes. In this study, we performed the first extensive investigation of ion transport and membrane depolarization in a bacterial system. We found that HAMLET, a human milk protein-lipid complex, kills Streptococcus pneumoniae (the pneumococcus) in a manner that shares features with activation of physiological death from starvation. Addition of HAMLET to pneumococci dissipated membrane polarity, but depolarization per se was not enough to trigger death. Rather, both HAMLET- and starvation-induced death of pneumococci specifically required a sodium-dependent calcium influx, as shown using calcium and sodium transport inhibitors. This mechanism was verified under low sodium conditions, and in the presence of ionomycin or monensin, which enhanced pneumococcal sensitivity to HAMLET- and starvation-induced death. Pneumococcal death was also inhibited by kinase inhibitors, and indicated the involvement of Ser/Thr kinases in these processes. The importance of this activation mechanism was made evident, as dysregulation and manipulation of physiological death was detrimental to biofilm formation, a hallmark of bacterial colonization. Overall, our findings provide novel information on the role of ion transport during bacterial death, with the potential to uncover future antimicrobial targets. PMID:22700972

Neuromuscular fatigue in racquet sports.

PubMed

Girard, Olivier; Millet, Grégoire P

2008-02-01

This article describes the physiologic and neural mechanisms that cause neuromuscular fatigue in racquet sports: table tennis, tennis, squash, and badminton. In these intermittent and dual activities, performance may be limited as a match progresses because of a reduced central activation, linked to changes in neurotransmitter concentration or in response to afferent sensory feedback. Alternatively, modulation of spinal loop properties may occur because of changes in metabolic or mechanical properties within the muscle. Finally, increased fatigue manifested by mistimed strokes, lower speed, and altered on-court movements may be caused by ionic disturbances and impairments in excitation-contraction coupling properties. These alterations in neuromuscular function contribute to decrease in racquet sports performance observed under fatigue.

Neuromuscular fatigue in racquet sports.

PubMed

Girard, Olivier; Millet, Grégoire P

2009-02-01

This article describes the physiologic and neural mechanisms that cause neuromuscular fatigue in racquet sports: table tennis, tennis, squash, and badminton. In these intermittent and dual activities, performance may be limited as a match progresses because of a reduced central activation, linked to changes in neurotransmitter concentration or in response to afferent sensory feedback. Alternatively, modulation of spinal loop properties may occur because of changes in metabolic or mechanical properties within the muscle. Finally, increased fatigue manifested by mistimed strokes, lower speed, and altered on-court movements may be caused by ionic disturbances and impairments in excitation-contraction coupling properties. These alterations in neuromuscular function contribute to decrease in racquet sports performance observed under fatigue.

[Magnesium disorder in metabolic bone diseases].

PubMed

Ishii, Akira; Imanishi, Yasuo

2012-08-01

Magnesium is abundantly distributed among the body. The half of the magnesium exists in the bone. In addition, magnesium is the second most abundant intracellular cation in vertebrates and essential for maintaining physiological function of the cells. Epidemiologic studies have demonstrated that magnesium deficiency is a risk factor for osteoporosis. The mechanism of bone fragility caused by magnesium deficiency has been intensely studied using animal models of magnesium deficiency. Magnesium deficiency causes decreased osteoblastic function and increased number of osteoclasts. Magnesium deficiency also accelerates mineralization in bone. These observations suggest that disturbed bone metabolic turnover and mineralization causes bone fragility.

Autonomic consequences of arousal from sleep: mechanisms and implications.

PubMed

Horner, R L

1996-12-01

Normal spontaneous arousals from sleep are associated with transient increases in blood pressure, heart rate, and ventilation caused by large transient changes in autonomic output. These autonomic changes are out of proportion to obvious physiological need and are in excess of those observed in later periods of quiet wakefulness. This paper discusses some of the mechanisms underlying the cardio-respiratory consequences of arousal from sleep, and discusses why the normal onset of wakefulness may be associated with such large changes in autonomic output.

Clinical Evidence for the Relationship between Nail Configuration and Mechanical Forces

PubMed Central

Ogawa, Rei

2014-01-01

Summary: Mechanobiology is an emerging field of science that focuses on the way physical forces and changes in cell or tissue mechanics contribute to development, physiology, and disease. As nails are always exposed to physical stimulation, mechanical forces may have a particularly pronounced effect on nail configuration and could be involved in the development of nail deformities. However, the role of mechanobiology in nail configuration and deformities has rarely been assessed. This review describes what is currently understood regarding the effect of mechanical force on nail configuration and deformities. On the basis of these observations, we hypothesize that nails have an automatic curvature function that allows them to adapt to the daily upward mechanical forces. Under normal conditions, the upward daily mechanical force and the automatic curvature force are well balanced. However, an imbalance between these 2 forces may cause nail deformation. For example, pincer nails may be caused by the absence of upward mechanical forces or a genetic propensity increase in the automatic curvature force, whereas koilonychias may occur when the upward mechanical force exceeds the automatic curvature force, thereby causing the nail to curve outward. This hypothesis is a new concept that could aid the development of innovative methods to prevent and treat nail deformities. PMID:25289309

Numerical investigation on effect of aortic root geometry on flow induced structural stresses developed in a bileaflet mechanical heart valve

NASA Astrophysics Data System (ADS)

Abbas, S. S.; Nasif, M. S.; Said, M. A. M.; Kadhim, S. K.

2017-10-01

Structural stresses developed in an artificial bileaflet mechanical heart valve (BMHV) due to pulsed blood flow may cause valve failure due to yielding. In this paper, von-Mises stresses are computed and compared for BMHV placed in two types of aortic root geometries that are aortic root with axisymmetric sinuses and with axisymmetric bulb, at different physiological blood flow rates. With BMHV placed in an aortic root with axisymmetric sinuses, the von-Mises stresses developed in the valve were found to be up to 47% higher than BMHV placed in aortic root with axisymmetric bulb under similar physiological conditions. High velocity vectors and therefore high von-Mises stresses have been observed for BMHV placed in aortic root with axisymmetric sinuses, that can lead to valve failure.

Bryophyte physiological responses to, and recovery from, long-term nitrogen deposition and phosphorus fertilisation in acidic grassland.

PubMed

Arróniz-Crespo, María; Leake, Jonathan R; Horton, Peter; Phoenix, Gareth K

2008-01-01

Atmospheric nitrogen deposition can cause major declines in bryophyte abundance yet the physiological basis for such declines is not fully understood. Bryophyte physiological responses may also be sensitive bioindicators of both the impacts of, and recovery from, N deposition. Here, responses of tissue nutrients (nitrogen (N), phosphorus (P) and potassium (K): NPK), N and P metabolism enzymes (nitrate reductase and phosphomonoesterase), photosynthetic pigments, chlorophyll fluorescence, sclerophylly and percentage cover of two common bryophytes (Pseudoscleropodium purum and Rhytidiadelphus squarrosus) to long-term (11 yr) enhanced N deposition (+3.5 and +14 g N m(-2) yr(-1)) are reported in factorial combination with P addition. Recovery of responses 22 months after treatment cessation were also assessed. Enhanced N deposition caused up to 90% loss of bryophyte cover but no recovery was observed. Phosphomonoesterase activity and tissue N:P ratios increased up to threefold in response to N loading and showed clear recovery, particularly in P. purum. Smaller responses and recovery were also seen in all chlorophyll fluorescence measurements and altered photosynthetic pigment composition. The P limitation of growth appears to be a key mechanism driving bryophyte loss along with damage to photosystem II. Physiological measurements are more sensitive than measurements of abundance as bioindicators of N deposition impact and of recovery in particular.

Electromechanical heterogeneity in the heart : A key to long QT syndrome?

PubMed

Dressler, F F; Brado, J; Odening, K E

2018-03-01

In the healthy heart, physiological heterogeneities in structure and in electrical and mechanical activity are crucial for normal, efficient excitation and pumping. Alterations of heterogeneity have been linked to arrhythmogenesis in various cardiac disorders such as long QT syndrome (LQTS). This inherited arrhythmia disorder is caused by mutations in different ion channel genes and is characterized by (heterogeneously) prolonged cardiac repolarization and increased risk for ventricular tachycardia, syncope and sudden cardiac death. Cardiac electrical and mechanical function are not independent of each other but interact in a bidirectional manner by electromechanical and mechano-electrical coupling. Therefore, changes in either process will affect the other. Recent experimental and clinical evidence suggests that LQTS, which is primarily considered an "electrical" disorder, also exhibits features of disturbed mechanical function and heterogeneity, which in turn appears to correlate with the risk of arrhythmia in the individual patient. In this review, we give a short overview of the current knowledge about physiological and pathological, long QT-related electrical and mechanical heterogeneity in the heart. Also, their respective roles for future risk prediction approaches in LQTS are discussed.

[Research Progress on the Interaction Effects and Its Neural Mechanisms between Physical Fatigue and Mental Fatigue].

PubMed

Zhang, Lixin; Zhang, Chuncui; He, Feng; Zhao, Xin; Qi, Hongzhi; Wan, Baikun; Ming, Dong

2015-10-01

Fatigue is an exhaustion state caused by prolonged physical work and mental work, which can reduce working efficiency and even cause industrial accidents. Fatigue is a complex concept involving both physiological and psychological factors. Fatigue can cause a decline of concentration and work performance and induce chronic diseases. Prolonged fatigue may endanger life safety. In most of the scenarios, physical and mental workloads co-lead operator into fatigue state. Thus, it is very important to study the interaction influence and its neural mechanisms between physical and mental fatigues. This paper introduces recent progresses on the interaction effects and discusses some research challenges and future development directions. It is believed that mutual influence between physical fatigue and mental fatigue may occur in the central nervous system. Revealing the basal ganglia function and dopamine release may be important to explore the neural mechanisms between physical fatigue and mental fatigue. Future effort is to optimize fatigue models, to evaluate parameters and to explore the neural mechanisms so as to provide scientific basis and theoretical guidance for complex task designs and fatigue monitoring.

Development and Validation of a Bioreactor System for Dynamic Loading and Mechanical Characterization of Whole Human Intervertebral Discs in Organ Culture

PubMed Central

Walter, BA; Illien-Junger, S; Nasser, P; Hecht, AC; Iatridis, JC

2014-01-01

Intervertebral disc (IVD) degeneration is a common cause of back pain, and attempts to develop therapies are frustrated by lack of model systems that mimic the human condition. Human IVD organ culture models can address this gap, yet current models are limited since vertebral endplates are removed to maintain cell viability, physiological loading is not applied, and mechanical behaviors are not measured. This study aimed to (i) establish a method for isolating human IVDs from autopsy with intact vertebral endplates, and (ii) develop and validate an organ culture loading system for human or bovine IVDs. Human IVDs with intact endplates were isolated from cadavers within 48 hours of death and cultured for up to 21 days. IVDs remained viable with ~80% cell viability in nucleus and annulus regions. A dynamic loading system was designed and built with the capacity to culture 9 bovine or 6 human IVDs simultaneously while applying simulated physiologic loads (maximum force: 4kN) and measuring IVD mechanical behaviors. The loading system accurately applied dynamic loading regimes (RMS error <2.5N and total harmonic distortion <2.45%), and precisely evaluated mechanical behavior of rubber and bovine IVDs. Bovine IVDs maintained their mechanical behavior and retained >85% viable cells throughout the 3 week culture period. This organ culture loading system can closely mimic physiological conditions and be used to investigate response of living human and bovine IVDs to mechanical and chemical challenges and to screen therapeutic repair techniques. PMID:24725441

The effect of extreme spring weather on body condition and stress physiology in Lapland longspurs and white-crowned sparrows breeding in the Arctic.

PubMed

Krause, Jesse S; Pérez, Jonathan H; Chmura, Helen E; Sweet, Shannan K; Meddle, Simone L; Hunt, Kathleen E; Gough, Laura; Boelman, Natalie; Wingfield, John C

2016-10-01

Climate change is causing rapid shifts in temperature while also increasing the frequency, duration, and intensity of extreme weather. In the northern hemisphere, the spring of 2013 was characterized as extreme due to record high snow cover and low temperatures. Studies that describe the effects of extreme weather on phenology across taxa are limited while morphological and physiological responses remain poorly understood. Stress physiology, as measured through baseline and stress-induced concentrations of cortisol or corticosterone, has often been studied to understand how organisms respond to environmental stressors. We compared body condition and stress physiology of two long-distance migrants breeding in low arctic Alaska - the white-crowned sparrow (Zonotrichia leucophrys) and Lapland longspur (Calcarius lapponicus) - in 2013, an extreme weather year, with three more typical years (2011, 2012, and 2014). The extended snow cover in spring 2013 caused measureable changes in phenology, body condition and physiology. Arrival timing for both species was delayed 4-5days compared to the other three years. Lapland longspurs had reduced fat stores, pectoralis muscle profiles, body mass, and hematocrit levels, while stress-induced concentrations of corticosterone were increased. Similarly, white-crowned sparrows had reduced pectoralis muscle profiles and hematocrit levels, but in contrast to Lapland longspurs, had elevated fat stores and no difference in mass or stress physiology relative to other study years. An understanding of physiological mechanisms that regulate coping strategies is of critical importance for predicting how species will respond to the occurrence of extreme events in the future due to global climate change. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Morpho-Physiological and Proteome Level Responses to Cadmium Stress in Sorghum

PubMed Central

Kamal, Abu Hena Mostafa; Kim, Sang-Woo; Oh, Myeong-Won; Lee, Moon-Soon; Chung, Keun-Yook; Xin, Zhanguo; Woo, Sun-Hee

2016-01-01

Cadmium (Cd) stress may cause serious morphological and physiological abnormalities in addition to altering the proteome in plants. The present study was performed to explore Cd-induced morpho-physiological alterations and their potential associated mechanisms in Sorghum bicolor leaves at the protein level. Ten-day-old sorghum seedlings were exposed to different concentrations (0, 100, and 150 μM) of CdCl2, and different morpho-physiological responses were recorded. The effects of Cd exposure on protein expression patterns in S. bicolor were investigated using two-dimensional gel electrophoresis (2-DE) in samples derived from the leaves of both control and Cd-treated seedlings. The observed morphological changes revealed that the plants treated with Cd displayed dramatically altered shoot lengths, fresh weights and relative water content. In addition, the concentration of Cd was markedly increased by treatment with Cd, and the amount of Cd taken up by the shoots was significantly and directly correlated with the applied concentration of Cd. Using the 2-DE method, a total of 33 differentially expressed protein spots were analyzed using MALDI-TOF/TOF MS. Of these, treatment with Cd resulted in significant increases in 15 proteins and decreases in 18 proteins. Major changes were absorbed in the levels of proteins known to be involved in carbohydrate metabolism, transcriptional regulation, translation and stress responses. Proteomic results revealed that Cd stress had an inhibitory effect on carbon fixation, ATP production and the regulation of protein synthesis. Our study provides insights into the integrated molecular mechanisms involved in responses to Cd and the effects of Cd on the growth and physiological characteristics of sorghum seedlings. We have aimed to provide a reference describing the mechanisms involved in heavy metal damage to plants. PMID:26919231

Thyrotoxicosis.

PubMed

Seigel, Stuart C; Hodak, Steven P

2012-03-01

Hyperthyroidism describes the sustained increase in thyroid hormone biosynthesis and secretion by a thyroid gland with increased metabolism. Although the use of radioiodine scanning serves as a useful surrogate that may help characterize the cause of thyrotoxicosis, it only indirectly addresses the underlying physiologic mechanism driving the increase in serum thyroid hormones. In this article, thyrotoxic states are divided into increased or decreased thyroid metabolic function. In addition to the diagnosis, clinical presentation, and treatment of the various causes of hyperthyroidism, a section on functional imaging and appropriate laboratory testing is included. Copyright © 2012 Elsevier Inc. All rights reserved.

Exacerbation of pre-existing diabetes insipidus during pregnancy, mechanisms and management.

PubMed

Tack, Lloyd J W; T'Sjoen, Guy; Lapauw, Bruno

2017-06-01

During pregnancy, physiological changes in osmotic homeostasis cause water retention. If excessive, this can cause gestational diabetes insipidus (DI), particularly in patients with already impaired vasopressin secretion. We present the case of a 34-year-old patient with pre-existing hypopituitarism who experienced a transient exacerbation of her DI during a twin pregnancy. In contrast to typical gestational DI, polyuria and polydipsia occurred during the first trimester and remained stable thereafter. This case highlights a challenging clinical entity of which pathophysiology, diagnostic approach and treatment will be discussed.

Channelopathies from Mutations in the Cardiac Sodium Channel Protein Complex

PubMed Central

Adsit, Graham S.; Vaidyanathan, Ravi; Galler, Carla M.; Kyle, John W.; Makielski, Jonathan C.

2013-01-01

The cardiac sodium current underlies excitability in heart, and inherited abnormalities of the proteins regulating and conducting this current cause inherited arrhythmia syndromes. This review focuses on inherited mutations in non-pore forming proteins of sodium channel complexes that cause cardiac arrhythmia, and the deduced mechanisms by which they affect function and dysfunction of the cardiac sodium current. Defining the structure and function of these complexes and how they are regulated will contribute to understanding the possible roles for this complex in normal and abnormal physiology and homeostasis. PMID:23557754

Investigation of erectile dysfunction.

PubMed

Patel, D V; Halls, J; Patel, U

2012-11-01

Erectile dysfunction (ED) represents a common and debilitating condition with a wide range of organic and non-organic causes. Physical aetiologies can be divided into disorders affecting arterial inflow, the venous occlusion mechanism or the penile structure itself. Various imaging modalities can be utilised to investigate the physical causes of ED, but penile Doppler sonography (PDS) is the most informative technique, indicated in those patients with ED who do not respond to oral pharmacological agents (e.g. phosphodiesterase type 5 inhibitors). This review will examine the anatomical and physiological basis of penile erection, the method for performing PDS and features of specific causes of ED, and will also consider the alternative imaging modalities available.

Modeling fatigue.

PubMed

Sumner, Walton; Xu, Jin Zhong

2002-01-01

The American Board of Family Practice is developing a patient simulation program to evaluate diagnostic and management skills. The simulator must give temporally and physiologically reasonable answers to symptom questions such as "Have you been tired?" A three-step process generates symptom histories. In the first step, the simulator determines points in time where it should calculate instantaneous symptom status. In the second step, a Bayesian network implementing a roughly physiologic model of the symptom generates a value on a severity scale at each sampling time. Positive, zero, and negative values represent increased, normal, and decreased status, as applicable. The simulator plots these values over time. In the third step, another Bayesian network inspects this plot and reports how the symptom changed over time. This mechanism handles major trends, multiple and concurrent symptom causes, and gradually effective treatments. Other temporal insights, such as observations about short-term symptom relief, require complimentary mechanisms.

Survival, physical and physiological changes of Taenia hydatigena eggs under different conditions of water stress.

PubMed

Sánchez Thevenet, Paula; Alvarez, Hector Manuel; Basualdo, Juan Angel

2017-06-01

Taenia hydatigena eggs were investigated for morphological and physiological changes under water stress conditions. Fresh eggs were exposed at 31%, 47% and 89% of relative humidity (RH), and survival, size and ultrastructural changes were accounted up to 365 days of exposition. The article shows how each RH environment affects the vitality of the eggs. Results of this study suggest that T. hydatigena eggs have mechanisms to withstand water stress, indicating that the eggs clustering improves protection against desiccation, and that endogenous metabolism using triacylglycerols play an important role in the maintenance of embryo vitality under low, medium and high relative humidity conditions. This contributes to understanding the water stress resistance mechanism in eggs belonging to Taeniidae family. The findings shown herein have provided a basis to better comprehend basic biology and epidemiology of the cysticercosis caused by T. hydatigena. Copyright © 2017 Elsevier Inc. All rights reserved.

Hatching behavior in turtles.

PubMed

Spencer, Ricky-John; Janzen, Fredric J

2011-07-01

Incubation temperature plays a prominent role in shaping the phenotypes and fitness of embryos, including affecting developmental rates. In many taxa, including turtles, eggs are deposited in layers such that thermal gradients alter developmental rates within a nest. Despite this thermal effect, a nascent body of experimental work on environmentally cued hatching in turtles has revealed unexpected synchronicity in hatching behavior. This review discusses environmental cues for hatching, physiological mechanisms behind synchronous hatching, proximate and ultimate causes for this behavior, and future directions for research. Four freshwater turtle species have been investigated experimentally, with hatching in each species elicited by different environmental cues and responding via various physiological mechanisms. Hatching of groups of eggs in turtles apparently involves some level of embryo-embryo communication and thus is not a purely passive activity. Although turtles are not icons of complex social behavior, life-history theory predicts that the group environment of the nest can drive the evolution of environmentally cued hatching.

Effects of exercise on tumor physiology and metabolism.

PubMed

Pedersen, Line; Christensen, Jesper Frank; Hojman, Pernille

2015-01-01

Exercise is a potent regulator of a range of physiological processes in most tissues. Solid epidemiological data show that exercise training can reduce disease risk and mortality for several cancer diagnoses, suggesting that exercise training may directly regulate tumor physiology and metabolism. Here, we review the body of literature describing exercise intervention studies performed in rodent tumor models and elaborate on potential mechanistic effects of exercise on tumor physiology. Exercise has been shown to reduce tumor incidence, tumor multiplicity, and tumor growth across numerous different transplantable, chemically induced or genetic tumor models. We propose 4 emerging mechanistic effects of exercise, including (1) vascularization and blood perfusion, (2) immune function, (3) tumor metabolism, and (4) muscle-to-cancer cross-talk, and discuss these in details. In conclusion, exercise training has the potential to be a beneficial and integrated component of cancer management, but has yet to fully elucidate its potential. Understanding the mechanistic effects of exercise on tumor physiology is warranted. Insight into these mechanistic effects is emerging, but experimental intervention studies are still needed to verify the cause-effect relationship between these mechanisms and the control of tumor growth.

The importance of physiological ecology in conservation biology

USGS Publications Warehouse

Tracy, C.R.; Nussear, K.E.; Esque, T.C.; Dean-Bradley, K.; DeFalco, L.A.; Castle, K.T.; Zimmerman, L.C.; Espinoza, R.E.; Barber, A.M.

2006-01-01

Many of the threats to the persistence of populations of sensitive species have physiological or pathological mechanisms, and those mechanisms are best understood through the inherently integrative discipline of physiological ecology. The desert tortoise was listed under the Endangered Species Act largely due to a newly recognized upper respiratory disease thought to cause mortality in individuals and severe declines in populations. Numerous hypotheses about the threats to the persistence of desert tortoise populations involve acquisition of nutrients, and its connection to stress and disease. The nutritional wisdom hypothesis posits that animals should forage not for particular food items, but instead, for particular nutrients such as calcium and phosphorus used in building bones. The optimal foraging hypothesis suggests that, in circumstances of resource abundance, tortoises should forage as dietary specialists as a means of maximizing intake of resources. The optimal digestion hypothesis suggests that tortoises should process ingesta in ways that regulate assimilation rate. Finally, the cost-of-switching hypothesis suggests that herbivores, like the desert tortoise, should avoid switching food types to avoid negatively affecting the microbe community responsible for fermenting plants into energy and nutrients. Combining hypotheses into a resource acquisition theory leads to novel predictions that are generally supported by data presented here. Testing hypotheses, and synthesizing test results into a theory, provides a robust scientific alternative to the popular use of untested hypotheses and unanalyzed data to assert the needs of species. The scientific approach should focus on hypotheses concerning anthropogenic modifications of the environment that impact physiological processes ultimately important to population phenomena. We show how measurements of such impacts as nutrient starvation, can cause physiological stress, and that the endocrine mechanisms involved with stress can result in disease. Finally, our new syntheses evince a new hypothesis. Free molecules of the stress hormone corticosterone can inhibit immunity, and the abundance of "free corticosterone" in the blood (thought to be the active form of the hormone) is regulated when the corticosterone molecules combine with binding globulins. The sex hormone, testosterone, combines with the same binding globulin. High levels of testosterone, naturally occurring in the breeding season, may be further enhanced in populations at high densities, and the resulting excess testosterone may compete with binding globulins, thereby releasing corticosterone and reducing immunity to disease. This sequence could result in physiological and pathological phenomena leading to population cycles with a period that would be essentially impossible to observe in desert tortoise. Such cycles could obscure population fluctuations of anthropogenic origin. ?? 2006 The Author(s).

Integration of the response to a dietary potassium load: a paleolithic perspective.

PubMed

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(+).

A mechanism for sickness sleep: lessons from invertebrates.

PubMed

Davis, Kristen C; Raizen, David M

2017-08-15

During health, animal sleep is regulated by an internal clock and by the duration of prior wakefulness. During sickness, sleep is regulated by cytokines released from either peripheral cells or from cells within the nervous system. These cytokines regulate central nervous system neurons to induce sleep. Recent research in the invertebrates Caenorhabditis elegans and Drosophila melanogaster has led to new insights into the mechanism of sleep during sickness. Sickness is triggered by exposure to environments such as infection, heat, or ultraviolet light irradiation, all of which cause cellular stress. Epidermal growth factor is released from stressed cells and signals to activate central neuroendocrine cell(s). These neuron(s) release neuropeptides including those containing an amidated arginine(R)-phenylalanine(F) motif at their C-termini (RFamide peptides). Importantly, mechanisms regulating sickness sleep are partially distinct from those regulating healthy sleep. We will here review key findings that have elucidated the central neuroendocrine mechanism of sleep during sickness. Adaptive mechanisms employed in the control of sickness sleep may play a role in correcting cellular homeostasis after various insults. We speculate that these mechanisms may play a maladaptive role in human pathological conditions such as in the fatigue and anorexia associated with autoimmune diseases, with major depression, and with unexplained chronic fatigue. © 2016 The Authors. The Journal of Physiology © 2016 The Physiological Society.

Basic mechanisms of urgency: roles and benefits of pharmacotherapy.

PubMed

Michel, Martin Christian; Chapple, Christopher R

2009-12-01

Since urgency is key to the overactive bladder syndrome, we have reviewed the mechanisms underlying how bladder filling and urgency are sensed, what causes urgency and how this relates to medical therapy. Review of published literature. As urgency can only be assessed in cognitively intact humans, mechanistic studies of urgency often rely on proxy or surrogate parameters, such as detrusor overactivity, but these may not necessarily be reliable. There is an increasing evidence base to suggest that the sensation of ‘urgency’ differs from the normal physiological urge to void upon bladder filling. While the relative roles of alterations in afferent processes, central nervous processing, efferent mechanisms and in intrinsic bladder smooth muscle function remain unclear, and not necessarily mutually exclusive, several lines of evidence support an important role for the latter. A better understanding of urgency and its causes may help to develop more effective treatments for voiding dysfunction.

Microbial stress-response physiology and its implications for ecosystem function.

PubMed

Schimel, Joshua; Balser, Teri C; Wallenstein, Matthew

2007-06-01

Microorganisms have a variety of evolutionary adaptations and physiological acclimation mechanisms that allow them to survive and remain active in the face of environmental stress. Physiological responses to stress have costs at the organismal level that can result in altered ecosystem-level C, energy, and nutrient flows. These large-scale impacts result from direct effects on active microbes' physiology and by controlling the composition of the active microbial community. We first consider some general aspects of how microbes experience environmental stresses and how they respond to them. We then discuss the impacts of two important ecosystem-level stressors, drought and freezing, on microbial physiology and community composition. Even when microbial community response to stress is limited, the physiological costs imposed on soil microbes are large enough that they may cause large shifts in the allocation and fate of C and N. For example, for microbes to synthesize the osmolytes they need to survive a single drought episode they may consume up to 5% of total annual net primary production in grassland ecosystems, while acclimating to freezing conditions switches Arctic tundra soils from immobilizing N during the growing season to mineralizing it during the winter. We suggest that more effectively integrating microbial ecology into ecosystem ecology will require a more complete integration of microbial physiological ecology, population biology, and process ecology.

Shared molecular and cellular mechanisms of premature ageing and ageing-associated diseases.

PubMed

Kubben, Nard; Misteli, Tom

2017-10-01

Ageing is the predominant risk factor for many common diseases. Human premature ageing diseases are powerful model systems to identify and characterize cellular mechanisms that underpin physiological ageing. Their study also leads to a better understanding of the causes, drivers and potential therapeutic strategies of common diseases associated with ageing, including neurological disorders, diabetes, cardiovascular diseases and cancer. Using the rare premature ageing disorder Hutchinson-Gilford progeria syndrome as a paradigm, we discuss here the shared mechanisms between premature ageing and ageing-associated diseases, including defects in genetic, epigenetic and metabolic pathways; mitochondrial and protein homeostasis; cell cycle; and stem cell-regenerative capacity.

The interruption of thyroid and interrenal and the inter-hormonal interference in fish: does it promote physiologic adaptation or maladaptation?

PubMed

Peter, Valsa S; Peter, M C Subhash

2011-12-01

Endocrines, the chief components of chemical centers which produce hormones in tune with intrinsic and extrinsic clues, create a chemical bridge between the organism and the environment. In fishes also hormones integrate and modulate many physiologic functions and its synthesis, release, biological actions and metabolic clearance are well regulated. Consequently, thyroid hormones (THs) and cortisol, the products of thyroid and interrenal axes, have been identified for their common integrative actions on metabolic and osmotic functions in fish. On the other hand, many anthropogenic chemical substances, popularly known as endocrine disrupting chemicals, have been shown to disrupt the hormone-receptor signaling pathways in a number fish species. These chemicals which are known for their ability to induce endocrine disruption particularly on thyroid and interrenals can cause malfunction or maladaptation of many vital processes which are involved in the development, growth and reproduction in fish. On the contrary, evidence is presented that the endocrine interrupting agents (EIAs) can cause interruption of thyroid and interrenals, resulting in physiologic compensatory mechanisms which can be adaptive, though such hormonal interactions are less recognized in fishes. The EIAs of physical, chemical and biological origins can specifically interrupt and modify the hormonal interactions between THs and cortisol, resulting in specific patterns of inter-hormonal interference. The physiologic analysis of these inter-hormonal interruptions during acclimation and post-acclimation to intrinsic or extrinsic EIAs reveals that combinations of anti-hormonal, pro-hormonal or stati-hormonal interference may help the fish to fine-tune their metabolic and osmotic performances as part of physiologic adaptation. This novel hypothesis on the phenomenon of inter-hormonal interference and its consequent physiologic interference during thyroid and interrenal interruption thus forms the basis of physiologic acclimation. This interfering action of TH and cortisol during hormonal interruption may subsequently promote ecological adaptation in fish as these physiologic processes ultimately favor them to survive in their hostile environment. Copyright © 2011 Elsevier Inc. All rights reserved.

Short-term and long-term effects of transient exogenous cortisol manipulation on oxidative stress in juvenile brown trout.

PubMed

Birnie-Gauvin, Kim; Peiman, Kathryn S; Larsen, Martin H; Aarestrup, Kim; Willmore, William G; Cooke, Steven J

2017-05-01

In the wild, animals are exposed to a growing number of stressors with increasing frequency and intensity, as a result of human activities and human-induced environmental change. To fully understand how wild organisms are affected by stressors, it is crucial to understand the physiology that underlies an organism's response to a stressor. Prolonged levels of elevated glucocorticoids are associated with a state of chronic stress and decreased fitness. Exogenous glucocorticoid manipulation reduces an individual's ability to forage, avoid predators and grow, thereby limiting the resources available for physiological functions like defence against oxidative stress. Using brown trout ( Salmo trutta ), we evaluated the short-term (2 weeks) and long-term (4 months over winter) effects of exogenous cortisol manipulations (versus relevant shams and controls) on the oxidative status of wild juveniles. Cortisol caused an increase in glutathione over a 2 week period and appeared to reduce glutathione over winter. Cortisol treatment did not affect oxidative stress levels or low molecular weight antioxidants. Cortisol caused a significant decrease in growth rates but did not affect predation risk. Over-winter survival in the stream was associated with low levels of oxidative stress and glutathione. Thus, oxidative stress may be a mechanism by which elevated cortisol causes negative physiological effects. © 2017. Published by The Company of Biologists Ltd.

[Emotional stress-induced Shanghuo syndrome increases disease susceptibility].

PubMed

Zhu, Si-Rui; Luo, Xiang; Li, Yi-Fang; Hiroshi, Kurihara; He, Rong-Rong

2018-04-01

Shanghuo(excessive internal heat) is a special organic state based on the concept of traditional Chinese medicine(TCM), commonly known as the abnormal heating syndrome of body in folks. With the acceleration of modern life rhythm and the increase of the social competition pressure, emotional stress has become an important cause for the spread of Shanghuo symptoms. What's more, Shanghuo can impact the body physiological functions to cause the onset, recurrence and progression of common diseases, harming the health of the body. According to the long-term research findings, the author found that Shanghuo referred to the imbalance of multiple physiological functions, such as nerve, immunity and metabolism, caused by emotional stress. "Shanghuo" is not a disease itself, but it can increase the susceptibility to a variety of diseases. This study reviewed the traditional medicine theory and the modern medical studies, and explored the relevance and correlation mechanisms between the Shanghuo symptoms and disease susceptibility, so as to provide a reference to improve the state of sub-health and prevent or treat modern diseases. Copyright© by the Chinese Pharmaceutical Association.

[Proposal of a different interpretation of the physiology of labor useful in more edifying teaching of obstetric psychoprophylaxis courses].

PubMed

Mergoni, A

1994-01-01

Without underestimating the undeniable benefit which can be achieved from various physical and mental relaxation exercises, the author expresses the conviction that the didactic and cultural aspect of preparative courses during pregnancy by definition improve, to a greater extent than is widely believed, the positive outcome of obstetric psychoprophylaxis. It is therefore opportune that the didactic part of courses should cover a wider and more detailed range than is usually the case, in particular including a more exhaustive and accurate description of the mechanical phenomenon of birth. Without a clear knowledge and awareness of such mechanical aspects, pregnant women will not feel prepared for and in full and rational control of her own labour. Given that a correct knowledge of the physiology of labour inevitably includes aspects which will enrich the pregnant woman's psyche, the author hopes that interest will soon be reawakened in the physiology of labour whose interpretation has for a long time contained a number of basic and unresolved problems. In order to rectify and further our knowledge of the physiology of labour, it is important to be willing to consider other interpretative models which differ from the traditional one. On this subject, the author aims to rediscuss one model in which Pascal's principle is recognised as the decisive cause of the majority of the mechanical phenomena of labour, and which, in addition to providing solutions to many unresolved problems, makes the teaching of preparative courses during pregnancy more edifying in psychological terms.

Altered Innate and Lymphocytic Immunity in Murine Splenocytes Following Short-Duration Spaceflight

NASA Technical Reports Server (NTRS)

Crucian, Brian E.; Hwang, Shen-An; Actor, Jeffrey K.; Quiriarte, Heather; Sams, Clarence F.

2011-01-01

Immune dysregulation has been demonstrated following spaceflight of varying durations and limited in-flight studies indicate this phenomenon may persist during spaceflight. Causes may include microgravity, physiological stress, isolation, confinement and disrupted circadian rhythms. To further investigate the mechanisms associated with flight-associated immune changes, murine splenocytes immune parameters were assessed following 14 day space flight on Space Shuttle mission STS-135.

Spatial mapping of extracellular oxidant production by a white rot basidiomycete on wood reveals details of ligninolytic mechanism

Treesearch

Christopher G. Hunt; Carl J. Houtman; Don C. Jones; Peter Kitin; Premsagar Korripally; Kenneth E. Hammel

2013-01-01

Oxidative cleavage of the recalcitrant plant polymer lignin is a crucial step in global carbon cycling, and is accomplished most efficiently by fungi that cause white rot of wood. These basidiomycetes secrete many enzymes and metabolites with proposed ligninolytic roles, and it is not clear whether all of these agents are physiologically important during attack on...

Toluene diisocyanate caused electrophysiological disturbances in the upper airways wall.

PubMed

Piskorska, Elzbieta; Hołyńska-Iwan, Iga; Kaczorowski, Piotr; Soczywko-Ciudzińska, Julita; Wiciński, Michał; Lampka, Magdalena; Smuszkiewicz, Piotr; Tyrakowski, Tomasz

2009-01-01

Toluene diisocyanate (TDI) due to its widespread use in industry is one of the most common and well-known causes of occupational asthma and Reactive Airways Dysfunction Syndrome (RADS). In this study the impact of TDI on the electrophysiological properties of the airways wall, particularly on the mechanisms of absorption of sodium ions and chloride ions secretion was evaluated. Isolated rabbit tracheal wall (from outbred stock animals) was mounted in an apparatus for electrophysiological experiments by means of Ussing method and was mechanically stimulated by the jet flux of specified fluid directed onto the mucosal surface of the tissue from a peristaltic pump. The measured parameters were: transepithelial potential difference under control conditions (PD, mV), after mechanical stimulation (dPD or physiological reaction of hyperpolarization, mV) and electric resistance (R, Omega cm2). When TDI (0.035 mM) was added to stimulation fluid, only the immediate reaction was identified and when it was added to incubation fluid and other experimental fluids, the late (post-incubation) reaction was determined. The experiments involving the inhibition of Na+ by amiloride and Cl- by bumetanide were also performed. A series of functional tests for 72 pieces of tracheal wall from 36 animals were performed. It has been shown that short-term exposure to TDI significantly changed the course of reactions to mechanical stimulation. Also after incubation in the presence of TDI, the reactions to mechanical stimulation were changed in relation to control conditions. The immediate reaction of the isolated rabbit tracheal wall after exposure to TDI depends on the duration of exposure and on the physiological condition of the tissue in respect of sodium and chloride ion transport.

Sexual dysfunction with antihypertensive and antipsychotic agents.

PubMed

Smith, P J; Talbert, R L

1986-05-01

The physiology of the normal sexual response, epidemiology of sexual dysfunction, and the pharmacologic mechanisms involved in antihypertensive- and antipsychotic-induced problems with sexual function are discussed, with recommendations for patient management. The physiologic mechanisms involved in the normal sexual response include neurogenic, psychogenic, vascular, and hormonal factors that are coordinated by centers in the hypothalamus, limbic system, and cerebral cortex. Sexual dysfunction is frequently attributed to antihypertensive and antipsychotic agents and is a cause of noncompliance. Drug-induced effects include diminished libido, delayed orgasm, ejaculatory disturbances, gynecomastia, impotence, and priapism. The pharmacologic mechanisms proposed to account for these adverse effects include adrenergic inhibition, adrenergic-receptor blockade, anticholinergic properties, and endocrine and sedative effects. The most frequently reported adverse effect on sexual function with the antihypertensive agents is impotence. It is seen most often with methyldopa, guanethidine, clonidine, and propranolol. In contrast, the most common adverse effect on sexual function with the antipsychotic agents involves ejaculatory disturbances. Thioridazine, with its potent anticholinergic and alpha-blocking properties, is cited most often. Drug-induced sexual dysfunction may be alleviated by switching to agents with dissimilar mechanisms to alter the observed adverse effect while maintaining adequate control of the patient's disease state.

Sex Differences: A Resultant of an Evolutionary Pressure?

PubMed

Della Torre, Sara; Maggi, Adriana

2017-03-07

Spurred by current research policy, we are witnessing a significant growth in the number of studies that observe and describe sexual diversities in human physiology and sex prevalence in a large number of pathologies. Yet we are far from the comprehension of the mechanisms underpinning these differences, which are the result of a long evolutionary history. This Essay is meant to underline female reproductive function as a driver for the positive selection of the specific physiological features that explain male and female differential susceptibility to diseases and metabolic disturbances, in particular. A clear understanding of the causes underlying sexual dimorphisms in the physio-pathology is crucial for precision medicine. Copyright © 2017 Elsevier Inc. All rights reserved.

Tetrahydrocannabinol and endocannabinoids in feeding and appetite.

PubMed

Berry, Elliot M; Mechoulam, Raphael

2002-08-01

The physiological control of appetite and satiety, in which numerous neurotransmitters and neuropeptides play a role, is extremely complex. Here we describe the involvement of endocannabinoids in these processes. These endogenous neuromodulators enhance appetite in animals. The same effect is observed in animals and in humans with the psychotropic plant cannabinoid Delta(9)-tetrahydrocannabinol, which is an approved appetite-enhancing drug. The CB(1) cannabinoid receptor antagonist SR141716A blocks the effects on feeding produced by the endocannabinoids. If administered to mice pups, this antagonist blocks suckling. In obese humans, it causes weight reduction. Very little is known about the physiological and biochemical mechanisms involved in the effects of Delta(9)-tetrahydrocannabinol and the cannabinoids in feeding and appetite.

Compromising σ-1 Receptors at the Endoplasmic Reticulum Render Cytotoxicity to Physiologically Relevant Concentrations of Dopamine in a Nuclear Factor-κB/Bcl-2-Dependent Mechanism: Potential Relevance to Parkinson's Disease

PubMed Central

Mori, Tomohisa; Hayashi, Teruo

2012-01-01

The endoplasmic reticulum (ER) chaperone σ-1 receptor (Sig-1R) is cytoprotective against ER stress-induced apoptosis. The level of Sig-1Rs in the brain was reported to be lower in early parkinsonian patients. Because dopamine (DA) toxicity is well known to be involved in the etiology of Parkinson's disease, we tested in this study whether a relationship might exist between Sig-1Rs and DA-induced cytotoxicity in a cellular model by using Chinese hamster ovary (CHO) cells. DA in physiological concentrations (e.g., lower than 10 μM) does not cause apoptosis. However, the same concentrations of DA cause apoptosis in Sig-1R knockdown CHO cells. In search of a mechanistic explanation, we found that unfolded protein response is not involved. Rather, the level of protective protein Bcl-2 is critically involved in this DA/Sig-1R knockdown-induced apoptosis. Specifically, the DA/Sig-1R knockdown causes a synergistic proteasomal conversion of nuclear factor κB (NF-κB) p105 to the active form of p50, which is known to down-regulate the transcription of Bcl-2. It is noteworthy that the DA/Sig-1R knockdown-induced apoptosis is blocked by the overexpression of Bcl-2. Our results therefore indicate that DA is involved in the activation of NF-κB and suggest that endogenous Sig-1Rs are tonically inhibiting the proteasomal conversion/activation of NF-κB caused by physiologically relevant concentrations of DA that would otherwise cause apoptosis. Thus, Sig-1Rs and associated ligands may represent new therapeutic targets for the treatment of parkinsonism. PMID:22399814

Fish is Fish: the use of experimental model species to reveal causes of skeletal diversity in evolution and disease

PubMed Central

Harris, M. P.; Henke, K.; Hawkins, M. B.; Witten, P. E.

2014-01-01

Summary Fishes are wonderfully diverse. This variety is a result of the ability of ray-finned fishes to adapt to a wide range of environments, and has made them more specious than the rest of vertebrates combined. With such diversity it is easy to dismiss comparisons between distantly related fishes in efforts to understand the biology of a particular fish species. However, shared ancestry and the conservation of developmental mechanisms, morphological features and physiology provide the ability to use comparative analyses between different organisms to understand mechanisms of development and physiology. The use of species that are amenable to experimental investigation provides tools to approach questions that would not be feasible in other ‘non-model’ organisms. For example, the use of small teleost fishes such as zebrafish and medaka has been powerful for analysis of gene function and mechanisms of disease in humans, including skeletal diseases. However, use of these fish to aid in understanding variation and disease in other fishes has been largely unexplored. This is especially evident in aquaculture research. Here we highlight the utility of these small laboratory fishes to study genetic and developmental factors that underlie skeletal malformations that occur under farming conditions. We highlight several areas in which model species can serve as a resource for identifying the causes of variation in economically important fish species as well as to assess strategies to alleviate the expression of the variant phenotypes in farmed fish. We focus on genetic causes of skeletal deformities in the zebrafish and medaka that closely resemble phenotypes observed both in farmed as well as natural populations of fishes. PMID:25221374

Swirling flow in bileaflet mechanical heart valve

NASA Astrophysics Data System (ADS)

Gataulin, Yakov A.; Khorobrov, Svyatoslav V.; Yukhnev, Andrey D.

2018-05-01

Bileaflet mechanical valves are most commonly used for heart valve replacement. Nowadays swirling blood flow is registered in different parts of the cardiovascular system: left ventricle, aorta, arteries and veins. In present contribution for the first time the physiological swirling flow inlet conditions are used for numerical simulation of aortic bileaflet mechanical heart valve hemodynamics. Steady 3-dimensional continuity and RANS equations are employed to describe blood motion. The Menter SST model is used to simulate turbulence effects. Boundary conditions are corresponded to systolic peak flow. The domain was discretized into hybrid tetrahedral and hexahedral mesh with an emphasis on wall boundary layer. A system of equations was solved in Ansys Fluent finite-volume package. Noticeable changes in the flow structure caused by inlet swirl are shown. The swirling flow interaction with the valve leaflets is analyzed. A central orifice jet changes its cross-section shape, which leads to redistribution of wall shear stress on the leaflets. Transvalvular pressure gradient and area-averaged leaflet wall shear stress increase. Physiological swirl intensity noticeably reduces downstream of the valve.

Regulation of Bim in Health and Disease

PubMed Central

Sionov, Ronit Vogt; Vlahopoulos, Spiros A.; Granot, Zvi

2015-01-01

The BH3-only Bim protein is a major determinant for initiating the intrinsic apoptotic pathway under both physiological and pathophysiological conditions. Tight regulation of its expression and activity at the transcriptional, translational and post-translational levels together with the induction of alternatively spliced isoforms with different pro-apoptotic potential, ensure timely activation of Bim. Under physiological conditions, Bim is essential for shaping immune responses where its absence promotes autoimmunity, while too early Bim induction eliminates cytotoxic T cells prematurely, resulting in chronic inflammation and tumor progression. Enhanced Bim induction in neurons causes neurodegenerative disorders including Alzheimer's, Parkinson's and Huntington's diseases. Moreover, type I diabetes is promoted by genetically predisposed elevation of Bim in β-cells. On the contrary, cancer cells have developed mechanisms that suppress Bim expression necessary for tumor progression and metastasis. This review focuses on the intricate network regulating Bim activity and its involvement in physiological and pathophysiological processes. PMID:26405162

Regulation of Bim in Health and Disease.

PubMed

Sionov, Ronit Vogt; Vlahopoulos, Spiros A; Granot, Zvi

2015-09-15

The BH3-only Bim protein is a major determinant for initiating the intrinsic apoptotic pathway under both physiological and pathophysiological conditions. Tight regulation of its expression and activity at the transcriptional, translational and post-translational levels together with the induction of alternatively spliced isoforms with different pro-apoptotic potential, ensure timely activation of Bim. Under physiological conditions, Bim is essential for shaping immune responses where its absence promotes autoimmunity, while too early Bim induction eliminates cytotoxic T cells prematurely, resulting in chronic inflammation and tumor progression. Enhanced Bim induction in neurons causes neurodegenerative disorders including Alzheimer's, Parkinson's and Huntington's diseases. Moreover, type I diabetes is promoted by genetically predisposed elevation of Bim in β-cells. On the contrary, cancer cells have developed mechanisms that suppress Bim expression necessary for tumor progression and metastasis. This review focuses on the intricate network regulating Bim activity and its involvement in physiological and pathophysiological processes.

[Morpha striata in the members of the genus Rana (Amphibia, Anura), the reasons of adaptability to environmental changes].

PubMed

Vershinin, V L

2008-01-01

Under investigation is a complex of inherited physiological properties of the morpha striata (a monogenous dominant mutation) in two species of the genus Rana. Insufficient effectiveness of the potassium-sodium pump responsible for the skin transport in amphibians had lead to formation of a number of compensative physiological mechanisms in this morpha. The yearlings of the morpha striata are characterized by highly dynamic hemopoetic system playing important role in individual adaptations to unstable environments. Such a high level of metabolism in the morpha striata promotes rising of adaptive potential of the nervous system due to decrease of the excitability threshold, but causes shortening the life span. Therefore, physiological differences correlated with polymorph structure of the close species can be of crucial importance in their adaptations under existence in the natural and artificial geochemical anomalies and in anthropogenically disturbed ecosystems.

No evidence for sex-specific effects of the maternal social environment on offspring development in Japanese quail (Coturnix japonica).

PubMed

Langen, Esther M A; von Engelhardt, Nikolaus; Goerlich-Jansson, Vivian C

2018-07-01

The social environment of reproducing females can cause physiological changes, with consequences for reproductive investment and offspring development. These prenatal maternal effects are often found to be sex-specific and may have evolved as adaptations, maximizing fitness of male and female offspring for their future environment. Female hormone levels during reproduction are considered a potential mechanism regulating sex allocation in vertebrates: high maternal androgens have repeatedly been linked to increased investment in sons, whereas high glucocorticoid levels are usually related to increased investment in daughters. However, results are not consistent across studies and therefore still inconclusive. In Japanese quail (Coturnix japonica), we previously found that pair-housed females had higher plasma androgen levels and tended to have higher plasma corticosterone levels than group-housed females. In the current study we investigate whether these differences in maternal social environment and physiology affect offspring sex allocation and physiology. Counter to our expectations, we find no effects of the maternal social environment on offspring sex ratio, sex-specific mortality, growth, circulating androgen or corticosterone levels. Also, maternal corticosterone or androgen levels do not correlate with offspring sex ratio or mortality. The social environment during reproduction therefore does not necessarily modify sex allocation and offspring physiology, even if it causes differences in maternal physiology. We propose that maternal effects of the social environment strongly depend upon the type of social stimuli and the timing of changes in the social environment and hormones with respect to the reproductive cycle and meiosis. Copyright © 2018 Elsevier Inc. All rights reserved.

X chromosome regulation: diverse patterns in development, tissues and disease

PubMed Central

Deng, Xinxian; Berletch, Joel B.; Nguyen, Di K.; Disteche, Christine M.

2014-01-01

Genes on the mammalian X chromosome are present in one copy in males and two copies in females. The complex mechanisms that regulate the X chromosome lead to evolutionary and physiological variability in gene expression between species, the sexes, individuals, developmental stages, tissues and cell types. In early development, delayed and incomplete X chromosome inactivation (XCI) in some species causes variability in gene expression. Additional diversity stems from escape from XCI and from mosaicism or XCI skewing in females. This causes sex-specific differences that manifest as differential gene expression and associated phenotypes. Furthermore, the complexity and diversity of X dosage regulation affect the severity of diseases caused by X-linked mutations. PMID:24733023

Elevated surface temperature depresses survival of banner-tailed kangaroo rats: will climate change cook a desert icon?

PubMed

Moses, Martin R; Frey, Jennifer K; Roemer, Gary W

2012-01-01

Modest increases in global temperature have been implicated in causing population extirpations and range shifts in taxa inhabiting colder environs and in ectotherms whose thermoregulation is more closely tied to environmental conditions. Many arid-adapted endotherms already experience conditions at their physiological limits, so it is conceivable that they could be similarly affected by warming temperatures. We explored how climatic variables might influence the apparent survival of the banner-tailed kangaroo rat (Dipodomys spectabilis), a rodent endemic to the Chihuahuan Desert of North America and renowned for its behavioral and physiological adaptations to arid environments. Relative variable weight, strength of variable relationships, and other criteria indicated that summer, diurnal land surface temperature (SD_LST) was the primary environmental driver of apparent survival in these arid-adapted rodents. Higher temperatures had a negative effect on apparent survival, which ranged from 0.15 (SE = 0.04) for subadults to 0.50 (SE = 0.07) for adults. Elevated SD_LST may negatively influence survival through multiple pathways, including increased water loss and energy expenditure that could lead to chronic stress and/or hyperthermia that could cause direct mortality. Land surface temperatures are predicted to increase by as much 6.5°C by 2099, reducing apparent survival of adults to ~0.15 in some regions of the species' range, possibly causing a shift in their distribution. The relationship between SD_LST and survival suggests a mechanism whereby physiological tolerances are exceeded resulting in a reduction to individual fitness that may ultimately cause a shift in the species' range over time.

Evolution of circadian rhythms: from bacteria to human.

PubMed

Bhadra, Utpal; Thakkar, Nirav; Das, Paromita; Pal Bhadra, Manika

2017-07-01

The human body persists in its rhythm as per its initial time zone, and transition always occur according to solar movements around the earth over 24 h. While traveling across different latitudes and longitudes, at the pace exceeding the earth's movement, the changes in the external cues exceed the level of toleration of the body's biological clock. This poses an alteration in our physiological activities of sleep-wake pattern, mental alertness, organ movement, and eating habits, causing them to temporarily lose the track of time. This is further re-synchronized with the physiological cues of the destination over time. The mechanism of resetting of the clocks with varying time zones and cues occur in organisms from bacteria to humans. It is the result of the evolution of different pathways and molecular mechanisms over the time. There has been evolution of numerous comprehensive mechanisms using various research tools to get a deeper insight into the rapid turnover of molecular mechanisms in various species. This review reports insights into the evolution of the circadian mechanism and its evolutionary shift which is vital and plays a major role in assisting different organisms to adapt in different zones and controls their internal biological clocks with changing external cues. Copyright © 2017 Elsevier B.V. All rights reserved.

Role of n-3 Polyunsaturated Fatty Acids in Ameliorating the Obesity-Induced Metabolic Syndrome in Animal Models and Humans

PubMed Central

Huang, Chao-Wei; Chien, Yi-Shan; Chen, Yu-Jen; Ajuwon, Kolapo M.; Mersmann, Harry M.; Ding, Shih-Torng

2016-01-01

The incidence of obesity and its comorbidities, such as insulin resistance and type II diabetes, are increasing dramatically, perhaps caused by the change in the fatty acid composition of common human diets. Adipose tissue plays a role as the major energy reservoir in the body. An excess of adipose mass accumulation caused by chronic positive energy balance results in obesity. The n-3 polyunsaturated fatty acids (n-3 PUFA), DHA (docosahexaenoic acid) and EPA (eicosapentaenoic acid) exert numerous beneficial effects to maintain physiological homeostasis. In the current review, the physiology of n-3 PUFA effects in the body is delineated from studies conducted in both human and animal experiments. Although mechanistic studies in human are limited, numerous studies conducted in animals and models in vitro provide potential molecular mechanisms of the effects of these fatty acids. Three aspects of n-3 PUFA in adipocyte regulation are discussed: (1) lipid metabolism, including adipocyte differentiation, lipolysis and lipogenesis; (2) energy expenditure, such as mitochondrial and peroxisomal fatty acid β-oxidation; and (3) inflammation, including adipokines and specialized pro-resolving lipid mediators. Additionally, the mechanisms by which n-3 PUFA regulate gene expression are highlighted. The beneficial effects of n-3 PUFA may help to reduce the incidence of obesity and its comorbidities. PMID:27735847

Integration of Cadmium Accumulation, Subcellular Distribution, and Physiological Responses to Understand Cadmium Tolerance in Apple Rootstocks

PubMed Central

Zhou, Jiangtao; Wan, Huixue; He, Jiali; Lyu, Deguo; Li, Huifeng

2017-01-01

Cadmium (Cd) is a nonessential and highly toxic element causing agricultural problems. However, little information is available about the variation in Cd tolerance among apple rootstocks and its underlying physiological regulation mechanisms. This study investigated Cd accumulation, subcellular distribution, and chemical forms as well as physiological changes among four apple rootstocks exposed to either 0 or 300 μM CdCl2. The results showed that variations in Cd tolerance existed among these rootstocks. Cd exposure caused decline in photosynthesis, chlorophyll and biomass in four apple rootstocks, which was less pronounced in M. baccata, indicating its higher Cd tolerance. This finding was corroborated with higher Cd tolerance indexes (TIs) of the whole plant in M. baccata than those in the other three apple rootstocks. Among the four apple rootstocks, M. baccata displayed the lowest Cd concentrations in roots, wood, and leaves, the smallest total Cd amounts as well as the lowest BCF. In apple rootstocks, it was found that to immobilize Cd in cell wall and soluble fraction (most likely in vacuole) and to convert it into pectate- or protein- integrated forms and undissolved Cd phosphate forms may be the primary strategies to reduce Cd mobility and toxicity. The physiological changes including ROS, carbohydrates and antioxidants were in line with the variations of Cd tolerance among four apple rootstocks. In comparison with the other three apple rootstocks, M. baccata had lower concentrations of ROS in roots and bark, H2O2 in roots and leaves and MDA in roots, wood and bark, but higher concentrations of soluble sugars in bark and starch in roots and leaves, and enhanced antioxidants. These results indicate that M. baccata are more tolerant to Cd stress than the other three apple rootstocks under the current experiment conditions, which is probably related to Cd accumulation, subcellular partitioning and chemical forms of Cd and well-coordinated antioxidant defense mechanisms. PMID:28638400

A tale of two CLCs: biophysical insights toward understanding ClC-5 and ClC-7 function in endosomes and lysosomes

PubMed Central

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

Mechanisms of PEDF-mediated protection against reactive oxygen species damage in diabetic retinopathy and neuropathy.

PubMed

Elahy, Mina; Baindur-Hudson, Swati; Cruzat, Vinicius F; Newsholme, Philip; Dass, Crispin R

2014-09-01

Pigment epithelium-derived factor (PEDF) is a pluripotent glycoprotein belonging to the serpin family. PEDF can stimulate several physiological processes such as angiogenesis, cell proliferation, and survival. Oxidative stress plays an important role in the occurrence of diabetic retinopathy (DR), which is the major cause of blindness in young diabetic adults. PEDF plays a protective role in DR and there is accumulating evidence of the neuroprotective effect of PEDF. In this paper, we review the role of PEDF and the mechanisms involved in its antioxidative, anti-inflammatory, and neuroprotective properties. © 2014 Society for Endocrinology.

ECVAM and new technologies for toxicity testing.

PubMed

Bouvier d'Yvoire, Michel; Bremer, Susanne; Casati, Silvia; Ceridono, Mara; Coecke, Sandra; Corvi, Raffaella; Eskes, Chantra; Gribaldo, Laura; Griesinger, Claudius; Knaut, Holger; Linge, Jens P; Roi, Annett; Zuang, Valérie

2012-01-01

The development of alternative empirical (testing) and non-empirical (non-testing) methods to traditional toxicological tests for complex human health effects is a tremendous task. Toxicants may potentially interfere with a vast number of physiological mechanisms thereby causing disturbances on various levels of complexity of human physiology. Only a limited number of mechanisms relevant for toxicity ('pathways' of toxicity) have been identified with certainty so far and, presumably, many more mechanisms by which toxicants cause adverse effects remain to be identified. Recapitulating in empirical model systems (i.e., in vitro test systems) all those relevant physiological mechanisms prone to be disturbed by toxicants and relevant for causing the toxicity effect in question poses an enormous challenge. First, the mechanism(s) of action of toxicants in relation to the most relevant adverse effects of a specific human health endpoint need to be identified. Subsequently, these mechanisms need to be modeled in reductionist test systems that allow assessing whether an unknown substance may operate via a specific (array of) mechanism(s). Ideally, such test systems should be relevant for the species of interest, i.e., based on human cells or modeling mechanisms present in humans. Since much of our understanding about toxicity mechanisms is based on studies using animal model systems (i.e., experimental animals or animal-derived cells), designing test systems that model mechanisms relevant for the human situation may be limited by the lack of relevant information from basic research. New technologies from molecular biology and cell biology, as well as progress in tissue engineering, imaging techniques and automated testing platforms hold the promise to alleviate some of the traditional difficulties associated with improving toxicity testing for complex endpoints. Such new technologies are expected (1) to accelerate the identification of toxicity pathways with human relevance that need to be modeled in test methods for toxicity testing (2) to enable the reconstruction of reductionist test systems modeling at a reduced level of complexity the target system/organ of interest (e.g., through tissue engineering, use of human-derived cell lines and stem cells etc.), (3) to allow the measurement of specific mechanisms relevant for a given health endpoint in such test methods (e.g., through gene and protein expression, changes in metabolites, receptor activation, changes in neural activity etc.), (4) to allow to measure toxicity mechanisms at higher throughput rates through the use of automated testing. In this chapter, we discuss the potential impact of new technologies on the development, optimization and use of empirical testing methods, grouped according to important toxicological endpoints. We highlight, from an ECVAM perspective, the areas of topical toxicity, skin absorption, reproductive and developmental toxicity, carcinogenicity/genotoxicity, sensitization, hematopoeisis and toxicokinetics and discuss strategic developments including ECVAM's database service on alternative methods. Neither the areas of toxicity discussed nor the highlighted new technologies represent comprehensive listings which would be an impossible endeavor in the context of a book chapter. However, we feel that these areas are of utmost importance and we predict that new technologies are likely to contribute significantly to test development in these fields. We summarize which new technologies are expected to contribute to the development of new alternative testing methods over the next few years and point out current and planned ECVAM projects for each of these areas.

Short- and long-term behavioural, physiological and stoichiometric responses to predation risk indicate chronic stress and compensatory mechanisms.

PubMed

Van Dievel, Marie; Janssens, Lizanne; Stoks, Robby

2016-06-01

Prey organisms are expected to use different short- and long-term responses to predation risk to avoid excessive costs. Contrasting both types of responses is important to identify chronic stress responses and possible compensatory mechanisms in order to better understand the full impact of predators on prey life history and population dynamics. Using larvae of the damselfly Enallagma cyathigerum, we contrasted the effects of short- and long-term predation risk, with special focus on consequences for body stoichiometry. Under short-term predation risk, larvae reduced growth rate, which was associated with a reduced food intake, increased metabolic rate and reduced glucose content. Under long-term predation risk, larvae showed chronic predator stress as indicated by persistent increases in metabolic rate and reduced food intake. Despite this, larvae were able to compensate for the short-term growth reduction under long-term predation risk by relying on physiological compensatory mechanisms, including reduced energy storage. Only under long-term predation risk did we observe an increase in body C:N ratio, as predicted under the general stress paradigm (GSP). Although this was caused by a predator-induced decrease in N content, there was no associated increase in C content. These stoichiometric changes could not be explained by GSP responses because, under chronic predation risk, there was no decrease in N-rich proteins or increase in C-rich fat and sugars; instead glycogen decreased. Our results highlight the importance of compensatory mechanisms and the value of explicitly integrating physiological mechanisms to obtain insights into the temporal dynamics of non-consumptive effects, including effects on body stoichiometry.

Biological Rhythms Modelisation of Vigilance and Sleep in Microgravity State with COSINOR and Volterra's Kernels Methods

NASA Astrophysics Data System (ADS)

Gaudeua de Gerlicz, C.; Golding, J. G.; Bobola, Ph.; Moutarde, C.; Naji, S.

2008-06-01

The spaceflight under microgravity cause basically biological and physiological imbalance in human being. Lot of study has been yet release on this topic especially about sleep disturbances and on the circadian rhythms (alternation vigilance-sleep, body, temperature...). Factors like space motion sickness, noise, or excitement can cause severe sleep disturbances. For a stay of longer than four months in space, gradual increases in the planned duration of sleep were reported. [1] The average sleep in orbit was more than 1.5 hours shorter than the during control periods on earth, where sleep averaged 7.9 hours. [2] Alertness and calmness were unregistered yield clear circadian pattern of 24h but with a phase delay of 4h.The calmness showed a biphasic component (12h) mean sleep duration was 6.4 structured by 3-5 non REM/REM cycles. Modelisations of neurophysiologic mechanisms of stress and interactions between various physiological and psychological variables of rhythms have can be yet release with the COSINOR method. [3

The biopsychology of salt hunger and sodium deficiency

PubMed Central

Hurley, Seth W.; Johnson, Alan Kim

2015-01-01

Sodium is a necessary dietary macromineral that tended to be sparsely distributed in mankind’s environment in the past. Evolutionary selection pressure shaped physiological mechanisms including hormonal systems and neural circuits that serve to promote sodium ingestion. Sodium deficiency triggers the activation of these hormonal systems and neural circuits to engage motivational processes that elicit a craving for salty substances and a state of reward when salty foods are consumed. Sodium deficiency also appears to be associated with aversive psychological states including anhedonia, impaired cognition, and fatigue. Under certain circumstances the psychological processes that promote salt intake can become powerful enough to cause “salt gluttony,” or salt intake far in excess of physiological need. The present review discusses three aspects of the biopsychology of salt hunger and sodium deficiency: 1) the psychological processes that promote salt intake during sodium deficiency, 2) the effects of sodium deficiency on mood and cognition, and 3) the sensitization of sodium appetite as a possible cause of salt gluttony. PMID:25572931

Nondrowning Asphyxia in Veterinary Forensic Pathology: Suffocation, Strangulation, and Mechanical Asphyxia.

PubMed

McEwen, B J

2016-09-01

Asphyxia in a forensic context refers to death by rapid cerebral anoxia or hypoxia due to accidental or nonaccidental injury. Death due to nondrowning asphyxia can occur with strangulation, suffocation, and mechanical asphyxia, each of which is categorized based on the mechanism of injury. Individuals dying due to various types of asphyxia may or may not have lesions, and even those lesions that are present may be due to other causes. The interpretation or opinion that death was due to asphyxia requires definitive and compelling evidence from the postmortem examination, death scene, and/or history. Beyond the postmortem examination, pathologists may be faced with questions of forensic importance that revolve around the behavioral and physiological responses in animals subjected to strangulation, suffocation, or mechanical asphyxia to determine if the animal suffered. While there is no prescriptive answer to these questions, it is apparent that, because of physiological and anatomical differences between humans and animals, for some mechanisms of asphyxia, consciousness is maintained for longer periods and the onset of death is later in animals than that described for people. Veterinary pathologists must be cognizant that direct extrapolation from the medical forensic literature to animals may be incorrect. This article reviews the terminology, classification, mechanisms, and lesions associated with asphyxial deaths in companion animals and highlights significant comparative differences of the response to various types of asphyxia in animals and people. © The Author(s) 2016.

Arsenic Uptake, Toxicity, Detoxification, and Speciation in Plants: Physiological, Biochemical, and Molecular Aspects

PubMed Central

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

Structure-Function Relations in Physiology Education: Where's the Mechanism?

ERIC Educational Resources Information Center

Lira, Matthew E.; Gardner, Stephanie M.

2017-01-01

Physiology demands systems thinking: reasoning within and between levels of biological organization and across different organ systems. Many physiological mechanisms explain how structures and their properties interact at one level of organization to produce emergent functions at a higher level of organization. Current physiology principles, such…

Mechanism of artemisinin phytotoxicity action: induction of reactive oxygen species and cell death in lettuce seedlings.

PubMed

Yan, Zhi-Qiang; Wang, Dan-Dan; Ding, Lan; Cui, Hai-Yan; Jin, Hui; Yang, Xiao-Yan; Yang, Jian-She; Qin, Bo

2015-03-01

Artemisinin has been recognized as an allelochemical that inhibits growth of several plant species. However, its mode of action is not well clarified. In this study, the mechanism of artemisinin phytotoxicity on lettuce seedlings was investigated. Root and shoot elongation of lettuce seedlings were inhibited by artemisinin in a concentration-dependent manner. The compound effectively arrested cell division and caused loss of cell viability in root tips of lettuce. Overproduction of reactive oxygen species (ROS) was induced by artemisinin. Lipid peroxidation, proline overproduction and reduction of chlorophyll content in lettuce seedlings were found after treatments. These results suggested that artemisinin could induce ROS overproduction, which caused membrane lipids peroxidation and cell death, and impacted mitosis and physiological processes, resulting in growth inhibition of receptor plants. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Non-coding RNAs and exercise: pathophysiological role and clinical application in the cardiovascular system.

PubMed

Gomes, Clarissa P C; de Gonzalo-Calvo, David; Toro, Rocio; Fernandes, Tiago; Theisen, Daniel; Wang, Da-Zhi; Devaux, Yvan

2018-05-23

There is overwhelming evidence that regular exercise training is protective against cardiovascular disease (CVD), the main cause of death worldwide. Despite the benefits of exercise, the intricacies of their underlying molecular mechanisms remain largely unknown. Non-coding RNAs (ncRNAs) have been recognized as a major regulatory network governing gene expression in several physiological processes and appeared as pivotal modulators in a myriad of cardiovascular processes under physiological and pathological conditions. However, little is known about ncRNA expression and role in response to exercise. Revealing the molecular components and mechanisms of the link between exercise and health outcomes will catalyse discoveries of new biomarkers and therapeutic targets. Here we review the current understanding of the ncRNA role in exercise-induced adaptations focused on the cardiovascular system and address their potential role in clinical applications for CVD. Finally, considerations and perspectives for future studies will be proposed. © 2018 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

Exploring the pH-Dependent Substrate Transport Mechanism of FocA Using Molecular Dynamics Simulation

PubMed Central

Lv, Xiaoying; Liu, Huihui; Ke, Meng; Gong, Haipeng

2013-01-01

FocA belongs to the formate-nitrate transporter family and plays an essential role in the export and uptake of formate in organisms. According to the available crystal structures, the N-terminal residues of FocA are structurally featureless at physiological conditions but at reduced pH form helices to harbor the cytoplasmic entrance of the substrate permeation pathway, which apparently explains the cessation of electrical signal observed in electrophysiological experiments. In this work, we found by structural analysis and molecular dynamics simulations that those N-terminal helices cannot effectively preclude the substrate permeation. Equilibrium simulations and thermodynamic calculations suggest that FocA is permeable to both formate and formic acid, the latter of which is transparent to electrophysiological studies as an electrically neutral species. Hence, the cease of electrical current at acidic pH may be caused by the change of the transported substrate from formate to formic acid. In addition, the mechanism of formate export at physiological pH is discussed. PMID:24359743

Chemoprevention in gastrointestinal physiology and disease. Anti-inflammatory approaches for colorectal cancer chemoprevention.

PubMed

Fajardo, Alexandra M; Piazza, Gary A

2015-07-15

Colorectal cancer (CRC) is one of the most common human malignancies and a leading cause of cancer-related deaths in developed countries. Identifying effective preventive strategies aimed at inhibiting the development and progression of CRC is critical for reducing the incidence and mortality of this malignancy. The prevention of carcinogenesis by anti-inflammatory agents including nonsteroidal anti-inflammatory drugs (NSAIDs), selective cyclooxygenase-2 (COX-2) inhibitors, and natural products is an area of considerable interest and research. Numerous anti-inflammatory agents have been identified as potential CRC chemopreventive agents but vary in their mechanism of action. This review will discuss the molecular mechanisms being studied for the CRC chemopreventive activity of NSAIDs (i.e., aspirin, sulindac, and ibuprofen), COX-2 inhibitors (i.e., celecoxib), natural products (i.e., curcumin, resveratrol, EGCG, genistein, and baicalein), and metformin. A deeper understanding of how these anti-inflammatory agents inhibit CRC will provide insight into the development of potentially safer and more effective chemopreventive drugs. Copyright © 2015 the American Physiological Society.

[Perioperative stroke following transurethral resection of prostate: high index of suspicion and stabilization of physiological parameters can save lives].

PubMed

Nag, Deb Sanjay; Chatterjee, Abhishek; Samaddar, Devi Prasad; Agarwal, Ajay

2017-01-09

We report a case of a 72 year old hypertensive male who developed severe hypertension followed by neurological deterioration in the immediate postoperative period after transurethral resection of prostate. While arterial blood gas and laboratory tests excluded transurethral resection of prostate syndrome or any other metabolic cause, reduction of blood pressure failed to ameliorate the symptoms. A cranial CT done 4hours after the onset of neurological symptoms revealed bilateral gangliocapsular and right thalamic infarcts. Oral aspirin was advised to prevent early recurrent stroke. Supportive treatment and mechanical ventilation ensured physiological stability and the patient recovered completely over the next few days without any residual neurological deficit. Copyright © 2016. Publicado por Elsevier Editora Ltda.

Effects of temperature and cellular interactions on the mechanics and morphology of human cancer cells investigated by atomic force microscopy.

PubMed

Li, Mi; Liu, LianQing; Xi, Ning; Wang, YueChao; Xiao, XiuBin; Zhang, WeiJing

2015-09-01

Cell mechanics plays an important role in cellular physiological activities. Recent studies have shown that cellular mechanical properties are novel biomarkers for indicating the cell states. In this article, temperature-controllable atomic force microscopy (AFM) was applied to quantitatively investigate the effects of temperature and cellular interactions on the mechanics and morphology of human cancer cells. First, AFM indenting experiments were performed on six types of human cells to investigate the changes of cellular Young's modulus at different temperatures and the results showed that the mechanical responses to the changes of temperature were variable for different types of cancer cells. Second, AFM imaging experiments were performed to observe the morphological changes in living cells at different temperatures and the results showed the significant changes of cell morphology caused by the alterations of temperature. Finally, by co-culturing human cancer cells with human immune cells, the mechanical and morphological changes in cancer cells were investigated. The results showed that the co-culture of cancer cells and immune cells could cause the distinct mechanical changes in cancer cells, but no significant morphological differences were observed. The experimental results improved our understanding of the effects of temperature and cellular interactions on the mechanics and morphology of cancer cells.

MRI-based three-dimensional thermal physiological characterization of thyroid gland of human body.

PubMed

Jin, Chao; He, Zhi Zhu; Yang, Yang; Liu, Jing

2014-01-01

This article is dedicated to present a MRI (magnetic resonance imaging) based three-dimensional finite element modeling on the thermal manifestations relating to the pathophysiology of thyroid gland. An efficient approach for identifying the metabolic dysfunctions of thyroid has also been demonstrated through tracking the localized non-uniform thermal distribution or enhanced dynamic imaging. The temperature features over the skin surface and thyroid domain have been characterized using the numerical simulation and experimental measurement which will help better interpret the thermal physiological mechanisms of the thyroid under steady-state or water-cooling condition. Further, parametric simulations on the hypermetabolism symptoms of hyperthyroidism and thermal effects within thyroid domain caused by varying breathing airflow in the trachea and blood-flow in artery and vein were performed. It was disclosed that among all the parameters, the airflow volume has the largest effect on the total heat flux of thyroid surface. However, thermal contributions caused by varying the breathing frequency and blood-flow velocity are negligibly small. The present study suggests a generalized way for simulating the close to reality physiological behavior or process of human thyroid, which is of significance for disease diagnosis and treatment planning. Copyright © 2013 IPEM. Published by Elsevier Ltd. All rights reserved.

Severe hypocalcaemia and hypophosphataemia following intravenous iron and denosumab: a novel drug interaction.

PubMed

Smyth, B; Ong, S

2016-03-01

We present the case of a 59-year-old woman with chronic kidney disease who suffered severe hypocalcaemia and hypophosphataemia after receiving denosumab and intravenous iron. This potentially life-threatening adverse drug interaction has never been reported before. We propose a mechanism to explain it with reference to the physiological derangements caused by both agents on calcium and phosphate homeostasis. © 2016 Royal Australasian College of Physicians.

Spacelab flight simulated by two monkeys at CERMA

NASA Technical Reports Server (NTRS)

Langereux, P.

1980-01-01

A semiautomatic module for two monkeys was designed. The module shelters two Rhesus monkeys seated side by side in a compartment, reducing the emotional stresses caused by isolation. Food pellets, water, and air are supplied and body wastes are automatically removed. Physiological and environmental parameters are continually monitored, making possible the performance of experiments concerning the pathophysiological mechanisms of the disorders of weightlessness. A ten day flight of the module in Spacelab was simulated.

Plasma fibronectin stabilizes Borrelia burgdorferi–endothelial interactions under vascular shear stress by a catch-bond mechanism

PubMed Central

Niddam, Alexandra F.; Ebady, Rhodaba; Bansal, Anil; Koehler, Anne; Hinz, Boris

2017-01-01

Bacterial dissemination via the cardiovascular system is the most common cause of infection mortality. A key step in dissemination is bacterial interaction with endothelia lining blood vessels, which is physically challenging because of the shear stress generated by blood flow. Association of host cells such as leukocytes and platelets with endothelia under vascular shear stress requires mechanically specialized interaction mechanisms, including force-strengthened catch bonds. However, the biomechanical mechanisms supporting vascular interactions of most bacterial pathogens are undefined. Fibronectin (Fn), a ubiquitous host molecule targeted by many pathogens, promotes vascular interactions of the Lyme disease spirochete Borrelia burgdorferi. Here, we investigated how B. burgdorferi exploits Fn to interact with endothelia under physiological shear stress, using recently developed live cell imaging and particle-tracking methods for studying bacterial–endothelial interaction biomechanics. We found that B. burgdorferi does not primarily target insoluble matrix Fn deposited on endothelial surfaces but, instead, recruits and induces polymerization of soluble plasma Fn (pFn), an abundant protein in blood plasma that is normally soluble and nonadhesive. Under physiological shear stress, caps of polymerized pFn at bacterial poles formed part of mechanically loaded adhesion complexes, and pFn strengthened and stabilized interactions by a catch-bond mechanism. These results show that B. burgdorferi can transform a ubiquitous but normally nonadhesive blood constituent to increase the efficiency, strength, and stability of bacterial interactions with vascular surfaces. Similar mechanisms may promote dissemination of other Fn-binding pathogens. PMID:28396443

Like cures like: a neuroimmunological model based on electromagnetic resonance.

PubMed

Shahabi, Shahram; Kasariyans, Aditya; Noorbakhsh, Farshid

2013-12-01

Recent investigations have pointed to the production of characteristic electromagnetic (EM) waves in highly diluted sterile filtrates of different microorganisms and their associated DNA molecules. Analysis of these diluted solutions that are prepared using methods almost identical to the way that homeopathic medicines are prepared has pointed to the existence of nanostructures capable of emitting EM waves. Combining these results with findings that point to the interaction of EM waves with sensory nerves with subsequent activation of homeostatic efferent pathways, we propose a model to describe mechanisms underlying the effects of homeopathic remedies. THE MODEL: Living cells and tissues are capable of generating EM waves in their physiological conditions. When a cell deviates from its physiological state, in addition to normal EM emissions, it starts to produce EM waves with altered characteristics. According to our model, the main cause of the therapeutic effects of homeopathic remedies is the occurrence of resonance between the non-physiological EM waves of the patient and extremely low-frequency EM waves produced by nanostructures present in the homeopathic remedy. Resonance occurs if the frequency and amplitude characteristics of the patient's non-physiological EM waves and those produced by nanostructures of the applied homeopathic remedy are similar. Once resonance occurs, stimulation of the patient's sensory neurons, which are sensitized due to inflammation of any origin, leads to triggering of different regulatory mechanisms, including the activation of descending antinociceptive and/or cholinergic anti-inflammatory pathways, which leads to the restoration of homeostasis.

Mechanisms Regulating Neuromuscular Junction Development and Function and Causes of Muscle Wasting.

PubMed

Tintignac, Lionel A; Brenner, Hans-Rudolf; Rüegg, Markus A

2015-07-01

The neuromuscular junction is the chemical synapse between motor neurons and skeletal muscle fibers. It is designed to reliably convert the action potential from the presynaptic motor neuron into the contraction of the postsynaptic muscle fiber. Diseases that affect the neuromuscular junction may cause failure of this conversion and result in loss of ambulation and respiration. The loss of motor input also causes muscle wasting as muscle mass is constantly adapted to contractile needs by the balancing of protein synthesis and protein degradation. Finally, neuromuscular activity and muscle mass have a major impact on metabolic properties of the organisms. This review discusses the mechanisms involved in the development and maintenance of the neuromuscular junction, the consequences of and the mechanisms involved in its dysfunction, and its role in maintaining muscle mass during aging. As life expectancy is increasing, loss of muscle mass during aging, called sarcopenia, has emerged as a field of high medical need. Interestingly, aging is also accompanied by structural changes at the neuromuscular junction, suggesting that the mechanisms involved in neuromuscular junction maintenance might be disturbed during aging. In addition, there is now evidence that behavioral paradigms and signaling pathways that are involved in longevity also affect neuromuscular junction stability and sarcopenia. Copyright © 2015 the American Physiological Society.

Negative regulation of multifunctional Ca2+/calmodulin-dependent protein kinases: physiological and pharmacological significance of protein phosphatases

PubMed Central

Ishida, A; Sueyoshi, N; Shigeri, Y; Kameshita, I

2008-01-01

Multifunctional Ca2+/calmodulin-dependent protein kinases (CaMKs) play pivotal roles in intracellular Ca2+ signaling pathways. There is growing evidence that CaMKs are involved in the pathogenic mechanisms underlying various human diseases. In this review, we begin by briefly summarizing our knowledge of the involvement of CaMKs in the pathogenesis of various diseases suggested to be caused by the dysfunction/dysregulation or aberrant expression of CaMKs. It is widely known that the activities of CaMKs are strictly regulated by protein phosphorylation/dephosphorylation of specific phosphorylation sites. Since phosphorylation status is balanced by protein kinases and protein phosphatases, the mechanism of dephosphorylation/deactivation of CaMKs, corresponding to their ‘switching off', is extremely important, as is the mechanism of phosphorylation/activation corresponding to their ‘switching on'. Therefore, we focus on the regulation of multifunctional CaMKs by protein phosphatases. We summarize the current understanding of negative regulation of CaMKs by protein phosphatases. We also discuss the biochemical properties and physiological significance of a protein phosphatase that we designated as Ca2+/calmodulin-dependent protein kinase phosphatase (CaMKP), and those of its homologue CaMKP-N. Pharmacological applications of CaMKP inhibitors are also discussed. These compounds may be useful not only for exploring the physiological functions of CaMKP/CaMKP-N, but also as novel chemotherapies for various diseases. PMID:18454172

Structure-function relations in physiology education: Where's the mechanism?

PubMed

Lira, Matthew E; Gardner, Stephanie M

2017-06-01

Physiology demands systems thinking: reasoning within and between levels of biological organization and across different organ systems. Many physiological mechanisms explain how structures and their properties interact at one level of organization to produce emergent functions at a higher level of organization. Current physiology principles, such as structure-function relations, selectively neglect mechanisms by not mentioning this term explicitly. We explored how students characterized mechanisms and functions to shed light on how students make sense of these terms. Students characterized mechanisms as 1 ) processes that occur at levels of organization lower than that of functions; and 2 ) as detailed events with many steps involved. We also found that students produced more variability in how they characterized functions compared with mechanisms: students characterized functions in relation to multiple levels of organization and multiple definitions. We interpret these results as evidence that students see mechanisms as holding a more narrow definition than used in the biological sciences, and that students struggle to coordinate and distinguish mechanisms from functions due to cognitive processes germane to learning in many domains. We offer the instructional suggestion that we scaffold student learning by affording students opportunities to relate and also distinguish between these terms so central to understanding physiology. Copyright © 2017 the American Physiological Society.

Obstructive sleep apnea.

PubMed

White, David P; Younes, Magdy K

2012-10-01

Obstructive sleep apnea (OSA) is a common disorder characterized by repetitive collapse of the pharyngeal airway during sleep. Control of pharyngeal patency is a complex process relating primarily to basic anatomy and the activity of many pharyngeal dilator muscles. The control of these muscles is regulated by a number of processes including respiratory drive, negative pressure reflexes, and state (sleep) effects. In general, patients with OSA have an anatomically small airway the patency of which is maintained during wakefulness by reflex-driven augmented dilator muscle activation. At sleep onset, muscle activity falls, thereby compromising the upper airway. However, recent data suggest that the mechanism of OSA differs substantially among patients, with variable contributions from several physiologic characteristics including, among others: level of upper airway dilator muscle activation required to open the airway, increase in chemical drive required to recruit the pharyngeal muscles, chemical control loop gain, and arousal threshold. Thus, the cause of sleep apnea likely varies substantially between patients. Other physiologic mechanisms likely contributing to OSA pathogenesis include falling lung volume during sleep, shifts in blood volume from peripheral tissues to the neck, and airway edema. Apnea severity may progress over time, likely due to weight gain, muscle/nerve injury, aging effects on airway anatomy/collapsibility, and changes in ventilatory control stability. © 2012 American Physiological Society

Mechanical property quantification of endothelial cells using scanning acoustic microscopy

NASA Astrophysics Data System (ADS)

Shelke, A.; Brand, S.; Kundu, T.; Bereiter-Hahn, J.; Blase, C.

2012-04-01

The mechanical properties of cells reflect dynamic changes of cellular organization which occur during physiologic activities like cell movement, cell volume regulation or cell division. Thus the study of cell mechanical properties can yield important information for understanding these physiologic activities. Endothelial cells form the thin inner lining of blood vessels in the cardiovascular system and are thus exposed to shear stress as well as tensile stress caused by the pulsatile blood flow. Endothelial dysfunction might occur due to reduced resistance to mechanical stress and is an initial step in the development of cardiovascular disease like, e.g., atherosclerosis. Therefore we investigated the mechanical properties of primary human endothelial cells (HUVEC) of different age using scanning acoustic microscopy at 1.2 GHz. The HUVECs are classified as young (tD < 90 h) and old (tD > 90 h) cells depending upon the generation time for the population doubling of the culture (tD). Longitudinal sound velocity and geometrical properties of cells (thickness) were determined using the material signature curve V(z) method for variable culture condition along spatial coordinates. The plane wave technique with normal incidence is assumed to solve two-dimensional wave equation. The size of the cells is modeled using multilayered (solid-fluid) system. The propagation of transversal wave and surface acoustic wave are neglected in soft matter analysis. The biomechanical properties of HUVEC cells are quantified in an age dependent manner.

Mechanical characterization of human red blood cells under different osmotic conditions by robotic manipulation with optical tweezers.

PubMed

Tan, Youhua; Sun, Dong; Wang, Jinzhi; Huang, Wenhao

2010-07-01

The physiological functions of human red blood cells (RBCs) play a crucial role to human health and are greatly influenced by their mechanical properties. Any alteration of the cell mechanics may cause human diseases. The osmotic condition is an important factor to the physiological environment, but its effect on RBCs has been little studied. To investigate this effect, robotic manipulation technology with optical tweezers is utilized in this paper to characterize the mechanical properties of RBCs in different osmotic conditions. The effectiveness of this technology is demonstrated first in the manipulation of microbeads. Then the optical tweezers are used to stretch RBCs to acquire the force-deformation relationships. To extract cell properties from the experimental data, a mechanical model is developed for RBCs in hypotonic conditions by extending our previous work , and the finite element model is utilized for RBCs in isotonic and hypertonic conditions. Through comparing the modeling results to the experimental data, the shear moduli of RBCs in different osmotic solutions are characterized, which shows that the cell stiffness increases with elevated osmolality. Furthermore, the property variation and potential biomedical significance of this study are discussed. In conclusion, this study indicates that the osmotic stress has a significant effect on the cell properties of human RBCs, which may provide insight into the pathology analysis and therapy of some human diseases.

Neuroendocrine Causes of Amenorrhea—An Update

PubMed Central

Fourman, Lindsay T.

2015-01-01

Context: Secondary amenorrhea—the absence of menses for three consecutive cycles—affects approximately 3–4% of reproductive age women, and infertility—the failure to conceive after 12 months of regular intercourse—affects approximately 6–10%. Neuroendocrine causes of amenorrhea and infertility, including functional hypothalamic amenorrhea and hyperprolactinemia, constitute a majority of these cases. Objective: In this review, we discuss the physiologic, pathologic, and iatrogenic causes of amenorrhea and infertility arising from perturbations in the hypothalamic-pituitary-adrenal axis, including potential genetic causes. We focus extensively on the hormonal mechanisms involved in disrupting the hypothalamic-pituitary-ovarian axis. Conclusions: A thorough understanding of the neuroendocrine causes of amenorrhea and infertility is critical for properly assessing patients presenting with these complaints. Prompt evaluation and treatment are essential to prevent loss of bone mass due to hypoestrogenemia and/or to achieve the time-sensitive treatment goal of conception. PMID:25581597

Physiological mechanisms associated with ovulation prediction using the CUE Ovulation Predictor.

PubMed

Fernando, R S; Regas, J; Betz, G

1988-05-01

It has been shown that monitoring of salivary electrical resistance (SR) enables prediction of ovulation several days in advance, since a peak in SR is seen 5-6 days before the LH peak. This paper explores physiological mechanisms that may account for this change. The pathway whereby oestrogen stimulates aldosterone (ALDO) secretion acting through the renin-angiotensin system was considered. It is shown that this mechanism would only result in increasing SR as oestrogen values rise during the follicular phase and therefore is not an explanation of the SR peak and declining SR 5-6 days before the LH peak. The reported trend of sodium in milk of ovulating women parallels that of SR. It is shown that these changes are most likely to be due to a similar change in aldosterone levels. A possible role for adrenocorticotrophic hormone (ACTH) in causing the changes in aldosterone is discussed and supported with data from other independent studies as well as with preliminary data obtained from two normally ovulating subjects. Peaks in ACTH, ALDO and SR were coincidental and occurred 6 days before the LH peak. The temporal relationship observed among these variables suggest that ACTH, by affecting ALDO, modifies salivary electrolytes and hence SR.

Salicylic acid-induced abiotic stress tolerance and underlying mechanisms in plants

PubMed Central

Khan, M. Iqbal R.; Fatma, Mehar; Per, Tasir S.; Anjum, Naser A.; Khan, Nafees A.

2015-01-01

Abiotic stresses (such as metals/metalloids, salinity, ozone, UV-B radiation, extreme temperatures, and drought) are among the most challenging threats to agricultural system and economic yield of crop plants. These stresses (in isolation and/or combination) induce numerous adverse effects in plants, impair biochemical/physiological and molecular processes, and eventually cause severe reductions in plant growth, development and overall productivity. Phytohormones have been recognized as a strong tool for sustainably alleviating adverse effects of abiotic stresses in crop plants. In particular, the significance of salicylic acid (SA) has been increasingly recognized in improved plant abiotic stress-tolerance via SA-mediated control of major plant-metabolic processes. However, the basic biochemical/physiological and molecular mechanisms that potentially underpin SA-induced plant-tolerance to major abiotic stresses remain least discussed. Based on recent reports, this paper: (a) overviews historical background and biosynthesis of SA under both optimal and stressful environments in plants; (b) critically appraises the role of SA in plants exposed to major abiotic stresses; (c) cross-talks potential mechanisms potentially governing SA-induced plant abiotic stress-tolerance; and finally (d) briefly highlights major aspects so far unexplored in the current context. PMID:26175738

Human thermoregulation and measurement of body temperature in exercise and clinical settings.

PubMed

Lim, Chin Leong; Byrne, Chris; Lee, Jason Kw

2008-04-01

This review discusses human thermoregulation during exercise and the measurement of body temperature in clinical and exercise settings. The thermoregulatory mechanisms play important roles in maintaining physiological homeostasis during rest and physical exercise. Physical exertion poses a challenge to thermoregulation by causing a substantial increase in metabolic heat production. However, within a non-thermolytic range, the thermoregulatory mechanisms are capable of adapting to sustain physiological functions under these conditions. The central nervous system may also rely on hyperthermia to protect the body from "overheating." Hyperthermia may serve as a self-limiting signal that triggers central inhibition of exercise performance when a temperature threshold is achieved. Exposure to sub-lethal heat stress may also confer tolerance against higher doses of heat stress by inducing the production of heat shock proteins, which protect cells against the thermolytic effects of heat. Advances in body temperature measurement also contribute to research in thermoregulation. Current evidence supports the use of oral temperature measurement in the clinical setting, although it may not be as convenient as tympanic temperature measurement using the infrared temperature scanner. Rectal and oesophagus temperatures are widely accepted surrogate measurements of core temperature (Tc), but they cause discomfort and are less likely to be accepted by users. Gastrointestinal temperature measurement using the ingestible temperature sensor provides an acceptable level of accuracy as a surrogate measure of Tc without causing discomfort to the user. This form of Tc measurement also allows Tc to be measured continuously in the field and has gained wider acceptance in the last decade.

Acoustically detectable cellular-level lung injury induced by fluid mechanical stresses in microfluidic airway systems.

PubMed

Huh, Dongeun; Fujioka, Hideki; Tung, Yi-Chung; Futai, Nobuyuki; Paine, Robert; Grotberg, James B; Takayama, Shuichi

2007-11-27

We describe a microfabricated airway system integrated with computerized air-liquid two-phase microfluidics that enables on-chip engineering of human airway epithelia and precise reproduction of physiologic or pathologic liquid plug flows found in the respiratory system. Using this device, we demonstrate cellular-level lung injury under flow conditions that cause symptoms characteristic of a wide range of pulmonary diseases. Specifically, propagation and rupture of liquid plugs that simulate surfactant-deficient reopening of closed airways lead to significant injury of small airway epithelial cells by generating deleterious fluid mechanical stresses. We also show that the explosive pressure waves produced by plug rupture enable detection of the mechanical cellular injury as crackling sounds.

Neurohumoral and mechanical factors in the modulation of left ventricular mass

NASA Technical Reports Server (NTRS)

Franklin, Eleanor I.; Hawthorne, Edward W.

1987-01-01

The goals for the research were to define, describe, and study those neuroendocrine and mechanical mechanisms that may play a role in the initiation and maintenance of an increase in, or cause regression of, the mass of the left ventricle. Dynamic changes in heart mass have been observed to occur in man and animals: (1) enlargement of the heart is frequently encountered in patients with hypertensive disease, and (2) decrease in heart mass has been reported for men exposed to prolonged space flight. The basic physiologic processes which may explain how these changes occur, and the effects of gain or loss of myocardial mass on cardiac performance were considered significant questions to be answered for the benefit of the National Aeronautics and Space Administration.

Influence of Global and Local Membrane Curvature on Mechanosensitive Ion Channels: A Finite Element Approach

PubMed Central

Bavi, Omid; Cox, Charles D.; Vossoughi, Manouchehr; Naghdabadi, Reza; Jamali, Yousef; Martinac, Boris

2016-01-01

Mechanosensitive (MS) channels are ubiquitous molecular force sensors that respond to a number of different mechanical stimuli including tensile, compressive and shear stress. MS channels are also proposed to be molecular curvature sensors gating in response to bending in their local environment. One of the main mechanisms to functionally study these channels is the patch clamp technique. However, the patch of membrane surveyed using this methodology is far from physiological. Here we use continuum mechanics to probe the question of how curvature, in a standard patch clamp experiment, at different length scales (global and local) affects a model MS channel. Firstly, to increase the accuracy of the Laplace’s equation in tension estimation in a patch membrane and to be able to more precisely describe the transient phenomena happening during patch clamping, we propose a modified Laplace’s equation. Most importantly, we unambiguously show that the global curvature of a patch, which is visible under the microscope during patch clamp experiments, is of negligible energetic consequence for activation of an MS channel in a model membrane. However, the local curvature (RL < 50) and the direction of bending are able to cause considerable changes in the stress distribution through the thickness of the membrane. Not only does local bending, in the order of physiologically relevant curvatures, cause a substantial change in the pressure profile but it also significantly modifies the stress distribution in response to force application. Understanding these stress variations in regions of high local bending is essential for a complete understanding of the effects of curvature on MS channels. PMID:26861405

Baroreflex and neurovascular responses to skeletal muscle mechanoreflex activation in humans: an exercise in integrative physiology.

PubMed

Drew, Rachel C

2017-12-01

Cardiovascular adjustments to exercise resulting in increased blood pressure (BP) and heart rate (HR) occur in response to activation of several neural mechanisms: the exercise pressor reflex, central command, and the arterial baroreflex. Neural inputs from these feedback and feedforward mechanisms integrate in the cardiovascular control centers in the brain stem and modulate sympathetic and parasympathetic neural outflow, resulting in the increased BP and HR observed during exercise. Another specific consequence of the central neural integration of these inputs during exercise is increased sympathetic neural outflow directed to the kidneys, causing renal vasoconstriction, a key reflex mechanism involved in blood flow redistribution during increased skeletal muscle work. Studies in humans have shown that muscle mechanoreflex activation inhibits cardiac vagal outflow, decreasing the sensitivity of baroreflex control of HR. Metabolite sensitization of muscle mechanoreceptors can lead to reduced sensitivity of baroreflex control of HR, with thromboxane being one of the metabolites involved, via greater inhibition of cardiac vagal outflow without affecting baroreflex control of BP or baroreflex resetting. Muscle mechanoreflex activation appears to play a predominant role in causing renal vasoconstriction, both in isolation and in the presence of local metabolites. Limited investigations in older adults and patients with cardiovascular-related disease have provided some insight into how the influence of muscle mechanoreflex activation on baroreflex function and renal vasoconstriction is altered in these populations. However, future research is warranted to better elucidate the specific effect of muscle mechanoreflex activation on baroreflex and neurovascular responses with aging and cardiovascular-related disease. Copyright © 2017 the American Physiological Society.

Impacts of extreme winter warming events on plant physiology in a sub-Arctic heath community.

PubMed

Bokhorst, Stef; Bjerke, Jarle W; Davey, Matthew P; Taulavuori, Kari; Taulavuori, Erja; Laine, Kari; Callaghan, Terry V; Phoenix, Gareth K

2010-10-01

Insulation provided by snow cover and tolerance of freezing by physiological acclimation allows Arctic plants to survive cold winter temperatures. However, both the protection mechanisms may be lost with winter climate change, especially during extreme winter warming events where loss of snow cover from snow melt results in exposure of plants to warm temperatures and then returning extreme cold in the absence of insulating snow. These events cause considerable damage to Arctic plants, but physiological responses behind such damage remain unknown. Here, we report simulations of extreme winter warming events using infrared heating lamps and soil warming cables in a sub-Arctic heathland. During these events, we measured maximum quantum yield of photosystem II (PSII), photosynthesis, respiration, bud swelling and associated bud carbohydrate changes and lipid peroxidation to identify physiological responses during and after the winter warming events in three dwarf shrub species: Empetrum hermaphroditum, Vaccinium vitis-idaea and Vaccinium myrtillus. Winter warming increased maximum quantum yield of PSII, and photosynthesis was initiated for E. hermaphroditum and V. vitis-idaea. Bud swelling, bud carbohydrate decreases and lipid peroxidation were largest for E. hermaphroditum, whereas V. myrtillus and V. vitis-idaea showed no or less strong responses. Increased physiological activity and bud swelling suggest that sub-Arctic plants can initiate spring-like development in response to a short winter warming event. Lipid peroxidation suggests that plants experience increased winter stress. The observed differences between species in physiological responses are broadly consistent with interspecific differences in damage seen in previous studies, with E. hermaphroditum and V. myrtillus tending to be most sensitive. This suggests that initiation of spring-like development may be a major driver in the damage caused by winter warming events that are predicted to become more frequent in some regions of the Arctic and that may ultimately drive plant community shifts. Copyright © Physiologia Plantarum 2010.

Evolution of time-keeping mechanisms: early emergence and adaptation to photoperiod

PubMed Central

Hut, R. A.; Beersma, D. G. M.

2011-01-01

Virtually all species have developed cellular oscillations and mechanisms that synchronize these cellular oscillations to environmental cycles. Such environmental cycles in biotic (e.g. food availability and predation risk) or abiotic (e.g. temperature and light) factors may occur on a daily, annual or tidal time scale. Internal timing mechanisms may facilitate behavioural or physiological adaptation to such changes in environmental conditions. These timing mechanisms commonly involve an internal molecular oscillator (a ‘clock’) that is synchronized (‘entrained’) to the environmental cycle by receptor mechanisms responding to relevant environmental signals (‘Zeitgeber’, i.e. German for time-giver). To understand the evolution of such timing mechanisms, we have to understand the mechanisms leading to selective advantage. Although major advances have been made in our understanding of the physiological and molecular mechanisms driving internal cycles (proximate questions), studies identifying mechanisms of natural selection on clock systems (ultimate questions) are rather limited. Here, we discuss the selective advantage of a circadian system and how its adaptation to day length variation may have a functional role in optimizing seasonal timing. We discuss various cases where selective advantages of circadian timing mechanisms have been shown and cases where temporarily loss of circadian timing may cause selective advantage. We suggest an explanation for why a circadian timing system has emerged in primitive life forms like cyanobacteria and we evaluate a possible molecular mechanism that enabled these bacteria to adapt to seasonal variation in day length. We further discuss how the role of the circadian system in photoperiodic time measurement may explain differential selection pressures on circadian period when species are exposed to changing climatic conditions (e.g. global warming) or when they expand their geographical range to different latitudes or altitudes. PMID:21690131

Cataract-associated P23T γD-crystallin retains a native-like fold in amorphous-looking aggregates formed at physiological pH

NASA Astrophysics Data System (ADS)

Boatz, Jennifer C.; Whitley, Matthew J.; Li, Mingyue; Gronenborn, Angela M.; van der Wel, Patrick C. A.

2017-05-01

Cataracts cause vision loss through the large-scale aggregation of eye lens proteins as a result of ageing or congenital mutations. The development of new treatments is hindered by uncertainty about the nature of the aggregates and their mechanism of formation. We describe the structure and morphology of aggregates formed by the P23T human γD-crystallin mutant associated with congenital cataracts. At physiological pH, the protein forms aggregates that look amorphous and disordered by electron microscopy, reminiscent of the reported formation of amorphous deposits by other crystallin mutants. Surprisingly, solid-state NMR reveals that these amorphous deposits have a high degree of structural homogeneity at the atomic level and that the aggregated protein retains a native-like conformation, with no evidence for large-scale misfolding. Non-physiological destabilizing conditions used in many in vitro aggregation studies are shown to yield qualitatively different, highly misfolded amyloid-like fibrils.

Is cell aging caused by respiration-dependent injury to the mitochondrial genome

NASA Technical Reports Server (NTRS)

Fleming, J. E.; Yengoyan, L. S.; Miquel, J.; Cottrell, S. F.; Economos, A. C.

1982-01-01

Though intrinsic mitochondrial aging has been considered before as a possible cause of cellular senescence, the mechanisms of such mitochondrial aging have remained obscure. In this article, the hypothesis of free-radical-induced inhibition of mitochondrial replenishment in fixed postmitotic cells is expanded. It is maintained that the respiration-dependent production of superoxide and hydroxyl radicals may not be fully counteracted, leading to a continuous production of lipoperoxides and malonaldehyde in actively respiring mitochondria. These compounds, in turn, can easily react with the mitochondrial DNA which is in close spatial relationship with the inner mitochondrial membrane, producing an injury that the mitochondria may be unable to counteract because of their apparent lack of adequate repair mechanisms. Mitochondrial division may thus be inhibited leading to age-related reduction of mitochondrial numbers, a deficit in energy production with a concomitant decrease in protein synthesis, deterioration of physiological performance, and, therefore, of organismic performance.

Generation and phenotypic analysis of mice lacking all urea transporters.

PubMed

Jiang, Tao; Li, Yingjie; Layton, Anita T; Wang, Weiling; Sun, Yi; Li, Min; Zhou, Hong; Yang, Baoxue

2017-02-01

Urea transporters (UT) are a family of transmembrane urea-selective channel proteins expressed in multiple tissues and play an important role in the urine concentrating mechanism of the mammalian kidney. UT inhibitors have diuretic activity and could be developed as novel diuretics. To determine if functional deficiency of all UTs in all tissues causes physiological abnormality, we established a novel mouse model in which all UTs were knocked out by deleting an 87 kb of DNA fragment containing most parts of Slc14a1 and Slc14a2 genes. Western blot analysis and immunofluorescence confirmed that there is no expression of urea transporter in these all-UT-knockout mice. Daily urine output was nearly 3.5-fold higher, with significantly lower urine osmolality in all-UT-knockout mice than that in wild-type mice. All-UT-knockout mice were not able to increase urinary urea concentration and osmolality after water deprivation, acute urea loading, or high protein intake. A computational model that simulated UT-knockout mouse models identified the individual contribution of each UT in urine concentrating mechanism. Knocking out all UTs also decreased the blood pressure and promoted the maturation of the male reproductive system. Thus, functional deficiency of all UTs caused a urea-selective urine-concentrating defect with little physiological abnormality in extrarenal organs. Copyright © 2016 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

Generation and phenotypic analysis of mice lacking all urea transporters

PubMed Central

Jiang, Tao; Li, Yingjie; Layton, Anita T.; Wang, Weiling; Sun, Yi; Li, Min; Zhou, Hong; Yang, Baoxue

2017-01-01

Urea transporters (UT) are a family of transmembrane urea-selective channel proteins expressed in multiple tissues and play an important role in the urine concentrating mechanism of the mammalian kidney. UT inhibitors have been identified to have diuretic activity and might be developed as novel diuretics. To determine if functional deficiency of all UTs in all tissues causes physiological abnormality, we established a novel mouse model in which all UTs were knocked out by deleting an 87 kb of DNA fragment containing most parts of Slc14a1 and Slc14a2 genes. Western blot analysis and immunofluorescence confirmed that there is no expression of urea transporter in all-UT-knockout mice. Daily urine output was nearly 3.5-fold higher, with significantly lower urine osmolality, in all-UT-knockout-mice than that in wild-type mice, and urine osmolality was significantly lower. All-UT-knockout mice were not able to increase urinary urea concentration and osmolality after water deprivation, acute urea loading or high protein intake. A computational model that simulated UT knockout mouse models identified the individual contribution of each UT in urine concentrating mechanism. Knocking out all UTs also decreased the blood pressure and promoted the maturation of the male reproductive system. These results revealed that functional deficiency of all UTs caused urea selective urine concentrating defect with little physiological abnormality in extrarenal organs. PMID:27914708

Pathogenesis of myasthenia gravis: update on disease types, models, and mechanisms.

PubMed

Phillips, William D; Vincent, Angela

2016-01-01

Myasthenia gravis is an autoimmune disease of the neuromuscular junction (NMJ) caused by antibodies that attack components of the postsynaptic membrane, impair neuromuscular transmission, and lead to weakness and fatigue of skeletal muscle. This can be generalised or localised to certain muscle groups, and involvement of the bulbar and respiratory muscles can be life threatening. The pathogenesis of myasthenia gravis depends upon the target and isotype of the autoantibodies. Most cases are caused by immunoglobulin (Ig)G1 and IgG3 antibodies to the acetylcholine receptor (AChR). They produce complement-mediated damage and increase the rate of AChR turnover, both mechanisms causing loss of AChR from the postsynaptic membrane. The thymus gland is involved in many patients, and there are experimental and genetic approaches to understand the failure of immune tolerance to the AChR. In a proportion of those patients without AChR antibodies, antibodies to muscle-specific kinase (MuSK), or related proteins such as agrin and low-density lipoprotein receptor-related protein 4 (LRP4), are present. MuSK antibodies are predominantly IgG4 and cause disassembly of the neuromuscular junction by disrupting the physiological function of MuSK in synapse maintenance and adaptation. Here we discuss how knowledge of neuromuscular junction structure and function has fed into understanding the mechanisms of AChR and MuSK antibodies. Myasthenia gravis remains a paradigm for autoantibody-mediated conditions and these observations show how much there is still to learn about synaptic function and pathological mechanisms.

Influence of hypo- and hyperthermia on death time estimation - A simulation study.

PubMed

Muggenthaler, H; Hubig, M; Schenkl, S; Mall, G

2017-09-01

Numerous physiological and pathological mechanisms can cause elevated or lowered body core temperatures. Deviations from the physiological level of about 37°C can influence temperature based death time estimations. However, it has not been investigated by means of thermodynamics, to which extent hypo- and hyperthermia bias death time estimates. Using numerical simulation, the present study investigates the errors inherent in temperature based death time estimation in case of elevated or lowered body core temperatures before death. The most considerable errors with regard to the normothermic model occur in the first few hours post-mortem. With decreasing body core temperature and increasing post-mortem time the error diminishes and stagnates at a nearly constant level. Copyright © 2017 Elsevier B.V. All rights reserved.

Physiological and molecular biochemical mechanisms of bile formation

PubMed Central

Reshetnyak, Vasiliy Ivanovich

2013-01-01

This review considers the physiological and molecular biochemical mechanisms of bile formation. The composition of bile and structure of a bile canaliculus, biosynthesis and conjugation of bile acids, bile phospholipids, formation of bile micellar structures, and enterohepatic circulation of bile acids are described. In general, the review focuses on the molecular physiology of the transporting systems of the hepatocyte sinusoidal and apical membranes. Knowledge of physiological and biochemical basis of bile formation has implications for understanding the mechanisms of development of pathological processes, associated with diseases of the liver and biliary tract. PMID:24259965

Conservation Physiology and Conservation Pathogens: White-Nose Syndrome and Integrative Biology for Host-Pathogen Systems.

PubMed

Willis, Craig K R

2015-10-01

Conservation physiology aims to apply an understanding of physiological mechanisms to management of imperiled species, populations, or ecosystems. One challenge for physiologists hoping to apply their expertise to conservation is connecting the mechanisms we study, often in the laboratory, with the vital rates of populations in the wild. There is growing appreciation that infectious pathogens can threaten populations and species, and represent an important issue for conservation. Conservation physiology has much to offer in terms of addressing the threat posed to some host species by infectious pathogens. At the same time, the well-developed theoretical framework of disease ecology could provide a model to help advance the application of physiology to a range of other conservation issues. Here, I use white-nose syndrome (WNS) in hibernating North American bats as an example of a conservation problem for which integrative physiological research has been a critical part of research and management. The response to WNS highlights the importance of a well-developed theoretical framework for the application of conservation physiology to a particular threat. I review what is known about physiological mechanisms associated with mortality from WNS and emphasize the value of combining a strong theoretical background with integrative physiological studies in order to connect physiological mechanisms with population processes and thereby maximize the potential benefits of conservation physiology. © The Author 2015. Published by Oxford University Press on behalf of the Society for Integrative and Comparative Biology. All rights reserved. For permissions please email: journals.permissions@oup.com.

A physiological perspective on fisheries-induced evolution.

PubMed

Hollins, Jack; Thambithurai, Davide; Koeck, Barbara; Crespel, Amelie; Bailey, David M; Cooke, Steven J; Lindström, Jan; Parsons, Kevin J; Killen, Shaun S

2018-06-01

There is increasing evidence that intense fishing pressure is not only depleting fish stocks but also causing evolutionary changes to fish populations. In particular, body size and fecundity in wild fish populations may be altered in response to the high and often size-selective mortality exerted by fisheries. While these effects can have serious consequences for the viability of fish populations, there are also a range of traits not directly related to body size which could also affect susceptibility to capture by fishing gears-and therefore fisheries-induced evolution (FIE)-but which have to date been ignored. For example, overlooked within the context of FIE is the likelihood that variation in physiological traits could make some individuals within species more vulnerable to capture. Specifically, traits related to energy balance (e.g., metabolic rate), swimming performance (e.g., aerobic scope), neuroendocrinology (e.g., stress responsiveness) and sensory physiology (e.g., visual acuity) are especially likely to influence vulnerability to capture through a variety of mechanisms. Selection on these traits could produce major shifts in the physiological traits within populations in response to fishing pressure that are yet to be considered but which could influence population resource requirements, resilience, species' distributions and responses to environmental change.

Stress response physiology of thermophiles.

PubMed

Ranawat, Preeti; Rawat, Seema

2017-04-01

Thermo (or hyperthermo) philic microorganisms are ubiquitous having a wide range of habitats from freshly fallen snow to pasteurized milk to geothermal areas like hot springs. The variations in physicochemical conditions, viz., temperature, pH, nutrient availability and light intensity in the habitats always pose stress conditions for the inhabitants leading to slow growth or cell death. The industrial processes used for harvesting secondary metabolites such as enzymes, toxins and organic acids also create stressed environments for thermophiles. The production of DNA-binding proteins, activation of reactive oxygen species detoxification system, compatible solute accumulation, expression of heat shock proteins and alterations in morphology are a few examples of physiological changes demonstrated by these microscopic lifeforms in stress. These microorganisms exhibit complex genetic and physiological changes to minimize, adapt to and repair damage caused by extreme environmental disturbances. These changes are termed as 'stress responses' which enable them to stabilize their homeostasis. The exploration of important thermophilic factors would pave the way in engineering the microbial strains for various biotechnological applications. This review article presents a picture of physiological responses of thermophiles against various stress conditions as their mechanisms to respond to stress make them model organisms to further explore them for basic and applied biology purposes.

Zinc: physiology, deficiency, and parenteral nutrition.

PubMed

Livingstone, Callum

2015-06-01

The essential trace element zinc (Zn) has a large number of physiologic roles, in particular being required for growth and functioning of the immune system. Adaptive mechanisms enable the body to maintain normal total body Zn status over a wide range of intakes, but deficiency can occur because of reduced absorption or increased gastrointestinal losses. Deficiency impairs physiologic processes, leading to clinical consequences that include failure to thrive, skin rash, and impaired wound healing. Mild deficiency that is not clinically overt may still cause nonspecific consequences, such as susceptibility to infection and poor growth. The plasma Zn concentration has poor sensitivity and specificity as a test of deficiency. Consequently, diagnosis of deficiency requires a combination of clinical assessment and biochemical tests. Patients receiving parenteral nutrition (PN) are susceptible to Zn deficiency and its consequences. Nutrition support teams should have a strategy for assessing Zn status and optimizing this by appropriate supplementation. Nutrition guidelines recommend generous Zn provision from the start of PN. This review covers the physiology of Zn, the consequences of its deficiency, and the assessment of its status, before discussing its role in PN. © 2015 American Society for Parenteral and Enteral Nutrition.

Overview on the effects of parasites on fish health

USGS Publications Warehouse

Iwanowicz, D.D.; Cipriano, R.C.; Bruckner, A.W.; Shchelkunov, I.S.

2011-01-01

It is believed by many that parasites are only as important as the fish they infect. Parasites are ubiquitous, primarily surviving in a dynamic equilibrium with their host(s) and they are often overlooked in fish health assessments. Changes in the environment, both anthropogenic and environmental, can alter the parasite/host equilibrium and cause disease or mortality in fish. Therefore it is imperative that we have knowledge of both parasites and parasitic communities within a given population. When fish kills occur, it can often be associated with changes in parasite density and community composition. Often the damage associated with these fish is relative to the rate of infestation with the parasite; a fish that is lightly infected will show few signs of the parasite, while a heavily infected fish may become physiologically impaired and even die. Parasites can cause mechanical damage (fusion of gill lamellae, tissue replacement), physiological damage (cell proliferation, immunomodulation, detrimental behavioral responses, altered growth) and reproductive damage. As parasitism is the most common lifestyle on the planet, understanding its role in the environment may help researchers understand changes in a given fish population or stream ecosystem.

Vegetable Grafting as a Tool to Improve Drought Resistance and Water Use Efficiency

PubMed Central

Kumar, Pradeep; Rouphael, Youssef; Cardarelli, Mariateresa; Colla, Giuseppe

2017-01-01

Drought is one of the most prevalent limiting factors causing considerable losses in crop productivity, inflicting economic as well as nutritional insecurity. One of the greatest challenges faced by the scientific community in the next few years is to minimize the yield losses caused by drought. Drought resistance is a complex quantitative trait controlled by many genes. Thus, introgression of drought resistance traits into high yielding genotypes has been a challenge to plant breeders. Vegetable grafting using rootstocks has emerged as a rapid tool in tailoring plants to better adapt to suboptimal growing conditions. This has induced changes in shoot physiology. Grafting applications have expanded mainly in Solanaceous crops and cucurbits, which are commonly grown in arid and semi-arid areas characterized by long drought periods. The current review gives an overview of the recent scientific literature on root-shoot interaction and rootstock-driven alteration of growth, yield, and fruit quality in grafted vegetable plants under drought stress. Further, we elucidate the drought resistance mechanisms of grafted vegetables at the morpho-physiological, biochemical, and molecular levels. PMID:28713405

Balancing tissue perfusion demands: cardiovascular dynamics of Cancer magister during exposure to low salinity and hypoxia.

PubMed

McGaw, Iain J; McMahon, Brian R

2003-01-01

Decapod crustaceans inhabit aquatic environments that are frequently subjected to changes in salinity and oxygen content. The physiological responses of decapod crustaceans to either salinity or hypoxia are well documented; however, there are many fewer reports on the physiological responses during exposure to these parameters in combination. We investigated the effects of simultaneous and sequential combinations of low salinity and hypoxia on the cardiovascular physiology of the Dungeness crab, Cancer magister. Heart rate, as well as haemolymph flow rates through the anterolateral, hepatic, sternal and posterior arteries were measured using a pulsed-Doppler flowmeter. Summation of flows allowed calculation of cardiac output and division of this by heart rate yielded stroke volume. When hypoxia and low salinity were encountered simultaneously, the observed changes in cardiac properties tended to be a mix of both factors. Hypoxia caused a bradycardia, whereas exposure to low salinity was associated with a tachycardia. However, the hypoxic conditions had the dominant effect on heart rate. Although hypoxia caused an increase in stroke volume of the heart, the low salinity had a more pronounced effect, causing an overall decrease in stroke volume. The patterns of haemolymph flow through the arterial system also varied when hypoxia and low salinity were offered together. The resulting responses were a mix of those resulting from exposure to either parameter alone. When low salinity and hypoxia were offered sequentially, the parameter experienced first tended to have the dominant effect on cardiac function and haemolymph flows. Low salinity exposure was associated with an increase in heart rate, a decrease in stroke volume and cardiac output, and a concomitant decrease in haemolymph flow rates. Subsequent exposure to hypoxic conditions caused a slight decrease in rate, but other cardiovascular variables were largely unaffected. In contrast, when low salinity followed acclimation to hypoxic conditions, apart from an increased heart rate, there were no other cardiovascular changes associated with the low salinity episode. The implications of these changes in cardiovascular dynamics are discussed in relation to physiological mechanisms and the ecology of decapod crustaceans, in hypoxic or low salinity environments. Copyright 2003, Wiley-Liss, Inc.

Glyphosate resistance in Ambrosia trifida: Part 2. Rapid response physiology and non-target-site resistance.

PubMed

Moretti, Marcelo L; Van Horn, Christopher R; Robertson, Renae; Segobye, Kabelo; Weller, Stephen C; Young, Bryan G; Johnson, William G; Douglas Sammons, R; Wang, Dafu; Ge, Xia; d' Avignon, André; Gaines, Todd A; Westra, Philip; Green, Amanda C; Jeffery, Taylor; Lespérance, Mackenzie A; Tardif, François J; Sikkema, Peter H; Christopher Hall, J; McLean, Michael D; Lawton, Mark B; Schulz, Burkhard

2018-05-01

The glyphosate-resistant rapid response (GR RR) resistance mechanism in Ambrosia trifida is not due to target-site resistance (TSR) mechanisms. This study explores the physiology of the rapid response and the possibility of reduced translocation and vacuolar sequestration as non-target-site resistance (NTSR) mechanisms. GR RR leaf discs accumulated hydrogen peroxide within minutes of glyphosate exposure, but only in mature leaf tissue. The rapid response required energy either as light or exogenous sucrose. The combination of phenylalanine and tyrosine inhibited the rapid response in a dose-dependent manner. Reduced glyphosate translocation was observed in GR RR, but only when associated with tissue death caused by the rapid response. Nuclear magnetic resonance studies indicated that glyphosate enters the cytoplasm and reaches chloroplasts, and it is not moved into the vacuole of GR RR, GR non-rapid response or glyphosate-susceptible A. trifida. The GR RR mechanism of resistance is not associated with vacuole sequestration of glyphosate, and the observed reduced translocation is likely a consequence of rapid tissue death. Rapid cell death was inhibited by exogenous application of aromatic amino acids phenylalanine and tyrosine. The mechanism by which these amino acids inhibit rapid cell death in the GR RR phenotype remains unknown, and it could involve glyphosate phytotoxicity or other agents generating reactive oxygen species. Implications of these findings are discussed. The GR RR mechanism is distinct from the currently described glyphosate TSR or NTSR mechanisms in other species. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

Mortality from desiccation contributes to a genotype–temperature interaction for cold survival in Drosophila melanogaster

PubMed Central

Kobey, Robert L.; Montooth, Kristi L.

2013-01-01

SUMMARY Survival at cold temperatures is a complex trait, primarily because of the fact that the physiological cause of injury may differ across degrees of cold exposure experienced within the lifetime of an ectothermic individual. In order to better understand how chill-sensitive insects experience and adapt to low temperatures, we investigated the physiological basis for cold survival across a range of temperature exposures from −4 to 6°C in five genetic lines of the fruit fly Drosophila melanogaster. Genetic effects on cold survival were temperature dependent and resulted in a significant genotype–temperature interaction for survival across cold temperature exposures that differ by as little as 2°C. We investigated desiccation as a potential mechanism of injury across these temperature exposures. Flies were dehydrated following exposures near 6°C, whereas flies were not dehydrated following exposures near −4°C. Furthermore, decreasing humidity during cold exposure decreased survival, and increasing humidity during cold exposure increased survival at 6°C, but not at −4°C. These results support the conclusion that in D. melanogaster there are multiple physiological mechanisms of cold-induced mortality across relatively small differences in temperature, and that desiccation contributes to mortality for exposures near 6°C but not for subzero temperatures. Because D. melanogaster has recently expanded its range from tropical to temperate latitudes, the complex physiologies underlying cold tolerance are likely to be important traits in the recent evolutionary history of this fruit fly. PMID:23197100

Olfactory regulation of the sexual behavior and reproductive physiology of the laboratory mouse: effects and neural mechanisms.

PubMed

Kelliher, Kevin R; Wersinger, Scott R

2009-01-01

In many species, chemical compounds emitted by conspecifics exert profound effects on reproductive physiology and sexual behavior. This is particularly true in the mouse, where such cues advance and delay puberty, suppress and facilitate estrous cycles, and cause the early termination of pregnancy. They also facilitate sexual behavior and inform mate selection. The mouse has a rich and complex repertoire of social behaviors. The technologies of molecular genetics are well developed in the mouse. Gene expression can be experimentally manipulated in the mouse relatively easily and in a time- and tissue-specific manner. Thus, the mouse is an excellent model in which to investigate the genetic, neural, and hormonal bases by which chemical compounds released by other mice affect physiology and behavior. These chemical cues are detected and processed by the olfactory system and other specialized but less well characterized sensory organs. The sensory information reaches brain regions that regulate hormone levels as well as those that are involved in behavior and alters the function of these brain regions. The effects of these chemical compounds have important implications for the laboratory animal facility as well as for researchers. We begin with an overview of the basic structure and function of the olfactory system and of the connections among brain regions that receive olfactory stimuli. We discuss the effects of chemosensory cues on the behavior and physiology of the organism along with what is known about the neural and hormonal mechanisms underlying these effects. We also describe some of the implications for the laboratory animal facility.

Titin Based Viscosity in Ventricular Physiology: An Integrative Investigation of PEVK-Actin Interactions

PubMed Central

Chung, Charles S; Methawasin, Methajit; Nelson, O Lynne; Radke, Michael H; Hidalgo, Carlos G; Gotthardt, Michael; Granzier, Henk L

2011-01-01

Viscosity is proposed to modulate diastolic function, but only limited understanding of the source(s) of viscosity exists. In-vitro experiments have shown that the proline-glutamic acid-valine-lysine (PEVK) rich element of titin interacts with actin, causing a viscous force in the sarcomere. It is unknown whether this mechanism contributes to viscosity in-vivo. We tested the hypothesis that PEVK-actin interaction causes cardiac viscosity and is important in-vivo via an integrative physiological study on a unique PEVK-knockout (KO) model. Both skinned cardiomyocytes and papillary muscle fibers were isolated from wildtype (WT) and PEVK KO mice and passive viscosity was examined using stretch-hold-release and sinusoidal analysis. Viscosity was reduced by ~60% in KO myocytes and ~50% in muscle fibers at room temperature. The PEVK-actin interaction was not modulated by temperature or diastolic calcium, but was increased by lattice compression. Stretch-hold and sinusoidal frequency protocols on intact isolated mouse hearts showed a smaller, 30–40% reduction in viscosity, possibly due to actomyosin interactions, and showed that microtubules did not contribute to viscosity. Transmitral Doppler echocardiography similarly revealed a 40% decrease in LV chamber viscosity in the PEVK KO in-vivo. This integrative study is the first to quantify the influence of a specific molecular (PEVK-actin) viscosity in-vivo and shows that PEVK-actin interactions are an important physiological source of viscosity. PMID:21708170

Response mechanisms of conifers to air pollutants

DOE Office of Scientific and Technical Information (OSTI.GOV)

Matyssek, R.; Reich, P.; Oren, R.

1995-07-01

Conifers are known to respond to SO{sub 2}, O{sub 3}, NO{sub x} and acid deposition. Of these pollutants, O{sub 3} is likely the most widespread and phytotoxic compound, and therefore of great interest to individuals concerned with forest resources Direct biological responses have a toxicological effects on metabolism which can then scale to effects on tree growth and forest ecology, including processes of competition and succession. Air pollution can cause reductions in photosynthesis and stomatal conductance, which are the physiological parameters most rigorously studied for conifers. Some effects air pollutants can have on plants are influenced by the presence ofmore » co-occurring environmental stresses. For example, drought usually reduces vulnerability of plants to air pollution. In addition, air pollution sensitivity may differ among species and with plant/leaf age. Plants may make short-term physiological adjustments to compensate for air pollution or may evolve resistance to air pollution through the processes of selection. Models are necessary to understand how physiological processes, growth processes, and ecological processes are affected by air pollutants. The process of defining the ecological risk that air pollutants pose for coniferous forests requires approaches that exploit existing databases, environmental monitoring of air pollutants and forest resources, experiments with well-defined air pollution treatments and environmental control/monitoring, modeling, predicting air pollution-caused changes in productivity and ecological processes over time and space, and integration of social values.« less

The Role of Medications in Causing Dry Eye

PubMed Central

Fraunfelder, Frederick T.; Sciubba, James J.; Mathers, William D.

2012-01-01

The purpose of this paper is to review the possible role of polypharmacy in causing dry eye disease (DED), reflecting the complex interactions and complications associated with the use of multiple systemic and topical ocular medications. The pharmacological, physiological, anatomical, and histological mechanisms causing dry mouth differ little from those causing dry eye. Oral polypharmacy is the most common cause of dry mouth, but has not been investigated as a cause of dry eye. Topical ocular polypharmacy has been shown to cause DED. Information on drugs that likely cause or aggravate DED and the controversial role of preservatives in topical ocular medications are examined. Systemic or topical ocular medications and preservatives used in topical ocular drugs may cause dry eye through the drug's therapeutic action, ocular surface effects, or preservatives, and the effects probably are additive. Long-term use of topical ocular medications, especially those containing preservatives such as BAK, may play an important role in DED and the role of polypharmacy needs further study. We review possible ways to decrease the risk of medication-related dry eye. PMID:23050121

Basic mechanisms of urgency: preclinical and clinical evidence.

PubMed

Michel, Martin C; Chapple, Christopher R

2009-08-01

Urgency is the core symptom of the overactive bladder symptom complex, but the underlying mechanisms are not fully understood. To review clinical and experimental studies related to how bladder filling and urgency are sensed and what causes urgency and to discuss how this process affects potential therapeutic strategies. Review of published reports. The definition of urgency as a desire implies that it can only be assessed in cognitively intact patients and that animal studies have to rely on surrogate markers thereof, such as detrusor overactivity (DO); however, DO and urgency are not always associated. While the precise mechanisms of how urgency is sensed remain unclear, accumulating evidence suggests that they may differ from the physiologic sensation of bladder filling. Studies on the neurophysiology of urgency sensing are hampered by reliance on the surrogate marker DO. Functional brain imaging may help to understand the central neurophysiology, but, until now, it has not specifically focused on urgency. With regard to causes of urgency, multiple theories have been forwarded. While none of them has been proven, it should be noted that they are not mutually exclusive, and, in specific patients, different causes may be present. The development of improved therapeutic strategies against urgency will be helped by a better understanding of how urgency is perceived and the underlying causes. Rigorous use of existing definitions and the search for reliable surrogate markers will aid such attempts.

Contextual processing in unpredictable auditory environments: the limited resource model of auditory refractoriness in the rhesus

PubMed Central

Gurnsey, Kate; Salisbury, Dean; Sweet, Robert A.

2016-01-01

Auditory refractoriness refers to the finding of smaller electroencephalographic (EEG) responses to tones preceded by shorter periods of silence. To date, its physiological mechanisms remain unclear, limiting the insights gained from findings of abnormal refractoriness in individuals with schizophrenia. To resolve this roadblock, we studied auditory refractoriness in the rhesus, one of the most important animal models of auditory function, using grids of up to 32 chronically implanted cranial EEG electrodes. Four macaques passively listened to sounds whose identity and timing was random, thus preventing animals from forming valid predictions about upcoming sounds. Stimulus onset asynchrony ranged between 0.2 and 12.8 s, thus encompassing the clinically relevant timescale of refractoriness. Our results show refractoriness in all 8 previously identified middle- and long-latency components that peaked between 14 and 170 ms after tone onset. Refractoriness may reflect the formation and gradual decay of a basic sensory memory trace that may be mirrored by the expenditure and gradual recovery of a limited physiological resource that determines generator excitability. For all 8 components, results were consistent with the assumption that processing of each tone expends ∼65% of the available resource. Differences between components are caused by how quickly the resource recovers. Recovery time constants of different components ranged between 0.5 and 2 s. This work provides a solid conceptual, methodological, and computational foundation to dissect the physiological mechanisms of auditory refractoriness in the rhesus. Such knowledge may, in turn, help develop novel pharmacological, mechanism-targeted interventions. PMID:27512021

The physiological effects of dehydration caused by sweat loss. [athletes

NASA Technical Reports Server (NTRS)

Israel, S.

1981-01-01

The mechanisms of fluid loss in the human body while sweating due to physical exercise are discussed. Trained and untrained persons were examined and compared. Since sweat is hypotonous, a disruption in the hydrosalinic balance occurs; the consequences of this finding, also pertaining to the fluid and electrolytic substitution, are presented. Further explanations on the problem of dehydration refer to reactions of individual organ systems, to alterations in bodily capabilities as well as to questions relating to sex and age.

Shared and distinct mechanisms of iron acquisition by bacterial and fungal pathogens of humans

PubMed Central

Caza, Mélissa; Kronstad, James W.

2013-01-01

Iron is the most abundant transition metal in the human body and its bioavailability is stringently controlled. In particular, iron is tightly bound to host proteins such as transferrin to maintain homeostasis, to limit potential damage caused by iron toxicity under physiological conditions and to restrict access by pathogens. Therefore, iron acquisition during infection of a human host is a challenge that must be surmounted by every successful pathogenic microorganism. Iron is essential for bacterial and fungal physiological processes such as DNA replication, transcription, metabolism, and energy generation via respiration. Hence, pathogenic bacteria and fungi have developed sophisticated strategies to gain access to iron from host sources. Indeed, siderophore production and transport, iron acquisition from heme and host iron-containing proteins such as hemoglobin and transferrin, and reduction of ferric to ferrous iron with subsequent transport are all strategies found in bacterial and fungal pathogens of humans. This review focuses on a comparison of these strategies between bacterial and fungal pathogens in the context of virulence and the iron limitation that occurs in the human body as a mechanism of innate nutritional defense. PMID:24312900

Impact of stress on female reproductive health disorders: Possible beneficial effects of shatavari (Asparagus racemosus).

PubMed

Pandey, Ajai K; Gupta, Anumegha; Tiwari, Meenakshi; Prasad, Shilpa; Pandey, Ashutosh N; Yadav, Pramod K; Sharma, Alka; Sahu, Kankshi; Asrafuzzaman, Syed; Vengayil, Doyil T; Shrivastav, Tulsidas G; Chaube, Shail K

2018-07-01

Stress is deeply rooted in the society and women are frequently exposed to psychological, physical and physiological stressors. Psychological stress disturbs reproductive health by inducing generation of reactive oxygen species (ROS) and thereby oxidative stress (OS). The increased OS may affect physiology of ovary, oocyte quality and cause female reproductive health disorders. To overcome stress-mediated reproductive health disorders in women, shatavari (Asparagus racemosus) is frequently recommended in Ayurvedic system of medicine. Although shatavari is one of the major health tonics and most popular rasayana drugs to treat reproductive ailments of women, underlying mechanism of shatavari action at the level of ovary remains poorly understood. Based on the existing studies, we propose that shatavari may improve female reproductive health complications including hormonal imbalance, polycystic ovarian syndrome (PCOS), follicular growth and development, oocyte quality and infertility possibly by reducing OS level and increasing antioxidants level in the body. Further studies are required to elucidate the mechanism of shatavari actions at the level of ovary and oocyte that directly impacts the reproductive health of women. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

[Stress-induced cellular adaptive mutagenesis].

PubMed

Zhu, Linjiang; Li, Qi

2014-04-01

The adaptive mutations exist widely in the evolution of cells, such as antibiotic resistance mutations of pathogenic bacteria, adaptive evolution of industrial strains, and cancerization of human somatic cells. However, how these adaptive mutations are generated is still controversial. Based on the mutational analysis models under the nonlethal selection conditions, stress-induced cellular adaptive mutagenesis is proposed as a new evolutionary viewpoint. The hypothetic pathway of stress-induced mutagenesis involves several intracellular physiological responses, including DNA damages caused by accumulation of intracellular toxic chemicals, limitation of DNA MMR (mismatch repair) activity, upregulation of general stress response and activation of SOS response. These responses directly affect the accuracy of DNA replication from a high-fidelity manner to an error-prone one. The state changes of cell physiology significantly increase intracellular mutation rate and recombination activity. In addition, gene transcription under stress condition increases the instability of genome in response to DNA damage, resulting in transcription-associated DNA mutagenesis. In this review, we summarize these two molecular mechanisms of stress-induced mutagenesis and transcription-associated DNA mutagenesis to help better understand the mechanisms of adaptive mutagenesis.

Biomechanical and ultrastructural comparison of cryopreservation and a novel cellular extraction of porcine aortic valve leaflets.

PubMed

Courtman, D W; Pereira, C A; Omar, S; Langdon, S E; Lee, J M; Wilson, G J

1995-12-01

Heart valve substitutes of biological origin often fail by degenerative mechanisms. Many authors have hypothesized that mechanical fatigue and structural degradation are instrumental to in vivo failure. Since the properties of the structural matrix at implantation may predetermine failure, we have examined the ultrastructure, fracture, mechanics, and uniaxial high-strain-rate viscoelastic properties of: (1) fresh, (2) cryopreserved, and (3) cellular extracted porcine aortic valve leaflets. The cellular extraction process is being developed in order to reduce immunological attack and calcification. Cryopreservation causes cellular disruption and necrotic changes throughout the tissue, whereas extraction removes all cells and lipid membranes. Both processes leave an intact collagen and elastin structural matrix and preserve the high-strain-rate viscoelastic characteristics of the fresh leaflets. Extraction does cause a 20% reduction in the fracture tension and increases tissue extensibility, with the percent strain at fracture rising to 45.3 +/- 4 (mean +/- SEM) from 31.5 +/- 3 for fresh leaflets. However, extraction does preserve matrix structure and mechanics over the physiological loading range. Glutaraldehyde fixation produces increased extensibility, increased elastic behavior, and, when applied to extracted leaflets, it causes a marked drop in fracture tension, to 50% of that for fresh leaflets. The combination of extraction and fixation may lead to early degenerative failure. The cellular extraction technique alone may be a useful alternative to glutaraldehyde fixation in preparing bioprosthetic heart valves.

What is conservation physiology? Perspectives on an increasingly integrated and essential science†

PubMed Central

Cooke, Steven J.; Sack, Lawren; Franklin, Craig E.; Farrell, Anthony P.; Beardall, John; Wikelski, Martin; Chown, Steven L.

2013-01-01

Globally, ecosystems and their constituent flora and fauna face the localized and broad-scale influence of human activities. Conservation practitioners and environmental managers struggle to identify and mitigate threats, reverse species declines, restore degraded ecosystems, and manage natural resources sustainably. Scientific research and evidence are increasingly regarded as the foundation for new regulations, conservation actions, and management interventions. Conservation biologists and managers have traditionally focused on the characteristics (e.g. abundance, structure, trends) of populations, species, communities, and ecosystems, and simple indicators of the responses to environmental perturbations and other human activities. However, an understanding of the specific mechanisms underlying conservation problems is becoming increasingly important for decision-making, in part because physiological tools and knowledge are especially useful for developing cause-and-effect relationships, and for identifying the optimal range of habitats and stressor thresholds for different organisms. When physiological knowledge is incorporated into ecological models, it can improve predictions of organism responses to environmental change and provide tools to support management decisions. Without such knowledge, we may be left with simple associations. ‘Conservation physiology’ has been defined previously with a focus on vertebrates, but here we redefine the concept universally, for application to the diversity of taxa from microbes to plants, to animals, and to natural resources. We also consider ‘physiology’ in the broadest possible terms; i.e. how an organism functions, and any associated mechanisms, from development to bioenergetics, to environmental interactions, through to fitness. Moreover, we consider conservation physiology to include a wide range of applications beyond assisting imperiled populations, and include, for example, the eradication of invasive species, refinement of resource management strategies to minimize impacts, and evaluation of restoration plans. This concept of conservation physiology emphasizes the basis, importance, and ecological relevance of physiological diversity at a variety of scales. Real advances in conservation and resource management require integration and inter-disciplinarity. Conservation physiology and its suite of tools and concepts is a key part of the evidence base needed to address pressing environmental challenges. PMID:27293585

Mechanisms of accelerated proteolysis in rat soleus muscle atrophy induced by unweighting or denervation

NASA Technical Reports Server (NTRS)

Tischler, Marc E.; Kirby, Christopher; Rosenberg, Sara; Tome, Margaret; Chase, Peter

1991-01-01

A hypothesis proposed by Tischler and coworkers (Henriksen et al., 1986; Tischler et al., 1990) concerning the mechanisms of atrophy induced by unweighting or denervation was tested using rat soleus muscle from animals subjected to hindlimb suspension and denervation of muscles. The procedure included (1) measuring protein degradation in isolated muscles and testing the effects of lysosome inhibitors, (2) analyzing the lysosome permeability and autophagocytosis, (3) testing the effects of altering calcium-dependent proteolysis, and (4) evaluating in vivo the effects of various agents to determine the physiological significance of the hypothesis. The results obtained suggest that there are major differences between the mechanisms of atrophies caused by unweighting and denervation, though slower protein synthesis is an important feature common for both.

Catch-up Growth: Cellular and Molecular Mechanisms

PubMed Central

Finkielstain, GP; Lui, JC; Baron, J

2012-01-01

In mammals, after a period of growth inhibition, body growth often does not just return to a normal rate but actually exceeds the normal rate, resulting in catch-up growth. Recent evidence suggests that catch-up growth occurs because growth-inhibiting conditions delay progression of the physiological mechanisms that normally cause body growth to slow and cease with age. As a result, following the period of growth inhibition, tissues retain a greater proliferative capacity than normal, and therefore grow more rapidly than normal for age. There is evidence that this mechanism contributes both to catch-up growth in terms of body length, which involves proliferation in the growth plate, and to catch-up growth in terms of organ mass, which involves proliferation in multiple non-skeletal tissues. PMID:23428687

Role of Airway Recruitment and Derecruitment in Lung Injury

PubMed Central

Ghadiali, S. N.; Huang, Y.

2011-01-01

The mechanical forces generated during the ventilation of patients with acute lung injury causes significant lung damage and inflammation. Low-volume ventilation protocols are commonly used to prevent stretch-related injury that occurs at high lung volumes. However, the cyclic closure and reopening of pulmonary airways at low lung volumes, i.e., derecruitment and recruitment, also causes significant lung damage and inflammation. In this review, we provide an overview of how biomedical engineering techniques are being used to elucidate the complex physiological and biomechanical mechanisms responsible for cellular injury during recruitment/derecruitment. We focus on the development of multiscale, multiphysics computational models of cell deformation and injury during airway reopening. These models, and the corresponding in vitro experiments, have been used to both elucidate the basic mechanisms responsible for recruitment/derecruitment injury and to develop alternative therapies that make the epithelium more resistant to injury. For example, models and experiments indicate that fluidization of the cytoskeleton is cytoprotective and that changes in cytoskeletal structure and cell mechanics can be used to mitigate the mechanotransduction of oscillatory pressure into inflammatory signaling. The continued application of biomedical engineering techniques to the problem of recruitment/derecruitment injury may therefore lead to novel and more effective therapies. PMID:22011235

The closing behavior of mechanical aortic heart valve prostheses.

PubMed

Lu, Po-Chien; Liu, Jia-Shing; Huang, Ren-Hong; Lo, Chi-Wen; Lai, Ho-Cheng; Hwang, Ned H C

2004-01-01

Mechanical artificial heart valves rely on reverse flow to close their leaflets. This mechanism creates regurgitation and water hammer effects that may form cavitations, damage blood cells, and cause thromboembolism. This study analyzes closing mechanisms of monoleaflet (Medtronic Hall 27), bileaflet (Carbo-Medics 27; St. Jude Medical 27; Duromedics 29), and trileaflet valves in a circulatory mock loop, including an aortic root with three sinuses. Downstream flow field velocity was measured via digital particle image velocimetry (DPIV). A high speed camera (PIVCAM 10-30 CCD video camera) tracked leaflet movement at 1000 frames/s. All valves open in 40-50 msec, but monoleaflet and bileaflet valves close in much less time (< 35 msec) than the trileaflet valve (>75 msec). During acceleration phase of systole, the monoleaflet forms a major and minor flow, the bileaflet has three jet flows, and the trileaflet produces a single central flow like physiologic valves. In deceleration phase, the aortic sinus vortices hinder monoleaflet and bileaflet valve closure until reverse flows and high negative transvalvular pressure push the leaflets rapidly for a hard closure. Conversely, the vortices help close the trileaflet valve more softly, probably causing less damage, lessening back flow, and providing a washing effect that may prevent thrombosis formation.

Antiarrhythmic properties of atrial pacing.

PubMed

Kliś, Magdalena; Sławuta, Agnieszka; Gajek, Jacek

2017-01-01

Bradycardia, atrial stretch and dilatation, autonomic nervous system disorders, and the presence of triggers such as atrial premature contractions, are factors which predispose a person to paroxysmal AF. Atrial pacing not only eliminates bradycardia but also prevents atrial premature contractions and dispersion of refractoriness, which are a substrate for atrial fibrillation. As the prolonged duration of atrial activation during pacing, especially from locations changing the physiological pattern of this activation (right atrium lateral wall, right atrium appendage), negatively influences both a mechanical and an electrical function of the atria, the atrial pacing site affects an atrial arrhythmogenesis. A conventional atrial lead location in the right atrium appendage causes non-physiological activation propagation, resulting in a prolongation of the activation time of both atria. This location is optimal according to a passive fixation of the atrial lead but the available contemporary active fixation leads could potentially be located in any area of the atrium. There is growing evidence of the benefit of pacing, imitating the physiological propagation of impulses within the atria. It seems that the Bachmann's bundle pacing is the best pacing site within the atria, not only positively influencing the atrial mechanical function but also best fulfilling the so-called atrial resynchronization function, in particular in patients with interatrial conduction delay. It can be effectively achieved using only one atrial electrode, and the slight shortening of atrioventricular conduction provides an additional benefit of this atrial pacing site.

Comparative Analysis of Zearalenone Effects on Thyroid Receptor Alpha (TRα) and Beta (TRβ) Expression in Rat Primary Cerebellar Cell Cultures.

PubMed

Kiss, David Sandor; Ioja, Eniko; Toth, Istvan; Barany, Zoltan; Jocsak, Gergely; Bartha, Tibor; Horvath, Tamas L; Zsarnovszky, Attila

2018-05-11

Thyroid receptors play an important role in postnatal brain development. Zearalenone (ZEN), a major mycotoxin of Fusarium fungi, is well known to cause serious health problems in animals and humans through various mechanisms, including the physiological pathways of thyroid hormone (TH). In the present study, we aimed to investigate the expression of thyroid receptors α (TRα) and β (TRβ) in primary cerebellar neurons in the presence or absence of glia and following ZEN treatment, using quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and Western blot. Primary cerebellar granule cells were treated with low doses of ZEN (0.1 nM) in combination with physiologically relevant concentrations of l-thyroxine (T4), 3,3',5-triiodo-l-thyronine (T3) and 17β-estradiol (E2). Expression levels of TRα and TRβ at mRNA and protein levels were slightly modified by ZEN administered alone; however, along with thyroid and steroid hormones, modelling the physiological conditions, expression levels of TRs varied highly depending on the given treatment. Gene expression levels were also highly modulated by the presence or absence of glial cells, with mostly contrasting effects. Our results demonstrate divergent transcriptional and translational mechanisms involved in the expression of TRs implied by ZEN and hormonal milieu, as well as culturing conditions.

Static and dynamic bending has minor effects on xylem hydraulics of conifer branches (Picea abies, Pinus sylvestris)

PubMed Central

Mayr, Stefan; Bertel, Clara; Dämon, Birgit; Beikircher, Barbara

2014-01-01

The xylem hydraulic efficiency and safety is usually measured on mechanically unstressed samples, although trees may be exposed to combined hydraulic and mechanical stress in the field. We analysed changes in hydraulic conductivity and vulnerability to drought-induced embolism during static bending of Picea abies and Pinus sylvestris branches as well as the effect of dynamic bending on the vulnerability. We hypothesized this mechanical stress to substantially impair xylem hydraulics. Intense static bending caused an only small decrease in hydraulic conductance (−19.5 ± 2.4% in P. abies) but no shift in vulnerability thresholds. Dynamic bending caused a 0.4 and 0.8 MPa decrease of the water potential at 50 and 88% loss of conductivity in P. sylvestris, but did not affect vulnerability thresholds in P. abies. With respect to applied extreme bending radii, effects on plant hydraulics were surprisingly small and are thus probably of minor eco-physiological importance. More importantly, results indicate that available xylem hydraulic analyses (of conifers) sufficiently reflect plant hydraulics under field conditions. PMID:24697679

Reintrepreting the cardiovascular system as a mechanical model

NASA Astrophysics Data System (ADS)

Lemos, Diogo; Machado, José; Minas, Graça; Soares, Filomena; Barros, Carla; Leão, Celina Pinto

2013-10-01

The simulation of the different physiological systems is very useful as a pedagogical tool, allowing a better understanding of the mechanisms and the functions of the processes. The observation of the physiological phenomena through mechanical simulators represents a great asset. Furthermore, the development of these simulators allows reinterpreting physiological systems, with the advantage of using the same transducers and sensors that are commonly used in diagnostic and therapeutic cardiovascular procedures for the monitoring of system' parameters. The cardiovascular system is one of the most important systems of the human body and has been the target of several biomedical studies. The present work describes a mechanical simulation of the cardiovascular system, in particularly, the systemic circulation, which can be described in terms of its hemodynamic variables. From the mechanical process and parameters, physiological system's behavior was reproduced, as accurately as possible.

Cushing's syndrome: from physiological principles to diagnosis and clinical care.

PubMed

Raff, Hershel; Carroll, Ty

2015-02-01

The physiological control of cortisol synthesis in the adrenal cortex involves stimulation of adrenocorticotrophic hormone (ACTH) by hypothalamic corticotrophin-releasing hormone (CRH) and then stimulation of the adrenal by ACTH. The control loop of the hypothalamic-pituitary-adrenal (HPA) axis is closed by negative feedback of cortisol on the hypothalamus and pituitary. Understanding this system is required to master the diagnosis, differential diagnosis and treatment of endogenous hypercortisolism--Cushing's syndrome. Endogenous Cushing's syndrome is caused either by excess ACTH secretion or by autonomous cortisol release from the adrenal cortex. Diagnosis of cortisol excess exploits three physiological principles: failure to achieve the normal nadir in the cortisol diurnal rhythm, loss of sensitivity of ACTH-secreting tumours to cortisol negative feedback, and increased excretion of free cortisol in the urine. Differentiating a pituitary source of excess ACTH (Cushing's disease) from an ectopic source is accomplished by imaging the pituitary and sampling for ACTH in the venous drainage of the pituitary. With surgical removal of ACTH or cortisol-secreting tumours, secondary adrenal insufficiency ensues because of the prior suppression of the HPA axis by glucocorticoid negative feedback. Medical therapy is targeted to the anatomical location of the dysregulated component of the HPA axis. Future research will focus on new diagnostics and treatments of Cushing's syndrome. These are elegant examples of translational research: understanding basic physiology informs the development of new approaches to diagnosis and treatment. Appreciating pathophysiology generates new areas for inquiry of basic physiological and biochemical mechanisms. © 2014 The Authors. The Journal of Physiology © 2014 The Physiological Society.

Does nutrition affect bone porosity and mineral tissue distribution in deer antlers? The relationship between histology, mechanical properties and mineral composition.

PubMed

Landete-Castillejos, T; Currey, J D; Ceacero, F; García, A J; Gallego, L; Gomez, S

2012-01-01

It is well known that porosity has an inverse relationship with the mechanical properties of bones. We examined cortical and trabecular porosity of antlers, and mineral composition, thickness and mechanical properties in the cortical wall. Samples belonged to two deer populations: a captive population of an experimental farm having a high quality diet, and a free-ranging population feeding on plants of lower nutritive quality. As shown for minerals and mechanical properties in previous studies by our group, cortical and trabecular porosity increased from the base distally. Cortical porosity was always caused by the presence of incomplete primary osteons. Porosity increased along the length of the antler much more in deer with lower quality diet. Despite cortical porosity being inversely related to mechanical properties and positively with K, Zn and other minerals indicating physiological effort, it was these minerals and not porosity that statistically better explained variability in mechanical properties. Histochemistry showed that the reason for this is that Zn is located around incomplete osteons and also in complete osteons that were still mineralizing, whereas K is located in non-osteonal bone, which constitutes a greater proportion of bone where osteons are incompletely mineralized. This suggests that, K, Zn and other minerals indicate reduction in mechanical performance even with little porosity. If a similar process occurred in internal bones, K, Zn and other minerals in the bone may be an early indicator of decrease in mechanical properties and future osteoporosis. In conclusion, porosity is related to diet and physiological effort in deer. Copyright © 2011 Elsevier Inc. All rights reserved.

The autodigestion hypothesis: Proteolytic receptor cleavage in rheological and cardiovascular cell dysfunction1

PubMed Central

Schmid-Schönbein, Geert W.

2017-01-01

Transformation of circulating leukocytes from a dormant into an activated state with changing rheological properties leads to a major shift of their behavior in the microcirculation. Low levels of pseudopod formation or expression of adhesion molecules facilitate relatively free passage through microvessels while activated leukocytes with pseudopods and enhanced levels of adhesion membrane proteins become trapped in microvessels, attach to the endothelium and migrate into the tissue. The transformation of leukocytes into an activated state is seen in many diseases. While mechanisms for activation due to infections, tissue trauma, as well as non-physiological biochemical or biophysical exposures are well recognized, the mechanisms for activation in many diseases have not been conclusively liked to these traditional mechanisms and remain unknown. We summarize our recent evidence suggesting a major and surprising role of digestive enzymes in the small intestine as root causes for leukocyte activation and microvascular disturbances. During normal digestion of food digestive enzymes are compartmentalized in the lumen of the intestine by the mucosal epithelial barrier. When permeability of this barrier increases, these powerful degrading enzymes leak into the wall of the intestine and into the systemic circulation. Leakage of digestive enzymes occurs for example in physiological shock and multi-organ failure. Entry of digestive enzymes into the wall of the small intestine leads to degradation of the intestinal tissue in an autodigestion process. The digestive enzymes and tissue/food fragments generate not only activate leukocytes but also cause numerous cell dysfunctions. For example, proteolytic destruction of membrane receptors, plasma proteins and other biomolecules occurs. We conclude that escape of digestive enzymes from the intestinal track serves as a major source of cell dysfunction, morbidity and even mortality, including abnormal leukocyte activation seen in rheological studies. PMID:28269737

How can the auditory efferent system protect our ears from noise-induced hearing loss? Let us count the ways

NASA Astrophysics Data System (ADS)

Marshall, Lynne; Miller, Judi A. Lapsley

2015-12-01

It is a cause for some debate as to how the auditory olivocochlear (OC) efferent system could protect hearing from noise trauma. In this review, we examined physiological research to find mechanisms that could effectively attenuate the response to sound. For each purported mechanism, we indicate which part of the OC-efferent system is responsible for the function and the site of action. These mechanisms include basilar-membrane phase shifts at high stimulus levels; changes in outer-hair-cell stiffness and phase lag associated with efferent slow effects; small decreases in endocochlear potentials causing small decreases in outer- and inner-hair-cell output; low-spontaneous-rate and medium-spontaneous-rate fibers showing OC-induced decrements at high levels; auditory-nerve initial-peak reduction; OC effect increasing over minutes; cholinergic activation of anti-apoptotic pathways; and anti-excitotoxicity. There are clearly multiple opportunities for the OC-efferent system to protect the inner ear from noise trauma. From further exploration into the mechanisms outlined here, as well as to-be-discovered mechanisms, we will gain a greater understanding of the protective nature of the OC-efferent system. These findings could aid our ability to design better predictive tests for people at risk for noise-induced hearing loss.

Nutritional State-Dependent Ghrelin Activation of Vasopressin Neurons via Retrograde Trans-Neuronal–Glial Stimulation of Excitatory GABA Circuits

PubMed Central

Haam, Juhee; Halmos, Katalin C.; Di, Shi

2014-01-01

Behavioral and physiological coupling between energy balance and fluid homeostasis is critical for survival. The orexigenic hormone ghrelin has been shown to stimulate the secretion of the osmoregulatory hormone vasopressin (VP), linking nutritional status to the control of blood osmolality, although the mechanism of this systemic crosstalk is unknown. Here, we show using electrophysiological recordings and calcium imaging in rat brain slices that ghrelin stimulates VP neurons in the hypothalamic paraventricular nucleus (PVN) in a nutritional state-dependent manner by activating an excitatory GABAergic synaptic input via a retrograde neuronal–glial circuit. In slices from fasted rats, ghrelin activation of a postsynaptic ghrelin receptor, the growth hormone secretagogue receptor type 1a (GHS-R1a), in VP neurons caused the dendritic release of VP, which stimulated astrocytes to release the gliotransmitter adenosine triphosphate (ATP). ATP activation of P2X receptors excited presynaptic GABA neurons to increase GABA release, which was excitatory to the VP neurons. This trans-neuronal–glial retrograde circuit activated by ghrelin provides an alternative means of stimulation of VP release and represents a novel mechanism of neuronal control by local neuronal–glial circuits. It also provides a potential cellular mechanism for the physiological integration of energy and fluid homeostasis. PMID:24790191

Pathogenesis of myasthenia gravis: update on disease types, models, and mechanisms

PubMed Central

Phillips, William D.; Vincent, Angela

2016-01-01

Myasthenia gravis is an autoimmune disease of the neuromuscular junction (NMJ) caused by antibodies that attack components of the postsynaptic membrane, impair neuromuscular transmission, and lead to weakness and fatigue of skeletal muscle. This can be generalised or localised to certain muscle groups, and involvement of the bulbar and respiratory muscles can be life threatening. The pathogenesis of myasthenia gravis depends upon the target and isotype of the autoantibodies. Most cases are caused by immunoglobulin (Ig)G1 and IgG3 antibodies to the acetylcholine receptor (AChR). They produce complement-mediated damage and increase the rate of AChR turnover, both mechanisms causing loss of AChR from the postsynaptic membrane. The thymus gland is involved in many patients, and there are experimental and genetic approaches to understand the failure of immune tolerance to the AChR. In a proportion of those patients without AChR antibodies, antibodies to muscle-specific kinase (MuSK), or related proteins such as agrin and low-density lipoprotein receptor-related protein 4 (LRP4), are present. MuSK antibodies are predominantly IgG4 and cause disassembly of the neuromuscular junction by disrupting the physiological function of MuSK in synapse maintenance and adaptation. Here we discuss how knowledge of neuromuscular junction structure and function has fed into understanding the mechanisms of AChR and MuSK antibodies. Myasthenia gravis remains a paradigm for autoantibody-mediated conditions and these observations show how much there is still to learn about synaptic function and pathological mechanisms. PMID:27408701

Insights from comparative analyses of aging in birds and mammals.

PubMed

Ricklefs, Robert E

2010-04-01

Many laboratory models used in aging research are inappropriate for understanding senescence in mammals, including humans, because of fundamental differences in life history, maintenance in artificial environments, and selection for early aging and high reproductive rate. Comparative studies of senescence in birds and mammals reveal a broad range in rates of aging among a variety of taxa with similar physiology and patterns of development. These comparisons suggest that senescence is a shared property of all vertebrates with determinate growth, that the rate of senescence has been modified by evolution in response to the potential life span allowed by extrinsic mortality factors, and that most variation among species in the rate of senescence is independent of commonly ascribed causes of aging, such as oxidative damage. Individuals of potentially long-lived species, particularly birds, appear to maintain high condition to near the end of life. Because most individuals in natural populations of such species die of aging-related causes, these populations likely harbor little genetic variation for mechanisms that could extend life further, or these mechanisms are very costly. This, and the apparent evolutionary conservatism in the rate of increase in mortality with age, suggests that variation in the rate of senescence reflects fundamental changes in organism structure, likely associated with the rate of development, rather than physiological or biochemical processes influenced by a few genes. Understanding these evolved differences between long-lived and short-lived organisms would seem to be an essential foundation for designing therapeutic interventions with respect to human aging and longevity.

Scavenging iron: a novel mechanism of plant immunity activation by microbial siderophores.

PubMed

Aznar, Aude; Chen, Nicolas W G; Rigault, Martine; Riache, Nassima; Joseph, Delphine; Desmaële, Didier; Mouille, Grégory; Boutet, Stéphanie; Soubigou-Taconnat, Ludivine; Renou, Jean-Pierre; Thomine, Sébastien; Expert, Dominique; Dellagi, Alia

2014-04-01

Siderophores are specific ferric iron chelators synthesized by virtually all microorganisms in response to iron deficiency. We have previously shown that they promote infection by the phytopathogenic enterobacteria Dickeya dadantii and Erwinia amylovora. Siderophores also have the ability to activate plant immunity. We have used complete Arabidopsis transcriptome microarrays to investigate the global transcriptional modifications in roots and leaves of Arabidopsis (Arabidopsis thaliana) plants after leaf treatment with the siderophore deferrioxamine (DFO). Physiological relevance of these transcriptional modifications was validated experimentally. Immunity and heavy-metal homeostasis were the major processes affected by DFO. These two physiological responses could be activated by a synthetic iron chelator ethylenediamine-di(o-hydroxyphenylacetic) acid, indicating that siderophores eliciting activities rely on their strong iron-chelating capacity. DFO was able to protect Arabidopsis against the pathogenic bacterium Pseudomonas syringae pv tomato DC3000. Siderophore treatment caused local modifications of iron distribution in leaf cells visible by ferrocyanide and diaminobenzidine-H₂O₂ staining. Metal quantifications showed that DFO causes a transient iron and zinc uptake at the root level, which is presumably mediated by the metal transporter iron regulated transporter1 (IRT1). Defense gene expression and callose deposition in response to DFO were compromised in an irt1 mutant. Consistently, plant susceptibility to D. dadantii was increased in the irt1 mutant. Our work shows that iron scavenging is a unique mechanism of immunity activation in plants. It highlights the strong relationship between heavy-metal homeostasis and immunity.

Scavenging Iron: A Novel Mechanism of Plant Immunity Activation by Microbial Siderophores1[C][W

PubMed Central

Aznar, Aude; Chen, Nicolas W.G.; Rigault, Martine; Riache, Nassima; Joseph, Delphine; Desmaële, Didier; Mouille, Grégory; Boutet, Stéphanie; Soubigou-Taconnat, Ludivine; Renou, Jean-Pierre; Thomine, Sébastien; Expert, Dominique; Dellagi, Alia

2014-01-01

Siderophores are specific ferric iron chelators synthesized by virtually all microorganisms in response to iron deficiency. We have previously shown that they promote infection by the phytopathogenic enterobacteria Dickeya dadantii and Erwinia amylovora. Siderophores also have the ability to activate plant immunity. We have used complete Arabidopsis transcriptome microarrays to investigate the global transcriptional modifications in roots and leaves of Arabidopsis (Arabidopsis thaliana) plants after leaf treatment with the siderophore deferrioxamine (DFO). Physiological relevance of these transcriptional modifications was validated experimentally. Immunity and heavy-metal homeostasis were the major processes affected by DFO. These two physiological responses could be activated by a synthetic iron chelator ethylenediamine-di(o-hydroxyphenylacetic) acid, indicating that siderophores eliciting activities rely on their strong iron-chelating capacity. DFO was able to protect Arabidopsis against the pathogenic bacterium Pseudomonas syringae pv tomato DC3000. Siderophore treatment caused local modifications of iron distribution in leaf cells visible by ferrocyanide and diaminobenzidine-H2O2 staining. Metal quantifications showed that DFO causes a transient iron and zinc uptake at the root level, which is presumably mediated by the metal transporter iron regulated transporter1 (IRT1). Defense gene expression and callose deposition in response to DFO were compromised in an irt1 mutant. Consistently, plant susceptibility to D. dadantii was increased in the irt1 mutant. Our work shows that iron scavenging is a unique mechanism of immunity activation in plants. It highlights the strong relationship between heavy-metal homeostasis and immunity. PMID:24501001

Allostatic load as a predictor of all-cause and cause-specific mortality in the general population: Evidence from the Scottish Health Survey.

PubMed

Robertson, Tony; Beveridge, Gayle; Bromley, Catherine

2017-01-01

Allostatic load is a multiple biomarker measure of physiological 'wear and tear' that has shown some promise as marker of overall physiological health, but its power as a risk predictor for mortality and morbidity is less well known. This study has used data from the 2003 Scottish Health Survey (SHeS) (nationally representative sample of Scottish population) linked to mortality records to assess how well allostatic load predicts all-cause and cause-specific mortality. From the sample, data from 4,488 men and women were available with mortality status at 5 and 9.5 (rounded to 10) years after sampling in 2003. Cox proportional hazard models estimated the risk of death (all-cause and the five major causes of death in the population) according to allostatic load score. Multiple imputation was used to address missing values in the dataset. Analyses were also adjusted for potential confounders (sex, age and deprivation). There were 258 and 618 deaths over the 5-year and 10-year follow-up period, respectively. In the fully-adjusted model, higher allostatic load (poorer physiological 'health') was not associated with an increased risk of all-cause mortality after 5 years (HR = 1.07, 95% CI 0.94 to 1.22; p = 0.269), but it was after 10 years (HR = 1.08, 95% CI 1.01 to 1.16; p = 0.026). Allostatic load was not associated with specific causes of death over the same follow-up period. In conclusions, greater physiological wear and tear across multiple physiological systems, as measured by allostatic load, is associated with an increased risk of death, but may not be as useful as a predictor for specific causes of death.

Allostatic load as a predictor of all-cause and cause-specific mortality in the general population: Evidence from the Scottish Health Survey

PubMed Central

Beveridge, Gayle; Bromley, Catherine

2017-01-01

Allostatic load is a multiple biomarker measure of physiological ‘wear and tear’ that has shown some promise as marker of overall physiological health, but its power as a risk predictor for mortality and morbidity is less well known. This study has used data from the 2003 Scottish Health Survey (SHeS) (nationally representative sample of Scottish population) linked to mortality records to assess how well allostatic load predicts all-cause and cause-specific mortality. From the sample, data from 4,488 men and women were available with mortality status at 5 and 9.5 (rounded to 10) years after sampling in 2003. Cox proportional hazard models estimated the risk of death (all-cause and the five major causes of death in the population) according to allostatic load score. Multiple imputation was used to address missing values in the dataset. Analyses were also adjusted for potential confounders (sex, age and deprivation). There were 258 and 618 deaths over the 5-year and 10-year follow-up period, respectively. In the fully-adjusted model, higher allostatic load (poorer physiological ‘health’) was not associated with an increased risk of all-cause mortality after 5 years (HR = 1.07, 95% CI 0.94 to 1.22; p = 0.269), but it was after 10 years (HR = 1.08, 95% CI 1.01 to 1.16; p = 0.026). Allostatic load was not associated with specific causes of death over the same follow-up period. In conclusions, greater physiological wear and tear across multiple physiological systems, as measured by allostatic load, is associated with an increased risk of death, but may not be as useful as a predictor for specific causes of death. PMID:28813505

Quantification of correlational selection on thermal physiology, thermoregulatory behavior, and energy metabolism in lizards

PubMed Central

Artacho, Paulina; Saravia, Julia; Ferrandière, Beatriz Decencière; Perret, Samuel; Le Galliard, Jean-François

2015-01-01

Phenotypic selection is widely accepted as the primary cause of adaptive evolution in natural populations, but selection on complex functional properties linking physiology, behavior, and morphology has been rarely quantified. In ectotherms, correlational selection on thermal physiology, thermoregulatory behavior, and energy metabolism is of special interest because of their potential coadaptation. We quantified phenotypic selection on thermal sensitivity of locomotor performance (sprint speed), thermal preferences, and resting metabolic rate in captive populations of an ectothermic vertebrate, the common lizard, Zootoca vivipara. No correlational selection between thermal sensitivity of performance, thermoregulatory behavior, and energy metabolism was found. A combination of high body mass and resting metabolic rate was positively correlated with survival and negatively correlated with fecundity. Thus, different mechanisms underlie selection on metabolism in lizards with small body mass than in lizards with high body mass. In addition, lizards that selected the near average preferred body temperature grew faster that their congeners. This is one of the few studies that quantifies significant correlational selection on a proxy of energy expenditure and stabilizing selection on thermoregulatory behavior. PMID:26380689

Quantification of correlational selection on thermal physiology, thermoregulatory behavior, and energy metabolism in lizards.

PubMed

Artacho, Paulina; Saravia, Julia; Ferrandière, Beatriz Decencière; Perret, Samuel; Le Galliard, Jean-François

2015-09-01

Phenotypic selection is widely accepted as the primary cause of adaptive evolution in natural populations, but selection on complex functional properties linking physiology, behavior, and morphology has been rarely quantified. In ectotherms, correlational selection on thermal physiology, thermoregulatory behavior, and energy metabolism is of special interest because of their potential coadaptation. We quantified phenotypic selection on thermal sensitivity of locomotor performance (sprint speed), thermal preferences, and resting metabolic rate in captive populations of an ectothermic vertebrate, the common lizard, Zootoca vivipara. No correlational selection between thermal sensitivity of performance, thermoregulatory behavior, and energy metabolism was found. A combination of high body mass and resting metabolic rate was positively correlated with survival and negatively correlated with fecundity. Thus, different mechanisms underlie selection on metabolism in lizards with small body mass than in lizards with high body mass. In addition, lizards that selected the near average preferred body temperature grew faster that their congeners. This is one of the few studies that quantifies significant correlational selection on a proxy of energy expenditure and stabilizing selection on thermoregulatory behavior.

[Potentiality of building-up the medical operations system for long-duration space missions by noncontact physiological functions recording during sleep time].

PubMed

Baevskiĭ, R M; Bogomolov, V V; Funtova, I I; Slepchenkova, I N; Chernikova, A G

2009-01-01

Methods of investigating the physiological functions in space crews on extended missions during night sleep are of much fundamental and practical substance. The design of experiment "Sonocard" utilizes the method of seismocardiography. Purpose of the experiment is to validate the procedures of noncontact in-sleep physiological data recoding which are potent to enhance the space crew medical operations system. The experiment was performed systematically by ISS Russian crew members starting from mission-16. The experimental procedure is easy and does not cause discomfort to human subjects. Results of the initial experimental sessions demonstrated that, as on Earth, sleep in microgravity is crucial for the recovery of body functional reserves and that the innovative technology is instrumental in studying the recovery processes as well as person unique patterns of adaptation to extended space mission. It also allows conclusions about sleep quality, mechanisms of recreation, and body functionality. These data may enrich substantially the information used by medical operators of the space missions control centers.

A novel role of thrombopoietin as a physiological modulator of coronary flow.

PubMed

Ramella, Roberta; Gallo, Maria Pia; Spatola, Tiziana; Lupia, Enrico; Alloatti, Giuseppe

2011-02-25

Thrombopoietin (TPO) is known for its ability to stimulate platelet production. However, little is currently known whether TPO plays a physiological function in the heart. The potential vasodilatory role of TPO was tested on the isolated rat heart. The expression of TPO receptor (c-mpl) and the TPO-dependent eNOS phosphorylation (P(Ser1179)) were studied on Cardiac-derived normal Human Micro Vascular Endothelial Cells (HMVEC-C) by Western blot analysis. While TPO (10-200 pg/mL) did not modify coronary flow (CF) under basal conditions, it reduced the coronary constriction caused by endothelin-1 (ET-1; 10nM) in a dose-dependent manner. This effect was blocked by both Wortmannin (100 nM) and L-NAME (100 nM); on HMVEC-C, TPO induced eNOS phosphorylation through a Wortmannin sensitive mechanism. Taken together, our data suggest a potential role of TPO as a physiological regulator of CF. By acting on specific receptors present on endothelial cells, TPO may induce PI3K/Akt-dependent eNOS phosphorylation and NO release. Copyright © 2011 Elsevier B.V. All rights reserved.

Next Steps Toward Understanding Human Habitation of Space: Environmental Impacts and Mechanisms

NASA Technical Reports Server (NTRS)

Globus, Ruth

2016-01-01

Entry into low earth orbit and beyond causes profound shifts in environmental conditions that have the potential to influence human productivity, long term health, and even survival. We now have evidence that microgravity, radiation and/or confinement in space can lead to demonstrably detrimental changes in the cardiovascular (e.g. vessel function, orthostatic intolerance), musculoskeletal (muscle atrophy, bone loss) and nervous (eye, neurovestibular) systems of astronauts. Because of both the limited number of astronauts who have flown (especially females) and the high degree of individual variability in the human population, important unanswered questions about responses to the space environment remain: What are the sex differences with respect to specific physiological systems? Are the responses age-dependent and/or reversible after return to Earth? Do observed detrimental changes that resemble accelerated aging progress continuously over time or plateau? What are the mechanisms of the biological responses? Answering these important questions certainly demands a multi-pronged approach, and the study of multicellular model organisms (such as rodents and flies) already has provided opportunities for exploring those questions in some detail. Recent long duration spaceflight experiments with rodents show that mice in space provide a mammalian model that uniquely combines the influence of reduced gravitational loading with increased physical activity. In addition, multiple investigators have shown that ground-based models that simulate aspects of spaceflight (including rodent hind limb unloading to mimic weightlessness and exposure to ionizing radiation), cause various transient and persistent detrimental consequences in multiple physiological systems. In general, we have found that adverse skeletal effects of simulated weightlessness and space radiation when combined, can be quantitatively, if not qualitatively, different from the influence of each environmental factor alone implying at least some shared underlying mechanisms. Thus, both ground based and spaceflight research utilizing model organisms provide the opportunity to better understand environmental factors and biological mechanisms that contribute to human health and survival in space.

Mucopolysaccharidosis type I: current knowledge on its pathophysiological mechanisms.

PubMed

Campos, Derbis; Monaga, Madelyn

2012-06-01

Mucopolysaccharidosis type I is one of the most frequent lysosomal storage diseases. It has a high morbidity and mortality, causing in many cases severe neurological and somatic damage in the first years of life. Although the clinical phenotypes have been described for decades, and the enzymatic deficiency and many of the mutations that cause this disease are well known, the underlying pathophysiological mechanisms that lead to its development are not completely understood. In this review we describe and discuss the different pathogenic mechanisms currently proposed for this disease regarding its neurological damage. Deficiency in the lysosomal degradation of heparan sulfate and dermatan sulfate, as well as its primary accumulation, may disrupt a variety of physiological and biochemical processes: the intracellular and extracellular homeostasis of these macromolecules, the pathways related to gangliosides metabolism, mechanisms related to the activation of inflammation, receptor-mediated signaling, oxidative stress and permeability of the lysosomal membrane, as well as alterations in intracellular ionic homeostasis and the endosomal pathway. Many of the pathogenic mechanisms proposed for mucopolysaccharidosis type I are also present in other lysosomal storage diseases with neurological implications. Results from the use of methods that allow the analysis of multiple genes and proteins, in both patients and animal models, will shed light on the role of each of these mechanisms and their combination in the development of different phenotypes due to the same deficiency.

The phenoptosis problem: what is causing the death of an organism? Lessons from acute kidney injury.

PubMed

Zorov, D B; Plotnikov, E Y; Jankauskas, S S; Isaev, N K; Silachev, D N; Zorova, L D; Pevzner, I B; Pulkova, N V; Zorov, S D; Morosanova, M A

2012-07-01

Programmed execution of various cells and intracellular structures is hypothesized to be not the only example of elimination of biological systems - the general mechanism can also involve programmed execution of organs and organisms. Modern rating of programmed cell death mechanisms includes 13 mechanistic types. As for some types, the mechanism of actuation and manifestation of cell execution has been basically elucidated, while the causes and intermediate steps of the process of fatal failure of organs and organisms remain unknown. The analysis of deaths resulting from a sudden heart arrest or multiple organ failure and other acute and chronic pathologies leads to the conclusion of a special role of mitochondria and oxidative stress activating the immune system. Possible mechanisms of mitochondria-mediated induction of the signaling cascades involved in organ failure and death of the organism are discussed. These mechanisms include generation of reactive oxygen species and damage-associated molecular patterns in mitochondria. Some examples of renal failure-induced deaths are presented with mechanisms and settings determined by some hypothetical super system rather than by the kidneys themselves. This system plays the key role in the process of physiological senescence and termination of an organism. The facts presented suggest that it is the immune system involved in mitochondrial signaling that can act as the system responsible for the organism's death.

Mechanics of the Nucleus

PubMed Central

Lammerding, Jan

2015-01-01

The nucleus is the distinguishing feature of eukaryotic cells. Until recently, it was often considered simply as a unique compartment containing the genetic information of the cell and associated machinery, without much attention to its structure and mechanical properties. This article provides compelling examples that illustrate how specific nuclear structures are associated with important cellular functions, and how defects in nuclear mechanics can cause a multitude of human diseases. During differentiation, embryonic stem cells modify their nuclear envelope composition and chromatin structure, resulting in stiffer nuclei that reflect decreased transcriptional plasticity. In contrast, neutrophils have evolved characteristic lobulated nuclei that increase their physical plasticity, enabling passage through narrow tissue spaces in their response to inflammation. Research on diverse cell types further demonstrates how induced nuclear deformations during cellular compression or stretch can modulate cellular function. Pathological examples of disturbed nuclear mechanics include the many diseases caused by mutations in the nuclear envelope proteins lamin A/C and associated proteins, as well as cancer cells that are often characterized by abnormal nuclear morphology. In this article, we will focus on determining the functional relationship between nuclear mechanics and cellular (dys-)function, describing the molecular changes associated with physiological and pathological examples, the resulting defects in nuclear mechanics, and the effects on cellular function. New insights into the close relationship between nuclear mechanics and cellular organization and function will yield a better understanding of normal biology and will offer new clues into therapeutic approaches to the various diseases associated with defective nuclear mechanics. PMID:23737203

Anatomy and Physiology of the Speech Mechanism.

ERIC Educational Resources Information Center

Sheets, Boyd V.

This monograph on the anatomical and physiological aspects of the speech mechanism stresses the importance of a general understanding of the process of verbal communication. Contents include "Positions of the Body,""Basic Concepts Linked with the Speech Mechanism,""The Nervous System,""The Respiratory System--Sound-Power Source,""The…

Skeletal Muscle-specific G Protein-coupled Receptor Kinase 2 Ablation Alters Isolated Skeletal Muscle Mechanics and Enhances Clenbuterol-stimulated Hypertrophy*

PubMed Central

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

Physiological, biochemical and transcriptional analysis of onion bulbs during storage

PubMed Central

Chope, Gemma A.; Cools, Katherine; Hammond, John P.; Thompson, Andrew J.; Terry, Leon A.

2012-01-01

Background and Aims During the transition from endo-dormancy to eco-dormancy and subsequent growth, the onion bulb undergoes the transition from sink organ to source, to sustain cell division in the meristematic tissue. The mechanisms controlling these processes are not fully understood. Here, a detailed analysis of whole onion bulb physiological, biochemical and transcriptional changes in response to sprouting is reported, enabling a better knowledge of the mechanisms regulating post-harvest onion sprout development. Methods Biochemical and physiological analyses were conducted on different cultivars (‘Wellington’, ‘Sherpa’ and ‘Red Baron’) grown at different sites over 3 years, cured at different temperatures (20, 24 and 28 °C) and stored under different regimes (1, 3, 6 and 6 → 1 °C). In addition, the first onion oligonucleotide microarray was developed to determine differential gene expression in onion during curing and storage, so that transcriptional changes could support biochemical and physiological analyses. Key Results There were greater transcriptional differences between samples at harvest and before sprouting than between the samples taken before and after sprouting, with some significant changes occurring during the relatively short curing period. These changes are likely to represent the transition from endo-dormancy to sprout suppression, and suggest that endo-dormancy is a relatively short period ending just after curing. Principal component analysis of biochemical and physiological data identified the ratio of monosaccharides (fructose and glucose) to disaccharide (sucrose), along with the concentration of zeatin riboside, as important factors in discriminating between sprouting and pre-sprouting bulbs. Conclusions These detailed analyses provide novel insights into key regulatory triggers for sprout dormancy release in onion bulbs and provide the potential for the development of biochemical or transcriptional markers for sprout initiation. Evidence presented herein also suggests there is no detrimental effect on bulb storage life and quality caused by curing at 20 °C, producing a considerable saving in energy and costs. PMID:22234560

Mechanisms involved in the development of diabetic retinopathy induced by oxidative stress.

PubMed

Guzman, David Calderón; Olguín, Hugo Juárez; García, Ernestina Hernández; Peraza, Armando Valenzuela; de la Cruz, Diego Zamora; Soto, Monica Punzo

2017-01-01

Diabetic retinopathy (DR) is one of the main complications in patients with diabetes and has been the leading cause of visual loss since 1990. Oxidative stress is a biological process resulting from excessive production of reactive oxygen species (ROS). This process contributes to the development of many diseases and disease complications. ROS interact with various cellular components to induce cell injury. Fortunately, there is an antioxidan t system that protects organisms against ROS. Indeed, when ROS exceed antioxidant capacity, the resulting cell injury can cause diverse physiological and pathological changes that could lead to a disease like DR. This paper reviews the possible mechanisms of common and novel biomarkers involved in the development of DR and explores how these biomarkers could be used to monitor the damage induced by oxidative stress in DR, which is a significant complication in people with diabetes. The poor control of glucemy in pacients with DB has been shown contribute to the development of complications in eyes as DR.

Genome-wide association meta-analysis highlights light-induced signaling as a driver for refractive error.

PubMed

Tedja, Milly S; Wojciechowski, Robert; Hysi, Pirro G; Eriksson, Nicholas; Furlotte, Nicholas A; Verhoeven, Virginie J M; Iglesias, Adriana I; Meester-Smoor, Magda A; Tompson, Stuart W; Fan, Qiao; Khawaja, Anthony P; Cheng, Ching-Yu; Höhn, René; Yamashiro, Kenji; Wenocur, Adam; Grazal, Clare; Haller, Toomas; Metspalu, Andres; Wedenoja, Juho; Jonas, Jost B; Wang, Ya Xing; Xie, Jing; Mitchell, Paul; Foster, Paul J; Klein, Barbara E K; Klein, Ronald; Paterson, Andrew D; Hosseini, S Mohsen; Shah, Rupal L; Williams, Cathy; Teo, Yik Ying; Tham, Yih Chung; Gupta, Preeti; Zhao, Wanting; Shi, Yuan; Saw, Woei-Yuh; Tai, E-Shyong; Sim, Xue Ling; Huffman, Jennifer E; Polašek, Ozren; Hayward, Caroline; Bencic, Goran; Rudan, Igor; Wilson, James F; Joshi, Peter K; Tsujikawa, Akitaka; Matsuda, Fumihiko; Whisenhunt, Kristina N; Zeller, Tanja; van der Spek, Peter J; Haak, Roxanna; Meijers-Heijboer, Hanne; van Leeuwen, Elisabeth M; Iyengar, Sudha K; Lass, Jonathan H; Hofman, Albert; Rivadeneira, Fernando; Uitterlinden, André G; Vingerling, Johannes R; Lehtimäki, Terho; Raitakari, Olli T; Biino, Ginevra; Concas, Maria Pina; Schwantes-An, Tae-Hwi; Igo, Robert P; Cuellar-Partida, Gabriel; Martin, Nicholas G; Craig, Jamie E; Gharahkhani, Puya; Williams, Katie M; Nag, Abhishek; Rahi, Jugnoo S; Cumberland, Phillippa M; Delcourt, Cécile; Bellenguez, Céline; Ried, Janina S; Bergen, Arthur A; Meitinger, Thomas; Gieger, Christian; Wong, Tien Yin; Hewitt, Alex W; Mackey, David A; Simpson, Claire L; Pfeiffer, Norbert; Pärssinen, Olavi; Baird, Paul N; Vitart, Veronique; Amin, Najaf; van Duijn, Cornelia M; Bailey-Wilson, Joan E; Young, Terri L; Saw, Seang-Mei; Stambolian, Dwight; MacGregor, Stuart; Guggenheim, Jeremy A; Tung, Joyce Y; Hammond, Christopher J; Klaver, Caroline C W

2018-06-01

Refractive errors, including myopia, are the most frequent eye disorders worldwide and an increasingly common cause of blindness. This genome-wide association meta-analysis in 160,420 participants and replication in 95,505 participants increased the number of established independent signals from 37 to 161 and showed high genetic correlation between Europeans and Asians (>0.78). Expression experiments and comprehensive in silico analyses identified retinal cell physiology and light processing as prominent mechanisms, and also identified functional contributions to refractive-error development in all cell types of the neurosensory retina, retinal pigment epithelium, vascular endothelium and extracellular matrix. Newly identified genes implicate novel mechanisms such as rod-and-cone bipolar synaptic neurotransmission, anterior-segment morphology and angiogenesis. Thirty-one loci resided in or near regions transcribing small RNAs, thus suggesting a role for post-transcriptional regulation. Our results support the notion that refractive errors are caused by a light-dependent retina-to-sclera signaling cascade and delineate potential pathobiological molecular drivers.

Light-driven changes in energy metabolism directly entrain the cyanobacterial circadian oscillator

PubMed Central

Rust, Michael J.; Golden, Susan S.; O'Shea, Erin K.

2012-01-01

Circadian clocks are self-sustained biological oscillators that can be entrained by environmental cues. Though this phenomenon has been studied in many organisms, the molecular mechanisms of entrainment remain unclear. Three cyanobacterial proteins and ATP are sufficient to generate oscillations in phosphorylation in vitro. We show that changes in illumination that induce a phase shift in cultured cyanobacteria also cause changes in the ATP/ADP ratio. When these nucleotide changes are simulated in the in vitro oscillator, they cause phase shifts similar to those observed in vivo. Physiological concentrations of ADP inhibit kinase activity in the oscillator and a mathematical model constrained by data shows that this effect is sufficient to quantitatively explain entrainment of the cyanobacterial circadian clock. PMID:21233390

Cyclic electron flow, NPQ and photorespiration are crucial for the establishment of young plants of Ricinus communis and Jatropha curcas exposed to drought.

PubMed

Lima Neto, M C; Cerqueira, J V A; da Cunha, J R; Ribeiro, R V; Silveira, J A G

2017-07-01

Although plant physiological responses to drought have been widely studied, the interaction between photoprotection, photorespiration and antioxidant metabolism in water-stressed plants is scarcely addressed. This study aimed to evaluate the physiological adjustments preserving photosynthesis and growth in two plant species with different tolerance to drought: Jatropha curcas and Ricinus communis. We measured stress indicators, gas exchange, photochemistry of PSII and PSI, antioxidant enzymes, cyclic electron flow and photorespiration. Physiological stress indicators associated with reduction in growth confirmed R. communis as sensitive and J. curcas as tolerant to drought. Drought induced loss of photosynthesis in R. communis, whereas J. curcas maintained higher leaf gas exchange and photochemistry under drought. In addition, J. curcas showed higher dissipation of excess energy and presented higher cyclic electron flow when exposed to drought. Although none of these mechanisms have been triggered in R. communis, this species showed increases in photorespiration. R. communis displayed loss of Rubisco content while the Rubisco relative abundance did not change in J. curcas under drought. Accordingly, the in vivo maximum Rubisco carboxylation rate (V cmax ) and the maximum photosynthetic electron transport rate driving RuBP regeneration (J max ) were less affected in J. curcas. Both species displayed an efficient antioxidant mechanism by increasing activities of ascorbate peroxidase (APX) and superoxide dismutase (SOD). Overall, we suggest that the modulation of different photoprotective mechanisms is crucial to mitigate the effects caused by excess energy, maintaining photosynthetic apparatus efficiency and promoting the establishment of young plants of these two species under drought. © 2017 German Botanical Society and The Royal Botanical Society of the Netherlands.

Short-term effects of cardiac steroids on intracellular membrane traffic in neuronal NT2 cells.

PubMed

Rosen, H; Glukmann, V; Feldmann, T; Fridman, E; Lichtstein, D

2006-12-30

Cardiac steroids (CS) are specific inhibitors of Na+, K+-ATPase activity. Although the presence of CS-like compounds in animal tissues has been established, their physiological role is not clear. In a previous study we showed that in pulse-chase membrane-labeling experiments, long term (hours) interaction of CS at physiological concentrations (nM) with Na+, K+-ATPase, caused changes in endocytosed membrane traffic in human NT2 cells. This was associated with the accumulation of large vesicles adjacent to the nucleus. For this sequence of events to function in the physiological setting, however, CS would be expected to modify membrane traffic upon short term (min) exposure and membrane labeling. We now demonstrate that CS affects membrane traffic also following a short exposure. This was reflected by the CS-induced accumulation of FM1-43 and transferrin in the cells, as well as by changes in their colocalization with Na+, K+-ATPase. We also show that the CS-induced changes in membrane traffic following up to 2 hrs exposure are reversible, whereas longer treatment induces irreversible effects. Based on these observations, we propose that endogenous CS-like compounds are physiological regulators of the recycling of endocytosed membrane proteins and cargo in neuronal cells, and may affect basic mechanisms such as neurotransmitter release and reuptake.

Misalignment with the external light environment drives metabolic and cardiac dysfunction.

PubMed

West, Alexander C; Smith, Laura; Ray, David W; Loudon, Andrew S I; Brown, Timothy M; Bechtold, David A

2017-09-12

Most organisms use internal biological clocks to match behavioural and physiological processes to specific phases of the day-night cycle. Central to this is the synchronisation of internal processes across multiple organ systems. Environmental desynchrony (e.g. shift work) profoundly impacts human health, increasing cardiovascular disease and diabetes risk, yet the underlying mechanisms remain unclear. Here, we characterise the impact of desynchrony between the internal clock and the external light-dark (LD) cycle on mammalian physiology. We reveal that even under stable LD environments, phase misalignment has a profound effect, with decreased metabolic efficiency and disrupted cardiac function including prolonged QT interval duration. Importantly, physiological dysfunction is not driven by disrupted core clock function, nor by an internal desynchrony between organs, but rather the altered phase relationship between the internal clockwork and the external environment. We suggest phase misalignment as a major driver of pathologies associated with shift work, chronotype and social jetlag.The misalignment between internal circadian rhythm and the day-night cycle can be caused by genetic, behavioural and environmental factors, and may have a profound impact on human physiology. Here West et al. show that desynchrony between the internal clock and the external environment alter metabolic parameters and cardiac function in mice.

Correlated physiological and perceptual effects of noise in a tactile stimulus.

PubMed

Lak, Armin; Arabzadeh, Ehsan; Harris, Justin A; Diamond, Mathew E

2010-04-27

We investigated connections between the physiology of rat barrel cortex neurons and the sensation of vibration in humans. One set of experiments measured neuronal responses in anesthetized rats to trains of whisker deflections, each train characterized either by constant amplitude across all deflections or by variable amplitude ("amplitude noise"). Firing rate and firing synchrony were, on average, boosted by the presence of noise. However, neurons were not uniform in their responses to noise. Barrel cortex neurons have been categorized as regular-spiking units (putative excitatory neurons) and fast-spiking units (putative inhibitory neurons). Among regular-spiking units, amplitude noise caused a higher firing rate and increased cross-neuron synchrony. Among fast-spiking units, noise had the opposite effect: It led to a lower firing rate and decreased cross-neuron synchrony. This finding suggests that amplitude noise affects the interaction between inhibitory and excitatory neurons. From these physiological effects, we expected that noise would lead to an increase in the perceived intensity of a vibration. We tested this notion using psychophysical measurements in humans. As predicted, subjects overestimated the intensity of noisy vibrations. Thus the physiological mechanisms present in barrel cortex also appear to be at work in the human tactile system, where they affect vibration perception.

Causes of Low and High Citation Potentials in Science: Citation Analysis of Biochemistry and Plant Physiology Journals.

ERIC Educational Resources Information Center

Marton, Janos

1983-01-01

Citation data of 16 biochemistry and plant physiology journals show that reasons for lower citation potentials of plant physiology articles are: (1) readership is narrower for plant physiology journals; (2) plant physiologists can cite fewer thematically relevant new articles; and (3) plant physiology research fields are more isolated. References…

Physiological responses to daily light exposure

NASA Astrophysics Data System (ADS)

Yang, Yefeng; Yu, Yonghua; Yang, Bo; Zhou, Hong; Pan, Jinming

2016-04-01

Long daylength artificial light exposure associates with disorders, and a potential physiological mechanism has been proposed. However, previous studies have examined no more than three artificial light treatments and limited metabolic parameters, which have been insufficient to demonstrate mechanical responses. Here, comprehensive physiological response curves were established and the physiological mechanism was strengthened. Chicks were illuminated for 12, 14, 16, 18, 20, or 22 h periods each day. A quadratic relationship between abdominal adipose weight (AAW) and light period suggested that long-term or short-term light exposure could decrease the amount of AAW. Quantitative relationships between physiological parameters and daily light period were also established in this study. The relationships between triglycerides (TG), cholesterol (TC), glucose (GLU), phosphorus (P) levels and daily light period could be described by quadratic regression models. TG levels, AAW, and BW positively correlated with each other, suggesting long-term light exposure significantly increased AAW by increasing TG thus resulting in greater BW. A positive correlation between blood triiodothyronine (T3) levels and BW suggested that daily long-term light exposure increased BW by thyroid hormone secretion. Though the molecular pathway remains unknown, these results suggest a comprehensive physiological mechanism through which light exposure affects growth.

The WNKs: atypical protein kinases with pleiotropic actions

PubMed Central

McCormick, James A.; Ellison, David H.

2011-01-01

WNKs are serine/threonine kinases that comprise a unique branch of the kinome. They are so-named owing to the unusual placement of an essential catalytic lysine. WNKs have now been identified in diverse organisms. In humans and other mammals, four genes encoding WNKs. WNKs are widely expressed at the message level, although data on protein expression is more limited. Soon after the WNKs were identified, mutations in genes encoding WNK 1 and 4 were determined to cause the human disease, Familial Hyperkalemic Hypertension (also known as pseudohypoaldosteronism II, or Gordon’s Syndrome). For this reason, a major focus of investigation has been to dissect the role of WNK kinases in renal regulation of ion transport. More recently, a different mutation in WNK1 was identified as the cause of hereditary sensory and autonomic neuropathy type II (HSANII), an early-onset autosomal disease of peripheral sensory nerves. Thus, the WNKs represent an important family of potential targets for the treatment of human disease, and further elucidation of their physiological actions outside of the kidney and brain is necessary. In this review, we describe the gene structure and mechanisms regulating expression and activity of the WNKs. Subsequently, we outline substrates and targets of WNKs, and effects of WNKs on cellular physiology, both in the kidney and elsewhere. Next, consequences of these effects on integrated physiological function are outlined. Finally, we discuss the known and putative pathophysiological relevance of the WNKs. PMID:21248166

Design of a knee joint mechanism that adapts to individual physiology.

PubMed

Jiun-Yih Kuan; Pasch, Kenneth A; Herr, Hugh M

2014-01-01

This paper describes the design of a new knee joint mechanism, called the Adaptive Coupling Joint (ACJ). The new mechanism has an adaptive trajectory of the center of rotations (COR) that automatically matches those of the attached biological joint. The detailed design is presented as well as characterization results of the ACJ. Conventional exoskeleton and assistive devices usually consider limb joints as a one to three degrees of freedom (DOFs) joint synthesized by multiple one-DOF hinge joints in a single plane. However, the biological joints are complex and usually rotate with respect to a changing COR. As a result, the mismatch between limb joint motion and mechanical interface motion can lead to forces that cause undesired ligament and muscle length changes and internal mechanical changes. These undesired changes contribute to discomfort, as well as to the slippage and sluggish interaction between humans and devices. It is shown that the ACJ can transmit planetary torques from either active or passive devices to the limbs without altering the normal biological joint motion.

Environmental, Physiological, and Cultural Injuries and Genetic Disorders

USDA-ARS?s Scientific Manuscript database

There are some disorders of citrus that are not currently known to be caused by a pathogenic agent, but appears to be inherited, physiologically based, or caused by environmental conditions. Environmental injuries include heat injury and sunburn; wind injury; smog; flooding; hail damage; lightning; ...

Ocean warming and acidification: Unifying physiological principles linking organism response to ecosystem change?

NASA Astrophysics Data System (ADS)

Pörtner, H. O.; Bock, C.; Lannig, G.; Lucassen, M.; Mark, F. C.; Stark, A.; Walther, K.; Wittmann, A.

2011-12-01

The effects of ocean warming and acidification on individual species of marine ectothermic animals may be based on some common denominators, i.e. physiological responses that can be assumed to reflect unifying principles, common to all marine animal phyla. Identification of these principles requires studies, which reach beyond the species-specific response, and consider multiple stressors, for example temperature, CO2 or extreme hypoxia. Analyses of response and acclimation include functional traits of physiological performance on various levels of biological organisation, from changes in the transcriptome to patterns of acid-base regulation and whole animal thermal tolerance. Conclusions are substantiated by comparisons of species and phyla from temperate, Arctic and Antarctic ecosystems and also benefit from the interpretation of paleo-patterns based on the use of a unifying physiological concept, suitable to integrate relevant environmental factors into a more comprehensive picture. Studying the differential specialization of animals on climate regimes and their sensitivity to climate leads to improved understanding of ongoing and past ecosystem change and should then support more reliable projections of future scenarios. For example, accumulating CO2 causes disturbances in acid-base status. Resilience to ocean acidification may be reflected in the capacity to compensate for these disturbances or their secondary effects. Ion and pH regulation comprise thermally sensitive active and passive transfer processes across membranes. Specific responses of ion transporter genes and their products to temperature and CO2 were found in fish, crustaceans and bivalves. However, compensation may cause unfavourable shifts in energy budget and beyond that hamper cellular and mitochondrial metabolism, which are directly linked to the animal's aerobic performance window. In crabs, oysters and, possibly, fishes, a narrowing of the thermal window is caused by moderate increases in CO2 levels. Furthermore, a decrease in the efficiency of energy production may occur and affect growth and fitness as well as larval development. Different sensitivities of life history stages indicate physiologically sensitive bottlenecks during the life cycle of marine organisms. Available evidence suggests that the concept of oxygen and capacity limited thermal tolerance (OCLTT) provides access to the physiological mechanisms closely defining the sensitivities and responses of species to various stressors. It provides causality and quantifies the levels and changes of performance and resistance, and supports more realistic estimates of species and ecosystem sensitivities to environmental change. The emerging picture of differential sensitivities across animal phyla is in line with existing categorizations of sensitivities from palaeo-observations during the Permian-Triassic mass extinctions (A.H. Knoll et al., Earth and Planetary Science Letters 256, 295-313, 2007).

Radioiodine therapy for thyroid cancer depicted uterine leiomyoma.

PubMed

Hirata, Kenji; Shiga, Tohru; Kubota, Kanako C; Okamoto, Shozo; Kamibayashi, Tomohito; Tamaki, Nagara

2009-03-01

A 55-year-old woman underwent radioiodine therapy for papillary carcinoma of the thyroid. Post-therapeutic I-131 scan revealed radioiodine uptake in the pelvic region and in the thyroid bed. CT revealed a huge mass connected to the uterus. The tumor was operated on and histologically proven to be a leiomyoma of the uterus. Some physiological conditions or nonthyroidal diseases can cause false positives in patients with postoperative thyroid cancer. We suggest that uterine leiomyoma might be added to the pitfall list, although the mechanism of I-131 uptake remains unclear.

Effective assessments of electroencephalography during stroke recovery: contemporary approaches and considerations.

PubMed

Iyer, Kartik K

2017-11-01

Stroke is one of the leading causes of permanent disability worldwide, relying conventionally on extended periods of physiotherapy to recover functional ability. While neuroimaging techniques and emerging neurorehabilitation paradigms have advanced our understanding of pathophysiological mechanisms underlying stroke, recent evidence has renewed focus on quantifying features of cortical activity present in electroencephalography recordings to greatly enhance our understanding of stroke treatment and recovery. This Neuro Forum article reviews these key advances and discusses the importance of quantifying electroencephalography in future assessments of stroke survivors. Copyright © 2017 the American Physiological Society.

Naturally produced citral can significantly inhibit normal physiology and induce cytotoxicity on Magnaporthe grisea.

PubMed

Li, Rong-Yu; Wu, Xiao-Mao; Yin, Xian-Hui; Long, You-Hua; Li, Ming

2015-02-01

Given the importance of finding alternatives to synthetic fungicides, the antifungal effects of natural product citral on six plant pathogenic fungi (Magnaporthe grisea, Gibberella zeae, Fusarium oxysporum, Valsa mali, Botrytis cinerea, and Rhizoctonia solani) were determined. Mycelial growth rate results showed that citral possessed high antifungal activities on those test fungi with EC50 values ranging from 39.52 to 193.00 µg/mL, which had the highest inhibition rates against M. grisea. Further action mechanism of citral on M. grisea was carried out. Citral treatment was found to alter the morphology of M. grisea hyphae by causing a loss of cytoplasm and distortion of mycelia. Moreover, citral was able to induce an increase in chitinase activity in M. grisea, indicating disruption of the cell wall. These results indicate that citral may act by disrupting cell wall integrity and membrane permeability, thus resulting in physiology changes and causing cytotoxicity. Importantly, the inhibitory effect of citral on M. grisea appears to be associated with its effects on mycelia reducing sugar, soluble protein, chitinase activity, pyruvate content, and malondialdehyde content. Copyright © 2014 Elsevier Inc. All rights reserved.

How dying cells alert the immune system to danger

PubMed Central

Kono, Hajime; Rock, Kenneth L.

2009-01-01

When a cell dies in vivo the event does not go unnoticed. The host has evolved mechanisms to detect the death of cells and rapidly investigate the nature of their demise. If cell death is a result of natural causes, that is, it is part of normal physiological processes, then there is little threat to the organism. In this situation, little else is done other than removing the corpse. However, if cells have died as the consequence of some violence or disease, then both defence and repair mechanisms are mobilized. The importance of this process to host defence and disease pathogenesis has only been appreciated relatively recently. This article will review our current knowledge of these processes. PMID:18340345

Different Facets of Copy Number Changes: Permanent, Transient, and Adaptive

PubMed Central

Mishra, Sweta

2016-01-01

Chromosomal copy number changes are frequently associated with harmful consequences and are thought of as an underlying mechanism for the development of diseases. However, changes in copy number are observed during development and occur during normal biological processes. In this review, we highlight the causes and consequences of copy number changes in normal physiologic processes as well as cover their associations with cancer and acquired drug resistance. We discuss the permanent and transient nature of copy number gains and relate these observations to a new mechanism driving transient site-specific copy gains (TSSGs). Finally, we discuss implications of TSSGs in generating intratumoral heterogeneity and tumor evolution and how TSSGs can influence the therapeutic response in cancer. PMID:26755558

The study of pain with blood oxygen level dependent functional magnetic resonance imaging

NASA Astrophysics Data System (ADS)

Ibinson, James W.

Using blood oxygen level dependent functional magnetic resonance imaging (BOLD FMRI), the brain areas activated by pain were studied. These initial studies led to interesting new findings about the body's response to pain and to the refinement of one method used in FMRI analysis for correction of physiologic noise (signal fluctuations caused by the cyclic and non-cyclic changes in the cardiovascular and respiratory status of the body). In the first study, evidence was provided suggesting that the multiple painful stimulations used in typical pain FMRI block designs may cause attenuation over time of the BOLD signal within activated areas. The effect this may have on pain investigations using multiple tasks has not been previously investigated. The demonstrated BOLD attenuation seems unique to pain studies. Several possible explanations exist, but two of the most likely are neural activity modulation by descending pain inhibitory mechanisms and changing hemodynamics caused by a physiologic response to pain. The second study began the investigation of hemodynamics by monitoring the physiologic response to pain for eight subjects in two phases. Phase one used a combination of standard operating suite monitors and research equipment to characterizing the physiologic response to pain. Phase two collected magnetic resonance quantitative flow images during painful nerve stimulation to test for changes in global cerebral blood flow. It is well established that changes in respiration and global blood flow can affect the BOLD response, leading to the final investigation of this dissertation. The brain activation induced by pain for the same eight subjects used in the physiologic response experiments described above was then studied by BOLD FMRI. By including the respiration signal and end-tidal carbon dioxide levels in the analysis of the images, the quantification and removal of image intensity variations correlated to breathing and end-tidal carbon dioxide changes could be performed. The technique generally accepted for this analysis, however, uses respiration signals averaged over a 3 second period. Because normal respiratory rate is approximately one breath every 3 to 5 seconds, it was hypothesized that performing the correction using the average breathing data set would miss much of the actual respiration induced variation in each image. Therefore, a new technique for removing signal that covaries with the actual breathing values present during the collection of each image was introduced. (Abstract shortened by UMI.)

Polyalanine expansions drive a shift into α-helical clusters without amyloid-fibril formation.

PubMed

Polling, Saskia; Ormsby, Angelique R; Wood, Rebecca J; Lee, Kristie; Shoubridge, Cheryl; Hughes, James N; Thomas, Paul Q; Griffin, Michael D W; Hill, Andrew F; Bowden, Quill; Böcking, Till; Hatters, Danny M

2015-12-01

Polyglutamine (polyGln) expansions in nine human proteins result in neurological diseases and induce the proteins' tendency to form β-rich amyloid fibrils and intracellular deposits. Less well known are at least nine other human diseases caused by polyalanine (polyAla)-expansion mutations in different proteins. The mechanisms of how polyAla aggregates under physiological conditions remain unclear and controversial. We show here that aggregation of polyAla is mechanistically dissimilar to that of polyGln and hence does not exhibit amyloid kinetics. PolyAla assembled spontaneously into α-helical clusters with diverse oligomeric states. Such clustering was pervasive in cells irrespective of visible aggregate formation, and it disrupted the normal physiological oligomeric state of two human proteins natively containing polyAla: ARX and SOX3. This self-assembly pattern indicates that polyAla expansions chronically disrupt protein behavior by imposing a deranged oligomeric status.

Interference with ethylene perception at receptor level sheds light on auxin and transcriptional circuits associated with the climacteric ripening of apple fruit (Malus x domestica Borkh.).

PubMed

Tadiello, Alice; Longhi, Sara; Moretto, Marco; Ferrarini, Alberto; Tononi, Paola; Farneti, Brian; Busatto, Nicola; Vrhovsek, Urska; Molin, Alessandra Dal; Avanzato, Carla; Biasioli, Franco; Cappellin, Luca; Scholz, Matthias; Velasco, Riccardo; Trainotti, Livio; Delledonne, Massimo; Costa, Fabrizio

2016-12-01

Apple (Malus x domestica Borkh.) is a model species for studying the metabolic changes that occur at the onset of ripening in fruit crops, and the physiological mechanisms that are governed by the hormone ethylene. In this study, to dissect the climacteric interplay in apple, a multidisciplinary approach was employed. To this end, a comprehensive analysis of gene expression together with the investigation of several physiological entities (texture, volatilome and content of polyphenolic compounds) was performed throughout fruit development and ripening. The transcriptomic profiling was conducted with two microarray platforms: a dedicated custom array (iRIPE) and a whole genome array specifically enriched with ripening-related genes for apple (WGAA). The transcriptomic and phenotypic changes following the application of 1-methylcyclopropene (1-MCP), an ethylene inhibitor leading to important modifications in overall fruit physiology, were also highlighted. The integrative comparative network analysis showed both negative and positive correlations between ripening-related transcripts and the accumulation of specific metabolites or texture components. The ripening distortion caused by the inhibition of ethylene perception, in addition to affecting the ethylene pathway, stimulated the de-repression of auxin-related genes, transcription factors and photosynthetic genes. Overall, the comprehensive repertoire of results obtained here advances the elucidation of the multi-layered climacteric mechanism of fruit ripening, thus suggesting a possible transcriptional circuit governed by hormones and transcription factors. © 2016 The Authors The Plant Journal © 2016 John Wiley & Sons Ltd.

Mitochondrial proton and electron leaks.

PubMed

Jastroch, Martin; Divakaruni, Ajit S; Mookerjee, Shona; Treberg, Jason R; Brand, Martin D

2010-01-01

Mitochondrial proton and electron leak have a major impact on mitochondrial coupling efficiency and production of reactive oxygen species. In the first part of this chapter, we address the molecular nature of the basal and inducible proton leak pathways, and their physiological importance. The basal leak is unregulated, and a major proportion can be attributed to mitochondrial anion carriers, whereas the proton leak through the lipid bilayer appears to be minor. The basal proton leak is cell-type specific and correlates with metabolic rate. The inducible leak through the ANT (adenine nucleotide translocase) and UCPs (uncoupling proteins) can be activated by fatty acids, superoxide or lipid peroxidation products. The physiological role of inducible leak through UCP1 in mammalian brown adipose tissue is heat production, whereas the roles of non-mammalian UCP1 and its paralogous proteins, in particular UCP2 and UCP3, are not yet resolved. The second part of the chapter focuses on the electron leak that occurs in the mitochondrial electron transport chain. Exit of electrons prior to the reduction of oxygen to water at cytochrome c oxidase causes superoxide production. As the mechanisms of electron leak are crucial to understanding their physiological relevance, we summarize the mechanisms and topology of electron leak from complexes I and III in studies using isolated mitochondria. We also highlight recent progress and challenges of assessing electron leak in the living cell. Finally, we emphasize the importance of proton and electron leak as therapeutic targets in body mass regulation and insulin secretion.

Multi-factorial in vivo stable isotope fractionation: causes, correlations, consequences and applications.

PubMed

Schmidt, Hanns-Ludwig; Robins, Richard J; Werner, Roland A

2015-01-01

Many physical and chemical processes in living systems are accompanied by isotope fractionation on H, C, N, O and S. Although kinetic or thermodynamic isotope effects are always the basis, their in vivo manifestation is often modulated by secondary influences. These include metabolic branching events or metabolite channeling, metabolite pool sizes, reaction mechanisms, anatomical properties and compartmentation of plants and animals, and climatological or environmental conditions. In the present contribution, the fundamentals of isotope effects and their manifestation under in vivo conditions are outlined. The knowledge about and the understanding of these interferences provide a potent tool for the reconstruction of physiological events in plants and animals, their geographical origin, the history of bulk biomass and the biosynthesis of defined representatives. It allows the use of isotope characteristics of biomass for the elucidation of biochemical pathways and reaction mechanisms and for the reconstruction of climatic, physiological, ecological and environmental conditions during biosynthesis. Thus, it can be used for the origin and authenticity control of food, the study of ecosystems and animal physiology, the reconstruction of present and prehistoric nutrition chains and paleaoclimatological conditions. This is demonstrated by the outline of fundamental and application-orientated examples for all bio-elements. The aim of the review is to inform (advanced) students from various disciplines about the whole potential and the scope of stable isotope characteristics and fractionations and to provide them with a comprehensive introduction to the literature on fundamental aspects and applications.

Early Developmental Conditioning of Later Health and Disease: Physiology or Pathophysiology?

PubMed Central

Hanson, M. A.; Gluckman, P. D.

2014-01-01

Extensive experimental animal studies and epidemiological observations have shown that environmental influences during early development affect the risk of later pathophysiological processes associated with chronic, especially noncommunicable, disease (NCD). This field is recognized as the developmental origins of health and disease (DOHaD). We discuss the extent to which DOHaD represents the result of the physiological processes of developmental plasticity, which may have potential adverse consequences in terms of NCD risk later, or whether it is the manifestation of pathophysiological processes acting in early life but only becoming apparent as disease later. We argue that the evidence suggests the former, through the operation of conditioning processes induced across the normal range of developmental environments, and we summarize current knowledge of the physiological processes involved. The adaptive pathway to later risk accords with current concepts in evolutionary developmental biology, especially those concerning parental effects. Outside the normal range, effects on development can result in nonadaptive processes, and we review their underlying mechanisms and consequences. New concepts concerning the underlying epigenetic and other mechanisms involved in both disruptive and nondisruptive pathways to disease are reviewed, including the evidence for transgenerational passage of risk from both maternal and paternal lines. These concepts have wider implications for understanding the causes and possible prevention of NCDs such as type 2 diabetes and cardiovascular disease, for broader social policy and for the increasing attention paid in public health to the lifecourse approach to NCD prevention. PMID:25287859

Modeling mechanical cardiopulmonary interactions for virtual environments.

PubMed

Kaye, J M

1997-01-01

We have developed a computer system for modeling mechanical cardiopulmonary behavior in an interactive, 3D virtual environment. The system consists of a compact, scalar description of cardiopulmonary mechanics, with an emphasis on respiratory mechanics, that drives deformable 3D anatomy to simulate mechanical behaviors of and interactions between physiological systems. Such an environment can be used to facilitate exploration of cardiopulmonary physiology, particularly in situations that are difficult to reproduce clinically. We integrate 3D deformable body dynamics with new, formal models of (scalar) cardiorespiratory physiology, associating the scalar physiological variables and parameters with corresponding 3D anatomy. Our approach is amenable to modeling patient-specific circumstances in two ways. First, using CT scan data, we apply semi-automatic methods for extracting and reconstructing the anatomy to use in our simulations. Second, our scalar models are defined in terms of clinically-measurable, patient-specific parameters. This paper describes our approach and presents a sample of results showing normal breathing and acute effects of pneumothoraces.

Hepatorenal syndrome.

PubMed

Papper, S

1980-01-01

Renal failure without apparent cause (the hepatorenal syndrome) may develop in the course of cirrhosis of the liver. While the development of renal failure bears a poor prognosis, spontaneous recovery can occur. The data suggest that for the most part patients die in rather than of renal failure. The latter seems to be only part of a broader more fundamental disturbance. The pathogenesis of HRS is unknown, but the evidence supports an impairment of effective renal perfusion. The two major hypotheses concerning the nature of the impaired perfusion are that it is a physiologic response to alterations in the extrarenal circulation, and that there is an unidentified humoral agent(s) produced by or inadequately inactivated by or bypassing the diseased liver and causing circulatory changes in the kidney as well as in other organs. It is possible that both mechanisms are operative. Treatment is unsatisfactory and emphasis is presently best placed upon searching for more treatable causes of renal functional impairment in individual patients.

Mutations causing syndromic autism define an axis of synaptic pathophysiology.

PubMed

Auerbach, Benjamin D; Osterweil, Emily K; Bear, Mark F

2011-11-23

Tuberous sclerosis complex and fragile X syndrome are genetic diseases characterized by intellectual disability and autism. Because both syndromes are caused by mutations in genes that regulate protein synthesis in neurons, it has been hypothesized that excessive protein synthesis is one core pathophysiological mechanism of intellectual disability and autism. Using electrophysiological and biochemical assays of neuronal protein synthesis in the hippocampus of Tsc2(+/-) and Fmr1(-/y) mice, here we show that synaptic dysfunction caused by these mutations actually falls at opposite ends of a physiological spectrum. Synaptic, biochemical and cognitive defects in these mutants are corrected by treatments that modulate metabotropic glutamate receptor 5 in opposite directions, and deficits in the mutants disappear when the mice are bred to carry both mutations. Thus, normal synaptic plasticity and cognition occur within an optimal range of metabotropic glutamate-receptor-mediated protein synthesis, and deviations in either direction can lead to shared behavioural impairments.

Pathogenesis of Hyperthyroidism.

PubMed

Singh, Ishita; Hershman, Jerome M

2016-12-06

Hyperthyroidism is a form of thyrotoxicosis in which there is excess thyroid hormone synthesis and secretion. Multiple etiologies can lead to a common clinical state of "thyrotoxicosis," which is a consequence of the high thyroid hormone levels and their action on different tissues of the body. The most common cause of thyrotoxicosis is Graves' disease, an autoimmune disorder in which stimulating thyrotropin receptor antibodies bind to thyroid stimulating hormone (TSH) receptors on thyroid cells and cause overproduction of thyroid hormones. Other etiologies include: forms of thyroiditis in which inflammation causes release of preformed hormone, following thyroid gland insult that is autoimmune, infectious, mechanical or medication induced; secretion of human chorionic gonadotropin in the setting of transient gestational thyrotoxicosis and trophoblastic tumors; pituitary thyrotropin release, and exposure to extra-thyroidal sources of thyroid hormone that may be endogenous or exogenous. © 2017 American Physiological Society. Compr Physiol 7:67-79, 2017. Copyright © 2017 John Wiley & Sons, Inc.

Mechanical interactions between ice crystals and red blood cells during directional solidification.

PubMed

Ishiguro, H; Rubinsky, B

1994-10-01

Experiments in which red blood cells were frozen on a directional solidification stage under a microscope show that there is a mechanical interaction between ice crystals and cells in which cells are pushed and deformed by the ice crystals. The mechanical interaction occurs during freezing of cells in physiological saline and is significantly inhibited by the addition of 20% v/v glycerol to the solution. The addition of osmotically insignificant quantities of antifreeze proteins from the winter flounder or ocean pout to the physiological saline with 20% v/v glycerol generates strong mechanical interactions between the ice and the cells. The cells were destroyed during freezing in physiological saline, survived freezing in physiological saline with glycerol, and were completely destroyed by the addition of antifreeze proteins to the solution with glycerol. The difference in cell survival through freezing and thawing appears to be related, in part, to the habit of ice crystal growing in the suspension of red blood cells and the nature of mechanical interaction between the ice crystal and the cells. This suggests that mechanical damage may be a factor during cryopreservation of cells.

Prostaglandins in the gut and their relationship to non-steroidal anti-inflammatory drugs.

PubMed

Semble, E L; Wu, W C

1989-08-01

Prostaglandins are long-chain, saturated, oxygenated fatty acids. Relatively large quantities of prostaglandins have been found in gut mucosa, suggesting that these substances play an important role in gastrointestinal physiology. Non-steroidal anti-inflammatory drugs (NSAIDs) cause damage to the gastric, intestinal, and colonic mucosa in experimental animals and in humans. Prostaglandins protect the gastric mucosa against injury induced by NSAIDs, and this property has been labelled cytoprotection. The mechanisms of cytoprotection have been extensively evaluated and are probably multifactorial, including effects on the gastric mucosal barrier, gastric blood flow, mucus, bicarbonate, and fluid section, ionic transport, cyclic AMP, and surface-active phospholipids. Prostaglandins may also prevent NSAID-induced injury in the small intestine and colon. The mechanisms responsible for prostaglandin protection in the lower gut against injurious agents are unknown. Further studies of the role of prostaglandins in the gut and their relationship to the effects of NSAIDs are needed. The results of these investigations may lead to a better understanding of the importance of prostaglandins in the physiology of the gastrointestinal tract, and may provide information regarding actions of NSAIDs on the functional integrity of the gastric, intestinal, and colonic mucosa.

Effect of proton pump inhibitors on magnesium balance: is there a link to cardiovascular risk?

PubMed

Pisani, Laura Francesca; Filippi, Elisabetta; Vavassori, Sara; Munizio, Nadia; Vecchi, Maurizio; Pastorelli, Luca

2016-03-01

Magnesium (Mg(2+)) is the second most copious element inside human cells and the fourth most abundant positively charged ion in the human body. It is of central importance for a broad variety of physiological processes, including intracellular signaling, neuronal excitability, muscle contraction, bone formation and enzyme activation. Its overall balance is tightly regulated by the concerted actions of the intestine, bones and kidneys. Disturbance of this balance can have serious consequences. Symptoms of hypomagnesaemia include tetany, seizures and cardiac arrhythmias, whereas hypermagnesaemia may cause cardiovascular and neuromuscular abnormalities. Drugs can interfere with Mg(2+) homoeostasis in several ways, and proton-pump inhibitors (PPIs) have been associated with hypomagnesaemia. A better understanding of the molecular mechanisms underlying the adverse effects of these medications on Mg(2+) balance will isuggest ideas for prevention and treatment, and might provide greater insight into Mg(2+) homoeostasis. This review gives an overview of the influence of PPIs on Mg(2+) homoeostasis and provides some understanding of the underlying physiological mechanisms. Moreover, we will discuss the potential link between PPI-induced changes in Mg(2+) homeostasis, and the reported cardiovascular risk observed in long-term PPI users.

Hyperinflation and intrinsic positive end-expiratory pressure: less room to breathe.

PubMed

Krieger, Bruce P

2009-01-01

Clinically, the symptoms and limited exercise capabilities of patients with chronic obstructive pulmonary disease (COPD) correlate better with changes in lung volumes than with airflow measurements. The realization of the clinical importance of hyperinflation has been overshadowed for decades by the use of forced expiratory volume during 1 s (FEV(1)) and the ratio of the FEV(1) to the forced expiratory vital capacity (FEV(1)/FVC) to categorize the severity and progression of COPD. Hyperinflation is defined as an elevation in the end-expiratory lung volume or functional residual capacity. When severe hyperinflation encroaches upon inspiratory capacity and limits vital capacity, it results in elevated intrinsic positive end-expiratory pressure (PEEPi) that places the diaphragm at a mechanical disadvantage and increases the work of breathing. Severe hyperinflation is the major physiologic cause of the resulting hypercarbic respiratory failure and patients' inability to transition (i.e. wean) from mechanical ventilatory support to spontaneous breathing. This paper reviews the basic physiologic principles of hyperinflation and its clinical manifestations as demonstrated by PEEPi. Also reviewed are the adverse effects of hyperinflation and PEEPi in critically ill patients with COPD, and methods for minimizing or counterbalancing these effects. Copyright 2009 S. Karger AG, Basel.

Impact of hypoxia stress on the physiological responses of sea cucumber Apostichopus japonicus: respiration, digestion, immunity and oxidative damage

PubMed Central

Huo, Da; Ru, Xiaoshang; Zhang, Libin; Lin, Chenggang; Xin, Xiaoke

2018-01-01

Hypoxia is one of the most frequently occurring stressors confronted by industrial cultures of sea cucumber and can cause large economic losses and resource degradation. However, its responsive mechanisms are still lacking. In this paper, the physiological responses of Apostichopus japonicus to oxygen deficiency was illustrated, including induced oxidative response and immune defense and changed digestive enzymes activities. Significantly increased activities of alpha-amylase (AMS), acid phosphatase (ACP), lactate dehydrogenase, catalase, peroxidase, succinate dehydrogenase and higher content of malondialdehyde, and decreased activities of lipase and trypsin (TRY) were observed after hypoxia exposure (dissolved oxygen [DO] 2 mg/L). Expressions of key genes showed that AMS, peptidase, ACP, alkaline phosphatase, lysozyme, heat shock protein 70 and glutathione peroxidase were increased and TRY was decreased under hypoxia. With the decline of the DO level, the decreased tendency of oxygen consumption rates was different in varied weight groups. Moreover, respiratory trees were observed degraded under long-term hypoxia stress, thus leading a negative effect of respiration. These results could help to develop a better understanding of the responsive mechanism of sea cucumber under hypoxia stress and provide a theoretical basis for the prevention of hypoxia risk. PMID:29719735

Worker Personality and Its Association with Spatially Structured Division of Labor

PubMed Central

Pamminger, Tobias; Foitzik, Susanne; Kaufmann, Katharina C.; Schützler, Natalie; Menzel, Florian

2014-01-01

Division of labor is a defining characteristic of social insects and fundamental to their ecological success. Many of the numerous tasks essential for the survival of the colony must be performed at a specific location. Consequently, spatial organization is an integral aspect of division of labor. The mechanisms organizing the spatial distribution of workers, separating inside and outside workers without central control, is an essential, but so far neglected aspect of division of labor. In this study, we investigate the behavioral mechanisms governing the spatial distribution of individual workers and its physiological underpinning in the ant Myrmica rubra. By investigating worker personalities we uncover position-associated behavioral syndromes. This context-independent and temporally stable set of correlated behaviors (positive association between movements and attraction towards light) could promote the basic separation between inside (brood tenders) and outside workers (foragers). These position-associated behavior syndromes are coupled with a high probability to perform tasks, located at the defined position, and a characteristic cuticular hydrocarbon profile. We discuss the potentially physiological causes for the observed behavioral syndromes and highlight how the study of animal personalities can provide new insights for the study of division of labor and self-organized processes in general. PMID:24497911

Literature Review and Annotated Bibliography: Water Requirements of Desert Ungulates

USGS Publications Warehouse

Cain, James W.; Krausman, Paul R.; Rosenstock, Steven S.; Turner, Jack C.

2005-01-01

Executive Summary Ungulates adapted to desert areas are able to survive extreme temperatures and limited water availability. This ability is largely due to behavioral, morphological, and physiological adaptations that allow these animals to avoid or tolerate extreme environmental conditions. The physiological adaptations possessed by ungulates for thermoregulation and maintenance of water balance have been the subject of numerous studies involving a wide range of species. In this report we review the behavioral, morphological, and physiological mechanisms used by ungulates and other desert mammals to maintain water and temperature balance in arid environments. We also review some of the more commonly used methods for studying the physiological mechanisms involved in water balance and thermoregulation, and the influence of dehydration on these mechanisms.

Estimation of the physiological mechanical conditioning in vascular tissue engineering by a predictive fluid-structure interaction approach.

PubMed

Tresoldi, Claudia; Bianchi, Elena; Pellegata, Alessandro Filippo; Dubini, Gabriele; Mantero, Sara

2017-08-01

The in vitro replication of physiological mechanical conditioning through bioreactors plays a crucial role in the development of functional Small-Caliber Tissue-Engineered Blood Vessels. An in silico scaffold-specific model under pulsatile perfusion provided by a bioreactor was implemented using a fluid-structure interaction (FSI) approach for viscoelastic tubular scaffolds (e.g. decellularized swine arteries, DSA). Results of working pressures, circumferential deformations, and wall shear stress on DSA fell within the desired physiological range and indicated the ability of this model to correctly predict the mechanical conditioning acting on the cells-scaffold system. Consequently, the FSI model allowed us to a priori define the stimulation pattern, driving in vitro physiological maturation of scaffolds, especially with viscoelastic properties.

Cushing's syndrome: from physiological principles to diagnosis and clinical care

PubMed Central

Raff, Hershel; Carroll, Ty

2015-01-01

The physiological control of cortisol synthesis in the adrenal cortex involves stimulation of adrenocorticotrophic hormone (ACTH) by hypothalamic corticotrophin-releasing hormone (CRH) and then stimulation of the adrenal by ACTH. The control loop of the hypothalamic–pituitary–adrenal (HPA) axis is closed by negative feedback of cortisol on the hypothalamus and pituitary. Understanding this system is required to master the diagnosis, differential diagnosis and treatment of endogenous hypercortisolism – Cushing's syndrome. Endogenous Cushing's syndrome is caused either by excess ACTH secretion or by autonomous cortisol release from the adrenal cortex. Diagnosis of cortisol excess exploits three physiological principles: failure to achieve the normal nadir in the cortisol diurnal rhythm, loss of sensitivity of ACTH-secreting tumours to cortisol negative feedback, and increased excretion of free cortisol in the urine. Differentiating a pituitary source of excess ACTH (Cushing's disease) from an ectopic source is accomplished by imaging the pituitary and sampling for ACTH in the venous drainage of the pituitary. With surgical removal of ACTH or cortisol-secreting tumours, secondary adrenal insufficiency ensues because of the prior suppression of the HPA axis by glucocorticoid negative feedback. Medical therapy is targeted to the anatomical location of the dysregulated component of the HPA axis. Future research will focus on new diagnostics and treatments of Cushing's syndrome. These are elegant examples of translational research: understanding basic physiology informs the development of new approaches to diagnosis and treatment. Appreciating pathophysiology generates new areas for inquiry of basic physiological and biochemical mechanisms. PMID:25480800

Inhaled environmental/occupational irritants and allergens: mechanisms of cardiovascular and systemic responses. Introduction.

PubMed

Yeates, D B; Mauderly, J L

2001-08-01

The articles in this monograph focus on the mechanisms whereby ambient particulate matter (PM) and co-pollutants deposited in the respiratory tract cause cardiovascular and systemic effects, especially in persons with preexisting conditions such as allergic hyperresponsiveness and pulmonary, cardiac, and vascular diseases. During the past few years, it has become clear that inhaled pollutants cause adverse effects outside the respiratory tract and that these effects may in some cases be more important than respiratory effects. Investigators pursuing traditional approaches to understanding mechanisms of air pollution effects need to be brought together with those outside that community who have expertise in pathogenetic mechanisms by which deposited air pollutants might affect nonrespiratory organs. To this end, a workshop was held and papers were developed from a broad range of scientists having specialized expertise in allergic and cardiovascular physiology. The overall goal of this monograph is to benchmark current thinking and enhance progress toward identifying and understanding the mechanisms by which nonrespiratory health effects occur and, by extension, to facilitate the appropriate management of relationships between air quality and health. This monograph contains a compilation of multidisciplinary research that forms a framework for generating and testing plausible new research hypotheses. Not only will this information stimulate the thinking of researchers, but it will also provide an improved foundation for funding agencies and advisory groups to frame research strategies, programs, and priorities.

Epithelial and endothelial cell plasticity in chronic obstructive pulmonary disease (COPD).

PubMed

Sohal, Sukhwinder Singh

2017-03-01

Chronic Obstructive Pulmonary Disease (COPD) is mainly caused by smoking and presents with shortness of breath that is progressive and irreversible. It is a worldwide health problem and the fourth most common cause of chronic disability and mortality (even in developed countries). It is a complex disease involving both the airway and lung parenchyma. Small-airway fibrosis is the main contributor to physiological airway dysfunction in COPD. One potential mechanism contributing to small-airway fibrosis is epithelial mesenchymal transition (EMT). When associated with angiogenesis (EMT-type-3), EMT may well also be linked to the development of airway epithelial cancer, which is closely associated with COPD and predominantly observed in large airways. Vascular remodeling has also been widely reported in smokers and patients with COPD but the mechanisms behind it are poorly understood. It is quite possible that the process of endothelial to mesenchymal transition (EndMT) is also active in COPD lungs, in addition to EMT. Understanding these pathological mechanisms will greatly enhance our knowledge of the immunopathology of smoking-related lung disease. Only by understanding these processes can new therapies be developed. Crown Copyright © 2016. Published by Elsevier B.V. All rights reserved.

Static and dynamic bending has minor effects on xylem hydraulics of conifer branches (Picea abies, Pinus sylvestris).

PubMed

Mayr, Stefan; Bertel, Clara; Dämon, Birgit; Beikircher, Barbara

2014-09-01

The xylem hydraulic efficiency and safety is usually measured on mechanically unstressed samples, although trees may be exposed to combined hydraulic and mechanical stress in the field. We analysed changes in hydraulic conductivity and vulnerability to drought-induced embolism during static bending of Picea abies and Pinus sylvestris branches as well as the effect of dynamic bending on the vulnerability. We hypothesized this mechanical stress to substantially impair xylem hydraulics. Intense static bending caused an only small decrease in hydraulic conductance (-19.5 ± 2.4% in P. abies) but no shift in vulnerability thresholds. Dynamic bending caused a 0.4 and 0.8 MPa decrease of the water potential at 50 and 88% loss of conductivity in P. sylvestris, but did not affect vulnerability thresholds in P. abies. With respect to applied extreme bending radii, effects on plant hydraulics were surprisingly small and are thus probably of minor eco-physiological importance. More importantly, results indicate that available xylem hydraulic analyses (of conifers) sufficiently reflect plant hydraulics under field conditions. © 2014 The Authors. Plant, Cell & Environment published by John Wiley & Sons Ltd.

Increased respiratory neural drive and work of breathing in exercise-induced laryngeal obstruction.

PubMed

Walsted, Emil S; Faisal, Azmy; Jolley, Caroline J; Swanton, Laura L; Pavitt, Matthew J; Luo, Yuan-Ming; Backer, Vibeke; Polkey, Michael I; Hull, James H

2018-02-01

Exercise-induced laryngeal obstruction (EILO), a phenomenon in which the larynx closes inappropriately during physical activity, is a prevalent cause of exertional dyspnea in young individuals. The physiological ventilatory impact of EILO and its relationship to dyspnea are poorly understood. The objective of this study was to evaluate exercise-related changes in laryngeal aperture on ventilation, pulmonary mechanics, and respiratory neural drive. We prospectively evaluated 12 subjects (6 with EILO and 6 healthy age- and gender-matched controls). Subjects underwent baseline spirometry and a symptom-limited incremental exercise test with simultaneous and synchronized recording of endoscopic video and gastric, esophageal, and transdiaphragmatic pressures, diaphragm electromyography, and respiratory airflow. The EILO and control groups had similar peak work rates and minute ventilation (V̇e) (work rate: 227 ± 35 vs. 237 ± 35 W; V̇e: 103 ± 20 vs. 98 ± 23 l/min; P > 0.05). At submaximal work rates (140-240 W), subjects with EILO demonstrated increased work of breathing ( P < 0.05) and respiratory neural drive ( P < 0.05), developing in close temporal association with onset of endoscopic evidence of laryngeal closure ( P < 0.05). Unexpectedly, a ventilatory increase ( P < 0.05), driven by augmented tidal volume ( P < 0.05), was seen in subjects with EILO before the onset of laryngeal closure; there were however no differences in dyspnea intensity between groups. Using simultaneous measurements of respiratory mechanics and diaphragm electromyography with endoscopic video, we demonstrate, for the first time, increased work of breathing and respiratory neural drive in association with the development of EILO. Future detailed investigations are now needed to understand the role of upper airway closure in causing exertional dyspnea and exercise limitation. NEW & NOTEWORTHY Exercise-induced laryngeal obstruction is a prevalent cause of exertional dyspnea in young individuals; yet, how laryngeal closure affects breathing is unknown. In this study we synchronized endoscopic video with respiratory physiological measurements, thus providing the first detailed commensurate assessment of respiratory mechanics and neural drive in relation to laryngeal closure. Laryngeal closure was associated with increased work of breathing and respiratory neural drive preceded by an augmented tidal volume and a rise in minute ventilation.

Nonstructural leaf carbohydrate dynamics of Pinus edulis during drought-induced tree mortality reveal role for carbon metabolism in mortality mechanism.

PubMed

Adams, Henry D; Germino, Matthew J; Breshears, David D; Barron-Gafford, Greg A; Guardiola-Claramonte, Maite; Zou, Chris B; Huxman, Travis E

2013-03-01

Vegetation change is expected with global climate change, potentially altering ecosystem function and climate feedbacks. However, causes of plant mortality, which are central to vegetation change, are understudied, and physiological mechanisms remain unclear, particularly the roles of carbon metabolism and xylem function. We report analysis of foliar nonstructural carbohydrates (NSCs) and associated physiology from a previous experiment where earlier drought-induced mortality of Pinus edulis at elevated temperatures was associated with greater cumulative respiration. Here, we predicted faster NSC decline for warmed trees than for ambient-temperature trees. Foliar NSC in droughted trees declined by 30% through mortality and was lower than in watered controls. NSC decline resulted primarily from decreased sugar concentrations. Starch initially declined, and then increased above pre-drought concentrations before mortality. Although temperature did not affect NSC and sugar, starch concentrations ceased declining and increased earlier with higher temperatures. Reduced foliar NSC during lethal drought indicates a carbon metabolism role in mortality mechanism. Although carbohydrates were not completely exhausted at mortality, temperature differences in starch accumulation timing suggest that carbon metabolism changes are associated with time to death. Drought mortality appears to be related to temperature-dependent carbon dynamics concurrent with increasing hydraulic stress in P. edulis and potentially other similar species. © 2013 The Authors. New Phytologist © 2013 New Phytologist Trust.

Dissecting the impact of CO2 and pH on the mechanisms of photosynthesis and calcification in the coccolithophore Emiliania huxleyi.

PubMed

Bach, Lennart T; Mackinder, Luke C M; Schulz, Kai G; Wheeler, Glen; Schroeder, Declan C; Brownlee, Colin; Riebesell, Ulf

2013-07-01

Coccolithophores are important calcifying phytoplankton predicted to be impacted by changes in ocean carbonate chemistry caused by the absorption of anthropogenic CO2 . However, it is difficult to disentangle the effects of the simultaneously changing carbonate system parameters (CO2 , bicarbonate, carbonate and protons) on the physiological responses to elevated CO2 . Here, we adopted a multifactorial approach at constant pH or CO2 whilst varying dissolved inorganic carbon (DIC) to determine physiological and transcriptional responses to individual carbonate system parameters. We show that Emiliania huxleyi is sensitive to low CO2 (growth and photosynthesis) and low bicarbonate (calcification) as well as low pH beyond a limited tolerance range, but is much less sensitive to elevated CO2 and bicarbonate. Multiple up-regulated genes at low DIC bear the hallmarks of a carbon-concentrating mechanism (CCM) that is responsive to CO2 and bicarbonate but not to pH. Emiliania huxleyi appears to have evolved mechanisms to respond to limiting rather than elevated CO2 . Calcification does not function as a CCM, but is inhibited at low DIC to allow the redistribution of DIC from calcification to photosynthesis. The presented data provides a significant step in understanding how E. huxleyi will respond to changing carbonate chemistry at a cellular level. © 2013 The Authors. New Phytologist © 2013 New Phytologist Trust.

Coping with thermal challenges: physiological adaptations to environmental temperatures.

PubMed

Tattersall, Glenn J; Sinclair, Brent J; Withers, Philip C; Fields, Peter A; Seebacher, Frank; Cooper, Christine E; Maloney, Shane K

2012-07-01

Temperature profoundly influences physiological responses in animals, primarily due to the effects on biochemical reaction rates. Since physiological responses are often exemplified by their rate dependency (e.g., rate of blood flow, rate of metabolism, rate of heat production, and rate of ion pumping), the study of temperature adaptations has a long history in comparative and evolutionary physiology. Animals may either defend a fairly constant temperature by recruiting biochemical mechanisms of heat production and utilizing physiological responses geared toward modifying heat loss and heat gain from the environment, or utilize biochemical modifications to allow for physiological adjustments to temperature. Biochemical adaptations to temperature involve alterations in protein structure that compromise the effects of increased temperatures on improving catalytic enzyme function with the detrimental influences of higher temperature on protein stability. Temperature has acted to shape the responses of animal proteins in manners that generally preserve turnover rates at animals' normal, or optimal, body temperatures. Physiological responses to cold and warmth differ depending on whether animals maintain elevated body temperatures (endothermic) or exhibit minimal internal heat production (ectothermic). In both cases, however, these mechanisms involve regulated neural and hormonal over heat flow to the body or heat flow within the body. Examples of biochemical responses to temperature in endotherms involve metabolic uncoupling mechanisms that decrease metabolic efficiency with the outcome of producing heat, whereas ectothermic adaptations to temperature are best exemplified by the numerous mechanisms that allow for the tolerance or avoidance of ice crystal formation at temperatures below 0°C. 2012 American Physiological Society. Compr Physiol 2:2037-2061, 2012.

Acute γ-secretase Inhibition of Nonhuman Primate CNS Shifts Amyloid Precursor Protein (APP) Metabolism from Amyloid-β Production to Alternative APP Fragments without Amyloid-β Rebound

PubMed Central

Cook, Jacquelynn J.; Wildsmith, Kristin R.; Gilberto, David B.; Holahan, Marie A.; Kinney, Gene G.; Mathers, Parker D.; Michener, Maria S.; Price, Eric A.; Shearman, Mark S.; Simon, Adam J.; Wang, Jennifer X.; Wu, Guoxin; Yarasheski, Kevin E.; Bateman, Randall J.

2010-01-01

The accumulation of amyloid beta (Aβ) in Alzheimer’s disease is caused by an imbalance of production and clearance, which leads to increased soluble Aβ species and extracellular plaque formation in the brain. Multiple Aβ-lowering therapies are currently in development: an important goal is to characterize the molecular mechanisms of action and effects on physiological processing of Aβ, as well as other amyloid precursor protein (APP) metabolites, in models which approximate human Aβ physiology. To this end, we report the translation of the human in vivo stable-isotope-labeling kinetics (SILK) method to a rhesus monkey cisterna magna ported (CMP) nonhuman primate model, and use the model to test the mechanisms of action of a γ-secretase inhibitor (GSI). A major concern of inhibiting the enzymes which produce Aβ (β- and γ-secretase) is that precursors of Aβ may accumulate and cause a rapid increase in Aβ production when enzyme inhibition discontinues. In this study, the GSI MK-0752 was administered to conscious CMP rhesus monkeys in conjunction with in vivo stable isotope labeling, and dose-dependently reduced newly generated CNS Aβ. In contrast to systemic Aβ metabolism, CNS Aβ production was not increased after the GSI was cleared. These results indicate that most of the CNS APP was metabolized to products other than Aβ, including C-terminal truncated forms of Aβ: 1–14, 1–15 and 1–16; this demonstrates an alternative degradation pathway for CNS amyloid precursor protein during γ-secretase inhibition. PMID:20463236

Constitutive activation and uncoupling of the atrial natriuretic peptide receptor by mutations at the dimer interface. Role of the dimer structure in signalling.

PubMed

Qiu, Yue; Ogawa, Haruo; Miyagi, Masaru; Misono, Kunio S

2004-02-13

The crystal packing of the extracellular hormone binding domain of the atrial natriuretic peptide (ANP) receptor contains two possible dimer pairs, the head-to-head (hh) and tail-to-tail (tt) dimer pairs associated through the membrane-distal and membrane-proximal subdomains, respectively. The tt-dimer structure has been proposed previously (van den Akker, F., Zhang, X., Miyagi, M., Huo, X., Misono, K. S., and Yee, V. C. (2000) Nature 406, 101-104). However, no direct evidence is available to identify the physiological dimer form. Here we report site-directed mutagenesis studies of residues at the two alternative dimer interfaces in the full-length receptor expressed on COS cells. The Trp74 to Arg mutation (W74R) or D71R at the hh-dimer interface caused partial constitutive guanylate cyclase activation, whereas mutation F96D or H99D caused receptor uncoupling. In contrast, mutation Y196D or L225D at the tt-interface had no such effect. His99 modification at the hh-dimer interface by ethoxyformic anhydride abolished ANP binding. These results suggest that the hh-dimer represents the physiological structure. Recently, we determined the crystal structure of ANPR complexed with ANP and proposed a hormone-induced rotation mechanism mediating transmembrane signaling (H. Ogawa, Y. Qiu, C. M. Ogata, and K. S. Misono, submitted for publication). The observed effects of mutations are consistent with the ANP-induced structural change identified from the crystal structures with and without ANP and support the proposed rotation mechanism for ANP receptor signaling.

Programmed Effects in Neurobehavior and Antioxidative Physiology in Zebrafish Embryonically Exposed to Cadmium: Observations and Hypothesized Adverse Outcome Pathway Framework.

PubMed

Ruiter, Sander; Sippel, Josefine; Bouwmeester, Manon C; Lommelaars, Tobias; Beekhof, Piet; Hodemaekers, Hennie M; Bakker, Frank; van den Brandhof, Evert-Jan; Pennings, Jeroen L A; van der Ven, Leo T M

2016-11-02

Non-communicable diseases (NCDs) are a major cause of premature mortality. Recent studies show that predispositions for NCDs may arise from early-life exposure to low concentrations of environmental contaminants. This developmental origins of health and disease (DOHaD) paradigm suggests that programming of an embryo can be disrupted, changing the homeostatic set point of biological functions. Epigenetic alterations are a possible underlying mechanism. Here, we investigated the DOHaD paradigm by exposing zebrafish to subtoxic concentrations of the ubiquitous contaminant cadmium during embryogenesis, followed by growth under normal conditions. Prolonged behavioral responses to physical stress and altered antioxidative physiology were observed approximately ten weeks after termination of embryonal exposure, at concentrations that were 50-3200-fold below the direct embryotoxic concentration, and interpreted as altered developmental programming. Literature was explored for possible mechanistic pathways that link embryonic subtoxic cadmium to the observed apical phenotypes, more specifically, the probability of molecular mechanisms induced by cadmium exposure leading to altered DNA methylation and subsequently to the observed apical phenotypes. This was done using the adverse outcome pathway model framework, and assessing key event relationship plausibility by tailored Bradford-Hill analysis. Thus, cadmium interaction with thiols appeared to be the major contributor to late-life effects. Cadmium-thiol interactions may lead to depletion of the methyl donor S -adenosyl-methionine, resulting in methylome alterations, and may, additionally, result in oxidative stress, which may lead to DNA oxidation, and subsequently altered DNA methyltransferase activity. In this way, DNA methylation may be affected at a critical developmental stage, causing the observed apical phenotypes.

Rapid Actions of Xenoestrogens Disrupt Normal Estrogenic Signaling

PubMed Central

Watson, Cheryl S.; Hu, Guangzhen; Paulucci-Holthauzen, Adriana A.

2014-01-01

Some chemicals used in consumer products or manufacturing (eg. plastics, surfactants, pesticides, resins) have estrogenic activities; these xenoestrogens (XEs) chemically resemble physiological estrogens and are one of the major categories of synthesized compounds that disrupt endocrine actions. Potent rapid actions of XEs via nongenomic mechanisms contribute significantly to their disruptive effects on functional endpoints (eg. cell proliferation/death, transport, peptide release). Membrane-initiated hormonal signaling in our pituitary cell model is predominantly driven by mERα with mERβ and GPR30 participation. We visualized ERα on plasma membranes using many techniques in the past (impeded ligands, antibodies to ERα ) and now add observations of epitope proximity with other membrane signaling proteins. We have demonstrated a range of rapid signals/protein activations by XEs including: calcium channels, cAMP/PKA, MAPKs, G proteins, caspases, and transcription factors. XEs can cause disruptions of the oscillating temporal patterns of nongenomic signaling elicited by endogenous estrogens. Concentration effects of XEs are nonmonotonic (a trait shared with natural hormones), making it difficult to design efficient (single concentration) toxicology tests to monitor their harmful effects. A plastics monomer, Bisphenol A, modified by waste treatment (chlorination) and other processes causes dephosphorylation of extracellular-regulated kinases, in contrast to having no effects as it does in genomic signaling. Mixtures of XEs, commonly found in contaminated environments, disrupt the signaling actions of physiological estrogens even more severely than do single XEs. Understanding the features of XEs that drive these disruptive mechanisms will allow us to redesign useful chemicals that exclude estrogenic or anti-estrogenic activities. PMID:24269739

Aluminum stress signaling in plants

PubMed Central

Baluska, Frantisek; Matsumoto, Hideaki

2009-01-01

Aluminum (Al) toxicity is a major constraint for crop production in acidic soil worldwide. When the soil pH is lower than 5, Al3+ is released to the soil and enters into root tip cell ceases root development of plant. In acid soil with high mineral content, Al is the major cause of phytotoxicity. The target of Al toxicity is the root tip, in which Al exposure causes inhibition of cell elongation and cell division, leading to root stunting accompanied by reduced water and nutrient uptake. A variety of genes have been identified that are induced or repressed upon Al exposure. At tissue level, the distal part of the transition zone is the most sensitive to Al. At cellular and molecular level, many cell components are implicated in the Al toxicity including DNA in nucleus, numerous cytoplastic compounds, mitochondria, the plasma membrane and the cell wall. Although it is difficult to distinguish the primary targets from the secondary effects so far, understanding of the target sites of the Al toxicity is helpful for elucidating the mechanisms by which Al exerts its deleterious effects on root growth. To develop high tolerance against Al stress is the major goal of plant sciences. This review examines our current understanding of the Al signaling with the physiological, genetic and molecular approaches to improve the crop performance under the Al toxicity. New discoveries will open up new avenues of molecular/physiological inquiry that should greatly advance our understanding of Al tolerance mechanisms. Additionally, these breakthroughs will provide new molecular resources for improving the crop Al tolerance via molecular-assisted breeding and biotechnology. PMID:19820334

Virtual reality applications in assessing the effect of anxiety on sensorimotor integration in human postural control.

PubMed

Widdowson, Christopher; Ganhotra, Jatin; Faizal, Mohammed; Wilko, Marissa; Parikh, Saurin; Adhami, Zainulabidin; Hernandez, Manuel E

2016-08-01

Falls are a leading cause of injury and mortality among adults over the age of 65 years. Given the strong relation between fear of falling and fall risk, identification of the mechanisms that underlie anxiety-related changes in postural control may pave the way to the development of novel therapeutic strategies aimed at reducing fall risk in older adults. First, we review potential mechanisms underlying anxiety-mediated changes in postural control in older adults with and without neurological conditions. We then present a system that allows for the simultaneous recording of neural, physiological, and behavioral data in an immersive virtual reality (VR) environment while implementing sensory and mechanical perturbations to evaluate alterations in sensorimotor integration under conditions with high postural threat. We also discuss applications of VR in minimizing falls in older adults and potential future studies.

Circadian glucocorticoid oscillations promote learning-dependent synapse formation and maintenance

PubMed Central

Liston, Conor; Cichon, Joseph M; Jeanneteau, Freddy; Jia, Zhengping; Chao, Moses V; Gan, Wen-Biao

2013-01-01

Excessive glucocorticoid exposure during chronic stress causes synapse loss and learning impairment. Under normal physiological conditions, glucocorticoid activity oscillates in synchrony with the circadian rhythm. Whether and how endogenous glucocorticoid oscillations modulate synaptic plasticity and learning is unknown. Here we show that circadian glucocorticoid peaks promote postsynaptic dendritic spine formation in the mouse cortex after motor skill learning, whereas troughs are required for stabilizing newly formed spines that are important for long-term memory retention. Conversely, chronic and excessive exposure to glucocorticoids eliminates learning-associated new spines and disrupts previously acquired memories. Furthermore, we show that glucocorticoids promote rapid spine formation through a non-transcriptional mechanism by means of the LIM kinase–cofilin pathway and increase spine elimination through transcriptional mechanisms involving mineralocorticoid receptor activation. Together, these findings indicate that tightly regulated circadian glucocorticoid oscillations are important for learning-dependent synaptic formation and maintenance. They also delineate a new signaling mechanism underlying these effects. PMID:23624512

Effects of Chitin and Its Derivative Chitosan on Postharvest Decay of Fruits: A Review

PubMed Central

Zhang, Hongyin; Li, Renping; Liu, Weimin

2011-01-01

Considerable economic losses to harvested fruits are caused by postharvest fungal decay during transportation and storage, which can be significantly controlled by synthetic fungicides. However, considering public concern over pesticide residues in food and the environment, there is a need for safer alternatives for the control of postharvest decay to substitute synthetic fungicides. As the second most abundant biopolymer renewable source in nature, chitin and its derivative chitosan are widely used in controlling postharvest decay of fruits. This review aims to introduce the effect of chitin and chitosan on postharvest decay in fruits and the possible modes of action involved. We found most of the actions discussed in these researches rest on physiological mechanisms. All of the mechanisms are summarized to lay the groundwork for further studies which should focus on the molecular mechanisms of chitin and chitosan in controlling postharvest decay of fruits. PMID:21541034

Physiologic Basis for Improved Pulmonary Function after Lung Volume Reduction

PubMed Central

Fessler, Henry E.; Scharf, Steven M.; Ingenito, Edward P.; McKenna, Robert J.; Sharafkhaneh, Amir

2008-01-01

It is not readily apparent how pulmonary function could be improved by resecting portions of the lung in patients with emphysema. In emphysema, elevation in residual volume relative to total lung capacity reduces forced expiratory volumes, increases inspiratory effort, and impairs inspiratory muscle mechanics. Lung volume reduction surgery (LVRS) better matches the size of the lungs to the size of the thorax containing them. This restores forced expiratory volumes and the mechanical advantage of the inspiratory muscles. In patients with heterogeneous emphysema, LVRS may also allow space occupied by cysts to be reclaimed by more normal lung. Newer, bronchoscopic methods for lung volume reduction seek to achieve similar ends by causing localized atelectasis, but may be hindered by the low collateral resistance of emphysematous lung. Understanding of the mechanisms of improved function after LVRS can help select patients more likely to benefit from this approach. PMID:18453348

Multidrug resistance in enteric and other gram-negative bacteria.

PubMed

George, A M

1996-05-15

In Gram-negative bacteria, multidrug resistance is a term that is used to describe mechanisms of resistance by chromosomal genes that are activated by induction or mutation caused by the stress of exposure to antibiotics in natural and clinical environments. Unlike plasmid-borne resistance genes, there is no alteration or degradation of drugs or need for genetic transfer. Exposure to a single drug leads to cross-resistance to many other structurally and functionally unrelated drugs. The only mechanism identified for multidrug resistance in bacteria is drug efflux by membrane transporters, even though many of these transporters remain to be identified. The enteric bacteria exhibit mostly complex multidrug resistance systems which are often regulated by operons or regulons. The purpose of this review is to survey molecular mechanisms of multidrug resistance in enteric and other Gram-negative bacteria, and to speculate on the origins and natural physiological functions of the genes involved.

Carbon catabolite regulation in Streptomyces: new insights and lessons learned.

PubMed

Romero-Rodríguez, Alba; Rocha, Diana; Ruiz-Villafán, Beatriz; Guzmán-Trampe, Silvia; Maldonado-Carmona, Nidia; Vázquez-Hernández, Melissa; Zelarayán, Augusto; Rodríguez-Sanoja, Romina; Sánchez, Sergio

2017-09-01

One of the most significant control mechanisms of the physiological processes in the genus Streptomyces is carbon catabolite repression (CCR). This mechanism controls the expression of genes involved in the uptake and utilization of alternative carbon sources in Streptomyces and is mostly independent of the phosphoenolpyruvate phosphotransferase system (PTS). CCR also affects morphological differentiation and the synthesis of secondary metabolites, although not all secondary metabolite genes are equally sensitive to the control by the carbon source. Even when the outcome effect of CCR in bacteria is the same, their essential mechanisms can be rather different. Although usually, glucose elicits this phenomenon, other rapidly metabolized carbon sources can also cause CCR. Multiple efforts have been put through to the understanding of the mechanism of CCR in this genus. However, a reasonable mechanism to explain the nature of this process in Streptomyces does not yet exist. Several examples of primary and secondary metabolites subject to CCR will be examined in this review. Additionally, recent advances in the metabolites and protein factors involved in the Streptomyces CCR, as well as their mechanisms will be described and discussed in this review.

Cellular and molecular mechanisms regulating vascular tone. Part 1: basic mechanisms controlling cytosolic Ca2+ concentration and the Ca2+-dependent regulation of vascular tone.

PubMed

Akata, Takashi

2007-01-01

General anesthetics cause hemodynamic instability and alter blood flow to various organs. There is mounting evidence that most general anesthetics, at clinical concentrations, influence a wide variety of cellular and molecular mechanisms regulating the contractile state of vascular smooth muscle cells (i.e., vascular tone). In addition, in current anesthetic practice, various types of vasoactive agents are often used to control vascular reactivity and to sustain tissue blood flow in high-risk surgical patients with impaired vital organ function and/or hemodynamic instability. Understanding the physiological mechanisms involved in the regulation of vascular tone thus would be beneficial for anesthesiologists. This review, in two parts, provides an overview of current knowledge about the cellular and molecular mechanisms regulating vascular tone-i.e., targets for general anesthetics, as well as for vasoactive drugs that are used in intraoperative circulatory management. This first part of the two-part review focuses on basic mechanisms regulating cytosolic Ca2+ concentration and the Ca2+-dependent regulation of vascular tone.

Observation of cavitation in a mechanical heart valve in a total artificial heart.

PubMed

Lee, Hwansung; Tsukiya, Tomonori; Homma, Akihiko; Kamimura, Tadayuki; Takewa, Yoshiaki; Nishinaka, Tomohiro; Tatsumi, Eisuke; Taenaka, Yoshiyuki; Takano, Hisateru; Kitamura, Soichiro

2004-01-01

Recently, cavitation on the surface of mechanical heart valves has been studied as a cause of fractures occurring in implanted mechanical heart valves. The cause of cavitation in mechanical heart valves was investigated using the 25 mm Medtronic Hall valve and the 23 mm Omnicarbon valve. Closing of these valves in the mitral position was simulated in an electrohydraulic totally artificial heart. Tests were conducted under physiologic pressures at heart rates from 60 to 100 beats per minute with cardiac outputs from 4.8 to 7.7 L/min. The disk closing motion was measured by a laser displacement sensor. A high-speed video camera was used to observe the cavitation bubbles in the mechanical heart valves. The maximum closing velocity of the Omnicarbon valve was faster than that of the Medtronic Hall valve. In both valves, the closing velocity of the leaflet, used as the cavitation threshold, was approximately 1.3-1.5 m/s. In the case of the Medtronic Hall valve, cavitation bubbles were generated by the squeeze flow and by the effects of the venturi and the water hammer. With the Omnicarbon valve, the cavitation bubbles were generated by the squeeze flow and the water hammer. The mechanism leading to the development of cavitation bubbles depended on the valve closing velocity and the valve stop geometry. Most of the cavitation bubbles were observed around the valve stop and were generated by the squeeze flow.

A chaotic model of sustaining attention problem in attention deficit disorder

NASA Astrophysics Data System (ADS)

Baghdadi, G.; Jafari, S.; Sprott, J. C.; Towhidkhah, F.; Hashemi Golpayegani, M. R.

2015-01-01

The problem of keeping an attention level is one of the common symptoms of attention deficit disorder. Dopamine deficiency is introduced as one of the causes of this disorder. Based on some physiological facts about the attention control mechanism and chaos intermittency, a behavioral model is presented in this paper. This model represents the problem of undesired alternation of attention level, and can also suggest different valuable predictions about a possible cause of attention deficit disorder. The proposed model reveals that there is a possible interaction between different neurotransmitters which help the individual to adaptively inhibit the attention switching over time. The result of this study can be used to examine and develop a new practical and more appropriate treatment for the problem of sustaining attention.

Development of life sciences equipment for microgravity and hypergravity simulation

NASA Technical Reports Server (NTRS)

Mulenburg, G. M.; Evans, J.; Vasques, M.; Gundo, D. P.; Griffith, J. B.; Harper, J.; Skundberg, T.

1994-01-01

The mission of the Life Science Division at the NASA Ames Research Center is to investigate the effects of gravity on living systems in the spectrum from cells to humans. The range of these investigations is from microgravity, as experienced in space, to Earth's gravity, and hypergravity. Exposure to microgravity causes many physiological changes in humans and other mammals including a headward shift of body fluids, atrophy of muscles - especially the large muscles of the legs - and changes in bone and mineral metabolism. The high cost and limited opportunity for research experiments in space create a need to perform ground based simulation experiments on Earth. Models that simulate microgravity are used to help identify and quantify these changes, to investigate the mechanisms causing these changes and, in some cases, to develop countermeasures.

Chloride: from Nutrient to Toxicant.

PubMed

Geilfus, Christoph-Martin

2018-05-01

In salinized soils in which chloride (Cl-) is the dominant salt anion, growth of plants that tolerate only low concentrations of salt (glycophytes) is disturbed by Cl- toxicity. Chlorotic discolorations precede necrotic lesions, causing yield reductions. Little is known about the effects of Cl- toxicity on these dysfunctions. A lack of understanding exists regarding (i) the molecular and physiological mechanisms that lead to Cl--induced damage and (ii) the adaptive aspects of induced tolerance to Cl- salinity. Here, mechanistic explanations for the Cl--induced stress responses are proposed and novel ideas and strategies by which glycophytic plants avoid the excessive accumulation of Cl- are reviewed. New experiments are suggested to test the proposed hypotheses. Cl- salinity constrains global food security and thus we urgently need more research into the causes and consequences of Cl- salinity.

Metals and lipid oxidation. Contemporary issues.

PubMed

Schaich, K M

1992-03-01

Lipid oxidation is now recognized to be a critically important reaction in physiological and toxicological processes as well as in food products. This provides compelling reasons to understand what causes lipid oxidation in order to be able to prevent or control the reactions. Redox-active metals are major factors catalyzing lipid oxidation in biological systems. Classical mechanisms of direct electron transfer to double bonds by higher valence metals and of reduction of hydroperoxides by lower valence metals do not always account for patterns of metal catalysis of lipid oxidation in multiphasic or compartmentalized biological systems. To explain why oxidation kinetics, mechanisms, and products in molecular environments which are both chemically and physically complex often do not follow classical patterns predicted by model system studies, increased consideration must be given to five contemporary issues regarding metal catalysis of lipid oxidation: hypervalent non-heme iron or iron-oxygen complexes, heme catalysis mechanism(s), compartmentalization of reactions and lipid phase reactions of metals, effects of metals on product mixes, and factors affecting the mode of metal catalytic action.

Mechanical Ventilation during Extracorporeal Membrane Oxygenation in Patients with Acute Severe Respiratory Failure.

PubMed

Zhang, Zhongheng; Gu, Wan-Jie; Chen, Kun; Ni, Hongying

2017-01-01

Conventionally, a substantial number of patients with acute respiratory failure require mechanical ventilation (MV) to avert catastrophe of hypoxemia and hypercapnia. However, mechanical ventilation per se can cause lung injury, accelerating the disease progression. Extracorporeal membrane oxygenation (ECMO) provides an alternative to rescue patients with severe respiratory failure that conventional mechanical ventilation fails to maintain adequate gas exchange. The physiology behind ECMO and its interaction with MV were reviewed. Next, we discussed the timing of ECMO initiation based on the risks and benefits of ECMO. During the running of ECMO, the protective ventilation strategy can be employed without worrying about catastrophic hypoxemia and carbon dioxide retention. There is a large body of evidence showing that protective ventilation with low tidal volume, high positive end-expiratory pressure, and prone positioning can provide benefits on mortality outcome. More recently, there is an increasing popularity on the use of awake and spontaneous breathing for patients undergoing ECMO, which is thought to be beneficial in terms of rehabilitation.

Mechanical Ventilation during Extracorporeal Membrane Oxygenation in Patients with Acute Severe Respiratory Failure

PubMed Central

Gu, Wan-Jie; Chen, Kun; Ni, Hongying

2017-01-01

Conventionally, a substantial number of patients with acute respiratory failure require mechanical ventilation (MV) to avert catastrophe of hypoxemia and hypercapnia. However, mechanical ventilation per se can cause lung injury, accelerating the disease progression. Extracorporeal membrane oxygenation (ECMO) provides an alternative to rescue patients with severe respiratory failure that conventional mechanical ventilation fails to maintain adequate gas exchange. The physiology behind ECMO and its interaction with MV were reviewed. Next, we discussed the timing of ECMO initiation based on the risks and benefits of ECMO. During the running of ECMO, the protective ventilation strategy can be employed without worrying about catastrophic hypoxemia and carbon dioxide retention. There is a large body of evidence showing that protective ventilation with low tidal volume, high positive end-expiratory pressure, and prone positioning can provide benefits on mortality outcome. More recently, there is an increasing popularity on the use of awake and spontaneous breathing for patients undergoing ECMO, which is thought to be beneficial in terms of rehabilitation. PMID:28127231

Possible mechanisms of postprandial physiological alterations following flavan 3-ol ingestion.

PubMed

Osakabe, Naomi; Terao, Junji

2018-03-01

Foods rich in flavan 3-ols are known to prevent cardiovascular diseases by reducing metabolic syndrome risks, such as hypertension, hyperglycemia, and dyslipidemia. However, the mechanisms involved in this reduction are unclear, particularly because of the poor bioavailability of flavan 3-ols. Recent metabolome analyses of feces produced after repeated ingestion of foods rich in flavan 3-ols may provide insight into the chronic physiological changes associated with the intake of flavan 3-ols. Substantial postprandial changes have been reported after flavan 3-ol ingestion, including hemodynamic and metabolic changes as well as autonomic and central nervous alterations. Taken together, the evidence suggests that flavan 3-ols have both postprandial and chronic effects, which could involve different or common mechanisms. In general, the accumulation of acute functional changes induces chronic physiological alteration. Therefore, this review highlights the postprandial action of flavan 3-ols in order to address the yet unknown mechanism(s) for their physiological function. © The Author(s) 2018. Published by Oxford University Press on behalf of the International Life Sciences Institute. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Induction of oxidative stress causes functional alterations in mouse urothelium via a TRPM8-mediated mechanism: implications for aging.

PubMed

Nocchi, Linda; Daly, Donna M; Chapple, Christopher; Grundy, David

2014-06-01

The incidence of bladder conditions such as overactive bladder syndrome and its associated urinary incontinence is highly prevalent in the elderly. However, the mechanisms underlying these disorders are unclear. Studies suggest that the urothelium forms a 'sensory network' with the underlying innervation, alterations in which, could compromise bladder function. As the accumulation of reactive oxygen species can cause functional alterations with age, the aim of this study was to investigate whether oxidative stress alters urothelial sensory signalling and whether the mechanism underlying the effect of oxidative stress on the urothelium plays a role in aging. Five-month-old(young) and 24-month-old (aged) mice were used. H2O2 , used to induce oxidative stress, resulted in an increase in bladder afferent nerve activity and urothelial intracellular calcium in preparations from young mice. These functional changes were concurrent with upregulation of TRPM8 in the urothelium. Moreover, application of a TRPM8 antagonist significantly attenuated the H2O2 -induced calcium responses. Interestingly, an upregulation of TRPM8 was also found in the urothelium from aged mice, where high oxidative stress levels were observed, together with a greater calcium response to the TRPM8 agonist WS12. Furthermore, these calcium responses were attenuated by pretreatment with the antioxidant N-acetyl-cysteine. This study shows that oxidative stress affects urothelial function involving a TRPM8-mediated mechanism and these effects may have important implications for aging. These data provide an insight into the possible mechanisms by which oxidative stress causes physiological alterations in the bladder, which may also occur in other organs susceptible to aging. © 2014 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

Induction of oxidative stress causes functional alterations in mouse urothelium via a TRPM8-mediated mechanism: implications for aging

PubMed Central

Nocchi, Linda; Daly, Donna M; Chapple, Christopher; Grundy, David

2014-01-01

The incidence of bladder conditions such as overactive bladder syndrome and its associated urinary incontinence is highly prevalent in the elderly. However, the mechanisms underlying these disorders are unclear. Studies suggest that the urothelium forms a ‘sensory network’ with the underlying innervation, alterations in which, could compromise bladder function. As the accumulation of reactive oxygen species can cause functional alterations with age, the aim of this study was to investigate whether oxidative stress alters urothelial sensory signalling and whether the mechanism underlying the effect of oxidative stress on the urothelium plays a role in aging. Five-month-old(young) and 24-month-old (aged) mice were used. H2O2, used to induce oxidative stress, resulted in an increase in bladder afferent nerve activity and urothelial intracellular calcium in preparations from young mice. These functional changes were concurrent with upregulation of TRPM8 in the urothelium. Moreover, application of a TRPM8 antagonist significantly attenuated the H2O2-induced calcium responses. Interestingly, an upregulation of TRPM8 was also found in the urothelium from aged mice, where high oxidative stress levels were observed, together with a greater calcium response to the TRPM8 agonist WS12. Furthermore, these calcium responses were attenuated by pretreatment with the antioxidant N-acetyl-cysteine. This study shows that oxidative stress affects urothelial function involving a TRPM8-mediated mechanism and these effects may have important implications for aging. These data provide an insight into the possible mechanisms by which oxidative stress causes physiological alterations in the bladder, which may also occur in other organs susceptible to aging. PMID:24593692

Body position-dependent shift in odor percept present only for perithreshold odors.

PubMed

Lundström, Johan N; Boyle, Julie A; Jones-Gotman, Marilyn

2008-01-01

We recently demonstrated that a supine position causes a decrease in olfactory sensitivity compared with an upright position. We pursued that initial finding in 3 separate experiments in which we explored the extent of, and mechanism underlying, this phenomenon. In Experiment 1, we replicated the decrease in olfactory sensitivity when in a supine compared with an upright position. In Experiment 2, we measured body position-dependent shifts in physiological variables and sniff measures while smelling suprathreshold odorants and performing a perithreshold odor intensity discrimination task. Olfactory performances were reduced while supine. However, no relationships between the shift in olfactory performances and either the physiological variables or sniff measures were found. In Experiment 3, we determined that there were no position-dependent shifts in ability to discriminate or identify suprathreshold odors or rate them for pleasantness, intensity, or familiarity. However, a drop in scores was observed, and performance was slowed, on a cognitive skill while supine. These results demonstrate a body position-dependent shift in olfactory sensitivity only for perithreshold odors that appears to be mediated by cognitive rather than physiological factors. Implications for olfactory imaging studies are discussed.

Physiological-based modelling of marine fish early life stages provides process knowledge on climate impacts

NASA Astrophysics Data System (ADS)

Peck, M. A.

2016-02-01

Gaining a cause-and-effect understanding of climate-driven changes in marine fish populations at appropriate spatial scales is important for providing robust advice for ecosystem-based fisheries management. Coupling long-term, retrospective analyses and 3-d biophysical, individual-based models (IBMs) shows great potential to reveal mechanism underlying historical changes and to project future changes in marine fishes. IBMs created for marine fish early life stages integrate organismal-level physiological responses and climate-driven changes in marine habitats (from ocean physics to lower trophic level productivity) to test and reveal processes affecting marine fish recruitment. Case studies are provided for hindcasts and future (A1 and B2 projection) simulations performed on some of the most ecologically- and commercially-important pelagic and demersal fishes in the North Sea including European anchovy, Atlantic herring, European sprat and Atlantic cod. We discuss the utility of coupling biophysical IBMs to size-spectrum models to better project indirect (trophodynamic) pathways of climate influence on the early life stages of these and other fishes. Opportunities and challenges are discussed regarding the ability of these physiological-based tools to capture climate-driven changes in living marine resources and food web dynamics of shelf seas.

Computational model of cerebral blood flow redistribution during cortical spreading depression

NASA Astrophysics Data System (ADS)

Verisokin, Andrey Y.; Verveyko, Darya V.; Postnov, Dmitry E.

2016-04-01

In recent decades modelling studies on cortical spreading depression (CSD) and migraine waves successfully contributed to formation of modern view on these fundamental phenomena of brain physiology. However, due to the extreme complexity of object under study (brain cortex) and the diversity of involved physiological pathways, the development of new mathematical models of CSD is still a very relevant and challenging research problem. In our study we follow the functional modelling approach aimed to map the action of known physiological pathways to the specific nonlinear mechanisms that govern formation and evolution of CSD wave patterns. Specifically, we address the role of cerebral blood flow (CBF) redistribution that is caused by excessive neuronal activity by means of neurovascular coupling and mediates a spatial pattern of oxygen and glucose delivery. This in turn changes the local metabolic status of neural tissue. To build the model we simplify the web of known cell-to-cell interactions within a neurovascular unit by selecting the most relevant ones, such as local neuron-induced elevation of extracellular potassium concentration and biphasic response of arteriole radius. We propose the lumped description of distance-dependent hemodynamic coupling that fits the most recent experimental findings.

Egg and Soy-Derived Peptides and Hydrolysates: A Review of Their Physiological Actions against Diabetes and Obesity.

PubMed

C de Campos Zani, Stepheny; Wu, Jianping; B Chan, Catherine

2018-04-28

Type 2 diabetes and obesity are two chronic conditions associated with the metabolic syndrome and their prevalences are increasing worldwide. The investigation of food protein-derived bioactive peptides that can improve the pathophysiology of diabetes or obesity while causing minimal side effects is desired. Egg and soy proteins generate bioactive peptides with multiple biological effects, exerting nutritional and physiological benefits. This review focuses on the anti-diabetic and anti-obesity effects of egg- and soy-derived peptides and hydrolysates in vivo and in vitro relevant to these conditions. Studies using the intact protein were considered only when comparing the results with the hydrolysate or peptides. In vivo evidence suggests that bioactive peptides from egg and soy can potentially be used to manage elements of glucose homeostasis in metabolic syndrome; however, the mechanisms of action on glucose and insulin metabolism, and the interaction between peptides and their molecular targets remain unclear. Optimizing the production of egg- and soy-derived peptides and standardizing the physiological models to study their effects on diabetes and obesity could help to clarify the effects of these bioactive peptides in metabolic syndrome-related conditions.

Intermediate filament proteins of digestive organs: physiology and pathophysiology.

PubMed

Omary, M Bishr

2017-06-01

Intermediate filament proteins (IFs), such as cytoplasmic keratins in epithelial cells and vimentin in mesenchymal cells and the nuclear lamins, make up one of the three major cytoskeletal protein families. Whether in digestive organs or other tissues, IFs share several unique features including stress-inducible overexpression, abundance, cell-selective and differentiation state expression, and association with >80 human diseases when mutated. Whereas most IF mutations cause disease, mutations in simple epithelial keratins 8, 18, or 19 or in lamin A/C predispose to liver disease with or without other tissue manifestations. Keratins serve major functions including protection from apoptosis, providing cellular and subcellular mechanical integrity, protein targeting to subcellular compartments, and scaffolding and regulation of cell-signaling processes. Keratins are essential for Mallory-Denk body aggregate formation that occurs in association with several liver diseases, whereas an alternate type of keratin and lamin aggregation occurs upon liver involvement in porphyria. IF-associated diseases have no known directed therapy, but high-throughput drug screening to identify potential therapies is an appealing ongoing approach. Despite the extensive current knowledge base, much remains to be discovered regarding IF physiology and pathophysiology in digestive and nondigestive organs. Copyright © 2017 the American Physiological Society.

Ionotropic Receptor 76b Is Required for Gustatory Aversion to Excessive Na+ in Drosophila.

PubMed

Lee, Min Jung; Sung, Ha Yeon; Jo, HyunJi; Kim, Hyung-Wook; Choi, Min Sung; Kwon, Jae Young; Kang, KyeongJin

2017-10-01

Avoiding ingestion of excessively salty food is essential for cation homeostasis that underlies various physiological processes in organisms. The molecular and cellular basis of the aversive salt taste, however, remains elusive. Through a behavioral reverse genetic screening, we discover that feeding suppression by Na + -rich food requires Ionotropic Receptor 76b ( Ir76b ) in Drosophila labellar gustatory receptor neurons (GRNs). Concentrated sodium solutions with various anions caused feeding suppression dependent on Ir76b . Feeding aversion to caffeine and high concentrations of divalent cations and sorbitol was unimpaired in Ir76b -deficient animals, indicating sensory specificity of Ir76b- dependent Na + detection and the irrelevance of hyperosmolarity-driven mechanosensation to Ir76b -mediated feeding aversion. Ir76b -dependent Na + -sensing GRNs in both L- and s-bristles are required for repulsion as opposed to the previous report where the L-bristle GRNs direct only low-Na + attraction. Our work extends the physiological implications of Ir76b from low-Na + attraction to high-Na + aversion, prompting further investigation of the physiological mechanisms that modulate two competing components of Na + -evoked gustation coded in heterogeneous Ir76b -positive GRNs.

The dark side of light at night: physiological, epidemiological, and ecological consequences.

PubMed

Navara, Kristen J; Nelson, Randy J

2007-10-01

Organisms must adapt to the temporal characteristics of their surroundings to successfully survive and reproduce. Variation in the daily light cycle, for example, acts through endocrine and neurobiological mechanisms to control several downstream physiological and behavioral processes. Interruptions in normal circadian light cycles and the resulting disruption of normal melatonin rhythms cause widespread disruptive effects involving multiple body systems, the results of which can have serious medical consequences for individuals, as well as large-scale ecological implications for populations. With the invention of electrical lights about a century ago, the temporal organization of the environment has been drastically altered for many species, including humans. In addition to the incidental exposure to light at night through light pollution, humans also engage in increasing amounts of shift-work, resulting in repeated and often long-term circadian disruption. The increasing prevalence of exposure to light at night has significant social, ecological, behavioral, and health consequences that are only now becoming apparent. This review addresses the complicated web of potential behavioral and physiological consequences resulting from exposure to light at night, as well as the large-scale medical and ecological implications that may result.

Direction-dependent regularization for improved estimation of liver and lung motion in 4D image data

NASA Astrophysics Data System (ADS)

Schmidt-Richberg, Alexander; Ehrhardt, Jan; Werner, René; Handels, Heinz

2010-03-01

The estimation of respiratory motion is a fundamental requisite for many applications in the field of 4D medical imaging, for example for radiotherapy of thoracic and abdominal tumors. It is usually done using non-linear registration of time frames of the sequence without further modelling of physiological motion properties. In this context, the accurate calculation of liver und lung motion is especially challenging because the organs are slipping along the surrounding tissue (i.e. the rib cage) during the respiratory cycle, which leads to discontinuities in the motion field. Without incorporating this specific physiological characteristic, common smoothing mechanisms cause an incorrect estimation along the object borders. In this paper, we present an extended diffusion-based model for incorporating physiological knowledge in image registration. By decoupling normal- and tangential-directed smoothing, we are able to estimate slipping motion at the organ borders while preventing gaps and ensuring smooth motion fields inside. We evaluate our model for the estimation of lung and liver motion on the basis of publicly accessible 4D CT and 4D MRI data. The results show a considerable increase of registration accuracy with respect to the target registration error and a more plausible motion estimation.

The effect of music therapy on physiological signs of anxiety in patients receiving mechanical ventilatory support.

PubMed

Korhan, Esra Akin; Khorshid, Leyla; Uyar, Mehmet

2011-04-01

The aim of this study was to investigate if relaxing music is an effective method of reducing the physiological signs of anxiety in patients receiving mechanical ventilatory support. Few studies have focused on the effect of music on physiological signs of anxiety in patients receiving mechanical ventilatory support. A study-case-control, experimental repeated measures design was used. Sixty patients aged 18-70 years, receiving mechanical ventilatory support and hospitalised in the intensive care unit, were taken as a convenience sample. Participants were randomised to a control group or intervention group, who received 60 minutes of music therapy. Classical music was played to patients using media player (MP3) and headphones. Subjects had physiological signs taken immediately before the intervention and at the 30th, 60th and 90th minutes of the intervention. Physiological signs of anxiety assessed in this study were mean systolic and diastolic blood pressure, pulse rate, respiratory rate and oxygen saturation in blood measured by pulse oxymetry. Data were collected over eight months in 2006-2007. The music group had significantly lower respiratory rates, and systolic and diastolic blood pressure, than the control group. This decrease improved progressively in the 30th, 60th and 90th minutes of the intervention, indicating a cumulative dose effect. Music can provide an effective method of reducing potentially harmful physiological responses arising from anxiety. As indicated by the results of this study, music therapy can be supplied to allay anxiety in patients receiving mechanical ventilation. Nurses may include music therapy in the routine care of patients receiving mechanical ventilation. © 2011 Blackwell Publishing Ltd.

Differential Mechanism of Escherichia coli Inactivation by (+)-Limonene as a Function of Cell Physiological State and Drug's Concentration

PubMed Central

Chueca, Beatriz; Pagán, Rafael; García-Gonzalo, Diego

2014-01-01

(+)-limonene is a lipophilic antimicrobial compound, extracted from citrus fruits' essential oils, that is used as a flavouring agent and organic solvent by the food industry. A recent study has proposed a common and controversial mechanism of cell death for bactericidal antibiotics, in which hydroxyl radicals ultimately inactivated cells. Our objective was to determine whether the mechanism of Escherichia coli MG1655 inactivation by (+)-limonene follows that of bactericidal antibiotics. A treatment with 2,000 μL/L (+)-limonene inactivated 4 log10 cycles of exponentially growing E. coli cells in 3 hours. On one hand, an increase of cell survival in the ΔacnB mutant (deficient in a TCA cycle enzyme), or in the presence of 2,2′-dipyridyl (inhibitor of Fenton reaction by iron chelation), thiourea, or cysteamine (hydroxyl radical scavengers) was observed. Moreover, the ΔrecA mutant (deficient in an enzyme involved in SOS response to DNA damage) was more sensitive to (+)-limonene. Thus, this indirect evidence indicates that the mechanism of exponentially growing E. coli cells inactivation by 2,000 μL/L (+)-limonene is due to the TCA cycle and Fenton-mediated hydroxyl radical formation that caused oxidative DNA damage, as observed for bactericidal drugs. However, several differences have been observed between the proposed mechanism for bactericidal drugs and for (+)-limonene. In this regard, our results demonstrated that E. coli inactivation was influenced by its physiological state and the drug's concentration: experiments with stationary-phase cells or 4,000 μL/L (+)-limonene uncovered a different mechanism of cell death, likely unrelated to hydroxyl radicals. Our research has also shown that drug's concentration is an important factor influencing the mechanism of bacterial inactivation by antibiotics, such as kanamycin. These results might help in improving and spreading the use of (+)-limonene as an antimicrobial compound, and in clarifying the controversy about the mechanism of inactivation by bactericidal antibiotics. PMID:24705541

Differential mechanism of Escherichia coli Inactivation by (+)-limonene as a function of cell physiological state and drug's concentration.

PubMed

Chueca, Beatriz; Pagán, Rafael; García-Gonzalo, Diego

2014-01-01

(+)-limonene is a lipophilic antimicrobial compound, extracted from citrus fruits' essential oils, that is used as a flavouring agent and organic solvent by the food industry. A recent study has proposed a common and controversial mechanism of cell death for bactericidal antibiotics, in which hydroxyl radicals ultimately inactivated cells. Our objective was to determine whether the mechanism of Escherichia coli MG1655 inactivation by (+)-limonene follows that of bactericidal antibiotics. A treatment with 2,000 μL/L (+)-limonene inactivated 4 log10 cycles of exponentially growing E. coli cells in 3 hours. On one hand, an increase of cell survival in the ΔacnB mutant (deficient in a TCA cycle enzyme), or in the presence of 2,2'-dipyridyl (inhibitor of Fenton reaction by iron chelation), thiourea, or cysteamine (hydroxyl radical scavengers) was observed. Moreover, the ΔrecA mutant (deficient in an enzyme involved in SOS response to DNA damage) was more sensitive to (+)-limonene. Thus, this indirect evidence indicates that the mechanism of exponentially growing E. coli cells inactivation by 2,000 μL/L (+)-limonene is due to the TCA cycle and Fenton-mediated hydroxyl radical formation that caused oxidative DNA damage, as observed for bactericidal drugs. However, several differences have been observed between the proposed mechanism for bactericidal drugs and for (+)-limonene. In this regard, our results demonstrated that E. coli inactivation was influenced by its physiological state and the drug's concentration: experiments with stationary-phase cells or 4,000 μL/L (+)-limonene uncovered a different mechanism of cell death, likely unrelated to hydroxyl radicals. Our research has also shown that drug's concentration is an important factor influencing the mechanism of bacterial inactivation by antibiotics, such as kanamycin. These results might help in improving and spreading the use of (+)-limonene as an antimicrobial compound, and in clarifying the controversy about the mechanism of inactivation by bactericidal antibiotics.

Lower body negative pressure as a tool for research in aerospace physiology and military medicine

NASA Technical Reports Server (NTRS)

Convertino, V. A.

2001-01-01

Lower body negative pressure (LBNP) has been extensively used for decades in aerospace physiological research as a tool to investigate cardiovascular mechanisms that are associated with or underlie performance in aerospace and military environments. In comparison with clinical stand and tilt tests, LBNP represents a relatively safe methodology for inducing highly reproducible hemodynamic responses during exposure to footward fluid shifts similar to those experienced under orthostatic challenge. By maintaining an orthostatic challenge in a supine posture, removal of leg support (muscle pump) and head motion (vestibular stimuli) during LBNP provides the capability to isolate cardiovascular mechanisms that regulate blood pressure. LBNP can be used for physiological measurements, clinical diagnoses and investigational research comparisons of subject populations and alterations in physiological status. The applications of LBNP to the study of blood pressure regulation in spaceflight, groundbased simulations of low gravity, and hemorrhage have provided unique insights and understanding for development of countermeasures based on physiological mechanisms underlying the operational problems.

Autoxidation of unsaturated lipids in food emulsion.

PubMed

Sun, Yue-E; Wang, Wei-Dong; Chen, Hong-Wei; Li, Chao

2011-05-01

Unsaturated lipids having various physiological roles are of significance in biochemistry, nutrition, medicine, and food. However, the susceptibility of lipids to oxidation is a major cause of quality deterioration in food emulsions. The reaction mechanism and factors that influence oxidation are appreciably different for emulsified lipids and bulk lipids. This article gives a brief overview of the current knowledge on autoxidation of oil-in-water food emulsions, especially those that contain unsaturated lipids, which are important in the food industry. Autoxidation of unsaturated lipids in oil-in-water emulsion is discussed, and so also their oxidation mechanism, the major factors influencing oxidation, determination measures, research status, and the problems encountered in recent years. Some effective strategies for controlling lipid oxidation in food emulsion have been presented in this review.

Cardiovascular function and basics of physiology in microgravity.

PubMed

Aubert, André E; Beckers, Frank; Verheyden, Bart

2005-04-01

Space exploration is a dream of mankind. However, this intriguing environment is not without risks. Life, and the human body, has developed all over evolution in the constant presence of gravity, especially from the moment on when living creatures left the ocean. When this gravitational force is no longer acting on the body, drastic changes occur. Some of these changes occur immediately, others progress only slowly. In the past 40 years of human space flight (first orbital flight by Yuri Gagarin on 12 April, 1961) several hazards for the human body have been identified. Bone mineral density is lost, muscle atrophy and cardiovascular deconditioning occur; pulmonary function, fluid regulating systems of the body, the sensory and the balance system are all disturbed by the lack of gravity. These changes in human physiology have to be reversed again when astronauts return to earth. This can cause adaptation problems, especially after long-duration space flights. Also the reaction of human physiology to radiation in space poses a huge risk at this moment. In this review the accent will be on cardiovascular function in space: how normal function is modified to reach a new equilibrium in space after short- and long-duration exposure to microgravity. In order to make long-duration space flight possible the mechanisms of this physiological adaptation must be understood to full extent. Only with this knowledge, effective countermeasures can be developed.

Physiological loading of joints prevents cartilage degradation through CITED2

PubMed Central

Leong, Daniel J.; Li, Yong H.; Gu, Xiang I.; Sun, Li; Zhou, Zuping; Nasser, Philip; Laudier, Damien M.; Iqbal, Jameel; Majeska, Robert J.; Schaffler, Mitchell B.; Goldring, Mary B.; Cardoso, Luis; Zaidi, Mone; Sun, Hui B.

2011-01-01

Both overuse and disuse of joints up-regulate matrix metalloproteinases (MMPs) in articular cartilage and cause tissue degradation; however, moderate (physiological) loading maintains cartilage integrity. Here, we test whether CBP/p300-interacting transactivator with ED-rich tail 2 (CITED2), a mechanosensitive transcriptional coregulator, mediates this chondroprotective effect of moderate mechanical loading. In vivo, hind-limb immobilization of Sprague-Dawley rats up-regulates MMP-1 and causes rapid, histologically detectable articular cartilage degradation. One hour of daily passive joint motion prevents these changes and up-regulates articular cartilage CITED2. In vitro, moderate (2.5 MPa, 1 Hz) intermittent hydrostatic pressure (IHP) treatment suppresses basal MMP-1 expression and up-regulates CITED2 in human chondrocytes, whereas high IHP (10 MPa) down-regulates CITED2 and increases MMP-1. Competitive binding and transcription assays demonstrate that CITED2 suppresses MMP-1 expression by competing with MMP transactivator, Ets-1 for its coactivator p300. Furthermore, CITED2 up-regulation in vitro requires the p38δ isoform, which is specifically phosphorylated by moderate IHP. Together, these studies identify a novel regulatory pathway involving CITED2 and p38δ, which may be critical for the maintenance of articular cartilage integrity under normal physical activity levels.—Leong, D. J., Li, Y. H., Gu, X. I., Sun, L., Zhou, Z., Nasser, P., Laudier, D. M., Iqbal, J., Majeska, R. J., Schaffler, M. B., Goldring, M. B., Cardoso, L., Zaidi, M., Sun, H. B. Physiological loading of joints prevents cartilage degradation through CITED2. PMID:20826544

Closed-loop mechanical ventilation for lung injury: a novel physiological-feedback mode following the principles of the open lung concept.

PubMed

Schwaiberger, David; Pickerodt, Philipp A; Pomprapa, Anake; Tjarks, Onno; Kork, Felix; Boemke, Willehad; Francis, Roland C E; Leonhardt, Steffen; Lachmann, Burkhard

2018-06-01

Adherence to low tidal volume (V T ) ventilation and selected positive end-expiratory pressures are low during mechanical ventilation for treatment of the acute respiratory distress syndrome. Using a pig model of severe lung injury, we tested the feasibility and physiological responses to a novel fully closed-loop mechanical ventilation algorithm based on the "open lung" concept. Lung injury was induced by surfactant washout in pigs (n = 8). Animals were ventilated following the principles of the "open lung approach" (OLA) using a fully closed-loop physiological feedback algorithm for mechanical ventilation. Standard gas exchange, respiratory- and hemodynamic parameters were measured. Electrical impedance tomography was used to quantify regional ventilation distribution during mechanical ventilation. Automatized mechanical ventilation provided strict adherence to low V T -ventilation for 6 h in severely lung injured pigs. Using the "open lung" approach, tidal volume delivery required low lung distending pressures, increased recruitment and ventilation of dorsal lung regions and improved arterial blood oxygenation. Physiological feedback closed-loop mechanical ventilation according to the principles of the open lung concept is feasible and provides low tidal volume ventilation without human intervention. Of importance, the "open lung approach"-ventilation improved gas exchange and reduced lung driving pressures by opening atelectasis and shifting of ventilation to dorsal lung regions.

The Proximate Causes of Sexual Size Dimorphism in Phrynocephalus przewalskii

PubMed Central

Zhao, Wei; Liu, Nai-fa

2014-01-01

Sexual size dimorphism (SSD) is a common phenomenon and is a central topic in evolutionary biology. Recently, the importance of pursuing an ontogenetic perspective of SSD has been emphasized, to elucidate the proximate physiological mechanisms leading to its evolution. However, such research has seldom focused on the critical periods when males and females diverge. Using mark-recapture data, we investigated the development of SSD, sex-specific survivorship, and growth rates in Phrynocephalus przewalskii (Agamidae). We demonstrated that both male and female lizards are reproductively mature at age 10–11 months (including 5 months hibernation). Male-biased SSD in snout-vent length (SVL) was only found in adults and was fully expressed at age 11 months (June of the first full season of activity), just after sexual maturation. However, male-biased SSD in tail length (TL), hind-limb length (LL), and head width (HW) were fully expressed at age 9–10 months, just before sexual maturation. Analysis of age-specific linear growth rates identified sexually dimorphic growth during the fifth growth month (age 10–11 months) as the proximate cause of SSD in SVL. The males experienced higher mortality than females in the first 2 years and only survived better than females after SSD was well developed. This suggests that the critical period of divergence in the sizes of male and female P. przewalskii occurs between 10 and 11 months of age (May to June during the first full season of activity), and that the sexual difference in growth during this period is the proximate cause. However, the sexual difference in survivorship cannot explain the male-biased SSD in SVL. Our results indicate that performance-related characteristics, such as TL, HW, and LL diverged earlier than SVL. The physiological mechanisms underlying the different growth patterns of males and females may reflect different energy allocations associated with their different reproductive statuses. PMID:24465815

A way forward for fire-caused tree mortality prediction: Modeling a physiological consequence of fire

Treesearch

Kathleen L. Kavanaugh; Matthew B. Dickinson; Anthony S. Bova

2010-01-01

Current operational methods for predicting tree mortality from fire injury are regression-based models that only indirectly consider underlying causes and, thus, have limited generality. A better understanding of the physiological consequences of tree heating and injury are needed to develop biophysical process models that can make predictions under changing or novel...

Physiological and molecular mechanism of defense in cotton against Verticillium dahliae.

PubMed

Shaban, Muhammad; Miao, Yuhuan; Ullah, Abid; Khan, Anam Qadir; Menghwar, Hakim; Khan, Aamir Hamid; Ahmed, Muhammad Mahmood; Tabassum, Muhammad Adnan; Zhu, Longfu

2018-04-01

Cotton, a natural fiber producing crop of huge importance for textile industry, has been reckoned as the backbone in the economy of many developing countries. Verticillium wilt caused by Verticillium dahliae reflected as the most devastating disease of cotton crop in several parts of the world. Average losses due to attack of this disease are tremendous every year. There is urgent need to develop strategies for effective control of this disease. In the last decade, progress has been made to understand the interaction between cotton-V. dahliae and several growth and pathogenicity related genes were identified. Still, most of the molecular components and mechanisms of cotton defense against Verticillium wilt are poorly understood. However, from existing knowledge, it is perceived that cotton defense mechanism primarily depends on the pre-formed defense structures including thick cuticle, synthesis of phenolic compounds and delaying or hindering the expansion of the invader through advanced measures such as reinforcement of cell wall structure, accumulation of reactive oxygen species (ROS), release of phytoalexins, the hypersensitive response and the development of broad spectrum resistance named as, systemic acquired resistance (SAR). Investigation of these defense tactics provide valuable information about the improvement of cotton breeding strategies for the development of durable, cost effective, and broad spectrum resistant varieties. Consequently, this management approach will help to reduce the use of fungicides and also minimize other environmental hazards. In the present paper, we summarized the V. dahliae virulence mechanism and comprehensively discussed the cotton molecular mechanisms of defense such as physiological, biochemical responses with the addition of signaling pathways that are implicated towards attaining resistance against Verticillium wilt. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

The Effect of Listening to Holy Quran Recitation on Weaning Patients Receiving Mechanical Ventilation in the Intensive Care Unit: A Pilot Study.

PubMed

Yadak, Mohammad; Ansari, Khalid Aziz; Qutub, Hatem; Al-Otaibi, Hajed; Al-Omar, Omar; Al-Onizi, Nawal; Farooqi, Faraz Ahmed

2017-09-30

Mechanical ventilation (MV) causes high level of stress in hospitalized patients. Weaning is the gradual process of decreasing ventilator support that in turn lead to termination of MV and increased respiratory effort, which may exacerbate symptoms and prolong MV. This study aimed to investigate the effect of listening to Holy Quran recitation (HQR) as a non-pharmacological intervention in patients during weaning from mechanical ventilation. This is a randomized controlled trial in which 55 patients admitted in the intensive care unit (ICU) and on mechanical ventilation were recruited. Patients were divided into experimental (case) and control group. In the experimental group, patients received 30 min of HQR, whereas in the control group, patients had 30 min of rest in bed before the start of the weaning. The physiological and/or clinical parameters of weaning were recorded. These parameters include rapid shallow breathing index, respiratory rate, heart rate, oxygen saturation, exhaled carbon dioxide, and blood pressure. The baseline demographic data for groups were presented in tables. The mean age was 54 ± 0.5 years for the experimental and 56.4 ± 18.5 years for the control groups. The physiological and clinical parameters were compared between case and control and found no significant difference. The preliminary findings of this pilot study suggest that there is no negative effect of HQR on weaning patients from mechanical ventilation in the ICU. The results also outline and explorthe possible utility of HQR further in ICU patients as an intervention in weaning patients off from ventilator in the ICU. Although there remains much to be done, our work generates important findings in the field of critical care management.

Cardiac ion channels

PubMed Central

Priest, Birgit T; McDermott, Jeff S

2015-01-01

Ion channels are critical for all aspects of cardiac function, including rhythmicity and contractility. Consequently, ion channels are key targets for therapeutics aimed at cardiac pathophysiologies such as atrial fibrillation or angina. At the same time, off-target interactions of drugs with cardiac ion channels can be the cause of unwanted side effects. This manuscript aims to review the physiology and pharmacology of key cardiac ion channels. The intent is to highlight recent developments for therapeutic development, as well as elucidate potential mechanisms for drug-induced cardiac side effects, rather than present an in-depth review of each channel subtype. PMID:26556552

Circadian Rhythm Sleep Disorders

PubMed Central

Zhu, Lirong; Zee, Phyllis C.

2012-01-01

There have been remarkable advances in our understanding of the molecular, cellular and physiological mechanisms underlying the regulation of circadian rhythms, as well as the impact of circadian dysfunction on health and disease. This information has transformed our understanding of the effect of circadian rhythm sleep disorders (CRSD) on health, performance and safety. CRSDs are caused by alterations of the central circadian time-keeping system, or a misalignment of the endogenous circadian rhythm and the external environment. In this section, we provide a review of circadian biology and discuss the pathophysiology, clinical features, diagnosis, and treatment of the most commonly encountered CRSDs in clinical practice. PMID:23099133

Post-infectious persistent cough: pathogenesis and therapeutic options.

PubMed

Capristo, Carlo; Rossi, Giovanni A

2017-10-01

Post-infectious cough is a common symptom associated with common colds and/or upper respiratory tract infection. This cough is expected to last for only for few days and resolve spontaneously, whilst when persists for longer than three weeks is defined "persistent" and is associated tickling or an irritating sensation in the throat which often leads to paroxysms of coughing. Persistent post-infectious cough can cause morbidity since it may interfere with usual living. Despite the recent advances in understanding the mechanisms that regulate cough, in physiological and pathological conditions, current therapeutic options for post-infectious cough are little or only moderately effective.

Immune and Inflammatory Role in Renal Disease

PubMed Central

Ryan, Michael J.

2013-01-01

Chronic and acute renal diseases, irrespective of the initiating cause, have inflammation and immune system activation as a common underlying mechanism. The purpose of this review is to provide a broad overview of immune cells and inflammatory proteins that contribute to the pathogenesis of renal disease, and to discuss some of the physiological changes that occur in the kidney as a result of immune system activation. An overview of common forms of acute and chronic renal disease is provided, followed by a discussion of common therapies that have antiinflammatory or immunosuppressive effects in the treatment of renal disease. PMID:23720336

Effect of environmental pollutants on taste and smell

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schiffman, S.S.; Nagle, H.T.

1992-06-01

Various man-made and naturally occurring chemicals and substances can modify the chemosensory systems of animals and man. This article provides an overview of research studies that investigate the impact of pollution on taste and smell perception. Acute and chronic alterations in taste and olfaction are discussed for solvents, herbicides, fungicides, pesticides, disinfectants, germicides, soil fumigants, dyes, pharmaceuticals, textile wastes, smog, tobacco smoke, perfumes, flavors, plastics, synthetic rubber, and other industrial substances. The mechanisms by which pollutants may cause physiologic and biologic changes are highlighted. Natural detoxification systems are discussed, as well as treatments for chemosensory deficits.89 references.

The role of transient receptor potential channels in joint diseases.

PubMed

Krupkova, O; Zvick, J; Wuertz-Kozak, K

2017-10-10

Transient receptor potential channels (TRP channels) are cation selective transmembrane receptors with diverse structures, activation mechanisms and physiological functions. TRP channels act as cellular sensors for a plethora of stimuli, including temperature, membrane voltage, oxidative stress, mechanical stimuli, pH and endogenous, as well as, exogenous ligands, thereby illustrating their versatility. As such, TRP channels regulate various functions in both excitable and non-excitable cells, mainly by mediating Ca2+ homeostasis. Dysregulation of TRP channels is implicated in many pathologies, including cardiovascular diseases, muscular dystrophies and hyperalgesia. However, the importance of TRP channel expression, physiological function and regulation in chondrocytes and intervertebral disc (IVD) cells is largely unexplored. Osteoarthritis (OA) and degenerative disc disease (DDD) are chronic age-related disorders that significantly affect the quality of life by causing pain, activity limitation and disability. Furthermore, currently available therapies cannot effectively slow-down or stop progression of these diseases. Both OA and DDD are characterised by reduced tissue cellularity, enhanced inflammatory responses and molecular, structural and mechanical alterations of the extracellular matrix, hence affecting load distribution and reducing joint flexibility. However, knowledge on how chondrocytes and IVD cells sense their microenvironment and respond to its changes is still limited. In this review, we introduced six families of mammalian TRP channels, their mechanisms of activation, as well as, activation-driven cellular consequences. We summarised the current knowledge on TRP channel expression and activity in chondrocytes and IVD cells, as well as, the significance of TRP channels as therapeutic targets for the treatment of OA and DDD.

Mechanical and biocompatible characterizations of a readily available multilayer vascular graft

PubMed Central

Madhavan, Krishna; Elliott, Winston H; Bonani, Walter; Monnet, Eric; Tan, Wei

2013-01-01

There is always a considerable clinical need for vascular grafts. Considering the availability, physical and mechanical properties, and regenerative potential, we have developed and characterized readily available, strong, and compliant multilayer grafts that support cell culture and ingrowth. The grafts were made from heterogeneous materials and structures, including a thin, dense, nanofibrous core composed of poly-ε-caprolactone (PCL), and a thick, porous, hydrogel sleeve composed of genipin-crosslinked collagen–chitosan (GCC). Because the difference in physicochemical properties between PCL and GCC caused layer separation, the layer adhesion was identified as a determinant to graft property and integrity under physiological conditions. Thus, strategies to modify the layer interface, including increasing porosity of the PCL surface, decreasing hydrophobicity, and increasing interlayer crosslinking, were developed. Results from microscopic images showed that increasing PCL porosity was characterized by improved layer adhesion. The resultant graft was characterized by high compliance (4.5%), and desired permeability (528 mL/cm2/min), burst strength (695 mmHg), and suture strength (2.38 N) for readily grafting. Results also showed that PCL mainly contributed to the graft mechanical properties, whereas GCC reduced the water permeability. In addition to their complementary contributions to physical and mechanical properties, the distinct graft layers also provided layer-specific structures for seeding and culture of vascular endothelial and smooth muscle cells in vitro. Acellular graft constructs were readily used to replace abdominal aorta of rabbits, resulting in rapid cell ingrowth and flow reperfusion. The multilayer constructs capable of sustaining physiological conditions and promoting cellular activities could serve as a platform for future development of regenerative vascular grafts. PMID:23165922

[The Research Advancement and Conception of the Deep-underground Medicine].

PubMed

Xie, He-Ping; Liu, Ji-Feng; Gao, Ming-Zhong; Wan, Xue-Hong; Liu, Shi-Xi; Zou, Jian; Wu, Jiang; Ma, Teng-Fei; Liu, Yi-Lin; Bu, Hong; Li, Wei-Min

2018-03-01

The 21th century is the century of exploring and utilizing the underground space. In the future, more and more people will spend more and more time living or/and working in the underground space. However,we know little about the effect on the health of human caused by the underground environment. Herein,we systematically put forward the strategic conception of the deep-underground medicine,in order to reveal relative effects and mechanism of the potential factors in the deep underground space on human's physiological and psychological healthy,and to work out the corresponding countermeasures. The original deep-underground medicine includes the following items. ①To model different depth of underground environment according to various parameters (such as temperature,radiation,air pressure, rock,microorganism), and to explore their quantitative character and effects on human health and mechanism. ② To study the psychological change, maintenance of homeostasis and biothythm of organism in the deep underground space. ③ To learn the association between psychological healthy of human and the depth, structure, physical environment and working time of underground space. ④ To investigate the effect of different terrane and lithology on healthy of human and to deliberate their contribution on organism growth. ⑤ To research the character and their mechanism of growth,metabolism,exchange of energy,response of growth, aging and adaptation of cells living in deep underground space. ⑥ To explore the physiological feature,growth of microbiome and it's interaction with host in the deep underground space. ⑦ To develop deep-underground simulation space, the biologically medical technology and equipments. As a research basis,a deep-underground medical lab under a rock thickness of about 1 470 m has been built,which aims to operate the research of the effect on living organism caused by different depth of underground environment. Copyright© by Editorial Board of Journal of Sichuan University (Medical Science Edition).

High intracellular trehalase activity prevents the storage of trehalose in the yeast Dekkera bruxellensis.

PubMed

Leite, F C B; Leite, D V da R; Pereira, L F; de Barros Pita, W; de Morais, M A

2016-09-01

Dekkera bruxellensis hit the spotlight in the past decade mostly due to its rather high ability to adapt to several different fermentation processes. This yeast relies on different genetic and physiological aspects to achieve and preserve its high industrial fitness and some of these traits are shared with Saccharomyces cerevisiae. We have previously described that D. bruxellensis is unable to make use of accumulating trehalose as a strategy for cell adaptation and survival in the industrial scenario, as opposed to S. cerevisiae. Since trehalose is often involved in mechanisms related to cell protection, we aimed to investigate both cause and effect of the absence of this metabolite in the cell adaptive capacity in the industrial environment. Our results indicate that the major cause for the nonaccumulation of trehalose is the high constitutive activity of neutral trehalase. Therefore, the rate of trehalose degradation could be higher than its rate of synthesis, preventing accumulation. Altogether, our data elucidate the mechanisms involved in the lack of trehalose accumulation in D. bruxellensis as well as evaluates the implications of this feature. Dekkera bruxellensis can successfully take advantage of its peculiar physiological and genetic traits in order to adapt and survive in fermentation processes. So far, tolerance to stress has been credited to trehalose synthesis. The data presented in this work provided information on the underlying mechanism that prevents trehalose accumulation and corroborated the recent information that trehalose itself is not implicated in yeast stress tolerance. Second, it showed that D. bruxellensis responds differently to Saccharomyces cerevisiae to excess of sugar, which may explain its preference for respiration (oxidative metabolism) over fermentation (reductive metabolism) even at limited oxygen supply. These findings help to understand the drop on ethanol production in processes overtaken by this yeast. © 2016 The Society for Applied Microbiology.

Analysis of Common and Specific Mechanisms of Liver Function Affected by Nitrotoluene Compounds

PubMed Central

Deng, Youping; Meyer, Sharon A.; Guan, Xin; Escalon, Barbara Lynn; Ai, Junmei; Wilbanks, Mitchell S.; Welti, Ruth; Garcia-Reyero, Natàlia; Perkins, Edward J.

2011-01-01

Background Nitrotoluenes are widely used chemical manufacturing and munitions applications. This group of chemicals has been shown to cause a range of effects from anemia and hypercholesterolemia to testicular atrophy. We have examined the molecular and functional effects of five different, but structurally related, nitrotoluenes on using an integrative systems biology approach to gain insight into common and disparate mechanisms underlying effects caused by these chemicals. Methodology/Principal Findings Sprague-Dawley female rats were exposed via gavage to one of five concentrations of one of five nitrotoluenes [2,4,6-trinitrotoluene (TNT), 2-amino-4,6-dinitrotoluene (2ADNT) 4-amino-2,6-dinitrotoulene (4ADNT), 2,4-dinitrotoluene (2,4DNT) and 2,6-dinitrotoluene (2,6DNT)] with necropsy and tissue collection at 24 or 48 h. Gene expression profile results correlated well with clinical data and liver histopathology that lead to the concept that hematotoxicity was followed by hepatotoxicity. Overall, 2,4DNT, 2,6DNT and TNT had stronger effects than 2ADNT and 4ADNT. Common functional terms, gene expression patterns, pathways and networks were regulated across all nitrotoluenes. These pathways included NRF2-mediated oxidative stress response, aryl hydrocarbon receptor signaling, LPS/IL-1 mediated inhibition of RXR function, xenobiotic metabolism signaling and metabolism of xenobiotics by cytochrome P450. One biological process common to all compounds, lipid metabolism, was found to be impacted both at the transcriptional and lipid production level. Conclusions/Significance A systems biology strategy was used to identify biochemical pathways affected by five nitroaromatic compounds and to integrate data that tie biochemical alterations to pathological changes. An integrative graphical network model was constructed by combining genomic, gene pathway, lipidomic, and physiological endpoint results to better understand mechanisms of liver toxicity and physiological endpoints affected by these compounds. PMID:21346803

System identification of closed-loop cardiovascular control: effects of posture and autonomic blockade

NASA Technical Reports Server (NTRS)

Mullen, T. J.; Appel, M. L.; Mukkamala, R.; Mathias, J. M.; Cohen, R. J.

1997-01-01

We applied system identification to the analysis of fluctuations in heart rate (HR), arterial blood pressure (ABP), and instantaneous lung volume (ILV) to characterize quantitatively the physiological mechanisms responsible for the couplings between these variables. We characterized two autonomically mediated coupling mechanisms [the heart rate baroreflex (HR baroreflex) and respiratory sinus arrhythmia (ILV-HR)] and two mechanically mediated coupling mechanisms [the blood pressure wavelet generated with each cardiac contraction (circulatory mechanics) and the direct mechanical effects of respiration on blood pressure (ILV-->ABP)]. We evaluated the method in humans studied in the supine and standing postures under control conditions and under conditions of beta-sympathetic and parasympathetic pharmacological blockades. Combined beta-sympathetic and parasympathetic blockade abolished the autonomically mediated couplings while preserving the mechanically mediated coupling. Selective autonomic blockade and postural changes also altered the couplings in a manner consistent with known physiological mechanisms. System identification is an "inverse-modeling" technique that provides a means for creating a closed-loop model of cardiovascular regulation for an individual subject without altering the underlying physiological control mechanisms.

ANF-RGC gene motif 669WTAPELL675 is vital for blood pressure regulation: Biochemical mechanism

PubMed Central

Duda, Teresa; Pertzev, Alexandre; Sharma, Rameshwar K.

2013-01-01

ANF-RGC is the prototype membrane guanylate cyclase, both the receptor and the signal transducer of the hormones ANF and BNP. After binding them at the extracellular domain it, at its intracellular domain, signals activation of the C-terminal catalytic module and accelerates production of the second messenger, cyclic GMP. This, in turn, controls the physiological processes of blood pressure, cardiovascular function, and fluid secretion, and others: metabolic syndrome, obesity and apoptosis. What is the biochemical mechanism by which this single molecule controls these diverse processes, explicitly of the blood pressure regulation is the subject of the present study. In line with the concept that the structural modules of ANF-RGC are designed to respond to more than one, yet distinctive signals, the study demonstrates the construction of a novel ANF-RGC-In-gene-669WTAPELL675 mouse model. Through this model, the study establishes that 669WTAPELL675 is a vital ANF signal transducer motif of the guanylate cyclase. Its striking physiological features linked with their biochemistry are that (1) it controls the hormonally-dependent cyclic GMP production in the kidney and the adrenal gland; (3) its deletion causes hypertension, and (3) cardiac hypertrophy; and (4) these mice show higher levels of the plasma aldosterone. For the first time, a mere 7-amino acid encoded motif of the mouse gene has been directly linked with the physiological control of the blood pressure regulation, a detailed biochemistry of this linkage has been established and a model for this linkage has been offered. PMID:23464624

Molecular determinants of force production in human skeletal muscle fibers: effects of myosin isoform expression and cross-sectional area.

PubMed

Miller, Mark S; Bedrin, Nicholas G; Ades, Philip A; Palmer, Bradley M; Toth, Michael J

2015-03-15

Skeletal muscle contractile performance is governed by the properties of its constituent fibers, which are, in turn, determined by the molecular interactions of the myofilament proteins. To define the molecular determinants of contractile function in humans, we measured myofilament mechanics during maximal Ca(2+)-activated and passive isometric conditions in single muscle fibers with homogenous (I and IIA) and mixed (I/IIA and IIA/X) myosin heavy chain (MHC) isoforms from healthy, young adult male (n = 5) and female (n = 7) volunteers. Fibers containing only MHC II isoforms (IIA and IIA/X) produced higher maximal Ca(2+)-activated forces over the range of cross-sectional areas (CSAs) examined than MHC I fibers, resulting in higher (24-42%) specific forces. The number and/or stiffness of the strongly bound myosin-actin cross bridges increased in the higher force-producing MHC II isoforms and, in all isoforms, better predicted force than CSA. In men and women, cross-bridge kinetics, in terms of myosin attachment time and rate of myosin force production, were independent of CSA, although women had faster (7-15%) kinetics. The relative proportion of cross bridges and/or their stiffness was reduced as fiber size increased, causing a decline in specific force. Results from our examination of molecular mechanisms across the range of physiological CSAs explain the variation in specific force among the different fiber types in human skeletal muscle, which may have relevance to understanding how various physiological and pathophysiological conditions modulate single-fiber and whole muscle contractility. Copyright © 2015 the American Physiological Society.

An overview of the issues: physiological effects of bed rest and restricted physical activity

NASA Technical Reports Server (NTRS)

Convertino, V. A.; Bloomfield, S. A.; Greenleaf, J. E.

1997-01-01

Reduction of exercise capacity with confinement to bed rest is well recognized. Underlying physiological mechanisms include dramatic reductions in maximal stroke volume, cardiac output, and oxygen uptake. However, bed rest by itself does not appear to contribute to cardiac dysfunction. Increased muscle fatigue is associated with reduced muscle blood flow, red cell volume, capillarization and oxidative enzymes. Loss of muscle mass and bone density may be reflected by reduced muscle strength and higher risk for injury to bones and joints. The resultant deconditioning caused by bed rest can be independent of the primary disease and physically debilitating in patients who attempt to reambulate to normal active living and working. A challenge to clinicians and health care specialists has been the identification of appropriate and effective methods to restore physical capacity of patients during or after restricted physical activity associated with prolonged bed rest. The examination of physiological responses to bed rest deconditioning and exercise training in healthy subjects has provided significant information to develop effective rehabilitation treatments. The successful application of acute exercise to enhance orthostatic stability, daily endurance exercise to maintain aerobic capacity, or specific resistance exercises to maintain musculoskeletal integrity rather than the use of surgical, pharmacological, and other medical treatments for clinical conditions has been enhanced by investigation and understanding of underlying mechanisms that distinguish physical deconditioning from the disease. This symposium presents an overview of cardiovascular and musculoskeletal deconditioning associated with reduced physical work capacity following prolonged bed rest and exercise training regimens that have proven successful in ameliorating or reversing these adverse effects.

Microglia PACAP and glutamate: Friends or foes in seizure-induced autonomic dysfunction and SUDEP?

PubMed

Bhandare, Amol M; Kapoor, Komal; Farnham, Melissa M J; Pilowsky, Paul M

2016-06-01

Seizure-induced cardiorespiratory autonomic dysfunction is a major cause of sudden unexpected death in epilepsy (SUDEP), and the underlying mechanism is unclear. Seizures lead to increased synthesis, and release of glutamate, pituitary adenylate cyclase activating polypeptide (PACAP), and other neurotransmitters, and cause extensive activation of microglia at multiple regions in the brain including central autonomic cardiorespiratory brainstem nuclei. Glutamate contributes to neurodegeneration, and inflammation in epilepsy. PACAP has neuroprotective, and anti-inflammatory properties, whereas microglia are key players in inflammatory responses in CNS. Seizure-induced increase in PACAP is neuroprotective. PACAP produces neuroprotective effects acting on microglial PAC1 and VPAC1 receptors. Microglia also express glutamate transporters, and their expression can be increased by PACAP in response to harmful or stressful situations such as seizures. Here we discuss the mechanism of autonomic cardiorespiratory dysfunction in seizure, and the role of PACAP, glutamate and microglia in regulating cardiorespiratory brainstem neurons in their physiological state that could provide future therapeutic options for SUDEP. Copyright © 2016 Elsevier B.V. All rights reserved.

Ultrasmall fluorescent nanoparticles derived from roast duck: their physicochemical characteristics and interaction with human serum albumin.

PubMed

Cong, Shuang; Bi, Jingran; Song, Xunyu; Yu, Chenxu; Tan, Mingqian

2018-04-25

Fluorescent nanoparticles (FNPs) produced from roast meat have drawn widespread attention due to their potential hazards to human health. In this paper, the presence of ultrasmall FNPs in roast duck and their interaction with human serum albumin (HSA) were reported. The processing-induced FNPs have an average size of 1.3 nm with a relative fluorescence quantum yield of 4.4%. X-ray photoelectron spectroscopy showed that the FNPs are composed of carbon (70.48%), nitrogen (6.25%), oxygen (22.17%) and sulfur (1.11%), with hydroxyl, carboxyl and amino groups present on their surface. The presence of FNPs could cause fluorescence quenching of HSA, which was ascribed to the static quenching mechanism via the electrostatic interaction as analyzed by isothermal titration calorimetry. The α-helix contents of HSA decreased after the addition of FNPs, demonstrating that these processing-induced FNPs could cause structural alteration of HSA. These results provided insights into the formation of nanoparticles in roast duck, and offered important information about the binding mechanism of these nanoparticles with HSA, which may have physiological implications.

Biomarkers in adult posthemorrhagic hydrocephalus.

PubMed

Hua, Cong; Zhao, Gang

2017-08-01

Posthemorrhagic hydrocephalus is a severe complication following intracranial hemorrhage. Posthemorrhagic hydrocephalus is often associated with high morbidity and mortality and serves as an important clinical predictor of adverse outcomes after intracranial hemorrhage. Currently, no effective medical intervention exists to improve functional outcomes in posthemorrhagic hydrocephalus patients because little is still known about the mechanisms of posthemorrhagic hydrocephalus pathogenesis. Because a better understanding of the posthemorrhagic hydrocephalus pathogenesis would facilitate development of clinical treatments, this is an active research area. The purpose of this review is to describe recent progress in elucidation of molecular mechanisms that cause posthemorrhagic hydrocephalus. What we are certain of is that the entry of blood into the ventricular system and subarachnoid space results in release of lytic blood products which cause a series of physiological and pathological changes in the brain. Blood components that can be linked to pathology would serve as disease biomarkers. From studies of posthemorrhagic hydrocephalus, such biomarkers are known to mutually synergize to initiate and promote posthemorrhagic hydrocephalus progression. These findings suggest that modulation of biomarker expression or function may benefit posthemorrhagic hydrocephalus patients.

Physiological Notch Signaling Maintains Bone Homeostasis via RBPjk and Hey Upstream of NFATc1

PubMed Central

Tu, Xiaolin; Chen, Jianquan; Lim, Joohyun; Karner, Courtney M.; Lee, Seung-Yon; Heisig, Julia; Wiese, Cornelia; Surendran, Kameswaran; Kopan, Raphael; Gessler, Manfred; Long, Fanxin

2012-01-01

Notch signaling between neighboring cells controls many cell fate decisions in metazoans both during embryogenesis and in postnatal life. Previously, we uncovered a critical role for physiological Notch signaling in suppressing osteoblast differentiation in vivo. However, the contribution of individual Notch receptors and the downstream signaling mechanism have not been elucidated. Here we report that removal of Notch2, but not Notch1, from the embryonic limb mesenchyme markedly increased trabecular bone mass in adolescent mice. Deletion of the transcription factor RBPjk, a mediator of all canonical Notch signaling, in the mesenchymal progenitors but not the more mature osteoblast-lineage cells, caused a dramatic high-bone-mass phenotype characterized by increased osteoblast numbers, diminished bone marrow mesenchymal progenitor pool, and rapid age-dependent bone loss. Moreover, mice deficient in Hey1 and HeyL, two target genes of Notch-RBPjk signaling, exhibited high bone mass. Interestingly, Hey1 bound to and suppressed the NFATc1 promoter, and RBPjk deletion increased NFATc1 expression in bone. Finally, pharmacological inhibition of NFAT alleviated the high-bone-mass phenotype caused by RBPjk deletion. Thus, Notch-RBPjk signaling functions in part through Hey1-mediated inhibition of NFATc1 to suppress osteoblastogenesis, contributing to bone homeostasis in vivo. PMID:22457635

Physiological loading of joints prevents cartilage degradation through CITED2.

PubMed

Leong, Daniel J; Li, Yong H; Gu, Xiang I; Sun, Li; Zhou, Zuping; Nasser, Philip; Laudier, Damien M; Iqbal, Jameel; Majeska, Robert J; Schaffler, Mitchell B; Goldring, Mary B; Cardoso, Luis; Zaidi, Mone; Sun, Hui B

2011-01-01

Both overuse and disuse of joints up-regulate matrix metalloproteinases (MMPs) in articular cartilage and cause tissue degradation; however, moderate (physiological) loading maintains cartilage integrity. Here, we test whether CBP/p300-interacting transactivator with ED-rich tail 2 (CITED2), a mechanosensitive transcriptional coregulator, mediates this chondroprotective effect of moderate mechanical loading. In vivo, hind-limb immobilization of Sprague-Dawley rats up-regulates MMP-1 and causes rapid, histologically detectable articular cartilage degradation. One hour of daily passive joint motion prevents these changes and up-regulates articular cartilage CITED2. In vitro, moderate (2.5 MPa, 1 Hz) intermittent hydrostatic pressure (IHP) treatment suppresses basal MMP-1 expression and up-regulates CITED2 in human chondrocytes, whereas high IHP (10 MPa) down-regulates CITED2 and increases MMP-1. Competitive binding and transcription assays demonstrate that CITED2 suppresses MMP-1 expression by competing with MMP transactivator, Ets-1 for its coactivator p300. Furthermore, CITED2 up-regulation in vitro requires the p38δ isoform, which is specifically phosphorylated by moderate IHP. Together, these studies identify a novel regulatory pathway involving CITED2 and p38δ, which may be critical for the maintenance of articular cartilage integrity under normal physical activity levels.

Modulation of ColE1-like Plasmid Replication for Recombinant Gene Expression

PubMed Central

Camps, Manel

2010-01-01

ColE1-like plasmids constitute the most popular vectors for recombinant protein expression. ColE1 plasmid replication is tightly controlled by an antisense RNA mechanism that is highly dynamic, tuning plasmid metabolic burden to the physiological state of the host. Plasmid homeostasis is upset upon induction of recombinant protein expression because of non-physiological levels of expression and because of the frequently biased amino acid composition of recombinant proteins. Disregulation of plasmid replication is the main cause of collapse of plasmid-based expression systems because of a simultaneous increase in the metabolic burden (due to increased average copy number) and in the probability of generation of plasmid-free cells (due to increased copy number variation). Interference between regulatory elements of co-resident plasmids causes comparable effects on plasmid stability (plasmid incompatibility). Modulating plasmid copy number for recombinant gene expression aims at achieving a high gene dosage while preserving the stability of the expression system. Here I present strategies targeting plasmid replication for optimizing recombinant gene expression. Specifically, I review approaches aimed at modulating the antisense regulatory system (as well as their implications for plasmid incompatibility) and innovative strategies involving modulation of host factors, of R-loop formation, and of the timing of recombinant gene expression. PMID:20218961

Infective endocarditis causing mitral valve stenosis - a rare but deadly complication: a case report.

PubMed

Hart, Michael A; Shroff, Gautam R

2017-02-17

Infective endocarditis rarely causes mitral valve stenosis. When present, it has the potential to cause severe hemodynamic decompensation and death. There are only 15 reported cases in the literature of mitral prosthetic valve bacterial endocarditis causing stenosis by obstruction. This case is even more unusual due to the mechanism by which functional mitral stenosis occurred. We report a case of a 23-year-old white woman with a history of intravenous drug abuse who presented with acute heart failure. Transthoracic echocardiography failed to show valvular vegetation, but high clinical suspicion led to transesophageal imaging that demonstrated infiltrative prosthetic valve endocarditis causing severe mitral stenosis. Despite extensive efforts from a multidisciplinary team, she died as a result of her critical illness. The discussion of this case highlights endocarditis physiology, the notable absence of stenosis in modified Duke criteria, and the utility of transesophageal echocardiography in clinching a diagnosis. It advances our knowledge of how endocarditis manifests, and serves as a valuable lesson for clinicians treating similar patients who present with stenosis but no regurgitation on transthoracic imaging, as a decision to forego a transesophageal echocardiography could cause this serious complication of endocarditis to be missed.

Migratory Behavior and Physiological Development as Potential Determinants of Life History Diversity in Fall Chinook Salmon in the Clearwater River

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tiffan, Kenneth F.; Kock, Tobias J.; Connor, William P.

We studied the influence of behavior, water velocity, and physiological development on the downstream movement of subyearling fall Chinook Salmon Oncorhynchus tshawytscha in free-flowing and impounded reaches of the Clearwater and Snake rivers as potential mechanisms that might explain life history diversity in this stock. Movement rates and the percentage of radio-tagged fish that moved faster than the average current velocity were highest in the free-flowing Clearwater River compared to impounded reaches. This provided support for our hypothesis that water velocity is a primary determinant of downstream movement regardless of a fish’s physiological development. In contrast, movement rates slowed andmore » detections became fewer in impounded reaches where velocities were much lower. The percentage of fish that moved faster than the average current velocity continued to decline and reached zero in the lower-most reach of Lower Granite Reservoir suggesting that behavioral disposition to move downstream was low. These findings contrast those of a similar, previous study of Snake River subyearlings in spite of hydrodynamic conditions being similar. Physiological differences between Snake and Clearwater river migrants shed light on this disparity. Subyearlings from the Clearwater River were parr-like in their development and never showed an increase in gill Na+/K+-ATPase activity as did smolts from the Snake River. The later emergence timing and cooler rearing temperatures in the Clearwater River may suppress normal physiological development that causes many fish to delay downstream movement and adopt a yearling life history strategy.« less

Towards physiologically meaningful water-use efficiency estimates from eddy covariance data.

PubMed

Knauer, Jürgen; Zaehle, Sönke; Medlyn, Belinda E; Reichstein, Markus; Williams, Christopher A; Migliavacca, Mirco; De Kauwe, Martin G; Werner, Christiane; Keitel, Claudia; Kolari, Pasi; Limousin, Jean-Marc; Linderson, Maj-Lena

2018-02-01

Intrinsic water-use efficiency (iWUE) characterizes the physiological control on the simultaneous exchange of water and carbon dioxide in terrestrial ecosystems. Knowledge of iWUE is commonly gained from leaf-level gas exchange measurements, which are inevitably restricted in their spatial and temporal coverage. Flux measurements based on the eddy covariance (EC) technique can overcome these limitations, as they provide continuous and long-term records of carbon and water fluxes at the ecosystem scale. However, vegetation gas exchange parameters derived from EC data are subject to scale-dependent and method-specific uncertainties that compromise their ecophysiological interpretation as well as their comparability among ecosystems and across spatial scales. Here, we use estimates of canopy conductance and gross primary productivity (GPP) derived from EC data to calculate a measure of iWUE (G 1 , "stomatal slope") at the ecosystem level at six sites comprising tropical, Mediterranean, temperate, and boreal forests. We assess the following six mechanisms potentially causing discrepancies between leaf and ecosystem-level estimates of G 1 : (i) non-transpirational water fluxes; (ii) aerodynamic conductance; (iii) meteorological deviations between measurement height and canopy surface; (iv) energy balance non-closure; (v) uncertainties in net ecosystem exchange partitioning; and (vi) physiological within-canopy gradients. Our results demonstrate that an unclosed energy balance caused the largest uncertainties, in particular if it was associated with erroneous latent heat flux estimates. The effect of aerodynamic conductance on G 1 was sufficiently captured with a simple representation. G 1 was found to be less sensitive to meteorological deviations between canopy surface and measurement height and, given that data are appropriately filtered, to non-transpirational water fluxes. Uncertainties in the derived GPP and physiological within-canopy gradients and their implications for parameter estimates at leaf and ecosystem level are discussed. Our results highlight the importance of adequately considering the sources of uncertainty outlined here when EC-derived water-use efficiency is interpreted in an ecophysiological context. © 2017 John Wiley & Sons Ltd.

A New Folding Kinetic Mechanism for Human Transthyretin and the Influence of the Amyloidogenic V30M Mutation.

PubMed

Jesus, Catarina S H; Almeida, Zaida L; Vaz, Daniela C; Faria, Tiago Q; Brito, Rui M M

2016-08-31

Protein aggregation into insoluble amyloid fibrils is the hallmark of several neurodegenerative diseases, chief among them Alzheimer's and Parkinson's. Although caused by different proteins, these pathologies share some basic molecular mechanisms with familial amyloidotic polyneuropathy (FAP), a rare hereditary neuropathy caused by amyloid formation and deposition by transthyretin (TTR) in the peripheral and autonomic nervous systems. Among the amyloidogenic TTR mutations known, V30M-TTR is the most common in FAP. TTR amyloidogenesis (ATTR) is triggered by tetramer dissociation, followed by partial unfolding and aggregation of the low conformational stability monomers formed. Thus, tetramer dissociation kinetics, monomer conformational stability and competition between refolding and aggregation pathways do play a critical role in ATTR. Here, we propose a new model to analyze the refolding kinetics of WT-TTR and V30M-TTR, showing that at pH and protein concentrations close to physiological, a two-step mechanism with a unimolecular first step followed by a second-order second step adjusts well to the experimental data. Interestingly, although sharing the same kinetic mechanism, V30M-TTR refolds at a much slower rate than WT-TTR, a feature that may favor the formation of transient species leading to kinetic partition into amyloidogenic pathways and, thus, significantly increasing the probability of amyloid formation in vivo.

A New Folding Kinetic Mechanism for Human Transthyretin and the Influence of the Amyloidogenic V30M Mutation

PubMed Central

Jesus, Catarina S. H.; Almeida, Zaida L.; Vaz, Daniela C.; Faria, Tiago Q.; Brito, Rui M. M.

2016-01-01

Protein aggregation into insoluble amyloid fibrils is the hallmark of several neurodegenerative diseases, chief among them Alzheimer’s and Parkinson’s. Although caused by different proteins, these pathologies share some basic molecular mechanisms with familial amyloidotic polyneuropathy (FAP), a rare hereditary neuropathy caused by amyloid formation and deposition by transthyretin (TTR) in the peripheral and autonomic nervous systems. Among the amyloidogenic TTR mutations known, V30M-TTR is the most common in FAP. TTR amyloidogenesis (ATTR) is triggered by tetramer dissociation, followed by partial unfolding and aggregation of the low conformational stability monomers formed. Thus, tetramer dissociation kinetics, monomer conformational stability and competition between refolding and aggregation pathways do play a critical role in ATTR. Here, we propose a new model to analyze the refolding kinetics of WT-TTR and V30M-TTR, showing that at pH and protein concentrations close to physiological, a two-step mechanism with a unimolecular first step followed by a second-order second step adjusts well to the experimental data. Interestingly, although sharing the same kinetic mechanism, V30M-TTR refolds at a much slower rate than WT-TTR, a feature that may favor the formation of transient species leading to kinetic partition into amyloidogenic pathways and, thus, significantly increasing the probability of amyloid formation in vivo. PMID:27589730

Design of a pulsatile flow facility to evaluate thrombogenic potential of implantable cardiac devices.

PubMed

Arjunon, Sivakkumar; Ardana, Pablo Hidalgo; Saikrishnan, Neelakantan; Madhani, Shalv; Foster, Brent; Glezer, Ari; Yoganathan, Ajit P

2015-04-01

Due to expensive nature of clinical trials, implantable cardiac devices should first be extensively characterized in vitro. Prosthetic heart valves (PHVs), an important class of these devices, have been shown to be associated with thromboembolic complications. Although various in vitro systems have been designed to quantify blood-cell damage and platelet activation caused by nonphysiological hemodynamic shear stresses in these PHVs, very few systems attempt to characterize both blood damage and fluid dynamics aspects of PHVs in the same test system. Various numerical modeling methodologies are also evolving to simulate the structural mechanics, fluid mechanics, and blood damage aspects of these devices. This article presents a completely hemocompatible small-volume test-platform that can be used for thrombogenicity studies and experimental fluid mechanics characterization. Using a programmable piston pump to drive freshly drawn human blood inside a cylindrical column, the presented system can simulate various physiological and pathophysiological conditions in testing PHVs. The system includes a modular device-mounting chamber, and in this presented case, a 23 mm St. Jude Medical (SJM) Regents® mechanical heart valve (MHV) in aortic position was used as the test device. The system was validated for its capability to quantify blood damage by measuring blood damage induced by the tester itself (using freshly drawn whole human blood). Blood damage levels were ascertained through clinically relevant assays on human blood while fluid dynamics were characterized using time-resolved particle image velocimetry (PIV) using a blood-mimicking fluid. Blood damage induced by the tester itself, assessed through Thrombin-anti-Thrombin (TAT), Prothrombin factor 1.2 (PF1.2), and hemolysis (Drabkins assay), was within clinically accepted levels. The hydrodynamic performance of the tester showed consistent, repeatable physiological pressure and flow conditions. In addition, the system contains proximity sensors to accurately capture leaflet motion during the entire cardiac cycle. The PIV results showed skewing of the leakage jet, caused by the asymmetric closing of the two leaflets. All these results are critical to characterizing the blood damage and fluid dynamics characteristics of the SJM Regents® MHV, proving the utility of this tester as a precise system for assessing the hemodynamics and thrombogenicity for various PHVs.

Multifractal spectrum of physiological signals: a mechanism-related approach

NASA Astrophysics Data System (ADS)

Pavlov, Alexey N.; Pavlova, Olga N.; Abdurashitov, Arkady S.; Arinushkin, Pavel A.; Runnova, Anastasiya E.; Semyachkina-Glushkovskaya, Oxana V.

2017-04-01

In this paper we discuss an approach for mechanism-related analysis of physiological signals performed with the wavelet-based multifractal formalism. This approach assumes estimation of the singularity spectrum for the band-pass filtered processes at different physiological conditions in order to provide explanation of the occurred changes in the Hölder exponents and the multi-fractality degree. We illustrate the considered approach using two examples, namely, the dynamics of the cerebral blood flow (CBF) and the electrical activity of the brain.

Psychological and Physiological Mechanisms by Which Discovery and Didactic Methods Work.

ERIC Educational Resources Information Center

Keegan, Mark

1995-01-01

Describes physiological, affective, and cognitive mechanisms by which didactic and discovery methods appear to work, as revealed by research literature. The optimal instructional method depends on the instructional objective, the educator's skills, and the nature of the students. Suggests more use of discovery methods. (69 references) (Author/MKR)

A Direct Role of Collagen Glycation in Bone Fracture

PubMed Central

Poundarik, Atharva A.; Wu, Ping-Cheng; Evis, Zafer; Sroga, Grazyna E.; Ural, Ani; Rubin, Mishaela; Vashishth, Deepak

2015-01-01

Non-enzymatic glycation (NEG) is an age-related process accelerated by diseases like diabetes, and causes the accumulation of advanced glycation end-products (AGEs). NEG-mediated modification of bone’s organic matrix, principally collagen type-I, has been implicated in impairing skeletal physiology and mechanics. Here, we present evidence, from in vitro and in vivo models, and establish a causal relationship between collagen glycation and alterations in bone fracture at multiple length scales. Through atomic force spectroscopy, we established that NEG impairs collagen’s ability to dissipate energy. Mechanical testing of in vitro glycated human bone specimen revealed that AGE accumulation due to NEG dramatically reduces the capacity of organic and mineralized matrix to creep and caused bone to fracture under impact at low levels of strain (3000–5000 μstrain) typically associated with fall. Fracture mechanics tests of NEG modified human cortical bone of varying ages, and their age-matched controls revealed that NEG disrupted microcracking based toughening mechanisms and reduced bone propagation and initiation fracture toughness across all age groups. A comprehensive mechanistic model, based on experimental and modeling data, was developed to explain how NEG and AGEs are causal to, and predictive of bone fragility. Furthermore, fracture mechanics and indentation testing on diabetic mice bones revealed that diabetes mediated NEG severely disrupts bone matrix quality in vivo. Finally, we show that AGEs are predictive of bone quality in aging humans and have diagnostic applications in fracture risk. PMID:26530231

Update on the management of constipation in the elderly: new treatment options

PubMed Central

Rao, Satish SC; Go, Jorge T

2010-01-01

Constipation disproportionately affects older adults, with a prevalences of 50% in community-dwelling elderly and 74% in nursing-home residents. Loss of mobility, medications, underlying diseases, impaired anorectal sensation, and ignoring calls to defecate are as important as dyssynergic defecation or irritable bowel syndrome in causing constipation. Detailed medical history on medications and co-morbid problems, and meticulous digital rectal examination may help identify causes of constipation. Likewise, blood tests and colonoscopy may identify organic causes such as colon cancer. Physiological tests such as colonic transit study with radio-opaque markers or wireless motility capsule, anorectal manometry, and balloon expulsion tests can identify disorders of colonic and anorectal function. However, in the elderly, there is usually more than one mechanism, requiring an individualized but multifactorial treatment approach. The management of constipation continues to evolve. Although osmotic laxatives such as polyethylene glycol remain mainstay, several new agents that target different mechanisms appear promising such as chloride-channel activator (lubiprostone), guanylate cyclase agonist (linaclotide), 5HT4 agonist (prucalopride), and peripherally acting μ-opioid receptor antagonists (alvimopan and methylnaltrexone) for opioid-induced constipation. Biofeedback therapy is efficacious for treating dyssynergic defecation and fecal impaction with soiling. However, data on efficacy and safety of drugs in elderly are limited and urgently needed. PMID:20711435

Mechanism of antifungal activity of antimicrobial peptide APP, a cell-penetrating peptide derivative, against Candida albicans: intracellular DNA binding and cell cycle arrest.

PubMed

Li, Lirong; Sun, Jin; Xia, Shufang; Tian, Xu; Cheserek, Maureen Jepkorir; Le, Guowei

2016-04-01

We investigated the antifungal properties and anti-candidal mechanism of antimicrobial peptide APP. The minimum inhibitory concentration of APP was 8 μM against Candida albicans and Aspeogillus flavus, the concentration against Saccharomyces cerevisiae and Cryptococcus neoformans was 16 μM, while 32 μM inhibited Aspergilla niger and Trichopyton rubrum. APP caused slight depolarization (12.32 ± 0.87%) of the membrane potential of intact C. albicans cells when it exerted its anti-candidal activity and only caused 21.52 ± 0.48% C. albicans cell membrane damage. APP interacted with cell wall membrane, caused potassium efflux and nucleotide leakage. However, confocal fluorescence microscopy experiment and flow cytometry confirmed that FITC-labeled APP penetrated C. albicans cell membrane with 52.31 ± 1.88% cell-penetrating efficiency and accumulated in the cytoplasm. Then, APP interact with C. albicans genomic DNA and completely suppressed DNA migration above weight ratio (peptide/DNA) of 2, and significantly arrested cell cycles during the S-phase (S-phase cell population was 27.09 ± 0.73%, p < 0.05) after penetrating the cell membrane. Results indicated that APP kills C. albicans for efficient cell-penetrating efficiency, strong DNA-binding affinity and significant physiological changes inducing S-phase arrest in intracellular environment.

Sulfide toxicity: Mechanical ventilation and hypotension determine survival rate and brain necrosis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Baldelli, R.J.; Green, F.H.Y.; Auer, R.N.

1993-09-01

Occupational exposure to hydrogen sulfide is one of the leading causes of sudden death in the workplace, especially in the oil and gas industry. High-dose exposure causes immediate neurogenic apnea and death; lower doses cause [open quotes]knockdown[close quotes] (transient loss of consciousness, with apnea). Because permanent neurological sequelae have been reported, the authors sought to determine whether sulfide can directly kill central nervous system neurons. Ventilated and unventilated rats were studied to allow administration of higher doses of sulfide and to facilitate physiological monitoring. It was extremely difficult to produce cerebral necrosis with sulfide. Only one of eight surviving unventilatedmore » rats given high-dose sulfide (a dose that was lethal in [ge]50% of animals) showed cerebral necrosis. Mechanical ventilation shifted the dose that was lethal in 50% of the animals to 190 mg/kg from 94 mg/kg in the unventilated rats. Sulfide was found to potently depress blood pressure. Cerebral necrosis was absent in the ventilated rats (n = 11), except in one rat that showed profound and sustained hypotension to [le]35 Torr. Electroencephalogram activity ceased during exposure but recovered when the animals regained consciousness. The authors conclude that very-high-dose sulfide is incapable of producing cerebral necrosis by a direct histotoxic effect. 32 refs., 5 figs.« less

Endogenous cGMP regulates adult longevity via the insulin signaling pathway in Caenorhabditis elegans.

PubMed

Hahm, Jeong-Hoon; Kim, Sunhee; Paik, Young-Ki

2009-08-01

G-proteins, including GPA-3, play an important role in regulating physiological responses in Caenorhabditis elegans. When confronted with an environmental stimulus such as dauer pheromone, or poor nutrients, C. elegans receives and integrates external signals through its nervous system (i.e. amphid neurons), which interprets and translates them into biological action. Here it is shown that a suppressed neuronal cGMP level caused by GPA-3 activation leads to a significant increase (47.3%) in the mean lifespan of adult C. elegans through forkhead transcription factor family O (FOXO)-mediated signal. A reduced neuronal cGMP level was found to be caused by an increased cGMP-specific phosphodiesterase activity at the transcriptional level. Our results using C. elegans mutants with specific deficits in TGF-beta and FOXO RNAi system suggest a mechanism in that cGMP, TGF-beta, and FOXO signaling interact to differentially produce the insulin-like molecules, ins-7 and daf-28, causing suppression of the insulin/IGF-1 pathway and promoting lifespan extension. Our findings provide not only a new mechanism of cGMP-mediated induction of longevity in adult C. elegans but also a possible therapeutic strategy for neuronal disease, which has been likened to brain diabetes.

Physiological Disorders in Closed, Controlled Environment Crops

NASA Technical Reports Server (NTRS)

Wheeler, Raymond M.; Morrow, Robert C.

2010-01-01

This slide presentation reviews some of the physiological disorders that affect crops grown in closed controlled environments. A physiological disorder is understood to be a problem resulting from the influence of environmental and horticultural factors on plan development other than a problem caused by a pathogen or some other abiotic cause. The topics that are addressed are: (1) Calcium-Related Disorders (2) Oedema (Intumescence) (3) Long-Photoperiod Injury (4) Light Spectral Quality Effects (5) Super-Elevated CO2 Injuries (6) Ethylene (7) Other Disorders (8) Considerations for Closed Space Environments. Views of plant with the disorders are shown.

Physiological Bases of Bulimia, and Antidepressant Treatment.

ERIC Educational Resources Information Center

Getzfeld, Andrew R.

This paper reviews the literature on the physiological causes of bulimia and investigates the rationale behind the usage of antidepressant medication in the treatment of bulimia nervosa. No definite conclusions can be stated regarding the physiology of bulimia, but a number of hypotheses are suggested. It appears that the hypothalamus is involved…

Chemotherapeutic-Induced Cardiovascular Dysfunction: Physiological Effects, Early Detection—The Role of Telomerase to Counteract Mitochondrial Defects and Oxidative Stress

PubMed Central

Quryshi, Nabeel; Norwood Toro, Laura E.; Ait-Aissa, Karima; Kong, Amanda; Beyer, Andreas M.

2018-01-01

Although chemotherapeutics can be highly effective at targeting malignancies, their ability to trigger cardiovascular morbidity is clinically significant. Chemotherapy can adversely affect cardiovascular physiology, resulting in the development of cardiomyopathy, heart failure and microvascular defects. Specifically, anthracyclines are known to cause an excessive buildup of free radical species and mitochondrial DNA damage (mtDNA) that can lead to oxidative stress-induced cardiovascular apoptosis. Therefore, oncologists and cardiologists maintain a network of communication when dealing with patients during treatment in order to treat and prevent chemotherapy-induced cardiovascular damage; however, there is a need to discover more accurate biomarkers and therapeutics to combat and predict the onset of cardiovascular side effects. Telomerase, originally discovered to promote cellular proliferation, has recently emerged as a potential mechanism to counteract mitochondrial defects and restore healthy mitochondrial vascular phenotypes. This review details mechanisms currently used to assess cardiovascular damage, such as C-reactive protein (CRP) and troponin levels, while also unearthing recently researched biomarkers, including circulating mtDNA, telomere length and telomerase activity. Further, we explore a potential role of telomerase in the mitigation of mitochondrial reactive oxygen species and maintenance of mtDNA integrity. Telomerase activity presents a promising indicator for the early detection and treatment of chemotherapy-derived cardiac damage. PMID:29534446

Photoinhibition of Phaeocystis globosa resulting from oxidative stress induced by a marine algicidal bacterium Bacillus sp. LP-10.

PubMed

Guan, Chengwei; Guo, Xiaoyun; Li, Yi; Zhang, Huajun; Lei, Xueqian; Cai, Guanjing; Guo, Jiajia; Yu, Zhiming; Zheng, Tianling

2015-11-25

Harmful algal blooms caused by Phaeocystis globosa have resulted in staggering losses to coastal countries because of their world-wide distribution. Bacteria have been studied for years to control the blooms of harmful alga, however, the action mechanism of them against harmful algal cells is still not well defined. Here, a previously isolated algicidal bacterium Bacillus sp. LP-10 was used to elucidate the potential mechanism involved in the dysfunction of P. globosa algal cells at physiological and molecular levels. Our results showed Bacillus sp. LP-10 induced an obvious rise of reactive oxygen species (ROS), which was supposed to be major reason for algal cell death. Meanwhile, the results revealed a significant decrease of photosynthetic physiological indexes and apparent down-regulated of photosynthesis-related genes (psbA and rbcS) and protein (PSII reaction center protein D1), after treated by Bacillus sp. LP-10 filtrates, suggesting photoinhibition occurred in the algal cells. Furthermore, our results indicated that light played important roles in the algal cell death. Our work demonstrated that the major lethal reason of P. globosa cells treated by the algicidal bacterium was the photoinhibition resulted from oxidative stress induced by Bacillus sp. LP-10.

Photoinhibition of Phaeocystis globosa resulting from oxidative stress induced by a marine algicidal bacterium Bacillus sp. LP-10

PubMed Central

Guan, Chengwei; Guo, Xiaoyun; Li, Yi; Zhang, Huajun; Lei, Xueqian; Cai, Guanjing; Guo, Jiajia; Yu, Zhiming; Zheng, Tianling

2015-01-01

Harmful algal blooms caused by Phaeocystis globosa have resulted in staggering losses to coastal countries because of their world-wide distribution. Bacteria have been studied for years to control the blooms of harmful alga, however, the action mechanism of them against harmful algal cells is still not well defined. Here, a previously isolated algicidal bacterium Bacillus sp. LP-10 was used to elucidate the potential mechanism involved in the dysfunction of P. globosa algal cells at physiological and molecular levels. Our results showed Bacillus sp. LP-10 induced an obvious rise of reactive oxygen species (ROS), which was supposed to be major reason for algal cell death. Meanwhile, the results revealed a significant decrease of photosynthetic physiological indexes and apparent down-regulated of photosynthesis-related genes (psbA and rbcS) and protein (PSII reaction center protein D1), after treated by Bacillus sp. LP-10 filtrates, suggesting photoinhibition occurred in the algal cells. Furthermore, our results indicated that light played important roles in the algal cell death. Our work demonstrated that the major lethal reason of P. globosa cells treated by the algicidal bacterium was the photoinhibition resulted from oxidative stress induced by Bacillus sp. LP-10. PMID:26601700

Store-Operated Calcium Channels

PubMed Central

Lewis, Richard S.

2015-01-01

Store-operated calcium channels (SOCs) are a major pathway for calcium signaling in virtually all metozoan cells and serve a wide variety of functions ranging from gene expression, motility, and secretion to tissue and organ development and the immune response. SOCs are activated by the depletion of Ca2+ from the endoplasmic reticulum (ER), triggered physiologically through stimulation of a diverse set of surface receptors. Over 15 years after the first characterization of SOCs through electrophysiology, the identification of the STIM proteins as ER Ca2+ sensors and the Orai proteins as store-operated channels has enabled rapid progress in understanding the unique mechanism of store-operate calcium entry (SOCE). Depletion of Ca2+ from the ER causes STIM to accumulate at ER-plasma membrane (PM) junctions where it traps and activates Orai channels diffusing in the closely apposed PM. Mutagenesis studies combined with recent structural insights about STIM and Orai proteins are now beginning to reveal the molecular underpinnings of these choreographic events. This review describes the major experimental advances underlying our current understanding of how ER Ca2+ depletion is coupled to the activation of SOCs. Particular emphasis is placed on the molecular mechanisms of STIM and Orai activation, Orai channel properties, modulation of STIM and Orai function, pharmacological inhibitors of SOCE, and the functions of STIM and Orai in physiology and disease. PMID:26400989

Individual variation and the endocrine regulation of behaviour and physiology in birds: a cellular/molecular perspective.

PubMed

Ball, Gregory F; Balthazart, Jacques

2008-05-12

Investigations of the cellular and molecular mechanisms of physiology and behaviour have generally avoided attempts to explain individual differences. The goal has rather been to discover general processes. However, understanding the causes of individual variation in many phenomena of interest to avian eco-physiologists will require a consideration of such mechanisms. For example, in birds, changes in plasma concentrations of steroid hormones are important in the activation of social behaviours related to reproduction and aggression. Attempts to explain individual variation in these behaviours as a function of variation in plasma hormone concentrations have generally failed. Cellular variables related to the effectiveness of steroid hormone have been useful in some cases. Steroid hormone target sensitivity can be affected by variables such as metabolizing enzyme activity, hormone receptor expression as well as receptor cofactor expression. At present, no general theory has emerged that might provide a clear guidance when trying to explain individual variability in birds or in any other group of vertebrates. One strategy is to learn from studies of large units of intraspecific variation such as population or sex differences to provide ideas about variables that might be important in explaining individual variation. This approach along with the use of newly developed molecular genetic tools represents a promising avenue for avian eco-physiologists to pursue.

Ultrasensitive, passive and wearable sensors for monitoring human muscle motion and physiological signals.

PubMed

Cai, Feng; Yi, Changrui; Liu, Shichang; Wang, Yan; Liu, Lacheng; Liu, Xiaoqing; Xu, Xuming; Wang, Li

2016-03-15

Flexible sensors have attracted more and more attention as a fundamental part of anthropomorphic robot research, medical diagnosis and physical health monitoring. Here, we constructed an ultrasensitive and passive flexible sensor with the advantages of low cost, lightness and wearability, electric safety and reliability. The fundamental mechanism of the sensor is based on triboelectric effect inducing electrostatic charges on the surfaces between two different materials. Just like a plate capacitor, current will be generated while the distance or size of the parallel capacitors changes caused by the small mechanical disturbance upon it and therefore the output current/voltage will be produced. Typically, the passive sensor unambiguously monitors muscle motions including hand motion from stretch-clench-stretch, mouth motion from open-bite-open, blink and respiration. Moreover, this sensor records the details of the consecutive phases in a cardiac cycle of the apex cardiogram, and identify the peaks including percussion wave, tidal wave and diastolic wave of the radial pulse wave. To record subtle human physiological signals including radial pulsilogram and apex cardiogram with excellent signal/noise ratio, stability and reproducibility, the sensor shows great potential in the applications of medical diagnosis and daily health monitoring. Copyright © 2015 Elsevier B.V. All rights reserved.

Preservation of potassium balance is strongly associated with insect cold tolerance in the field: a seasonal study of Drosophila subobscura.

PubMed

MacMillan, Heath A; Schou, Mads F; Kristensen, Torsten N; Overgaard, Johannes

2016-05-01

There is interest in pinpointing genes and physiological mechanisms explaining intra- and interspecific variations in cold tolerance, because thermal tolerance phenotypes strongly impact the distribution and abundance of wild animals. Laboratory studies have highlighted that the capacity to preserve water and ion homeostasis is linked to low temperature survival in insects. It remains unknown, however, whether adaptive seasonal acclimatization in free-ranging insects is governed by the same physiological mechanisms. Here, we test whether cold tolerance in field-caught Drosophila subobscura is high in early spring and lower during summer and whether this transition is associated with seasonal changes in the capacity of flies to preserve water and ion balance during cold stress. Indeed, flies caught during summer were less cold tolerant, and exposure of these flies to sub-zero temperatures caused a loss of haemolymph water and increased the concentration of K(+) in the haemolymph (as in laboratory-reared insects). This pattern of ion and water balance disruption was not observed in more cold-tolerant flies caught in early spring. Thus, we here provide a field verification of hypotheses based on laboratory studies and conclude that the ability to maintain ion homeostasis is important for the ability of free-ranging insects to cope with chilling. © 2016 The Author(s).

Caffeine and exercise.

PubMed

Paluska, Scott A

2003-08-01

Caffeine is the most commonly consumed drug in the world, and athletes frequently use it as an ergogenic aid. It improves performance and endurance during prolonged, exhaustive exercise. To a lesser degree it also enhances short-term, high-intensity athletic performance. Caffeine improves concentration, reduces fatigue, and enhances alertness. Habitual intake does not diminish caffeine's ergogenic properties. Several mechanisms have been proposed to explain the physiologic effects of caffeine, but adenosine receptor antagonism most likely accounts for the primary mode of action. It is relatively safe and has no known negative performance effects, nor does it cause significant dehydration or electrolyte imbalance during exercise. Routine caffeine consumption may cause tolerance or dependence, and abrupt discontinuation produces irritability, mood shifts, headache, drowsiness, or fatigue. Major sport governing bodies ban excessive use of caffeine, but current monitoring techniques are inadequate, and ethical dilemmas persist regarding caffeine intake by athletes.

Skeletal Muscle-specific G Protein-coupled Receptor Kinase 2 Ablation Alters Isolated Skeletal Muscle Mechanics and Enhances Clenbuterol-stimulated Hypertrophy.

PubMed

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.

Evolution of adaptation mechanisms: Adaptation energy, stress, and oscillating death.

PubMed

Gorban, Alexander N; Tyukina, Tatiana A; Smirnova, Elena V; Pokidysheva, Lyudmila I

2016-09-21

In 1938, Selye proposed the notion of adaptation energy and published 'Experimental evidence supporting the conception of adaptation energy.' Adaptation of an animal to different factors appears as the spending of one resource. Adaptation energy is a hypothetical extensive quantity spent for adaptation. This term causes much debate when one takes it literally, as a physical quantity, i.e. a sort of energy. The controversial points of view impede the systematic use of the notion of adaptation energy despite experimental evidence. Nevertheless, the response to many harmful factors often has general non-specific form and we suggest that the mechanisms of physiological adaptation admit a very general and nonspecific description. We aim to demonstrate that Selye׳s adaptation energy is the cornerstone of the top-down approach to modelling of non-specific adaptation processes. We analyze Selye׳s axioms of adaptation energy together with Goldstone׳s modifications and propose a series of models for interpretation of these axioms. Adaptation energy is considered as an internal coordinate on the 'dominant path' in the model of adaptation. The phenomena of 'oscillating death' and 'oscillating remission' are predicted on the base of the dynamical models of adaptation. Natural selection plays a key role in the evolution of mechanisms of physiological adaptation. We use the fitness optimization approach to study of the distribution of resources for neutralization of harmful factors, during adaptation to a multifactor environment, and analyze the optimal strategies for different systems of factors. Copyright © 2016 Elsevier Ltd. All rights reserved.

Climate warming causes life-history evolution in a model for Atlantic cod (Gadus morhua).

PubMed

Holt, Rebecca E; Jørgensen, Christian

2014-01-01

Climate change influences the marine environment, with ocean warming being the foremost driving factor governing changes in the physiology and ecology of fish. At the individual level, increasing temperature influences bioenergetics and numerous physiological and life-history processes, which have consequences for the population level and beyond. We provide a state-dependent energy allocation model that predicts temperature-induced adaptations for life histories and behaviour for the North-East Arctic stock (NEA) of Atlantic cod (Gadus morhua) in response to climate warming. The key constraint is temperature-dependent respiratory physiology, and the model includes a number of trade-offs that reflect key physiological and ecological processes. Dynamic programming is used to find an evolutionarily optimal strategy of foraging and energy allocation that maximizes expected lifetime reproductive output given constraints from physiology and ecology. The optimal strategy is then simulated in a population, where survival, foraging behaviour, growth, maturation and reproduction emerge. Using current forcing, the model reproduces patterns of growth, size-at-age, maturation, gonad production and natural mortality for NEA cod. The predicted climate responses are positive for this stock; under a 2°C warming, the model predicted increased growth rates and a larger asymptotic size. Maturation age was unaffected, but gonad weight was predicted to more than double. Predictions for a wider range of temperatures, from 2 to 7°C, show that temperature responses were gradual; fish were predicted to grow faster and increase reproductive investment at higher temperatures. An emergent pattern of higher risk acceptance and increased foraging behaviour was also predicted. Our results provide important insight into the effects of climate warming on NEA cod by revealing the underlying mechanisms and drivers of change. We show how temperature-induced adaptations of behaviour and several life-history traits are not only mediated by physiology but also by trade-offs with survival, which has consequences for conservation physiology.

White-nose syndrome initiates a cascade of physiologic disturbances in the hibernating bat host.

PubMed

Verant, Michelle L; Meteyer, Carol U; Speakman, John R; Cryan, Paul M; Lorch, Jeffrey M; Blehert, David S

2014-12-09

The physiological effects of white-nose syndrome (WNS) in hibernating bats and ultimate causes of mortality from infection with Pseudogymnoascus (formerly Geomyces) destructans are not fully understood. Increased frequency of arousal from torpor described among hibernating bats with late-stage WNS is thought to accelerate depletion of fat reserves, but the physiological mechanisms that lead to these alterations in hibernation behavior have not been elucidated. We used the doubly labeled water (DLW) method and clinical chemistry to evaluate energy use, body composition changes, and blood chemistry perturbations in hibernating little brown bats (Myotis lucifugus) experimentally infected with P. destructans to better understand the physiological processes that underlie mortality from WNS. These data indicated that fat energy utilization, as demonstrated by changes in body composition, was two-fold higher for bats with WNS compared to negative controls. These differences were apparent in early stages of infection when torpor-arousal patterns were equivalent between infected and non-infected animals, suggesting that P. destructans has complex physiological impacts on its host prior to onset of clinical signs indicative of late-stage infections. Additionally, bats with mild to moderate skin lesions associated with early-stage WNS demonstrated a chronic respiratory acidosis characterized by significantly elevated dissolved carbon dioxide, acidemia, and elevated bicarbonate. Potassium concentrations were also significantly higher among infected bats, but sodium, chloride, and other hydration parameters were equivalent to controls. Integrating these novel findings on the physiological changes that occur in early-stage WNS with those previously documented in late-stage infections, we propose a multi-stage disease progression model that mechanistically describes the pathologic and physiologic effects underlying mortality of WNS in hibernating bats. This model identifies testable hypotheses for better understanding this disease, knowledge that will be critical for defining effective disease mitigation strategies aimed at reducing morbidity and mortality that results from WNS.

Climate warming causes life-history evolution in a model for Atlantic cod (Gadus morhua)

PubMed Central

Holt, Rebecca E.; Jørgensen, Christian

2014-01-01

Climate change influences the marine environment, with ocean warming being the foremost driving factor governing changes in the physiology and ecology of fish. At the individual level, increasing temperature influences bioenergetics and numerous physiological and life-history processes, which have consequences for the population level and beyond. We provide a state-dependent energy allocation model that predicts temperature-induced adaptations for life histories and behaviour for the North-East Arctic stock (NEA) of Atlantic cod (Gadus morhua) in response to climate warming. The key constraint is temperature-dependent respiratory physiology, and the model includes a number of trade-offs that reflect key physiological and ecological processes. Dynamic programming is used to find an evolutionarily optimal strategy of foraging and energy allocation that maximizes expected lifetime reproductive output given constraints from physiology and ecology. The optimal strategy is then simulated in a population, where survival, foraging behaviour, growth, maturation and reproduction emerge. Using current forcing, the model reproduces patterns of growth, size-at-age, maturation, gonad production and natural mortality for NEA cod. The predicted climate responses are positive for this stock; under a 2°C warming, the model predicted increased growth rates and a larger asymptotic size. Maturation age was unaffected, but gonad weight was predicted to more than double. Predictions for a wider range of temperatures, from 2 to 7°C, show that temperature responses were gradual; fish were predicted to grow faster and increase reproductive investment at higher temperatures. An emergent pattern of higher risk acceptance and increased foraging behaviour was also predicted. Our results provide important insight into the effects of climate warming on NEA cod by revealing the underlying mechanisms and drivers of change. We show how temperature-induced adaptations of behaviour and several life-history traits are not only mediated by physiology but also by trade-offs with survival, which has consequences for conservation physiology. PMID:27293671

Differential regulation of metabolism by nitric oxide and S-nitrosothiols in endothelial cells

PubMed Central

Diers, Anne R.; Broniowska, Katarzyna A.; Darley-Usmar, Victor M.

2011-01-01

S-nitrosation of thiols in key proteins in cell signaling pathways is thought to be an important contributor to nitric oxide (NO)-dependent control of vascular (patho)physiology. Multiple metabolic enzymes are targets of both NO and S-nitrosation, including those involved in glycolysis and oxidative phosphorylation. Thus it is important to understand how these metabolic pathways are integrated by NO-dependent mechanisms. Here, we compared the effects of NO and S-nitrosation on both glycolysis and oxidative phosphorylation in bovine aortic endothelial cells using extracellular flux technology to determine common and unique points of regulation. The compound S-nitroso-l-cysteine (l-CysNO) was used to initiate intracellular S-nitrosation since it is transported into cells and results in stable S-nitrosation in vitro. Its effects were compared with the NO donor DetaNONOate (DetaNO). DetaNO treatment caused only a decrease in the reserve respiratory capacity; however, l-CysNO impaired both this parameter and basal respiration in a concentration-dependent manner. In addition, DetaNO stimulated extracellular acidification rate (ECAR), a surrogate marker of glycolysis, whereas l-CysNO stimulated ECAR at low concentrations and inhibited it at higher concentrations. Moreover, a temporal relationship between NO- and S-nitrosation-mediated effects on metabolism was identified, whereby NO caused a rapid impairment in mitochondrial function, which was eventually overwhelmed by S-nitrosation-dependent processes. Taken together, these results suggest that severe pharmacological nitrosative stress may differentially regulate metabolic pathways through both intracellular S-nitrosation and NO-dependent mechanisms. Moreover, these data provide insight into the role of NO and related compounds in vascular (patho)physiology. PMID:21685262

Differential regulation of metabolism by nitric oxide and S-nitrosothiols in endothelial cells.

PubMed

Diers, Anne R; Broniowska, Katarzyna A; Darley-Usmar, Victor M; Hogg, Neil

2011-09-01

S-nitrosation of thiols in key proteins in cell signaling pathways is thought to be an important contributor to nitric oxide (NO)-dependent control of vascular (patho)physiology. Multiple metabolic enzymes are targets of both NO and S-nitrosation, including those involved in glycolysis and oxidative phosphorylation. Thus it is important to understand how these metabolic pathways are integrated by NO-dependent mechanisms. Here, we compared the effects of NO and S-nitrosation on both glycolysis and oxidative phosphorylation in bovine aortic endothelial cells using extracellular flux technology to determine common and unique points of regulation. The compound S-nitroso-L-cysteine (L-CysNO) was used to initiate intracellular S-nitrosation since it is transported into cells and results in stable S-nitrosation in vitro. Its effects were compared with the NO donor DetaNONOate (DetaNO). DetaNO treatment caused only a decrease in the reserve respiratory capacity; however, L-CysNO impaired both this parameter and basal respiration in a concentration-dependent manner. In addition, DetaNO stimulated extracellular acidification rate (ECAR), a surrogate marker of glycolysis, whereas L-CysNO stimulated ECAR at low concentrations and inhibited it at higher concentrations. Moreover, a temporal relationship between NO- and S-nitrosation-mediated effects on metabolism was identified, whereby NO caused a rapid impairment in mitochondrial function, which was eventually overwhelmed by S-nitrosation-dependent processes. Taken together, these results suggest that severe pharmacological nitrosative stress may differentially regulate metabolic pathways through both intracellular S-nitrosation and NO-dependent mechanisms. Moreover, these data provide insight into the role of NO and related compounds in vascular (patho)physiology.

Pulmonary ventilation-perfusion mismatch: a novel hypothesis for how diving vertebrates may avoid the bends.

PubMed

Garcia Párraga, Daniel; Moore, Michael; Fahlman, Andreas

2018-04-25

Hydrostatic lung compression in diving marine mammals, with collapsing alveoli blocking gas exchange at depth, has been the main theoretical basis for limiting N 2 uptake and avoiding gas emboli (GE) as they ascend. However, studies of beached and bycaught cetaceans and sea turtles imply that air-breathing marine vertebrates may, under unusual circumstances, develop GE that result in decompression sickness (DCS) symptoms. Theoretical modelling of tissue and blood gas dynamics of breath-hold divers suggests that changes in perfusion and blood flow distribution may also play a significant role. The results from the modelling work suggest that our current understanding of diving physiology in many species is poor, as the models predict blood and tissue N 2 levels that would result in severe DCS symptoms (chokes, paralysis and death) in a large fraction of natural dive profiles. In this review, we combine published results from marine mammals and turtles to propose alternative mechanisms for how marine vertebrates control gas exchange in the lung, through management of the pulmonary distribution of alveolar ventilation ([Formula: see text]) and cardiac output/lung perfusion ([Formula: see text]), varying the level of [Formula: see text] in different regions of the lung. Man-made disturbances, causing stress, could alter the [Formula: see text] mismatch level in the lung, resulting in an abnormally elevated uptake of N 2 , increasing the risk for GE. Our hypothesis provides avenues for new areas of research, offers an explanation for how sonar exposure may alter physiology causing GE and provides a new mechanism for how air-breathing marine vertebrates usually avoid the diving-related problems observed in human divers. © 2018 The Authors.

Programmed Effects in Neurobehavior and Antioxidative Physiology in Zebrafish Embryonically Exposed to Cadmium: Observations and Hypothesized Adverse Outcome Pathway Framework

PubMed Central

Ruiter, Sander; Sippel, Josefine; Bouwmeester, Manon C.; Lommelaars, Tobias; Beekhof, Piet; Hodemaekers, Hennie M.; Bakker, Frank; van den Brandhof, Evert-Jan; Pennings, Jeroen L. A.; van der Ven, Leo T. M.

2016-01-01

Non-communicable diseases (NCDs) are a major cause of premature mortality. Recent studies show that predispositions for NCDs may arise from early-life exposure to low concentrations of environmental contaminants. This developmental origins of health and disease (DOHaD) paradigm suggests that programming of an embryo can be disrupted, changing the homeostatic set point of biological functions. Epigenetic alterations are a possible underlying mechanism. Here, we investigated the DOHaD paradigm by exposing zebrafish to subtoxic concentrations of the ubiquitous contaminant cadmium during embryogenesis, followed by growth under normal conditions. Prolonged behavioral responses to physical stress and altered antioxidative physiology were observed approximately ten weeks after termination of embryonal exposure, at concentrations that were 50–3200-fold below the direct embryotoxic concentration, and interpreted as altered developmental programming. Literature was explored for possible mechanistic pathways that link embryonic subtoxic cadmium to the observed apical phenotypes, more specifically, the probability of molecular mechanisms induced by cadmium exposure leading to altered DNA methylation and subsequently to the observed apical phenotypes. This was done using the adverse outcome pathway model framework, and assessing key event relationship plausibility by tailored Bradford-Hill analysis. Thus, cadmium interaction with thiols appeared to be the major contributor to late-life effects. Cadmium-thiol interactions may lead to depletion of the methyl donor S-adenosyl-methionine, resulting in methylome alterations, and may, additionally, result in oxidative stress, which may lead to DNA oxidation, and subsequently altered DNA methyltransferase activity. In this way, DNA methylation may be affected at a critical developmental stage, causing the observed apical phenotypes. PMID:27827847

The Vascular Pathogen Verticillium longisporum Does Not Affect Water Relations and Plant Responses to Drought Stress of Its Host, Brassica napus.

PubMed

Lopisso, Daniel Teshome; Knüfer, Jessica; Koopmann, Birger; von Tiedemann, Andreas

2017-04-01

Verticillium longisporum is a host-specific vascular pathogen of oilseed rape (Brassica napus L.) that causes economic crop losses by impairing plant growth and inducing premature senescence. This study investigates whether plant damage through Verticillium stem striping is due to impaired plant water relations, whether V. longisporum affects responses of a susceptible B. napus variety to drought stress, and whether drought stress, in turn, affects plant responses to V. longisporum. Two-factorial experiments on a susceptible cultivar of B. napus infected or noninfected with V. longisporum and exposed to three watering levels (30, 60, and 100% field capacity) revealed that drought stress and V. longisporum impaired plant growth by entirely different mechanisms. Although both stresses similarly affected plant growth parameters (plant height, hypocotyl diameter, and shoot and root dry matter), infection of B. napus with V. longisporum did not affect any drought-related physiological or molecular genetic plant parameters, including transpiration rate, stomatal conductance, photosynthesis rate, water use efficiency, relative leaf water content, leaf proline content, or the expression of drought-responsive genes. Thus, this study provides comprehensive physiological and molecular genetic evidence explaining the lack of wilt symptoms in B. napus infected with V. longisporum. Likewise, drought tolerance of B. napus was unaffected by V. longisporum, as was the level of disease by drought conditions, thus excluding a concerted action of both stresses in the field. Although it is evident that drought and vascular infection with V. longisporum impair plant growth by different mechanisms, it remains to be determined by which other factors V. longisporum causes crop loss.

Influence of bovine serum albumin in Hanks' solution on the corrosion and stress corrosion cracking of a magnesium alloy.

PubMed

Harandi, Shervin Eslami; Banerjee, Parama Chakraborty; Easton, Christopher D; Singh Raman, R K

2017-11-01

It is essential for any temporary implant to possess adequate strength to maintain their mechanical integrity under the synergistic effects of mechanical loading characteristics of human body and the corrosive physiological environment. Such synergistic effects can cause stress corrosion cracking (SCC). The aim of the present study is to investigate the effect of the addition of bovine serum albumin (BSA) to Hanks' solution in corrosion and SCC susceptibility of AZ91D magnesium alloy. The electrochemical impedance spectroscopy (EIS) results indicated that the addition of BSA increased corrosion resistance of the alloy during the first 48h of immersion and then decreased it rapidly. The energy-dispersive X-ray spectroscopy (EDS) and X-ray photoelectron spectroscopy (XPS) analyses indicated adsorption of BSA on the alloy surface during initial hours of immersion. However, with the increasing immersion time, BSA chelated with the corrosion products causing disruption of the protective film; thus, it accelerated the corrosion of the alloy. Both the mechanical data and fractographic evidence have confirmed susceptibility of the alloy to SCC. However, in the presence of BSA, the alloy suffered greater SCC which was attributed to its increased susceptibility towards localized corrosion. Copyright © 2017. Published by Elsevier B.V.

Injectable silk foams for the treatment of cervical insufficiency

NASA Astrophysics Data System (ADS)

Fournier, Eric P.

Preterm birth is the leading cause of neonatal mortality, resulting in over 4,000 deaths each year. A significant risk factor for preterm birth is cervical insufficiency, the weakening and subsequent deformation of cervical tissue. Cervical insufficiency is both detectable and treatable but current treatments are lacking. The most common approach requires multiple invasive procedures. This work investigates the injection of silk foams, a minimally-invasive method for supporting cervical tissue. Silk offers many advantages for use as a biomaterial including strength, versatility, and biocompatibility. Injectable silk foams will minimize patient discomfort while also providing more targeted and personalized treatment. A battery of mechanical testing was undertaken to determine silk foam response under physiologically relevant loading and environmental conditions. Mechanical testing was paired with analysis of foam morphology and structure that illustrated the effects of injection on pore geometry and size. Biological response to silk foams was evaluated using an in vitro degradation study and subcutaneous in vivo implantation in a mouse model. Results showed that foams exceeded the mechanical requirements for stiffening cervical tissue, although the current injection process limits foam size. Injection was shown to cause measurable but localized foam deformation. This work indicates that silk foams are a feasible treatment option for cervical insufficiency but challenges remain with foam delivery.

Salinity Tolerance Mechanism of Economic Halophytes From Physiological to Molecular Hierarchy for Improving Food Quality

PubMed Central

Xu, Chongzhi; Tang, Xiaoli; Shao, Hongbo; Wang, Hongyan

2016-01-01

Soil salinity is becoming the key constraints factor to agricultural production. Therefore, the plant especially the crops possessing capacities of salt tolerance will be of great economic significance. The adaptation or tolerance of plant to salinity stress involves a series of physiological, metabolic and molecular mechanisms. Halophytes are the kind of organisms which acquire special salt tolerance mechanisms to respond to the salt tress and ensure normal growth and development under saline conditions in their lengthy evolutionary adaptation, so understanding how halophytes respond to salinity stress will provide us with methods and tactics to foster and develop salt resistant varieties of crops. The strategies in physiological and molecular level adopted by halophytes are various including the changes in photosynthetic and transpiration rate, the sequestration of Na+ to extracellular or vacuole, the regulation of stomata aperture and stomatal density, the accumulation and synthesis of the phytohormones as well as the relevant gene expression underlying these physiological traits, such as the stress signal transduction, the regulation of the transcription factors, the activation and expression of the transporter genes, the activation or inhibition of the synthetases and so on. This review focuses on the research advances of the regulating mechanisms in halophytes from physiological to molecular, which render the halophytes tolerance and adaption to salinity stress. PMID:27252587

Effects of experimentally elevated traffic noise on nestling white-crowned sparrow stress physiology, immune function and life history.

PubMed

Crino, Ondi L; Johnson, Erin E; Blickley, Jessica L; Patricelli, Gail L; Breuner, Creagh W

2013-06-01

Roads have been associated with behavioral and physiological changes in wildlife. In birds, roads decrease reproductive success and biodiversity and increase physiological stress. Although the consequences of roads on individuals and communities have been well described, the mechanisms through which roads affect birds remain largely unexplored. Here, we examine one mechanism through which roads could affect birds: traffic noise. We exposed nestling mountain white-crowned sparrows (Zonotrichia leucophrys oriantha) to experimentally elevated traffic noise for 5 days during the nestling period. Following exposure to traffic noise we measured nestling stress physiology, immune function, body size, condition and survival. Based on prior studies, we expected the traffic noise treatment to result in elevated stress hormones (glucocorticoids), and declines in immune function, body size, condition and survival. Surprisingly, nestlings exposed to traffic noise had lower glucocorticoid levels and improved condition relative to control nests. These results indicate that traffic noise does affect physiology and development in white-crowned sparrows, but not at all as predicted. Therefore, when evaluating the mechanisms through which roads affect avian populations, other factors (e.g. edge effects, pollution and mechanical vibration) may be more important than traffic noise in explaining elevated nestling stress responses in this species.

Mechanism of UES relaxation initiated by gastric air distension.

PubMed

Lang, Ivan M; Medda, Bidyut K; Shaker, Reza

2014-08-15

The aim of this study was to determine the mechanism of initiation of transient upper esophageal sphincter relaxation (TUESR) caused by gastric air distension. Cats (n = 31) were decerebrated, EMG electrodes were placed on the cricopharyngeus, a gastric fistula was formed, and a strain gauge was sewn on the lower esophageal sphincter (n = 8). Injection of air (114 ± 13 ml) in the stomach caused TUESR (n = 18) and transient lower esophageal sphincter relaxation (TLESR, n = 6), and this effect was not significantly (P > 0.05) affected by thoracotomy. Free air or bagged air (n = 6) activated TLESR, but only free air activated TUESR. Closure of the gastroesophageal junction blocked TUESR (9/9), but not TLESR (4/4), caused by air inflation of the stomach. Venting air from distal esophagus during air inflation of the stomach prevented TUESR (n = 12) but did not prevent air escape from the stomach to the esophagus (n = 4). Rapid injection of air on the esophageal mucosa always caused TUESR (9/9) but did not always (7/9) cause an increase in esophageal pressure. The time delay between the TUESR and the rapid air pulse was significantly more variable (P < 0.05) than the time delay between the rapid air pulse and the rise in esophageal pressure. We concluded that the TUESR caused by gastric air distension is dependent on air escape from the stomach, which stimulates receptors in the esophagus, but is not dependent on distension of the stomach or esophagus, or the TLESR. Therefore, the TUESR caused by gastric air distension is initiated by stimulation of receptors in the esophageal mucosa. Copyright © 2014 the American Physiological Society.

The sleepy teenager - diagnostic challenges.

PubMed

Landtblom, Anne-Marie; Engström, Maria

2014-01-01

The sleepy teenager puts the doctor in a, often tricky, situation where it must be decided if we deal with normal physiology or if we should suspect pathological conditions. What medical investigations are proper to consider? What differential diagnoses should be considered in the first place? And what tools do we actually have? The symptoms and problems that usually are presented at the clinical visit can be both of medical and psychosocial character - and actually they are often a mixture of both. Subsequently, the challenge to investigate the sleepy teenager often includes the examination of a complex behavioral pattern. It is important to train and develop diagnostic skills and to realize that the physiological or pathological conditions that can cause the symptoms may have different explanations. Research in sleep disorders has shown different pathological mechanisms congruent with the variations in the clinical picture. There are probably also different patterns of involved neuronal circuits although common pathways may exist. The whole picture remains to be drawn in this interesting and challenging area.

The Sleepy Teenager – Diagnostic Challenges

PubMed Central

Landtblom, Anne-Marie; Engström, Maria

2014-01-01

The sleepy teenager puts the doctor in a, often tricky, situation where it must be decided if we deal with normal physiology or if we should suspect pathological conditions. What medical investigations are proper to consider? What differential diagnoses should be considered in the first place? And what tools do we actually have? The symptoms and problems that usually are presented at the clinical visit can be both of medical and psychosocial character – and actually they are often a mixture of both. Subsequently, the challenge to investigate the sleepy teenager often includes the examination of a complex behavioral pattern. It is important to train and develop diagnostic skills and to realize that the physiological or pathological conditions that can cause the symptoms may have different explanations. Research in sleep disorders has shown different pathological mechanisms congruent with the variations in the clinical picture. There are probably also different patterns of involved neuronal circuits although common pathways may exist. The whole picture remains to be drawn in this interesting and challenging area. PMID:25136329

Stress corrosion cracking of an aluminum alloy used in external fixation devices.

PubMed

Cartner, Jacob L; Haggard, Warren O; Ong, Joo L; Bumgardner, Joel D

2008-08-01

Treatment for compound and/or comminuted fractures is frequently accomplished via external fixation. To achieve stability, the compositions of external fixators generally include aluminum alloy components due to their high strength-to-weight ratios. These alloys are particularly susceptible to corrosion in chloride environments. There have been several clinical cases of fixator failure in which corrosion was cited as a potential mechanism. The aim of this study was to evaluate the effects of physiological environments on the corrosion susceptibility of aluminum 7075-T6, since it is used in orthopedic external fixation devices. Electrochemical corrosion curves and alternate immersion stress corrosion cracking tests indicated aluminum 7075-T6 is susceptible to corrosive attack when placed in physiological environments. Pit initiated stress corrosion cracking was the primary form of alloy corrosion, and subsequent fracture, in this study. Anodization of the alloy provided a protective layer, but also caused a decrease in passivity ranges. These data suggest that once the anodization layer is disrupted, accelerated corrosion processes occur. (c) 2007 Wiley Periodicals, Inc.

Antiangiogenic immunotherapy targeting Flk-1, DNA vaccine and adoptive T cell transfer, inhibits ocular neovascularization

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, Han; Sonoda, Koh-Hei, E-mail: sonodak@med.kyushu-u.ac.jp; Hijioka, Kuniaki

2009-04-17

Ocular neovascularization (NV) is the primary cause of blindness in a wide range of ocular diseases. The exact mechanism underlying the pathogenesis of ocular NV is not yet well understood, and so there is no satisfactory therapy for ocular NV. Here, we describe a strategy targeting Flk-1, a self-antigen overexpressed on proliferating endothelial cells in ocular NV, by antiangiogenic immunotherapy-DNA vaccine and adoptive T cell therapy. An oral DNA vaccine encoding Flk-1 carried by attenuated Salmonella typhimurium markedly suppressed development of laser-induced choroidal NV. We further demonstrated that adoptive transfer of vaccine-induced CD8{sup +} T cells reduced pathological preretinal NV,more » with a concomitant facilitation of physiological revascularization after oxygen-induced retinal vessel obliteration. However, physiological retinal vascular development was unaffected in neonatal mice transferred with vaccine-induced CD8{sup +} T cells. These findings suggested that antiangiogenic immunotherapy targeting Flk-1 such as vaccination and adoptive immunotherapy may contribute to future therapies for ocular NV.« less

O-GlcNAc transferase enables AgRP neurons to suppress browning of white fat

PubMed Central

Ruan, Hai-Bin; Dietrich, Marcelo O.; Liu, Zhong-Wu; Zimmer, Marcelo R.; Li, Min-Dian; Singh, Jay Prakash; Zhang, Kaisi; Yin, Ruonan; Wu, Jing; Horvath, Tamas L.; Yang, Xiaoyong

2014-01-01

SUMMARY Induction of beige cells causes the browning of white fat and improves energy metabolism. However, the central mechanism that controls adipose tissue browning and its physiological relevance are largely unknown. Here we demonstrate that fasting and chemical-genetic activation of orexigenic AgRP neurons in the hypothalamus suppress the browning of white fat. O-linked β-N-acetylglucosamine (O-GlcNAc) modification of cytoplasmic and nuclear proteins regulates fundamental cellular processes. The levels of O-GlcNAc transferase (OGT) and O-GlcNAc modification are enriched in AgRP neurons and are elevated by fasting. Genetic ablation of OGT in AgRP neurons inhibits neuronal excitability through the voltage-dependent potassium channel, promotes white adipose tissue browning, and protects mice against diet-induced obesity and insulin resistance. These data reveal adipose tissue browning as a highly dynamic physiological process under central control, in which O-GlcNAc signaling in AgRP neurons is essential for suppressing thermogenesis to conserve energy in response to fasting. PMID:25303527

Physiological mechanisms of sustained fumagillin-induced weight loss.

PubMed

An, Jie; Wang, Liping; Patnode, Michael L; Ridaura, Vanessa K; Haldeman, Jonathan M; Stevens, Robert D; Ilkayeva, Olga; Bain, James R; Muehlbauer, Michael J; Glynn, Erin L; Thomas, Steven; Muoio, Deborah; Summers, Scott A; Vath, James E; Hughes, Thomas E; Gordon, Jeffrey I; Newgard, Christopher B

2018-03-08

Current obesity interventions suffer from lack of durable effects and undesirable complications. Fumagillin, an inhibitor of methionine aminopeptidase-2, causes weight loss by reducing food intake, but with effects on weight that are superior to pair-feeding. Here, we show that feeding of rats on a high-fat diet supplemented with fumagillin (HF/FG) suppresses the aggressive feeding observed in pair-fed controls (HF/PF) and alters expression of circadian genes relative to the HF/PF group. Multiple indices of reduced energy expenditure are observed in HF/FG but not HF/PF rats. HF/FG rats also exhibit changes in gut hormones linked to food intake, increased energy harvest by gut microbiota, and caloric spilling in the urine. Studies in gnotobiotic mice reveal that effects of fumagillin on energy expenditure but not feeding behavior may be mediated by the gut microbiota. In sum, fumagillin engages weight loss-inducing behavioral and physiologic circuits distinct from those activated by simple caloric restriction.

Physiological mechanisms of sustained fumagillin-induced weight loss

PubMed Central

An, Jie; Patnode, Michael L.; Haldeman, Jonathan M.; Stevens, Robert D.; Ilkayeva, Olga; Bain, James R.; Muehlbauer, Michael J.; Glynn, Erin L.; Thomas, Steven; Muoio, Deborah; Summers, Scott A.; Vath, James E.; Hughes, Thomas E.; Gordon, Jeffrey I.; Newgard, Christopher B.

2018-01-01

Current obesity interventions suffer from lack of durable effects and undesirable complications. Fumagillin, an inhibitor of methionine aminopeptidase-2, causes weight loss by reducing food intake, but with effects on weight that are superior to pair-feeding. Here, we show that feeding of rats on a high-fat diet supplemented with fumagillin (HF/FG) suppresses the aggressive feeding observed in pair-fed controls (HF/PF) and alters expression of circadian genes relative to the HF/PF group. Multiple indices of reduced energy expenditure are observed in HF/FG but not HF/PF rats. HF/FG rats also exhibit changes in gut hormones linked to food intake, increased energy harvest by gut microbiota, and caloric spilling in the urine. Studies in gnotobiotic mice reveal that effects of fumagillin on energy expenditure but not feeding behavior may be mediated by the gut microbiota. In sum, fumagillin engages weight loss–inducing behavioral and physiologic circuits distinct from those activated by simple caloric restriction. PMID:29515039

Eccentric Contraction-Induced Muscle Injury: Reproducible, Quantitative, Physiological Models to Impair Skeletal Muscle’s Capacity to Generate Force

PubMed Central

Call, Jarrod A.; Lowe, Dawn A.

2018-01-01

In order to investigate the molecular and cellular mechanisms of muscle regeneration an experimental injury model is required. Advantages of eccentric contraction-induced injury are that it is a controllable, reproducible, and physiologically relevant model to cause muscle injury, with injury being defined as a loss of force generating capacity. While eccentric contractions can be incorporated into conscious animal study designs such as downhill treadmill running, electrophysiological approaches to elicit eccentric contractions and examine muscle contractility, for example before and after the injurious eccentric contractions, allows researchers to circumvent common issues in determining muscle function in a conscious animal (e.g., unwillingness to participate). Herein, we describe in vitro and in vivo methods that are reliable, repeatable, and truly maximal because the muscle contractions are evoked in a controlled, quantifiable manner independent of subject motivation. Both methods can be used to initiate eccentric contraction-induced injury and are suitable for monitoring functional muscle regeneration hours to days to weeks post-injury. PMID:27492161

The Arabidopsis thaliana aquaporin AtPIP1;2 is a physiologically relevant CO₂ transport facilitator.

PubMed

Heckwolf, Marlies; Pater, Dianne; Hanson, David T; Kaldenhoff, Ralf

2011-09-01

Cellular exchange of carbon dioxide (CO₂) is of extraordinary importance for life. Despite this significance, its molecular mechanisms are still unclear and a matter of controversy. In contrast to other living organisms, plants are physiologically limited by the availability of CO₂. In most plants, net photosynthesis is directly dependent on CO₂ diffusion from the atmosphere to the chloroplast. Thus, it is important to analyze CO₂ transport with regards to its effect on photosynthesis. A mutation of the Arabidopsis thaliana AtPIP1;2 gene, which was characterized as a non-water transporting but CO₂ transport-facilitating aquaporin in heterologous expression systems, correlated with a reduction in photosynthesis under a wide range of atmospheric CO₂ concentrations. Here, we could demonstrate that the effect was caused by reduced CO₂ conductivity in leaf tissue. It is concluded that the AtPIP1;2 gene product limits CO₂ diffusion and photosynthesis in leaves. © 2011 The Authors. The Plant Journal © 2011 Blackwell Publishing Ltd.

Two nematicidal furocoumarins from Ficus carica L. leaves and their physiological effects on pine wood nematode (Bursaphelenchus xylophilus).

PubMed

Guo, Qunqun; Du, Guicai; He, Hongwei; Xu, Hongkai; Guo, Daosen; Li, Ronggui

2016-09-01

The ethanol extract of the Ficus carica L. leaves was tested to show strong nematicidal activity against pine wood nematode (PWN), Bursaphelenchus xylophilus, causing 90.93% corrected mortality within 72 h at 1.0 mg/mL. From the ethyl acetate soluble fraction of the F. carica L. leaves extract, the main nematicidal constituents were obtained by bioassay-guided isolation and identified as linear furocoumarins bergapten (1) and psoralen (2) by mass and NMR spectral data analysis. Bergapten and psoralen had significant nematicidal activity against PWN with the LC50 values of 97.08 aKSnd 115.03  μ g/mL within 72 h, respectively. The two furocoumarins could inhibit the activities of amylase, cellulase and acetylcholinesterase (AchE) from PWN. The morphologies of PWNs changed much after they were treated by bergapten and psoralen. The physiological effects of bergapten and psoralen on PWN might provide helpful clues to elucidate their nematicidal mechanisms.

Low Incubation Temperature Induces DNA Hypomethylation in Lizard Brains.

PubMed

Paredes, Ursula; Radersma, Reinder; Cannell, Naomi; While, Geoffrey M; Uller, Tobias

2016-07-01

Developmental stress can have organizational effects on suites of physiological, morphological, and behavioral characteristics. In lizards, incubation temperature is perhaps the most significant environmental variable affecting embryonic development. Wall lizards (Podarcis muralis) recently introduced by humans from Italy to England experience stressfully cool incubation conditions, which we here show reduce growth and increase the incidence of scale malformations. Using a methylation-sensitive AFLP protocol optimized for vertebrates, we demonstrate that this low incubation temperature also causes hypomethylation of DNA in brain tissue. A consistent pattern across methylation-susceptible AFLP loci suggests that hypomethylation is a general response and not limited to certain CpG sites. The functional consequences of hypomethylation are unknown, but it could contribute to genome stability and regulation of gene expression. Further studies of the effects of incubation temperature on DNA methylation in ectotherm vertebrates may reveal mechanisms that explain why the embryonic thermal environment often has physiological and behavioral consequences for offspring. © 2016 Wiley Periodicals, Inc.

Computational cardiology and risk stratification for sudden cardiac death: one of the grand challenges for cardiology in the 21st century.

PubMed

Hill, Adam P; Perry, Matthew D; Abi-Gerges, Najah; Couderc, Jean-Philippe; Fermini, Bernard; Hancox, Jules C; Knollmann, Bjorn C; Mirams, Gary R; Skinner, Jon; Zareba, Wojciech; Vandenberg, Jamie I

2016-12-01

Risk stratification in the context of sudden cardiac death has been acknowledged as one of the major challenges facing cardiology for the past four decades. In recent years, the advent of high performance computing has facilitated organ-level simulation of the heart, meaning we can now examine the causes, mechanisms and impact of cardiac dysfunction in silico. As a result, computational cardiology, largely driven by the Physiome project, now stands at the threshold of clinical utility in regards to risk stratification and treatment of patients at risk of sudden cardiac death. In this white paper, we outline a roadmap of what needs to be done to make this translational step, using the relatively well-developed case of acquired or drug-induced long QT syndrome as an exemplar case. © 2016 The Authors. The Journal of Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.

Antiangiogenic immunotherapy targeting Flk-1, DNA vaccine and adoptive T cell transfer, inhibits ocular neovascularization.

PubMed

Zhang, Han; Sonoda, Koh-Hei; Hijioka, Kuniaki; Qiao, Hong; Oshima, Yuji; Ishibashi, Tatsuro

2009-04-17

Ocular neovascularization (NV) is the primary cause of blindness in a wide range of ocular diseases. The exact mechanism underlying the pathogenesis of ocular NV is not yet well understood, and so there is no satisfactory therapy for ocular NV. Here, we describe a strategy targeting Flk-1, a self-antigen overexpressed on proliferating endothelial cells in ocular NV, by antiangiogenic immunotherapy-DNA vaccine and adoptive T cell therapy. An oral DNA vaccine encoding Flk-1 carried by attenuated Salmonella typhimurium markedly suppressed development of laser-induced choroidal NV. We further demonstrated that adoptive transfer of vaccine-induced CD8+ T cells reduced pathological preretinal NV, with a concomitant facilitation of physiological revascularization after oxygen-induced retinal vessel obliteration. However, physiological retinal vascular development was unaffected in neonatal mice transferred with vaccine-induced CD8+ T cells. These findings suggested that antiangiogenic immunotherapy targeting Flk-1 such as vaccination and adoptive immunotherapy may contribute to future therapies for ocular NV.

A graphical simulation software for instruction in cardiovascular mechanics physiology.

PubMed

Wildhaber, Reto A; Verrey, François; Wenger, Roland H

2011-01-25

Computer supported, interactive e-learning systems are widely used in the teaching of physiology. However, the currently available complimentary software tools in the field of the physiology of cardiovascular mechanics have not yet been adapted to the latest systems software. Therefore, a simple-to-use replacement for undergraduate and graduate students' education was needed, including an up-to-date graphical software that is validated and field-tested. Software compatible to Windows, based on modified versions of existing mathematical algorithms, has been newly developed. Testing was performed during a full term of physiological lecturing to medical and biology students. The newly developed CLabUZH software models a reduced human cardiovascular loop containing all basic compartments: an isolated heart including an artificial electrical stimulator, main vessels and the peripheral resistive components. Students can alter several physiological parameters interactively. The resulting output variables are printed in x-y diagrams and in addition shown in an animated, graphical model. CLabUZH offers insight into the relations of volume, pressure and time dependency in the circulation and their correlation to the electrocardiogram (ECG). Established mechanisms such as the Frank-Starling Law or the Windkessel Effect are considered in this model. The CLabUZH software is self-contained with no extra installation required and runs on most of today's personal computer systems. CLabUZH is a user-friendly interactive computer programme that has proved to be useful in teaching the basic physiological principles of heart mechanics.

Cavopulmonary support with a microaxial pump for the failing Fontan physiology.

PubMed

Zhu, Jiaquan; Kato, Hideyuki; Fu, Yaqin Y; Zhao, Lisa; Foreman, Celeste; Davey, Lisa; Weisel, Richard D; Van Arsdell, Glen S; Honjo, Osami

2015-01-01

The number of patients with the failing Fontan physiology is increasing. We tested a novel in situ microaxial pump (Impella) to support the failing atrio-pulmonary Fontan circulation in an acute pig model. A Fontan model was established in eight juvenile pigs by connecting the right atrium to the main pulmonary artery after tricuspid valve destruction. The Impella pump was inserted retrograde from the distal main pulmonary artery into the right atrium. Hemodynamics, blood gas, and echocardiographic data were compared among baseline, pure Fontan physiology (10 minutes), and mechanically assisted Fontan physiology (up to 12 hours). The Impella system generated a blood flow of 75-85 ml/kg/minute in six animals, and 55-65 ml/kg/minute in two animals. The mechanically assisted Fontan attained a significantly higher mean blood pressure (39.6 ± 7 vs. 24.7 ± 3.3 mm Hg, p < 0.01), lower central venous pressure (5 ± 2.4 vs. 12.8 ± 1.7 mm Hg, p < 0.01), and higher mixed venous saturation (60.4 ± 10.8 vs. 23.4 ± 8.4 mm Hg, p < 0.01) compared with pure Fontan physiology. Cardiac output and stroke volume were similar during baseline and mechanically assisted Fontan (p = not significant). This acute pig study demonstrated the feasibility of mechanical circulatory support in the failing Fontan physiology. The in situ microaxial pump maintained cardiac output while increasing blood pressure and reducing venous pressure.

Human Physiology in an Aquatic Environment.

PubMed

Pendergast, David R; Moon, Richard E; Krasney, John J; Held, Heather E; Zamparo, Paola

2015-09-20

Water covers over 70% of the earth, has varying depths and temperatures and contains much of the earth's resources. Head-out water immersion (HOWI) or submersion at various depths (diving) in water of thermoneutral (TN) temperature elicits profound cardiorespiratory, endocrine, and renal responses. The translocation of blood into the thorax and elevation of plasma volume by autotransfusion of fluid from cells to the vascular compartment lead to increased cardiac stroke volume and output and there is a hyperperfusion of some tissues. Pulmonary artery and capillary hydrostatic pressures increase causing a decline in vital capacity with the potential for pulmonary edema. Atrial stretch and increased arterial pressure cause reflex autonomic responses which result in endocrine changes that return plasma volume and arterial pressure to preimmersion levels. Plasma volume is regulated via a reflex diuresis and natriuresis. Hydrostatic pressure also leads to elastic loading of the chest, increasing work of breathing, energy cost, and thus blood flow to respiratory muscles. Decreases in water temperature in HOWI do not affect the cardiac output compared to TN; however, they influence heart rate and the distribution of muscle and fat blood flow. The reduced muscle blood flow results in a reduced maximal oxygen consumption. The properties of water determine the mechanical load and the physiological responses during exercise in water (e.g. swimming and water based activities). Increased hydrostatic pressure caused by submersion does not affect stroke volume; however, progressive bradycardia decreases cardiac output. During submersion, compressed gas must be breathed which introduces the potential for oxygen toxicity, narcosis due to nitrogen, and tissue and vascular gas bubbles during decompression and after may cause pain in joints and the nervous system. Copyright © 2015 John Wiley & Sons, Inc.

Underlying mechanism of the cyclic migrating motor complex in Suncus murinus: a change in gastrointestinal pH is the key regulator.

PubMed

Mondal, Anupom; Koyama, Kouhei; Mikami, Takashi; Horita, Taichi; Takemi, Shota; Tsuda, Sachiko; Sakata, Ichiro; Sakai, Takafumi

2017-01-01

In the fasted gastrointestinal (GI) tract, a characteristic cyclical rhythmic migrating motor complex (MMC) occurs in an ultradian rhythm, at 90-120 min time intervals, in many species. However, the underlying mechanism directing this ultradian rhythmic MMC pattern is yet to be completely elucidated. Therefore, this study aimed to identify the possible causes or factors that involve in the occurrence of the fasting gastric contractions by using Suncus murinus a small model animal featuring almost the same rhythmic MMC as that found in humans and dogs. We observed that either intraduodenal infusion of saline at pH 8 evoked the strong gastric contraction or continuously lowering duodenal pH to 3-evoked gastric phase II-like and phase III-like contractions, and both strong contractions were essentially abolished by the intravenous administration of MA 2029 (motilin receptor antagonist) and D-Lys3-GHRP6 (ghrelin receptor antagonist) in a vagus-independent manner. Moreover, we observed that the prostaglandin E2-alpha (PGE2 - α) and serotonin type 4 (5HT4) receptors play important roles as intermediate molecules in changes in GI pH and motilin release. These results suggest a clear insight mechanism that change in the duodenal pH to alkaline condition is an essential factor for stimulating the endogenous release of motilin and governs the fasting MMC in a vagus-independent manner. Finally, we believe that the changes in duodenal pH triggered by flowing gastric acid and the release of duodenal bicarbonate through the involvement of PGE2 - α and 5HT4 receptor are the key events in the occurrence of the MMC. © 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

The 34th Annual Fall Meeting of the American Physiological Society and the International Conference on Hydrogen Ion Transport in Epithelia.

ERIC Educational Resources Information Center

Physiologist, 1983

1983-01-01

Provided are abstracts of papers presented at the annual American Physiological Society meeting and International Conference on Hydrogen Ion Transport in Epithelia. Papers are grouped by such topic areas as lung fluid balance, renal cardiovascular integration, smooth muscle physiology, neuroendocrines (pituitary), exercise physiology, mechanics of…

Predictable 'meta-mechanisms' emerge from feedbacks between transpiration and plant growth and cannot be simply deduced from short-term mechanisms.

PubMed

Tardieu, François; Parent, Boris

2017-06-01

Growth under water deficit is controlled by short-term mechanisms but, because of numerous feedbacks, the combination of these mechanisms over time often results in outputs that cannot be deduced from the simple inspection of individual mechanisms. It can be analysed with dynamic models in which causal relationships between variables are considered at each time-step, allowing calculation of outputs that are routed back to inputs for the next time-step and that can change the system itself. We first review physiological mechanisms involved in seven feedbacks of transpiration on plant growth, involving changes in tissue hydraulic conductance, stomatal conductance, plant architecture and underlying factors such as hormones or aquaporins. The combination of these mechanisms over time can result in non-straightforward conclusions as shown by examples of simulation outputs: 'over production of abscisic acid (ABA) can cause a lower concentration of ABA in the xylem sap ', 'decreasing root hydraulic conductance when evaporative demand is maximum can improve plant performance' and 'rapid root growth can decrease yield'. Systems of equations simulating feedbacks over numerous time-steps result in logical and reproducible emergent properties that can be viewed as 'meta-mechanisms' at plant level, which have similar roles as mechanisms at cell level. © 2016 John Wiley & Sons Ltd.

Validation of Intensive Care and Mechanical Ventilation Codes in Medicare Data.

PubMed

Wunsch, Hannah; Kramer, Andrew; Gershengorn, Hayley B

2017-07-01

To assess the reliability of codes relevant to critically ill patients in administrative data. Retrospective cohort study linking data from Acute Physiology and Chronic Health Evaluation Outcomes, a clinical database of ICU patients with data from Medicare Provider Analysis and Review. We linked data based on matching for sex, date of birth, hospital, and date of admission to hospital. Forty-six hospitals in the United States participating in Acute Physiology and Chronic Health Evaluation Outcomes. All patients in Acute Physiology and Chronic Health Evaluation Outcomes greater than or equal to 65 years old who could be linked with hospitalization records in Medicare Provider Analysis and Review from January 1, 2009, through September 30, 2012. Of 62,451 patients in the Acute Physiology and Chronic Health Evaluation Outcomes dataset, 80.1% were matched with data in Medicare Provider Analysis and Review. All but 2.7% of Acute Physiology and Chronic Health Evaluation Outcomes ICU patients had either an ICU or coronary care unit charge in Medicare Provider Analysis and Review. In Acute Physiology and Chronic Health Evaluation Outcomes, 37.0% received mechanical ventilation during the ICU stay versus 24.1% in Medicare Provider Analysis and Review. The Medicare Provider Analysis and Review procedure codes for mechanical ventilation had high specificity (96.0%; 95% CI, 95.8-96.2), but only moderate sensitivity (58.4%; 95% CI, 57.7-59.1), with a positive predictive value of 89.6% (95% CI, 89.1-90.1) and negative predictive value of 79.7% (95% CI, 79.4-80.1). For patients with mechanical ventilation codes, Medicare Provider Analysis and Review overestimated the percentage with a duration greater than 96 hours (36.6% vs 27.3% in Acute Physiology and Chronic Health Evaluation Outcomes). There was discordance in the hospital discharge status (alive or dead) for only 0.47% of all linked records (κ = 1.00). Medicare Provider Analysis and Review data contain robust information on hospital mortality for patients admitted to the ICU but have limited ability to identify all patients who received mechanical ventilation during a critical illness. Estimates of use of mechanical ventilation in the United States should likely be revised upward.

Redox-Responsive Fluorescent Probes with Different Design Strategies.

PubMed

Lou, Zhangrong; Li, Peng; Han, Keli

2015-05-19

In an aerobic organism, reactive oxygen species (ROS) are an inevitable metabolic byproduct. Endogenously produced ROS have a significant role in physiological processes, but excess ROS can cause oxidative stress and can damage tissue. Cells possess elaborate mechanisms to regulate their internal redox status. The intracellular redox homeostasis plays an essential role in maintaining cellular function. However, moderate alterations in redox balance can accompany major transitions in a cell's life cycle. Because of the role of ROS in physiology and in pathology, researchers need new tools to study redox chemistry in biological systems.In recent years, researchers have made remarkable progress in developing new, highly sensitive and selective fluorescent probes that respond to redox changes, and in this Account we highlight related research, primarily from our own group. We present an overview of the design, photophysical properties, and fluorescence transduction mechanisms of reported molecules that probe redox changes. We have designed and synthesized a series of fluorescent probes for redox cycles in biological systems relying on the active center of glutathione peroxidase (GPx). We have also constructed probes based on the oxidation and reduction of hydroquinone and of 2,2,6,6-tetramethylpiperidinooxy (TEMPO). Most of these probes exhibit high sensitivity and good selectivity, absorb in the near-infrared, and respond rapidly. Such probes are useful for confocal fluorescence microscopy, a dynamic imaging technique that could allow researchers to observe biologically important ROS and antioxidants in real time. This technique and these probes provide potentially useful tools for exploring the generation, transport, physiological function, and pathogenic mechanisms of ROS and antioxidants.We also describe features that could improve the properties of redox-responsive fluorescent probes: greater photostability; rapid, dynamic, cyclic and ratiometric responses; and broader absorption in the near-IR region. In addition, fluorescent probes that include organochalcogens such as selenium and tellurium show promise for a new class of fluorescent redox probes that are both chemically stable and robustly reversible. However, further investigations of the chemical and fluorescence transduction mechanisms of selenium-based probes in response to ROS are needed.

Protocol of the PLeural Effusion And Symptom Evaluation (PLEASE) study on the pathophysiology of breathlessness in patients with symptomatic pleural effusions.

PubMed

Thomas, Rajesh; Azzopardi, Maree; Muruganandan, Sanjeevan; Read, Catherine; Murray, Kevin; Eastwood, Peter; Jenkins, Sue; Singh, Bhajan; Lee, Y C Gary

2016-08-03

Pleural effusion is a common clinical problem that can complicate many medical conditions. Breathlessness is the most common symptom of pleural effusion of any cause and the most common reason for pleural drainage. However, improvement in breathlessness following drainage of an effusion is variable; some patients experience either no benefit or a worsening of their breathlessness. The physiological mechanisms underlying breathlessness in patients with a pleural effusion are unclear and likely to be multifactorial with patient-related and effusion-related factors contributing. A comprehensive study of the physiological and symptom responses to drainage of pleural effusions may provide a clearer understanding of these mechanisms, and may identify predictors of benefit from drainage. The ability to identify those patients whose breathlessness will (or will not) improve after pleural fluid drainage can help avoid unnecessary pleural drainage procedures, their associated morbidities and costs. The PLeural Effusion And Symptom Evaluation (PLEASE) study is a prospective study to comprehensively evaluate factors contributing to pleural effusion-related breathlessness. The PLEASE study is a single-centre prospective study of 150 patients with symptomatic pleural effusions that require therapeutic drainage. The study aims to identify key factors that underlie breathlessness in patients with pleural effusions and develop predictors of improvement in breathlessness following effusion drainage. Participants will undergo evaluation pre-effusion and post-effusion drainage to assess their level of breathlessness at rest and during exercise, respiratory and other physiological responses as well as respiratory muscle mechanics. Pre-drainage and post-drainage parameters will be collected and compared to identify the key factors and mechanisms that correlate with improvement in breathlessness. Approved by the Sir Charles Gairdner Group Human Research Ethics Committee (HREC number 2014-079). Registered with the Australian New Zealand Clinical Trials Registry (ACTRN12616000820404). Results will be published in peer-reviewed journals and presented at scientific meetings. ACTRN12616000820404; Pre-results. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

The pathophysiology of migraine: implications for clinical management.

PubMed

Charles, Andrew

2018-02-01

The understanding of migraine pathophysiology is advancing rapidly. Improved characterisation and diagnosis of its clinical features have led to the view of migraine as a complex, variable disorder of nervous system function rather than simply a vascular headache. Recent studies have provided important new insights into its genetic causes, anatomical and physiological features, and pharmacological mechanisms. The identification of new migraine-associated genes, the visualisation of brain regions that are activated at the earliest stages of a migraine attack, a greater appreciation of the potential role of the cervical nerves, and the recognition of the crucial role for neuropeptides are among the advances that have led to novel targets for migraine therapy. Future management of migraine will have the capacity to tailor treatments based on the distinct mechanisms of migraine that affect individual patients. Copyright © 2018 Elsevier Ltd. All rights reserved.

Motion Artifact Reduction in Ultrasound Based Thermal Strain Imaging of Atherosclerotic Plaques Using Time Series Analysis

PubMed Central

Dutta, Debaditya; Mahmoud, Ahmed M.; Leers, Steven A.; Kim, Kang

2013-01-01

Large lipid pools in vulnerable plaques, in principle, can be detected using US based thermal strain imaging (US-TSI). One practical challenge for in vivo cardiovascular application of US-TSI is that the thermal strain is masked by the mechanical strain caused by cardiac pulsation. ECG gating is a widely adopted method for cardiac motion compensation, but it is often susceptible to electrical and physiological noise. In this paper, we present an alternative time series analysis approach to separate thermal strain from the mechanical strain without using ECG. The performance and feasibility of the time-series analysis technique was tested via numerical simulation as well as in vitro water tank experiments using a vessel mimicking phantom and an excised human atherosclerotic artery where the cardiac pulsation is simulated by a pulsatile pump. PMID:24808628

The Pathophysiology of Malabsorption

PubMed Central

Keller, Jutta; Layer, Peter

2014-01-01

Summary Physiological digestion and absorption of nutrients within the gastrointestinal tract requires a complex interaction between motor, secretory, digestive, and absorptive functions that is vulnerable to a multitude of potential disturbances which may lead to global or specific malabsorption syndromes. Potential pathomechanisms that are illustrated in this article include insufficient mechanical breakdown of harder food components due to chewing problems and/or decreased antral contractility, critical reduction of time for absorption in patients with markedly enhanced upper gastrointestinal transit (e.g. dumping syndrome), impaired digestion and absorption of nutrient components caused by reduced gastric acid secretion, pancreatic exocrine insufficiency or reduced biliary secretion, defects of the enteral mucosa with enzyme deficiencies (e.g. disaccharidases) or lack of specific carrier mechanisms (e.g. hexose or aminoacid transporters), and critical quantitative loss of intestinal mucosa in patients with short bowel syndrome. PMID:26288588

[Change in laryngeal vibratory mechanism: a physiological entity].

PubMed

Roubeau, B; Chevrie-Muller, C; Arabia, C; Arragon, C

1993-01-01

The purpose of this paper is to examine the change of laryngeal vibratory mechanism in 10 males and 9 females trained and untrained singers. The electroglottographic (E.G.G.) data analysis demonstrated strong evidence to support the view that such event could be considered as a whole physiological entity. In fact findings clearly indicated biomechanical, neuromuscular and central levels in the control of the laryngeal vibration involved in the change of mechanism.

AFM of the ultrastructural and mechanical properties of lipid-raft-disrupted and/or cold-treated endothelial cells.

PubMed

Wu, Li; Huang, Jie; Yu, Xiaoxue; Zhou, Xiaoqing; Gan, Chaoye; Li, Ming; Chen, Yong

2014-02-01

The nonionic detergent extraction at 4 °C and the cholesterol-depletion-induced lipid raft disruption are the two widely used experimental strategies for lipid raft research. However, the effects of raft disruption and/or cold treatment on the ultrastructural and mechanical properties of cells are still unclear. Here, we evaluated the effects of raft disruption and/or cold (4 °C) treatment on these properties of living human umbilical vein endothelial cells (HUVECs). At first, the cholesterol-depletion-induced raft disruption was visualized by confocal microscopy and atomic force microscopy (AFM) in combination with fluorescent quantum dots. Next, the cold-induced cell contraction and the formation of end-branched filopodia were observed by confocal microscopy and AFM. Then, the cell-surface ultrastructures were imaged by AFM, and the data showed that raft disruption and cold treatment induced opposite effects on cell-surface roughness (a significant decrease and a significant increase, respectively). Moreover, the cell-surface mechanical properties (stiffness and adhesion force) of raft-disrupted- and/or cold-treated HUVECs were measured by the force measurement function of AFM. We found that raft disruption and cold treatment induced parallel effects on cell stiffness (increase) or adhesion force (decrease) and that the combination of the two treatments caused dramatically strengthened effects. Finally, raft disruption was found to significantly impair cell migration as previously reported, whereas temporary cold treatment only caused a slight but nonsignificant decrease in cell migration performed at physiological temperature. Although the mechanisms for causing these results might be complicated and more in-depth studies will be needed, our data may provide important information for better understanding the effects of raft disruption or cold treatment on cells and the two strategies for lipid raft research.

Characteristics and mechanisms of cardiopulmonary injury caused by mine blasts in shoals: a randomized controlled study in a rabbit model.

PubMed

Han, Gengfen; Wang, Ziming; Wang, Jianmin; Yang, Weixiao; Chen, Jing; Kang, Jianyi; Zhang, Sen; Wang, Aimin; Lai, Xinan

2013-01-01

Because the characteristics of blast waves in water are different from those in air and because kinetic energy is liberated by a pressure wave at the water-air interface, thoracic injuries from mine blasts in shoals may be serious. The aim of the present study was to investigate the characteristics and mechanisms of cardiopulmonary injury caused by mine blasts in shoals. To study the characteristics of cardiopulmonary injury, 56 animals were divided randomly into three experimental groups (12 animals in the sham group, 22 animals in the land group and 22 animals in the shoal group). To examine the biomechanics of injury, 20 animals were divided randomly into the land group and the shoal group. In the experimental model, the water surface was at the level of the rabbit's xiphoid process, and paper electric detonators (600 mg RDX) were used to simulate mines. Electrocardiography and echocardiography were conducted, and arterial blood gases, serum levels of cardiac troponin I and creatine kinase-MB and other physiologic parameters were measured over a 12-hour period after detonation. Pressures in the thorax and abdomen and the acceleration of the thorax were measured. The results indicate that severe cardiopulmonary injury and dysfunction occur following exposure to mine blasts in shoals. Therefore, the mechanisms of cardiopulmonary injury may result from shear waves that produce strain at the water-air interface. Another mechanism of injury includes the propagation of the shock wave from the planta to the thorax, which causes a much higher peak overpressure in the abdomen than in the thorax; as a result, the abdominal organs and diaphragm are thrust into the thorax, damaging the lungs and heart.

Estimated Tissue and Blood N(2) Levels and Risk of Decompression Sickness in Deep-, Intermediate-, and Shallow-Diving Toothed Whales during Exposure to Naval Sonar.

PubMed

Kvadsheim, P H; Miller, P J O; Tyack, P L; Sivle, L D; Lam, F P A; Fahlman, A

2012-01-01

Naval sonar has been accused of causing whale stranding by a mechanism which increases formation of tissue N(2) gas bubbles. Increased tissue and blood N(2) levels, and thereby increased risk of decompression sickness (DCS), is thought to result from changes in behavior or physiological responses during diving. Previous theoretical studies have used hypothetical sonar-induced changes in both behavior and physiology to model blood and tissue N(2) tension [Formula: see text], but this is the first attempt to estimate the changes during actual behavioral responses to sonar. We used an existing mathematical model to estimate blood and tissue N(2) tension [Formula: see text] from dive data recorded from sperm, killer, long-finned pilot, Blainville's beaked, and Cuvier's beaked whales before and during exposure to Low- (1-2 kHz) and Mid- (2-7 kHz) frequency active sonar. Our objectives were: (1) to determine if differences in dive behavior affects risk of bubble formation, and if (2) behavioral- or (3) physiological responses to sonar are plausible risk factors. Our results suggest that all species have natural high N(2) levels, with deep diving generally resulting in higher end-dive [Formula: see text] as compared with shallow diving. Sonar exposure caused some changes in dive behavior in both killer whales, pilot whales and beaked whales, but this did not lead to any increased risk of DCS. However, in three of eight exposure session with sperm whales, the animal changed to shallower diving, and in all these cases this seem to result in an increased risk of DCS, although risk was still within the normal risk range of this species. When a hypothetical removal of the normal dive response (bradycardia and peripheral vasoconstriction), was added to the behavioral response during model simulations, this led to an increased variance in the estimated end-dive N(2) levels, but no consistent change of risk. In conclusion, we cannot rule out the possibility that a combination of behavioral and physiological responses to sonar have the potential to alter the blood and tissue end-dive N(2) tension to levels which could cause DCS and formation of in vivo bubbles, but the actually observed behavioral responses of cetaceans to sonar in our study, do not imply any significantly increased risk of DCS.

Plant physiology and proteomics reveals the leaf response to drought in alfalfa (Medicago sativa L.)

PubMed Central

Aranjuelo, Iker; Molero, Gemma; Erice, Gorka; Avice, Jean Christophe; Nogués, Salvador

2011-01-01

Despite its relevance, protein regulation, metabolic adjustment, and the physiological status of plants under drought is not well understood in relation to the role of nitrogen fixation in nodules. In this study, nodulated alfalfa plants were exposed to drought conditions. The study determined the physiological, metabolic, and proteomic processes involved in photosynthetic inhibition in relation to the decrease in nitrogenase (Nase) activity. The deleterious effect of drought on alfalfa performance was targeted towards photosynthesis and Nase activity. At the leaf level, photosynthetic inhibition was mainly caused by the inhibition of Rubisco. The proteomic profile and physiological measurements revealed that the reduced carboxylation capacity of droughted plants was related to limitations in Rubisco protein content, activation state, and RuBP regeneration. Drought also decreased amino acid content such as asparagine, and glutamic acid, and Rubisco protein content indicating that N availability limitations were caused by Nase activity inhibition. In this context, drought induced the decrease in Rubisco binding protein content at the leaf level and proteases were up-regulated so as to degrade Rubisco protein. This degradation enabled the reallocation of the Rubisco-derived N to the synthesis of amino acids with osmoregulant capacity. Rubisco degradation under drought conditions was induced so as to remobilize Rubisco-derived N to compensate for the decrease in N associated with Nase inhibition. Metabolic analyses showed that droughted plants increased amino acid (proline, a major compound involved in osmotic regulation) and soluble sugar (D-pinitol) levels to contribute towards the decrease in osmotic potential (Ψs). At the nodule level, drought had an inhibitory effect on Nase activity. This decrease in Nase activity was not induced by substrate shortage, as reflected by an increase in total soluble sugars (TSS) in the nodules. Proline accumulation in the nodule could also be associated with an osmoregulatory response to drought and might function as a protective agent against ROS. In droughted nodules, the decrease in N2 fixation was caused by an increase in oxygen resistance that was induced in the nodule. This was a mechanism to avoid oxidative damage associated with reduced respiration activity and the consequent increase in oxygen content. This study highlighted that even though drought had a direct effect on leaves, the deleterious effects of drought on nodules also conditioned leaf responsiveness. PMID:20797998

Combined application of compost and Bacillus sp. CIK-512 ameliorated the lead toxicity in radish by regulating the homeostasis of antioxidants and lead.

PubMed

Ahmad, Iftikhar; Akhtar, Muhammad Javed; Mehmood, Shehzad; Akhter, Kalsoom; Tahir, Muhammad; Saeed, Muhammad Farhan; Hussain, Muhammad Baqir; Hussain, Saddam

2018-02-01

Lead (Pb) contamination is ubiquitous and usually causes toxicity to plants. Nevertheless, application of compost and plant growth promoting rhizobacteria synergistically may ameliorate the Pb toxicity in radish. The present study assessed the effects of compost and Bacillus sp. CIK-512 on growth, physiology, antioxidants and uptake of Pb in contaminated soil and explored the possible mechanism for Pb phytotoxicity amelioration. Treatments comprised of un-inoculated control, compost, CIK-512, and compost + CIK-512; plants were grown in soil contaminated with Pb (500mgkg -1 ) and without Pb in pot culture. Lead caused reduction in shoot dry biomass, photosynthetic rate, stomatal conductance, relative water contents, whereas enhanced root dry biomass, ascorbate peroxidase, catalase, malondialdehyde and electrolyte leakage in comparison with non-contaminated control. Plants inoculated with strain CIK-512 and compost produced significantly higher dry biomass, photosynthetic rate and stomatal conductance in normal and contaminated soils. Bacterial strain CIK-512 and compost synergy improved growth and physiology of radish in contaminated soil possibly through homeostasis of antioxidant activities, reduced membrane leakage and Pb accumulation in shoot. Possibly, Pb-induced production of reactive oxygen species resulted in increased electrolyte leakage and malondialdehyde contents (r = 0.88-0.92), which led to reduction in growth (r = -0.97) and physiology (r = -0.38 to -0.80), however, such negative effects were ameliorated by the regulation of antioxidants (r = 0.78-0.87). The decreased activity of antioxidants coupled with Pb accumulation in aerial part of the radish indicates the Pb-phytotoxicity amelioration through synergistic application of compost and Bacillus sp. CIK-512. Copyright © 2017 Elsevier Inc. All rights reserved.

The targeted anti-oxidant MitoQ causes mitochondrial swelling and depolarization in kidney tissue.

PubMed

Gottwald, Esther M; Duss, Michael; Bugarski, Milica; Haenni, Dominik; Schuh, Claus D; Landau, Ehud M; Hall, Andrew M

2018-04-01

Kidney proximal tubules (PTs) contain a high density of mitochondria, which are required to generate ATP to power solute transport. Mitochondrial dysfunction is implicated in the pathogenesis of numerous kidney diseases. Damaged mitochondria are thought to produce excess reactive oxygen species (ROS), which can lead to oxidative stress and activation of cell death pathways. MitoQ is a mitochondrial targeted anti-oxidant that has shown promise in preclinical models of renal diseases. However, recent studies in nonkidney cells have suggested that MitoQ might also have adverse effects. Here, using a live imaging approach, and both in vitro and ex vivo models, we show that MitoQ induces rapid swelling and depolarization of mitochondria in PT cells, but these effects were not observed with SS-31, another targeted anti-oxidant. MitoQ consists of a lipophilic cation (Tetraphenylphosphonium [TPP]) joined to an anti-oxidant component (quinone) by a 10-carbon alkyl chain, which is thought to insert into the inner mitochondrial membrane (IMM). We found that mitochondrial swelling and depolarization was also induced by dodecyltriphenylphosphomium (DTPP), which consists of TPP and the alkyl chain, but not by TPP alone. Surprisingly, MitoQ-induced mitochondrial swelling occurred in the absence of a decrease in oxygen consumption rate. We also found that DTPP directly increased the permeability of artificial liposomes with a cardiolipin content similar to that of the IMM. In summary, MitoQ causes mitochondrial swelling and depolarization in PT cells by a mechanism unrelated to anti-oxidant activity, most likely because of increased IMM permeability due to insertion of the alkyl chain. © 2018 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

Sickle cell anemia mice develop a unique cardiomyopathy with restrictive physiology

PubMed Central

Bakeer, Nihal; James, Jeanne; Roy, Swarnava; Wansapura, Janaka; Shanmukhappa, Shiva Kumar; Lorenz, John N.; Osinska, Hanna; Backer, Kurt; Huby, Anne-Cecile; Shrestha, Archana; Niss, Omar; Fleck, Robert; Quinn, Charles T.; Taylor, Michael D.; Purevjav, Enkhsaikhan; Aronow, Bruce J.; Towbin, Jeffrey A.; Malik, Punam

2016-01-01

Cardiopulmonary complications are the leading cause of mortality in sickle cell anemia (SCA). Elevated tricuspid regurgitant jet velocity, pulmonary hypertension, diastolic, and autonomic dysfunction have all been described, but a unifying pathophysiology and mechanism explaining the poor prognosis and propensity to sudden death has been elusive. Herein, SCA mice underwent a longitudinal comprehensive cardiac analysis, combining state-of-the-art cardiac imaging with electrocardiography, histopathology, and molecular analysis to determine the basis of cardiac dysfunction. We show that in SCA mice, anemia-induced hyperdynamic physiology was gradually superimposed with restrictive physiology, characterized by progressive left atrial enlargement and diastolic dysfunction with preserved systolic function. This phenomenon was absent in WT mice with experimentally induced chronic anemia of similar degree and duration. Restrictive physiology was associated with microscopic cardiomyocyte loss and secondary fibrosis detectable as increased extracellular volume by cardiac-MRI. Ultrastructural mitochondrial changes were consistent with severe chronic hypoxia/ischemia and sarcomere diastolic-length was shortened. Transcriptome analysis revealed up-regulation of genes involving angiogenesis, extracellular-matrix, circadian-rhythm, oxidative stress, and hypoxia, whereas ion-channel transport and cardiac conduction were down-regulated. Indeed, progressive corrected QT prolongation, arrhythmias, and ischemic changes were noted in SCA mice before sudden death. Sudden cardiac death is common in humans with restrictive cardiomyopathies and long QT syndromes. Our findings may thus provide a unifying cardiac pathophysiology that explains the reported cardiac abnormalities and sudden death seen in humans with SCA. PMID:27503873

The cardiovascular system after exercise.

PubMed

Romero, Steven A; Minson, Christopher T; Halliwill, John R

2017-04-01

Recovery from exercise refers to the time period between the end of a bout of exercise and the subsequent return to a resting or recovered state. It also refers to specific physiological processes or states occurring after exercise that are distinct from the physiology of either the exercising or the resting states. In this context, recovery of the cardiovascular system after exercise occurs across a period of minutes to hours, during which many characteristics of the system, even how it is controlled, change over time. Some of these changes may be necessary for long-term adaptation to exercise training, yet some can lead to cardiovascular instability during recovery. Furthermore, some of these changes may provide insight into when the cardiovascular system has recovered from prior training and is physiologically ready for additional training stress. This review focuses on the most consistently observed hemodynamic adjustments and the underlying causes that drive cardiovascular recovery and will highlight how they differ following resistance and aerobic exercise. Primary emphasis will be placed on the hypotensive effect of aerobic and resistance exercise and associated mechanisms that have clinical relevance, but if left unchecked, can progress to symptomatic hypotension and syncope. Finally, we focus on the practical application of this information to strategies to maximize the benefits of cardiovascular recovery, or minimize the vulnerabilities of this state. We will explore appropriate field measures, and discuss to what extent these can guide an athlete's training. Copyright © 2017 the American Physiological Society.

ALS mutations in FUS cause neuronal dysfunction and death in Caenorhabditis elegans by a dominant gain-of-function mechanism

PubMed Central

Murakami, Tetsuro; Yang, Seung-Pil; Xie, Lin; Kawano, Taizo; Fu, Donald; Mukai, Asuka; Bohm, Christopher; Chen, Fusheng; Robertson, Janice; Suzuki, Hiroshi; Tartaglia, Gian Gaetano; Vendruscolo, Michele; Kaminski Schierle, Gabriele S.; Chan, Fiona T.S.; Moloney, Aileen; Crowther, Damian; Kaminski, Clemens F.; Zhen, Mei; St George-Hyslop, Peter

2012-01-01

It is unclear whether mutations in fused in sarcoma (FUS) cause familial amyotrophic lateral sclerosis via a loss-of-function effect due to titrating FUS from the nucleus or a gain-of-function effect from cytoplasmic overabundance. To investigate this question, we generated a series of independent Caenorhabditis elegans lines expressing mutant or wild-type (WT) human FUS. We show that mutant FUS, but not WT-FUS, causes cytoplasmic mislocalization associated with progressive motor dysfunction and reduced lifespan. The severity of the mutant phenotype in C. elegans was directly correlated with the severity of the illness caused by the same mutation in humans, arguing that this model closely replicates key features of the human illness. Importantly, the mutant phenotype could not be rescued by overexpression of WT-FUS, even though WT-FUS had physiological intracellular localization, and was not recruited to the cytoplasmic mutant FUS aggregates. Our data suggest that FUS mutants cause neuronal dysfunction by a dominant gain-of-function effect related either to neurotoxic aggregates of mutant FUS in the cytoplasm or to dysfunction in its RNA-binding functions. PMID:21949354

ALS mutations in FUS cause neuronal dysfunction and death in Caenorhabditis elegans by a dominant gain-of-function mechanism.

PubMed

Murakami, Tetsuro; Yang, Seung-Pil; Xie, Lin; Kawano, Taizo; Fu, Donald; Mukai, Asuka; Bohm, Christopher; Chen, Fusheng; Robertson, Janice; Suzuki, Hiroshi; Tartaglia, Gian Gaetano; Vendruscolo, Michele; Kaminski Schierle, Gabriele S; Chan, Fiona T S; Moloney, Aileen; Crowther, Damian; Kaminski, Clemens F; Zhen, Mei; St George-Hyslop, Peter

2012-01-01

It is unclear whether mutations in fused in sarcoma (FUS) cause familial amyotrophic lateral sclerosis via a loss-of-function effect due to titrating FUS from the nucleus or a gain-of-function effect from cytoplasmic overabundance. To investigate this question, we generated a series of independent Caenorhabditis elegans lines expressing mutant or wild-type (WT) human FUS. We show that mutant FUS, but not WT-FUS, causes cytoplasmic mislocalization associated with progressive motor dysfunction and reduced lifespan. The severity of the mutant phenotype in C. elegans was directly correlated with the severity of the illness caused by the same mutation in humans, arguing that this model closely replicates key features of the human illness. Importantly, the mutant phenotype could not be rescued by overexpression of WT-FUS, even though WT-FUS had physiological intracellular localization, and was not recruited to the cytoplasmic mutant FUS aggregates. Our data suggest that FUS mutants cause neuronal dysfunction by a dominant gain-of-function effect related either to neurotoxic aggregates of mutant FUS in the cytoplasm or to dysfunction in its RNA-binding functions.

Biological causal links on physiological and evolutionary time scales.

PubMed

Karmon, Amit; Pilpel, Yitzhak

2016-04-26

Correlation does not imply causation. If two variables, say A and B, are correlated, it could be because A causes B, or that B causes A, or because a third factor affects them both. We suggest that in many cases in biology, the causal link might be bi-directional: A causes B through a fast-acting physiological process, while B causes A through a slowly accumulating evolutionary process. Furthermore, many trained biologists tend to consistently focus at first on the fast-acting direction, and overlook the slower process in the opposite direction. We analyse several examples from modern biology that demonstrate this bias (codon usage optimality and gene expression, gene duplication and genetic dispensability, stem cell division and cancer risk, and the microbiome and host metabolism) and also discuss an example from linguistics. These examples demonstrate mutual effects between the fast physiological processes and the slow evolutionary ones. We believe that building awareness of inference biases among biologists who tend to prefer one causal direction over another could improve scientific reasoning.

Mapping of Mechanical Strains and Stresses around Quiescent Engineered Three-Dimensional Epithelial Tissues

PubMed Central

Gjorevski, Nikolce; Nelson, Celeste M.

2012-01-01

Understanding how physical signals guide biological processes requires qualitative and quantitative knowledge of the mechanical forces generated and sensed by cells in a physiologically realistic three-dimensional (3D) context. Here, we used computational modeling and engineered epithelial tissues of precise geometry to define the experimental parameters that are required to measure directly the mechanical stress profile of 3D tissues embedded within native type I collagen. We found that to calculate the stresses accurately in these settings, we had to account for mechanical heterogeneities within the matrix, which we visualized and quantified using confocal reflectance and atomic force microscopy. Using this technique, we were able to obtain traction forces at the epithelium-matrix interface, and to resolve and quantify patterns of mechanical stress throughout the surrounding matrix. We discovered that whereas single cells generate tension by contracting and pulling on the matrix, the contraction of multicellular tissues can also push against the matrix, causing emergent compression. Furthermore, tissue geometry defines the spatial distribution of mechanical stress across the epithelium, which communicates mechanically over distances spanning hundreds of micrometers. Spatially resolved mechanical maps can provide insight into the types and magnitudes of physical parameters that are sensed and interpreted by multicellular tissues during normal and pathological processes. PMID:22828342

The mechanical and morphological properties of bone beneath internal fixation plates of differing rigidity.

PubMed

Claes, L

1989-01-01

The internal fixation of diaphyseal fractures by bone plates is a well recognized treatment. The normal physiological stress of bone is reduced by plates that cause a negative balance of bone-remodeling processes. Many investigators have shown that the degree of stress protection is dependent on the rigidity of the plates. It was the aim of this study to quantify mechanical and morphological changes at different locations in a plated diaphyseal bone as a function of differing plate rigidity. Two types of plates with the same size but different materials were used. The stainless steel plates had a modulus of elasticity and bending stiffness 3.2 times higher than the carbon fiber reinforced carbon plates. Both types of plates were applied to the intact right and left femora of six foxhounds for 6 months. The stiffer stainless steel plates led to a significantly higher bone loss and correspondingly greater loss of mechanical properties. These effects were greatest directly beneath the plate and less with increasing distance from the plate.

Matrix mechanics controls FHL2 movement to the nucleus to activate p21 expression

PubMed Central

Nakazawa, Naotaka; Sathe, Aneesh R.; Shivashankar, G. V.; Sheetz, Michael P.

2016-01-01

Substrate rigidity affects many physiological processes through mechanochemical signals from focal adhesion (FA) complexes that subsequently modulate gene expression. We find that shuttling of the LIM domain (domain discovered in the proteins, Lin11, Isl-1, and Mec-3) protein four-and-a-half LIM domains 2 (FHL2) between FAs and the nucleus depends on matrix mechanics. In particular, on soft surfaces or after the loss of force, FHL2 moves from FAs into the nucleus and concentrates at RNA polymerase (Pol) II sites, where it acts as a transcriptional cofactor, causing an increase in p21 gene expression that will inhibit growth on soft surfaces. At the molecular level, shuttling requires a specific tyrosine in FHL2, as well as phosphorylation by active FA kinase (FAK). Thus, we suggest that FHL2 phosphorylation by FAK is a critical, mechanically dependent step in signaling from soft matrices to the nucleus to inhibit cell proliferation by increasing p21 expression. PMID:27742790

The physical mechanism of successful treatment for cervical insufficiency

NASA Astrophysics Data System (ADS)

Baumer, Alexa; Amechi, Alexis; Codrington, Paige; Leftwich, Megan C.

2017-11-01

Cervical insufficiency is a medical condition during pregnancy in which the uterine cervix softens and begins to dilate before reaching full term, usually between 18 and 22 weeks gestation. It is the most common cause of second trimester pregnancy loss. One clinical technique used to treat cervical insufficiency is the cervical cerclage, a procedure to close the cervix with a purse-string stitch. There are conflicting findings on the efficacy of a cerclage, with most studies relying on statistical evidence. The purpose of this investigation is to examine the mechanical limitations of a cervical cerclage by pressurizing a stitched, synthetic cervix until rupture. A synthetic model of the cervix is generated using ultrasound images collected by clinical collaborators and fabricated with silicon to imitate physiological properties. Medical residents from The George Washington University Hospital stitch the synthetic cervixes using clinical techniques. Pressure transducers record the maximum force on the stitch before rupture. The results of this study will provide insight into the most effective clinical interventions and the mechanism of their success.

Gibberellins Are Required for Seed Development and Pollen Tube Growth in Arabidopsis

PubMed Central

Singh, Davinder P.; Jermakow, Angelica M.; Swain, Stephen M.

2002-01-01

Gibberellins (GAs) are tetracyclic diterpenoids that are essential endogenous regulators of plant growth and development. GA levels within the plant are regulated by a homeostatic mechanism that includes changes in the expression of a family of GA-inactivating enzymes known as GA 2-oxidases. Ectopic expression of a pea GA 2-oxidase2 cDNA caused seed abortion in Arabidopsis, extending and confirming previous observations obtained with GA-deficient mutants of pea, suggesting that GAs have an essential role in seed development. A new physiological role for GAs in pollen tube growth in vivo also has been identified. The growth of pollen tubes carrying the 35S:2ox2 transgene was reduced relative to that of nontransgenic pollen, and this phenotype could be reversed partially by GA application in vitro or by combining with spy-5, a mutation that increases GA response. Treatment of wild-type pollen tubes with an inhibitor of GA biosynthesis in vitro also suggested that GAs are required for normal pollen tube growth. These results extend the known physiological roles of GAs in Arabidopsis development and suggest that GAs are required for normal pollen tube growth, a physiological role for GAs that has not been established previously. PMID:12468732

Multimodal Pressure-Flow Analysis: Application of Hilbert Huang Transform in Cerebral Blood Flow Regulation

NASA Astrophysics Data System (ADS)

Lo, Men-Tzung; Hu, Kun; Liu, Yanhui; Peng, C.-K.; Novak, Vera

2008-12-01

Quantification of nonlinear interactions between two nonstationary signals presents a computational challenge in different research fields, especially for assessments of physiological systems. Traditional approaches that are based on theories of stationary signals cannot resolve nonstationarity-related issues and, thus, cannot reliably assess nonlinear interactions in physiological systems. In this review we discuss a new technique called multimodal pressure flow (MMPF) method that utilizes Hilbert-Huang transformation to quantify interaction between nonstationary cerebral blood flow velocity (BFV) and blood pressure (BP) for the assessment of dynamic cerebral autoregulation (CA). CA is an important mechanism responsible for controlling cerebral blood flow in responses to fluctuations in systemic BP within a few heart-beats. The MMPF analysis decomposes BP and BFV signals into multiple empirical modes adaptively so that the fluctuations caused by a specific physiologic process can be represented in a corresponding empirical mode. Using this technique, we showed that dynamic CA can be characterized by specific phase delays between the decomposed BP and BFV oscillations, and that the phase shifts are significantly reduced in hypertensive, diabetics and stroke subjects with impaired CA. Additionally, the new technique can reliably assess CA using both induced BP/BFV oscillations during clinical tests and spontaneous BP/BFV fluctuations during resting conditions.

Physiologically Persistent Corpora lutea in Eurasian Lynx (Lynx lynx) – Longitudinal Ultrasound and Endocrine Examinations Intra-Vitam

PubMed Central

Painer, Johanna; Jewgenow, Katarina; Dehnhard, Martin; Arnemo, Jon M.; Linnell, John D. C.; Odden, John; Hildebrandt, Thomas B.; Goeritz, Frank

2014-01-01

Felids generally follow a poly-estrous reproductive strategy. Eurasian lynx (Lynx lynx) display a different pattern of reproductive cyclicity where physiologically persistent corpora lutea (CLs) induce a mono-estrous condition which results in highly seasonal reproduction. The present study was based around a sono-morphological and endocrine study of captive Eurasian lynx, and a control-study on free-ranging lynx. We verified that CLs persist after pregnancy and pseudo-pregnancy for at least a two-year period. We could show that lynx are able to enter estrus in the following year, while CLs from the previous years persisted in structure and only temporarily reduced their function for the period of estrus onset or birth, which is unique among felids. The almost constant luteal progesterone secretion (average of 5 ng/ml serum) seems to prevent folliculogenesis outside the breeding season and has converted a poly-estrous general felid cycle into a mono-estrous cycle specific for lynx. The hormonal regulation mechanism which causes lynx to have the longest CL lifespan amongst mammals remains unclear. The described non-felid like ovarian physiology appears to be a remarkably non-plastic system. The lynx's reproductive ability to adapt to environmental and anthropogenic changes needs further investigation. PMID:24599348

Sustainability of industrial yeast serial repitching practice studied by gene expression and correlation analysis.

PubMed

Bühligen, Franziska; Rüdinger, Philipp; Fetzer, Ingo; Stahl, Frank; Scheper, Thomas; Harms, Hauke; Müller, Susann

2013-12-01

Bottom-fermenting Saccharomyces pastorianus strains driving brewing fermentation processes are usually reused several times. It is still unclear, whether the number of successions may have an impact on cell physiology prompting consequences for brewing quality. In this study, fermentation performance of up to twenty consecutive runs in a brewery was investigated. For each run mRNA expression levels of cellular marker molecules, which are known to correlate with metabolism, hexose transport, aging processes, stress response mechanisms and flocculation capability was estimated to obtain information on changes in cell physiology over the successive runs. Low-density microarrays were used for this purpose and the resulting gene expression profiles were finally correlated with changes in the abiotic micro-environments. A surprising stability of the marker molecule expression profiles within each specific serial repitching was stated. Loss of flocculation or an advanced aging could not be detected during serial repitching in the analyzed brewery. However, certain runs of the serial repitchings showed high variation in stress response which was found to be caused by perturbations of the abiotic conditions. Regardless, the study showed that S. pastorianus can be used repeatedly in serial repitching processes without loss of prominent physiological characteristics. Copyright © 2013 Elsevier B.V. All rights reserved.

Evaluation and treatment of transfusional iron overload in children.

PubMed

Ware, Hannah M; Kwiatkowski, Janet L

2013-12-01

Red blood cell transfusions are increasingly used in the management of various anemias, including thalassemia and sickle cell disease. Because the body lacks physiologic mechanisms for removing excess iron, transfusional iron overload is a common complication in children receiving regular transfusions. Iron chelation is necessary to remove the excess iron that causes injury to the heart, liver, and endocrine organs. Three chelators, deferoxamine, deferasirox, and deferiprone, are currently available in the United States. When choosing a chelator regimen, patients, parents, and providers may consider a variety of factors, including the severity of iron overload, administration schedule, and adverse effect profile. Copyright © 2013 Elsevier Inc. All rights reserved.

Bioengineered vascular constructs as living models for in vitro cardiovascular research.

PubMed

Wolf, Frederic; Vogt, Felix; Schmitz-Rode, Thomas; Jockenhoevel, Stefan; Mela, Petra

2016-09-01

Cardiovascular diseases represent the most common cause of morbidity and mortality worldwide. In this review, we explore the potential of bioengineered vascular constructs as living models for in vitro cardiovascular research to advance the current knowledge of pathophysiological processes and support the development of clinical therapies. Bioengineered vascular constructs capable of recapitulating the cellular and mechanical environment of native vessels represent a valuable platform to study cellular interactions and signaling cascades, test drugs and medical devices under (patho)physiological conditions, with the additional potential benefit of reducing the number of animals required for preclinical testing. Copyright © 2016 Elsevier Ltd. All rights reserved.

Toxicology of sulfur in ruminants: review

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kandylis, K.

1984-10-01

This review deals with the toxicology of sulfur in ruminants including toxicity, neurotoxic effects, and mechanism of toxic action of hydrogen sulfide, clinical signs, and treatment. It will report effects of excessive intake of sulfur by ruminants on feed intake, animal performance, ruminal digestion and motility, rumination, and other physiological functions. Poisoning of animals with sulfur from industrial emissions (sulfur dioxide) also is discussed. Excessive quantities of dietary sulfur (above .3 to .4%) as sulfate or elemental sulfur may cause toxic effects and in extreme cases can be fatal. The means is discussed whereby consumption of excessive amounts of sulfurmore » leads to toxic effects. 53 references, 1 table.« less

Potential impact on fertility of new systemic therapies for cystic fibrosis.

PubMed

Jones, Gareth Huw; Walshaw, Martin John

2015-10-01

Cystic fibrosis is primarily considered a respiratory disease with superadded pancreatic dysfunction; however the underlying genetic mutation results in the abnormal function of cells throughout the body - including tissues involved in reproduction. Practically all males and up to 50% of females with CF will suffer fertility issues - the causes of which are multifactorial and could be improved by treatments that target the underlying physiological deficit, such as ivacaftor. We consider the mechanisms by which the rapidly developing field of systemic treatments for CF could impact on the fertility of this group and review the available real world evidence. Copyright © 2015 Elsevier Ltd. All rights reserved.

Elementary theory of synchronous arterio-arterial blood pumps

NASA Technical Reports Server (NTRS)

Jones, R. T.; Petscheck, H. E.; Kantrowitz, A. R.

1976-01-01

In the technique of arterio-arterial pumping, a volume of fluid is withdrawn from the aorta during systole and reinjected during diastole, thereby reducing the systolic pressure of the heart and adding energy to the systemic circulation. It is found that an upper bound for the effectiveness of such devices is given by a formula that considers stroke output of the unaided heart and the increment caused by the pump with a stroke. The division of effort of the pump between the reduction of pressure and the increase of flow depends on the physiological mechanical impedance of the heart. The total effect is, however, independent of the impedance.

Progranulin: A Proteolytically Processed Protein at the Crossroads of Inflammation and Neurodegeneration*

PubMed Central

Cenik, Basar; Sephton, Chantelle F.; Kutluk Cenik, Bercin; Herz, Joachim; Yu, Gang

2012-01-01

GRN mutations cause frontotemporal lobar degeneration with TDP-43-positive inclusions. The mechanism of pathogenesis is haploinsufficiency. Recently, homozygous GRN mutations were detected in two patients with neuronal ceroid lipofuscinosis, a lysosomal storage disease. It is unknown whether the pathogenesis of these two conditions is related. Progranulin is cleaved into smaller peptides called granulins. Progranulin and granulins are attributed with roles in cancer, inflammation, and neuronal physiology. Cell surface receptors for progranulin, but not granulin peptides, have been reported. Revealing the cell surface receptors and the intracellular functions of granulins and progranulin is crucial for understanding their contributions to neurodegeneration. PMID:22859297

Coronary microvascular dysfunction in diabetes mellitus

PubMed Central

Selthofer-Relatic, Kristina; Drenjancevic, Ines; Bacun, Tatjana; Bosnjak, Ivica; Kibel, Dijana; Gros, Mario

2017-01-01

The significance, mechanisms and consequences of coronary microvascular dysfunction associated with diabetes mellitus are topics into which we have insufficient insight at this time. It is widely recognized that endothelial dysfunction that is caused by diabetes in various vascular beds contributes to a wide range of complications and exerts unfavorable effects on microcirculatory regulation. The coronary microcirculation is precisely regulated through a number of interconnected physiological processes with the purpose of matching local blood flow to myocardial metabolic demands. Dysregulation of this network might contribute to varying degrees of pathological consequences. This review discusses the most important findings regarding coronary microvascular dysfunction in diabetes from pre-clinical and clinical perspectives. PMID:28643578

A new concept of endometriosis and adenomyosis: tissue injury and repair (TIAR).

PubMed

Leyendecker, Gerhard; Wildt, Ludwig

2011-03-01

Pelvic endometriosis, deeply infiltrating endometriosis and uterine adenomyosis share a common pathophysiology and may be integrated into the physiological mechanism and new nosological concept of 'tissue injury and repair' (TIAR) and may, in this context, just represent the extreme of a basically physiological, estrogen-related mechanism that is pathologically exaggerated in an extremely estrogen-sensitive reproductive organ. The acronym TIAR describes a fundamental and apparently ubiquitous biological system that becomes operative in mesenchymal tissues following tissue injury and, upon activation, results in the local production of estradiol. Endometriosis and adenomyosis are caused by trauma. In the spontaneously developing disease, chronic uterine peristaltic activity or phases of hyperperistalsis induce, at the endometrial-myometrial interface near the fundo-cornual raphe, microtraumatisations, with activation of the TIAR mechanism. With ongoing traumatisations, such sites of inflammation might accumulate and the increasingly produced estrogens interfere in a paracrine fashion with ovarian control over uterine peristaltic activity, resulting in permanent hyperperistalsis and a self-perpetuation of the disease process. Overt autotraumatisation of the uterus with dislocation of fragments of basal endometrium into the peritoneal cavity and infiltration of basal endometrium into the depth of the myometrial wall ensues. In most cases of endometriosis/adenomyosis a causal event early in the reproductive period of life must be postulated, rapidly leading to archimetral hyperestrogenism and uterine hyperperistalsis. In late premenopausal adenomyosis such an event might not have occurred. However, as indicated by the high prevalence of the disease, it appears to be unavoidable that, with time, chronic normoperistalsis throughout the reproductive period of life accumulates to the same extent of microtraumatisation. With activation of the TIAR mechanism followed by chronic inflammation and infiltrative growth, endometriosis/adenomyosis of the younger woman and premenopausal adenomyosis share in principal the same pathophysiology.

A review of techniques for visualising soft tissue microstructure deformation and quantifying strain Ex Vivo.

PubMed

Disney, C M; Lee, P D; Hoyland, J A; Sherratt, M J; Bay, B K

2018-04-14

Many biological tissues have a complex hierarchical structure allowing them to function under demanding physiological loading conditions. Structural changes caused by ageing or disease can lead to loss of mechanical function. Therefore, it is necessary to characterise tissue structure to understand normal tissue function and the progression of disease. Ideally intact native tissues should be imaged in 3D and under physiological loading conditions. The current published in situ imaging methodologies demonstrate a compromise between imaging limitations and maintaining the samples native mechanical function. This review gives an overview of in situ imaging techniques used to visualise microstructural deformation of soft tissue, including three case studies of different tissues (tendon, intervertebral disc and artery). Some of the imaging techniques restricted analysis to observational mechanics or discrete strain measurement from invasive markers. Full-field local surface strain measurement has been achieved using digital image correlation. Volumetric strain fields have successfully been quantified from in situ X-ray microtomography (micro-CT) studies of bone using digital volume correlation but not in soft tissue due to low X-ray transmission contrast. With the latest developments in micro-CT showing in-line phase contrast capability to resolve native soft tissue microstructure, there is potential for future soft tissue mechanics research where 3D local strain can be quantified. These methods will provide information on the local 3D micromechanical environment experienced by cells in healthy, aged and diseased tissues. It is hoped that future applications of in situ imaging techniques will impact positively on the design and testing of potential tissue replacements or regenerative therapies. © 2018 The Authors Journal of Microscopy © 2018 Royal Microscopical Society.

Bone's mechanostat: a 2003 update.

PubMed

Frost, Harold M

2003-12-01

The still-evolving mechanostat hypothesis for bones inserts tissue-level realities into the former knowledge gap between bone's organ-level and cell-level realities. It concerns load-bearing bones in postnatal free-living bony vertebrates, physiologic bone loading, and how bones adapt their strength to the mechanical loads on them. Voluntary mechanical usage determines most of the postnatal strength of healthy bones in ways that minimize nontraumatic fractures and create a bone-strength safety factor. The mechanostat hypothesis predicts 32 things that occur, including the gross anatomical bone abnormalities in osteogenesis imperfecta; it distinguishes postnatal situations from baseline conditions at birth; it distinguishes bones that carry typical voluntary loads from bones that have other chief functions; and it distinguishes traumatic from nontraumatic fractures. It provides functional definitions of mechanical bone competence, bone quality, osteopenias, and osteoporoses. It includes permissive hormonal and other effects on bones, a marrow mediator mechanism, some limitations of clinical densitometry, a cause of bone "mass" plateaus during treatment, an "adaptational lag" in some children, and some vibration effects on bones. The mechanostat hypothesis may have analogs in nonosseous skeletal organs as well. Copyright 2003 Wiley-Liss, Inc.

Developmental theory of aging revisited: focus on causal and mechanistic links between development and senescence.

PubMed

Walker, Richard F

2011-08-01

Senescence violates the most basic tenet of natural selection by causing death rather than individual survival. Thus, current theories favor the concept of antagonistic pleiotropy (AP) to explain how aging emerged in metazoans. Presumably, pleiotropic genes reduce vigor and limit longevity in adults. However, they also promote fitness and reproduction in juveniles, causing them to be selected and retained in the gene pool. The general hypothesis presented herein is a special case of AP that identifies the common cause and mechanism of aging in iteroparous (i.e., capable of reproducing multiple times) animals. It ascribes senescence to unremitting, nonprogrammed change or remodeling forced upon the adult soma by postmaturation expression of developmental gene(s) affecting dynamic transformation of the single-celled conceptus into a complex, multicellular organism. Whereas persistent somatic change is necessary for development to proceed normally, it also has the potential to erode homeostasis in adults after maturation is complete. Thus, developmental inertia is the primary cause of senescence, whereas decay of internal order and integrated function among interdependent systems of the body is the general mechanism by which aging progresses over time. Accordingly, this global pathogenic process creates an environment in which the many recognized, age-associated physiologic and metabolic sequelae can arise as consequences of senescence rather than causes of it. Paradoxically, the genes that promote somatic remodeling essential for development and survival also guarantee aging and death by the same action whose outcomes differ only by the time it is expressed relevant to maturation.

Changes in gametophyte physiology of Pteris multifida induced by the leaf leachate treatment of the invasive Bidens pilosa.

PubMed

Zhang, Kai-Mei; Shen, Yu; Fang, Yan-Ming; Liu, Ying

2016-02-01

In recent years, the response of fern gametophytes to environment has raised much attention. However, studies on the influence of plant invasion to fern gametophytes are scarce. Allelopathy plays an important role in biological invasion. Hence, it is necessary to study the allelopathic effects of invasive plants on fern gametophytes and elucidate the mechanisms by which invasive plants cause phytotoxicity. As one of the main invasive plants in China, Bidens pilosa exhibits allelopathic effects on spermatophyte growth. Field investigation shows that many ferns are threatened by the invasion of B. pilosa. The distribution of Pteris multifida overlaps with that of B. pilosa in China. To examine the potential involvement of allelopathic mechanisms of B. pilosa leaves, changes in the physiology in P. multifida gametophytes are analyzed. We found that cell membrane and antioxidant enzyme activities as well as photosynthesis pigment contents of the gametophytes were affected by B. pilosa leachates. Gametophytes of P. multifida exposed to B. pilosa had increased damages to cell membranes, expressed in thiobarbituric acid reacting substance (TBARS) concentrations, malondialdehyde (MDA), electrolyte leakage (membrane permeability), and degree of injury. Enzyme activities, assessed by superoxide dismutase (SOD) and catalase (CAT) as well as guaiacol peroxidase (GPX) enhanced with the increase in leachate concentration after 2-day exposure. Meanwhile, lower chlorophyll a (Chl a), chlorophyll b (Chl b), carotenoid (Car), and the total chlorophyll were measured as leachate concentrations increased. At day 10, leaf leachates of B. pilosa exhibited the greatest inhibition. These results suggest that the observed inhibitory or stimulatory effects on the physiology studied can have an adverse effect on P. multifida and that allelopathic interference seems to have involved in this process.

[Variability patterns of nest construction, physiological state, and morphometric traits in honey bee].

PubMed

Es'kov, E K; Es'kova, M D

2014-01-01

High variability of cells size is used selectively for reproduction of working bees and drones. A decrease in both distance between cells and cells size themselves causes similar effects to body mass and morphometric traits of developing individuals. Adaptation of honey bees to living in shelters has led to their becoming tolerant to hypoxia. Improvement of ethological and physiological mechanisms of thermal regulation is associated with limitation of ecological valence and acquiring of stenothermic features by breed. Optimal thermal conditions for breed are limited by the interval 33-34.5 degrees C. Deviations of temperature by 3-4 degrees C beyond this range have minimum lethal effect at embryonic stage of development and medium effect at the stage of pre-pupa and pupa. Developing at the low bound of the vital range leads to increasing, while developing at the upper bound--to decreasing of body mass, mandibular and hypopharyngeal glands, as well as other organs, which, later, affects the variability of these traits during the adult stage of development. Eliminative and teratogenic efficiency of ecological factors that affect a breed is most often manifested in underdevelopment of wings. However, their size (in case of wing laminas formation). is characterized by relatively low variability and size-dependent asymmetry. Asymmetry variability of wings and other pair organs is expressed through realignment of size excess from right- to left-side one with respect to their increase. Selective elimination by those traits whose emerging probability increases as developmental conditions deviate from the optimal ones promotes restrictions on individual variability. Physiological mechanisms that facilitate adaptability enhancement under conditions of increasing anthropogenic contamination of eivironment and trophic substrates consumed by honey bees, arrear to be toxicants accumulation in rectum and crops' ability to absorb contaminants from nectar in course of its processing to honey.

Finite element analysis on the biomechanical stability of open porous titanium scaffolds for large segmental bone defects under physiological load conditions.

PubMed

Wieding, Jan; Souffrant, Robert; Mittelmeier, Wolfram; Bader, Rainer

2013-04-01

Repairing large segmental defects in long bones caused by fracture, tumour or infection is still a challenging problem in orthopaedic surgery. Artificial materials, i.e. titanium and its alloys performed well in clinical applications, are plenary available, and can be manufactured in a wide range of scaffold designs. Although the mechanical properties are determined, studies about the biomechanical behaviour under physiological loading conditions are rare. The goal of our numerical study was to determine the suitability of open-porous titanium scaffolds to act as bone scaffolds. Hence, the mechanical stability of fourteen different scaffold designs was characterized under both axial compression and biomechanical loading within a large segmental distal femoral defect of 30mm. This defect was stabilized with an osteosynthesis plate and physiological hip reaction forces as well as additional muscle forces were implemented to the femoral bone. Material properties of titanium scaffolds were evaluated from experimental testing. Scaffold porosity was varied between 64 and 80%. Furthermore, the amount of material was reduced up to 50%. Uniaxial compression testing revealed a structural modulus for the scaffolds between 3.5GPa and 19.1GPa depending on porosity and material consumption. The biomechanical testing showed defect gap alterations between 0.03mm and 0.22mm for the applied scaffolds and 0.09mm for the intact bone. Our results revealed that minimizing the amount of material of the inner core has a smaller influence than increasing the porosity when the scaffolds are loaded under biomechanical loading. Furthermore, an advanced scaffold design was found acting similar as the intact bone. Copyright © 2012 IPEM. Published by Elsevier Ltd. All rights reserved.

Interactive effects of elevated temperature and CO2 levels on energy metabolism and biomineralization of marine bivalves Crassostrea virginica and Mercenaria mercenaria.

PubMed

Ivanina, Anna V; Dickinson, Gary H; Matoo, Omera B; Bagwe, Rita; Dickinson, Ashley; Beniash, Elia; Sokolova, Inna M

2013-09-01

The continuing increase of carbon dioxide (CO2) levels in the atmosphere leads to increases in global temperatures and partial pressure of CO2 (PCO2) in surface waters, causing ocean acidification. These changes are especially pronounced in shallow coastal and estuarine waters and are expected to significantly affect marine calcifiers including bivalves that are ecosystem engineers in estuarine and coastal communities. To elucidate potential effects of higher temperatures and PCO2 on physiology and biomineralization of marine bivalves, we exposed two bivalve species, the eastern oysters Crassostrea virginica and the hard clams Mercenaria mercenaria to different combinations of PCO2 (~400 and 800μatm) and temperatures (22 and 27°C) for 15weeks. Survival, bioenergetic traits (tissue levels of lipids, glycogen, glucose and high energy phosphates) and biomineralization parameters (mechanical properties of the shells and activity of carbonic anhydrase, CA) were determined in clams and oysters under different temperature and PCO2 regimes. Our analysis showed major inter-species differences in shell mechanical traits and bioenergetics parameters. Elevated temperature led to the depletion of tissue energy reserves indicating energy deficiency in both species and resulted in higher mortality in oysters. Interestingly, while elevated PCO2 had a small effect on the physiology and metabolism of both species, it improved survival in oysters. At the same time, a combination of high temperature and elevated PCO2 lead to a significant decrease in shell hardness in both species, suggesting major changes in their biomineralization processes. Overall, these studies show that global climate change and ocean acidification might have complex interactive effects on physiology, metabolism and biomineralization in coastal and estuarine marine bivalves. Copyright © 2013 Elsevier Inc. All rights reserved.

Hydrogel tissue construct-based high-content compound screening.

PubMed

Lam, Vy; Wakatsuki, Tetsuro

2011-01-01

Current pharmaceutical compound screening systems rely on cell-based assays to identify therapeutic candidates and potential toxicities. However, cells grown on 2D substrata or in suspension do not exhibit the mechanical or physiological properties of cells in vivo. To address this limitation, the authors developed an in vitro, high-throughput, 3D hydrogel tissue construct (HTC)-based assay system to quantify cell and tissue mechanical properties and multiple parameters of physiology. HTC mechanics was quantified using an automated device, and physiological status was assessed using spectroscopy-based indicators that were read on microplate readers. To demonstrate the application of this system, the authors screened 4 test compounds--rotenone (ROT), cytochalasin D (CD), 2,4-dinitrophenol (DNP), and Rho kinase inhibitor (H-1152)--for their ability to modulate HTC contractility without affecting actin integrity, mitochondrial membrane potential (MMP), or viability. All 4 compounds dose-dependently reduced HTC contractility. However, ROT was toxic, DNP dissipated MMP, and CD reduced both intracellular F-actin and viability. H-1152 was found to be the best candidate compound since it reduced HTC contractility with minimal side effects. The authors propose that their HTC-based assay system can be used to screen for compounds that modulate HTC contractility and assess the underlying physiological mechanism(s) of compound activity and toxicity.

Electrophysiological experiments in microgravity: lessons learned and future challenges.

PubMed

Wuest, Simon L; Gantenbein, Benjamin; Ille, Fabian; Egli, Marcel

2018-01-01

Advances in electrophysiological experiments have led to the discovery of mechanosensitive ion channels (MSCs) and the identification of the physiological function of specific MSCs. They are believed to play important roles in mechanosensitive pathways by allowing for cells to sense their mechanical environment. However, the physiological function of many MSCs has not been conclusively identified. Therefore, experiments have been developed that expose cells to various mechanical loads, such as shear flow, membrane indentation, osmotic challenges and hydrostatic pressure. In line with these experiments, mechanical unloading, as experienced in microgravity, represents an interesting alternative condition, since exposure to microgravity leads to a series of physiological adaption processes. As outlined in this review, electrophysiological experiments performed in microgravity have shown an influence of gravity on biological functions depending on ion channels at all hierarchical levels, from the cellular level to organs. In this context, calcium signaling represents an interesting cellular pathway, as it involves the direct action of calcium-permeable ion channels, and specific gravitatic cells have linked graviperception to this pathway. Multiple key proteins in the graviperception pathways have been identified. However, measurements on vertebrae cells have revealed controversial results. In conclusion, electrophysiological experiments in microgravity have shown that ion-channel-dependent physiological processes are altered in mechanically unloaded conditions. Future experiments may provide a better understanding of the underlying mechanisms.

Proceedings of the Symposium Teaching Cardiovascular Physiology Outside the Lecture Hall.

ERIC Educational Resources Information Center

Michael, Joel A.; Rovick, Allen A., Eds.

1983-01-01

Provided are 10 papers presented during a symposium on teaching cardiovascular physiology outside the lecture hall. Topics addressed include a mechanical model of the cardiovascular system for effective teaching, separate course for experiments in cardiovascular physiology, selective laboratory (alternative to cookbook experiments), cardiovascular…

The Relationship between Rumination and Affective, Cognitive, and Physiological Responses to Stress in Adolescents.

PubMed

Aldao, Amelia; McLaughlin, Katie A; Hatzenbuehler, Mark L; Sheridan, Margaret A

Although previous studies have established that rumination influences responses to stressful life events, the mechanisms underlying this relationship remain inadequately understood. The current study examines the relationship between trait rumination and affective, cognitive, and physiological responses to a standardized laboratory-based stressor in adolescents. A community-based sample of adolescents (N = 157) aged 13-17 completed the Trier Social Stress Test (TSST). Affective, cognitive, and physiological responses were obtained before, during, and after the TSST. Adolescents who engaged in habitual rumination experienced greater negative affect and more negative cognitive appraisals in response to the TSST than adolescents with lower levels of rumination. Rumination was unrelated to heart rate reactivity, but predicted slower heart rate recovery from the TSST, indicating that rumination might be specifically associated with physiological recovery from stress. Rumination is associated with negative affective, cognitive, and physiological responses following stressors, suggesting potential mechanisms through which it might increase risk for psychopathology.

The esophagiome: integrated anatomical, mechanical, and physiological analysis of the esophago-gastric segment.

PubMed

Zhao, Jingbo; McMahon, Barry; Fox, Mark; Gregersen, Hans

2018-06-10

Esophageal diseases are highly prevalent and carry significant socioeconomic burden. Despite the apparently simple function of the esophagus, we still struggle to better understand its physiology and pathophysiology. The assessment of large data sets and application of multiscale mathematical organ models have gained attention as part of the Physiome Project. This has long been recognized in cardiology but has only recently gained attention for the gastrointestinal(GI) tract. The term "esophagiome" implies a holistic assessment of esophageal function, from cellular and muscle physiology to the mechanical responses that transport and mix fluid contents. These anatomical, mechanical, and physiological models underlie the development of a "virtual esophagus" modeling framework to characterize and analyze function and disease. Functional models incorporate anatomical details with sensory-motor responses, especially related to biomechanical functions such as bolus transport. Our review builds on previous reviews and focuses on assessment of detailed anatomical and geometric data using advanced imaging technology for evaluation of gastro-esophageal reflux disease (GERD), and on esophageal mechanophysiology assessed using technologies that distend the esophagus. Integration of mechanics- and physiology-based analysis is a useful characteristic of the esophagiome. Experimental data on pressures and geometric characteristics are useful for the validation of mathematical and computer models of the esophagus that may provide predictions of novel endoscopic, surgical, and pharmaceutical treatment options. © 2018 New York Academy of Sciences.

Physiological and biochemical effects of nickel on rainbow trout (Oncorhynchus mykiss) tissues: Assessment of nuclear factor kappa B activation, oxidative stress and histopathological changes.

PubMed

Topal, Ahmet; Atamanalp, Muhammed; Oruç, Ertan; Erol, Hüseyin Serkan

2017-01-01

We investigated changes in nuclear factor kappa B (NFkB) activity, antioxidant responses and histopathological effects in the liver, gill and kidney tissues of rainbow trout exposed to nickel chloride (Ni). Two different concentrations (1 mg/L and 2 mg/L) were administrated to fish for 21 days. Tissues were taken from all fish for NFkB activity, histopathological examination and determination of superoxide dismutase (SOD), catalase (CAT) enzyme activity and of lipid peroxidation (LPO), and glutathione (GSH) levels. The findings of this study indicated that Ni exposure led to a significant increase in LPO indicating peroxidative damage and antioxidant enzymes SOD and CAT activity in tissues (p < 0.05), but 2 mg/Ni concentration caused a significant decrease in CAT activity in kidney tissues (p < 0.05). One of mechanism in the antioxidant defense system seems to be GSH, which increased in gill and kidney tissues of fish exposed to Ni (p < 0.05). NFkB immunopositivity was detected in all tissues. Ni exposure caused lamellar thickening, cellular infiltration in gill tissues, hydropic degeneration of hepatocytes in liver tissues, hyalinous accumulation within the glomeruli and tubular degeneration in kidney tissues. Our results suggested that Ni toxicity may disturb the biochemical and physiological functions of fish by causing changes in NFkB activity and oxidative and histopathological damage in the tissues of rainbow trout. This study can provide useful information for understanding of Ni-induced toxicity. Copyright © 2016 Elsevier Ltd. All rights reserved.

Suppression of glycolate oxidase causes glyoxylate accumulation that inhibits photosynthesis through deactivating Rubisco in rice.

PubMed

Lu, Yusheng; Li, Yong; Yang, Qiaosong; Zhang, Zhisheng; Chen, Yan; Zhang, Sheng; Peng, Xin-Xiang

2014-03-01

Glycolate oxidase (GLO) is a key enzyme for photorespiration in plants. Previous studies have demonstrated that suppression of GLO causes photosynthetic inhibition, and the accumulated glycolate with the deactivated Rubisco is likely involved in the regulation. Using isolated Rubisco and chloroplasts, it has been found that only glyoxylate can effectively inactivate Rubisco and meanwhile inhibit photosynthesis, but little in vivo evidence has been acquired and reported. In this study, we have generated the transgenic rice (Oryza sativa) plants with GLO being constitutively silenced, and conducted the physiological and biochemical analyses on these plants to explore the regulatory mechanism. When GLO was downregulated, the net photosynthetic rate (Pn) was reduced and the plant growth was correspondingly stunted. Surprisingly, glyoxylate, as a product of the GLO catalysis, was accumulated in response to the GLO suppression, like its substrate glycolate. Furthermore, the glyoxylate content was found to be inversely proportional to the Pn while the Pn is directly proportional to the Rubisco activation state in the GLO-suppressed plants. A mathematical fitting equation using least square method also demonstrated that the Rubisco activation state was inversely proportional to the glyoxylate content. Despite that the further analyses we have conducted failed to reveal how glyoxylate was accumulated in response to the GLO suppression, the current results do strongly suggest that there may exist an unidentified, alternative pathway to produce glyoxylate, and that the accumulated glyoxylate inhibits photosynthesis by deactivating Rubisco, and causes the photorespiratory phenotype in the GLO-suppressed rice plants. © 2013 Scandinavian Plant Physiology Society.

Life cycle ecophysiology of small pelagic fish and climate-driven changes in populations

NASA Astrophysics Data System (ADS)

Peck, Myron A.; Reglero, Patricia; Takahashi, Motomitsu; Catalán, Ignacio A.

2013-09-01

Due to their population characteristics and trophodynamic role, small pelagic fishes are excellent bio-indicators of climate-driven changes in marine systems world-wide. We argue that making robust projections of future changes in the productivity and distribution of small pelagics will require a cause-and-effect understanding of historical changes based upon physiological principles. Here, we reviewed the ecophysiology of small pelagic (clupeiform) fishes including a matrix of abiotic and biotic extrinsic factors (e.g., temperature, salinity, light, and prey characteristics) and stage-specific vital rates: (1) adult spawning, (2) survival and development of eggs and yolk sac larvae, and (3) feeding and growth of larvae, post-larvae and juveniles. Emphasis was placed on species inhabiting Northwest Pacific and Northeast Atlantic (European) waters for which summary papers are particularly scarce compared to anchovy and sardine in upwelling systems. Our review revealed that thermal niches (optimal and sub-optimal ranges in temperatures) were species- and stage-specific but that temperature effects only partly explained observed changes in the distribution and/or productivity of populations in the Northwest Pacific and Northeast Atlantic; changes in temperature may be necessary but not sufficient to induce population-level shifts. Prey availability during the late larval and early juvenile period was a common, density-dependent mechanism linked to fluctuations in populations but recruitment mechanisms were system-specific suggesting that generalizations of climate drivers across systems should be avoided. We identified gaps in knowledge regarding basic elements of the growth physiology of each life stage that will require additional field and laboratory study. Avenues of research are recommended that will aid the development of models that provide more robust, physiological-based projections of the population dynamics of these and other small pelagic fish. In our opinion, the continued development of biophysical models that close the life cycle (depict all life stages) offers the best chance of revealing processes causing historical fluctuations on the productivity and distribution of small pelagic fishes and to project future climate-driven impacts. Correctly representing physiological-based mechanisms will increase confidence in the outcomes of models simulating the potential impacts of bottom-up processes, a first step towards evaluating the mixture of factors and processes (e.g. intra-guild dynamics, predation, fisheries exploitation) which interact with climate to affect populations of small pelagic fishes. Understand the impacts of reduced growth rates during the juvenile stage on the process of maturation and spawning condition of small pelagic fishes. Examine the effects of changes in prey quality on the duration and magnitude of spawning by small pelagic fishes to capture how climate-driven changes in zooplankton species composition might act as a “bottom-up” regulator of fish productivity. Identify the drivers for spawning location and timing to better understand how spawning dynamics may be influenced by climate change (e.g. changes in water salinity or turbidity resulting from changes in river discharges or wind-driven turbulence, respectively).

Regulated endocytosis of opioid receptors: cellular mechanisms and proposed roles in physiological adaptation to opiate drugs.

PubMed

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.

Gut feedback mechanisms and food intake: a physiological approach to slow carbohydrate bioavailability.

PubMed

Zhang, Genyi; Hasek, Like Y; Lee, Byung-Hoo; Hamaker, Bruce R

2015-04-01

Glycemic carbohydrates in foods are an important macronutrient providing the biological fuel of glucose for a variety of physiological processes. A classification of glycemic carbohydrates into rapidly digestible carbohydrate (RDC) and slowly digestible carbohydrate (SDC) has been used to specify their nutritional quality related to glucose homeostasis that is essential to normal functioning of the brain and critical to life. Although there have been many studies and reviews on slowly digestible starch (SDS) and SDC, the mechanisms of their slow digestion and absorption were mostly investigated from the material side without considering the physiological processes of their in vivo digestion, absorption, and most importantly interactions with other food components and the gastrointestinal tract. In this article, the physiological processes modulating the bioavailability of carbohydrates, specifically the rate and extent of their digestion and absorption as well as the related locations, in a whole food context, will be discussed by focusing on the activities of the gastrointestinal tract including glycolytic enzymes and glucose release, sugar sensing, gut hormones, and neurohormonal negative feedback mechanisms. It is hoped that a deep understanding of these physiological processes will facilitate the development of innovative dietary approaches to achieve desired carbohydrate or glucose bioavailability for improved health.

Current status of iron metabolism: Clinical and therapeutic implications.

PubMed

Conde Diez, Susana; de Las Cuevas Allende, Ricardo; Conde García, Eulogio

2017-03-03

Hepcidin is the main regulator of iron metabolism and a pathogenic factor in iron disorders. Hepcidin deficiency causes iron overload, whereas hepcidin excess causes or contributes to the development of iron-restricted anaemia in chronic inflammatory diseases. We know the mechanisms involved in the synthesis of hepcidin and, under physiological conditions, there is a balance between activating signals and inhibitory signals that regulate its synthesis. The former include those related to plasmatic iron level and also those related to chronic inflammatory diseases. The most important inhibitory signals are related to active erythropoiesis and to matriptase-2. Knowing how hepcidin is synthesised has helped design new pharmacological treatments whose main target is the hepcidin. In the near future, there will be effective treatments aimed at correcting the defect of many of these iron metabolism disorders. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

Direct Cytoskeleton Forces Cause Membrane Softening in Red Blood Cells

PubMed Central

Rodríguez-García, Ruddi; López-Montero, Iván; Mell, Michael; Egea, Gustavo; Gov, Nir S.; Monroy, Francisco

2015-01-01

Erythrocytes are flexible cells specialized in the systemic transport of oxygen in vertebrates. This physiological function is connected to their outstanding ability to deform in passing through narrow capillaries. In recent years, there has been an influx of experimental evidence of enhanced cell-shape fluctuations related to metabolically driven activity of the erythroid membrane skeleton. However, no direct observation of the active cytoskeleton forces has yet been reported to our knowledge. Here, we show experimental evidence of the presence of temporally correlated forces superposed over the thermal fluctuations of the erythrocyte membrane. These forces are ATP-dependent and drive enhanced flickering motions in human erythrocytes. Theoretical analyses provide support for a direct force exerted on the membrane by the cytoskeleton nodes as pulses of well-defined average duration. In addition, such metabolically regulated active forces cause global membrane softening, a mechanical attribute related to the functional erythroid deformability. PMID:26083919

Diseases of Pulmonary Surfactant Homeostasis

PubMed Central

Whitsett, Jeffrey A.; Wert, Susan E.; Weaver, Timothy E.

2015-01-01

Advances in physiology and biochemistry have provided fundamental insights into the role of pulmonary surfactant in the pathogenesis and treatment of preterm infants with respiratory distress syndrome. Identification of the surfactant proteins, lipid transporters, and transcriptional networks regulating their expression has provided the tools and insights needed to discern the molecular and cellular processes regulating the production and function of pulmonary surfactant prior to and after birth. Mutations in genes regulating surfactant homeostasis have been associated with severe lung disease in neonates and older infants. Biophysical and transgenic mouse models have provided insight into the mechanisms underlying surfactant protein and alveolar homeostasis. These studies have provided the framework for understanding the structure and function of pulmonary surfactant, which has informed understanding of the pathogenesis of diverse pulmonary disorders previously considered idiopathic. This review considers the pulmonary surfactant system and the genetic causes of acute and chronic lung disease caused by disruption of alveolar homeostasis. PMID:25621661

Hepatic Hemangioendothelioma Presenting as Sudden Unexpected Death in Infancy: A Case Report

PubMed Central

Dempers, Johan; Wadee, Shabbir Ahmed; Boyd, Theonia; Wright, Colleen; OdendaaL, Hein J; Sens, Mary Ann

2014-01-01

The classification of an unexpected infant death as the sudden infant death syndrome (SIDS) depends upon a complete autopsy, death scene investigation and review of medical history to exclude known causes of death. Death from occult neoplastic disease in infancy is extremely rare but is within the broad differential of SIDS. We report the sudden and unexpected death of a one-month-old infant from a hepatic (infantile) hemangioendothelioma. The physiologic mechanism of death was likely cardiac failure induced by the circulatory demands of this large vascular tumor and respiratory compromise from diaphragmatic thoracic incursion. The clinical progression and pathology of these relatively common tumors of infant livers are extremely variable. This case dramatically illustrates the potential for fatal outcome of this tumor, as well as the need for the autopsy to determine the cause of sudden and unexpected death in an infant PMID:20465426

A computational model unifies apparently contradictory findings concerning phantom pain

PubMed Central

Boström, Kim J.; de Lussanet, Marc H. E.; Weiss, Thomas; Puta, Christian; Wagner, Heiko

2014-01-01

Amputation often leads to painful phantom sensations, whose pathogenesis is still unclear. Supported by experimental findings, an explanatory model has been proposed that identifies maladaptive reorganization of the primary somatosensory cortex (S1) as a cause of phantom pain. However, it was recently found that BOLD activity during voluntary movements of the phantom positively correlates with phantom pain rating, giving rise to a model of persistent representation. In the present study, we develop a physiologically realistic, computational model to resolve the conflicting findings. Simulations yielded that both the amount of reorganization and the level of cortical activity during phantom movements were enhanced in a scenario with strong phantom pain as compared to a scenario with weak phantom pain. These results suggest that phantom pain, maladaptive reorganization, and persistent representation may all be caused by the same underlying mechanism, which is driven by an abnormally enhanced spontaneous activity of deafferented nociceptive channels. PMID:24931344

Application of Acceleration Sensors in Physiological Experiments

NASA Astrophysics Data System (ADS)

Vavrinský, Erik; Moskal'vá, Daniela; Darříček, Martin; Donoval, Martin; Horínek, František; Popovič, Marían; Miklovič, Peter

2014-09-01

This paper illustrates a promising application of an accelerometer sensor in physiological research, we demonstrated use of accelerometers for monitoring the standard proband physical activity (PA) and also in special applications like respiration and mechanical heart activity, the so-called seismocardiography (SCG) monitoring, physiological activation monitoring and mechanomyography (MMG)

Resistance Training: Physiological Responses and Adaptations (Part 2 of 4).

ERIC Educational Resources Information Center

Fleck, Stephen J.; Kraerner, William J.

1988-01-01

Resistance training causes a variety of physiological reactions, including changes in muscle size, connective tissue size, and bone mineral content. This article summarizes data from a variety of studies and research. (JL)

Aroma Effects on Physiologic and Cognitive Function Following Acute Stress: A Mechanism Investigation

PubMed Central

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

State-dependent and reflex drives to the upper airway: basic physiology with clinical implications

PubMed Central

Hughes, Stuart W.; Malhotra, Atul

2013-01-01

The root cause of the most common and serious of the sleep disorders is impairment of breathing, and a number of factors predispose a particular individual to hypoventilation during sleep. In turn, obstructive hypopneas and apneas are the most common of the sleep-related respiratory problems and are caused by dysfunction of the upper airway as a conduit for airflow. The overarching principle that underpins the full spectrum of clinical sleep-related breathing disorders is that the sleeping brain modifies respiratory muscle activity and control mechanisms and diminishes the ability to respond to respiratory distress. Depression of upper airway muscle activity and reflex responses, and suppression of arousal (i.e., “waking-up”) responses to respiratory disturbance, can also occur with commonly used sedating agents (e.g., hypnotics and anesthetics). Growing evidence indicates that the sometimes critical problems of sleep and sedation-induced depression of breathing and arousal responses may be working through common brain pathways acting on common cellular mechanisms. To identify these state-dependent pathways and reflex mechanisms, as they affect the upper airway, is the focus of this paper. Major emphasis is on the synthesis of established and recent findings. In particular, we specifically focus on 1) the recently defined mechanism of genioglossus muscle inhibition in rapid-eye-movement sleep; 2) convergence of diverse neurotransmitters and signaling pathways onto one root mechanism that may explain pharyngeal motor suppression in sleep and drug-induced brain sedation; 3) the lateral reticular formation as a key hub of respiratory and reflex drives to the upper airway. PMID:23970535

[Mechanisms of urinary tract sterility maintenance].

PubMed

Okrągła, Emilia; Szychowska, Katarzyna; Wolska, Lidia

2014-06-02

Physiologically, urine and the urinary tract are maintained sterile because of physical and chemical properties of urine and the innate immune system's action. The urinary tract is constantly exposed to the invasion of microorganisms from the exterior environment, also because of the anatomical placement of the urethra, in the vicinity of the rectum. Particularly vulnerable to urinary tract infections (UTI) are women (an additional risk factor is pregnancy), but also the elderly and children. The main pathogens causing UTI are bacteria; in 70-95% of cases it is the bacterium Escherichia coli. Infections caused by viruses and fungi are less common and are associated with decreased immunity, pharmacotherapy, or some diseases. Bacteria have evolved a number of factors that facilitate the colonization of the urinary tract: the cover and cell membrane antigens O and K1, lipopolysaccharide (LPS), fimbriae, pile and cilia. On the other hand, the human organism has evolved mechanisms to hinder colonization of the urinary tract: mechanisms arising from the anatomical structure of the urinary tract, the physicochemical properties of the urine and the activity of the innate immune system, also known as non-specific, which isolates and destroys pathogens using immunological processes, and the mechanisms for release of antimicrobial substances such as Tamm-Horsfall protein, mucopolysaccharides, immunoglobulins IgA and IgG, lactoferrin, lipocalin, neutrophils, cytokines and antimicrobial peptides. This review aims to analyze the state of knowledge on the mechanisms to maintain the sterility of the urinary tract used by the human organism and bacterial virulence factors to facilitate the colonization of the urinary tract.

Mechanisms of plant survival and mortality during drought: Why do some plants survive while others succumb to drought?

USGS Publications Warehouse

McDowell, Nate G.; Pockman, William T.; Allen, Craig D.; Breshears, David D.; Cobb, Neil; Kolb, Thomas; Plaut, Jennifer; Sperry, John; West, Adam; Williams, David G.; Yepez, Enrico A.

2008-01-01

Severe droughts have been associated with regional-scale forest mortality worldwide. Climate change is expected to exacerbate regional mortality events; however, prediction remains difficult because the physiological mechanisms underlying drought survival and mortality are poorly understood. We developed a hydraulically based theory considering carbon balance and insect resistance that allowed development and examination of hypotheses regarding survival and mortality. Multiple mechanisms may cause mortality during drought. A common mechanism for plants with isohydric regulation of water status results from avoidance of drought-induced hydraulic failure via stomatal closure, resulting in carbon starvation and a cascade of downstream effects such as reduced resistance to biotic agents. Mortality by hydraulic failure per se may occur for isohydric seedlings or trees near their maximum height. Although anisohydric plants are relatively drought-tolerant, they are predisposed to hydraulic failure because they operate with narrower hydraulic safety margins during drought. Elevated temperatures should exacerbate carbon starvation and hydraulic failure. Biotic agents may amplify and be amplified by drought-induced plant stress. Wet multidecadal climate oscillations may increase plant susceptibility to drought-induced mortality by stimulating shifts in hydraulic architecture, effectively predisposing plants to water stress. Climate warming and increased frequency of extreme events will probably cause increased regional mortality episodes. Isohydric and anisohydric water potential regulation may partition species between survival and mortality, and, as such, incorporating this hydraulic framework may be effective for modeling plant survival and mortality under future climate conditions.

Syndecan-4 Signaling Is Required for Exercise-Induced Cardiac Hypertrophy

PubMed Central

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

A physiologist's view of homeostasis

PubMed Central

Cliff, William; Michael, Joel; McFarland, Jenny; Wenderoth, Mary Pat; Wright, Ann

2015-01-01

Homeostasis is a core concept necessary for understanding the many regulatory mechanisms in physiology. Claude Bernard originally proposed the concept of the constancy of the “milieu interieur,” but his discussion was rather abstract. Walter Cannon introduced the term “homeostasis” and expanded Bernard's notion of “constancy” of the internal environment in an explicit and concrete way. In the 1960s, homeostatic regulatory mechanisms in physiology began to be described as discrete processes following the application of engineering control system analysis to physiological systems. Unfortunately, many undergraduate texts continue to highlight abstract aspects of the concept rather than emphasizing a general model that can be specifically and comprehensively applied to all homeostatic mechanisms. As a result, students and instructors alike often fail to develop a clear, concise model with which to think about such systems. In this article, we present a standard model for homeostatic mechanisms to be used at the undergraduate level. We discuss common sources of confusion (“sticky points”) that arise from inconsistencies in vocabulary and illustrations found in popular undergraduate texts. Finally, we propose a simplified model and vocabulary set for helping undergraduate students build effective mental models of homeostatic regulation in physiological systems. PMID:26628646

Performance assessment techniques for Doppler radar physiological sensors.

PubMed

Hafner, Noah; Lubecke, Victor

2009-01-01

This paper presents a technique for assessing the performance of continuous wave Doppler radar systems for physiological sensing. The technique includes an artificial target for testing physiological sensing radar systems with motion analogous to human heart movement and software algorithms leveraging the capabilities of this target to simply test radar system performance. The mechanical target provides simple to complex patterns of motion that are stable and repeatable. Details of radar system performance can be assessed and the effects of configuration changes that might not appear with a human target can be observed when using this mechanical target.

Concerted changes in N and C primary metabolism in alfalfa (Medicago sativa) under water restriction.

PubMed

Aranjuelo, Iker; Tcherkez, Guillaume; Molero, Gemma; Gilard, Françoise; Avice, Jean-Christophe; Nogués, Salvador

2013-02-01

Although the mechanisms of nodule N(2) fixation in legumes are now well documented, some uncertainty remains on the metabolic consequences of water deficit. In most cases, little consideration is given to other organs and, therefore, the coordinated changes in metabolism in leaves, roots, and nodules are not well known. Here, the effect of water restriction on exclusively N(2)-fixing alfalfa (Medicago sativa L.) plants was investigated, and proteomic, metabolomic, and physiological analyses were carried out. It is shown that the inhibition of nitrogenase activity caused by water restriction was accompanied by concerted alterations in metabolic pathways in nodules, leaves, and roots. The data suggest that nodule metabolism and metabolic exchange between plant organs nearly reached homeostasis in asparagine synthesis and partitioning, as well as the N demand from leaves. Typically, there was (i) a stimulation of the anaplerotic pathway to sustain the provision of C skeletons for amino acid (e.g. glutamate and proline) synthesis; (ii) re-allocation of glycolytic products to alanine and serine/glycine; and (iii) subtle changes in redox metabolites suggesting the implication of a slight oxidative stress. Furthermore, water restriction caused little change in both photosynthetic efficiency and respiratory cost of N(2) fixation by nodules. In other words, the results suggest that under water stress, nodule metabolism follows a compromise between physiological imperatives (N demand, oxidative stress) and the lower input to sustain catabolism.

Leaf proteome alterations in the context of physiological and morphological responses to drought and heat stress in barley (Hordeum vulgare L.)

PubMed Central

von Korff, M.

2013-01-01

The objective of this study was to identify barley leaf proteins differentially regulated in response to drought and heat and the combined stresses in context of the morphological and physiological changes that also occur. The Syrian landrace Arta and the Australian cultivar Keel were subjected to drought, high temperature, or a combination of both treatments starting at heading. Changes in the leaf proteome were identified using differential gel electrophoresis and mass spectrometry. The drought treatment caused strong reductions of biomass and yield, while photosynthetic performance and the proteome were not significantly changed. In contrast, the heat treatment and the combination of heat and drought reduced photosynthetic performance and caused changes of the leaf proteome. The proteomic analysis identified 99 protein spots differentially regulated in response to heat treatment, 14 of which were regulated in a genotype-specific manner. Differentially regulated proteins predominantly had functions in photosynthesis, but also in detoxification, energy metabolism, and protein biosynthesis. The analysis indicated that de novo protein biosynthesis, protein quality control mediated by chaperones and proteases, and the use of alternative energy resources, i.e. glycolysis, play important roles in adaptation to heat stress. In addition, genetic variation identified in the proteome, in plant growth and photosynthetic performance in response to drought and heat represent stress adaption mechanisms to be exploited in future crop breeding efforts. PMID:23918963

Loss of cabin pressurization in U.S. Naval aircraft: 1969-90.

PubMed

Bason, R; Yacavone, D W

1992-05-01

During the 22-year period from 1 January 1969 to 31 December 1990, there were 205 reported cases of loss of cabin pressure in US Naval aircraft; 21 were crew-initiated and 184 were deemed accidental. The ambient altitudes varied from 10,000 ft (3048 m) to 40,000 ft. (12192 m). The most common reason for crew-initiated decompression was to clear smoke and fumes from the cockpit/cabin (95%). The most common cause for accidental loss of cabin pressure was mechanical (73.37%), with aircraft structural damage accounting for the remaining 26.63%. Serious physiological problems included 1 pneumothorax, 11 cases of Type I decompression sickness, 23 cases of mild to moderate hypoxia with no loss of consciousness, 18 cases of hypoxia with loss of consciousness, and 3 lost aircraft with 4 fatalities due to incapacitation by hypoxia. In addition, 12 ejections were attributed to loss of cockpit pressure. Nine of the ejections were deliberate and three were accidental, caused by wind blast activation of the face curtain. Three aviators lost their lives following ejection and seven aircraft were lost. While the incidence of loss of cabin pressure in Naval aircraft appears low, it none-the-less presents a definite risk to the aircrew. Lectures on the loss of cabin/cockpit pressurization should continue during indoctrination and refresher physiology training.

Mechanisms of haptoglobin protection against hemoglobin peroxidation triggered endothelial damage.

PubMed

Schaer, C A; Deuel, J W; Bittermann, A G; Rubio, I G; Schoedon, G; Spahn, D R; Wepf, R A; Vallelian, F; Schaer, D J

2013-11-01

Extracellular hemoglobin (Hb) has been recognized as a disease trigger in hemolytic conditions such as sickle cell disease, malaria, and blood transfusion. In vivo, many of the adverse effects of free Hb can be attenuated by the Hb scavenger acute-phase protein haptoglobin (Hp). The primary physiologic disturbances that can be caused by free Hb are found within the cardiovascular system and Hb-triggered oxidative toxicity toward the endothelium has been promoted as a potential mechanism. The molecular mechanisms of this toxicity as well as of the protective activities of Hp are not yet clear. Within this study, we systematically investigated the structural, biochemical, and cell biologic nature of Hb toxicity in an endothelial cell system under peroxidative stress. We identified two principal mechanisms of oxidative Hb toxicity that are mediated by globin degradation products and by modified lipoprotein species, respectively. The two damage pathways trigger diverse and discriminative inflammatory and cytotoxic responses. Hp provides structural stabilization of Hb and shields Hb's oxidative reactions with lipoproteins, providing dramatic protection against both pathways of toxicity. By these mechanisms, Hp shifts Hb's destructive pseudo-peroxidative reaction to a potential anti-oxidative function during peroxidative stress.

Mechanical factors direct mouse aortic remodelling during early maturation

PubMed Central

Le, Victoria P.; Cheng, Jeffrey K.; Kim, Jungsil; Staiculescu, Marius C.; Ficker, Shawn W.; Sheth, Saahil C.; Bhayani, Siddharth A.; Mecham, Robert P.; Yanagisawa, Hiromi; Wagenseil, Jessica E.

2015-01-01

Numerous diseases have been linked to genetic mutations that lead to reduced amounts or disorganization of arterial elastic fibres. Previous work has shown that mice with reduced amounts of elastin (Eln+/−) are able to live a normal lifespan through cardiovascular adaptations, including changes in haemodynamic stresses, arterial geometry and arterial wall mechanics. It is not known if the timeline and presence of these adaptations are consistent in other mouse models of elastic fibre disease, such as those caused by the absence of fibulin-5 expression (Fbln5−/−). Adult Fbln5−/− mice have disorganized elastic fibres, decreased arterial compliance and high blood pressure. We examined mechanical behaviour of the aorta in Fbln5−/− mice through early maturation when the elastic fibres are being assembled. We found that the physiologic circumferential stretch, stress and modulus of Fbln5−/− aorta are maintained near wild-type levels. Constitutive modelling suggests that elastin contributions to the total stress are decreased, whereas collagen contributions are increased. Understanding how collagen fibre structure and mechanics compensate for defective elastic fibres to meet the mechanical requirements of the maturing aorta may help to better understand arterial remodelling in human elastinopathies. PMID:25652465

Influencing Mechanism of Ocean Acidification on Byssus Performance in the Pearl Oyster Pinctada fucata.

PubMed

Li, Shiguo; Liu, Chuang; Zhan, Aibin; Xie, Liping; Zhang, Rongqing

2017-07-05

The byssus is an important adhesive structure by which bivalves robustly adhere to underwater substrates. It is susceptible to carbon dioxide-driven ocean acidification (OA). Previous investigations have documented significant adverse effects of OA on the performance of byssal threads, but the mechanisms remain largely unknown. In this study, multiple approaches were employed to reveal the underlying mechanisms for the effects of OA on byssus production and mechanical properties in the pearl oyster Pinctada fucata. The results showed that OA altered the abundance and secondary structure of byssal proteins and affected the contents of metal ions in distal threads, which together reduced the byssus diameter and amplified byssus nanocavity, causing reductions in mechanical properties (strength and extensibility). Expression analysis of key foot protein genes further confirmed changes in byssal protein abundance. Moreover, comparative transcriptome analysis revealed enrichment of ion transportation- and apoptosis-related categories, up-regulation of apoptosis-related pathways, and down-regulation of the "extracellular matrix-receptor interaction" pathway, which may influence foot locomotion physiology, leading to a decrease in byssus production. This study provides mechanistic insight into the effects of OA on pearl oyster byssus, which should broaden our overall understanding of the impacts of OA on marine ecosystem.

Eccentric and concentric cardiac hypertrophy induced by exercise training: microRNAs and molecular determinants.

PubMed

Fernandes, T; Soci, U P R; Oliveira, E M

2011-09-01

Among the molecular, biochemical and cellular processes that orchestrate the development of the different phenotypes of cardiac hypertrophy in response to physiological stimuli or pathological insults, the specific contribution of exercise training has recently become appreciated. Physiological cardiac hypertrophy involves complex cardiac remodeling that occurs as an adaptive response to static or dynamic chronic exercise, but the stimuli and molecular mechanisms underlying transduction of the hemodynamic overload into myocardial growth are poorly understood. This review summarizes the physiological stimuli that induce concentric and eccentric physiological hypertrophy, and discusses the molecular mechanisms, sarcomeric organization, and signaling pathway involved, also showing that the cardiac markers of pathological hypertrophy (atrial natriuretic factor, β-myosin heavy chain and α-skeletal actin) are not increased. There is no fibrosis and no cardiac dysfunction in eccentric or concentric hypertrophy induced by exercise training. Therefore, the renin-angiotensin system has been implicated as one of the regulatory mechanisms for the control of cardiac function and structure. Here, we show that the angiotensin II type 1 (AT1) receptor is locally activated in pathological and physiological cardiac hypertrophy, although with exercise training it can be stimulated independently of the involvement of angiotensin II. Recently, microRNAs (miRs) have been investigated as a possible therapeutic approach since they regulate the translation of the target mRNAs involved in cardiac hypertrophy; however, miRs in relation to physiological hypertrophy have not been extensively investigated. We summarize here profiling studies that have examined miRs in pathological and physiological cardiac hypertrophy. An understanding of physiological cardiac remodeling may provide a strategy to improve ventricular function in cardiac dysfunction.

Microbiota and metabolic diseases.

PubMed

Pascale, Alessia; Marchesi, Nicoletta; Marelli, Cristina; Coppola, Adriana; Luzi, Livio; Govoni, Stefano; Giustina, Andrea; Gazzaruso, Carmine

2018-05-02

The microbiota is a complex ecosystem of microorganisms consisting of bacteria, viruses, protozoa, and fungi, living in different districts of the human body, such as the gastro-enteric tube, skin, mouth, respiratory system, and the vagina. Over 70% of the microbiota lives in the gastrointestinal tract in a mutually beneficial relationship with its host. The microbiota plays a major role in many metabolic functions, including modulation of glucose and lipid homeostasis, regulation of satiety, production of energy and vitamins. It exerts a role in the regulation of several biochemical and physiological mechanisms through the production of metabolites and substances. In addition, the microbiota has important anti-carcinogenetic and anti-inflammatory actions. There is growing evidence that any modification in the microbiota composition can lead to several diseases, including metabolic diseases, such as obesity and diabetes, and cardiovascular diseases. This is because alterations in the microbiota composition can cause insulin resistance, inflammation, vascular, and metabolic disorders. The causes of the microbiota alterations and the mechanisms by which microbiota modifications can act on the development of metabolic and cardiovascular diseases have been reported. Current and future preventive and therapeutic strategies to prevent these diseases by an adequate modulation of the microbiota have been also discussed.

Mechanisms of chromium (VI)-induced apoptosis in anterior pituitary cells.

PubMed

Quinteros, Fernanda A; Machiavelli, Leticia I; Miler, Eliana A; Cabilla, Jimena P; Duvilanski, Beatriz H

2008-07-30

Hexavalent chromium (Cr (VI)) is a highly toxic metal. Exposure to Cr (VI) compounds may affect reproductive functions. Due to the importance of anterior pituitary hormones on reproductive physiology we have studied the effects of Cr (VI) on anterior pituitary. We previously demonstrated that, after in vivo Cr (VI) administration, Cr accumulates in the pituitary gland and affects prolactin secretion. In vitro, Cr (VI) causes apoptosis in anterior pituitary cells due to oxidative stress generation. To better understand the mechanisms involved in Cr (VI)-induced apoptosis we studied: (a) whether Cr (VI) affects the intracellular antioxidant response and (b) which of the apoptotic factors participates in Cr (VI) effect. Our results show that Cr (VI) treatment induces a decrease in catalase and glutathione peroxidase (GPx) activity but does not modify glutathione reductase (GR) activity. Cr (VI) exposure causes an increase of GSH levels. p53 and Bax mRNA are also upregulated by the metal. Pifithrin alpha, a p53 transcriptional inhibitor, increases Cr (VI) cytotoxicity, suggesting a role of p53 as a survival molecule. The antioxidant N-acetyl-cysteine (NAC) could prevent Bax mRNA increase and caspase 3 activation, confirming that Cr (VI)-induced apoptosis involves oxidative stress generation.

[Difference in target antigens between central tolerance and peripheral tolerance deficiencies].

PubMed

Chida, Natsuko; Kobayashi, Ichiro

2015-01-01

Failure of the immunotolerance mechanisms causes multiple organ-specific autoimmune disorders. Mutations of autoimmune regulator (AIRE) gene result in central immunotolerance deficiency named autoimmune polyendocrinopathy, candidiasis, ectodermal dystrophy (APECED). Mutations of FOXP3 genes cause regulatory T cell (Treg) deficiency named immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome. Because T cell tolerance influences B cell tolerance, autoantibodies seem to reflect the presence of autoreactive T cells with the same antigen specificity. To date many differences in both clinical features and autoantibody profiles have been described between APECED and IPEX syndrome. In addition to the differences in target organs, we have found differences in the target antigens in the same organ, small intestine, between both disorders; anti-autoimmune enteropathy-related 75 kDa antigen (AIE-75) antibodies are specific to IPEX syndrome, whereas anti-tryptophan hydroxylase-1 (TPH-1) antibodies are specific to APECED. These facts suggest that immunotolerance to AIE-75 depends on the Treg, whereas the tolerance to TPH-1 depends on the central mechanisms. Furthermore, given the earlier onset and more serious clinical features of IPEX syndrome than APECED, physiological roles of Aire on the selection of Treg may be, if present, limited.

Cascading effects of thermally-induced anemone bleaching on associated anemonefish hormonal stress response and reproduction.

PubMed

Beldade, Ricardo; Blandin, Agathe; O'Donnell, Rory; Mills, Suzanne C

2017-10-10

Organisms can behaviorally, physiologically, and morphologically adjust to environmental variation via integrative hormonal mechanisms, ultimately allowing animals to cope with environmental change. The stress response to environmental and social changes commonly promotes survival at the expense of reproduction. However, despite climate change impacts on population declines and diversity loss, few studies have attributed hormonal stress responses, or their regulatory effects, to climate change in the wild. Here, we report hormonal and fitness responses of individual wild fish to a recent large-scale sea warming event that caused widespread bleaching on coral reefs. This 14-month monitoring study shows a strong correlation between anemone bleaching (zooxanthellae loss), anemonefish stress response, and reproductive hormones that decreased fecundity by 73%. These findings suggest that hormone stress responses play a crucial role in changes to population demography following climate change and plasticity in hormonal responsiveness may be a key mechanism enabling individual acclimation to climate change.Elevated temperatures can cause anemones to bleach, with unknown effects on their associated symbiotic fish. Here, Beldade and colleagues show that climate-induced bleaching alters anemonefish hormonal stress response, resulting in decreased reproductive hormones and severely impacted reproduction.

Structural and Mechanical Repair of Diffuse Damage in Cortical Bone in vivo

PubMed Central

Seref-Ferlengez, Zeynep; Basta-Pljakic, Jelena; Kennedy, Oran D.; Philemon, Claudy J.; Schaffler, Mitchell B.

2014-01-01

Physiological wear and tear causes bone microdamage at several hierarchical levels, and these have different biological consequences. Bone remodeling is widely held to be the mechanism by which bone microdamage is repaired. However, recent studies showed that unlike typical linear microcracks, small crack damage, the clusters of submicron-sized matrix cracks also known as diffuse damage (Dif.Dx), does not activate remodeling. Thus, the fate of diffuse damage in vivo is not known. To examine this, we induced selectively Dif.Dx in rat ulnae in vivo by using end-load ulnar bending creep model. Changes in damage content were assessed by histomorphometry and mechanical testing immediately after loading (i.e., acute loaded) or at 14 days after damage induction (i.e., survival ulnae). Dif.Dx area was markedly reduced over the 14-day survival period after loading (p<0.02). We did not observe any intracortical resorption and there was no increase in cortical bone area in survival ulnae. The reduction in whole bone stiffness in acute loaded ulnae was restored to baseline levels in survival ulnae (p>0.6). Microindentation studies showed that Dif.Dx caused a highly localized reduction in elastic modulus in diffuse damage regions of the ulnar cortex. Moduli in these previously damaged bone areas were restored to control values by 14 days after loading. Our current findings indicate that small crack damage in bone can be repaired without bone remodeling, and suggest that alternative repair mechanisms exist in bone to deal with submicron-sized matrix cracks. Those mechanisms are currently unknown and further investigations are needed to elucidate the mechanisms by which this direct repair occurs. PMID:25042459

A Novel Cardiotoxic Mechanism for a Pervasive Global Pollutant

NASA Astrophysics Data System (ADS)

Brette, Fabien; Shiels, Holly A.; Galli, Gina L. J.; Cros, Caroline; Incardona, John P.; Scholz, Nathaniel L.; Block, Barbara A.

2017-01-01

The Deepwater Horizon disaster drew global attention to the toxicity of crude oil and the potential for adverse health effects amongst marine life and spill responders in the northern Gulf of Mexico. The blowout released complex mixtures of polycyclic aromatic hydrocarbons (PAHs) into critical pelagic spawning habitats for tunas, billfishes, and other ecologically important top predators. Crude oil disrupts cardiac function and has been associated with heart malformations in developing fish. However, the precise identity of cardiotoxic PAHs, and the mechanisms underlying contractile dysfunction are not known. Here we show that phenanthrene, a PAH with a benzene 3-ring structure, is the key moiety disrupting the physiology of heart muscle cells. Phenanthrene is a ubiquitous pollutant in water and air, and the cellular targets for this compound are highly conserved across vertebrates. Our findings therefore suggest that phenanthrene may be a major worldwide cause of vertebrate cardiac dysfunction.

Innate immune activation in neurodegenerative disease.

PubMed

Heneka, Michael T; Kummer, Markus P; Latz, Eicke

2014-07-01

The triggering of innate immune mechanisms is emerging as a crucial component of major neurodegenerative diseases. Microglia and other cell types in the brain can be activated in response to misfolded proteins or aberrantly localized nucleic acids. This diverts microglia from their physiological and beneficial functions, and leads to their sustained release of pro-inflammatory mediators. In this Review, we discuss how the activation of innate immune signalling pathways - in particular, the NOD-, LRR- and pyrin domain-containing 3 (NLRP3) inflammasome - by aberrant host proteins may be a common step in the development of diverse neurodegenerative disorders. During chronic activation of microglia, the sustained exposure of neurons to pro-inflammatory mediators can cause neuronal dysfunction and contribute to cell death. As chronic neuroinflammation is observed at relatively early stages of neurodegenerative disease, targeting the mechanisms that drive this process may be useful for diagnostic and therapeutic purposes.

Light-induced vibration in the hearing organ

PubMed Central

Ren, Tianying; He, Wenxuan; Li, Yizeng; Grosh, Karl; Fridberger, Anders

2014-01-01

The exceptional sensitivity of mammalian hearing organs is attributed to an active process, where force produced by sensory cells boost sound-induced vibrations, making soft sounds audible. This process is thought to be local, with each section of the hearing organ capable of amplifying sound-evoked movement, and nearly instantaneous, since amplification can work for sounds at frequencies up to 100 kHz in some species. To test these fundamental precepts, we developed a method for focally stimulating the living hearing organ with light. Light pulses caused intense and highly damped mechanical responses followed by traveling waves that developed with considerable delay. The delayed response was identical to movements evoked by click-like sounds. This shows that the active process is neither local nor instantaneous, but requires mechanical waves traveling from the cochlear base toward its apex. A physiologically-based mathematical model shows that such waves engage the active process, enhancing hearing sensitivity. PMID:25087606

The neurophysiology of sexual arousal.

PubMed

Schober, Justine M; Pfaff, Donald

2007-09-01

Our understanding of the process and initiation of sexual arousal is being enhanced by both animal and human studies, inclusive of basic science principles and research on clinical outcomes. Sexual arousal is dependent on neural (sensory and cognitive) factors, hormonal factors, genetic factors and, in the human case, the complex influences of culture and context. Sexual arousal activates the cognitive and physiologic processes that can eventually lead to sexual behavior. Sexual arousal comprises a particular subset of central nervous system arousal functions which depend on primitive, fundamental arousal mechanisms that cause generalized brain activity, but are manifest in a sociosexual context. The neurophysiology of sexual arousal is seen as a bidirectional system universal to all vertebrates. The following review includes known neural and genomic mechanisms of a hormone-dependent circuit for simple sex behavior. New information about hormone effects on causal steps related to sex hormones' nuclear receptor isoforms expressed by hypothalamic neurons continues to enrich our understanding of this neurophysiology.

Mitochondria in the Aging Muscles of Flies and Mice: New Perspectives for Old Characters

PubMed Central

2016-01-01

Sarcopenia is the loss of muscle mass accompanied by a decrease in muscle strength and resistance and is the main cause of disability among the elderly. Muscle loss begins long before there is any clear physical impact in the senior adult. Despite all this, the molecular mechanisms underlying muscle aging are far from being understood. Recent studies have identified that not only mitochondrial metabolic dysfunction but also mitochondrial dynamics and mitochondrial calcium uptake could be involved in the degeneration of skeletal muscle mass. Mitochondrial homeostasis influences muscle quality which, in turn, could play a triggering role in signaling of systemic aging. Thus, it has become apparent that mitochondrial status in muscle cells could be a driver of whole body physiology and organismal aging. In the present review, we discuss the existing evidence for the mitochondria related mechanisms underlying the appearance of muscle aging and sarcopenia in flies and mice. PMID:27630760

Mitochondria in the Aging Muscles of Flies and Mice: New Perspectives for Old Characters.

PubMed

Del Campo, Andrea; Jaimovich, Enrique; Tevy, Maria Florencia

2016-01-01

Sarcopenia is the loss of muscle mass accompanied by a decrease in muscle strength and resistance and is the main cause of disability among the elderly. Muscle loss begins long before there is any clear physical impact in the senior adult. Despite all this, the molecular mechanisms underlying muscle aging are far from being understood. Recent studies have identified that not only mitochondrial metabolic dysfunction but also mitochondrial dynamics and mitochondrial calcium uptake could be involved in the degeneration of skeletal muscle mass. Mitochondrial homeostasis influences muscle quality which, in turn, could play a triggering role in signaling of systemic aging. Thus, it has become apparent that mitochondrial status in muscle cells could be a driver of whole body physiology and organismal aging. In the present review, we discuss the existing evidence for the mitochondria related mechanisms underlying the appearance of muscle aging and sarcopenia in flies and mice.

The overwintering physiology of the emerald ash borer, Agrilus planipennis fairmaire (coleoptera: buprestidae).

PubMed

Crosthwaite, Jill C; Sobek, Stephanie; Lyons, D Barry; Bernards, Mark A; Sinclair, Brent J

2011-01-01

Ability to survive cold is an important factor in determining northern range limits of insects. The emerald ash borer (Agrilus planipennis) is an invasive beetle introduced from Asia that is causing extensive damage to ash trees in North America, but little is known about its cold tolerance. Herein, the cold tolerance strategy and mechanisms involved in the cold tolerance of the emerald ash borer were investigated, and seasonal changes in these mechanisms monitored. The majority of emerald ash borers survive winter as freeze-intolerant prepupae. In winter, A. planipennis prepupae have low supercooling points (approximately -30°C), which they achieve by accumulating high concentrations of glycerol (approximately 4M) in their body fluids and by the synthesis of antifreeze agents. Cuticular waxes reduce inoculation from external ice. This is the first comprehensive study of seasonal changes in cold tolerance in a buprestid beetle. 2010 Elsevier Ltd. All rights reserved.

Multicellular microorganisms: laboratory versus nature.

PubMed

Palková, Zdena

2004-05-01

Our present in-depth knowledge of the physiology and regulatory mechanisms of microorganisms has arisen from our ability to remove them from their natural, complex ecosystems into pure liquid cultures. These cultures are grown under optimized laboratory conditions and allow us to study microorganisms as individuals. However, microorganisms naturally grow in conditions that are far from optimal, which causes them to become organized into multicellular communities that are better protected against the harmful environment. Moreover, this multicellular existence allows individual cells to differentiate and acquire specific properties, such as forming resistant spores, which benefit the whole population. The relocation of natural microorganisms to the laboratory can result in their adaptation to these favourable conditions, which is accompanied by complex changes that include the repression of some protective mechanisms that are essential in nature. Laboratory microorganisms that have been cultured for long periods under optimized conditions might therefore differ markedly from those that exist in natural ecosystems.

Heart failure drug changes the mechanoenzymology of the cardiac myosin powerstroke.

PubMed

Rohde, John A; Thomas, David D; Muretta, Joseph M

2017-03-07

Omecamtiv mecarbil (OM), a putative heart failure therapeutic, increases cardiac contractility. We hypothesize that it does this by changing the structural kinetics of the myosin powerstroke. We tested this directly by performing transient time-resolved FRET on a ventricular cardiac myosin biosensor. Our results demonstrate that OM stabilizes myosin's prepowerstroke structural state, supporting previous measurements showing that the drug shifts the equilibrium constant for myosin-catalyzed ATP hydrolysis toward the posthydrolysis biochemical state. OM slowed the actin-induced powerstroke, despite a twofold increase in the rate constant for actin-activated phosphate release, the biochemical step in myosin's ATPase cycle associated with force generation and the conversion of chemical energy into mechanical work. We conclude that OM alters the energetics of cardiac myosin's mechanical cycle, causing the powerstroke to occur after myosin weakly binds to actin and releases phosphate. We discuss the physiological implications for these changes.

Voltage gating of mechanosensitive PIEZO channels.

PubMed

Moroni, Mirko; Servin-Vences, M Rocio; Fleischer, Raluca; Sánchez-Carranza, Oscar; Lewin, Gary R

2018-03-15

Mechanosensitive PIEZO ion channels are evolutionarily conserved proteins whose presence is critical for normal physiology in multicellular organisms. Here we show that, in addition to mechanical stimuli, PIEZO channels are also powerfully modulated by voltage and can even switch to a purely voltage-gated mode. Mutations that cause human diseases, such as xerocytosis, profoundly shift voltage sensitivity of PIEZO1 channels toward the resting membrane potential and strongly promote voltage gating. Voltage modulation may be explained by the presence of an inactivation gate in the pore, the opening of which is promoted by outward permeation. Older invertebrate (fly) and vertebrate (fish) PIEZO proteins are also voltage sensitive, but voltage gating is a much more prominent feature of these older channels. We propose that the voltage sensitivity of PIEZO channels is a deep property co-opted to add a regulatory mechanism for PIEZO activation in widely different cellular contexts.

Apoptosis-mediated endothelial toxicity but not direct calcification or functional changes in anti-calcification proteins defines pathogenic effects of calcium phosphate bions

NASA Astrophysics Data System (ADS)

Kutikhin, Anton G.; Velikanova, Elena A.; Mukhamadiyarov, Rinat A.; Glushkova, Tatiana V.; Borisov, Vadim V.; Matveeva, Vera G.; Antonova, Larisa V.; Filip'Ev, Dmitriy E.; Golovkin, Alexey S.; Shishkova, Daria K.; Burago, Andrey Yu.; Frolov, Alexey V.; Dolgov, Viktor Yu.; Efimova, Olga S.; Popova, Anna N.; Malysheva, Valentina Yu.; Vladimirov, Alexandr A.; Sozinov, Sergey A.; Ismagilov, Zinfer R.; Russakov, Dmitriy M.; Lomzov, Alexander A.; Pyshnyi, Dmitriy V.; Gutakovsky, Anton K.; Zhivodkov, Yuriy A.; Demidov, Evgeniy A.; Peltek, Sergey E.; Dolganyuk, Viatcheslav F.; Babich, Olga O.; Grigoriev, Evgeniy V.; Brusina, Elena B.; Barbarash, Olga L.; Yuzhalin, Arseniy E.

2016-06-01

Calcium phosphate bions (CPB) are biomimetic mineralo-organic nanoparticles which represent a physiological mechanism regulating the function, transport and disposal of calcium and phosphorus in the human body. We hypothesised that CPB may be pathogenic entities and even a cause of cardiovascular calcification. Here we revealed that CPB isolated from calcified atherosclerotic plaques and artificially synthesised CPB are morphologically and chemically indistinguishable entities. Their formation is accelerated along with the increase in calcium salts-phosphates/serum concentration ratio. Experiments in vitro and in vivo showed that pathogenic effects of CPB are defined by apoptosis-mediated endothelial toxicity but not by direct tissue calcification or functional changes in anti-calcification proteins. Since the factors underlying the formation of CPB and their pathogenic mechanism closely resemble those responsible for atherosclerosis development, further research in this direction may help us to uncover triggers of this disease.

Effects of short-term hypothermal and contrast exposure on immunophysiological parameters of laboratory animals.

PubMed

Kalenova, L F; Fisher, T A; Suhovey, J G; Besedin, I M

2009-05-01

Experiments on inbred animals showed that short-term exposure in cold water significantly modified structural and functional parameters of the immune system at different levels of its organization, from bone marrow hemopoiesis to effector stage of the immune response to antigen. The thermal factor caused changes in nonspecific and specific mechanisms of the immune system. Hypothermal exposure (7-9 degrees C, 5 sec) increased the thymic index and bone marrow lymphocyte count, reduced absorption capacity and stimulated metabolic activity of phagocytes, stimulated cell-mediated and suppressed humoral immunity. Contrast exposure in cold and hot water (7-9 degrees C, 5 sec/40-42 degrees C, 30 sec) increased monocyte count in bone marrow and reduced it in the their peripheral blood, reduced metabolic activity of phagocytes, stimulated cell-mediated and suppressed humoral immunity. These data demonstrate physiological mechanisms of interactions between the thermoregulatory and immune systems.

A hormone-related female anti-aphrodisiac signals temporary infertility and causes sexual abstinence to synchronize parental care.

PubMed

Engel, Katharina C; Stökl, Johannes; Schweizer, Rebecca; Vogel, Heiko; Ayasse, Manfred; Ruther, Joachim; Steiger, Sandra

2016-03-22

The high energetic demand of parental care requires parents to direct their resources towards the support of existing offspring rather than investing into the production of additional young. However, how such a resource flow is channelled appropriately is poorly understood. In this study, we provide the first comprehensive analysis of the physiological mechanisms coordinating parental and mating effort in an insect exhibiting biparental care. We show a hormone-mediated infertility in female burying beetles during the time the current offspring is needy and report that this temporary infertility is communicated via a pheromone to the male partner, where it inhibits copulation. A shared pathway of hormone and pheromone system ensures the reliability of the anti-aphrodisiac. Female infertility and male sexual abstinence provide for the concerted investment of parental resources into the existing developing young. Our study thus contributes to our deeper understanding of the mechanisms underlying adaptive parental decisions.

Free radicals in the regulation of damage and cell death - basic mechanisms and prevention.

PubMed

Silva, J P; Coutinho, O P

2010-06-01

Reactive oxygen (ROS) and nitrogen (RNS) species are known to accumulate intracellularly due to both exogenous and/or endogenous factors. In normal physiological conditions, these reactive species are maintained in an equilibrium state by the cells' antioxidant defence systems. In addition, they are recognised to play important roles in several physiological functions. However, when an imbalance in the equilibrium between oxidants and antioxidants occurs in favour of the former, we come to a situation defined as oxidative stress. ROS/RNS can cause damage to all biomolecules (namely proteins, lipids and DNA) and ultimately participate in the regulation of mechanisms leading to cell death, being implicated in the etiology of several pathologies (like neurodegenerative and cardiovascular diseases). To cope with oxidative stress, cells possess effective enzymatic (e.g. superoxide dismutase, catalase, glutathione peroxidase) and non-enzymatic (e.g. glutathione, thioredoxin, coenzyme Q) antioxidant systems. In addition, several compounds present in plants and vegetables (e.g. vitamins C and E, polyphenols) have been described to react with free radicals. However, some drawbacks associated to these natural compounds are in part responsible for the undergoing development of novel synthetic compounds capable of acting as antioxidants and protect cells against oxidative stress-induced cell death. Here, we review the basic mechanisms of ROS/RNS formation, as well as their interaction with biomolecules and regulation of cell death, in order to identify possible drug targets. We also report the importance of natural antioxidant systems and the ongoing research leading to the development of more powerful and effective antioxidant drugs.

Gene-environment interaction and male reproductive function

PubMed Central

Axelsson, Jonatan; Bonde, Jens Peter; Giwercman, Yvonne L.; Rylander, Lars; Giwercman, Aleksander

2010-01-01

As genetic factors can hardly explain the changes taking place during short time spans, environmental and lifestyle-related factors have been suggested as the causes of time-related deterioration of male reproductive function. However, considering the strong heterogeneity of male fecundity between and within populations, genetic variants might be important determinants of the individual susceptibility to the adverse effects of environment or lifestyle. Although the possible mechanisms of such interplay in relation to the reproductive system are largely unknown, some recent studies have indicated that specific genotypes may confer a larger risk of male reproductive disorders following certain exposures. This paper presents a critical review of animal and human evidence on how genes may modify environmental effects on male reproductive function. Some examples have been found that support this mechanism, but the number of studies is still limited. This type of interaction studies may improve our understanding of normal physiology and help us to identify the risk factors to male reproductive malfunction. We also shortly discuss other aspects of gene-environment interaction specifically associated with the issue of reproduction, namely environmental and lifestyle factors as the cause of sperm DNA damage. It remains to be investigated to what extent such genetic changes, by natural conception or through the use of assisted reproductive techniques, are transmitted to the next generation, thereby causing increased morbidity in the offspring. PMID:20348940

Physiologically relevant organs on chips

PubMed Central

Yum, Kyungsuk; Hong, Soon Gweon; Lee, Luke P.

2015-01-01

Recent advances in integrating microengineering and tissue engineering have generated promising microengineered physiological models for experimental medicine and pharmaceutical research. Here we review the recent development of microengineered physiological systems, or organs on chips, that reconstitute the physiologically critical features of specific human tissues and organs and their interactions. This technology uses microengineering approaches to construct organ-specific microenvironments, reconstituting tissue structures, tissue–tissue interactions and interfaces, and dynamic mechanical and biochemical stimuli found in specific organs, to direct cells to assemble into functional tissues. We first discuss microengineering approaches to reproduce the key elements of physiologically important, dynamic mechanical microenvironments, biochemical microenvironments, and microarchitectures of specific tissues and organs in microfluidic cell culture systems. This is followed by examples of microengineered individual organ models that incorporate the key elements of physiological microenvironments into single microfluidic cell culture systems to reproduce organ-level functions. Finally, microengineered multiple organ systems that simulate multiple organ interactions to better represent human physiology, including human responses to drugs, is covered in this review. This emerging organs-on-chips technology has the potential to become an alternative to 2D and 3D cell culture and animal models for experimental medicine, human disease modeling, drug development, and toxicology. PMID:24357624

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)

Nitric oxide: a physiologic messenger.

PubMed

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.

Mendelian randomization analysis associates increased serum urate, due to genetic variation in uric acid transporters, with improved renal function.

PubMed

Hughes, Kim; Flynn, Tanya; de Zoysa, Janak; Dalbeth, Nicola; Merriman, Tony R

2014-02-01

Increased serum urate predicts chronic kidney disease independent of other risk factors. The use of xanthine oxidase inhibitors coincides with improved renal function. Whether this is due to reduced serum urate or reduced production of oxidants by xanthine oxidase or another physiological mechanism remains unresolved. Here we applied Mendelian randomization, a statistical genetics approach allowing disentangling of cause and effect in the presence of potential confounding, to determine whether lowering of serum urate by genetic modulation of renal excretion benefits renal function using data from 7979 patients of the Atherosclerosis Risk in Communities and Framingham Heart studies. Mendelian randomization by the two-stage least squares method was done with serum urate as the exposure, a uric acid transporter genetic risk score as instrumental variable, and estimated glomerular filtration rate and serum creatinine as the outcomes. Increased genetic risk score was associated with significantly improved renal function in men but not in women. Analysis of individual genetic variants showed the effect size associated with serum urate did not correlate with that associated with renal function in the Mendelian randomization model. This is consistent with the possibility that the physiological action of these genetic variants in raising serum urate correlates directly with improved renal function. Further studies are required to understand the mechanism of the potential renal function protection mediated by xanthine oxidase inhibitors.

Physiologic mechanisms of circulatory and body fluid losses in weightlessness identified by mathematical modeling

NASA Technical Reports Server (NTRS)

Simanonok, K. E.; Srinivasan, R. S.; Charles, J. B.

1993-01-01

Central volume expansion due to fluid shifts in weightlessness is believed to activate adaptive reflexes which ultimately result in a reduction of the total circulating blood volume. However, the flight data suggests that a central volume overdistention does not persist, in which case some other factor or factors must be responsible for body fluid losses. We used a computer simulation to test the hypothesis that factors other than central volume overdistention are involved in the loss of blood volume and other body fluid volumes observed in weightlessness and in weightless simulations. Additionally, the simulation was used to identify these factors. The results predict that atrial volumes and pressures return to their prebedrest baseline values within the first day of exposure to head down tilt (HDT) as the blood volume is reduced by an elevated urine formation. They indicate that the mechanisms for large and prolonged body fluid losses in weightlessness is red cell hemoconcentration that elevates blood viscosity and peripheral resistance, thereby lowering capillary pressure. This causes a prolonged alteration of the balance of Starling forces, depressing the extracellular fluid volume until the hematocrit is returned to normal through a reduction of the red cell mass, which also allows some restoration of the plasma volume. We conclude that the red cell mass becomes the physiologic driver for a large 'undershoot' of the body fluid volumes after the normalization of atrial volumes and pressures.

Fetal Mouse Cardiovascular Imaging Using a High-frequency Ultrasound (30/45MHZ) System.

PubMed

Touma, Marlin

2018-05-05

Congenital heart defects (CHDs) are the most common cause of childhood morbidity and early mortality. Prenatal detection of the underlying molecular mechanisms of CHDs is crucial for inventing new preventive and therapeutic strategies. Mutant mouse models are powerful tools to discover new mechanisms and environmental stress modifiers that drive cardiac development and their potential alteration in CHDs. However, efforts to establish the causality of these putative contributors have been limited to histological and molecular studies in non-survival animal experiments, in which monitoring the key physiological and hemodynamic parameters is often absent. Live imaging technology has become an essential tool to establish the etiology of CHDs. In particular, ultrasound imaging can be used prenatally without surgically exposing the fetuses, allowing maintaining their baseline physiology while monitoring the impact of environmental stress on the hemodynamic and structural aspects of cardiac chamber development. Herein, we use the High-Frequency Ultrasound (30/45) system to examine the cardiovascular system in fetal mice at E18.5 in utero at the baseline and in response to prenatal hypoxia exposure. We demonstrate the feasibility of the system to measure cardiac chamber size, morphology, ventricular function, fetal heart rate, and umbilical artery flow indices, and their alterations in fetal mice exposed to systemic chronic hypoxia in utero in real time.

From Tusko to Titin: the role for comparative physiology in an era of molecular discovery.

PubMed

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.

A PP2A-mediated feedback mechanism controls Ca2+-dependent NO synthesis under physiological oxygen.

PubMed

Keeley, Thomas P; Siow, Richard C M; Jacob, Ron; Mann, Giovanni E

2017-12-01

Intracellular O 2 is a key regulator of NO signaling, yet most in vitro studies are conducted in atmospheric O 2 levels, hyperoxic with respect to the physiologic milieu. We investigated NO signaling in endothelial cells cultured in physiologic (5%) O 2 and stimulated with histamine or shear stress. Culture of cells in 5% O 2 (>5 d) decreased histamine- but not shear stress-stimulated endothelial (e)NOS activity. Unlike cells adapted to a hypoxic environment (1% O 2 ), those cultured in 5% O 2 still mobilized sufficient Ca 2+ to activate AMPK. Enhanced expression and membrane targeting of PP2A-C was observed in 5% O 2 , resulting in greater interaction with eNOS in response to histamine. Moreover, increased dephosphorylation of eNOS in 5% O 2 was Ca 2+ -sensitive and reversed by okadaic acid or PP2A-C siRNA. The present findings establish that Ca 2+ mobilization stimulates both NO synthesis and PP2A-mediated eNOS dephosphorylation, thus constituting a novel negative feedback mechanism regulating eNOS activity not present in response to shear stress. This, coupled with enhanced NO bioavailability, underpins differences in NO signaling induced by inflammatory and physiologic stimuli that are apparent only in physiologic O 2 levels. Furthermore, an explicit delineation between physiologic normoxia and genuine hypoxia is defined here, with implications for our understanding of pathophysiological hypoxia.-Keeley, T. P., Siow, R. C. M., Jacob, R., Mann, G. E. A PP2A-mediated feedback mechanism controls Ca 2+ -dependent NO synthesis under physiological oxygen. © The Author(s).

A three-dimensional virtual environment for modeling mechanical cardiopulmonary interactions.

PubMed

Kaye, J M; Primiano, F P; Metaxas, D N

1998-06-01

We have developed a real-time computer system for modeling mechanical physiological behavior in an interactive, 3-D virtual environment. Such an environment can be used to facilitate exploration of cardiopulmonary physiology, particularly in situations that are difficult to reproduce clinically. We integrate 3-D deformable body dynamics with new, formal models of (scalar) cardiorespiratory physiology, associating the scalar physiological variables and parameters with the corresponding 3-D anatomy. Our framework enables us to drive a high-dimensional system (the 3-D anatomical models) from one with fewer parameters (the scalar physiological models) because of the nature of the domain and our intended application. Our approach is amenable to modeling patient-specific circumstances in two ways. First, using CT scan data, we apply semi-automatic methods for extracting and reconstructing the anatomy to use in our simulations. Second, our scalar physiological models are defined in terms of clinically measurable, patient-specific parameters. This paper describes our approach, problems we have encountered and a sample of results showing normal breathing and acute effects of pneumothoraces.

Beta-phenylethylamine inhibits K+ currents in neocortical neurons of the rat: a possible mechanism of beta-phenylethylamine-induced seizures.

PubMed

Kitamura, Taro; Munakata, Mitsutoshi; Haginoya, Kazuhiro; Tsuchiya, Shigeru; Iinuma, Kazuie

2008-08-01

beta-Phenylethylamine (beta-PEA), an endogenous amine synthesized in the brain, serves as a neuromodulator and is involved in the pathophysiology of various neurological disorders such as depression, schizophrenia, and attention-deficit hyperactivity disorder. beta-PEA fully exerts the physiological effects within the nanomolar concentration range via the trace amine receptors, but beta-PEA also causes convulsions at much higher concentrations via an as yet unknown mechanism. To investigate the electrophysiological mechanism by which beta-PEA induces convulsions, we examined the effect of beta-PEA on ionic currents passing through the cell membrane of dissociated rat cerebral cortical neurons, using a patch-clamp technique. The external application of beta-PEA suppressed ionic currents which continuously flowed when the membrane potential was held at -25 mV. The suppression was in a concentration-dependent manner and a half-maximal effective concentration was 540 muM. These currents suppressed by beta-PEA consisted of two K(+) currents: a time- and voltage-dependent K(+) current (M-current) and a leakage K(+) current. The suppression of the M-current reduces the efficacy of the current in limiting excessive neuronal firing, and the suppression of the leakage K(+) current can cause membrane depolarization and thus promote neuronal excitation. Reducing both of these currents in concert may produce neuronal seizing activity, which could conceivably underlie the convulsions induced by high-dose beta-PEA.

The desmosome and pemphigus

PubMed Central

2008-01-01

Desmosomes are patch-like intercellular adhering junctions (“maculae adherentes”), which, in concert with the related adherens junctions, provide the mechanical strength to intercellular adhesion. Therefore, it is not surprising that desmosomes are abundant in tissues subjected to significant mechanical stress such as stratified epithelia and myocardium. Desmosomal adhesion is based on the Ca2+-dependent, homo- and heterophilic transinteraction of cadherin-type adhesion molecules. Desmosomal cadherins are anchored to the intermediate filament cytoskeleton by adaptor proteins of the armadillo and plakin families. Desmosomes are dynamic structures subjected to regulation and are therefore targets of signalling pathways, which control their molecular composition and adhesive properties. Moreover, evidence is emerging that desmosomal components themselves take part in outside-in signalling under physiologic and pathologic conditions. Disturbed desmosomal adhesion contributes to the pathogenesis of a number of diseases such as pemphigus, which is caused by autoantibodies against desmosomal cadherins. Beside pemphigus, desmosome-associated diseases are caused by other mechanisms such as genetic defects or bacterial toxins. Because most of these diseases affect the skin, desmosomes are interesting not only for cell biologists who are inspired by their complex structure and molecular composition, but also for clinical physicians who are confronted with patients suffering from severe blistering skin diseases such as pemphigus. To develop disease-specific therapeutic approaches, more insights into the molecular composition and regulation of desmosomes are required. PMID:18386043

A Physiologic-Based Approach to the Treatment of Acute Hyperkalemia

PubMed Central

Shingarev, Roman; Allon, Michael

2014-01-01

Hyperkalemia is a common and potentially lethal disorder. Given its variable presentation clinicians should have a high index of suspicion, especially in patients with chronic kidney disease. The present case highlights key physiological mechanisms in the development of hyperkalemia and provides an outline for emergent treatment. In this context, we discuss specific mechanisms of action of available treatments of hyperkalemia. PMID:20570423

Physiological Disorders of Pear Shoot Cultures

USDA-ARS?s Scientific Manuscript database

Physiological disorders are some of the most difficult challenges in micropropagation. Little is known of the causes of plant growth disorders which include callus formation, hyperhydricity, shoot tip necrosis, leaf lesions, epinasty, fasciation and hypertrophy. During our study of mineral nutritio...

The body's tailored suit: Skin as a mechanical interface.

PubMed

Tissot, Floriane S; Boulter, Etienne; Estrach, Soline; Féral, Chloé C

2016-11-01

Skin, by nature, is very similar to the Rouquayrol-Denayrouze suit mentioned by Jules Verne in Twenty Thousand Leagues Under the Sea: it allows "to risk (…) new physiological conditions without suffering any organic disorder". Mechanical cues, to the same extent as other environmental parameters, are such "new physiological conditions". Indeed, skin's primary function is to form a protective barrier to shield inner tissues from the external environment. This requires unique mechanical properties as well as the ability to sense mechanical cues from the environment in order to prevent or repair mechanical damages as well as to function as the primary mechanosensory interface of the whole body. Copyright © 2016 Elsevier GmbH. All rights reserved.

Environmental control and control of the environment: the basis of longevity in bivalves.

PubMed

Abele, Doris; Philipp, Eva

2013-01-01

Longevity and ageing are two sides of a coin, leaving the question open as to which one is the cause and which one the effect. At the individual level, the physiological rate of ageing determines the length of life (= individual longevity, as long as death results from old age and not from disease or other impacts). Individual longevity depends on the direct influence of environmental conditions with respect to nutrition, and the possibility for and timing of reproduction, as well as on the energetic costs animals invest in behavioural and physiological stress defence. All these environmental effectors influence hormonal and cellular signalling pathways that modify the individual physiological condition, the reproductive strategy, and the rate of ageing. At the species level, longevity (= maximum lifespan) is the result of an evolutionary process and, thus, largely determined by the species' behavioural and physiological adaptations to its ecological niche. Specifically, reproductive and breeding strategies have to be optimized in relation to local environmental conditions in different habitats. As a result of adaptive and evolutionary processes, species longevity is genetically underpinned, not necessarily by a few ageing genes, but by an evolutionary process that has hierarchically shaped and optimized species genomes to function in a specific niche or environmental system. Importantly, investigations and reviews attempting to unravel the mechanistic basis of the ageing process need to differentiate clearly between the evolutionary process shaping longevity at the species level and the regulatory mechanisms that alter the individual rate of ageing. Copyright © 2012 S. Karger AG, Basel.

Sex-related differences in stress tolerance in dioecious plants: a critical appraisal in a physiological context.

PubMed

Juvany, Marta; Munné-Bosch, Sergi

2015-10-01

Sex-related differences in reproductive effort can lead to differences in vegetative growth and stress tolerance. However, do all dioecious plants show sex-related differences in stress tolerance? To what extent can the environmental context and modularity mask sex-related differences in stress tolerance? Finally, to what extent can physiological measurements help us understand secondary sexual dimorphism? This opinion paper aims to answer these three basic questions with special emphasis on developments in research in this area over the last decade. Compelling evidence indicates that dimorphic species do not always show differences in stress tolerance between sexes; and when sex-related differences do occur, they seem to be highly species-specific, with greater stress tolerance in females than males in some species, and the opposite in others. The causes of such sex-related species-specific differences are still poorly understood, and more physiological studies and diversity of plant species that allow comparative analyses are needed. Furthermore, studies performed thus far demonstrate that the expression of dioecy can lead to sex-related differences in physiological traits-from leaf gas exchange to gene expression-but the biological significance of modularity and sectoriality governing such differences has been poorly investigated. Future studies that consider the importance of modularity and sectoriality are essential for unravelling the mechanisms underlying stress adaptation in male and female plants growing in their natural habitat. © The Author 2015. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Impact of physiology, structure and BRDF in hyperspectral time series of a Citrus orchard

NASA Astrophysics Data System (ADS)

Stuckens, J.; Dzikiti, S.; Verstraeten, W. W.; Verreynne, J. S.; Swinnen, R.; Coppin, P.

2010-05-01

Monitoring of plant production systems using remote sensing requires an understanding of the mechanisms in which physiological and structural changes as well as the quality and direction of incident light alter the measured canopy reflectance. Due to the evergreen nature of Citrus, the benefits of year-round monitoring of spectral changes are counterweighted by more subtle changes and seasonal trends than in other perennials. This study presents the results of a 14 months field measurement campaign in a commercial Citrus sinensis ‘Midknight Valencia' orchard in Wellington, Western Cape Province, South-Africa. Hyperspectral data were collected of canopy and leaf reflectance (350 - 2500 nm) of 16 representative trees at monthly intervals and supplemented with local climatology, orchard management records, sap stream, water potential and leaf and soil nutrient analysis. The aim of this research is to translate spectral changes and trends at the leaf and at canopy levels into physiological processes such as plant nutrient and carbohydrate balances and stress responses. Specific research questions include the spectral detection of flowering (date of anthesis, flowering intensity), fruit drop, fruit number and coloration, vegetative flushes, leaf senescence and drop and pruning. Attention is paid to the detection and the impact of sunburn (photo-damage). In order to separate physiological and structural changes from changes caused by seasonal changes in solar elevation during measurement time (bidirectional reflectance) a normalization function is constructed using simulated and measured data. Additional research is done to up-scale measurements from tree level to orchard level, which includes the tree variability, the influence of soil and weeds and different amounts of shading.

Motivational intensity modulates the effects of positive emotions on set shifting after controlling physiological arousal.

PubMed

Zhou, Ya; Siu, Angela F Y

2015-12-01

Recent research on the construct of emotion suggests the integration of a motivational dimension into the traditional two-dimension (subjective valence and physiological arousal) model. The motivational intensity of an emotional state should be taken into account while investigating the emotion-cognition relationship. This study examined how positive emotional states varying in motivational intensity influenced set shifting, after controlling the potential confounding impacts of physiological arousal. In Experiment 1, 155 volunteers performed a set-shifting task after being randomly assigned to five states: high- vs. low-motivating positive affect (interest vs. serenity), high- vs. low-motivating negative affect (disgust vs. anxiety), and neutral state. Eighty-five volunteers participated in Experiment 2, which further examined the effects of higher vs. lower degree of interest. Both experiments measured and compared participants' physiological arousal (blood pressure and pulse rate) under the normal and experimental conditions as the covariate. Results showed no difference in switching performance between the neutral and serenity groups. As compared with the neutral state, the high-motivating positive affect significantly increased set-switching reaction time costs, but reduced error rate costs; the higher the motivational intensity, the greater the time-costs impairment. This indicates a role of the high-motivating positive affect in regulating the balance between the flexible and stable cognitive control. Motivational intensity also modulated the effects of negative emotional states, i.e., disgust caused a larger increase in time costs than anxiety. Further exploration into neurobiological mechanisms that may mediate the emotional effects on set shifting is warranted. © 2015 Scandinavian Psychological Associations and John Wiley & Sons Ltd.

Endogenously Released Neuropeptide Y Suppresses Hippocampal Short-Term Facilitation and Is Impaired by Stress-Induced Anxiety

PubMed Central

Li, Qin; Bartley, Aundrea F.

2017-01-01

Neuropeptide Y (NPY) has robust anxiolytic properties and is reduced in patients with anxiety disorders. However, the mechanisms by which NPY modulates circuit function to reduce anxiety behavior are not known. Anxiolytic effects of NPY are mediated in the CA1 region of hippocampus, and NPY injection into hippocampus alleviates anxiety symptoms in the predator scent stress model of stress-induced anxiety. The mechanisms that regulate NPY release, and its effects on CA1 synaptic function, are not fully understood. Here we show in acute hippocampal slices from mice that endogenous NPY, released in response to optogenetic stimulation or synaptically evoked spiking of NPY+ cells, suppresses both of the feedforward pathways to CA1. Stimulation of temporoammonic synapses with a physiologically derived spike train causes NPY release that reduces short-term facilitation, whereas the release of NPY that modulates Schaffer collateral synapses requires integration of both the Schaffer collateral and temporoammonic pathways. Pathway specificity of NPY release is conferred by three functionally distinct NPY+ cell types, with differences in intrinsic excitability and short-term plasticity of their inputs. Predator scent stress abolishes the release of endogenous NPY onto temporoammonic synapses, a stress-sensitive pathway, thereby causing enhanced short-term facilitation. Our results demonstrate how stress alters CA1 circuit function through the impairment of endogenous NPY release, potentially contributing to heightened anxiety. SIGNIFICANCE STATEMENT Neuropeptide Y (NPY) has robust anxiolytic properties, and its levels are reduced in patients with post-traumatic stress disorder. The effects of endogenously released NPY during physiologically relevant stimulation, and the impact of stress-induced reductions in NPY on circuit function, are unknown. By demonstrating that NPY release modulates hippocampal synaptic plasticity and is impaired by predator scent stress, our results provide a novel mechanism by which stress-induced anxiety alters circuit function. These studies fill an important gap in knowledge between the molecular and behavioral effects of NPY. This article also advances the understanding of NPY+ cells and the factors that regulate their spiking, which could pave the way for new therapeutic targets to increase endogenous NPY release in patients in a spatially and temporally appropriate manner. PMID:28053027

A new method for measuring mechanical properties of laryngeal mucosa.

PubMed

Hemler, R J; Wieneke, G H; van Riel, A M; Lebacq, J; Dejonckere, P H

2001-03-01

A study of the effect of exogenous hazardous agents or conditions on the mechanical characteristics of vocal fold mucosa should meet three methodological criteria. 1) The outer surface of the mucosa should be exposed to the agent or condition while the inner surface is exposed to a physiological environment. 2) Even slight changes in mechanical characteristics should be detected. 3) The applied strain should be within physiological ranges. To date, no such method has been described in the literature. A method meeting the listed criteria is proposed and evaluated here.

[Functional childhood gastrointestinal disorders. II. Constipation and solitary encopresis: physiology and pathophysiology].

PubMed

van Ginkel, R; Büller, H A; Heymans, H S; Taminiau, J A; Boeckxstaens, G E; Benninga, M A

2003-06-28

The childhood prevalences of constipation and encopresis are 0.3-8% and 1-3% respectively. Following a recent stricter definition and classification, constipation and solitary encopresis are now recognised to be two separate entities. Constipation is characterised by infrequent defecation, often in combination with involuntary loss of faeces. Solitary encopresis most often occurs once a day after school hours. When there is no defecation, the frequency of encopresis increases, the abdominal pain becomes more severe and the appetite becomes less, until a large quantity of faeces is produced (often once per week). The physiology of the defecation and continence mechanism is complex and has only been unravelled in part. The multiple physiological mechanisms involved have a complementary and compensatory effect on each other. This makes it difficult to determine the underlying pathophysiological mechanisms of these functional disorders.

Mechanics and pathomechanics in the overhead athlete.

PubMed

Kibler, W Ben; Wilkes, Trevor; Sciascia, Aaron

2013-10-01

Optimal performance of the overhead throwing task requires precise mechanics that involve coordinated kinetic and kinematic chains to develop, transfer, and regulate the forces the body needs to withstand the inherent demands of the task and to allow optimal performance. These chains have been evaluated and the basic components, called nodes, have been identified. Impaired performance and/or injury, the DTS, is associated with alterations in the mechanics that are called pathomechanics. They can occur at multiple locations throughout the kinetic chain. They must be evaluated and treated as part of the overall problem. Observational analysis of the mechanics and pathomechanics using the node analysis method can be useful in highlighting areas of alteration that can be evaluated for anatomic injury or altered physiology. The comprehensive kinetic chain examination can evaluate sites of kinetic chain breakage, and a detailed shoulder examination can assess joint internal derangement of altered physiology that may contribute to the pathomechanics. Treatment of the DTS should be comprehensive, directed toward restoring physiology and mechanics and optimizing anatomy. This maximizes the body’s ability to develop normal mechanics to accomplish the overhead throwing task. Copyright © 2013 Elsevier Inc. All rights reserved.

Role of Thyroid Hormones in Skeletal Development and Bone Maintenance

PubMed Central

Bassett, J. H. Duncan

2016-01-01

The skeleton is an exquisitely sensitive and archetypal T3-target tissue that demonstrates the critical role for thyroid hormones during development, linear growth, and adult bone turnover and maintenance. Thyrotoxicosis is an established cause of secondary osteoporosis, and abnormal thyroid hormone signaling has recently been identified as a novel risk factor for osteoarthritis. Skeletal phenotypes in genetically modified mice have faithfully reproduced genetic disorders in humans, revealing the complex physiological relationship between centrally regulated thyroid status and the peripheral actions of thyroid hormones. Studies in mutant mice also established the paradigm that T3 exerts anabolic actions during growth and catabolic effects on adult bone. Thus, the skeleton represents an ideal physiological system in which to characterize thyroid hormone transport, metabolism, and action during development and adulthood and in response to injury. Future analysis of T3 action in individual skeletal cell lineages will provide new insights into cell-specific molecular mechanisms and may ultimately identify novel therapeutic targets for chronic degenerative diseases such as osteoporosis and osteoarthritis. This review provides a comprehensive analysis of the current state of the art. PMID:26862888

Mass emergency water-based foam depopulation of poultry.

PubMed

Benson, E R; Alphin, R L; Rankin, M K; Caputo, M P; Hougentogler, D P; Johnson, A L

2012-12-01

When an avian influenza or virulent Newcastle disease outbreak occurs within commercial poultry, a large number of birds that are infected or suspected of infection must be destroyed on site to prevent the rapid spread of disease. The choice of mass emergency depopulation procedures is limited, and all options have limitations. Water-based foam mass emergency depopulation of poultry was developed in 2006 and conditionally approved by the U.S. Department of Agriculture and American Veterinary Medical Association. Water-based foam causes mechanical hypoxia and can be used for broilers, layers, turkeys, and ducks. The time to physiologic states was evaluated for broilers, layer hens, turkeys, and ducks, comparing water-based foam and CO2 gas using electroencephalogram (unconsciousness and brain death), electrocardiogram (altered terminal cardiac activity), and accelerometer (motion cessation). In broilers, turkeys, and layer hens, water-based foam results in equivalent times to unconsciousness, terminal convulsions, and altered terminal cardiac activity. With Pekin ducks, however, CO2 gas resulted in shorter times to key physiologic states, in particular unconsciousness, altered terminal cardiac activity, motion cessation, and brain death.

Mitotic Dysfunction Associated with Aging Hallmarks.

PubMed

Macedo, Joana Catarina; Vaz, Sara; Logarinho, Elsa

2017-01-01

Aging is a biological process characterized by the progressive deterioration of physiological functions known to be the main risk factor for chronic diseases and declining health. There has been an emerging connection between aging and aneuploidy, an aberrant number of chromosomes, even though the molecular mechanisms behind age-associated aneuploidy remain largely unknown. In recent years, several genetic pathways and biochemical processes controlling the rate of aging have been identified and proposed as aging hallmarks. Primary hallmarks that cause the accumulation of cellular damage include genomic instability, telomere attrition, epigenetic alterations and loss of proteostasis (López-Otín et al., Cell 153:1194-1217, 2013). Here we review the provocative link between these aging hallmarks and the loss of chromosome segregation fidelity during cell division, which could support the correlation between aging and aneuploidy seen over the past decades. Secondly, we review the systemic impacts of aneuploidy in cell physiology and emphasize how these include some of the primary hallmarks of aging. Based on the evidence, we propose a mutual causality between aging and aneuploidy, and suggest modulation of mitotic fidelity as a potential means to ameliorate healthy lifespan.

Theoretical study on the constricted flow phenomena in arteries

NASA Astrophysics Data System (ADS)

Sen, S.; Chakravarty, S.

2012-12-01

The present study is dealt with the constricted flow characteristics of blood in arteries by making use of an appropriate mathematical model. The constricted artery experiences the generated wall shear stress due to flow disturbances in the presence of constriction. The disturbed flow in the stenosed arterial segment causes malfunction of the cardiovascular system leading to serious health problems in the form of heart attack and stroke. The flowing blood contained in the stenosed artery is considered to be non-Newtonian while the flow is treated to be two-dimensional. The present pursuit also accounts for the motion of the arterial wall and its effect on local fluid mechanics. The flow analysis applies the time-dependent, two-dimensional incompressible nonlinear Navier-Stokes equations for non-Newtonian fluid representing blood. An extensive quantitative analysis presented at the end of the paper based on large scale numerical computations of the quantities of major physiological significance enables one to estimate the constricted flow characteristics in the arterial system under consideration which deviates significantly from that of normal physiological flow conditions.

Optical imaging characterizing brain response to thermal insult in injured rodent

NASA Astrophysics Data System (ADS)

Abookasis, David; Shaul, Oren; Meitav, Omri; Pinhasi, Gadi A.

2018-02-01

We used spatially modulated optical imaging system to assess the effect of temperature elevation on intact brain tissue in a mouse heatstress model. Heatstress or heatstroke is a medical emergency defined by abnormally elevated body temperature that causes biochemical, physiological and hematological changes. During experiments, brain temperature was measured concurrently with a thermal camera while core body temperature was monitored with rectal thermocouple probe. Changes in a battery of macroscopic brain physiological parameters, such as hemoglobin oxygen saturation level, cerebral water content, as well as intrinsic tissue optical properties were monitored during temperature elevation. These concurrent changes reflect the pathophysiology of the brain during heatstress and demonstrate successful monitoring of thermoregulation mechanisms. In addition, the variation of tissue refractive index was calculated showing a monotonous decrease with increasing wavelength. We found increased temperature to greatly affect both the scattering properties and refractive index which represent cellular and subcellular swelling indicative of neuronal damage. The overall trends detected in brain tissue parameters were consistent with previous observations using conventional medical devices and optical modalities.

Quantum dots induce charge-specific amyloid-like fibrillation of insulin at physiological conditions

NASA Astrophysics Data System (ADS)

Sukhanova, Alyona; Poly, Simon; Shemetov, Anton; Nabiev, Igor R.

2012-10-01

Agglomeration of some proteins may give rise to aggregates that have been identified as the main cause of amyloid diseases. For example, fibrillation of insulin is related to diabetes mellitus. Quantum dots (QDs) are of special interest as tagging agents for diagnostic and therapeutic studies due to their broad absorption spectra, narrow emission spectra, and high photostability. In this study, PEGylated CdSe/ZnS QDs have been shown to induce the formation of amyloid-like fibrils of human insulin under physiological conditions, this process being dependent on the variation of the surface charge of the nanoparticles (NPs) used. Circular dichroism (CD), protein secondary structure analysis, thioflavin T (ThT) fluorescence assay, and the dynamic light scattering (DLS) technique have been used for comparative analysis of different stages of the fibrillation process. In particular, insulin secondary structure remodelling accompanied by a considerable increase in the rate of amyloid fiber formation have been observed after insulin was mixed with PEGylated QDs. Nanoparticles may significantly influence the rate of protein fibrillation and induce new mechanisms of amyloid diseases, as well as offer opportunities for their treatment.

Crystallization and preliminary X-ray diffraction analysis of the phosphate-binding protein PhoX from Xanthomonas citri

PubMed Central

Pegos, Vanessa R.; Medrano, Francisco Javier; Balan, Andrea

2014-01-01

Xanthomonas axonopodis pv. citri (X. citri) is an important bacterium that causes citrus canker disease in plants in Brazil and around the world, leading to significant economic losses. Determination of the physiology and mechanisms of pathogenesis of this bacterium is an important step in the development of strategies for its containment. Phosphate is an essential ion in all microrganisms owing its importance during the synthesis of macromolecules and in gene and protein regulation. Interestingly, X. citri has been identified to present two periplasmic binding proteins that have not been further characterized: PstS, from an ATP-binding cassette for high-affinity uptake and transport of phosphate, and PhoX, which is encoded by an operon that also contains a putative porin for the transport of phosphate. Here, the expression, purification and crystallization of the phosphate-binding protein PhoX and X-ray data collection at 3.0 Å resolution are described. Biochemical, biophysical and structural data for this protein will be helpful in the elucidation of its function in phosphate uptake and the physiology of the bacterium. PMID:25484207

Physiological and toxicological aspects of smoke produced during the combustion of polymeric materials.

PubMed Central

Einhorn, I N

1975-01-01

Normally one expects that flame contact is the major cause of injury and death during fires. Analysis of the factors involved in numerous fires has revealed that most deaths were not due to flame contact, but were a consequence of the production of carbon monoxide, nitrogen oxides, and other combustion products, such as aldehydes, low molecular weight alcohols, hydrogen cyanide, and other noxious species. The major emphasis within the scope of this paper relates to the physiological and toxicological aspects of smoke produced during the combustion of materials. Special emphasis is directed toward laboratory procedures which have been developed to determine the qualitative and quantitative analysis of smoke, factors pertaining to smoke development, and to measure the response of laboratory animals exposed to smoke. The effects that fire retardants, incorporated into polymeric materials as a means of improving flammability characteristics, may have on smoke development, the mechanism of polymer degradation, and on the survival response of laboratory animals are also considered. Images FIGURE 1. FIGURE 2. FIGURE 3. FIGURE 4. FIGURE 5. FIGURE 6. FIGURE 7. FIGURE 8. FIGURE 9. PMID:170077

A quantitative systems physiology model of renal function and blood pressure regulation: Model description.

PubMed

Hallow, K M; Gebremichael, Y

2017-06-01

Renal function plays a central role in cardiovascular, kidney, and multiple other diseases, and many existing and novel therapies act through renal mechanisms. Even with decades of accumulated knowledge of renal physiology, pathophysiology, and pharmacology, the dynamics of renal function remain difficult to understand and predict, often resulting in unexpected or counterintuitive therapy responses. Quantitative systems pharmacology modeling of renal function integrates this accumulated knowledge into a quantitative framework, allowing evaluation of competing hypotheses, identification of knowledge gaps, and generation of new experimentally testable hypotheses. Here we present a model of renal physiology and control mechanisms involved in maintaining sodium and water homeostasis. This model represents the core renal physiological processes involved in many research questions in drug development. The model runs in R and the code is made available. In a companion article, we present a case study using the model to explore mechanisms and pharmacology of salt-sensitive hypertension. © 2017 The Authors CPT: Pharmacometrics & Systems Pharmacology published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics.

Mechanisms of physiological and pathological cardiac hypertrophy.

PubMed

Nakamura, Michinari; Sadoshima, Junichi

2018-04-19

Cardiomyocytes exit the cell cycle and become terminally differentiated soon after birth. Therefore, in the adult heart, instead of an increase in cardiomyocyte number, individual cardiomyocytes increase in size, and the heart develops hypertrophy to reduce ventricular wall stress and maintain function and efficiency in response to an increased workload. There are two types of hypertrophy: physiological and pathological. Hypertrophy initially develops as an adaptive response to physiological and pathological stimuli, but pathological hypertrophy generally progresses to heart failure. Each form of hypertrophy is regulated by distinct cellular signalling pathways. In the past decade, a growing number of studies have suggested that previously unrecognized mechanisms, including cellular metabolism, proliferation, non-coding RNAs, immune responses, translational regulation, and epigenetic modifications, positively or negatively regulate cardiac hypertrophy. In this Review, we summarize the underlying molecular mechanisms of physiological and pathological hypertrophy, with a particular emphasis on the role of metabolic remodelling in both forms of cardiac hypertrophy, and we discuss how the current knowledge on cardiac hypertrophy can be applied to develop novel therapeutic strategies to prevent or reverse pathological hypertrophy.

Physiological regulation through learnt control of appetites by contingencies among signals from external and internal environments.

PubMed

Booth, David A

2008-11-01

As reviewed by [Cooper, S. J. (2008). From Claude Bernard to Walter Cannon: emergence of the concept of homeostasis. Appetite 51, 419-27.] Claude Bernard's idea of stabilisation of bodily states, as realised in Walter B. Cannon's conception of homeostasis, took mathematical form during the 1940s in the principle that externally originating disturbance of a physiological parameter can feed an informative signal around the brain to trigger counteractive processes--a corrective mechanism known as negative feedback, in practice reliant on feedforward. Three decades later, enough was known of the physiology and psychology of eating and drinking for calculations to show how experimentally demonstrated mechanisms of feedforward that had been learnt from negative feedback combine to regulate exchanges of water and energy between the body and the surroundings. Subsequent systemic physiology, molecular neuroscience and experimental psychology, however, have been traduced by a misconception that learnt controls of intake are 'non-homeostatic', the myth of biological 'set points' and an historic failure to address evidence for the ingestion-adapting information-processing mechanisms on which an operationally integrative theory of eating and drinking relies.

Diagnosis and management of heart failure in the fetus

PubMed Central

DAVEY, B.; SZWAST, A.; RYCHIK, J.

2015-01-01

Heart failure can be defined as the inability of the heart to sufficiently support the circulation. In the fetus, heart failure can be caused by a myriad of factors that include fetal shunting abnormalities, genetic cardiomyopathies, extracardiac malformations, arrhythmias and structural congenital heart disease. With advances in ultrasound has come the ability to characterize many complex conditions, previously poorly understood. Fetal echocardiography provides the tools necessary to evaluate and understand the various physiologies that contribute to heart failure in the fetus. In this review, we will explore the different mechanisms of heart failure in this unique patient population and highlight the role of fetal echocardiography in the current management of these conditions PMID:22992530

Neural mechanisms of oculomotor abnormalities in the infantile strabismus syndrome.

PubMed

Walton, Mark M G; Pallus, Adam; Fleuriet, Jérome; Mustari, Michael J; Tarczy-Hornoch, Kristina

2017-07-01

Infantile strabismus is characterized by numerous visual and oculomotor abnormalities. Recently nonhuman primate models of infantile strabismus have been established, with characteristics that closely match those observed in human patients. This has made it possible to study the neural basis for visual and oculomotor symptoms in infantile strabismus. In this review, we consider the available evidence for neural abnormalities in structures related to oculomotor pathways ranging from visual cortex to oculomotor nuclei. These studies provide compelling evidence that a disturbance of binocular vision during a sensitive period early in life, whatever the cause, results in a cascade of abnormalities through numerous brain areas involved in visual functions and eye movements. Copyright © 2017 the American Physiological Society.

[Caenorhabditis elegans: a powerful tool for drug discovery].

PubMed

Jia, Xi-Hua; Cao, Cheng

2009-07-01

A simple model organism Caenorhabditis elegans has contributed substantially to the fundamental researches in biology. In an era of functional genomics, nematode worm has been developed into a multi-purpose tool that can be exploited to identify disease-causing or disease-associated genes, validate potential drug targets. This, coupled with its genetic amenability, low cost experimental manipulation and compatibility with high throughput screening in an intact physiological condition, makes the model organism into an effective toolbox for drug discovery. This review shows the unique features of C. elegans, how it can play a valuable role in our understanding of the molecular mechanism of human diseases and finding drug leads in drug development process.

Induced pluripotent stem cell-derived myeloid phagocytes: disease modeling and therapeutic applications.

PubMed

Goodridge, Helen S

2014-06-01

Myeloid phagocytes (neutrophils, monocytes, macrophages and dendritic cells) have key roles in immune defense, as well as in tissue repair and remodeling. Defective or dysregulated myeloid phagocyte production or function can cause immune dysfunction, blood cell malignancies and inflammatory diseases. The tumor microenvironment can also condition myeloid phagocytes to promote tumor growth. Studies of their physiological and pathophysiological roles and the mechanisms regulating their production and function are crucial for the identification of novel therapeutic targets. In this review, we examine the use of induced pluripotent stem cells to study myeloid phagocytes in human diseases and develop future therapeutic strategies. Copyright © 2014 Elsevier Ltd. All rights reserved.

Hippocampal mechanisms for the context-dependent retrieval of episodes

PubMed Central

Hasselmo, Michael E.; Eichenbaum, Howard B.

2008-01-01

Behaviors ranging from delivering newspapers to waiting tables depend on remembering previous episodes to avoid incorrect repetition. Physiologically, this requires mechanisms for long-term storage and selective retrieval of episodes based on time of occurrence, despite variable intervals and similarity of events in a familiar environment. Here, this process has been modeled based on physiological properties of the hippocampal formation, including mechanisms for sustained activity in entorhinal cortex and theta rhythm oscillations in hippocampal subregions. The model simulates the context-sensitive firing properties of hippocampal neurons including trial specific firing during spatial alternation and trial by trial changes in theta phase precession on a linear track. This activity is used to guide behavior, and lesions of the hippocampal network impair memory-guided behavior. The model links data at the cellular level to behavior at the systems level, describing a physiologically plausible mechanism for the brain to recall a given episode which occurred at a specific place and time. PMID:16263240

Parkinson-causing α-synuclein missense mutations shift native tetramers to monomers as a mechanism for disease initiation

PubMed Central

Dettmer, Ulf; Newman, Andrew J.; Soldner, Frank; Luth, Eric S.; Kim, Nora C.; von Saucken, Victoria E.; Sanderson, John B.; Jaenisch, Rudolf; Bartels, Tim; Selkoe, Dennis

2015-01-01

β-Sheet-rich α-synuclein (αS) aggregates characterize Parkinson's disease (PD). αS was long believed to be a natively unfolded monomer, but recent work suggests it also occurs in α-helix-rich tetramers. Crosslinking traps principally tetrameric αS in intact normal neurons, but not after cell lysis, suggesting a dynamic equilibrium. Here we show that freshly biopsied normal human brain contains abundant αS tetramers. The PD-causing mutation A53T decreases tetramers in mouse brain. Neurons derived from an A53T patient have decreased tetramers. Neurons expressing E46K do also, and adding 1-2 E46K-like mutations into the canonical αS repeat motifs (KTKEGV) further reduces tetramers, decreases αS solubility and induces neurotoxicity and round inclusions. The other three fPD missense mutations likewise decrease tetramer:monomer ratios. The destabilization of physiological tetramers by PD-causing missense mutations and the neurotoxicity and inclusions induced by markedly decreasing tetramers suggest that decreased α-helical tetramers and increased unfolded monomers initiate pathogenesis. Tetramer-stabilizing compounds should prevent this. PMID:26076669

Pathophysiological responses to meals in the Zollinger-Ellison syndrome: I. Paradoxical postprandial inhibition of gastric secretion.

PubMed Central

Malagelada, J R

1978-01-01

The gastric acid, pepsin, and secretory volume output in response to a mixed meal were measured in six patients with Zollinger-Ellison syndrome caused by a gastrin-producing tumour proved subsequently at surgery. The patients were all normocalcaemic, and none had previous abdominal surgery. In four of the six patients, ingestion of the meal markedly inhibited the gastric secretory output, which decreased to below fasting levels, returning later to basal values. In two other patients, whose fasting acid output was considerably lower, the secretory output increased after the meal, but some inhibiton of gastric secretion was also apparent for variable intervals of time. The serum gastrin concentration in all patients remained essentially unchanged or increased after the meal. Two patients were restudied after successful removal of the duodenal gastrin-producing tumour, and in each the normal gastric secretory and gastrin-releasing responses were completely restored. Our studies suggest that, in patients with the Zollinger-Ellison syndrome caused by a gastrinoma, physiological regulatory mechanisms triggered by food reduce the continuous stimulation of gastric secretion caused by their tumoural hypergastrinaemia. PMID:25828

Pathophysiological responses to meals in the Zollinger-Ellison syndrome: I. Paradoxical postprandial inhibition of gastric secretion.

PubMed

Malagelada, J R

1978-04-01

The gastric acid, pepsin, and secretory volume output in response to a mixed meal were measured in six patients with Zollinger-Ellison syndrome caused by a gastrin-producing tumour proved subsequently at surgery. The patients were all normocalcaemic, and none had previous abdominal surgery. In four of the six patients, ingestion of the meal markedly inhibited the gastric secretory output, which decreased to below fasting levels, returning later to basal values. In two other patients, whose fasting acid output was considerably lower, the secretory output increased after the meal, but some inhibiton of gastric secretion was also apparent for variable intervals of time. The serum gastrin concentration in all patients remained essentially unchanged or increased after the meal. Two patients were restudied after successful removal of the duodenal gastrin-producing tumour, and in each the normal gastric secretory and gastrin-releasing responses were completely restored. Our studies suggest that, in patients with the Zollinger-Ellison syndrome caused by a gastrinoma, physiological regulatory mechanisms triggered by food reduce the continuous stimulation of gastric secretion caused by their tumoural hypergastrinaemia.

An Active Learning Exercise to Facilitate Understanding of Nephron Function: Anatomy and Physiology of Renal Transporters

ERIC Educational Resources Information Center

Dirks-Naylor, Amie J.

2016-01-01

Renal transport is a central mechanism underlying electrolyte homeostasis, acid base balance and other essential functions of the kidneys in human physiology. Thus, knowledge of the anatomy and physiology of the nephron is essential for the understanding of kidney function in health and disease. However, students find this content difficult to…

Functions and Mechanisms of Sleep

PubMed Central

Zielinski, Mark R.; McKenna, James T.; McCarley, Robert W.

2017-01-01

Sleep is a complex physiological process that is regulated globally, regionally, and locally by both cellular and molecular mechanisms. It occurs to some extent in all animals, although sleep expression in lower animals may be co-extensive with rest. Sleep regulation plays an intrinsic part in many behavioral and physiological functions. Currently, all researchers agree there is no single physiological role sleep serves. Nevertheless, it is quite evident that sleep is essential for many vital functions including development, energy conservation, brain waste clearance, modulation of immune responses, cognition, performance, vigilance, disease, and psychological state. This review details the physiological processes involved in sleep regulation and the possible functions that sleep may serve. This description of the brain circuitry, cell types, and molecules involved in sleep regulation is intended to further the reader’s understanding of the functions of sleep. PMID:28413828

Letterman Army Institute of Research Annual Research Progress Report, FY 1981.

DTIC Science & Technology

1981-10-01

with physiology and mech- anisms of skin damage and repair. The mechanisms by which nerve agents and vesicants produce physiologic aberration and...enzyme vital for nerve function. Organophos- phates react rapidly and covalently with the enzyme to produce an in- active enzyme. Reactivation of the...warfare agents . These organic molecules may also alter the natural defense mechanism by activating or deactivating enzymes in the skin that destroy

Magnesium alloys as body implants: fracture mechanism under dynamic and static loadings in a physiological environment.

PubMed

Choudhary, Lokesh; Raman, R K Singh

2012-02-01

It is essential that a metallic implant material possesses adequate resistance to cracking/fracture under the synergistic action of a corrosive physiological environment and mechanical loading (i.e. stress corrosion cracking (SCC)), before the implant can be put to actual use. This paper presents a critique of the fundamental issues with an assessment of SCC of a rapidly corroding material such as magnesium alloys, and describes an investigation into the mechanism of SCC of a magnesium alloy in a physiological environment. The SCC susceptibility of the alloy in a simulated human body fluid was established by slow strain rate tensile (SSRT) testing using smooth specimens under different electrochemical conditions for understanding the mechanism of SCC. However, to assess the life of the implant devices that often possess fine micro-cracks, SCC susceptibility of notched specimens was investigated by circumferential notch tensile (CNT) testing. CNT tests also produced important design data, i.e. threshold stress intensity for SCC (KISCC) and SCC crack growth rate. Fractographic features of SCC were examined using scanning electron microscopy. The SSRT and CNT results, together with fractographic evidence, confirmed the SCC susceptibility of both smooth and notched specimens of a magnesium alloy in the physiological environment. Copyright © 2011 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

An Integrative Model for the Neural Mechanism of Eye Movement Desensitization and Reprocessing (EMDR).

PubMed

Coubard, Olivier A

2016-01-01

Since the seminal report by Shapiro that bilateral stimulation induces cognitive and emotional changes, 26 years of basic and clinical research have examined the effects of Eye Movement Desensitization and Reprocessing (EMDR) in anxiety disorders, particularly in post-traumatic stress disorder (PTSD). The present article aims at better understanding EMDR neural mechanism. I first review procedural aspects of EMDR protocol and theoretical hypothesis about EMDR effects, and develop the reasons why the scientific community is still divided about EMDR. I then slide from psychology to physiology describing eye movements/emotion interaction from the physiological viewpoint, and introduce theoretical and technical tools used in movement research to re-examine EMDR neural mechanism. Using a recent physiological model for the neuropsychological architecture of motor and cognitive control, the Threshold Interval Modulation with Early Release-Rate of rIse Deviation with Early Release (TIMER-RIDER)-model, I explore how attentional control and bilateral stimulation may participate to EMDR effects. These effects may be obtained by two processes acting in parallel: (i) activity level enhancement of attentional control component; and (ii) bilateral stimulation in any sensorimotor modality, both resulting in lower inhibition enabling dysfunctional information to be processed and anxiety to be reduced. The TIMER-RIDER model offers quantitative predictions about EMDR effects for future research about its underlying physiological mechanisms.

Endophyte-Mediated Modulation of Defense-Related Genes and Systemic Resistance in Withania somnifera (L.) Dunal under Alternaria alternata Stress.

PubMed

Mishra, Aradhana; Singh, Satyendra Pratap; Mahfooz, Sahil; Singh, Surendra Pratap; Bhattacharya, Arpita; Mishra, Nishtha; Nautiyal, C S

2018-04-15

Endophytes have been explored and found to perform an important role in plant health. However, their effects on the host physiological function and disease management remain elusive. The present study aimed to assess the potential effects of endophytes, singly as well as in combination, in Withania somnifera (L.) Dunal, on various physiological parameters and systemic defense mechanisms against Alternaria alternata Seeds primed with the endophytic bacteria Bacillus amyloliquefaciens and Pseudomonas fluorescens individually and in combination demonstrated an enhanced vigor index and germination rate. Interestingly, plants treated with the two-microbe combination showed the lowest plant mortality rate (28%) under A. alternata stress. Physiological profiling of treated plants showed improved photosynthesis, respiration, transpiration, and stomatal conductance under pathogenic stress. Additionally, these endophytes not only augmented defense enzymes and antioxidant activity in treated plants but also enhanced the expression of salicylic acid- and jasmonic acid-responsive genes in the stressed plants. Reductions in reactive oxygen species (ROS) and reactive nitrogen species (RNS) along with enhanced callose deposition in host plant leaves corroborated well with the above findings. Altogether, the study provides novel insights into the underlying mechanisms behind the tripartite interaction of endophyte- A. alternata - W. somnifera and underscores their ability to boost plant health under pathogen stress. IMPORTANCE W. somnifera is well known for producing several medicinally important secondary metabolites. These secondary metabolites are required by various pharmaceutical sectors to produce life-saving drugs. However, the cultivation of W. somnifera faces severe challenge from leaf spot disease caused by A. alternata To keep pace with the rising demand for this plant and considering its capacity for cultivation under field conditions, the present study was undertaken to develop approaches to enhance production of W. somnifera through intervention using endophytes. Application of bacterial endophytes not only suppresses the pathogenicity of A. alternata but also mitigates excessive ROS/RNS generation via enhanced physiological processes and antioxidant machinery. Expression profiling of plant defense-related genes further validates the efficacy of bacterial endophytes against leaf spot disease. Copyright © 2018 American Society for Microbiology.

Dysfunctional breathing and reaching one’s physiological limit as causes of exercise-induced dyspnoea

PubMed Central

Everard, Mark L.

2016-01-01

Key points Excessive exercise-induced shortness of breath is a common complaint. For some, exercise-induced bronchoconstriction is the primary cause and for a small minority there may be an alternative organic pathology. However for many, the cause will be simply reaching their physiological limit or be due to a functional form of dysfunctional breathing, neither of which require drug therapy. The physiological limit category includes deconditioned individuals, such as those who have been through intensive care and require rehabilitation, as well as the unfit and the fit competitive athlete who has reached their limit with both of these latter groups requiring explanation and advice. Dysfunctional breathing is an umbrella term for an alteration in the normal biomechanical patterns of breathing that result in intermittent or chronic symptoms, which may be respiratory and/or nonrespiratory. This alteration may be due to structural causes or, much more commonly, be functional as exemplified by thoracic pattern disordered breathing (PDB) and extrathoracic paradoxical vocal fold motion disorder (pVFMD). Careful history and examination together with spirometry may identify those likely to have PDB and/or pVFMD. Where there is doubt about aetiology, cardiopulmonary exercise testing may be required to identify the deconditioned, unfit or fit individual reaching their physiological limit and PDB, while continuous laryngoscopy during exercise is increasingly becoming the benchmark for assessing extrathoracic causes. Accurate assessment and diagnosis can prevent excessive use of drug therapy and result in effective management of the cause of the individual’s complaint through cost-effective approaches such as reassurance, advice, breathing retraining and vocal exercises. This review provides an overview of the spectrum of conditions that can present as exercise-­induced breathlessness experienced by young subjects participating in sport and aims to promote understanding of the need for accurate assessment of an individual’s symptoms. We will highlight the high incidence of nonasthmatic causes, which simply require reassurance or simple interventions from respiratory physiotherapists or speech pathologists. PMID:27408630