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Sample records for regulate multiple physiological

  1. TAM receptors regulate multiple features of microglial physiology.

    Science.gov (United States)

    Fourgeaud, Lawrence; Través, Paqui G; Tufail, Yusuf; Leal-Bailey, Humberto; Lew, Erin D; Burrola, Patrick G; Callaway, Perri; Zagórska, Anna; Rothlin, Carla V; Nimmerjahn, Axel; Lemke, Greg

    2016-04-14

    Microglia are damage sensors for the central nervous system (CNS), and the phagocytes responsible for routine non-inflammatory clearance of dead brain cells. Here we show that the TAM receptor tyrosine kinases Mer and Axl regulate these microglial functions. We find that adult mice deficient in microglial Mer and Axl exhibit a marked accumulation of apoptotic cells specifically in neurogenic regions of the CNS, and that microglial phagocytosis of the apoptotic cells generated during adult neurogenesis is normally driven by both TAM receptor ligands Gas6 and protein S. Using live two-photon imaging, we demonstrate that the microglial response to brain damage is also TAM-regulated, as TAM-deficient microglia display reduced process motility and delayed convergence to sites of injury. Finally, we show that microglial expression of Axl is prominently upregulated in the inflammatory environment that develops in a mouse model of Parkinson's disease. Together, these results establish TAM receptors as both controllers of microglial physiology and potential targets for therapeutic intervention in CNS disease.

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

    Science.gov (United States)

    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). 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.

  3. Physiological and Pathogenic Roles of Prolyl Isomerase Pin1 in Metabolic Regulations via Multiple Signal Transduction Pathway Modulations

    Directory of Open Access Journals (Sweden)

    Yusuke Nakatsu

    2016-09-01

    Full Text Available Prolyl isomerases are divided into three groups, the FKBP family, Cyclophilin and the Parvulin family (Pin1 and Par14. Among these isomerases, Pin1 is a unique prolyl isomerase binding to the motif including pSer/pThr-Pro that is phosphorylated by kinases. Once bound, Pin1 modulates the enzymatic activity, protein stability or subcellular localization of target proteins by changing the cis- and trans-formations of proline. Several studies have examined the roles of Pin1 in the pathogenesis of cancers and Alzheimer’s disease. On the other hand, recent studies have newly demonstrated Pin1 to be involved in regulating glucose and lipid metabolism. Interestingly, while Pin1 expression is markedly increased by high-fat diet feeding, Pin1 KO mice are resistant to diet-induced obesity, non-alcoholic steatohepatitis and diabetic vascular dysfunction. These phenomena result from the binding of Pin1 to several key factors regulating metabolic functions, which include insulin receptor substrate-1, AMPK, Crtc2 and NF-κB p65. In this review, we focus on recent advances in elucidating the physiological roles of Pin1 as well as the pathogenesis of disorders involving this isomerase, from the viewpoint of the relationships between signal transductions and metabolic functions.

  4. Exploring transcriptional signalling mediated by OsWRKY13, a potential regulator of multiple physiological processes in rice

    Directory of Open Access Journals (Sweden)

    Li Xianghua

    2009-06-01

    Full Text Available Abstract Background Rice transcription regulator OsWRKY13 influences the functioning of more than 500 genes in multiple signalling pathways, with roles in disease resistance, redox homeostasis, abiotic stress responses, and development. Results To determine the putative transcriptional regulation mechanism of OsWRKY13, the putative cis-acting elements of OsWRKY13-influenced genes were analyzed using the whole genome expression profiling of OsWRKY13-activated plants generated with the Affymetrix GeneChip Rice Genome Array. At least 39 transcription factor genes were influenced by OsWRKY13, and 30 of them were downregulated. The promoters of OsWRKY13-upregulated genes were overrepresented with W-boxes for WRKY protein binding, whereas the promoters of OsWRKY13-downregulated genes were enriched with cis-elements putatively for binding of MYB and AP2/EREBP types of transcription factors. Consistent with the distinctive distribution of these cis-elements in up- and downregulated genes, nine WRKY genes were influenced by OsWRKY13 and the promoters of five of them were bound by OsWRKY13 in vitro; all seven differentially expressed AP2/EREBP genes and six of the seven differentially expressed MYB genes were suppressed by in OsWRKY13-activated plants. A subset of OsWRKY13-influenced WRKY genes were involved in host-pathogen interactions. Conclusion These results suggest that OsWRKY13-mediated signalling pathways are partitioned by different transcription factors. WRKY proteins may play important roles in the monitoring of OsWRKY13-upregulated genes and genes involved in pathogen-induced defence responses, whereas MYB and AP2/EREBP proteins may contribute most to the control of OsWRKY13-downregulated genes.

  5. Bile acids in regulation of intestinal physiology.

    LENUS (Irish Health Repository)

    Keating, Niamh

    2009-10-01

    In addition to their roles in facilitating lipid digestion and absorption, bile acids are recognized as important regulators of intestinal function. Exposure to bile acids can dramatically influence intestinal transport and barrier properties; in recent years, they have also become appreciated as important factors in regulating cell growth and survival. Indeed, few cells reside within the intestinal mucosa that are not altered to some degree by exposure to bile acids. The past decade saw great advances in the knowledge of how bile acids exert their actions at the cellular and molecular levels. In this review, we summarize the current understanding of the role of bile acids in regulation of intestinal physiology.

  6. Regulating plant physiology with organic electronics.

    Science.gov (United States)

    Poxson, David J; Karady, Michal; Gabrielsson, Roger; Alkattan, Aziz Y; Gustavsson, Anna; Doyle, Siamsa M; Robert, Stéphanie; Ljung, Karin; Grebe, Markus; Simon, Daniel T; Berggren, Magnus

    2017-05-02

    The organic electronic ion pump (OEIP) provides flow-free and accurate delivery of small signaling compounds at high spatiotemporal resolution. To date, the application of OEIPs has been limited to delivery of nonaromatic molecules to mammalian systems, particularly for neuroscience applications. However, many long-standing questions in plant biology remain unanswered due to a lack of technology that precisely delivers plant hormones, based on cyclic alkanes or aromatic structures, to regulate plant physiology. Here, we report the employment of OEIPs for the delivery of the plant hormone auxin to induce differential concentration gradients and modulate plant physiology. We fabricated OEIP devices based on a synthesized dendritic polyelectrolyte that enables electrophoretic transport of aromatic substances. Delivery of auxin to transgenic Arabidopsis thaliana seedlings in vivo was monitored in real time via dynamic fluorescent auxin-response reporters and induced physiological responses in roots. Our results provide a starting point for technologies enabling direct, rapid, and dynamic electronic interaction with the biochemical regulation systems of plants.

  7. Cell volume regulation: physiology and pathophysiology

    DEFF Research Database (Denmark)

    Lambert, I H; Hoffmann, E K; Pedersen, Stine Helene Falsig

    2008-01-01

    are sensed are still far from clear, significant progress has been made with respect to the nature of the sensors, transducers and effectors that convert a change in cell volume into a physiological response. In the present review, we summarize recent major developments in the field, and emphasize......Cell volume perturbation initiates a wide array of intracellular signalling cascades, leading to protective and adaptive events and, in most cases, activation of volume-regulatory osmolyte transport, water loss, and hence restoration of cell volume and cellular function. Cell volume is challenged....../hypernatremia. On the other hand, it has recently become clear that an increase or reduction in cell volume can also serve as a specific signal in the regulation of physiological processes such as transepithelial transport, cell migration, proliferation and death. Although the mechanisms by which cell volume perturbations...

  8. Physiological correlates of emotional reactivity and regulation in early adolescents.

    Science.gov (United States)

    Latham, Melissa D; Cook, Nina; Simmons, Julian G; Byrne, Michelle L; Kettle, Jonathan W L; Schwartz, Orli; Vijayakumar, Nandita; Whittle, Sarah; Allen, Nicholas B

    2017-07-01

    Few studies have examined physiological correlates of emotional reactivity and regulation in adolescents, despite the occurrence in this group of significant developmental changes in emotional functioning. The current study employed multiple physiological measures (i.e., startle-elicited eyeblink and ERP, skin conductance, facial EMG) to assess the emotional reactivity and regulation of 113 early adolescents in response to valenced images. Reactivity was measured while participants viewed images, and regulation was measured when they were asked to discontinue or maintain their emotional reactions to the images. Adolescent participants did not exhibit fear-potentiated startle blink. However, they did display affect-consistent zygomatic and corrugator activity during reactivity, as well as inhibition of some of these facial patterns during regulation. Skin conductance demonstrated arousal dependent activity during reactivity, and overall decreases during regulation. These findings suggest that early adolescents display reactivity to valenced pictures, but not to startle probes. Psychophysiological patterns during emotion regulation indicate additional effort and/or attention during the regulation process. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Physiology of cell volume regulation in vertebrates

    DEFF Research Database (Denmark)

    Hoffmann, Else K; Lambert, Ian H; Pedersen, Stine F

    2009-01-01

    and their regulation by, e.g., membrane deformation, ionic strength, Ca(2+), protein kinases and phosphatases, cytoskeletal elements, GTP binding proteins, lipid mediators, and reactive oxygen species, upon changes in cell volume. We also discuss the nature of the upstream elements in volume sensing in vertebrate...... organisms. Importantly, cell volume impacts on a wide array of physiological processes, including transepithelial transport; cell migration, proliferation, and death; and changes in cell volume function as specific signals regulating these processes. A discussion of this issue concludes the review.......The ability to control cell volume is pivotal for cell function. Cell volume perturbation elicits a wide array of signaling events, leading to protective (e.g., cytoskeletal rearrangement) and adaptive (e.g., altered expression of osmolyte transporters and heat shock proteins) measures and, in most...

  10. Physiological Self-Regulation and Adaptive Automation

    Science.gov (United States)

    Prinzell, Lawrence J.; Pope, Alan T.; Freeman, Frederick G.

    2007-01-01

    Adaptive automation has been proposed as a solution to current problems of human-automation interaction. Past research has shown the potential of this advanced form of automation to enhance pilot engagement and lower cognitive workload. However, there have been concerns voiced regarding issues, such as automation surprises, associated with the use of adaptive automation. This study examined the use of psychophysiological self-regulation training with adaptive automation that may help pilots deal with these problems through the enhancement of cognitive resource management skills. Eighteen participants were assigned to 3 groups (self-regulation training, false feedback, and control) and performed resource management, monitoring, and tracking tasks from the Multiple Attribute Task Battery. The tracking task was cycled between 3 levels of task difficulty (automatic, adaptive aiding, manual) on the basis of the electroencephalogram-derived engagement index. The other two tasks remained in automatic mode that had a single automation failure. Those participants who had received self-regulation training performed significantly better and reported lower National Aeronautics and Space Administration Task Load Index scores than participants in the false feedback and control groups. The theoretical and practical implications of these results for adaptive automation are discussed.

  11. Multiple regression for physiological data analysis: the problem of multicollinearity.

    Science.gov (United States)

    Slinker, B K; Glantz, S A

    1985-07-01

    Multiple linear regression, in which several predictor variables are related to a response variable, is a powerful statistical tool for gaining quantitative insight into complex in vivo physiological systems. For these insights to be correct, all predictor variables must be uncorrelated. However, in many physiological experiments the predictor variables cannot be precisely controlled and thus change in parallel (i.e., they are highly correlated). There is a redundancy of information about the response, a situation called multicollinearity, that leads to numerical problems in estimating the parameters in regression equations; the parameters are often of incorrect magnitude or sign or have large standard errors. Although multicollinearity can be avoided with good experimental design, not all interesting physiological questions can be studied without encountering multicollinearity. In these cases various ad hoc procedures have been proposed to mitigate multicollinearity. Although many of these procedures are controversial, they can be helpful in applying multiple linear regression to some physiological problems.

  12. Towards Integration of Biological and Physiological Functions at Multiple Levels

    Directory of Open Access Journals (Sweden)

    Taishin eNomura

    2010-12-01

    Full Text Available An aim of systems physiology today can be stated as to establish logical and quantitative bridges between phenomenological attributes of physiological entities such as cells and organs and physical attributes of biological entities, i.e., biological molecules, allowing us to describe and better understand physiological functions in terms of underlying biological functions. This article illustrates possible schema that can be used for promoting systems physiology by integrating quantitative knowledge of biological and physiological functions at multiple levels of time and space with the use of information technology infrastructure. Emphasis will be made for systematic, modular, hierarchical, and standardized descriptions of mathematical models of the functions and advantages for the use of them.

  13. SREBP-regulated lipid metabolism: convergent physiology - divergent pathophysiology.

    Science.gov (United States)

    Shimano, Hitoshi; Sato, Ryuichiro

    2017-12-01

    Cellular lipid metabolism and homeostasis are controlled by sterol regulatory-element binding proteins (SREBPs). In addition to performing canonical functions in the transcriptional regulation of genes involved in the biosynthesis and uptake of lipids, genome-wide system analyses have revealed that these versatile transcription factors act as important nodes of convergence and divergence within biological signalling networks. Thus, they are involved in myriad physiological and pathophysiological processes, highlighting the importance of lipid metabolism in biology. Changes in cell metabolism and growth are reciprocally linked through SREBPs. Anabolic and growth signalling pathways branch off and connect to multiple steps of SREBP activation and form complex regulatory networks. In addition, SREBPs are implicated in numerous pathogenic processes such as endoplasmic reticulum stress, inflammation, autophagy and apoptosis, and in this way, they contribute to obesity, dyslipidaemia, diabetes mellitus, nonalcoholic fatty liver disease, nonalcoholic steatohepatitis, chronic kidney disease, neurodegenerative diseases and cancers. This Review aims to provide a comprehensive understanding of the role of SREBPs in physiology and pathophysiology at the cell, organ and organism levels.

  14. Integrating physiological regulation with stem cell and tissue homeostasis

    Science.gov (United States)

    Nakada, Daisuke; Levi, Boaz P.; Morrison, Sean J.

    2015-01-01

    Summary Stem cells are uniquely able to self-renew, to undergo multilineage differentiation, and to persist throughout life in a number of tissues. Stem cells are regulated by a combination of shared and tissue-specific mechanisms and are distinguished from restricted progenitors by differences in transcriptional and epigenetic regulation. Emerging evidence suggests that other aspects of cellular physiology, including mitosis, signal transduction, and metabolic regulation also differ between stem cells and their progeny. These differences may allow stem cells to be regulated independently of differentiated cells in response to circadian rhythms, changes in metabolism, diet, exercise, mating, aging, infection, and disease. This allows stem cells to sustain homeostasis or to remodel relevant tissues in response to physiological change. Stem cells are therefore not only regulated by short-range signals that maintain homeostasis within their tissue of origin, but also by long-range signals that integrate stem cell function with systemic physiology. PMID:21609826

  15. Sleep regulation: physiological models and hypotheses.

    Science.gov (United States)

    Borbély, A A

    1995-06-01

    The elucidation of sleep regulation is not an easy task. On one side, there is a multitude of solid yet disparate data, on the other side, the topic is tempting for engaging in wild speculation, particularly with respect to the functions of sleep. Models may exert a moderating influence by mediating between the two extremes. However, also they navigate between the risk of banality in reformulating the obvious, and the peril of fancy in losing touch with empirical reality.

  16. Flexible carbon nanotube nanocomposite sensor for multiple physiological parameter monitoring

    KAUST Repository

    Nag, Anindya

    2016-10-16

    The paper presents the design, development, and fabrication of a flexible and wearable sensor based on carbon nanotube nanocomposite for monitoring specific physiological parameters. Polydimethylsiloxane (PDMS) was used as the substrate with a thin layer of a nanocomposite comprising functionalized multi-walled carbon nanotubes (MWCNTs) and PDMS as electrodes. The sensor patch functionalized on strain-sensitive capacitive sensing from interdigitated electrodes which were patterned with a laser on the nanocomposite layer. The thickness of the electrode layer was optimized regarding strain and conductivity. The sensor patch was connected to a monitoring device from one end and attached to the body on the other for examining purposes. Experimental results show the capability of the sensor patch used to detect respiration and limb movements. This work is a stepping stone of the sensing system to be developed for multiple physiological parameters.

  17. Flexible carbon nanotube nanocomposite sensor for multiple physiological parameter monitoring

    KAUST Repository

    Nag, Anindya; Mukhopadhyay, Subhas Chandra; Kosel, Jü rgen

    2016-01-01

    The paper presents the design, development, and fabrication of a flexible and wearable sensor based on carbon nanotube nanocomposite for monitoring specific physiological parameters. Polydimethylsiloxane (PDMS) was used as the substrate with a thin layer of a nanocomposite comprising functionalized multi-walled carbon nanotubes (MWCNTs) and PDMS as electrodes. The sensor patch functionalized on strain-sensitive capacitive sensing from interdigitated electrodes which were patterned with a laser on the nanocomposite layer. The thickness of the electrode layer was optimized regarding strain and conductivity. The sensor patch was connected to a monitoring device from one end and attached to the body on the other for examining purposes. Experimental results show the capability of the sensor patch used to detect respiration and limb movements. This work is a stepping stone of the sensing system to be developed for multiple physiological parameters.

  18. Metabolic-flux dependent regulation of microbial physiology.

    Science.gov (United States)

    Litsios, Athanasios; Ortega, Álvaro D; Wit, Ernst C; Heinemann, Matthias

    2018-04-01

    According to the most prevalent notion, changes in cellular physiology primarily occur in response to altered environmental conditions. Yet, recent studies have shown that changes in metabolic fluxes can also trigger phenotypic changes even when environmental conditions are unchanged. This suggests that cells have mechanisms in place to assess the magnitude of metabolic fluxes, that is, the rate of metabolic reactions, and use this information to regulate their physiology. In this review, we describe recent evidence for metabolic flux-sensing and flux-dependent regulation. Furthermore, we discuss how such sensing and regulation can be mechanistically achieved and present a set of new candidates for flux-signaling metabolites. Similar to metabolic-flux sensing, we argue that cells can also sense protein translation flux. Finally, we elaborate on the advantages that flux-based regulation can confer to cells. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  19. Physiological regulation of epithelial sodium channel by proteolysis

    DEFF Research Database (Denmark)

    Svenningsen, Per; Friis, Ulla G; Bistrup, Claus

    2011-01-01

    PURPOSE OF REVIEW: Activation of epithelial sodium channel (ENaC) by proteolysis appears to be relevant for day-to-day physiological regulation of channel activity in kidney and other epithelial tissues. Pathophysiogical, proteolytic activation of ENaC in kidney has been demonstrated in proteinuric...

  20. Plasma Membrane H(+)-ATPase Regulation in the Center of Plant Physiology.

    Science.gov (United States)

    Falhof, Janus; Pedersen, Jesper Torbøl; Fuglsang, Anja Thoe; Palmgren, Michael

    2016-03-07

    The plasma membrane (PM) H(+)-ATPase is an important ion pump in the plant cell membrane. By extruding protons from the cell and generating a membrane potential, this pump energizes the PM, which is a prerequisite for growth. Modification of the autoinhibitory terminal domains activates PM H(+)-ATPase activity, and on this basis it has been hypothesized that these regulatory termini are targets for physiological factors that activate or inhibit proton pumping. In this review, we focus on the posttranslational regulation of the PM H(+)-ATPase and place regulation of the pump in an evolutionary and physiological context. The emerging picture is that multiple signals regulating plant growth interfere with the posttranslational regulation of the PM H(+)-ATPase. Copyright © 2016 The Author. Published by Elsevier Inc. All rights reserved.

  1. Noninvasive optical monitoring multiple physiological parameters response to cytokine storm

    Science.gov (United States)

    Li, Zebin; Li, Ting

    2018-02-01

    Cancer and other disease originated by immune or genetic problems have become a main cause of death. Gene/cell therapy is a highlighted potential method for the treatment of these diseases. However, during the treatment, it always causes cytokine storm, which probably trigger acute respiratory distress syndrome and multiple organ failure. Here we developed a point-of-care device for noninvasive monitoring cytokine storm induced multiple physiological parameters simultaneously. Oxy-hemoglobin, deoxy-hemoglobin, water concentration and deep-tissue/tumor temperature variations were simultaneously measured by extended near infrared spectroscopy. Detection algorithms of symptoms such as shock, edema, deep-tissue fever and tissue fibrosis were developed and included. Based on these measurements, modeling of patient tolerance and cytokine storm intensity were carried out. This custom device was tested on patients experiencing cytokine storm in intensive care unit. The preliminary data indicated the potential of our device in popular and milestone gene/cell therapy, especially, chimeric antigen receptor T-cell immunotherapy (CAR-T).

  2. Assessing interactions among multiple physiological systems during walking outside a laboratory: An Android based gait monitor

    Science.gov (United States)

    Sejdić, E.; Millecamps, A.; Teoli, J.; Rothfuss, M. A.; Franconi, N. G.; Perera, S.; Jones, A. K.; Brach, J. S.; Mickle, M. H.

    2015-01-01

    Gait function is traditionally assessed using well-lit, unobstructed walkways with minimal distractions. In patients with subclinical physiological abnormalities, these conditions may not provide enough stress on their ability to adapt to walking. The introduction of challenging walking conditions in gait can induce responses in physiological systems in addition to the locomotor system. There is a need for a device that is capable of monitoring multiple physiological systems in various walking conditions. To address this need, an Android-based gait-monitoring device was developed that enabled the recording of a patient's physiological systems during walking. The gait-monitoring device was tested during self-regulated overground walking sessions of fifteen healthy subjects that included 6 females and 9 males aged 18 to 35 years. The gait-monitoring device measures the patient's stride interval, acceleration, electrocardiogram, skin conductance and respiratory rate. The data is stored on an Android phone and is analyzed offline through the extraction of features in the time, frequency and time-frequency domains. The analysis of the data depicted multisystem physiological interactions during overground walking in healthy subjects. These interactions included locomotion-electrodermal, locomotion-respiratory and cardiolocomotion couplings. The current results depicting strong interactions between the locomotion system and the other considered systems (i.e., electrodermal, respiratory and cardivascular systems) warrant further investigation into multisystem interactions during walking, particularly in challenging walking conditions with older adults. PMID:26390946

  3. Circadian regulation of hormone signaling and plant physiology.

    Science.gov (United States)

    Atamian, Hagop S; Harmer, Stacey L

    2016-08-01

    The survival and reproduction of plants depend on their ability to cope with a wide range of daily and seasonal environmental fluctuations during their life cycle. Phytohormones are plant growth regulators that are involved in almost every aspect of growth and development as well as plant adaptation to myriad abiotic and biotic conditions. The circadian clock, an endogenous and cell-autonomous biological timekeeper that produces rhythmic outputs with close to 24-h rhythms, provides an adaptive advantage by synchronizing plant physiological and metabolic processes to the external environment. The circadian clock regulates phytohormone biosynthesis and signaling pathways to generate daily rhythms in hormone activity that fine-tune a range of plant processes, enhancing adaptation to local conditions. This review explores our current understanding of the interplay between the circadian clock and hormone signaling pathways.

  4. Physiological roles of Regulated Ire1 Dependent Decay

    Directory of Open Access Journals (Sweden)

    Dina S. Coelho

    2014-04-01

    Full Text Available Ire1 is an important transducer of the Unfolded Protein Response (UPR that is activated by the accumulation of misfolded proteins in the Endoplamic Reticulum (ER stress. Activated Ire1 mediates the splicing of an intron from the mRNA of Xbp1, causing a frame-shift during translation and introducing a new carboxyl domain in the Xbp1 protein, which only then becomes a fully functional transcription factor. Studies using cell culture systems demonstrated that Ire1 also promotes the degradation of mRNAs encoding mostly ER-targeted proteins, to reduce the load of incoming ER client proteins during ER stress. This process was called RIDD (regulated Ire1-dependent decay, but its physiological significance remained poorly characterized beyond cell culture systems. Here we review several recent studies that have highlighted the physiological roles of RIDD in specific biological paradigms, such as photoreceptor differentiation in Drosophila or mammalian liver and endocrine pancreas function. These studies demonstrate the importance of RIDD in tissues undergoing intense secretory function and highlight the physiologic role of RIDD during UPR activation in cells and organisms.

  5. Barratt Impulsivity and Neural Regulation of Physiological Arousal.

    Directory of Open Access Journals (Sweden)

    Sheng Zhang

    Full Text Available Theories of personality have posited an increased arousal response to external stimulation in impulsive individuals. However, there is a dearth of studies addressing the neural basis of this association.We recorded skin conductance in 26 individuals who were assessed with Barratt Impulsivity Scale (BIS-11 and performed a stop signal task during functional magnetic resonance imaging. Imaging data were processed and modeled with Statistical Parametric Mapping. We used linear regressions to examine correlations between impulsivity and skin conductance response (SCR to salient events, identify the neural substrates of arousal regulation, and examine the relationship between the regulatory mechanism and impulsivity.Across subjects, higher impulsivity is associated with greater SCR to stop trials. Activity of the ventromedial prefrontal cortex (vmPFC negatively correlated to and Granger caused skin conductance time course. Furthermore, higher impulsivity is associated with a lesser strength of Granger causality of vmPFC activity on skin conductance, consistent with diminished control of physiological arousal to external stimulation. When men (n = 14 and women (n = 12 were examined separately, however, there was evidence suggesting association between impulsivity and vmPFC regulation of arousal only in women.Together, these findings confirmed the link between Barratt impulsivity and heightened arousal to salient stimuli in both genders and suggested the neural bases of altered regulation of arousal in impulsive women. More research is needed to explore the neural processes of arousal regulation in impulsive individuals and in clinical conditions that implicate poor impulse control.

  6. Barratt Impulsivity and Neural Regulation of Physiological Arousal.

    Science.gov (United States)

    Zhang, Sheng; Hu, Sien; Hu, Jianping; Wu, Po-Lun; Chao, Herta H; Li, Chiang-shan R

    2015-01-01

    Theories of personality have posited an increased arousal response to external stimulation in impulsive individuals. However, there is a dearth of studies addressing the neural basis of this association. We recorded skin conductance in 26 individuals who were assessed with Barratt Impulsivity Scale (BIS-11) and performed a stop signal task during functional magnetic resonance imaging. Imaging data were processed and modeled with Statistical Parametric Mapping. We used linear regressions to examine correlations between impulsivity and skin conductance response (SCR) to salient events, identify the neural substrates of arousal regulation, and examine the relationship between the regulatory mechanism and impulsivity. Across subjects, higher impulsivity is associated with greater SCR to stop trials. Activity of the ventromedial prefrontal cortex (vmPFC) negatively correlated to and Granger caused skin conductance time course. Furthermore, higher impulsivity is associated with a lesser strength of Granger causality of vmPFC activity on skin conductance, consistent with diminished control of physiological arousal to external stimulation. When men (n = 14) and women (n = 12) were examined separately, however, there was evidence suggesting association between impulsivity and vmPFC regulation of arousal only in women. Together, these findings confirmed the link between Barratt impulsivity and heightened arousal to salient stimuli in both genders and suggested the neural bases of altered regulation of arousal in impulsive women. More research is needed to explore the neural processes of arousal regulation in impulsive individuals and in clinical conditions that implicate poor impulse control.

  7. The central regulation of plant physiology by adenylates.

    Science.gov (United States)

    Geigenberger, Peter; Riewe, David; Fernie, Alisdair R

    2010-02-01

    There have been many recent developments concerning the metabolic, transport and signalling functions of adenylates in plants, suggesting new roles for these compounds as central regulators of plant physiology. For example, altering the expression levels of enzymes involved in the equilibration, salvaging, synthesis and transport of adenylates leads to perturbations in storage, growth and stress responses, implying a role for adenylates as important signals. Furthermore, sensing of the internal energy status involves SNF1-related kinases, which control the expression and phosphorylation of key metabolic enzymes. ATP also acts as an apoplastic signalling molecule to control cell growth and pathogen responses. These new results could shed light on the emerging question of whether energy homeostasis in plant cells differs from mechanisms found in microbes and mammals. Copyright 2009 Elsevier Ltd. All rights reserved.

  8. Cell volume regulation in epithelial physiology and cancer

    DEFF Research Database (Denmark)

    Pedersen, Stine Helene Falsig; Hoffmann, Else Kay; Novak, Ivana

    2013-01-01

    expression of ion transporters and channels is now recognized as one of the hallmarks of cancer, it is timely to consider this especially for epithelia. Epithelial cells are highly proliferative and epithelial cancers, carcinomas, account for about 90% of all cancers. In this review we will focus on ion...... such as cancer, transepithelial and cell volume regulatory ion transport are dys-regulated. Furthermore, epithelial architecture and coordinated ion transport function are lost, cell survival/death balance is altered, and new interactions with the stroma arise, all contributing to drug resistance. Since altered...... transporters and channels with key physiological functions in epithelia and known roles in the development of cancer in these tissues. Their roles in cell survival, cell cycle progression, and development of drug resistance in epithelial cancers will be discussed....

  9. Biomass chemicals: improvement in quality and quantity with physiological regulators

    Energy Technology Data Exchange (ETDEWEB)

    Kossuth, S.V.

    1984-01-01

    The search for alternative biomass energy forms has centered on two approaches: (1) production of cellulose fiber in biomass of low net energy value per unit weight, such as wood and bagasse, and (2) hydrocarbons of high net energy value per unit weight for use as chemical feedstocks and substitutes for petroleum. Major plant chemical products include oleoresin from pine (Pinus elliottii Engelm., P. palustris Mill.) rubber from the rubber tree (Hevea brasiliensis Muell.), and guayule shrub (Parthenium argentatum Gray) and sugar from sugarcane (Saccharum species). Ethylene may be a unifying natural bioregulator that can increase deposition of biomass chemicals in all four of these systems. Examples of bioregulators include the use of paraquat, diquat, and 2-chloroethylphosphonic acid (CEPA) for stimulating the synthesis of oleoresin, CEPA for prolonging the flow of rubber and increasing rubber synthesis in the rubber tree, and triethylamines of chlorinated phenoxy compounds for stimulating rubber production in guayule. In sugarcane, gibberellic acid (GA3) increases internodal elongation. Glyphosate, CEPA and other regulators increase the deposition of sucrose, diquat and CEPA inhibit flowering, and paraquat desiccates leaves to facilitate leaf removal or burning just prior to harvest. The cellular compartmentalization for the synthesis of these plant chemicals is unique for each species, and dictates cultural and harvest techniques. The mode of action and pathways for the success of these physiological regulators are discussed. 42 references.

  10. The hypocretins/orexins: integrators of multiple physiological functions

    Science.gov (United States)

    Li, Jingcheng; Hu, Zhian; Lecea, Luis

    2014-01-01

    The hypocretins (Hcrts), also known as orexins, are two peptides derived from a single precursor produced in the posterior lateral hypothalamus. Over the past decade, the orexin system has been associated with numerous physiological functions, including sleep/arousal, energy homeostasis, endocrine, visceral functions and pathological states, such as narcolepsy and drug abuse. Here, we review the discovery of Hcrt/orexins and their receptors and propose a hypothesis as to how the orexin system orchestrates these multifaceted physiological functions. Linked ArticlesThis article is part of a themed section on Orexin Receptors. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2014.171.issue-2 PMID:24102345

  11. Nitrite disrupts multiple physiological functions in aquatic animals

    DEFF Research Database (Denmark)

    Jensen, Frank Bo

    2003-01-01

    be inhibited, while changes in ammonia and urea levels and excretion rates reflect an influence of nitrite on nitrogen metabolism. Detoxification of nitrite occurs via endogenous oxidation to nitrate, and elimination of nitrite takes place both via gills and urine. The susceptibility to nitrite varies between...... nitrite-induced vasodilation (possibly via nitric oxide generated from nitrite) that is countered by increased cardiac pumping to re-establish blood pressure. Nitrite can form and/or mimic nitric oxide and thereby interfere with processes regulated by this local hormone. Steroid hormone synthesis may...

  12. Regulating Intracellular Calcium in Plants: From Molecular Genetics to Physiology

    International Nuclear Information System (INIS)

    Sze, Heven

    2008-01-01

    To grow, develop, adapt, and reproduce, plants have evolved mechanisms to regulate the uptake, translocation and sorting of calcium ions into different cells and subcellular compartments. Yet how plants accomplish this remarkable feat is still poorly understood. The spatial and temporal changes in intracellular (Ca2+) during growth and during responses to hormonal and environmental stimuli indicate that Ca2+ influx and efflux transporters are diverse and tightly regulated in plants. The specific goals were to determine the biological roles of multiple Ca pumps (ECAs) in the model plant Arabidopsis thaliana. We had pioneered the use of K616 yeast strain to functionally express plant Ca pumps, and demonstrated two distinct types of Ca pumps in plants (Sze et al., 2000. Annu Rev Plant Biol. 51,433). ACA2 represented one type that was auto-inhibited by the N-terminal region and stimulated by calmodulin. ECA1 represented another type that was not sensitive to calmodulin and phylogenetically distinct from ACAs. The goal to determine the biological roles of multiple ECA-type Ca pumps in Arabidopsis has been accomplished. Although we demonstrated ECA1 was a Ca pump by functional expression in yeast, the in vivo roles of ECAs was unclear. A few highlights are described. ECA1 and/or ECA4 are Ca/Mn pumps localized to the ER and are highly expressed in all cell types. Using homozygous T-DNA insertional mutants of eca1, we demonstrated that the ER-bound ECA1 supports growth and confers tolerance of plants growing on medium low in Ca or containing toxic levels of Mn. This is the first genetic study to determine the in vivo function of a Ca pump in plants. A phylogenetically distinct ECA3 is also a Ca/Mn pump that is localized to endosome, such as post-Golgi compartments. Although it is expressed at lower levels than ECA1, eca3 mutants are impaired in Ca-dependent root growth and in pollen tube elongation. Increased secretion of wall proteins in mutants suggests that Ca and Mn

  13. Individual Differences in Trajectories of Emotion Regulation Processes: The Effects of Maternal Depressive Symptomatology and Children's Physiological Regulation

    Science.gov (United States)

    Blandon, Alysia Y.; Calkins, Susan D.; Keane, Susan P.; O'Brien, Marion

    2008-01-01

    Trajectories of emotion regulation processes were examined in a community sample of 269 children across the ages of 4 to 7 using hierarchical linear modeling. Maternal depressive symptomatology (Symptom Checklist-90) and children's physiological reactivity (respiratory sinus arrhythmia [RSA]) and vagal regulation ([delta]RSA) were explored as…

  14. Dietary composition regulates Drosophila mobility and cardiac physiology

    Science.gov (United States)

    Bazzell, Brian; Ginzberg, Sara; Healy, Lindsey; Wessells, R. J.

    2013-01-01

    SUMMARY The impact of dietary composition on exercise capacity is a subject of intense study in both humans and model organisms. Interactions between diet and genetics are a crucial component of optimized dietary design. However, the genetic factors governing exercise response are still not well understood. The recent development of invertebrate models for endurance exercise is likely to facilitate study designs examining the conserved interactions between diet, exercise and genetics. As a first step, we used the Drosophila model to describe the effects of varying dietary composition on several physiological indices, including fatigue tolerance and climbing speed, cardiac performance, lipid storage and autophagy. We found that flies of two divergent genetic backgrounds optimize endurance and cardiac performance on relatively balanced low calorie diets. When flies are provided with unbalanced diets, diets higher in sugar than in yeast facilitate greater endurance at the expense of cardiac performance. Importantly, we found that dietary composition has a profound effect on various physiological indices, whereas total caloric intake per se has very little predictive value for performance. We also found that the effects of diet on endurance are completely reversible within 48 h if flies are switched to a different diet. PMID:23155082

  15. AKAP-scaffolding proteins and regulation of cardiac physiology

    Science.gov (United States)

    Mauban, JRH; O'Donnell, M; Warrier, S; Manni, S; Bond, M

    2009-01-01

    A kinase anchoring proteins (AKAPs) compose a growing list of diverse but functionally related proteins defined by their ability to bind to the regulatory subunit of protein kinase A. AKAPs perform an integral role in the spatiotemporal modulation of a multitude of cellular signaling pathways. This review highlights the extensive role of AKAPs in cardiac excitation/contraction coupling and cardiac physiology. The literature shows that particular AKAPs are involved in cardiac Ca2+ influx, release, re-uptake, and myocyte repolarization. Studies have also suggested roles for AKAPs in cardiac remodeling. Transgenic studies show functional effects of AKAPs, not only in the cardiovascular system, but in other organ systems as well. PMID:19364910

  16. Silicon Regulates Potential Genes Involved in Major Physiological Processes in Plants to Combat Stress

    Directory of Open Access Journals (Sweden)

    Abinaya Manivannan

    2017-08-01

    Full Text Available Silicon (Si, the quasi-essential element occurs as the second most abundant element in the earth's crust. Biological importance of Si in plant kingdom has become inevitable particularly under stressed environment. In general, plants are classified as high, medium, and low silicon accumulators based on the ability of roots to absorb Si. The uptake of Si directly influence the positive effects attributed to the plant but Si supplementation proves to mitigate stress and recover plant growth even in low accumulating plants like tomato. The application of Si in soil as well as soil-less cultivation systems have resulted in the enhancement of quantitative and qualitative traits of plants even under stressed environment. Silicon possesses several mechanisms to regulate the physiological, biochemical, and antioxidant metabolism in plants to combat abiotic and biotic stresses. Nevertheless, very few reports are available on the aspect of Si-mediated molecular regulation of genes with potential role in stress tolerance. The recent advancements in the era of genomics and transcriptomics have opened an avenue for the determination of molecular rationale associated with the Si amendment to the stress alleviation in plants. Therefore, the present endeavor has attempted to describe the recent discoveries related to the regulation of vital genes involved in photosynthesis, transcription regulation, defense, water transport, polyamine synthesis, and housekeeping genes during abiotic and biotic stress alleviation by Si. Furthermore, an overview of Si-mediated modulation of multiple genes involved in stress response pathways such as phenylpropanoid pathway, jasmonic acid pathway, ABA-dependent or independent regulatory pathway have been discussed in this review.

  17. Maladaptive autonomic regulation in PTSD accelerates physiological aging

    Directory of Open Access Journals (Sweden)

    John B Williamson

    2015-01-01

    Full Text Available A core manifestation of posttraumatic stress disorder is a disconnection between physiological state and psychological and behavior processes necessary to adequately respond to environmental demands. Patients with PTSD experience oscillations in autonomic states that support either fight and flight behaviors or withdrawal, immobilization, and dissociation without an intervening calm state that would provide opportunities for positive social interactions. This defensive autonomic disposition is adaptive in dangerous and life threatening situations, but in the context of every-day life may lead to significant psychosocial distress and deteriorating social relationships. The perpetuation of these maladaptive autonomic responses, may contribute to the development of comorbid mental health issues such as depression, loneliness, and hostility that further modify the nature of cardiovascular behavior in the context of internal and external stressors. Over time, changes in autonomic, endocrine, and immune function contribute to deteriorating health, which is potently expressed in brain dysfunction and cardiovascular health. In this theoretical review paper, we review the literature on the chronic health effects of post-traumatic stress disorder. We discuss the brain networks underlying post-traumatic stress disorder in the context of autonomic efferent and afferent contributions and how disruption of these networks leads to poor health outcomes. Finally, we discuss treatments based on our theoretical model of posttraumatic stress disorder.

  18. Liver physiological polyploidization: MicroRNA-122 a key regulator.

    Science.gov (United States)

    Celton-Morizur, Séverine; Desdouets, Chantal

    2017-03-01

    Polyploidy is defined as an increase in genome DNA content and is observed in all mammalian species. Polyploidy is a common characteristic of hepatocytes. Polyploidization occurs mainly during liver development, but also in adults with increasing age or due to cellular stress. During liver development, hepatocytes polyploidization occurs through cytokinesis failure leading to the genesis of binucleate hepatocytes. Recently, Hsu et al. demonstrated that miR-122 is a key regulator of hepatic binucleation. In fact, during liver development, miR-122 directly antagonizes procytokinesis targets and thus induces cytokinesis failure leading to the genesis of binucleate hepatocytes. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  19. Multiple regulatory roles of the mouse transmembrane adaptor protein NTAL in gene transcription and mast cell physiology.

    Directory of Open Access Journals (Sweden)

    Iva Polakovicova

    Full Text Available Non-T cell activation linker (NTAL; also called LAB or LAT2 is a transmembrane adaptor protein that is expressed in a subset of hematopoietic cells, including mast cells. There are conflicting reports on the role of NTAL in the high affinity immunoglobulin E receptor (FcεRI signaling. Studies carried out on mast cells derived from mice with NTAL knock out (KO and wild type mice suggested that NTAL is a negative regulator of FcεRI signaling, while experiments with RNAi-mediated NTAL knockdown (KD in human mast cells and rat basophilic leukemia cells suggested its positive regulatory role. To determine whether different methodologies of NTAL ablation (KO vs KD have different physiological consequences, we compared under well defined conditions FcεRI-mediated signaling events in mouse bone marrow-derived mast cells (BMMCs with NTAL KO or KD. BMMCs with both NTAL KO and KD exhibited enhanced degranulation, calcium mobilization, chemotaxis, tyrosine phosphorylation of LAT and ERK, and depolymerization of filamentous actin. These data provide clear evidence that NTAL is a negative regulator of FcεRI activation events in murine BMMCs, independently of possible compensatory developmental alterations. To gain further insight into the role of NTAL in mast cells, we examined the transcriptome profiles of resting and antigen-activated NTAL KO, NTAL KD, and corresponding control BMMCs. Through this analysis we identified several genes that were differentially regulated in nonactivated and antigen-activated NTAL-deficient cells, when compared to the corresponding control cells. Some of the genes seem to be involved in regulation of cholesterol-dependent events in antigen-mediated chemotaxis. The combined data indicate multiple regulatory roles of NTAL in gene expression and mast cell physiology.

  20. Teacher regulation of multiple computer-supported collaborating groups

    NARCIS (Netherlands)

    Van Leeuwen, Anouschka; Janssen, Jeroen; Erkens, Gijsbert; Brekelmans, Mieke

    2015-01-01

    Teachers regulating groups of students during computer-supported collaborative learning (CSCL) face the challenge of orchestrating their guidance at student, group, and class level. During CSCL, teachers can monitor all student activity and interact with multiple groups at the same time. Not much is

  1. Educators' emotion regulation strategies and their physiological indicators of chronic stress over 1 year.

    Science.gov (United States)

    Katz, Deirdre A; Harris, Alexis; Abenavoli, Rachel; Greenberg, Mark T; Jennings, Patricia A

    2018-04-01

    Studies show teaching is a highly stressful profession and that chronic work stress is associated with adverse health outcomes. This study analysed physiological markers of stress and self-reported emotion regulation strategies in a group of middle school teachers over 1 year. Chronic physiological stress was assessed with diurnal cortisol measures at three time points over 1 year (fall, spring, fall). The aim of this longitudinal study was to investigate the changes in educators' physiological level of stress. Results indicate that compared to those in the fall, cortisol awakening responses were blunted in the spring. Further, this effect was ameliorated by the summer break. Additionally, self-reported use of the emotion regulation strategy reappraisal buffered the observed blunting that occurred in the spring. Copyright © 2017 John Wiley & Sons, Ltd.

  2. The benefit of self-testing and interleaving for synthesizing concepts across multiple physiology texts.

    Science.gov (United States)

    Linderholm, Tracy; Dobson, John; Yarbrough, Mary Beth

    2016-09-01

    A testing-based learning strategy is one that relies on the act of recalling (i.e., testing) information after exposure, and interleaving is a strategy in which the learning materials are presented in a serial order (e.g., texts 1, 2, 3, 1, 2, 3, 1, 2, 3) versus a blocked order (e.g., texts 1, 1, 1, 2, 2, 2, 3, 3, 3). Although both learning strategies have been thoroughly investigated, few studies have examined their additive effect with higher-order cognitive tasks such as the ability to identify themes across multiple texts, and none of those did so using physiology information. The purpose of the present study was to compare recall and thematic processing across five different physiology texts. Participants were randomly assigned to learn the texts using one of the following four learning strategies: 1) study-study-study (S-S-S) using a blocked order, 2) S-S-S using an interleaved order, 3) study-test-study (S-T-S) using a blocked order, and 4) S-T-S using an interleaved order. Over the course of the following week, the S-T-S groups had more stable recall of key text ideas compared with the S-S-S groups, and the S-T-S group had more stable recall of thematic information than the S-S-S group when interleaving was used as the presentation order. Copyright © 2016 The American Physiological Society.

  3. FGF21 as an Endocrine Regulator in Lipid Metabolism: From Molecular Evolution to Physiology and Pathophysiology

    Directory of Open Access Journals (Sweden)

    Yusuke Murata

    2011-01-01

    Full Text Available The FGF family comprises twenty-two structurally related proteins with functions in development and metabolism. The Fgf21 gene was generated early in vertebrate evolution. FGF21 acts as an endocrine regulator in lipid metabolism. Hepatic Fgf21 expression is markedly induced in mice by fasting or a ketogenic diet. Experiments with Fgf21 transgenic mice and cultured cells indicate that FGF21 exerts pharmacological effects on glucose and lipid metabolism in hepatocytes and adipocytes via cell surface FGF receptors. However, experiments with Fgf21 knockout mice indicate that FGF21 inhibits lipolysis in adipocytes during fasting and attenuates torpor induced by a ketogenic diet but maybe not a physiological regulator for these hepatic functions. These findings suggest the pharmacological effects to be distinct from the physiological roles. Serum FGF21 levels are increased in patients with metabolic diseases having insulin resistance, indicating that FGF21 is a metabolic regulator and a biomarker for these diseases.

  4. Leptin expression in ruminants: nutritional and physiological regulations in relation with energy metabolism.

    Science.gov (United States)

    Chilliard, Y; Delavaud, C; Bonnet, M

    2005-07-01

    Leptin, mainly produced in adipose tissue (AT), is a protein involved in the central and/or peripheral regulation of body homeostasis, energy intake, storage and expenditure, fertility and immune functions. Its role is well documented in rodent and human species, but less in ruminants. This review is focused on some intrinsic and extrinsic factors which regulate adipose tissue leptin gene expression and leptinemia in cattle, sheep, goat and camel: age, physiological status (particularly pregnancy and lactation) in interaction with long-term (adiposity) and short-term effects of feeding level, energy intake and balance, diet composition, specific nutrients and hormones (insulin, glucose and fatty acids), and seasonal non-dietary factors such as photoperiod. Body fatness strongly regulates leptin and its responses to other factors. For example, leptinemia is higher after underfeeding or during lactation in fat than in lean animals. Physiological status per se also modulates leptin expression, with lactation down-regulating leptinemia, even when energy balance (EB) is positive. These results suggest that leptin could be a link between nutritional history and physiological regulations, which integrates the animal's requirements (e.g., for a pregnancy-lactation cycle), predictable food availability (e.g., due to seasonal variations) and potential for survival (e.g., body fatness level). Reaching permissive leptin thresholds should be necessary for pubertal or postpartum reproductive activity. In addition to the understanding of leptin yield regulation, these data are helpful to understand the physiological significance of changes in leptin secretion and leptin effects, and how husbandry strategies could integrate the adaptative capacities of ruminant species to their environment.

  5. Life under Multiple Extreme Conditions: Diversity and Physiology of the Halophilic Alkalithermophiles

    Science.gov (United States)

    Wiegel, Juergen

    2012-01-01

    Around the world, there are numerous alkaline, hypersaline environments that are heated either geothermally or through intense solar radiation. It was once thought that such harsh environments were inhospitable and incapable of supporting a variety of life. However, numerous culture-dependent and -independent studies revealed the presence of an extensive diversity of aerobic and anaerobic bacteria and archaea that survive and grow under these multiple harsh conditions. This diversity includes the halophilic alkalithermophiles, a novel group of polyextremophiles that require for growth and proliferation the multiple extremes of high salinity, alkaline pH, and elevated temperature. Life under these conditions undoubtedly involves the development of unique physiological characteristics, phenotypic properties, and adaptive mechanisms that enable control of membrane permeability, control of intracellular osmotic balance, and stability of the cell wall, intracellular proteins, and other cellular constituents. This minireview highlights the ecology and growth characteristics of the extremely halophilic alkalithermophiles that have been isolated thus far. Biochemical, metabolic, and physiological properties of the extremely halophilic alkalithermophiles are described, and their roles in resistance to the combined stressors of high salinity, alkaline pH, and high temperature are discussed. The isolation of halophilic alkalithermophiles broadens the physicochemical boundaries for life and extends the boundaries for the combinations of the maximum salinity, pH, and temperature that can support microbial growth. PMID:22492435

  6. A new approach to homeostatic regulation: towards a unified view of physiological and ecological concepts.

    Directory of Open Access Journals (Sweden)

    Cédric L Meunier

    Full Text Available Stoichiometric homeostasis is the ability of an organism to keep its body chemical composition constant, despite varying inputs. Stoichiometric homeostasis therefore constrains the metabolic needs of consumers which in turn often feed on resources not matching these requirements. In a broader context, homeostasis also relates to the capacity of an organism to maintain other biological parameters (e.g. body temperature at a constant level over ambient environmental variations. Unfortunately, there are discrepancies in the literature and ecological and physiological definitions of homeostasis are disparate and partly contradictory. Here, we address this matter by reviewing the existing knowledge considering two distinct groups, regulators and conformers and, based on examples of thermo- and osmoregulation, we propose a new approach to stoichiometric homeostasis, unifying ecological and physiological concepts. We suggest a simple and precise graphical way to identify regulators and conformers: for any given biological parameter (e.g. nutrient stoichiometry, temperature, a sigmoidal relation between internal and external conditions can be observed for conformers while an inverse sigmoidal response is characteristic of regulators. This new definition and method, based on well-studied physiological mechanisms, unifies ecological and physiological approaches and is a useful tool for understanding how organisms are affected by and affect their environment.

  7. Children’s Play as a Context for Managing Physiological Arousal and Learning Emotion Regulation

    Directory of Open Access Journals (Sweden)

    Peter LaFreniere

    2013-09-01

    Full Text Available In this paper I examine children’s play as a context for managing physiological arousal and learning to regulate strong emotions. I define emotion regulation as the process by which children monitor and control their emotional states and their expression to adapt to different social situations or demands. Age trends and gender differences in emotion regulation problems and competencies are described. I then review the development of play, deprivation studies, and the biological functions of different forms of play in primates before discussing children’s play. Vigorous social play benefits children by promoting the development of communication, perspective-taking and emotion regulation skills. For boys especially, rough-and-tumble play in early childhood provides a scaffold for learning emotion regulation skills related to managing anger and aggression.

  8. Multiple roles for the actin cytoskeleton during regulated exocytosis

    Science.gov (United States)

    Porat-Shliom, Natalie; Milberg, Oleg; Masedunskas, Andrius; Weigert, Roberto

    2014-01-01

    Regulated exocytosis is the main mechanism utilized by specialized secretory cells to deliver molecules to the cell surface by virtue of membranous containers (i.e. secretory vesicles). The process involves a series of highly coordinated and sequential steps, which include the biogenesis of the vesicles, their delivery to the cell periphery, their fusion with the plasma membrane and the release of their content into the extracellular space. Each of these steps is regulated by the actin cytoskeleton. In this review, we summarize the current knowledge regarding the involvement of actin and its associated molecules during each of the exocytic steps in vertebrates, and suggest that the overall role of the actin cytoskeleton during regulated exocytosis is linked to the architecture and the physiology of the secretory cells under examination. Specifically, in neurons, neuroendocrine, endocrine, and hematopoietic cells, which contain small secretory vesicles that undergo rapid exocytosis (on the order of milliseconds), the actin cytoskeleton plays a role in pre-fusion events, where it acts primarily as a functional barrier and facilitates docking. In exocrine and other secretory cells, which contain large secretory vesicles that undergo slow exocytosis (seconds to minutes), the actin cytoskeleton plays a role in post-fusion events, where it regulates the dynamics of the fusion pore, facilitates the integration of the vesicles into the plasma membrane, provides structural support, and promotes the expulsion of large cargo molecules. PMID:22986507

  9. Baseline and strategic effects behind mindful emotion regulation: behavioral and physiological investigation.

    Directory of Open Access Journals (Sweden)

    Alessandro Grecucci

    Full Text Available One of the consequences of extensive mindfulness practice is a reduction of anxiety and depression, but also a capacity to regulate negative emotions. In this study, we explored four key questions concerning mindfulness training: (1 What are the processes by which mindfulness regulates our emotions? (2 Can mindfulness be applied to social emotions? (3 Does mindfulness training affect emotionally driven behavior towards others? (4 Does mindfulness alter physiological reactivity? To address these questions, we tested, in two experiments, the ability of mindfulness meditators to regulate interpersonal emotions (Experiment 1 and interactive behaviors (Experiment 2 as compared to naïve controls. To better understand the mechanisms by which mindfulness regulates emotions, we asked participants to apply two strategies: a cognitive strategy (mentalizing, a form of reappraisal focused on the intentions of others and an experiential strategy derived from mindfulness principles (mindful detachment. Both groups were able to regulate interpersonal emotions by means of cognitive (mentalizing and experiential (mindful detachment strategies. In Experiment 1, a simple effect of meditation, independent from the implementation of the strategies, resulted in reduced emotional and physiological reactivity, as well as in increased pleasantness for meditators when compared to controls, providing evidence of baseline regulation. In Experiment 2, one visible effect of the strategy was that meditators outperformed controls in the experiential (mindful detachment but not in the cognitive (mentalize strategy, showing stronger modulation of their interactive behavior (less punishments and providing evidence of a strategic behavioral regulation. Based on these results, we suggest that mindfulness can influence interpersonal emotional reactions through an experiential mechanism, both at a baseline level and a strategic level, thereby altering the subjective and physiological

  10. Self-regulation method: psychological, physiological and clinical considerations. An overview.

    Science.gov (United States)

    Ikemi, A; Tomita, S; Kuroda, M; Hayashida, Y; Ikemi, Y

    1986-01-01

    Body-oriented therapies as relaxation training and certain forms of meditation are gaining popularity in the treatment and prevention of psychosomatic disorders. In this paper, a new method of self-control called self-regulation method (SRM), derived from autogenic training and Zen meditation, is presented. The technique of SRM is introduced. Secondly, physiological studies on SRM using skin temperature, galvanic skin response, and cortical evoked potentials are presented. Thirdly, the results of psychological tests conducted on SRM are presented. These psycho-physiological studies suggest that SRM may elicit a state of 'relaxed alertness'. Fourthly, clinical applications of SRM are discussed, and 3 cases are presented. Finally, SRM is discussed in relation to the psychology and physiology of 'relaxed alertness'.

  11. Novel Molecules Regulating Energy Homeostasis: Physiology and Regulation by Macronutrient Intake and Weight Loss

    Directory of Open Access Journals (Sweden)

    Anna Gavrieli

    2016-09-01

    Full Text Available Excess energy intake, without a compensatory increase of energy expenditure, leads to obesity. Several molecules are involved in energy homeostasis regulation and new ones are being discovered constantly. Appetite regulating hormones such as ghrelin, peptide tyrosine-tyrosine and amylin or incretins such as the gastric inhibitory polypeptide have been studied extensively while other molecules such as fibroblast growth factor 21, chemerin, irisin, secreted frizzle-related protein-4, total bile acids, and heme oxygenase-1 have been linked to energy homeostasis regulation more recently and the specific role of each one of them has not been fully elucidated. This mini review focuses on the above mentioned molecules and discusses them in relation to their regulation by the macronutrient composition of the diet as well as diet-induced weight loss.

  12. Integration of Genome Scale Metabolic Networks and Gene Regulation of Metabolic Enzymes With Physiologically Based Pharmacokinetics.

    Science.gov (United States)

    Maldonado, Elaina M; Leoncikas, Vytautas; Fisher, Ciarán P; Moore, J Bernadette; Plant, Nick J; Kierzek, Andrzej M

    2017-11-01

    The scope of physiologically based pharmacokinetic (PBPK) modeling can be expanded by assimilation of the mechanistic models of intracellular processes from systems biology field. The genome scale metabolic networks (GSMNs) represent a whole set of metabolic enzymes expressed in human tissues. Dynamic models of the gene regulation of key drug metabolism enzymes are available. Here, we introduce GSMNs and review ongoing work on integration of PBPK, GSMNs, and metabolic gene regulation. We demonstrate example models. © 2017 The Authors CPT: Pharmacometrics & Systems Pharmacology published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics.

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

    Science.gov (United States)

    Larsen, Brianna; Snow, Rod; Vincent, Grace; Tran, Jacqueline; Wolkow, Alexander; Aisbett, Brad

    2015-01-01

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

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

    Science.gov (United States)

    Larsen, Brianna; Snow, Rod; Vincent, Grace; Tran, Jacqueline; Wolkow, Alexander; Aisbett, Brad

    2015-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Brianna Larsen

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

  16. Exercise and multiple sclerosis: physiological, psychological, and quality of life issues.

    Science.gov (United States)

    Sutherland, G; Andersen, M B

    2001-12-01

    The case for the benefits of physical activity has been well documented in healthy individuals, and the potential for reducing the risk of mental and physical ill health is substantial. Yet, individuals with multiple sclerosis (MS) have long been advised to avoid participation in exercise in order to minimise the risk of exacerbations and symptoms of fatigue. There is, however, increasing interest in how acute and chronic exercise affect physiological and psychological functioning in MS. Much of the research has examined physiological tolerance to exercise and focused on responses in terms of heart rate, blood pressure, cardiorespiratory fitness, muscle function, and symptom stability. Little research has focused on understanding how exercise affects psychosocial functioning and brings about changes in depression, affect, mood, well-being, and quality of life. This paper provides a summary of the research exploring the efficacy of physical activity for people with MS. In addition, the key issues that face clinical practice are examined, and considerations for research are discussed.

  17. [Construction and analysis of a monitoring system with remote real-time multiple physiological parameters based on cloud computing].

    Science.gov (United States)

    Zhu, Lingyun; Li, Lianjie; Meng, Chunyan

    2014-12-01

    There have been problems in the existing multiple physiological parameter real-time monitoring system, such as insufficient server capacity for physiological data storage and analysis so that data consistency can not be guaranteed, poor performance in real-time, and other issues caused by the growing scale of data. We therefore pro posed a new solution which was with multiple physiological parameters and could calculate clustered background data storage and processing based on cloud computing. Through our studies, a batch processing for longitudinal analysis of patients' historical data was introduced. The process included the resource virtualization of IaaS layer for cloud platform, the construction of real-time computing platform of PaaS layer, the reception and analysis of data stream of SaaS layer, and the bottleneck problem of multi-parameter data transmission, etc. The results were to achieve in real-time physiological information transmission, storage and analysis of a large amount of data. The simulation test results showed that the remote multiple physiological parameter monitoring system based on cloud platform had obvious advantages in processing time and load balancing over the traditional server model. This architecture solved the problems including long turnaround time, poor performance of real-time analysis, lack of extensibility and other issues, which exist in the traditional remote medical services. Technical support was provided in order to facilitate a "wearable wireless sensor plus mobile wireless transmission plus cloud computing service" mode moving towards home health monitoring for multiple physiological parameter wireless monitoring.

  18. Novel multiple sclerosis susceptibility loci implicated in epigenetic regulation.

    Science.gov (United States)

    Andlauer, Till F M; Buck, Dorothea; Antony, Gisela; Bayas, Antonios; Bechmann, Lukas; Berthele, Achim; Chan, Andrew; Gasperi, Christiane; Gold, Ralf; Graetz, Christiane; Haas, Jürgen; Hecker, Michael; Infante-Duarte, Carmen; Knop, Matthias; Kümpfel, Tania; Limmroth, Volker; Linker, Ralf A; Loleit, Verena; Luessi, Felix; Meuth, Sven G; Mühlau, Mark; Nischwitz, Sandra; Paul, Friedemann; Pütz, Michael; Ruck, Tobias; Salmen, Anke; Stangel, Martin; Stellmann, Jan-Patrick; Stürner, Klarissa H; Tackenberg, Björn; Then Bergh, Florian; Tumani, Hayrettin; Warnke, Clemens; Weber, Frank; Wiendl, Heinz; Wildemann, Brigitte; Zettl, Uwe K; Ziemann, Ulf; Zipp, Frauke; Arloth, Janine; Weber, Peter; Radivojkov-Blagojevic, Milena; Scheinhardt, Markus O; Dankowski, Theresa; Bettecken, Thomas; Lichtner, Peter; Czamara, Darina; Carrillo-Roa, Tania; Binder, Elisabeth B; Berger, Klaus; Bertram, Lars; Franke, Andre; Gieger, Christian; Herms, Stefan; Homuth, Georg; Ising, Marcus; Jöckel, Karl-Heinz; Kacprowski, Tim; Kloiber, Stefan; Laudes, Matthias; Lieb, Wolfgang; Lill, Christina M; Lucae, Susanne; Meitinger, Thomas; Moebus, Susanne; Müller-Nurasyid, Martina; Nöthen, Markus M; Petersmann, Astrid; Rawal, Rajesh; Schminke, Ulf; Strauch, Konstantin; Völzke, Henry; Waldenberger, Melanie; Wellmann, Jürgen; Porcu, Eleonora; Mulas, Antonella; Pitzalis, Maristella; Sidore, Carlo; Zara, Ilenia; Cucca, Francesco; Zoledziewska, Magdalena; Ziegler, Andreas; Hemmer, Bernhard; Müller-Myhsok, Bertram

    2016-06-01

    We conducted a genome-wide association study (GWAS) on multiple sclerosis (MS) susceptibility in German cohorts with 4888 cases and 10,395 controls. In addition to associations within the major histocompatibility complex (MHC) region, 15 non-MHC loci reached genome-wide significance. Four of these loci are novel MS susceptibility loci. They map to the genes L3MBTL3, MAZ, ERG, and SHMT1. The lead variant at SHMT1 was replicated in an independent Sardinian cohort. Products of the genes L3MBTL3, MAZ, and ERG play important roles in immune cell regulation. SHMT1 encodes a serine hydroxymethyltransferase catalyzing the transfer of a carbon unit to the folate cycle. This reaction is required for regulation of methylation homeostasis, which is important for establishment and maintenance of epigenetic signatures. Our GWAS approach in a defined population with limited genetic substructure detected associations not found in larger, more heterogeneous cohorts, thus providing new clues regarding MS pathogenesis.

  19. Ethylene and the Regulation of Physiological and Morphological Responses to Nutrient Deficiencies

    Science.gov (United States)

    García, María José; Romera, Francisco Javier; Lucena, Carlos; Alcántara, Esteban; Pérez-Vicente, Rafael

    2015-01-01

    To cope with nutrient deficiencies, plants develop both morphological and physiological responses. The regulation of these responses is not totally understood, but some hormones and signaling substances have been implicated. It was suggested several years ago that ethylene participates in the regulation of responses to iron and phosphorous deficiency. More recently, its role has been extended to other deficiencies, such as potassium, sulfur, and others. The role of ethylene in so many deficiencies suggests that, to confer specificity to the different responses, it should act through different transduction pathways and/or in conjunction with other signals. In this update, the data supporting a role for ethylene in the regulation of responses to different nutrient deficiencies will be reviewed. In addition, the results suggesting the action of ethylene through different transduction pathways and its interaction with other hormones and signaling substances will be discussed. PMID:26175512

  20. Stress and serial adult metamorphosis: Multiple roles for the stress axis in socially regulated sex change

    Directory of Open Access Journals (Sweden)

    Tessa K Solomon-Lane

    2013-11-01

    Full Text Available Socially regulated sex change in teleost fishes is a striking example of social status information regulating biological function in the service of reproductive success. The establishment of social dominance in sex changing species is translated into a cascade of changes in behavior, physiology, neuroendocrine function, and morphology that transforms a female into a male, or vice versa. The hypothalamic-pituitary-interrenal axis (HPI, homologous to HP-adrenal axis in mammals and birds has been hypothesized to play a mechanistic role linking status to sex change. The HPA/I axis responds to environmental stressors by integrating relevant external and internal cues and coordinating biological responses including changes in behavior, energetics, physiology, and morphology (i.e., metamorphosis. Through actions of both corticotropin-releasing factor and glucocorticoids (GCs, the HPA/I axis has been implicated in processes central to sex change, including the regulation of agonistic behavior, social status, energetic investment, and life history transitions. In this paper, we review the hypothesized roles of the HPA/I axis in the regulation of sex change and how those hypotheses have been tested to date. We include original data on sex change in the bluebanded goby (Lythyrpnus dalli, a highly social fish capable of bidirectional sex change. We then propose a model for HPA/I involvement in sex change and discuss how these ideas might be tested in the future. Understanding the regulation of sex change has the potential to elucidate evolutionarily conserved mechanisms responsible for translating pertinent information about the environment into coordinated biological changes along multiple body axes.

  1. Stress and serial adult metamorphosis: multiple roles for the stress axis in socially regulated sex change.

    Science.gov (United States)

    Solomon-Lane, Tessa K; Crespi, Erica J; Grober, Matthew S

    2013-01-01

    Socially regulated sex change in teleost fishes is a striking example of social status information regulating biological function in the service of reproductive success. The establishment of social dominance in sex changing species is translated into a cascade of changes in behavior, physiology, neuroendocrine function, and morphology that transforms a female into a male, or vice versa. The hypothalamic-pituitary-interrenal axis (HPI, homologous to HP-adrenal axis in mammals and birds) has been hypothesized to play a mechanistic role linking status to sex change. The HPA/I axis responds to environmental stressors by integrating relevant external and internal cues and coordinating biological responses including changes in behavior, energetics, physiology, and morphology (i.e., metamorphosis). Through actions of both corticotropin-releasing factor and glucocorticoids, the HPA/I axis has been implicated in processes central to sex change, including the regulation of agonistic behavior, social status, energetic investment, and life history transitions. In this paper, we review the hypothesized roles of the HPA/I axis in the regulation of sex change and how those hypotheses have been tested to date. We include original data on sex change in the bluebanded goby (Lythyrpnus dalli), a highly social fish capable of bidirectional sex change. We then propose a model for HPA/I involvement in sex change and discuss how these ideas might be tested in the future. Understanding the regulation of sex change has the potential to elucidate evolutionarily conserved mechanisms responsible for translating pertinent information about the environment into coordinated biological changes along multiple body axes.

  2. Mother and newborn baby: mutual regulation of physiology and behavior--a selective review.

    Science.gov (United States)

    Winberg, Jan

    2005-11-01

    This article reviews 30 years of work demonstrating that interactions between mother and newborn infant in the period just after birth influence the physiology and behavior of both. Close body contact of the infant with his/her mother helps regulate the newborn's temperature, energy conservation, acid-base balance, adjustment of respiration, crying, and nursing behaviors. Similarly, the baby may regulate--i.e., increase--the mother's attention to his/her needs, the initiation and maintenance of breastfeeding, and the efficiency of her energy economy through vagus activation and a surge of gastrointestinal tract hormone release resulting in better exploitation of ingested calories. The effects of some of these changes can be detected months later. Parallels to animal research and possible mechanisms are discussed.

  3. THERMAL REGULATION OF THE BRAIN -AN ANATOMICAL AND PHYSIOLOGICAL REVIEW FOR CLINICAL NEUROSCIENTISTS

    Directory of Open Access Journals (Sweden)

    Huan (John eWang

    2016-01-01

    Full Text Available Humans, like all mammals and birds, maintain a nearly constant core body temperature (36 -37.5°C over a wide range of environmental conditions and are thus referred to as endotherms. The evolution of the brain and its supporting structures in mammals and birds coincided with this development of endothermy. Despite the recognition that a more evolved and complicated brain with all of its temperature-dependent cerebral circuitry and neuronal processes would require more sophisticated thermal control mechanisms, the current understanding of brain temperature regulation remains limited. To optimize the development and maintenance of the brain in health and to accelerate its healing and restoration in illness, focused and committed efforts are much needed to advance the fundamental understanding of brain temperature. In order to effectively study and examine brain temperature regulation, it is critical to first understand the relevant anatomical and physiological properties in the head-neck regions.

  4. CRISPR/Cas systems: new players in gene regulation and bacterial physiology

    Directory of Open Access Journals (Sweden)

    David eWeiss

    2014-04-01

    Full Text Available CRISPR-Cas systems are bacterial defenses against foreign nucleic acids derived from bacteriophages, plasmids or other sources. These systems are targeted in an RNA-dependent, sequence-specific manner, and are also adaptive, providing protection against previously encountered foreign elements. In addition to their canonical function in defense against foreign nucleic acid, their roles in various aspects of bacterial physiology are now being uncovered. We recently revealed a role for a Cas9-based Type II CRISPR-Cas system in the control of endogenous gene expression, a novel form of prokaryotic gene regulation. Cas9 functions in association with two small RNAs to target and alter the stability of an endogenous transcript encoding a bacterial lipoprotein (BLP. Since BLPs are recognized by the host innate immune protein Toll-like Receptor 2 (TLR2, CRISPR-Cas-mediated repression of BLP expression facilitates evasion of TLR2 by the intracellular bacterial pathogen Francisella novicida, and is essential for its virulence. Here we describe the Cas9 regulatory system in detail, as well as data on its role in controlling virulence traits of Neisseria meningitidis and Campylobacter jejuni. We also discuss potential roles of CRISPR-Cas systems in the response to envelope stress and other aspects of bacterial physiology. Since ~45% of bacteria and ~83% of Archaea encode these machineries, the newly appreciated regulatory functions of CRISPR-Cas systems are likely to play broad roles in controlling the pathogenesis and physiology of diverse prokaryotes.

  5. Physiological regulation through learnt control of appetites by contingencies among signals from external and internal environments.

    Science.gov (United States)

    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.

  6. Branched-chain amino acid catabolism is a conserved regulator of physiological ageing.

    Science.gov (United States)

    Mansfeld, Johannes; Urban, Nadine; Priebe, Steffen; Groth, Marco; Frahm, Christiane; Hartmann, Nils; Gebauer, Juliane; Ravichandran, Meenakshi; Dommaschk, Anne; Schmeisser, Sebastian; Kuhlow, Doreen; Monajembashi, Shamci; Bremer-Streck, Sibylle; Hemmerich, Peter; Kiehntopf, Michael; Zamboni, Nicola; Englert, Christoph; Guthke, Reinhard; Kaleta, Christoph; Platzer, Matthias; Sühnel, Jürgen; Witte, Otto W; Zarse, Kim; Ristow, Michael

    2015-12-01

    Ageing has been defined as a global decline in physiological function depending on both environmental and genetic factors. Here we identify gene transcripts that are similarly regulated during physiological ageing in nematodes, zebrafish and mice. We observe the strongest extension of lifespan when impairing expression of the branched-chain amino acid transferase-1 (bcat-1) gene in C. elegans, which leads to excessive levels of branched-chain amino acids (BCAAs). We further show that BCAAs reduce a LET-363/mTOR-dependent neuro-endocrine signal, which we identify as DAF-7/TGFβ, and that impacts lifespan depending on its related receptors, DAF-1 and DAF-4, as well as ultimately on DAF-16/FoxO and HSF-1 in a cell-non-autonomous manner. The transcription factor HLH-15 controls and epistatically synergizes with BCAT-1 to modulate physiological ageing. Lastly and consistent with previous findings in rodents, nutritional supplementation of BCAAs extends nematodal lifespan. Taken together, BCAAs act as periphery-derived metabokines that induce a central neuro-endocrine response, culminating in extended healthspan.

  7. Multiple layers of posttranslational regulation refine circadian clock activity in Arabidopsis.

    Science.gov (United States)

    Seo, Pil Joon; Mas, Paloma

    2014-01-01

    The circadian clock is a cellular time-keeper mechanism that regulates biological rhythms with a period of ~24 h. The circadian rhythms in metabolism, physiology, and development are synchronized by environmental cues such as light and temperature. In plants, proper matching of the internal circadian time with the external environment confers fitness advantages on plant survival and propagation. Accordingly, plants have evolved elaborated regulatory mechanisms that precisely control the circadian oscillations. Transcriptional feedback regulation of several clock components has been well characterized over the past years. However, the importance of additional regulatory mechanisms such as chromatin remodeling, protein complexes, protein phosphorylation, and stability is only starting to emerge. The multiple layers of circadian regulation enable plants to properly synchronize with the environmental cycles and to fine-tune the circadian oscillations. This review focuses on the diverse posttranslational events that regulate circadian clock function. We discuss the mechanistic insights explaining how plants articulate a high degree of complexity in their regulatory networks to maintain circadian homeostasis and to generate highly precise waveforms of circadian expression and activity.

  8. Relationship between cognitive emotion regulation, social support, resilience and acute stress responses in Chinese soldiers: Exploring multiple mediation model.

    Science.gov (United States)

    Cai, Wen-Peng; Pan, Yu; Zhang, Shui-Miao; Wei, Cun; Dong, Wei; Deng, Guang-Hui

    2017-10-01

    The current study aimed to explore the association of cognitive emotion regulation, social support, resilience and acute stress responses in Chinese soldiers and to understand the multiple mediation effects of social support and resilience on the relationship between cognitive emotion regulation and acute stress responses. A total of 1477 male soldiers completed mental scales, including the cognitive emotion regulation questionnaire-Chinese version, the perceived social support scale, the Chinese version of the Connor-Davidson resilience scale, and the military acute stress scale. As hypothesized, physiological responses, psychological responses, and acute stress were associated with negative-focused cognitive emotion regulation, and negatively associated with positive-focused cognitive emotion regulation, social supports and resilience. Besides, positive-focused cognitive emotion regulation, social support, and resilience were significantly associated with one another, and negative-focused cognitive emotion regulation was negatively associated with social support. Regression analysis and bootstrap analysis showed that social support and resilience had partly mediating effects on negative strategies and acute stress, and fully mediating effects on positive strategies and acute stress. These results thus indicate that military acute stress is significantly associated with cognitive emotion regulation, social support, and resilience, and that social support and resilience have multiple mediation effects on the relationship between cognitive emotion regulation and acute stress responses. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Adrenal clocks and the role of adrenal hormones in the regulation of circadian physiology.

    Science.gov (United States)

    Leliavski, Alexei; Dumbell, Rebecca; Ott, Volker; Oster, Henrik

    2015-02-01

    The mammalian circadian timing system consists of a master pacemaker in the suprachiasmatic nucleus (SCN) and subordinate clocks that disseminate time information to various central and peripheral tissues. While the function of the SCN in circadian rhythm regulation has been extensively studied, we still have limited understanding of how peripheral tissue clock function contributes to the regulation of physiological processes. The adrenal gland plays a special role in this context as adrenal hormones show strong circadian secretion rhythms affecting downstream physiological processes. At the same time, they have been shown to affect clock gene expression in various other tissues, thus mediating systemic entrainment to external zeitgebers and promoting internal circadian alignment. In this review, we discuss the function of circadian clocks in the adrenal gland, how they are reset by the SCN and may further relay time-of-day information to other tissues. Focusing on glucocorticoids, we conclude by outlining the impact of adrenal rhythm disruption on neuropsychiatric, metabolic, immune, and malignant disorders. © 2014 The Author(s).

  10. Novel multiple sclerosis susceptibility loci implicated in epigenetic regulation

    Science.gov (United States)

    Andlauer, Till F. M.; Buck, Dorothea; Antony, Gisela; Bayas, Antonios; Bechmann, Lukas; Berthele, Achim; Chan, Andrew; Gasperi, Christiane; Gold, Ralf; Graetz, Christiane; Haas, Jürgen; Hecker, Michael; Infante-Duarte, Carmen; Knop, Matthias; Kümpfel, Tania; Limmroth, Volker; Linker, Ralf A.; Loleit, Verena; Luessi, Felix; Meuth, Sven G.; Mühlau, Mark; Nischwitz, Sandra; Paul, Friedemann; Pütz, Michael; Ruck, Tobias; Salmen, Anke; Stangel, Martin; Stellmann, Jan-Patrick; Stürner, Klarissa H.; Tackenberg, Björn; Then Bergh, Florian; Tumani, Hayrettin; Warnke, Clemens; Weber, Frank; Wiendl, Heinz; Wildemann, Brigitte; Zettl, Uwe K.; Ziemann, Ulf; Zipp, Frauke; Arloth, Janine; Weber, Peter; Radivojkov-Blagojevic, Milena; Scheinhardt, Markus O.; Dankowski, Theresa; Bettecken, Thomas; Lichtner, Peter; Czamara, Darina; Carrillo-Roa, Tania; Binder, Elisabeth B.; Berger, Klaus; Bertram, Lars; Franke, Andre; Gieger, Christian; Herms, Stefan; Homuth, Georg; Ising, Marcus; Jöckel, Karl-Heinz; Kacprowski, Tim; Kloiber, Stefan; Laudes, Matthias; Lieb, Wolfgang; Lill, Christina M.; Lucae, Susanne; Meitinger, Thomas; Moebus, Susanne; Müller-Nurasyid, Martina; Nöthen, Markus M.; Petersmann, Astrid; Rawal, Rajesh; Schminke, Ulf; Strauch, Konstantin; Völzke, Henry; Waldenberger, Melanie; Wellmann, Jürgen; Porcu, Eleonora; Mulas, Antonella; Pitzalis, Maristella; Sidore, Carlo; Zara, Ilenia; Cucca, Francesco; Zoledziewska, Magdalena; Ziegler, Andreas; Hemmer, Bernhard; Müller-Myhsok, Bertram

    2016-01-01

    We conducted a genome-wide association study (GWAS) on multiple sclerosis (MS) susceptibility in German cohorts with 4888 cases and 10,395 controls. In addition to associations within the major histocompatibility complex (MHC) region, 15 non-MHC loci reached genome-wide significance. Four of these loci are novel MS susceptibility loci. They map to the genes L3MBTL3, MAZ, ERG, and SHMT1. The lead variant at SHMT1 was replicated in an independent Sardinian cohort. Products of the genes L3MBTL3, MAZ, and ERG play important roles in immune cell regulation. SHMT1 encodes a serine hydroxymethyltransferase catalyzing the transfer of a carbon unit to the folate cycle. This reaction is required for regulation of methylation homeostasis, which is important for establishment and maintenance of epigenetic signatures. Our GWAS approach in a defined population with limited genetic substructure detected associations not found in larger, more heterogeneous cohorts, thus providing new clues regarding MS pathogenesis. PMID:27386562

  11. Photoperiod- and Triiodothyronine-dependent Regulation of Reproductive Neuropeptides, Proinflammatory Cytokines, and Peripheral Physiology in Siberian Hamsters (Phodopus sungorus).

    Science.gov (United States)

    Banks, Ruth; Delibegovic, Mirela; Stevenson, Tyler J

    2016-06-01

    Seasonal trade-offs in reproduction and immunity are ubiquitous in nature. The mechanisms that govern transitions across seasonal physiological states appear to involve reciprocal switches in the local synthesis of thyroid hormone. In long-day (LD) summer-like conditions, increased hypothalamic triiodothyronine (T3) stimulates gonadal development. Alternatively, short-day (SD) winter-like conditions increase peripheral leukocytes and enhance multiple aspects of immune function. These data indicate that the localized effects of T3 in the hypothalamus and leukocytes are photoperiod dependent. We tested the hypothesis that increased peripheral T3 in SD conditions would increase aspects of reproductive physiology and inhibit immune function, whereas T3 injections in LD conditions would facilitate aspects of immune function (i.e., leukocytes). In addition, we also examined whether T3 regulates hypothalamic neuropeptide expression as well as hypothalamic and splenic proinflammatory cytokine expression. Adult male Siberian hamsters were maintained in LD (15L:9D) or transferred to SD (9L:15D) for 8 weeks. A subset of LD and SD hamsters was treated daily with 5 µg T3 for 2 weeks. LD and SD controls were injected with saline. Daily T3 administration in SD hamsters (SD+T3) resulted in a rapid and substantial decrease in peripheral leukocyte concentrations and stimulated gonadal development. T3 treatment in LD (LD+T3) had no effect on testicular volumes but significantly increased leukocyte concentrations. Molecular analyses revealed that T3 stimulated interleukin 1β messenger RNA (mRNA) expression in the spleen and inhibited RFamide Related Peptide-3 mRNA expression in the hypothalamus. Moreover, there was a photoperiod-dependent decrease in splenic tumor necrosis factor-α mRNA expression. These findings reveal that T3 has tissue-specific and photoperiod-dependent regulation of seasonal rhythms in reproduction and immune function. © 2016 The Author(s).

  12. Relationship Between Physiological and Perceived Fall Risk in People With Multiple Sclerosis: Implications for Assessment and Management.

    Science.gov (United States)

    Gunn, Hilary; Cameron, Michelle; Hoang, Phu; Lord, Stephen; Shaw, Steve; Freeman, Jennifer

    2018-04-24

    This study evaluated the relationship between physiological and perceived fall risk in people with multiple sclerosis (MS). Secondary analysis of data from prospective cohort studies undertaken in Australia, the United Kingdom, and the United States. Community. Ambulatory people with MS (N=416) (age 51.5±12.0 years; 73% female; 62% relapsing-remitting MS; 13.7±9.9 years disease duration). Not applicable. All participants completed measures of physiological (Physiological Profile Assessment [PPA]) and perceived (Falls Efficacy Scale-international [FESi]) fall risk and prospectively recorded falls for 3 months. 155 (37%) of the participants were recurrent fallers (≥2 falls). Mean PPA and FESi scores were high (PPA 2.14±1.87, FESi 34.27±11.18). The PPA and the FESi independently predicted faller classification in logistic regression, which indicated that the odds of being classified as a recurrent faller significantly increased with increasing scores (PPA odds ratio [OR] 1.30 [95% CI 1.17-1.46], FESi OR 1.05 [95% CI 1.03-1.07]). Classification and regression tree analysis divided the sample into four groups based on cutoff values for the PPA: (1) low physiological/low perceived risk (PPA 27.5), (3) high physiological/low perceived risk (PPA >2.83, FESi 35.5). Over 50% of participants had a disparity between perceived and physiological fall risk; most were in group 2. It is possible that physiological risk factors not detected by the PPA may also be influential. This study highlights the importance of considering both physiological and perceived fall risk in MS and the need for further research to explore the complex interrelationships of perceptual and physiological risk factors in this population. This study also supports the importance of developing behavioral and physical interventions that can be tailored to the individual's needs. Copyright © 2018 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

  13. A physiologically based pharmacokinetic (PB/PK) model for multiple exposure routes for soman in multiple species

    NARCIS (Netherlands)

    Sweeney, R.E.; Langenberg, J.P.; Maxwell, D.M.

    2006-01-01

    A physiologically based pharmacokinetic (PB/PK) model has been developed in advanced computer simulation language (ACSL) to describe blood and tissue concentration-time profiles of the C(±)P(-) stereoisomers of soman after inhalation, subcutaneous and intravenous exposures at low (0.8-1.0 × LD50),

  14. [New theory of holistic integrative physiology and medicine. I: New insight of mechanism of control and regulation of breathing].

    Science.gov (United States)

    Sun, Xing-guo

    2015-07-01

    The modern systemic physiology, based on limit-understand functional classification, has significant limitation and one-sidedness. Human being is organic; we should approach the mechanism of control and regulation of breathing integrating all the systems. We use new theory of holistic integrative physiology and medicine to explain the mechanism of control and regulation of breathing. Except the mean level information, the up-down "W" waveform information of arterial blood gas (ABG) is core signal to control and regulate breathing. In order to do so, we must integrate all systems together. New theory will help to explain some unanswered questions in physiology and medicine, for example: fetal does not breathing; how first breath generate; how respiratory rhythm and frequency generate, etc. Breathing is the sign of life. Mechanism of control and regulation of breathing has to integrate respiration, circulation, nerves, metabolism, exercise, sleep and digestion, absorption and elimination and etc altogether.

  15. Regulation of increased blood flow (hyperemia) to muscles during exercise: a hierarchy of competing physiological needs.

    Science.gov (United States)

    Joyner, Michael J; Casey, Darren P

    2015-04-01

    This review focuses on how blood flow to contracting skeletal muscles is regulated during exercise in humans. The idea is that blood flow to the contracting muscles links oxygen in the atmosphere with the contracting muscles where it is consumed. In this context, we take a top down approach and review the basics of oxygen consumption at rest and during exercise in humans, how these values change with training, and the systemic hemodynamic adaptations that support them. We highlight the very high muscle blood flow responses to exercise discovered in the 1980s. We also discuss the vasodilating factors in the contracting muscles responsible for these very high flows. Finally, the competition between demand for blood flow by contracting muscles and maximum systemic cardiac output is discussed as a potential challenge to blood pressure regulation during heavy large muscle mass or whole body exercise in humans. At this time, no one dominant dilator mechanism accounts for exercise hyperemia. Additionally, complex interactions between the sympathetic nervous system and the microcirculation facilitate high levels of systemic oxygen extraction and permit just enough sympathetic control of blood flow to contracting muscles to regulate blood pressure during large muscle mass exercise in humans. Copyright © 2015 the American Physiological Society.

  16. Voltage-Gated Sodium Channel β1/β1B Subunits Regulate Cardiac Physiology and Pathophysiology

    Directory of Open Access Journals (Sweden)

    Nnamdi Edokobi

    2018-04-01

    Full Text Available Cardiac myocyte contraction is initiated by a set of intricately orchestrated electrical impulses, collectively known as action potentials (APs. Voltage-gated sodium channels (NaVs are responsible for the upstroke and propagation of APs in excitable cells, including cardiomyocytes. NaVs consist of a single, pore-forming α subunit and two different β subunits. The β subunits are multifunctional cell adhesion molecules and channel modulators that have cell type and subcellular domain specific functional effects. Variants in SCN1B, the gene encoding the Nav-β1 and -β1B subunits, are linked to atrial and ventricular arrhythmias, e.g., Brugada syndrome, as well as to the early infantile epileptic encephalopathy Dravet syndrome, all of which put patients at risk for sudden death. Evidence over the past two decades has demonstrated that Nav-β1/β1B subunits play critical roles in cardiac myocyte physiology, in which they regulate tetrodotoxin-resistant and -sensitive sodium currents, potassium currents, and calcium handling, and that Nav-β1/β1B subunit dysfunction generates substrates for arrhythmias. This review will highlight the role of Nav-β1/β1B subunits in cardiac physiology and pathophysiology.

  17. Multiple upstream modules regulate zebrafish myf5 expression

    Directory of Open Access Journals (Sweden)

    Weng Chih-Wei

    2007-01-01

    Full Text Available Abstract Background Myf5 is one member of the basic helix-loop-helix family of transcription factors, and it functions as a myogenic factor that is important for the specification and differentiation of muscle cells. The expression of myf5 is somite- and stage-dependent during embryogenesis through a delicate regulation. However, this complex regulatory mechanism of myf5 is not clearly understood. Results We isolated a 156-kb bacterial artificial chromosome clone that includes an upstream 80-kb region and a downstream 70-kb region of zebrafish myf5 and generated a transgenic line carrying this 156-kb segment fused to a green fluorescent protein (GFP reporter gene. We find strong GFP expression in the most rostral somite and in the presomitic mesoderm during segmentation stages, similar to endogenous myf5 expression. Later, the GFP signals persist in caudal somites near the tail bud but are down-regulated in the older, rostral somites. During the pharyngula period, we detect GFP signals in pectoral fin buds, dorsal rostral myotomes, hypaxial myotomes, and inferior oblique and superior oblique muscles, a pattern that also corresponds well with endogenous myf5 transcripts. To characterize the specific upstream cis-elements that regulate this complex and dynamic expression pattern, we also generated several transgenic lines that harbor various lengths within the upstream 80-kb segment. We find that (1 the -80 kb/-9977 segment contains a fin and cranial muscle element and a notochord repressor; (2 the -9977/-6213 segment contains a strong repressive element that does not include the notochord-specific repressor; (3 the -6212/-2938 segment contains tissue-specific elements for bone and spinal cord; (4 the -2937/-291 segment contains an eye enhancer, and the -2937/-2457 segment is required for notochord and myocyte expression; and (5 the -290/-1 segment is responsible for basal transcription in somites and the presomitic mesoderm. Conclusion We suggest

  18. Regulation of the syncytin-1 promoter in human astrocytes by multiple sclerosis-related cytokines

    International Nuclear Information System (INIS)

    Mameli, Giuseppe; Astone, Vito; Khalili, Kamel; Serra, Caterina; Sawaya, Bassel E.; Dolei, Antonina

    2007-01-01

    Syncytin-1 has a physiological role during early pregnancy, as mediator of trophoblast fusion into the syncytiotrophoblast layer, hence allowing embryo implantation. In addition, its expression in nerve tissue has been proposed to contribute to the pathogenesis of multiple sclerosis (MS). Syncytin-1 is the env glycoprotein of the ERVWE1 component of the W family of human endogenous retroviruses (HERV), located on chromosome 7q21-22, in a candidate region for genetic susceptibility to MS. The mechanisms of ERVWE1 regulation in nerve tissue remain to be identified. Since there are correlations between some cytokines and MS outcome, we examined the regulation of the syncytin-1 promoter by MS-related cytokines in human U-87MG astrocytic cells. Using transient transfection assays, we observed that the MS-detrimental cytokines TNFα, interferon-γ, interleukin-6, and interleukin-1 activate the ERVWE1 promoter, while the MS-protective interferon-β is inhibitory. The effects of cytokines are reduced by the deletion of the cellular enhancer domain of the promoter that contains binding sites for several transcription factors. In particular, we found that TNFα had the ability to activate the ERVWE1 promoter through an NF-κB-responsive element located within the enhancer domain of the promoter. Electrophoretic mobility shift and ChIP assays showed that TNFα enhances the binding of the p65 subunit of NF-κB, to its cognate site within the promoter. The effect of TNFα is abolished by siRNA directed against p65. Taken together, these results illustrate a role for p65 in regulating the ERVWE1 promoter and in TNFα-mediated induction of syncytin-1 in multiple sclerosis

  19. A female sex offender with multiple paraphilias: a psychologic, physiologic (laboratory sexual arousal) and endocrine case study.

    Science.gov (United States)

    Cooper, A J; Swaminath, S; Baxter, D; Poulin, C

    1990-05-01

    A 20 year old female pedophile exhibiting multiple paraphilias and who had been both a victim of incest and an active participant, undertook extensive clinical, psychometric, endocrine and laboratory sexual arousal studies. Her psychiatric, psychometric and physiologic arousal profiles showed similarities to those of a sizable proportion of male child molesters, especially incestors. It is suggested that laboratory arousal tests (using the vaginal photoplethysmograph) may have a role in the assessment of some female sex offenders.

  20. Gastrin is not a physiological regulator of pancreatic exocrine secretion in the dog

    International Nuclear Information System (INIS)

    Koehler, E.; Beglinger, C.; Eysselein, V.; Groetzinger, U.; Gyr, K.

    1987-01-01

    The role of gastrin as a regulator of exocrine pancreatic secretion has not been proven adequately. In the present study the authors therefore compared the relative molar potencies of sulfated and unsulfated gastrin 17 with structurally related CCK peptides (synthetic CCK-8 and natural porcine CCK-33) in stimulating exocrine pancreatic secretion in conscious dogs. Dose response curves were constructed for pancreatic and gastric acid secretion. Plasma gastrin levels after exogenous gastrin 17-I and -II were compared with postprandial gastrin concentrations. The molar potency estimates calculated with synthetic CCK8 as standard for pancreatic protein secretion were natural porcine 50% pure CCK-33 1.60, gastrin 17-I 0.12, and gastrin 17-II 0.16. All four peptides induced a dose-dependent increase in pancreatic bicarbonate output. However, the blood concentrations needed to stimulate pancreatic secretion were above the postprandial gastrin levels. The data indicate that both gastrin 17 peptides are not physiological regulators of pancreatic enzyme secretion in dogs

  1. Physiological and Proteomics Analyses Reveal Low-Phosphorus Stress Affected the Regulation of Photosynthesis in Soybean.

    Science.gov (United States)

    Chu, Shanshan; Li, Hongyan; Zhang, Xiangqian; Yu, Kaiye; Chao, Maoni; Han, Suoyi; Zhang, Dan

    2018-06-06

    Previous studies have revealed a significant genetic relationship between phosphorus (P)-efficiency and photosynthesis-related traits in soybean. In this study, we used proteome profiling in combination with expression analysis, biochemical investigations, and leaf ultrastructural analysis to identify the underlying physiological and molecular responses. The expression analysis and ultrastructural analysis showed that the photosynthesis key genes were decreased at transcript levels and the leaf mesophyll and chloroplast were severely damaged after low-P stress. Approximately 55 protein spots showed changes under low-P condition by mass spectrometry, of which 17 were involved in various photosynthetic processes. Further analysis revealed the depression of photosynthesis caused by low-P stress mainly involves the regulation of leaf structure, adenosine triphosphate (ATP) synthesis, absorption and transportation of CO₂, photosynthetic electron transport, production of assimilatory power, and levels of enzymes related to the Calvin cycle. In summary, our findings indicated that the existence of a stringent relationship between P supply and the genomic control of photosynthesis in soybean. As an important strategy to protect soybean photosynthesis, P could maintain the stability of cell structure, up-regulate the enzymes’ activities, recover the process of photosystem II (PSII), and induce the expression of low-P responsive genes and proteins.

  2. Distinct RNAi Pathways in the Regulation of Physiology and Development in the Fungus Mucor circinelloides.

    Science.gov (United States)

    Ruiz-Vázquez, Rosa M; Nicolás, Francisco E; Torres-Martínez, Santiago; Garre, Victoriano

    2015-01-01

    The basal fungus Mucor circinelloides has become, in recent years, a valuable model to study RNA-mediated gene silencing or RNA interference (RNAi). Serendipitously discovered in the late 1900s, the gene silencing in M. circinelloides is a landscape of consensus and dissents. Although similar to other classical fungal models in the basic design of the essential machinery that is responsible for silencing of gene expression, the existence of small RNA molecules of different sizes generated during this process and the presence of a mechanism that amplifies the silencing signal, give it a unique identity. In addition, M. circinelloides combines the components of RNAi machinery to carry out functions that not only limit themselves to the defense against foreign genetic material, but it uses some of these elements to regulate the expression of its own genes. Thus, different combinations of RNAi elements produce distinct classes of endogenous small RNAs (esRNAs) that regulate different physiological and developmental processes in response to environmental signals. The recent discovery of a new RNAi pathway involved in the specific degradation of endogenous mRNAs, using a novel RNase protein, adds one more element to the exciting puzzle of the gene silencing in M. circinelloides, in addition to providing hints about the evolutionary origin of the RNAi mechanism. Copyright © 2015 Elsevier Inc. All rights reserved.

  3. Highly stable and degradable multifunctional microgel for self-regulated insulin delivery under physiological conditions

    Science.gov (United States)

    Zhang, Xinjie; Lü, Shaoyu; Gao, Chunmei; Chen, Chen; Zhang, Xuan; Liu, Mingzhu

    2013-06-01

    The response to glucose, pH and temperature, high drug loading capacity, self-regulated drug delivery and degradation in vivo are simultaneously probable by applying a multifunctional microgel under a rational design in a colloid chemistry method. Such multifunctional microgels are fabricated with N-isopropylacrylamide (NIPAAm), (2-dimethylamino)ethyl methacrylate (DMAEMA) and 3-acrylamidephenylboronic acid (AAPBA) through a precipitation emulsion method and cross-linked by reductive degradable N,N'-bis(arcyloyl)cystamine (BAC). This novel kind of microgel with a narrow size distribution (~250 nm) is suitable for diabetes because it can adapt to the surrounding medium of different glucose concentrations over a clinically relevant range (0-20 mM), control the release of preloaded insulin and is highly stable under physiological conditions (pH 7.4, 0.15 M NaCl, 37 °C). When synthesized multifunctional microgels regulate drug delivery, they gradually degrade as time passes and, as a result, show enhanced biocompatibility. This exhibits a new proof-of-concept for diabetes treatment that takes advantage of the properties of each building block from a multifunctional micro-object. These highly stable and versatile multifunctional microgels have the potential to be used for self-regulated therapy and monitoring of the response to treatment, or even simultaneous diagnosis as nanobiosensors.The response to glucose, pH and temperature, high drug loading capacity, self-regulated drug delivery and degradation in vivo are simultaneously probable by applying a multifunctional microgel under a rational design in a colloid chemistry method. Such multifunctional microgels are fabricated with N-isopropylacrylamide (NIPAAm), (2-dimethylamino)ethyl methacrylate (DMAEMA) and 3-acrylamidephenylboronic acid (AAPBA) through a precipitation emulsion method and cross-linked by reductive degradable N,N'-bis(arcyloyl)cystamine (BAC). This novel kind of microgel with a narrow size

  4. Regulation of ribonucleotide reductase by Spd1 involves multiple mechanisms

    DEFF Research Database (Denmark)

    Nestoras, Konstantinos; Mohammed, Asma Hadi; Schreurs, Ann-Sofie

    2010-01-01

    The correct levels of deoxyribonucleotide triphosphates and their relative abundance are important to maintain genomic integrity. Ribonucleotide reductase (RNR) regulation is complex and multifaceted. RNR is regulated allosterically by two nucleotide-binding sites, by transcriptional control, and...

  5. The Mask of Sanity : Facial Expressive, Self-Reported, and Physiological Consequences of Emotion Regulation in Psychopathic Offenders

    NARCIS (Netherlands)

    Nentjes, L.; Bernstein, D.P.; Meijer, E.; Arntz, A.; Wiers, R.W.

    2016-01-01

    This study investigated the physiological, self-reported, and facial correlates of emotion regulation in psychopathy. Specifically, we compared psychopathic offenders (n = 42), nonpsychopathic offenders (n = 42), and nonoffender controls (n = 26) in their ability to inhibit and express emotion while

  6. EFFECT OF PHYSIOLOGICAL AGE AND GROWTH REGULATORS ON CALLUS BROWNING OF COCONUT ENDOSPERM CULTURE IN VITRO

    Directory of Open Access Journals (Sweden)

    LAZARUS AGUS SUKAMTO

    2011-01-01

    Full Text Available The possibility of physiological age and growth regulators affecting callus browning ofcoconut endosperm was investigated. Solid endosperm explants of four coconut fruits fromsame brunches of two coconut cultivars “Samoan Dwarf ” were grown on modified Murashigeand Skoog (MS formula with addition of 10 mg l putresine, 2.50 g l activated charcoal (AC,1.70 g l phytagel, 0, 10 , 10 , 10 , 10 M 2,4-dichlorophenoxyacetic acid (2,4-D or 4-amino-3,5,6-trichloropicolinic acid (Picloram combined with 10 M 6-benzylaminopurine (BA.Callogenesis occurred on 98.83% of explants. Callus browning between different physiologicalages (antipodal and micropylar tissues of coconut endosperm at 9, 26 and 31 weeks of culture(WOC was significantly different, but not at 16 and 21 WOC. Auxins of 2,4-D and Picloramdid not affect significantly callus browning of endosperm cultures. Auxin doses at 10 , 10 , and10 M decreased significantly callus browning at 9 and 16 WOC, respectively, but at 10 Mbrowning was less significant compared to other doses at 21 WOC. Auxin dose at 10 M causedless significant browning compared to other doses at 31 WOC. The addition of BA decreasedsignificantly callus browning at 9 WOC, but did not affect callus browning thereafter.

  7. The regulation of coralline algal physiology, an in situ study of Corallina officinalis (Corallinales, Rhodophyta)

    Science.gov (United States)

    Williamson, Christopher James; Perkins, Rupert; Voller, Matthew; Yallop, Marian Louise; Brodie, Juliet

    2017-10-01

    Calcified macroalgae are critical components of marine ecosystems worldwide, but face considerable threat both from climate change (increasing water temperatures) and ocean acidification (decreasing ocean pH and carbonate saturation). It is thus fundamental to constrain the relationships between key abiotic stressors and the physiological processes that govern coralline algal growth and survival. Here we characterize the complex relationships between the abiotic environment of rock pool habitats and the physiology of the geniculate red coralline alga, Corallina officinalis (Corallinales, Rhodophyta). Paired assessment of irradiance, water temperature and carbonate chemistry, with C. officinalis net production (NP), respiration (R) and net calcification (NG) was performed in a south-western UK field site, at multiple temporal scales (seasonal, diurnal and tidal). Strong seasonality was observed in NP and night-time R, with a Pmax of 22.35 µmol DIC (g DW)-1 h-1, Ek of 300 µmol photons m-2 s-1 and R of 3.29 µmol DIC (g DW)-1 h-1 determined across the complete annual cycle. NP showed a significant exponential relationship with irradiance (R2 = 0.67), although was temperature dependent given ambient irradiance > Ek for the majority of the annual cycle. Over tidal emersion periods, dynamics in NP highlighted the ability of C. officinalis to acquire inorganic carbon despite significant fluctuations in carbonate chemistry. Across all data, NG was highly predictable (R2 = 0.80) by irradiance, water temperature and carbonate chemistry, providing a NGmax of 3.94 µmol CaCO3 (g DW)-1 h-1 and Ek of 113 µmol photons m-2 s-1. Light NG showed strong seasonality and significant coupling to NP (R2 = 0.65) as opposed to rock pool water carbonate saturation. In contrast, the direction of dark NG (dissolution vs. precipitation) was strongly related to carbonate saturation, mimicking abiotic precipitation dynamics. Data demonstrated that C. officinalis is adapted to both long

  8. Stakeholder cooperation: regulating a uranium mine with multiple statutory approvals

    International Nuclear Information System (INIS)

    Bush, M.

    2010-01-01

    Ranger Uranium Mine operates under an Authorisation issued by the Northern Territory Government. In addition, the site is regulated by a set of Environmental Requirements attached to the uranium export permit issued by the Australian Government Department of Resources, Energy and Tourism. A Heap Leach facility proposed for the site could result in a third approval being issued, in accordance with the Environmental Protection and Biodiversity Conservation Act 1999 (EPBC Act). Finding the correct balance to regulate the mine in light of these approvals will be a challenge for the range of stakeholders involved in regulation and oversight of this operation. (author)

  9. Listening to music and physiological and psychological functioning: the mediating role of emotion regulation and stress reactivity.

    Science.gov (United States)

    Thoma, M V; Scholz, U; Ehlert, U; Nater, U M

    2012-01-01

    Music listening has been suggested to have short-term beneficial effects. The aim of this study was to investigate the association and potential mediating mechanisms between various aspects of habitual music-listening behaviour and physiological and psychological functioning. An internet-based survey was conducted in university students, measuring habitual music-listening behaviour, emotion regulation, stress reactivity, as well as physiological and psychological functioning. A total of 1230 individuals (mean = 24.89 ± 5.34 years, 55.3% women) completed the questionnaire. Quantitative aspects of habitual music-listening behaviour, i.e. average duration of music listening and subjective relevance of music, were not associated with physiological and psychological functioning. In contrast, qualitative aspects, i.e. reasons for listening (especially 'reducing loneliness and aggression', and 'arousing or intensifying specific emotions') were significantly related to physiological and psychological functioning (all p = 0.001). These direct effects were mediated by distress-augmenting emotion regulation and individual stress reactivity. The habitual music-listening behaviour appears to be a multifaceted behaviour that is further influenced by dispositions that are usually not related to music listening. Consequently, habitual music-listening behaviour is not obviously linked to physiological and psychological functioning.

  10. Redox regulation and pro-oxidant reactions in the physiology of circadian systems.

    Science.gov (United States)

    Méndez, Isabel; Vázquez-Martínez, Olivia; Hernández-Muñoz, Rolando; Valente-Godínez, Héctor; Díaz-Muñoz, Mauricio

    2016-05-01

    Rhythms of approximately 24 h are pervasive in most organisms and are known as circadian. There is a molecular circadian clock in each cell sustained by a feedback system of interconnected "clock" genes and transcription factors. In mammals, the timing system is formed by a central pacemaker, the suprachiasmatic nucleus, in coordination with a collection of peripheral oscillators. Recently, an extensive interconnection has been recognized between the molecular circadian clock and the set of biochemical pathways that underlie the bioenergetics of the cell. A principle regulator of metabolic networks is the flow of electrons between electron donors and acceptors. The concomitant reduction and oxidation (redox) reactions directly influence the balance between anabolic and catabolic processes. This review summarizes and discusses recent findings concerning the mutual and dynamic interactions between the molecular circadian clock, redox reactions, and redox signaling. The scope includes the regulatory role played by redox coenzymes (NAD(P)+/NAD(P)H, GSH/GSSG), reactive oxygen species (superoxide anion, hydrogen peroxide), antioxidants (melatonin), and physiological events that modulate the redox state (feeding condition, circadian rhythms) in determining the timing capacity of the molecular circadian clock. In addition, we discuss a purely metabolic circadian clock, which is based on the redox enzymes known as peroxiredoxins and is present in mammalian red blood cells and in other biological systems. Both the timing system and the metabolic network are key to a better understanding of widespread pathological conditions such as the metabolic syndrome, obesity, and diabetes. Copyright © 2015 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.

  11. Physiology and biochemistry of source-regulated protein accumulation in the wheat grain.

    Science.gov (United States)

    Barneix, Atilio J

    2007-05-01

    Wheat is unique among cereals for the baking qualities of its flour, which are dependent upon the type and concentration of its proteins. As a consequence, the grain protein concentration (GPC) is one of the main determinants of wheat international market price. More than 50-70% of the final grain N is accumulated before flowering and later remobilized to the grain, N fertilization being the common practice used to produce high GPC. However, after incremental additions of N fertilizer, GPC reaches a maximum and then remains constant, without any increase in N uptake or remobilization by the crop, thus decreasing the efficiency of N fertilizer. Although, the genetic and molecular mechanisms that regulate N uptake by the roots are being clarified quickly, the regulation and physiology of N transport from the leaves to the grain remains less clear. In this review, the possible regulatory points involved in N transport to the grain and the difficulties for increasing GPC are discussed. It has been demonstrated that protein synthesis in the grain is source-limited, and that the grain can accumulate protein limited only by the amino acids provided by the phloem. It has also been shown that there is no limitation in the amino acid/sugar ratios that can be exported to the phloem. On the other hand, NO(3)(-) uptake transporters are depressed when the plant concentration of some amino acids, such as glutamine, is high. It has also been shown that a high N supply increases cytokinins concentration, preventing leaf senescence and proteolysis. Based on this information, it is postulated that there are two main regulatory points during grain filling when plant N status is ample. On the one hand, the N uptake transporters in the roots are depressed due to the high amino acids concentration in the tissues, and N uptake is low. On the other, a high amino acids concentration keeps the cytokinins level high, repressing leaf protein degradation and decreasing amino acid export to the

  12. a New Approach to Physiologic Triggering in Medical Imaging Using Multiple Heart Sounds Alone.

    Science.gov (United States)

    Groch, Mark Walter

    A new method for physiological synchronization of medical image acquisition using both the first and second heart sound has been developed. Heart sounds gating (HSG) circuitry has been developed which identifies, individually, both the first (S1) and second (S2) heart sounds from their timing relationship alone, and provides two synchronization points during the cardiac cycle. Identification of first and second heart sounds from their timing relationship alone and application to medical imaging has, heretofore, not been performed in radiology or nuclear medicine. The heart sounds are obtained as conditioned analog signals from a piezoelectric transducer microphone placed on the patient's chest. The timing relationships between the S1 to S2 pulses and the S2 to S1 pulses are determined using a logic scheme capable of distinguishing the S1 and S2 pulses from the heart sounds themselves, using their timing relationships, and the assumption that initially the S1-S2 interval will be shorter than the S2-S1 interval. Digital logic circuitry is utilized to continually track the timing intervals and extend the S1/S2 identification to heart rates up to 200 beats per minute (where the S1-S2 interval is not shorter than the S2-S1 interval). Clinically, first heart sound gating may be performed to assess the systolic ejection portion of the cardiac cycle, with S2 gating utilized for reproduction of the diastolic filling portion of the cycle. One application of HSG used for physiologic synchronization is in multigated blood pool (MGBP) imaging in nuclear medicine. Heart sounds gating has been applied to twenty patients who underwent analysis of ventricular function in Nuclear Medicine, and compared to conventional ECG gated MGBP. Left ventricular ejection fractions calculated from MGBP studies using a S1 and a S2 heart sound trigger correlated well with conventional ECG gated acquisitions in patients adequately gated by HSG and ECG. Heart sounds gating provided superior

  13. Physiological Correlates of Multiple Parasitic Infections in Side-Blotched Lizards.

    Science.gov (United States)

    Spence, Austin R; Durso, Andrew M; Smith, Geoffrey D; Skinner, Heather M; French, Susannah S

    We investigated the presence of ectoparasites and hemoparasites in side-blotched lizards (Uta stansburiana) across a large part of their range and measured how parasitic infection related to several key physiological indicators of health. Blood samples were collected from 132 lizards from central Arizona, southern Utah, and eastern Oregon. Hemoparasites were found in 22 individuals (3.2% prevalence in Arizona, 19.1% in Utah, and 6.3% in Oregon), and ectoparasites were found on 51 individuals (56.3% prevalence in Arizona, 56.1% in Utah, and 6.7% in Oregon), with 11 individuals infected with both. Hemoparasites and ectoparasites were found in all three states. Immunocompetence was higher in individuals infected with both hemoparasites and ectoparasites. Body condition, glucocorticoid levels, and reproductive investment were not related to infection status. Our study provides evidence that parasitic infection is associated with an active immune system in wild reptiles but may not impose other costs usually associated with parasites.

  14. The interactive effects of multiple stressors on physiological stress responses and club cell investment in fathead minnows

    International Nuclear Information System (INIS)

    Manek, Aditya K.; Ferrari, Maud C.O.; Niyogi, Som; Chivers, Douglas P.

    2014-01-01

    Anthropogenic activities have dramatically increased over the past decades, with the consequence that many organisms are simultaneously exposed to multiple stressors. Understanding how organisms respond to these stressors is a key focus for scientists from many disciplines. Here we investigated the interactive effects of two stressors, UV radiation (UVR) and cadmium (Cd) exposure on a common freshwater fish, fathead minnow (Pimephales promelas). UVR is known to influence the density of epidermal club cells (ECCs), which are not only a key component of the innate immune system of fishes, but are also the source of chemical alarm cues that serve to warn other fishes of nearby predators. In contrast, Cd impairs the physiological stress response and ability of fish to respond to alarm cues. We used an integrative approach to examine physiological stress response as well as investment in ECCs. Fish exposed to UVR had higher levels of cortisol than non-exposed controls, but Cd reduced cortisol levels substantially for fish exposed to UVR. Fish exposed to UVR, either in the presence or absence of Cd, showed consistent decreases in ECC investment compared to non-exposed controls. Despite differences in ECC number, there was no difference in the potency of alarm cues prepared from the skin of UVR and Cd exposed or non-exposed fish indicating that UVR and Cd exposure combined may have little influence on chemically-mediated predator–prey interactions. - Highlights: • UV radiation caused a physiological stress response (cortisol release) in fish. • Cd reduced cortisol levels substantially for fish exposed to UV. • Fish exposed to UV, with or without Cd, showed decreases in club cell investment. • There was no difference in alarm cues potency from UV and Cd exposed fish. • Our work highlights the difficulty of untangling effects of multiple stressors

  15. The interactive effects of multiple stressors on physiological stress responses and club cell investment in fathead minnows

    Energy Technology Data Exchange (ETDEWEB)

    Manek, Aditya K., E-mail: aditya.manek@usask.ca [Department of Biology, University of Saskatchewan, Saskatoon, S7N 5E2 SK (Canada); Ferrari, Maud C.O. [Department of Biomedical Sciences, WCVM, University of Saskatchewan, Saskatoon, SK S7N 5B4 (Canada); Niyogi, Som; Chivers, Douglas P. [Department of Biology, University of Saskatchewan, Saskatoon, S7N 5E2 SK (Canada)

    2014-04-01

    Anthropogenic activities have dramatically increased over the past decades, with the consequence that many organisms are simultaneously exposed to multiple stressors. Understanding how organisms respond to these stressors is a key focus for scientists from many disciplines. Here we investigated the interactive effects of two stressors, UV radiation (UVR) and cadmium (Cd) exposure on a common freshwater fish, fathead minnow (Pimephales promelas). UVR is known to influence the density of epidermal club cells (ECCs), which are not only a key component of the innate immune system of fishes, but are also the source of chemical alarm cues that serve to warn other fishes of nearby predators. In contrast, Cd impairs the physiological stress response and ability of fish to respond to alarm cues. We used an integrative approach to examine physiological stress response as well as investment in ECCs. Fish exposed to UVR had higher levels of cortisol than non-exposed controls, but Cd reduced cortisol levels substantially for fish exposed to UVR. Fish exposed to UVR, either in the presence or absence of Cd, showed consistent decreases in ECC investment compared to non-exposed controls. Despite differences in ECC number, there was no difference in the potency of alarm cues prepared from the skin of UVR and Cd exposed or non-exposed fish indicating that UVR and Cd exposure combined may have little influence on chemically-mediated predator–prey interactions. - Highlights: • UV radiation caused a physiological stress response (cortisol release) in fish. • Cd reduced cortisol levels substantially for fish exposed to UV. • Fish exposed to UV, with or without Cd, showed decreases in club cell investment. • There was no difference in alarm cues potency from UV and Cd exposed fish. • Our work highlights the difficulty of untangling effects of multiple stressors.

  16. Five Conditions Commonly Used to Down-regulate Tor Complex 1 Generate Different Physiological Situations Exhibiting Distinct Requirements and Outcomes*

    Science.gov (United States)

    Tate, Jennifer J.; Cooper, Terrance G.

    2013-01-01

    Five different physiological conditions have been used interchangeably to establish the sequence of molecular events needed to achieve nitrogen-responsive down-regulation of TorC1 and its subsequent regulation of downstream reporters: nitrogen starvation, methionine sulfoximine (Msx) addition, nitrogen limitation, rapamycin addition, and leucine starvation. Therefore, we tested a specific underlying assumption upon which the interpretation of data generated by these five experimental perturbations is premised. It is that they generate physiologically equivalent outcomes with respect to TorC1, i.e. its down-regulation as reflected by TorC1 reporter responses. We tested this assumption by performing head-to-head comparisons of the requirements for each condition to achieve a common outcome for a downstream proxy of TorC1 inactivation, nuclear Gln3 localization. We demonstrate that the five conditions for down-regulating TorC1 do not elicit physiologically equivalent outcomes. Four of the methods exhibit hierarchical Sit4 and PP2A phosphatase requirements to elicit nuclear Gln3-Myc13 localization. Rapamycin treatment required Sit4 and PP2A. Nitrogen limitation and short-term nitrogen starvation required only Sit4. G1 arrest-correlated, long-term nitrogen starvation and Msx treatment required neither PP2A nor Sit4. Starving cells of leucine or treating them with leucyl-tRNA synthetase inhibitors did not elicit nuclear Gln3-Myc13 localization. These data indicate that the five commonly used nitrogen-related conditions of down-regulating TorC1 are not physiologically equivalent and minimally involve partially differing regulatory mechanisms. Further, identical requirements for Msx treatment and long-term nitrogen starvation raise the possibility that their effects are achieved through a common regulatory pathway with glutamine, a glutamate or glutamine metabolite level as the sensed metabolic signal. PMID:23935103

  17. miR-181a regulates multiple pathways in hypopharyngeal ...

    African Journals Online (AJOL)

    Expression of four pathway reporters were significantly increased (p53/DNA damage, TGFβ, MAPK/ERK and MAPK/JNK), while expression of two pathway reporters were decreased (Wnt and NFkB) upon miR-181a down-regulation. Notch, Myc/Max, hypoxia and cell cycle/pRB-E2F pathways were not significantly affected ...

  18. Supporting Affect Regulation in Children With Multiple Disabilities During Psychotherapy: A Multiple Case Design Study of Therapeutic Attachment. [Miscellaneous Article

    NARCIS (Netherlands)

    Schuengel, C; Sterkenburg, P S; Jeczynski, P; Janssen, C G C; Jongbloed, G

    2009-01-01

    : In a controlled multiple case design study, the development of a therapeutic relationship and its role in affect regulation were studied in 6 children with visual disabilities, severe intellectual disabilities, severe challenging behavior, and prolonged social deprivation. In the 1st phase,

  19. Stress and serial adult metamorphosis: Multiple roles for the stress axis in socially regulated sex change

    OpenAIRE

    Tessa K Solomon-Lane; Erica J Crespi; Erica J Crespi; Matthew Scott Grober; Matthew Scott Grober

    2013-01-01

    Socially regulated sex change in teleost fishes is a striking example of social status information regulating biological function in the service of reproductive success. The establishment of social dominance in sex changing species is translated into a cascade of changes in behavior, physiology, neuroendocrine function, and morphology that transforms a female into a male, or vice versa. The hypothalamic-pituitary-interrenal axis (HPI, homologous to HP-adrenal axis in mammals and birds) has ...

  20. Stress and serial adult metamorphosis: multiple roles for the stress axis in socially regulated sex change

    OpenAIRE

    Solomon-Lane, Tessa K.; Crespi, Erica J.; Grober, Matthew S.

    2013-01-01

    Socially regulated sex change in teleost fishes is a striking example of social status information regulating biological function in the service of reproductive success. The establishment of social dominance in sex changing species is translated into a cascade of changes in behavior, physiology, neuroendocrine function, and morphology that transforms a female into a male, or vice versa. The hypothalamic-pituitary-interrenal axis (HPI, homologous to HP-adrenal axis in mammals and birds) has be...

  1. [Autonomic regulation at emotional stress under hypoxic conditions in the elderly with physiological and accelerated aging: effect of hypoxic training].

    Science.gov (United States)

    Os'mak, E D; Asanov, É O

    2014-01-01

    The effect of hypoxic training on autonomic regulation in psycho-emotional stress conditions in hypoxic conditions in older people with physiological (25 people) and accelerated (28 people) aging respiratory system. It is shown that hypoxic training leads to an increase in vagal activity indicators (HF) and reduced simpatovagal index (LF/HF), have a normalizing effect on the autonomic balance during stress loads in older people with different types of aging respiratory system.

  2. [New theory of holistic integrative physiology and medicine. II: New insight of the control and regulation of circulation].

    Science.gov (United States)

    Sun, Xing-guo

    2015-07-01

    The interpretation of control and regulation of circulatory parameters in traditional physiology has some limitations. Human being is an organic, circulatory control and regulation should involve all the systems. Based upon the theory of holistic integrative physiology and medicine, we approach to explain the circulatory control and regulation from its purpose. The main purpose of circulation is to maintain a stable metabolism of cells, i.e. transport oxygen (from lung) and nutrients (from gastrointestinal tract) to cells, and return carbon dioxide and metabolic products back for elimination. Based on this goal, all respiration and gastrointestinal digestion, absorption, urinary excretion, etc. are integrative together for regulation to maintain the supply-demand balance at any metabolic status of resting, exercise and sleep. So that, we can explain many existing problems and questions, for example: why and how the foramen ovale closed after birth; mechanism of Cheyne-Stokes respiration; blood flow redistribution during exercise; variabilities of systolic blood pressure, heart rate and autonomic tone. The circulatory control and regulation is the integration of all systems of the body.

  3. Mouse ribosomal RNA genes contain multiple differentially regulated variants.

    Directory of Open Access Journals (Sweden)

    Hung Tseng

    2008-03-01

    Full Text Available Previous cytogenetic studies suggest that various rDNA chromosomal loci are not equally active in different cell types. Consistent with this variability, rDNA polymorphism is well documented in human and mouse. However, attempts to identify molecularly rDNA variant types, which are regulated individually (i.e., independent of other rDNA variants and tissue-specifically, have not been successful. We report here the molecular cloning and characterization of seven mouse rDNA variants (v-rDNA. The identification of these v-rDNAs was based on restriction fragment length polymorphisms (RFLPs, which are conserved among individuals and mouse strains. The total copy number of the identified variants is less than 100 and the copy number of each individual variant ranges from 4 to 15. Sequence analysis of the cloned v-rDNA identified variant-specific single nucleotide polymorphisms (SNPs in the transcribed region. These SNPs were used to develop a set of variant-specific PCR assays, which permitted analysis of the v-rDNAs' expression profiles in various tissues. These profiles show that three v-rDNAs are expressed in all tissues (constitutively active, two are expressed in some tissues (selectively active, and two are not expressed (silent. These expression profiles were observed in six individuals from three mouse strains, suggesting the pattern is not randomly determined. Thus, the mouse rDNA array likely consists of genetically distinct variants, and some are regulated tissue-specifically. Our results provide the first molecular evidence for cell-type-specific regulation of a subset of rDNA.

  4. Method and Apparatus for Encouraging Physiological Self-Regulation Through Modulation of an Operator's Control Input to a Video Game or Training Simulator

    Science.gov (United States)

    Palsson, Olafur S. (Inventor); Harris, Randall L., Sr. (Inventor); Pope, Alan T. (Inventor)

    2002-01-01

    Apparatus and methods for modulating the control authority (i.e., control function) of a computer simulation or game input device (e.g., joystick, button control) using physiological information so as to affect the user's ability to impact or control the simulation or game with the input device. One aspect is to use the present invention, along with a computer simulation or game, to affect physiological state or physiological self-regulation according to some programmed criterion (e.g., increase, decrease, or maintain) in order to perform better at the game task. When the affected physiological state or physiological self-regulation is the target of self-regulation or biofeedback training, the simulation or game play reinforces therapeutic changes in the physiological signal(s).

  5. Tyrosine Residues Regulate Multiple Nuclear Functions of P54nrb.

    Science.gov (United States)

    Lee, Ahn R; Hung, Wayne; Xie, Ning; Liu, Liangliang; He, Leye; Dong, Xuesen

    2017-04-01

    The non-POU-domain-containing octamer binding protein (NONO; also known as p54nrb) has various nuclear functions ranging from transcription, RNA splicing, DNA synthesis and repair. Although tyrosine phosphorylation has been proposed to account for the multi-functional properties of p54nrb, direct evidence on p54nrb as a phosphotyrosine protein remains unclear. To investigate the tyrosine phosphorylation status of p54nrb, we performed site-directed mutagenesis on the five tyrosine residues of p54nrb, replacing the tyrosine residues with phenylalanine or alanine, and immunoblotted for tyrosine phosphorylation. We then preceded with luciferase reporter assays, RNA splicing minigene assays, co-immunoprecipitation, and confocal microscopy to study the function of p54nrb tyrosine residues on transcription, RNA splicing, protein-protein interaction, and cellular localization. We found that p54nrb was not phosphorylated at tyrosine residues. Rather, it has non-specific binding affinity to anti-phosphotyrosine antibodies. However, replacement of tyrosine with phenylalanine altered p54nrb activities in transcription co-repression and RNA splicing in gene context-dependent fashions by means of differential regulation of p54nrb protein association with its interacting partners and co-regulators of transcription and splicing. These results demonstrate that tyrosine residues, regardless of phosphorylation status, are important for p54nrb function. J. Cell. Physiol. 232: 852-861, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  6. L-Arginine improves multiple physiological parameters in mice exposed to diet-induced metabolic disturbances

    DEFF Research Database (Denmark)

    Clemmensen, Christoffer; Madsen, Andreas Nygaard; Smajilovic, Sanela

    2012-01-01

    L: -Arginine (L: -Arg) is a conditionally essential amino acid and a natural constituent of dietary proteins. Studies in obese rats and type 2 diabetic humans have indicated that dietary supplementation with L: -Arg can diminish gain in white adipose tissue (WAT) and improve insulin sensitivity....... However, the effects of L: -Arg on glucose homeostasis, body composition and energy metabolism remain unclear. In addition, no studies have, to our knowledge, examined whether L: -Arg has beneficial effects as a dietary supplement in the mouse model. In the present study, we investigated the effects of L...... groups. Glucose homeostasis experiments revealed a major effect of L: -Arg supplementation on glucose tolerance and insulin sensitivity, interestingly, independent of a parallel regulation in whole-body adiposity. Increased L: -Arg ingestion also raised energy expenditure; however, no concurrent effect...

  7. A comparative study of students' performance in preclinical physiology assessed by multiple choice and short essay questions.

    Science.gov (United States)

    Oyebola, D D; Adewoye, O E; Iyaniwura, J O; Alada, A R; Fasanmade, A A; Raji, Y

    2000-01-01

    This study was designed to compare the performance of medical students in physiology when assessed by multiple choice questions (MCQs) and short essay questions (SEQs). The study also examined the influence of factors such as age, sex, O/level grades and JAMB scores on performance in the MCQs and SEQs. A structured questionnaire was administered to 264 medical students' four months before the Part I MBBS examination. Apart from personal data of each student, the questionnaire sought information on the JAMB scores and GCE O' Level grades of each student in English Language, Biology, Chemistry, Physics and Mathematics. The physiology syllabus was divided into five parts and the students were administered separate examinations (tests) on each part. Each test consisted of MCQs and SEQs. The performance in MCQs and SEQs were compared. Also, the effects of JAMB scores and GCE O/level grades on the performance in both the MCQs and SEQs were assessed. The results showed that the students performed better in all MCQ tests than in the SEQs. JAMB scores and O' level English Language grade had no significant effect on students' performance in MCQs and SEQs. However O' level grades in Biology, Chemistry, Physics and Mathematics had significant effects on performance in MCQs and SEQs. Inadequate knowledge of physiology and inability to present information in a logical sequence are believed to be major factors contributing to the poorer performance in the SEQs compared with MCQs. In view of the finding of significant association between performance in MCQs and SEQs and GCE O/level grades in science subjects and mathematics, it was recommended that both JAMB results and the GCE results in the four O/level subjects above may be considered when selecting candidates for admission into the medical schools.

  8. Host physiological condition regulates parasitic plant performance: Arceuthobium vaginatum subsp. cryptopodum on Pinus ponderosa.

    Science.gov (United States)

    Bickford, Christopher P; Kolb, Thomas E; Geils, Brian W

    2005-12-01

    Much research has focused on effects of plant parasites on host-plant physiology and growth, but little is known about effects of host physiological condition on parasite growth. Using the parasitic dwarf mistletoe Arceuthobium vaginatum subsp. cryptopodum (Viscaceae) and its host Pinus ponderosa, we investigated whether changes in host physiological condition influenced mistletoe shoot development in northern Arizona forests. We conducted two studies in two consecutive years and used forest thinning (i.e., competitive release) to manipulate host physiological condition. We removed dwarf mistletoe shoots in April, before the onset of the growing season, and measured the amount of regrowth in the first season after forest thinning (Study I: n=38 trees; Study II: n=35 trees). Thinning increased tree uptake of water and carbon in both studies, but had no effect on leaf N concentration or delta13C. Mistletoe shoot growth was greater on trees with high uptake of water and carbon in thinned stands than trees with low uptake in unthinned stands. These findings show that increased resource uptake by host trees increases resources to these heterotrophic dwarf mistletoes, and links mistletoe performance to changes in host physiological condition.

  9. Intersections between cardiac physiology, emotion regulation and interpersonal warmth in preschoolers: Implications for drug abuse prevention from translational neuroscience.

    Science.gov (United States)

    Clark, Caron A C; Skowron, Elizabeth A; Giuliano, Ryan J; Fisher, Philip A

    2016-06-01

    Early childhood is characterized by dramatic gains in emotion regulation skills that support social adjustment and mental health. Understanding the physiological substrates of healthy emotion regulation may offer new directions for altering trajectories toward initiation and escalation of substance abuse. Here, we describe the intersections between parasympathetic and sympathetic tone, emotion regulation and prosocial behavior in a high-risk sample of preschoolers. Fifty-two 3-6 year old children completed an assessment of attention regulation in response to affective stimuli. Cardiac respiratory sinus arrhythmia, an index of parasympathetic tone, and pre-ejection period, a marker of sympathetic activation, were recorded at rest and while children engaged in social interactions with their mothers and an unfamiliar research assistant. Mothers reported on children's emotional reactivity and prosocial behavior. Controlling for age and psychosocial risk, higher parasympathetic tone predicted better attention regulation in response to angry emotion and higher levels of prosocial behavior, whereas a reciprocal pattern of higher parasympathetic tone and lower sympathetic arousal predicted better attention in response to positive emotion and lower emotional reactivity. Children exposed to fewer risk factors and higher levels of maternal warmth were more able to sustain a high level of parasympathetic tone during interaction episodes. Findings suggest that autonomic measures represent biomarkers for socio-emotional competence in young children. They also point to the importance of early experiences in the establishment of physiological regulation and the promise of family-based intervention to promote healthy emotion regulation and prevent substance dependence in high-risk populations. Copyright © 2016 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

  10. The Physiological Regulation of Skeletal Muscle Fatty Acid Supply and Oxidation During Moderate-Intensity Exercise

    DEFF Research Database (Denmark)

    van Hall, Gerrit

    2015-01-01

    ) in the muscle of the very-low-density lipoproteins and in the (semi) post-prandial state chylomicrons may also contribute. In this review, the NEFA fluxes and oxidation by skeletal muscle during prolonged moderate-intensity exercise are described in terms of the integration of physiological systems. Steps...... demand of the exercising muscle is the main driving force for all physiological regulatory processes. It elicits functional hyperemia, increasing the recruitment of capillaries and muscle blood flow resulting in increased NEFA delivery and accessibility to NEFA transporters and LPL. It also releases...

  11. Physiological Functions and Regulation of the Na+/H+ Exchanger [NHE1] in Renal Tubule Epithelial Cells

    Directory of Open Access Journals (Sweden)

    Patricia G Vallés

    2015-08-01

    Full Text Available The sodium-hydrogen exchanger isoform-1 [NHE1] is a ubiquitously expressed plasma membrane protein that plays a central role in intracellular pH and cell volume homeostasis by catalyzing an electroneutral exchange of extracellular sodium and intracellular hydrogen. Outside of this important physiological function, the NHE1 cytosolic tail domain acts as a molecular scaffold regulating cell survival and actin cytoskeleton organization through NHE1-dependent signaling proteins. NHE1 plays main roles in response to physiological stress conditions which in addition to cell shrinkage and acidification, include hypoxia and mechanical stimuli, such as cell stretch. NHE1-mediated modulation of programmed cell death results from the exchanger-mediated changes in pHi, cell volume, and/or [Na+]I; and, it has recently become known that regulation of cellular signaling pathways are involved as well. This review focuses on NHE1 functions and regulations. We describe evidence showing how these structural actions integrate with ion translocation in regulating renal tubule epithelial cell survival.

  12. Multiple complexes of nitrogen assimilatory enzymes in spinach chloroplasts: possible mechanisms for the regulation of enzyme function.

    Directory of Open Access Journals (Sweden)

    Yoko Kimata-Ariga

    Full Text Available Assimilation of nitrogen is an essential biological process for plant growth and productivity. Here we show that three chloroplast enzymes involved in nitrogen assimilation, glutamate synthase (GOGAT, nitrite reductase (NiR and glutamine synthetase (GS, separately assemble into distinct protein complexes in spinach chloroplasts, as analyzed by western blots under blue native electrophoresis (BN-PAGE. GOGAT and NiR were present not only as monomers, but also as novel complexes with a discrete size (730 kDa and multiple sizes (>120 kDa, respectively, in the stromal fraction of chloroplasts. These complexes showed the same mobility as each monomer on two-dimensional (2D SDS-PAGE after BN-PAGE. The 730 kDa complex containing GOGAT dissociated into monomers, and multiple complexes of NiR reversibly converted into monomers, in response to the changes in the pH of the stromal solvent. On the other hand, the bands detected by anti-GS antibody were present not only in stroma as a conventional decameric holoenzyme complex of 420 kDa, but also in thylakoids as a novel complex of 560 kDa. The polypeptide in the 560 kDa complex showed slower mobility than that of the 420 kDa complex on the 2D SDS-PAGE, implying the assembly of distinct GS isoforms or a post-translational modification of the same GS protein. The function of these multiple complexes was evaluated by in-gel GS activity under native conditions and by the binding ability of NiR and GOGAT with their physiological electron donor, ferredoxin. The results indicate that these multiplicities in size and localization of the three nitrogen assimilatory enzymes may be involved in the physiological regulation of their enzyme function, in a similar way as recently described cases of carbon assimilatory enzymes.

  13. PAC1- and VPAC2 receptors in light regulated behavior and physiology: Studies in single and double mutant mice.

    Directory of Open Access Journals (Sweden)

    Jens Hannibal

    Full Text Available The two sister peptides, pituitary adenylate cyclase activating polypeptide (PACAP and vasoactive intestinal polypeptide (VIP and their receptors, the PAC1 -and the VPAC2 receptors, are involved in regulation of the circadian timing system. PACAP as a neurotransmitter in the retinohypothalamic tract (RHT and VIP as a neurotransmitter, involved in synchronization of SCN neurons. Behavior and physiology in VPAC2 deficient mice are strongly regulated by light most likely as a result of masking. Consequently, we used VPAC2 and PAC1/VPAC2 double mutant mice in comparison with PAC1 receptor deficient mice to further elucidate the role of PACAP in the light mediated regulation of behavior and physiology of the circadian system. We compared circadian rhythms in mice equipped with running wheels or implanted radio-transmitter measuring core body temperature kept in a full photoperiod ((FPP(12:12 h light dark-cycles (LD and skeleton photo periods (SPP at high and low light intensity. Furthermore, we examined the expression of PAC1- and VPAC2 receptors in the SCN of the different genotypes in combination with visualization of PACAP and VIP and determined whether compensatory changes in peptide and/or receptor expression in the reciprocal knockouts (KO (PAC1 and VPAC2 had occurred. Our data demonstrate that in although being closely related at both ligand and receptor structure/sequence, PACAP/PAC1 receptor signaling are independent of VIP/VPAC2 receptor signaling and vice versa. Furthermore, lack of either of the receptors does not result in compensatory changes at neither the physiological or anatomical level. PACAP/PAC1 signaling is important for light regulated behavior, VIP/VPAC2signaling for stable clock function and both signaling pathways may play a role in shaping diurnality versus nocturnality.

  14. Physiological and anatomic evidence for regulation of the heart by suprachiasmatic nucleus in rats

    NARCIS (Netherlands)

    Scheer, F. A.; ter Horst, G. J.; van der Vliet, J.; Buijs, R. M.

    2001-01-01

    The suprachiasmatic nucleus (SCN) is the mammalian biological clock that generates the daily rhythms in physiology and behavior. Light can phase shift the rhythm of the SCN but can also acutely affect SCN activity and output, e.g., output to the pineal. Recently, multisynaptic SCN connections to

  15. Physiological and anatomic evidence for regulation of the heart by suprachiasmatic nucleus in rats

    NARCIS (Netherlands)

    Scheer, FAJL; Ter Horst, GJ; Van der Vliet, J

    The suprachiasmatic nucleus (SCN) is the mammalian biological clock that generates the daily rhythms in physiology and behavior. Light can phase shift the rhythm of the SCN but can also acutely affect SCN activity and output, e.g., output to the pineal. Recently, multisynaptic SCN connections to

  16. EEN regulates the proliferation and survival of multiple myeloma cells by potentiating IGF-1 secretion

    International Nuclear Information System (INIS)

    Huang, Er-Wen; Xue, Sheng-Jiang; Li, Xiao-Yan; Xu, Suo-Wen; Cheng, Jian-Ding; Zheng, Jin-Xiang; Shi, He; Lv, Guo-Li; Li, Zhi-Gang; Li, Yue; Liu, Chang-Hui; Chen, Xiao-Hui; Liu, Hong; Li, Jie; Liu, Chao

    2014-01-01

    Highlights: • Levels of EEN expression paralleled with the rate of cell proliferation. • EEN was involved in the proliferation and survival of multiple myeloma (MM) cells. • EEN regulated the activity of IGF-1-Akt/mTOR pathway. • EEN regulated proliferation and survival of MM cells by enhancing IGF-1 secretion. - Abstract: The molecular mechanisms of multiple myeloma are not well defined. EEN is an endocytosis-regulating molecule. Here we report that EEN regulates the proliferation and survival of multiple myeloma cells, by regulating IGF-1 secretion. In the present study, we observed that EEN expression paralleled with cell proliferation, EEN accelerated cell proliferation, facilitated cell cycle transition from G1 to S phase by regulating cyclin-dependent kinases (CDKs) pathway, and delayed cell apoptosis via Bcl2/Bax-mitochondrial pathway. Mechanistically, we found that EEN was indispensable for insulin-like growth factor-1 (IGF-1) secretion and the activation of protein kinase B-mammalian target of rapamycin (Akt-mTOR) pathway. Exogenous IGF-1 overcame the phenotype of EEN depletion, while IGF-1 neutralization overcame that of EEN over-expression. Collectively, these data suggest that EEN may play a pivotal role in excessive cell proliferation and insufficient cell apoptosis of bone marrow plasma cells in multiple myeloma. Therefore, EEN may represent a potential diagnostic marker or therapeutic target for multiple myeloma

  17. EEN regulates the proliferation and survival of multiple myeloma cells by potentiating IGF-1 secretion

    Energy Technology Data Exchange (ETDEWEB)

    Huang, Er-Wen [Guangzhou Institute of Forensic Science, Guangzhou (China); Department of Forensic Pathology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou (China); Xue, Sheng-Jiang [Department of Forensic Pathology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou (China); Li, Xiao-Yan [Department of Pharmacy, The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou (China); Xu, Suo-Wen [Department of Pharmacology and Toxicology, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou (China); Cheng, Jian-Ding; Zheng, Jin-Xiang [Department of Forensic Pathology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou (China); Shi, He; Lv, Guo-Li; Li, Zhi-Gang; Li, Yue; Liu, Chang-Hui; Chen, Xiao-Hui; Liu, Hong [Guangzhou Institute of Forensic Science, Guangzhou (China); Li, Jie, E-mail: mdlijie@sina.com [Department of Anaesthesiology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou (China); Liu, Chao, E-mail: liuchaogaj@21cn.com [Guangzhou Institute of Forensic Science, Guangzhou (China)

    2014-05-02

    Highlights: • Levels of EEN expression paralleled with the rate of cell proliferation. • EEN was involved in the proliferation and survival of multiple myeloma (MM) cells. • EEN regulated the activity of IGF-1-Akt/mTOR pathway. • EEN regulated proliferation and survival of MM cells by enhancing IGF-1 secretion. - Abstract: The molecular mechanisms of multiple myeloma are not well defined. EEN is an endocytosis-regulating molecule. Here we report that EEN regulates the proliferation and survival of multiple myeloma cells, by regulating IGF-1 secretion. In the present study, we observed that EEN expression paralleled with cell proliferation, EEN accelerated cell proliferation, facilitated cell cycle transition from G1 to S phase by regulating cyclin-dependent kinases (CDKs) pathway, and delayed cell apoptosis via Bcl2/Bax-mitochondrial pathway. Mechanistically, we found that EEN was indispensable for insulin-like growth factor-1 (IGF-1) secretion and the activation of protein kinase B-mammalian target of rapamycin (Akt-mTOR) pathway. Exogenous IGF-1 overcame the phenotype of EEN depletion, while IGF-1 neutralization overcame that of EEN over-expression. Collectively, these data suggest that EEN may play a pivotal role in excessive cell proliferation and insufficient cell apoptosis of bone marrow plasma cells in multiple myeloma. Therefore, EEN may represent a potential diagnostic marker or therapeutic target for multiple myeloma.

  18. The barley anion channel, HvALMT1, has multiple roles in guard cell physiology and grain metabolism.

    Science.gov (United States)

    Xu, Muyun; Gruber, Benjamin D; Delhaize, Emmanuel; White, Rosemary G; James, Richard A; You, Jiangfeng; Yang, Zhenming; Ryan, Peter R

    2015-01-01

    The barley (Hordeum vulgare) gene HvALMT1 encodes an anion channel in guard cells and in certain root tissues indicating that it may perform multiple roles. The protein localizes to the plasma membrane and facilitates malate efflux from cells when constitutively expressed in barley plants and Xenopus oocytes. This study investigated the function of HvALMT1 further by identifying its tissue-specific expression and by generating and characterizing RNAi lines with reduced HvALMT1 expression. We show that transgenic plants with 18-30% of wild-type HvALMT1 expression had impaired guard cell function. They maintained higher stomatal conductance in low light intensity and lost water more rapidly from excised leaves than the null segregant control plants. Tissue-specific expression of HvALMT1 was investigated in developing grain and during germination using transgenic barley lines expressing the green fluorescent protein (GFP) with the HvALMT1 promoter. We found that HvALMT1 is expressed in the nucellar projection, the aleurone layer and the scutellum of developing barley grain. Malate release measured from isolated aleurone layers prepared from imbibed grain was significantly lower in the RNAi barley plants compared with control plants. These data provide molecular and physiological evidence that HvALMT1 functions in guard cells, in grain development and during germination. We propose that HvALMT1 releases malate and perhaps other anions from guard cells to promote stomatal closure. The likely roles of HvALMT1 during seed development and grain germination are also discussed. © 2014 Scandinavian Plant Physiology Society.

  19. Multiple ETS family proteins regulate PF4 gene expression by binding to the same ETS binding site.

    Directory of Open Access Journals (Sweden)

    Yoshiaki Okada

    Full Text Available In previous studies on the mechanism underlying megakaryocyte-specific gene expression, several ETS motifs were found in each megakaryocyte-specific gene promoter. Although these studies suggested that several ETS family proteins regulate megakaryocyte-specific gene expression, only a few ETS family proteins have been identified. Platelet factor 4 (PF4 is a megakaryocyte-specific gene and its promoter includes multiple ETS motifs. We had previously shown that ETS-1 binds to an ETS motif in the PF4 promoter. However, the functions of the other ETS motifs are still unclear. The goal of this study was to investigate a novel functional ETS motif in the PF4 promoter and identify proteins binding to the motif. In electrophoretic mobility shift assays and a chromatin immunoprecipitation assay, FLI-1, ELF-1, and GABP bound to the -51 ETS site. Expression of FLI-1, ELF-1, and GABP activated the PF4 promoter in HepG2 cells. Mutation of a -51 ETS site attenuated FLI-1-, ELF-1-, and GABP-mediated transactivation of the promoter. siRNA analysis demonstrated that FLI-1, ELF-1, and GABP regulate PF4 gene expression in HEL cells. Among these three proteins, only FLI-1 synergistically activated the promoter with GATA-1. In addition, only FLI-1 expression was increased during megakaryocytic differentiation. Finally, the importance of the -51 ETS site for the activation of the PF4 promoter during physiological megakaryocytic differentiation was confirmed by a novel reporter gene assay using in vitro ES cell differentiation system. Together, these data suggest that FLI-1, ELF-1, and GABP regulate PF4 gene expression through the -51 ETS site in megakaryocytes and implicate the differentiation stage-specific regulation of PF4 gene expression by multiple ETS factors.

  20. Regulation and physiological role of silicon in alleviating drought stress of mango.

    Science.gov (United States)

    Helaly, Mohamed Naser; El-Hoseiny, Hanan; El-Sheery, Nabil Ibrahim; Rastogi, Anshu; Kalaji, Hazem M

    2017-09-01

    Improvement of drought stress of mango plants requires intensive research that focuses on physiological processes. In three successive seasons (2014, 2015and 2016) field experiments with four different strains of mango were subjected to two water regimes. The growth and physiological parameters of possible relevance for drought stress tolerances in mango were investigated. Yield and its components were also evaluated. The data showed that all growth and physiological parameters were increased under K 2 SiO 3 (Si) supplement and were followed by the interaction treatment (Si treatment and its combination with drought stress) compared to that of the controlled condition. Drought stress decreased the concentration of auxins (IAA), gibberellins (GA) and cytokinins (CK) in the three mango cultivars leaves, whereas, it increased the concentration of abscisic acid (ABA). On the contrary, IAA, GA, and CK (promoters) endogenous levels were improved by supplementing Si, in contrary ABA was decreased. Drought stress increased the activity of peroxidase (POX), catalase (CAT), and superoxide dismutase (SOD) in the leaves of all mango cultivars grown during three experimental seasons. However, Si supplementation reduced the levels of all these antioxidative enzymes, especially the concentration of SOD when compared to that of control leaves. Fruit quality was improved in three successive seasons when Si was applied. Our results clearly show that the increment in drought tolerance was associated with an increase in antioxidative enzyme activity, allowing mango plants to cope better with drought stress. Si possesses an efficient system for scavenging reactive oxygen species, which protects the plant against destructive oxidative reactions, thereby improving the ability of the mango trees to withstand environmental stress in arid regions. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  1. [Importance of preservation of biophysical organization of isolated mitochondria for revealing physiological regulation of their functions].

    Science.gov (United States)

    Zakharchenko, M V; Khunderiakova, N V; Kondrashova, M N

    2011-01-01

    A method has been elaborated that preserves the mitochondrial-reticular network in lymphocytes in composition to the physiological one. Physiologicalby the immobilization of a blood smear on glass and its subsequent incubation in a medium closeresponses of respiration to excitation in the ition of early responses of ions. The recogn organism are well pronounced on these preparat mitochondria to pathogenic agents in the organism is a timely problem of basic and medicinal e- investigations since they play a leading role in the development of pathological states.

  2. Thyroid Hormone Receptor Beta in the Ventromedial Hypothalamus Is Essential for the Physiological Regulation of Food Intake and Body Weight

    Directory of Open Access Journals (Sweden)

    Saira Hameed

    2017-06-01

    Full Text Available The obesity epidemic is a significant global health issue. Improved understanding of the mechanisms that regulate appetite and body weight will provide the rationale for the design of anti-obesity therapies. Thyroid hormones play a key role in metabolic homeostasis through their interaction with thyroid hormone receptors (TRs, which function as ligand-inducible transcription factors. The TR-beta isoform (TRβ is expressed in the ventromedial hypothalamus (VMH, a brain area important for control of energy homeostasis. Here, we report that selective knockdown of TRβ in the VMH of adult mice results in severe obesity due to hyperphagia and reduced energy expenditure. The observed increase in body weight is of a similar magnitude to murine models of the most extreme forms of monogenic obesity. These data identify TRβ in the VMH as a major physiological regulator of food intake and energy homeostasis.

  3. Silicon Mitigates Salinity Stress by Regulating the Physiology, Antioxidant Enzyme Activities, and Protein Expression in Capsicum annuum 'Bugwang'.

    Science.gov (United States)

    Manivannan, Abinaya; Soundararajan, Prabhakaran; Muneer, Sowbiya; Ko, Chung Ho; Jeong, Byoung Ryong

    2016-01-01

    Silicon- (Si-) induced salinity stress resistance was demonstrated at physiological and proteomic levels in Capsicum annuum for the first time. Seedlings of C. annuum were hydroponically treated with NaCl (50 mM) with or without Si (1.8 mM) for 15 days. The results illustrated that saline conditions significantly reduced plant growth and biomass and photosynthetic parameters and increased the electrolyte leakage potential, lipid peroxidation, and hydrogen peroxide level. However, supplementation of Si allowed the plants to recover from salinity stress by improving their physiology and photosynthesis. During salinity stress, Si prevented oxidative damage by increasing the activities of antioxidant enzymes. Furthermore, Si supplementation recovered the nutrient imbalance that had occurred during salinity stress. Additionally, proteomic analysis by two-dimensional gel electrophoresis (2DE) followed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) revealed that Si treatment upregulated the accumulation of proteins involved in several metabolic processes, particularly those associated with nucleotide binding and transferase activity. Moreover, Si modulated the expression of vital proteins involved in ubiquitin-mediated nucleosome pathway and carbohydrate metabolism. Overall, the results illustrate that Si application induced resistance against salinity stress in C. annuum by regulating the physiology, antioxidant metabolism, and protein expression.

  4. Silicon Mitigates Salinity Stress by Regulating the Physiology, Antioxidant Enzyme Activities, and Protein Expression in Capsicum annuum ‘Bugwang'

    Science.gov (United States)

    Manivannan, Abinaya; Soundararajan, Prabhakaran; Muneer, Sowbiya; Ko, Chung Ho

    2016-01-01

    Silicon- (Si-) induced salinity stress resistance was demonstrated at physiological and proteomic levels in Capsicum annuum for the first time. Seedlings of C. annuum were hydroponically treated with NaCl (50 mM) with or without Si (1.8 mM) for 15 days. The results illustrated that saline conditions significantly reduced plant growth and biomass and photosynthetic parameters and increased the electrolyte leakage potential, lipid peroxidation, and hydrogen peroxide level. However, supplementation of Si allowed the plants to recover from salinity stress by improving their physiology and photosynthesis. During salinity stress, Si prevented oxidative damage by increasing the activities of antioxidant enzymes. Furthermore, Si supplementation recovered the nutrient imbalance that had occurred during salinity stress. Additionally, proteomic analysis by two-dimensional gel electrophoresis (2DE) followed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) revealed that Si treatment upregulated the accumulation of proteins involved in several metabolic processes, particularly those associated with nucleotide binding and transferase activity. Moreover, Si modulated the expression of vital proteins involved in ubiquitin-mediated nucleosome pathway and carbohydrate metabolism. Overall, the results illustrate that Si application induced resistance against salinity stress in C. annuum by regulating the physiology, antioxidant metabolism, and protein expression. PMID:27088085

  5. Cell physiology regulation by hypoxia inducible factor-1: Targeting oxygen-related nanomachineries of hypoxic cells.

    Science.gov (United States)

    Eskandani, Morteza; Vandghanooni, Somayeh; Barar, Jaleh; Nazemiyeh, Hossein; Omidi, Yadollah

    2017-06-01

    Any dysfunctionality in maintaining the oxygen homeostasis by mammalian cells may elicit hypoxia/anoxia, which results in inescapable oxidative stress and possible subsequent detrimental impacts on certain cells/tissues with high demands to oxygen molecules. The ischemic damage in turn can trigger initiation of a number of diseases including organs ischemia, metabolic disorders, inflammatory diseases, different types of malignancies, and alteration in wound healing process. Thus, full comprehension of molecular mechanism(s) and cellular physiology of the oxygen homeostasis is the cornerstone of the mammalian cells metabolism, energetic pathways and health and disease conditions. An imbalance in oxygen content within the cellular microenvironment activates a cascade of molecular events that are often compensated, otherwise pathologic condition occurs through a complexed network of biomolecules. Hypoxia inducible factor-1 (HIF-1) plays a key transcriptional role in the adaptation of cell physiology in relation with the oxygen content within a cell. In this current study, we provide a comprehensive review on the molecular mechanisms of oxygen sensing and homeostasis and the impacts of HIF-1 in hypoxic/anoxic conditions. Moreover, different molecular and biochemical responses of the cells to the surrounding environment are discussed in details. Finally, modern technological approaches for targeting the hypoxia related proteins are articulated. Copyright © 2017. Published by Elsevier B.V.

  6. Regulation of lipid deposition in farm animals: Parallels between agriculture and human physiology.

    Science.gov (United States)

    Bergen, Werner G; Brandebourg, Terry D

    2016-06-01

    For many years, clinically oriented scientists and animal scientists have focused on lipid metabolism and fat deposition in various fat depots. While dealing with a common biology across species, the goals of biomedical and food animals lipid metabolism research differ in emphasis. In humans, mechanisms and regulation of fat synthesis, accumulation of fat in regional fat depots, lipid metabolism and dysmetabolism in adipose, liver and cardiac tissues have been investigated. Further, energy balance and weight control have also been extensively explored in humans. Finally, obesity and associated maladies including high cholesterol and atherosclerosis, cardiovascular disease, insulin resistance, hypertension, metabolic syndrome and health outcomes have been widely studied. In food animals, the emphasis has been on regulation of fatty acid synthesis and lipid deposition in fat depots and deposition of intramuscular fat. For humans, understanding the regulation of energy balance and body weight and of prevention or treatment of obesity and associated maladies have been important clinical outcomes. In production of food animals lowering fat content in muscle foods while enhancing intramuscular fat (marbling) have been major targets. In this review, we summarize how our laboratories have addressed the goal of providing lean but yet tasty and juicy muscle food products to consumers. In addition, we here describe efforts in the development of a new porcine model to study regulation of fat metabolism and obesity. Commonalities and differences in regulation of lipid metabolism between humans, rodents and food animals are emphasized throughout this review. © 2016 by the Society for Experimental Biology and Medicine.

  7. Neural plasticity in hypocretin neurons: the basis of hypocretinergic regulation of physiological and behavioral functions in animals

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    Xiao-Bing eGao

    2015-10-01

    Full Text Available The neuronal system that resides in the perifornical and lateral hypothalamus (Pf/LH and synthesizes the neuropeptide hypocretin/orexin participates in critical brain functions across species from fish to human. The hypocretin system regulates neural activity responsible for daily functions (such as sleep/wake homeostasis, energy balance, appetite, etc and long-term behavioral changes (such as reward seeking and addiction, stress response, etc in animals. The most recent evidence suggests that the hypocretin system undergoes substantial plastic changes in response to both daily fluctuations (such as food intake and sleep-wake regulation and long-term changes (such as cocaine seeking in neuronal activity in the brain. The understanding of these changes in the hypocretin system is essential in addressing the role of the hypocretin system in normal physiological functions and pathological conditions in animals and humans. In this review, the evidence demonstrating that neural plasticity occurs in hypocretin-containing neurons in the Pf/LH will be presented and possible physiological behavioral, and mental health implications of these findings will be discussed.

  8. Neural plasticity in hypocretin neurons: the basis of hypocretinergic regulation of physiological and behavioral functions in animals

    Science.gov (United States)

    Gao, Xiao-Bing; Hermes, Gretchen

    2015-01-01

    The neuronal system that resides in the perifornical and lateral hypothalamus (Pf/LH) and synthesizes the neuropeptide hypocretin/orexin participates in critical brain functions across species from fish to human. The hypocretin system regulates neural activity responsible for daily functions (such as sleep/wake homeostasis, energy balance, appetite, etc.) and long-term behavioral changes (such as reward seeking and addiction, stress response, etc.) in animals. The most recent evidence suggests that the hypocretin system undergoes substantial plastic changes in response to both daily fluctuations (such as food intake and sleep-wake regulation) and long-term changes (such as cocaine seeking) in neuronal activity in the brain. The understanding of these changes in the hypocretin system is essential in addressing the role of the hypocretin system in normal physiological functions and pathological conditions in animals and humans. In this review, the evidence demonstrating that neural plasticity occurs in hypocretin-containing neurons in the Pf/LH will be presented and possible physiological, behavioral, and mental health implications of these findings will be discussed. PMID:26539086

  9. The interaction of psychological and physiological homeostatic drives and role of general control principles in the regulation of physiological systems, exercise and the fatigue process - The Integrative Governor theory.

    Science.gov (United States)

    St Clair Gibson, A; Swart, J; Tucker, R

    2018-02-01

    Either central (brain) or peripheral (body physiological system) control mechanisms, or a combination of these, have been championed in the last few decades in the field of Exercise Sciences as how physiological activity and fatigue processes are regulated. In this review, we suggest that the concept of 'central' or 'peripheral' mechanisms are both artificial constructs that have 'straight-jacketed' research in the field, and rather that competition between psychological and physiological homeostatic drives is central to the regulation of both, and that governing principles, rather than distinct physical processes, underpin all physical system and exercise regulation. As part of the Integrative Governor theory we develop in this review, we suggest that both psychological and physiological drives and requirements are underpinned by homeostatic principles, and that regulation of the relative activity of each is by dynamic negative feedback activity, as the fundamental general operational controller. Because of this competitive, dynamic interplay, we propose that the activity in all systems will oscillate, that these oscillations create information, and comparison of this oscillatory information with either prior information, current activity, or activity templates create efferent responses that change the activity in the different systems in a similarly dynamic manner. Changes in a particular system are always the result of perturbations occurring outside the system itself, the behavioural causative 'history' of this external activity will be evident in the pattern of the oscillations, and awareness of change occurs as a result of unexpected rather than planned change in physiological activity or psychological state.

  10. A Hox Gene, Antennapedia, Regulates Expression of Multiple Major Silk Protein Genes in the Silkworm Bombyx mori.

    Science.gov (United States)

    Tsubota, Takuya; Tomita, Shuichiro; Uchino, Keiro; Kimoto, Mai; Takiya, Shigeharu; Kajiwara, Hideyuki; Yamazaki, Toshimasa; Sezutsu, Hideki

    2016-03-25

    Hoxgenes play a pivotal role in the determination of anteroposterior axis specificity during bilaterian animal development. They do so by acting as a master control and regulating the expression of genes important for development. Recently, however, we showed that Hoxgenes can also function in terminally differentiated tissue of the lepidopteranBombyx mori In this species,Antennapedia(Antp) regulates expression of sericin-1, a major silk protein gene, in the silk gland. Here, we investigated whether Antpcan regulate expression of multiple genes in this tissue. By means of proteomic, RT-PCR, and in situ hybridization analyses, we demonstrate that misexpression of Antpin the posterior silk gland induced ectopic expression of major silk protein genes such assericin-3,fhxh4, and fhxh5 These genes are normally expressed specifically in the middle silk gland as is Antp Therefore, the evidence strongly suggests that Antpactivates these silk protein genes in the middle silk gland. The putativesericin-1 activator complex (middle silk gland-intermolt-specific complex) can bind to the upstream regions of these genes, suggesting that Antpdirectly activates their expression. We also found that the pattern of gene expression was well conserved between B. moriand the wild species Bombyx mandarina, indicating that the gene regulation mechanism identified here is an evolutionarily conserved mechanism and not an artifact of the domestication of B. mori We suggest that Hoxgenes have a role as a master control in terminally differentiated tissues, possibly acting as a primary regulator for a range of physiological processes. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  11. Stress Regulation in Adolescents: Physiological Reactivity during the Adult Attachment Interview and Conflict Interaction

    Science.gov (United States)

    Beijersbergen, Marielle D.; Bakermans-Kranenburg, Marian J.; van IJzendoorn, Marinus H.; Juffer, Femmie

    2008-01-01

    The current study examined whether adolescents' attachment representations were associated with differences in emotion regulation during the Adult Attachment Interview (AAI; C. George, N. Kaplan, & M. Main, 1996) and during a mother-adolescent conflict interaction task (Family Interaction Task [FIT]; J. P. Allen et al., 2003). Participants…

  12. Discrete Emotion Regulation Strategy Repertoires and Parasympathetic Physiology Characterize Psychopathology Symptoms in Childhood

    Science.gov (United States)

    Quiñones-Camacho, Laura E.; Davis, Elizabeth L.

    2018-01-01

    Certain psychopathologies are often linked to dysregulation of specific emotions (e.g., anxiety is associated with dysregulation of fear), but few studies have examined how regulatory repertoires for specific emotions (e.g., the strategies a person uses to regulate fear) relate to psychopathology, and fewer still have examined this in childhood. A…

  13. Expression of the central growth regulator BIG BROTHER is regulated by multiple cis-elements

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    Breuninger Holger

    2012-03-01

    Full Text Available Abstract Background Much of the organismal variation we observe in nature is due to differences in organ size. The observation that even closely related species can show large, stably inherited differences in organ size indicates a strong genetic component to the control of organ size. Despite recent progress in identifying factors controlling organ growth in plants, our overall understanding of this process remains limited, partly because the individual factors have not yet been connected into larger regulatory pathways or networks. To begin addressing this aim, we have studied the upstream regulation of expression of BIG BROTHER (BB, a central growth-control gene in Arabidopsis thaliana that prevents overgrowth of organs. Final organ size and BB expression levels are tightly correlated, implying the need for precise control of its expression. BB expression mirrors proliferative activity, yet the gene functions to limit proliferation, suggesting that it acts in an incoherent feedforward loop downstream of growth activators to prevent over-proliferation. Results To investigate the upstream regulation of BB we combined a promoter deletion analysis with a phylogenetic footprinting approach. We were able to narrow down important, highly conserved, cis-regulatory elements within the BB promoter. Promoter sequences of other Brassicaceae species were able to partially complement the A. thaliana bb-1 mutant, suggesting that at least within the Brassicaceae family the regulatory pathways are conserved. Conclusions This work underlines the complexity involved in precise quantitative control of gene expression and lays the foundation for identifying important upstream regulators that determine BB expression levels and thus final organ size.

  14. Non-photoperiodic regulation of reproductive physiology in the flexibly breeding pine siskin (Spinus pinus)

    OpenAIRE

    Watts, Heather E.; Hahn, Thomas P.

    2012-01-01

    In order to time reproduction to coincide with favorable conditions, animals use environmental cues to up- and down-regulate the reproductive axis appropriately. Although photoperiodic cues are one of the best studied of such environmental cues, animals also attend to others such as temperature, food availability, rainfall and social cues. Such non-photic cues are expected to be particularly important for tropical species and temperate-zone species that exhibit flexible or opportunistic breed...

  15. TASK-2: a K2P K+ channel with complex regulation and diverse physiological functions

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    Luis Pablo Cid

    2013-07-01

    Full Text Available TASK-2 (K2P5.1 is a two-pore domain K+ channel belonging to the TALK subgroup of the K2P family of proteins. TASK-2 has been shown to be activated by extra- and intracellular alkalinisation. Extra- and intracellular pH-sensors reside at arginine 224 and lysine 245 and might affect separate selectivity filter and inner gates respectively. TASK-2 is modulated by changes in cell volume and a regulation by direct G-protein interaction has also been proposed. Activation by extracellular alkalinisation has been associated with a role of TASK-2 in kidney proximal tubule bicarbonate reabsorption, whilst intracellular pH-sensitivity might be the mechanism for its participation in central chemosensitive neurons. In addition to these functions TASK-2 has been proposed to play a part in apoptotic volume decrease in kidney cells and in volume regulation of glial cells and T-lymphocytes. TASK-2 is present in chondrocytes of hyaline cartilage, where it is proposed to play a central role in stabilizing the membrane potential. Additional sites of expression are dorsal root ganglion neurons, endocrine and exocrine pancreas and intestinal smooth muscle cells. TASK-2 has been associated with the regulation of proliferation of breast cancer cells and could become target for breast cancer therapeutics. Further work in native tissues and cells together with genetic modification will no doubt reveal the details of TASK-2 functions that we are only starting to suspect.

  16. The complex contribution of NOS interneurons in the physiology of cerebrovascular regulation

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    Sonia eDuchemin

    2012-08-01

    Full Text Available Following the discovery of the vasorelaxant properties of nitric oxide (NO by Furchgott and Ignarro, the finding by Bredt and coll. of a constitutively expressed NO synthase in neurons (nNOS led to the presumption that neuronal NO may control cerebrovascular functions. Consequently, numerous studies have sought to determine whether neuraly-derived NO is involved in the regulation of cerebral blood flow. Anatomically, axons, dendrites or somata of NO neurons have been found to contact the basement membrane of blood vessels or perivascular astrocytes in all segments of the cortical microcirculation. Functionally, various experimental approaches support a role of neuronal NO in the maintenance of resting cerebral blood flow as well as in the vascular response to neuronal activity. Since decades, it has been assumed that neuronal NO simply diffuses to the local blood vessels and produce vasodilation through a cGMP-PKG dependent mechanism. However, NO is not the sole mediator of vasodilation in the cerebral microcirculation and is known to interact with a myriad of signaling pathways also involved in vascular control. In addition, cerebrovascular regulation is the result of a complex orchestration between all components of the neurovascular unit (i.e. neuronal, glial and vascular cells also known to produce NO. In this review article, the role of NO interneuron in the regulation of cortical microcirculation will be discussed in the context of the neurovascular unit.

  17. Evidence for the different physiological significance of the 6- and 2-minute walk tests in multiple sclerosis

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    Motl Robert W

    2012-03-01

    Full Text Available Abstract Background Researchers have recently advocated for the 2-minute walk (2MW as an alternative for the 6-minute walk (6MW to assess long distance ambulation in persons with multiple sclerosis (MS. This recommendation has not been based on physiological considerations such as the rate of oxygen consumption (V·O2 over the 6MW range. Objective This study examined the pattern of change in V·O2 over the range of the 6MW in a large sample of persons with MS who varied as a function of disability status. Method Ninety-five persons with clinically-definite MS underwent a neurological examination for generating an Expanded Disability Status Scale (EDSS score, and then completion of the 6MW protocol while wearing a portable metabolic unit and an accelerometer. Results There was a time main effect on V·O2 during the 6MW (p = .0001 such that V·O2 increased significantly every 30 seconds over the first 3 minutes of the 6MW, and then remained stable over the second 3 minutes of the 6MW. This occurred despite no change in cadence across the 6MW (p = .84. Conclusions The pattern of change in V·O2 indicates that there are different metabolic systems providing energy for ambulation during the 6MW in MS subjects and steady state aerobic metabolism is reached during the last 3 minutes of the 6MW. By extension, the first 3 minutes would represent a test of mixed aerobic and anaerobic work, whereas the second 3 minutes would represent a test of aerobic work during walking.

  18. Changes in the physiological activity of soybean (Glycine max L. Merr. under the influence of exogenous growth regulators

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    Anna Nowak

    2015-07-01

    Full Text Available In a two-year pot experiment (2008–2009 conducted at the Vegetation Hall, West Pomeranian University of Technology in Szczecin, we investigated the influence of exogenous growth regulators, i.e. indole-3-butyric acid (IBA and 6-benzylaminopurine (BAP and their mixture, on the activity of gas exchange and selected physiological features of soybeans (Glycine max L. Merr.. The experimental factors included the following Polish soybean cultivars: ‘Aldana’, ‘Progres’ and ‘Jutro’. During plant growth, CO2 assimilation (A, transpiration rate (E, stomatal conductance (gs, and substomatal CO2 concentration (ci were determined. Two soybean cultivars, i.e. ‘Jutro’ and ‘Progres’, showed a significant increase in the intensity of assimilation and transpiration after using all kinds of growth regulators as compared with the control plants. It was found that the ‘Jutro’ cultivar, after using a mixture of growth regulators (IBA + BAP, was characterized by the significantly highest CO2 assimilation (A and transpiration (E as well as the highest stomatal conductance (gs. The ‘Aldana’ cultivar, on the other hand, responded by a significant reduction in the transpiration rate, stomatal conductance and subsomatal CO2 concentration. The spraying of the plants with exogenous growth regulators had a significant influence on the increase in the number of stomata and stomatal pore length, mostly on the lower epidermis of the lamina. It was also found that plants from the ‘Jutro’ and ‘Aldana’ cultivars sprayed with IBA and IBA + BAP were characterized by the highest yield, as compared with the control plants. In the case of the ‘Jutro’ cultivar, after using the growth regulators, a positive correlation was observed between the assimilation and transpiration rates and the length of stomata, which in consequence produced increased yields.

  19. Multiple oxygen tension environments reveal diverse patterns of transcriptional regulation in primary astrocytes.

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    Wayne Chadwick

    Full Text Available The central nervous system normally functions at O(2 levels which would be regarded as hypoxic by most other tissues. However, most in vitro studies of neurons and astrocytes are conducted under hyperoxic conditions without consideration of O(2-dependent cellular adaptation. We analyzed the reactivity of astrocytes to 1, 4 and 9% O(2 tensions compared to the cell culture standard of 20% O(2, to investigate their ability to sense and translate this O(2 information to transcriptional activity. Variance of ambient O(2 tension for rat astrocytes resulted in profound changes in ribosomal activity, cytoskeletal and energy-regulatory mechanisms and cytokine-related signaling. Clustering of transcriptional regulation patterns revealed four distinct response pattern groups that directionally pivoted around the 4% O(2 tension, or demonstrated coherent ascending/decreasing gene expression patterns in response to diverse oxygen tensions. Immune response and cell cycle/cancer-related signaling pathway transcriptomic subsets were significantly activated with increasing hypoxia, whilst hemostatic and cardiovascular signaling mechanisms were attenuated with increasing hypoxia. Our data indicate that variant O(2 tensions induce specific and physiologically-focused transcript regulation patterns that may underpin important physiological mechanisms that connect higher neurological activity to astrocytic function and ambient oxygen environments. These strongly defined patterns demonstrate a strong bias for physiological transcript programs to pivot around the 4% O(2 tension, while uni-modal programs that do not, appear more related to pathological actions. The functional interaction of these transcriptional 'programs' may serve to regulate the dynamic vascular responsivity of the central nervous system during periods of stress or heightened activity.

  20. Research perspectives on the regulation and physiological functions of FGF21 and its association with NAFLD

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    Takeshi eInagaki

    2015-09-01

    Full Text Available Fibroblast growth factor 21 (FGF21 is a metabolic hormone primarily secreted from the liver and functions in multiple tissues. Various transcription factors induce FGF21 expression in the liver, which indicates that FGF21 is a mediator of multiple environmental cues. FGF21 alters metabolism under starvation conditions, protects the body from energy depletion, and extends life span. Pharmacological administration of FGF21 alleviates dyslipidemia and induces weight loss in obese animals. In addition to the well-studied functions of FG21, several lines of recent evidence indicate a possible link between FGF21 and nonalcoholic fatty liver disease (NAFLD. High serum levels of FGF21 are associated with NAFLD and its risk factors such as endoplasmic reticulum stress and chronic inflammation. In addition, FGF21 alleviates the major risk factors of NAFLD including obesity, dyslipidemia and insulin insensitivity. Thus, FGF21 is a potential drug candidate for diseases such as NAFLD, dyslipidemia, and type 2 diabetes. In this review, the research perspectives of FGF21 and therapeutic potencies of FGF21 as a modulator of NAFLD are summarized.

  1. Phytohormonal regulation of biomass allocation and morphological and physiological traits of leaves in response to environmental changes in Polygonum cuspidatum

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    Daisuke Sugiura

    2016-08-01

    Full Text Available Plants plastically change their morphological and physiological traits in response to environmental changes, which are accompanied by changes in endogenous levels of phytohormones. Although roles of phytohormones in various aspects of plant growth and development were elucidated, their importance in the regulation of biomass allocation was not fully investigated. This study aimed to determine causal relationships among changes in biomass allocation, morphological and physiological traits, and endogenous levels of phytohormones such as gibberellins (GAs and cytokinins (CKs in response to environmental changes in Polygonum cuspidatum. Seedlings of P. cuspidatum were grown under two light intensities, each at three nitrogen availabilities. The seedlings grown in high light intensity and high nitrogen availability (HH were subjected to three additional treatments: defoliating half of the leaves (Def, transferral to low nitrogen availability (LowN or low light intensity (LowL. Biomass allocation at the whole-plant level, morphological and physiological traits of each leaf, and endogenous levels of phytohormones in each leaf and shoot apex were measured. Age-dependent changes in leaf traits were also investigated. After the treatments, endogenous levels of GAs in the shoot apex and leaves significantly increased in Def, decreased in LowN, and did not change in LowL compared with HH seedlings. Among all of the seedlings, the levels of GAs in the shoot apex and leaves were strongly correlated with biomass allocation ratio between leaves and roots. The levels of GAs in the youngest leaves were highest, while the levels of CKs were almost consistent in each leaf. The levels of CKs were positively correlated with leaf nitrogen content in each leaf, whereas the levels of GAs were negatively correlated with the total non-structural carbohydrate content in each leaf. These results support our hypothesis that GAs and CKs are key regulatory factors that control

  2. Physiological condition of juvenile wading birds in relation to multiple landscape stressors in the Florida Everglades: effects of hydrology, prey availability, and mercury bioaccumulation

    Science.gov (United States)

    Herring, Garth; Eagles-Smith, Collin A.; Gawlik, Dale E.; Beerens, James M.; Ackerman, Joshua T.

    2014-01-01

    The physiological condition of juvenile birds can be influenced by multiple ecological stressors, and few studies have concurrently considered the effects of environmental contaminants in combination with ecological attributes that can influence foraging conditions and prey availability. Using three temporally distinct indices of physiological condition, we compared the physiological response of nestling great egrets (Ardea alba) and white ibises (Eudocimus albus) to changing prey availability, hydrology (water depth, recession rate), and mercury exposure in the Florida Everglades. We found that the physiological response of chicks varied between species and among environmental variables. Chick body condition (short-term index) and fecal corticosterone levels (medium-term) were influenced by wetland water depth, prey availability, region, and age, but not by mercury contamination. However, mercury exposure did influence heat shock protein 70 (HSP70) in egret chicks, indicating a longer-term physiological response to contamination. Our results indicate that the physiological condition of egret and ibis chicks were influenced by several environmental stressors, and the time frame of the effect may depend on the specialized foraging behavior of the adults provisioning the chicks.

  3. Physiological condition of juvenile wading birds in relation to multiple landscape stressors in the Florida Everglades: effects of hydrology, prey availability, and mercury bioaccumulation.

    Directory of Open Access Journals (Sweden)

    Garth Herring

    Full Text Available The physiological condition of juvenile birds can be influenced by multiple ecological stressors, and few studies have concurrently considered the effects of environmental contaminants in combination with ecological attributes that can influence foraging conditions and prey availability. Using three temporally distinct indices of physiological condition, we compared the physiological response of nestling great egrets (Ardea alba and white ibises (Eudocimus albus to changing prey availability, hydrology (water depth, recession rate, and mercury exposure in the Florida Everglades. We found that the physiological response of chicks varied between species and among environmental variables. Chick body condition (short-term index and fecal corticosterone levels (medium-term were influenced by wetland water depth, prey availability, region, and age, but not by mercury contamination. However, mercury exposure did influence heat shock protein 70 (HSP70 in egret chicks, indicating a longer-term physiological response to contamination. Our results indicate that the physiological condition of egret and ibis chicks were influenced by several environmental stressors, and the time frame of the effect may depend on the specialized foraging behavior of the adults provisioning the chicks.

  4. Physiological condition of juvenile wading birds in relation to multiple landscape stressors in the Florida Everglades: effects of hydrology, prey availability, and mercury bioaccumulation.

    Science.gov (United States)

    Herring, Garth; Eagles-Smith, Collin A; Gawlik, Dale E; Beerens, James M; Ackerman, Joshua T

    2014-01-01

    The physiological condition of juvenile birds can be influenced by multiple ecological stressors, and few studies have concurrently considered the effects of environmental contaminants in combination with ecological attributes that can influence foraging conditions and prey availability. Using three temporally distinct indices of physiological condition, we compared the physiological response of nestling great egrets (Ardea alba) and white ibises (Eudocimus albus) to changing prey availability, hydrology (water depth, recession rate), and mercury exposure in the Florida Everglades. We found that the physiological response of chicks varied between species and among environmental variables. Chick body condition (short-term index) and fecal corticosterone levels (medium-term) were influenced by wetland water depth, prey availability, region, and age, but not by mercury contamination. However, mercury exposure did influence heat shock protein 70 (HSP70) in egret chicks, indicating a longer-term physiological response to contamination. Our results indicate that the physiological condition of egret and ibis chicks were influenced by several environmental stressors, and the time frame of the effect may depend on the specialized foraging behavior of the adults provisioning the chicks.

  5. PHYSIOLOGICAL REGULATION OF PROTEASE AND ANTIBIOTICS IN PENICILLIUM SP. USING SUBMERGED AND SOLID STATE FERMENTATION TECHNIQUES

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    HAIDER M. HAMZAH

    2009-03-01

    Full Text Available A fungal strain belonging to the genus Penicillium was isolated from soil sample and has been diagnosed as Penicillium sp. according to its morphological characteristics of the colonies on solid media and also microscopical examination of the fungal parts. Antibiotics, protease activity and pH values were determined after cultivation of the fungus using submerged fermentation (SF and solid state fermentation (SSF. The two different patterns of fermentation processes seem to influence the physiological behavior of the fungus differently. Experiments were made using nutrient broth medium (N.B for SF and wheat bran in SSF. The pH values were adjacent to 5.5. Wheat bran was enriched with fish scales and egg shale in a ratio of (1:2:0.005 w/w and the mixture was moistened by adding (30 ml whey solution. After 7 days of incubation, the pH value of SF was increased to 8.0 at 30ºC. The SF was appeared efficient for antibiotics production. Using well diffusion technique the extracted antibiotics solution was active against some pathogenic bacteria such as Staphylococcus aureus, E. coli, Proteus sp., Salmonella sp., Pseudomonas aeruginosa and Streptococcus sp. In SSF relative proteases concentrations were found to be highly reactive than SF. This was proved by the appearance of the zone (20 mm and 32 mm due to the hydrolysis of milk and blood proteins respectively using pH 5.5 at 30ºC for 24 hrs. The activity of proteases was (10.4 U/ml.

  6. Plant growth regulators and ascorbic acid effects on physiological quality of wheat seedlings obtained from deteriorated seeds

    International Nuclear Information System (INIS)

    Moori, S.; Eisv, H.R.

    2017-01-01

    This study attempted to examine the effect of seed priming using plant growth regulators and vitamin C on the physiological traits of non-aged and aged seeds of wheat and their obtained seedlings. Accelerated aging (AA) method (40 degree C, RH=100% for 72h) was used for aging seeds. The seeds were pre-treated by gibberellin (GA), salicylic acid (SA), brassinosteroid (BR), and ascorbic acid (AS). Some seed traits such as germination and electric conductivity (EC) and seedling traits such as malondialdehyde (MDA) content, activity of some antioxidant enzymes, soluble protein content (SP), soluble sugar (SS), and proline were measured seven days after germination. The results showed that accelerated aging of seeds reduces the germination percentage and speed, increases soluble sugar, and reduces soluble protein, activity of catalase (CAT), peroxidase (POD) and superoxide dismutase (SOD) in the seedling. Pre-treatment of the aged seed by GA had the maximum positive impact on seed germination and seedling growth. Priming improved germination indices, quality of seedling, and seedling resistance against the oxidative stress caused by AA. It also improved cell membrane integrity and thus reduced seeds’ EC. Priming increased the activity of CAT, POD and SOD enzymes in both aged and non-aged seeds. When the deteriorated seeds were primed, proline and SS contents of the seedling increased significantly, but SP and MDA decreased. In general, pre-treatment of the non-aged and aged seeds by gibberellin improved the physiological quality of the seed and seedling. (author)

  7. The Mask of Sanity: Facial Expressive, Self-Reported, and Physiological Consequences of Emotion Regulation in Psychopathic Offenders.

    Science.gov (United States)

    Nentjes, Lieke; Bernstein, David P; Meijer, Ewout; Arntz, Arnoud; Wiers, Reinout W

    2016-12-01

    This study investigated the physiological, self-reported, and facial correlates of emotion regulation in psychopathy. Specifically, we compared psychopathic offenders (n = 42), nonpsychopathic offenders (n = 42), and nonoffender controls (n = 26) in their ability to inhibit and express emotion while watching affective films (fear, happy, and sad). Results showed that all participants were capable of drastically diminishing facial emotions under inhibition instructions. Contrary to expectation, psychopaths were not superior in adopting such a "poker face." Further, the inhibition of emotion was associated with cardiovascular changes, an effect that was also not dependent on psychopathy (or its factors), suggesting emotion inhibition to be an effortful process in psychopaths as well. Interestingly, psychopathic offenders did not differ from nonpsychopaths in the capacity to show content-appropriate facial emotions during the expression condition. Taken together, these data challenge the view that psychopathy is associated with either superior emotional inhibitory capacities or a generalized impairment in showing facial affect.

  8. Effect of regulated deficit irrigation on the morphology, physiology, carbon allocation and nonstructural carbohydrates of three Kentucky bluegrasses

    International Nuclear Information System (INIS)

    Liu, J. R.; Ma, L.; Liu, Y. K.; Liu, T. J.; Lu, J. N.; Wang, D. N.

    2015-01-01

    Regulated deficit irrigation (RDI) has been assessed in a wide number of field and fruit crops. However, few are the studies dealing with turfgrass. This study was conducted to investigate the morphology, physiology and carbon metabolic responses to regulated deficit irrigation for three Kentucky bluegrass (Poa pratensis L.) cultivars. Three Kentucky bluegrass cultivars were grown in PVC (polyvinyl chloride) tubes in a greenhouse and subjected to three soil water treatments in a growth chamber: 1) full irrigation; 2) drought stress, 21 days without water after full irrigation; and 3) drought recovery, stressed plants were re-watered for an additional 21 d. The present study indicated that drought resulted in a decline in turf quality (TQ), leaf relative water content (RWC), and photochemical efficiency (Fv/Fm) and an increase in electrolyte leakage (EL) for the cultivars. The turf quality, RWC, and Fv/Fm of the three Kentucky bluegrass cultivars increased with re-watering. The allocation of /sup 14/ C increased in the roots of these cultivars during the initial phase of drought stress, where a /sup 14/ C distribution shift from the roots to the stem and leaves appeared with further drought stress. Moreover, there was a significant accumulation of total nonstructural carbohydrates (TNC) in the leaves and stem. The TNC content in the leaves, stem, and roots did not completely return to the control levels following 21 d of re-watering, which was consistent with the recovery of TQ, RWC, Fv/Fm, and EL. In addition, during the re-watering treatment, the reduction in the TNC content may be due to increases in the demand or usage as a result of a rapid recovery in the growth and physiological activities as shown by increased TQ, RWC, and Fv/Fm and decreased EL. Our results suggested that the changes in the carbon allocation model and the accumulation and storage of TNC, as well as the changes in TQ, RWC, Fv/Fm, and EL, for the three cultivars are an adaptive reaction to

  9. L-3,4-Dihydroxyphenylalanine (l-DOPA) induces neuroendocrinological, physiological, and immunological regulation in white shrimp, Litopenaeus vannamei.

    Science.gov (United States)

    Mapanao, Ratchaneegorn; Kuo, Hsin-Wei; Chang, Chin-Chuan; Liu, Kuan-Fu; Cheng, Winton

    2018-03-01

    L-3,4-Dihydroxyphenylalanine (l-DOPA) is a precursor for dopamine (DA) synthesis. Assessments were conducted to analyze the effects of l-DOPA on mediating regulation of neuroendocrinological, immunological, and physiological parameters in the shrimp, Litopenaeus vannamei when they were individually injected with 0.01 N HCl or l-DOPA at 0.5 or 1.0 μmol shrimp -1 for 60, 120, and 240 min. For catecholamine synthesis evaluation, tyrosine hydroxylase (TH) and DA beta hydroxylase (DBH) activities, l-DOPA, DA, and norepinephrine (NE) levels in hemolymph were determined. The total hemocyte count (THC), differential hemocyte count (DHC), phenoloxidase (PO) activity, respiratory bursts (RBs), superoxide dismutase (SOD) activity, phagocytic activity, and clearance efficiency in response to the pathogen, Vibrio alginolyticus were assessed for immune responses, and plasma glucose and lactate levels were for physiological response. Results showed that the TH activity, THC, hyaline cells (HCs), and semigranular cells (SGCs) at 120 min, DA levels at 60-240 min, PO activity in hemocytes per 50 μL of hemolymph at 60-120 min, and PO activity per granulocyte (granular cells (GCs) + SGCs) at 60 min significantly increased, but TH activity, l-DOPA levels, GCs, SGCs, and respiratory bursts in hemocytes per 10 μL of hemolymph at 60 min, respiratory bursts per hemocyte and SOD activity at 120 min, phagocytic activity at 60-240 min, and the clearance efficiency at 60-120 min significantly decreased in shrimp injected with l-DOPA at 1.0 μmol shrimp -1 . In another experiment, 60 min after shrimp had received l-DOPA at 0.5 or 1.0 μmol shrimp -1 , they were challenged with an injection of V. alginolyticus at 2 × 10 5  colony-forming units (cfu) shrimp -1 . The injection of l-DOPA at 1.0 μmol shrimp -1 also significantly increased the cumulative mortality of shrimp by 16.7%, compared to the HCl-challenged control after 120 h. These results suggest

  10. Physiological potential of Oryza sativa seeds treated with growth regulators at low temperatures

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    Mara Grohs

    Full Text Available ABSTRACT The rapid and uniform establishment of rice crops is important for improving production. However, this condition is influenced by several factors, including the soil temperature when planting, which may delay seed germination and compromise the final stand. The aim of this study was to evaluate the behaviour of substances which have the effect of growth regulator when applied to the seeds of different rice cultivars under low-temperature conditions. The experiment was carried out in a completely randomised design with four replications in a bi-factorial scheme, where factor A was represented by the different products (gibberellic acid - AG3, tiamethoxam - TMX, Haf Plus® - HAF, and a control with water - TEST, and factor B by the irrigated rice cultivars (IRGA 424, IRGA 425, Puitá INTA CL, and Avaxi CL. In addition, the experiment was repeated at temperatures of 17 °C and 25 °C in order to simulate low-temperature conditions. The results showed that AG3 is effective in increasing seed vigour in the rice cultivars at both temperatures, with the AG3, TMX and HAF responsible for increasing germination percentage only at the temperature of 17 °C. The effect of the products is more pronounced at low temperatures, and is dependent on the cultivar; in cultivars which are sensitive to cold there is no effect from the products used.

  11. Astrocyte-like glial cells physiologically regulate olfactory processing through the modification of ORN-PN synaptic strength in Drosophila.

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    Liu, He; Zhou, Bangyu; Yan, Wenjun; Lei, Zhengchang; Zhao, Xiaoliang; Zhang, Ke; Guo, Aike

    2014-09-01

    Astrocyte-like glial cells are abundant in the central nervous system of adult Drosophila and exhibit morphology similar to astrocytes of mammals. Previous evidence has shown that astrocyte-like glial cells are strongly associated with synapses in the antennal lobe (AL), the first relay of the olfactory system, where olfactory receptor neurons (ORNs) transmit information into projection neurons (PNs). However, the function of astrocyte-like glia in the AL remains obscure. In this study, using in vivo calcium imaging, we found that astrocyte-like glial cells exhibited spontaneous microdomain calcium elevations. Using simultaneous manipulation of glial activity and monitoring of neuronal function, we found that the astrocyte-like glial activation, but not ensheathing glial activation, could inhibit odor-evoked responses of PNs. Ensheathing glial cells are another subtype of glia, and are of functional importance in the AL. Electrophysiological experiments indicated that astrocyte-like glial activation decreased the amplitude and slope of excitatory postsynaptic potentials evoked through electrical stimulation of the antennal nerve. These results suggest that astrocyte-like glial cells may regulate olfactory processing through negative regulation of ORN-PN synaptic strength. Beyond the antennal lobe we observed astrocyte-like glial spontaneous calcium activities in the ventromedial protocerebrum, indicating that astrocyte-like glial spontaneous calcium elevations might be general in the adult fly brain. Overall, our study demonstrates a new function for astrocyte-like glial cells in the physiological modulation of olfactory information transmission, possibly through regulating ORN-PN synapse strength. © 2014 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  12. Functional adaptation to loading of a single bone is neuronally regulated and involves multiple bones.

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    Sample, Susannah J; Behan, Mary; Smith, Lesley; Oldenhoff, William E; Markel, Mark D; Kalscheur, Vicki L; Hao, Zhengling; Miletic, Vjekoslav; Muir, Peter

    2008-09-01

    Regulation of load-induced bone formation is considered a local phenomenon controlled by osteocytes, although it has also been hypothesized that functional adaptation may be neuronally regulated. The aim of this study was to examine bone formation in multiple bones, in response to loading of a single bone, and to determine whether adaptation may be neuronally regulated. Load-induced responses in the left and right ulnas and humeri were determined after loading of the right ulna in male Sprague-Dawley rats (69 +/- 16 days of age). After a single period of loading at -760-, -2000-, or -3750-microepsilon initial peak strain, rats were given calcein to label new bone formation. Bone formation and bone neuropeptide concentrations were determined at 10 days. In one group, temporary neuronal blocking was achieved by perineural anesthesia of the brachial plexus with bupivicaine during loading. We found right ulna loading induces adaptive responses in other bones in both thoracic limbs compared with Sham controls and that neuronal blocking during loading abrogated bone formation in the loaded ulna and other thoracic limb bones. Skeletal adaptation was more evident in distal long bones compared with proximal long bones. We also found that the single period of loading modulated bone neuropeptide concentrations persistently for 10 days. We conclude that functional adaptation to loading of a single bone in young rapidly growing rats is neuronally regulated and involves multiple bones. Persistent changes in bone neuropeptide concentrations after a single loading period suggest that plasticity exists in the innervation of bone.

  13. The genome sequence of Geobacter metallireducens: features of metabolism, physiology and regulation common and dissimilar to Geobacter sulfurreducens

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    Aklujkar, Muktak; Krushkal, Julia; DiBartolo, Genevieve; Lapidus, Alla; Land, Miriam L.; Lovley, Derek R.

    2008-12-01

    Background: The genome sequence of Geobacter metallireducens is the second to be completed from the metal-respiring genus Geobacter, and is compared in this report to that of Geobacter sulfurreducens in order to understand their metabolic, physiological and regulatory similarities and differences. Results: The experimentally observed greater metabolic versatility of G. metallireducens versus G. sulfurreducens is borne out by the presence of more numerous genes for metabolism of organic acids including acetate, propionate, and pyruvate. Although G. metallireducens lacks a dicarboxylic acid transporter, it has acquired a second succinate dehydrogenase/fumarate reductase complex, suggesting that respiration of fumarate was important until recently in its evolutionary history. Vestiges of the molybdate (ModE) regulon of G. sulfurreducens can be detected in G. metallireducens, which has lost the global regulatory protein ModE but retained some putative ModE-binding sites and multiplied certain genes of molybdenum cofactor biosynthesis. Several enzymes of amino acid metabolism are of different origin in the two species, but significant patterns of gene organization are conserved. Whereas most Geobacteraceae are predicted to obtain biosynthetic reducing equivalents from electron transfer pathways via a ferredoxin oxidoreductase, G. metallireducens can derive them from the oxidative pentose phosphate pathway. In addition to the evidence of greater metabolic versatility, the G. metallireducens genome is also remarkable for the abundance of multicopy nucleotide sequences found in intergenic regions and even within genes. Conclusion: The genomic evidence suggests that metabolism, physiology and regulation of gene expression in G. metallireducens may be dramatically different from other Geobacteraceae.

  14. Research on Healthy Anomaly Detection Model Based on Deep Learning from Multiple Time-Series Physiological Signals

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    Kai Wang

    2016-01-01

    Full Text Available Health is vital to every human being. To further improve its already respectable medical technology, the medical community is transitioning towards a proactive approach which anticipates and mitigates risks before getting ill. This approach requires measuring the physiological signals of human and analyzes these data at regular intervals. In this paper, we present a novel approach to apply deep learning in physiological signals analysis that allows doctor to identify latent risks. However, extracting high level information from physiological time-series data is a hard problem faced by the machine learning communities. Therefore, in this approach, we apply model based on convolutional neural network that can automatically learn features from raw physiological signals in an unsupervised manner and then based on the learned features use multivariate Gauss distribution anomaly detection method to detect anomaly data. Our experiment is shown to have a significant performance in physiological signals anomaly detection. So it is a promising tool for doctor to identify early signs of illness even if the criteria are unknown a priori.

  15. The Drosophila Perlecan gene trol regulates multiple signaling pathways in different developmental contexts

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    Perry Trinity L

    2007-11-01

    Full Text Available Abstract Background Heparan sulfate proteoglycans modulate signaling by a variety of growth factors. The mammalian proteoglycan Perlecan binds and regulates signaling by Sonic Hedgehog, Fibroblast Growth Factors (FGFs, Vascular Endothelial Growth Factor (VEGF and Platelet Derived Growth Factor (PDGF, among others, in contexts ranging from angiogenesis and cardiovascular development to cancer progression. The Drosophila Perlecan homolog trol has been shown to regulate the activity of Hedgehog and Branchless (an FGF homolog to control the onset of stem cell proliferation in the developing brain during first instar. Here we extend analysis of trol mutant phenotypes to show that trol is required for a variety of developmental events and modulates signaling by multiple growth factors in different situations. Results Different mutations in trol allow developmental progression to varying extents, suggesting that trol is involved in multiple cell-fate and patterning decisions. Analysis of the initiation of neuroblast proliferation at second instar demonstrated that trol regulates this event by modulating signaling by Hedgehog and Branchless, as it does during first instar. Trol protein is distributed over the surface of the larval brain, near the regulated neuroblasts that reside on the cortical surface. Mutations in trol also decrease the number of circulating plasmatocytes. This is likely to be due to decreased expression of pointed, the response gene for VEGF/PDGF signaling that is required for plasmatocyte proliferation. Trol is found on plasmatocytes, where it could regulate VEGF/PDGF signaling. Finally, we show that in second instar brains but not third instar brain lobes and eye discs, mutations in trol affect signaling by Decapentaplegic (a Transforming Growth Factor family member, Wingless (a Wnt growth factor and Hedgehog. Conclusion These studies extend the known functions of the Drosophila Perlecan homolog trol in both developmental and

  16. Choline Catabolism in Burkholderia thailandensis Is Regulated by Multiple Glutamine Amidotransferase 1-Containing AraC Family Transcriptional Regulators.

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    Nock, Adam M; Wargo, Matthew J

    2016-09-15

    Burkholderia thailandensis is a soil-dwelling bacterium that shares many metabolic pathways with the ecologically similar, but evolutionarily distant, Pseudomonas aeruginosa Among the diverse nutrients it can utilize is choline, metabolizable to the osmoprotectant glycine betaine and subsequently catabolized as a source of carbon and nitrogen, similar to P. aeruginosa Orthologs of genes in the choline catabolic pathway in these two bacteria showed distinct differences in gene arrangement as well as an additional orthologous transcriptional regulator in B. thailandensis In this study, we showed that multiple glutamine amidotransferase 1 (GATase 1)-containing AraC family transcription regulators (GATRs) are involved in regulation of the B. thailandensis choline catabolic pathway (gbdR1, gbdR2, and souR). Using genetic analyses and sequencing the transcriptome in the presence and absence of choline, we identified the likely regulons of gbdR1 (BTH_II1869) and gbdR2 (BTH_II0968). We also identified a functional ortholog for P. aeruginosa souR, a GATR that regulates the metabolism of sarcosine to glycine. GbdR1 is absolutely required for expression of the choline catabolic locus, similar to P. aeruginosa GbdR, while GbdR2 is important to increase expression of the catabolic locus. Additionally, the B. thailandensis SouR ortholog (BTH_II0994) is required for catabolism of choline and its metabolites as carbon sources, whereas in P. aeruginosa, SouR function can by bypassed by GbdR. The strategy employed by B. thailandensis represents a distinct regulatory solution to control choline catabolism and thus provides both an evolutionary counterpoint and an experimental system to analyze the acquisition and regulation of this pathway during environmental growth and infection. Many proteobacteria that occupy similar environmental niches have horizontally acquired orthologous genes for metabolism of compounds useful in their shared environment. The arrangement and differential

  17. MiR-155 Enhances Insulin Sensitivity by Coordinated Regulation of Multiple Genes in Mice

    Science.gov (United States)

    Lin, Taoyan; Lin, Xia; Chen, Li; Zeng, Hui; Han, Yanjiang; Wu, Lihong; Huang, Shun; Wang, Meng; Huang, Shenhao; Xie, Raoying; Liang, Liqi; Liu, Yu; Liu, Ruiyu; Zhang, Tingting; Li, Jing; Wang, Shengchun; Sun, Penghui; Huang, Wenhua; Yao, Kaitai; Xu, Kang; Du, Tao; Xiao, Dong

    2016-01-01

    miR-155 plays critical roles in numerous physiological and pathological processes, however, its function in the regulation of blood glucose homeostasis and insulin sensitivity and underlying mechanisms remain unknown. Here, we reveal that miR-155 levels are downregulated in serum from type 2 diabetes (T2D) patients, suggesting that miR-155 might be involved in blood glucose control and diabetes. Gain-of-function and loss-of-function studies in mice demonstrate that miR-155 has no effects on the pancreatic β-cell proliferation and function. Global transgenic overexpression of miR-155 in mice leads to hypoglycaemia, improved glucose tolerance and insulin sensitivity. Conversely, miR-155 deficiency in mice causes hyperglycemia, impaired glucose tolerance and insulin resistance. In addition, consistent with a positive regulatory role of miR-155 in glucose metabolism, miR-155 positively modulates glucose uptake in all cell types examined, while mice overexpressing miR-155 transgene show enhanced glycolysis, and insulin-stimulated AKT and IRS-1 phosphorylation in liver, adipose tissue or skeletal muscle. Furthermore, we reveal these aforementioned phenomena occur, at least partially, through miR-155-mediated repression of important negative regulators (i.e. C/EBPβ, HDAC4 and SOCS1) of insulin signaling. Taken together, these findings demonstrate, for the first time, that miR-155 is a positive regulator of insulin sensitivity with potential applications for diabetes treatment. PMID:27711113

  18. Estrogens regulate the hepatic effects of Growth Hormone, a hormonal interplay with multiple fates

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    Leandro eFernandez-Perez

    2013-06-01

    Full Text Available The liver responds to estrogens and GH which are critical regulators of body growth, gender-related hepatic functions, and intermediate metabolism. The effects of estrogens on liver can be direct, through the direct actions of hepatic ER, or indirect, which include the crosstalk with endocrine, metabolic, and sex-differentiated functions of GH. Most previous studies have been focused on the influence of estrogens on pituitary GH secretion, which has a great impact on hepatic transcriptional regulation. However, there is strong evidence that estrogens can influence the GH-regulated endocrine and metabolic functions in the human liver by acting at the level of GHR-STAT5 signaling pathway. This cross-talk is relevant because the widespread exposition of estrogen or estrogen-related compounds in human. Therefore, GH or estrogen signaling deficiency as well as the influence of estrogens on GH biology can cause a dramatic impact in liver physiology during mammalian development and in adulthood. In this review, we will summarize the current status of the influence of estrogen on GH actions in liver. A better understanding of estrogen-GH interplay in liver will lead to improved therapy of children with growth disorders and of adults with GH deficiency.

  19. Sodium Glucose Cotransporter 2 (SGLT2 Plays as a Physiological Glucose Sensor and Regulates Cellular Contractility in Rat Mesangial Cells.

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    Masanori Wakisaka

    Full Text Available Mesangial cells play an important role in regulating glomerular filtration by altering their cellular tone. We report the presence of a sodium glucose cotransporter (SGLT in rat mesangial cells. This study in rat mesangial cells aimed to evaluate the expression and role of SGLT2.The SGLT2 expression in rat mesangial cells was assessed by Western blotting and reverse transcription-polymerase chain reaction (RT-PCR. Changes in the mesangial cell surface area at different glucose concentrations and the effects of extracellular Na+ and Ca2+ and of SGLT and Na+/Ca2+ exchanger (NCX inhibitors on cellular size were determined. The cellular sizes and the contractile response were examined during a 6-day incubation with high glucose with or without phlorizin, an SGLT inhibitor.Western blotting revealed an SGLT2 band, and RT-PCR analysis of SGLT2 revealed the predicted 422-bp band in both rat mesangial and renal proximal tubular epithelial cells. The cell surface area changed according to the extracellular glucose concentration. The glucose-induced contraction was abolished by the absence of either extracellular Na+ or Ca2+ and by SGLT and NCX inhibitors. Under the high glucose condition, the cell size decreased for 2 days and increased afterwards; these cells did not contract in response to angiotensin II, and the SGLT inhibitor restored the abolished contraction.These data suggest that SGLT2 is expressed in rat mesangial cells, acts as a normal physiological glucose sensor and regulates cellular contractility in rat mesangial cells.

  20. Physiological regulation of isocitrate dehydrogenase and the role of 2-oxoglutarate in Prochlorococcus sp. strain PCC 9511.

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    María Agustina Domínguez-Martín

    Full Text Available The enzyme isocitrate dehydrogenase (ICDH; EC 1.1.1.42 catalyzes the oxidative decarboxylation of isocitrate, to produce 2-oxoglutarate. The incompleteness of the tricarboxylic acids cycle in marine cyanobacteria confers a special importance to isocitrate dehydrogenase in the C/N balance, since 2-oxoglutarate can only be metabolized through the glutamine synthetase/glutamate synthase pathway. The physiological regulation of isocitrate dehydrogenase was studied in cultures of Prochlorococcus sp. strain PCC 9511, by measuring enzyme activity and concentration using the NADPH production assay and Western blotting, respectively. The enzyme activity showed little changes under nitrogen or phosphorus starvation, or upon addition of the inhibitors DCMU, DBMIB and MSX. Azaserine, an inhibitor of glutamate synthase, induced clear increases in the isocitrate dehydrogenase activity and icd gene expression after 24 h, and also in the 2-oxoglutarate concentration. Iron starvation had the most significant effect, inducing a complete loss of isocitrate dehydrogenase activity, possibly mediated by a process of oxidative inactivation, while its concentration was unaffected. Our results suggest that isocitrate dehydrogenase responds to changes in the intracellular concentration of 2-oxoglutarate and to the redox status of the cells in Prochlorococcus.

  1. Response of morphological and physiological growth attributes to foliar application of plant growth regulators in gladiolus 'white prosperity'

    International Nuclear Information System (INIS)

    Sajjad, Y.; Jaskani, M. J.; Qasim, M.

    2014-01-01

    Gladiolus is very popular among ornamental bulbous plants mainly used as cut flower and greatly demanded in the world floral market. Production of inferior quality spikes is one of the major hurdles for their export. The research was conducted under Faisalabad conditions to evaluate the use of plant growth regulators in order to improve the vegetative, floral and physiological attributes. Gladiolus plants were sprayed thrice with different concentrations (0.1, 0.4, 0.7 and 1mM) of gibberellic acid, benzylaminopurine and salicylic acid at three leaf stage, five leaf stage and slipping stage. Foliar application of 1mM gibberellic acid increased the plant height (122.14cm), spike length (58.41cm), florets spike-1 (13.49), corm diameter (4.43cm), corm weight (25.34g) and total cormel weight (20.45g) compared to benzylaminopurine and salicylic acid. Gibberellic acid at 1mM concentration also increased the total chlorophyll content to 7.72mg/g, total carotenoids (1.61mg/g), total soluble sugars (3.68mg/g) followed by application of benzylaminopurine. Salicylic acid application at 1mM concentration decreased the number of days to flower (64.93) compared to 76.12 days in non treated plants. (author)

  2. The regulation of coralline algal physiology, an in situ study of Corallina officinalis (Corallinales, Rhodophyta

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    C. J. Williamson

    2017-10-01

    Full Text Available Calcified macroalgae are critical components of marine ecosystems worldwide, but face considerable threat both from climate change (increasing water temperatures and ocean acidification (decreasing ocean pH and carbonate saturation. It is thus fundamental to constrain the relationships between key abiotic stressors and the physiological processes that govern coralline algal growth and survival. Here we characterize the complex relationships between the abiotic environment of rock pool habitats and the physiology of the geniculate red coralline alga, Corallina officinalis (Corallinales, Rhodophyta. Paired assessment of irradiance, water temperature and carbonate chemistry, with C. officinalis net production (NP, respiration (R and net calcification (NG was performed in a south-western UK field site, at multiple temporal scales (seasonal, diurnal and tidal. Strong seasonality was observed in NP and night-time R, with a Pmax of 22.35 µmol DIC (g DW−1 h−1, Ek of 300 µmol photons m−2 s−1 and R of 3.29 µmol DIC (g DW−1 h−1 determined across the complete annual cycle. NP showed a significant exponential relationship with irradiance (R2 = 0.67, although was temperature dependent given ambient irradiance  > Ek for the majority of the annual cycle. Over tidal emersion periods, dynamics in NP highlighted the ability of C. officinalis to acquire inorganic carbon despite significant fluctuations in carbonate chemistry. Across all data, NG was highly predictable (R2 = 0.80 by irradiance, water temperature and carbonate chemistry, providing a NGmax of 3.94 µmol CaCO3 (g DW−1 h−1 and Ek of 113 µmol photons m−2 s−1. Light NG showed strong seasonality and significant coupling to NP (R2 = 0.65 as opposed to rock pool water carbonate saturation. In contrast, the direction of dark NG (dissolution vs. precipitation was strongly related to carbonate saturation, mimicking

  3. Robust set-point regulation for ecological models with multiple management goals.

    Science.gov (United States)

    Guiver, Chris; Mueller, Markus; Hodgson, Dave; Townley, Stuart

    2016-05-01

    Population managers will often have to deal with problems of meeting multiple goals, for example, keeping at specific levels both the total population and population abundances in given stage-classes of a stratified population. In control engineering, such set-point regulation problems are commonly tackled using multi-input, multi-output proportional and integral (PI) feedback controllers. Building on our recent results for population management with single goals, we develop a PI control approach in a context of multi-objective population management. We show that robust set-point regulation is achieved by using a modified PI controller with saturation and anti-windup elements, both described in the paper, and illustrate the theory with examples. Our results apply more generally to linear control systems with positive state variables, including a class of infinite-dimensional systems, and thus have broader appeal.

  4. Addressing the regulatory and scientific challenges in multiple sclerosis--a statement from the EU regulators.

    Science.gov (United States)

    Balabanov, Pavel; Haas, Manuel; Elferink, Andre; Bakchine, Serge; Broich, Karl

    2014-09-01

    Improving and facilitating the process of making new drugs available to patients with multiple sclerosis (MS) requires cooperation among the regulators and other stakeholders. This cooperation will also positively contribute towards developing guidelines of the highest quality in medical, regulatory and scientific aspects. This would be beneficial both in areas that require further guideline development, but also in fields where existing guidance should be adapted to take into account evolution in science. Considering the input from all stakeholders, the European Medicines Agency confirmed its intention to update the relevant guideline and apply a flexible approach towards new drug development strategies in MS. This article is the first official position from the EU regulators, presenting the main changes to be expected in the guidance document. © The Author(s) 2014.

  5. Autonomic cardiac regulation and morpho-physiological responses to eight week training preparation in junior soccer players

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    Michal Botek

    2014-09-01

    Full Text Available Background: Training preparation in soccer is thought to improve body composition and performance level, especially the maximal aerobic capacity (VO2max. However, an enhancement in performance may be attenuated by the increase of fatigue. Heart rate variability (HRV as a non-invasive index of autonomic nervous system (ANS activity has been considered to be a sensitive tool in fatigue assessment. Objective: This study was focused to evaluate the response of ANS activity and morpho-physiological parameters to eight week training preparation. Methods: Study included 12 trained soccer players aged 17.2 ± 1.2 years. Athletes underwent pre- and post-preparation testing that included the ANS activity assessment by spectral analysis of HRV in supine and upright position. Further, body composition was analyzed via electrical bio-impedance method and physiological parameters were assessed during maximal stress tests. ANS activity and subjective feeling of fatigue was assessed continuously within subsequent weeks of preparation. Results: No significant differences in all HRV variables within weeks were found. Pre vs. post analyses revealed a significant (p < .05 increase in body weight, fat free mass, body mass index, and peak power. A significant decline in mean maximal heart rate (HR and resting HR at standing was identified at the end of preparation. Since no significant changes between pre- post-preparation in the mean VO2max occurred, the positive correlation between the individual change in VO2max and the vagally related HRV [supine LnHF (r = .78, Ln rMSSD (r = .63, and the standing LnHF (r = .73, p < .05] was found. Conclusions: This study showed that an 8 week training program modified particularly fat free mass and short-term endurance, whereas both the autonomic cardiac regulation and the feeling of fatigue remained almost unaffected. Standing position seems to be more sensitive in terms of the HR response in relation to fatigue

  6. A system dynamics model integrating physiology and biochemical regulation predicts extent of crassulacean acid metabolism (CAM) phases.

    Science.gov (United States)

    Owen, Nick A; Griffiths, Howard

    2013-12-01

    A system dynamics (SD) approach was taken to model crassulacean acid metabolism (CAM) expression from measured biochemical and physiological constants. SD emphasizes state-dependent feedback interaction to describe the emergent properties of a complex system. These mechanisms maintain biological systems with homeostatic limits on a temporal basis. Previous empirical studies on CAM have correlated biological constants (e.g. enzyme kinetic parameters) with expression over the CAM diel cycle. The SD model integrates these constants within the architecture of the CAM 'system'. This allowed quantitative causal connections to be established between biological inputs and the four distinct phases of CAM delineated by gas exchange and malic acid accumulation traits. Regulation at flow junctions (e.g. stomatal and mesophyll conductance, and malic acid transport across the tonoplast) that are subject to feedback control (e.g. stomatal aperture, malic acid inhibition of phosphoenolpyruvate carboxylase, and enzyme kinetics) was simulated. Simulated expression for the leaf-succulent Kalanchoë daigremontiana and more succulent tissues of Agave tequilana showed strong correlation with measured gas exchange and malic acid accumulation (R(2)  = 0.912 and 0.937, respectively, for K. daigremontiana and R(2)  = 0.928 and 0.942, respectively, for A. tequilana). Sensitivity analyses were conducted to quantitatively identify determinants of diel CO2 uptake. The transition in CAM expression from low to high volume/area tissues (elimination of phase II-IV carbon-uptake signatures) was achieved largely by the manipulation three input parameters. © 2013 The Authors. New Phytologist © 2013 New Phytologist Trust.

  7. Exogenously applied plant growth regulators enhance the morpho-physiological growth and yield of rice under high temperature

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    Shah Fahad

    2016-08-01

    Full Text Available A two-year experiment was conducted to ascertain the effects of exogenously applied plant growth regulators (PGR on rice growth and yield attributes under high day (HDT and high night temperature (HNT. Two rice cultivars (IR-64 and Huanghuazhan were subjected to temperature treatments in controlled growth chambers and four different combinations of ascorbic acid (Vc, alpha-tocopherol (Ve, brassinosteroids (Br, methyl jasmonates (MeJA and triazoles (Tr were applied. High temperature severely affected rice morphology, and also reduced leaf area, above- and below-ground biomass, photosynthesis, and water use efficiency, while increased the leaf water potential of both rice cultivars. Grain yield and its related attributes except number of panicles, were reduced under high temperature. The HDT posed more negative effects on rice physiological attributes, while HNT was more detrimental for grain formation and yield. The Huanghuazhan performed better than IR-64 under high temperature stress with better growth and higher grain yield. Exogenous application of PGRs was helpful in alleviating the adverse effects of high temperature. Among PGR combinations, the Vc+Ve+MejA+Br was the most effective treatment for both cultivars under high temperature stress. The highest grain production by Vc+Ve+MejA+Br treated plants was due to enhanced photosynthesis, spikelet fertility and grain filling, which compensated the adversities of high temperature stress. Taken together, these results will be of worth for further understanding the adaptation and survival mechanisms of rice to high temperature and will assist in developing heat-resistant rice germplasm in future.

  8. ANGUSTIFOLIA mediates one of the multiple SCRAMBLED signaling pathways regulating cell growth pattern in Arabidopsis thaliana.

    Science.gov (United States)

    Kwak, Su-Hwan; Song, Sang-Kee; Lee, Myeong Min; Schiefelbein, John

    2015-09-25

    In Arabidopsis thaliana, an atypical leucine-rich repeat receptor-like kinase, SCRAMBLED (SCM), is required for multiple developmental processes including root epidermal cell fate determination, silique dehiscence, inflorescence growth, ovule morphogenesis, and tissue morphology. Previous work suggested that SCM regulates these multiple pathways using distinct mechanisms via interactions with specific downstream factors. ANGUSTIFOLIA (AN) is known to regulate cell and tissue morphogenesis by influencing cortical microtubule arrangement, and recently, the AN protein was reported to interact with the SCM protein. Therefore, we examined whether AN might be responsible for mediating some of the SCM-dependent phenotypes. We discovered that both scm and an mutant lines cause an abnormal spiral or twisting growth of roots, but only the scm mutant affected root epidermal patterning. The siliques of the an and scm mutants also exhibited spiral growth, as previously reported, but only the scm mutant altered silique dehiscence. Interestingly, we discovered that the spiral growth of roots and siliques of the scm mutant is rescued by a truncated SCM protein that lacks its kinase domain, and that a juxtamembrane domain of SCM was sufficient for AN binding in the yeast two-hybrid analysis. These results suggest that the AN protein is one of the critical downstream factors of SCM pathways specifically responsible for mediating its effects on cell/tissue morphogenesis through cortical microtubule arrangement. Copyright © 2015 Elsevier Inc. All rights reserved.

  9. Inhibition of Ubc13-mediated Ubiquitination by GPS2 Regulates Multiple Stages of B Cell Development.

    Science.gov (United States)

    Lentucci, Claudia; Belkina, Anna C; Cederquist, Carly T; Chan, Michelle; Johnson, Holly E; Prasad, Sherry; Lopacinski, Amanda; Nikolajczyk, Barbara S; Monti, Stefano; Snyder-Cappione, Jennifer; Tanasa, Bogdan; Cardamone, M Dafne; Perissi, Valentina

    2017-02-17

    Non-proteolytic ubiquitin signaling mediated by Lys 63 ubiquitin chains plays a critical role in multiple pathways that are key to the development and activation of immune cells. Our previous work indicates that GPS2 (G-protein Pathway Suppressor 2) is a multifunctional protein regulating TNFα signaling and lipid metabolism in the adipose tissue through modulation of Lys 63 ubiquitination events. However, the full extent of GPS2-mediated regulation of ubiquitination and the underlying molecular mechanisms are unknown. Here, we report that GPS2 is required for restricting the activation of TLR and BCR signaling pathways and the AKT/FOXO1 pathway in immune cells based on direct inhibition of Ubc13 enzymatic activity. Relevance of this regulatory strategy is confirmed in vivo by B cell-targeted deletion of GPS2, resulting in developmental defects at multiple stages of B cell differentiation. Together, these findings reveal that GPS2 genomic and non-genomic functions are critical for the development and cellular homeostasis of B cells. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  10. Regulation of hTERT by BCR-ABL at multiple levels in K562 cells

    International Nuclear Information System (INIS)

    Chai, Juin Hsien; Zhang, Yong; Tan, Wei Han; Chng, Wee Joo; Li, Baojie; Wang, Xueying

    2011-01-01

    The cytogenetic characteristic of Chronic Myeloid Leukemia (CML) is the formation of the Philadelphia chromosome gene product, BCR-ABL. Given that BCR-ABL is the specific target of Gleevec in CML treatment, we investigated the regulation of the catalytic component of telomerase, hTERT, by BCR-ABL at multiple levels in K562 cells. Molecular techniques such as over expression, knockdown, real-time PCR, immunoprecipitation, western blotting, reporter assay, confocal microscopy, telomerase assays and microarray were used to suggest that hTERT expression and activity is modulated by BCR-ABL at multiple levels. Our results suggest that BCR-ABL plays an important role in regulating hTERT in K562 (BCR-ABL positive human leukemia) cells. When Gleevec inhibited the tyrosine kinase activity of BCR-ABL, phosphorylation of hTERT was downregulated, therefore suggesting a positive correlation between BCR-ABL and hTERT. Gleevec treatment inhibited hTERT at mRNA level and significantly reduced telomerase activity (TA) in K562 cells, but not in HL60 or Jurkat cells (BCR-ABL negative cells). We also demonstrated that the transcription factor STAT5a plays a critical role in hTERT gene regulation in K562 cells. Knockdown of STAT5a, but not STAT5b, resulted in a marked downregulation of hTERT mRNA level, TA and hTERT protein level in K562 cells. Furthermore, translocation of hTERT from nucleoli to nucleoplasm was observed in K562 cells induced by Gleevec. Our data reveal that BCR-ABL can regulate TA at multiple levels, including transcription, post-translational level, and proper localization. Thus, suppression of cell growth and induction of apoptosis by Gleevec treatment may be partially due to TA inhibition. Additionally, we have identified STAT5a as critical mediator of the hTERT gene expression in BCR-ABL positive CML cells, suggesting that targeting STAT5a may be a promising therapeutic strategy for BCR-ABL positive CML patients

  11. [New theory of holistic integrative physiology and medicine. III: New insight of neurohumoral mechanism and pattern of control and regulation for core axe of respiration, circulation and metabolism].

    Science.gov (United States)

    Sun, Xing-guo

    2015-07-01

    Systemic mechanism of neurohumoral control and regulation for human is limited. We used the new theory of holistic integrative physiology and medicine to approach the mechanism and pattern of neurohumoral control and regulation for life. As the core of human life, there are two core axes of functions. The first one is the common goal of respiration and circulation to transport oxygen and carbon dioxide for cells, and the second one is the goal of gastrointestinal tract and circulation to transport energy material and metabolic product for cells. These two core axes maintain the metabolism. The neurohumoral regulation is holistically integrated and unified for all functions in human body. We simplified explain the mechanism of neurohumoral control and regulation life (respiration and circulation) as the example pattern of sound system. Based upon integrated regulation of life, we described the neurohumoral pattern to control respiration and circulation.

  12. C/EBPβ Mediates Growth Hormone-Regulated Expression of Multiple Target Genes

    Science.gov (United States)

    Cui, Tracy X.; Lin, Grace; LaPensee, Christopher R.; Calinescu, Anda-Alexandra; Rathore, Maanjot; Streeter, Cale; Piwien-Pilipuk, Graciela; Lanning, Nathan; Jin, Hui; Carter-Su, Christin; Qin, Zhaohui S.

    2011-01-01

    Regulation of c-Fos transcription by GH is mediated by CCAAT/enhancer binding protein β (C/EBPβ). This study examines the role of C/EBPβ in mediating GH activation of other early response genes, including Cyr61, Btg2, Socs3, Zfp36, and Socs1. C/EBPβ depletion using short hairpin RNA impaired responsiveness of these genes to GH, as seen for c-Fos. Rescue with wild-type C/EBPβ led to GH-dependent recruitment of the coactivator p300 to the c-Fos promoter. In contrast, rescue with C/EBPβ mutated at the ERK phosphorylation site at T188 failed to induce GH-dependent recruitment of p300, indicating that ERK-mediated phosphorylation of C/EBPβ at T188 is required for GH-induced recruitment of p300 to c-Fos. GH also induced the occupancy of phosphorylated C/EBPβ and p300 on Cyr61, Btg2, and Socs3 at predicted C/EBP-cAMP response element-binding protein motifs in their promoters. Consistent with a role for ERKs in GH-induced expression of these genes, treatment with U0126 to block ERK phosphorylation inhibited their GH-induced expression. In contrast, GH-dependent expression of Zfp36 and Socs1 was not inhibited by U0126. Thus, induction of multiple early response genes by GH in 3T3-F442A cells is mediated by C/EBPβ. A subset of these genes is regulated similarly to c-Fos, through a mechanism involving GH-stimulated ERK 1/2 activation, phosphorylation of C/EBPβ, and recruitment of p300. Overall, these studies suggest that C/EBPβ, like the signal transducer and activator of transcription proteins, regulates multiple genes in response to GH. PMID:21292824

  13. Fine tuning of RFX/DAF-19-regulated target gene expression through binding to multiple sites in Caenorhabditis elegans

    OpenAIRE

    Chu, Jeffery S. C.; Tarailo-Graovac, Maja; Zhang, Di; Wang, Jun; Uyar, Bora; Tu, Domena; Trinh, Joanne; Baillie, David L.; Chen, Nansheng

    2011-01-01

    In humans, mutations of a growing list of regulatory factor X (RFX) target genes have been associated with devastating genetics disease conditions including ciliopathies. However, mechanisms underlying RFX transcription factors (TFs)-mediated gene expression regulation, especially differential gene expression regulation, are largely unknown. In this study, we explore the functional significance of the co-existence of multiple X-box motifs in regulating differential gene expression in Caenorha...

  14. The multiple functions of the endocannabinoid system: a focus on the regulation of food intake

    Directory of Open Access Journals (Sweden)

    Tibiriça Eduardo

    2010-01-01

    Full Text Available Abstract Background Cannabis sativa (also known as marijuana has been cultivated by man for more than 5,000 years. However, there was a rise in its use in the 20th century for recreational, religious or spiritual, and medicinal purposes. The main psychoactive constituent of cannabis, whose structure was identified in the 1960's, is Δ9-tetrahydrocannabinol. On the other hand, the discovery of cannabinoid receptors and their endogenous agonists took place only very recently. In fact, the first cannabinoid receptor (CB1 was cloned in 1990, followed 3 years later by the characterization of a second cannabinoid receptor (CB2. Since the 19th century, the use of cannabis has been reported to stimulate appetite and increase the consumption of sweet and tasty food, sometimes resulting in significant weight gain. The recent description of the endocannabinoid system, not only in the central nervous system but also in peripheral tissues, points to its involvement in the regulation of appetite, food intake and energy metabolism. Consequently, the pharmacological modulation of the over-activity of this system could be useful in the treatment of the metabolic syndrome. Conclusions The endocannabinoid system has important physiological functions not only in the central nervous system but also in peripheral tissues. The activation of central CB1 receptors, particularly in hypothalamic nuclei and in the limbic system, is involved in the regulation of feeding behavior, and especially in the control of the intake of palatable food. In the periphery, cannabinoid receptors are present in adipocytes, skeletal muscle, gastrointestinal tract and liver, modulating energy metabolism.

  15. Effect of regulated deficit irrigation on growth, flowering and physiological responses of potted Syringa meyeri ‘Palibin’

    Directory of Open Access Journals (Sweden)

    Michał Koniarski

    2014-01-01

    Full Text Available The aim of this study was to analyze the physiological and morphological response of Syringa meyeri ‘Palibin’ to different levels of irrigation and to evaluate regulated deficit irrigation (RDI as a possible technique for saving water in nursery production and promoting of flowering. Plants were grown in 3 liter containers in an unheated greenhouse and were subjected to six irrigation treatments for 18 weeks from the be- ginning of June to mid-October 2011. A drip irrigation system was used. Irrigation treatments were established on the basis of evapotranspiration (ETp. Three constant irrigation treatments were used: 1 1 ETp; 2 0.75 ETp; 3 0.5 ETp, while the other three with irrigation varying between phases were as follows: 4 1–0.5–1; 5 1–0.25–1; and 6 0.5–1–0.5 ETp. The 0.75 ETp and 0.5 ETp irrigation regimes adversely affected the growth and visual quality index of plants as well as they resulted in reduced leaf conductance, transpiration, maximum quantum efficiency of photosystem II (Fv/Fm and CCI (chlorophyll content index. Plants grown under the 1–0.5–1 ETp regime had the same morphological parameters as plants grown under the 0.5 ETp treatment. A further reduction of water quantity supplied to plants in the 1–0.25–1 ETp regime resulted in further deterioration of the visual quality index of plants. In this study, the quality index of plants exposed to 0.5–1–0.5 ETp was similar to control plants (1 ETp. These plants were lower, more compact, and had smaller leaves than control plants. The irrigation regimes imposed in this study had no significant effect on the number of floral buds formed in relation to the control regime, except for 1–0.25–1 ETp where this number decreased.

  16. Progranulin acts as a shared chaperone and regulates multiple lysosomal enzymes

    Directory of Open Access Journals (Sweden)

    Jinlong Jian

    2017-09-01

    Full Text Available Multifunctional factor progranulin (PGRN plays an important role in lysosomes, and its mutations and insufficiency are associated with lysosomal storage diseases, including neuronal ceroid lipofuscinosis and Gaucher disease (GD. The first breakthrough in understanding the molecular mechanisms of PGRN as regulator of lysosomal storage diseases came unexpectedly while investigating the role of PGRN in inflammation. Challenged PGRN null mice displayed typical features of GD. In addition, GRN gene variants were identified in GD patients and the serum levels of PGRN were significantly lower in GD patients. PGRN directly binds to and functions as a chaperone of the lysosomal enzyme β-glucocerebrosidase (GCaase, whose mutations cause GD. In addition, its C-terminus containing granulin E domain, termed Pcgin (PGRN C-terminus for GCase Interaction, is required for the association between PGRN and GCase. The concept that PGRN acts as a chaperone of lysosomal enzymes was further supported and extended by a recent article showing that PGRN acts as a chaperone molecule of lysosomal enzyme cathepsin D (CSTD, and the association between PGRN and CSTD is also mediated by PGRN's C-terminal granulin E domain. Collectively, these reports suggest that PGRN may act as a shared chaperone and regulates multiple lysosomal enzymes.

  17. Dual mechanisms regulating glutamate decarboxylases and accumulation of gamma-aminobutyric acid in tea (Camellia sinensis) leaves exposed to multiple stresses.

    Science.gov (United States)

    Mei, Xin; Chen, Yiyong; Zhang, Lingyun; Fu, Xiumin; Wei, Qing; Grierson, Don; Zhou, Ying; Huang, Yahui; Dong, Fang; Yang, Ziyin

    2016-03-29

    γ-Aminobutyric acid (GABA) is one of the major inhibitory neurotransmitters in the central nervous system. It has multiple positive effects on mammalian physiology and is an important bioactive component of tea (Camellia sinensis). GABA generally occurs at a very low level in plants but GABA content increases substantially after exposure to a range of stresses, especially oxygen-deficiency. During processing of tea leaves, a combination of anoxic stress and mechanical damage are essential for the high accumulation of GABA. This is believed to be initiated by a change in glutamate decarboxylase activity, but the underlying mechanisms are unclear. In the present study we characterized factors regulating the expression and activity of three tea glutamate decarboxylase genes (CsGAD1, 2, and 3), and their encoded enzymes. The results suggests that, unlike the model plant Arabidopsis thaliana, there are dual mechanisms regulating the accumulation of GABA in tea leaves exposed to multiple stresses, including activation of CsGAD1 enzymatic activity by calmodulin upon the onset of the stress and accumulation of high levels of CsGAD2 mRNA induced by a combination of anoxic stress and mechanical damage.

  18. Plant growth regulator interactions in physiological processes for controlling plant regeneration and in vitro development of Tulbaghia simmleri

    Czech Academy of Sciences Publication Activity Database

    Kumari, A.; Baskaran, P.; Plačková, Lenka; Omámiková, Hana; Nisler, Jaroslav; Doležal, Karel; Van Staden, J.

    2018-01-01

    Roč. 223, APR (2018), s. 65-71 ISSN 0176-1617 R&D Projects: GA MŠk(CZ) LO1204 Institutional support: RVO:61389030 Keywords : Endogenous hormone * Exogenous hormone application * In vitro regeneration * Ornamental and medicinal plant * Physiological process * Tulbaghia simmleri Subject RIV: EB - Genetics ; Molecular Biology OBOR OECD: Plant sciences, botany Impact factor: 3.121, year: 2016

  19. Regulation of average 24h human plasma leptin level; the influence of exercise and physiological changes in energy balance.

    NARCIS (Netherlands)

    Aggel-Leijssen, D.P.; van Baak, M.A.; Tenenbaum, R.; Campfield, L.A.; Saris, W.H.M.

    1999-01-01

    OBJECTIVE: The effects of short-term moderate physiological changes in energy flux and energy balance, by exercise and over- or underfeeding, on a 24h plasma leptin profile, were investigated. DESIGN: Subjects were studied over 24h in four randomized conditions: no exercise/energy balance (energy

  20. The Assessment of Cognitive Emotion Regulation Strategies, Sensory Processing Sensitivity and Anxiety Sensitivity in Patients with Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    Esmeil Soleymani

    2016-11-01

    Full Text Available Abstract Background: The purpose of this study was to compare the cognitive emotional regulation strategies, sensory processing sensitivity and anxiety sensitivity in patients with multiple sclerosis and normal people. Materials and Methods: Statistical population of this study was all of patients with multiple sclerosis that referred to M.S association of Iran in the tehran. Sample of this study was 30 individuals of patients with multiple sclerosis selected by available sampling method and were matched with 30 individuals of normal people. Two groups completed cognitive emotion regulation, high sensory processing sensitivity and anxiety sensitivity questionnaires. Data were analyzed by one-way analysis of variance and Multivariate Analysis of Variance. Results: The results indicated that there is significant difference between two groups in view of cognitive emotion regulation strategies in which the mean of scores of patients with multiple sclerosis in maladaptive strategies of self- blame, catastrophizing and other blame were more than normal people and mean of scores of them in adaptive strategies of positive refocusing, positive reappraisal and putting into perspective were less than normal people. The results also indicated that there is a significant difference between two groups in anxiety sensitivity and sensory processing sensitivity. Conclusion: The most of emotional problems in patients with multiple sclerosis can be the result of more application of maladaptive strategies of cognitive emotion regulation, high sensory processing sensitivity and high anxiety sensitivity.

  1. Effects of Goal Relations on Self-Regulated Learning in Multiple Goal Pursuits: Performance, the Self-Regulatory Process, and Task Enjoyment

    Science.gov (United States)

    Lee, Hyunjoo

    2012-01-01

    The purpose of this study was to investigate the effects of goal relations on self-regulation in the pursuit of multiple goals, focusing on self-regulated performance, the self-regulatory process, and task enjoyment. The effect of multiple goal relations on self-regulation was explored in a set of three studies. Goal relations were divided into…

  2. Carbon storage regulator A contributes to the virulence of Haemophilus ducreyi in humans by multiple mechanisms.

    Science.gov (United States)

    Gangaiah, Dharanesh; Li, Wei; Fortney, Kate R; Janowicz, Diane M; Ellinger, Sheila; Zwickl, Beth; Katz, Barry P; Spinola, Stanley M

    2013-02-01

    The carbon storage regulator A (CsrA) controls a wide variety of bacterial processes, including metabolism, adherence, stress responses, and virulence. Haemophilus ducreyi, the causative agent of chancroid, harbors a homolog of csrA. Here, we generated an unmarked, in-frame deletion mutant of csrA to assess its contribution to H. ducreyi pathogenesis. In human inoculation experiments, the csrA mutant was partially attenuated for pustule formation compared to its parent. Deletion of csrA resulted in decreased adherence of H. ducreyi to human foreskin fibroblasts (HFF); Flp1 and Flp2, the determinants of H. ducreyi adherence to HFF cells, were downregulated in the csrA mutant. Compared to its parent, the csrA mutant had a significantly reduced ability to tolerate oxidative stress and heat shock. The enhanced sensitivity of the mutant to oxidative stress was more pronounced in bacteria grown to stationary phase compared to that in bacteria grown to mid-log phase. The csrA mutant also had a significant survival defect within human macrophages when the bacteria were grown to stationary phase but not to mid-log phase. Complementation in trans partially or fully restored the mutant phenotypes. These data suggest that CsrA contributes to virulence by multiple mechanisms and that these contributions may be more profound in bacterial cell populations that are not rapidly dividing in the human host.

  3. Regulation of hemoglobin AIc formation in human erythrocytes in vitro. Effects of physiologic factors other than glucose.

    OpenAIRE

    Smith, R J; Koenig, R J; Binnerts, A; Soeldner, J S; Aoki, T T

    1982-01-01

    The formation of hemoglobin AIc was studied in intact human erythrocytes in vitro. Satisfactory methods were developed for maintaining erythrocytes under physiologic conditions for greater than 8 d with less than 10% hemolysis. Hemoglobin AIc levels were determined chromatographically on erythrocyte hemolysates after removal of reversible components by incubation for 6 h at 37 degree C. Hemoglobin AIc concentration was found to increase linearly with time during 8 d of incubation. The rate of...

  4. Physiological and brain activity after a combined cognitive behavioral treatment plus video game therapy for emotional regulation in bulimia nervosa: a case report.

    Science.gov (United States)

    Fagundo, Ana Beatriz; Via, Esther; Sánchez, Isabel; Jiménez-Murcia, Susana; Forcano, Laura; Soriano-Mas, Carles; Giner-Bartolomé, Cristina; Santamaría, Juan J; Ben-Moussa, Maher; Konstantas, Dimitri; Lam, Tony; Lucas, Mikkel; Nielsen, Jeppe; Lems, Peter; Cardoner, Narcís; Menchón, Jose M; de la Torre, Rafael; Fernandez-Aranda, Fernando

    2014-08-12

    PlayMancer is a video game designed to increase emotional regulation and reduce general impulsive behaviors, by training to decrease arousal and improve decision-making and planning. We have previously demonstrated the usefulness of PlayMancer in reducing impulsivity and improving emotional regulation in bulimia nervosa (BN) patients. However, whether these improvements are actually translated into brain changes remains unclear. The aim of this case study was to report on a 28-year-old Spanish woman with BN, and to examine changes in physiological variables and brain activity after a combined treatment of video game therapy (VGT) and cognitive behavioral therapy (CBT). Ten VGT sessions were carried out on a weekly basis. Anxiety, physiological, and impulsivity measurements were recorded. The patient was scanned in a 1.5-T magnetic resonance scanner, prior to and after the 10-week VGT/CBT combined treatment, using two paradigms: (1) an emotional face-matching task, and (2) a multi-source interference task (MSIT). Upon completing the treatment, a decrease in average heart rate was observed. The functional magnetic resonance imaging (fMRI) results indicated a post-treatment reduction in reaction time along with high accuracy. The patient engaged areas typically active in healthy controls, although the cluster extension of the active areas decreased after the combined treatment. These results suggest a global improvement in emotional regulation and impulsivity control after the VGT therapy in BN, demonstrated by both physiological and neural changes. These promising results suggest that a combined treatment of CBT and VGT might lead to functional cerebral changes that ultimately translate into better cognitive and emotional performances.

  5. Physiological and Brain Activity After a Combined Cognitive Behavioral Treatment Plus Video Game Therapy for Emotional Regulation in Bulimia Nervosa: A Case Report

    Science.gov (United States)

    Fagundo, Ana Beatriz; Via, Esther; Sánchez, Isabel; Jiménez-Murcia, Susana; Forcano, Laura; Soriano-Mas, Carles; Giner-Bartolomé, Cristina; Santamaría, Juan J; Ben-Moussa, Maher; Konstantas, Dimitri; Lam, Tony; Lucas, Mikkel; Nielsen, Jeppe; Lems, Peter; Cardoner, Narcís; Menchón, Jose M; de la Torre, Rafael

    2014-01-01

    Background PlayMancer is a video game designed to increase emotional regulation and reduce general impulsive behaviors, by training to decrease arousal and improve decision-making and planning. We have previously demonstrated the usefulness of PlayMancer in reducing impulsivity and improving emotional regulation in bulimia nervosa (BN) patients. However, whether these improvements are actually translated into brain changes remains unclear. Objective The aim of this case study was to report on a 28-year-old Spanish woman with BN, and to examine changes in physiological variables and brain activity after a combined treatment of video game therapy (VGT) and cognitive behavioral therapy (CBT). Methods Ten VGT sessions were carried out on a weekly basis. Anxiety, physiological, and impulsivity measurements were recorded. The patient was scanned in a 1.5-T magnetic resonance scanner, prior to and after the 10-week VGT/CBT combined treatment, using two paradigms: (1) an emotional face-matching task, and (2) a multi-source interference task (MSIT). Results Upon completing the treatment, a decrease in average heart rate was observed. The functional magnetic resonance imaging (fMRI) results indicated a post-treatment reduction in reaction time along with high accuracy. The patient engaged areas typically active in healthy controls, although the cluster extension of the active areas decreased after the combined treatment. Conclusions These results suggest a global improvement in emotional regulation and impulsivity control after the VGT therapy in BN, demonstrated by both physiological and neural changes. These promising results suggest that a combined treatment of CBT and VGT might lead to functional cerebral changes that ultimately translate into better cognitive and emotional performances. PMID:25116416

  6. Connections between Future Time Perspectives and Self-Regulated Learning for Mid-Year Engineering Students: A Multiple Case Study

    Science.gov (United States)

    Chasmar, Justine

    2017-01-01

    This dissertation presents multiple studies with the purpose of understanding the connections between undergraduate engineering students' motivations, specifically students' Future Time Perspectives (FTPs) and Self-Regulated Learning (SRL). FTP refers to the views students hold about the future and how their perceptions of current tasks are…

  7. The Zymomonas mobilis regulator hfq contributes to tolerance against multiple lignocellulosic pretreatment inhibitors

    Directory of Open Access Journals (Sweden)

    Lu Tse-Yuan S

    2010-05-01

    mutant construction in Z. mobilis, and constructed a Gateway compatible expression plasmid for use in Z. mobilis for the first time. We have also used genetics to show Z. mobilis Hfq and S. cerevisiae Lsm proteins play important roles in resisting multiple, important industrially relevant inhibitors. The conserved nature of this global regulator offers the potential to apply insights from these fundamental studies for further industrial strain development.

  8. High dietary fat and sucrose results in an extensive and time-dependent deterioration in health of multiple physiological systems in mice.

    Science.gov (United States)

    Burchfield, James G; Kebede, Melkam A; Meoli, Christopher C; Stöckli, Jacqueline; Whitworth, P Tess; Wright, Amanda L; Hoffman, Nolan J; Minard, Annabel Y; Ma, Xiuquan; Krycer, James R; Nelson, Marin E; Tan, Shi-Xiong; Yau, Belinda; Thomas, Kristen C; Wee, Natalie K Y; Khor, Ee-Cheng; Enriquez, Ronaldo F; Vissel, Bryce; Biden, Trevor J; Baldock, Paul A; Hoehn, Kyle L; Cantley, James; Cooney, Gregory J; James, David E; Fazakerley, Daniel J

    2018-04-13

    Obesity is associated with metabolic dysfunction, including insulin resistance and hyperinsulinemia, and with disorders such as cardiovascular disease, osteoporosis, and neurodegeneration. Typically, these pathologies are examined in discrete model systems and with limited temporal resolution, and whether these disorders co-occur is therefore unclear. To address this question, here we examined multiple physiological systems in male C57BL/6J mice following prolonged exposure to a high-fat/high-sucrose diet (HFHSD). HFHSD-fed mice rapidly exhibited metabolic alterations, including obesity, hyperleptinemia, physical inactivity, glucose intolerance, peripheral insulin resistance, fasting hyperglycemia, ectopic lipid deposition, and bone deterioration. Prolonged exposure to HFHSD resulted in morbid obesity, ectopic triglyceride deposition in liver and muscle, extensive bone loss, sarcopenia, hyperinsulinemia, and impaired short-term memory. Although many of these defects are typically associated with aging, HFHSD did not alter telomere length in white blood cells, indicating that this diet did not generally promote all aspects of aging. Strikingly, glucose homeostasis was highly dynamic. Glucose intolerance was evident in HFHSD-fed mice after 1 week and was maintained for 24 weeks. Beyond 24 weeks, however, glucose tolerance improved in HFHSD-fed mice, and by 60 weeks, it was indistinguishable from that of chow-fed mice. This improvement coincided with adaptive β-cell hyperplasia and hyperinsulinemia, without changes in insulin sensitivity in muscle or adipose tissue. Assessment of insulin secretion in isolated islets revealed that leptin, which inhibited insulin secretion in the chow-fed mice, potentiated glucose-stimulated insulin secretion in the HFHSD-fed mice after 60 weeks. Overall, the excessive calorie intake was accompanied by deteriorating function of numerous physiological systems. © 2018 by The American Society for Biochemistry and Molecular Biology, Inc.

  9. Molecular Regulation of the Mitochondrial F1Fo-ATPsynthase: Physiological and Pathological Significance of the Inhibitory Factor 1 (IF 1

    Directory of Open Access Journals (Sweden)

    Danilo Faccenda

    2012-01-01

    Full Text Available In mammals, the mitochondrial F1Fo-ATPsynthase sets out the energy homeostasis by producing the bulk of cellular ATP. As for every enzyme, the laws of thermodynamics command it; however, it is privileged to have a dedicated molecular regulator that controls its rotation. This is the so-called ATPase Inhibitory Factor 1 (IF1 that blocks its reversal to avoid the consumption of cellular ATP when the enzyme acts as an ATP hydrolase. Recent evidence has also demonstrated that IF1 may control the alignment of the enzyme along the mitochondrial inner membrane, thus increasing the interest for the molecule. We conceived this review to outline the fundamental knowledge of the F1Fo-ATPsynthase and link it to the molecular mechanisms by which IF1 regulates its way of function, with the ultimate goal to highlight this as an important and possibly unique means to control this indispensable enzyme in both physiological and pathological settings.

  10. Intracellular Calreticulin Regulates Multiple Steps in Fibrillar Collagen Expression, Trafficking, and Processing into the Extracellular Matrix*

    OpenAIRE

    Van Duyn Graham, Lauren; Sweetwyne, Mariya T.; Pallero, Manuel A.; Murphy-Ullrich, Joanne E.

    2009-01-01

    Calreticulin (CRT), a chaperone and Ca2+ regulator, enhances wound healing, and its expression correlates with fibrosis in animal models, suggesting that CRT regulates production of the extracellular matrix. However, direct regulation of collagen matrix by CRT has not been previously demonstrated. We investigated the role of CRT in the regulation of fibrillar collagen expression, secretion, processing, and deposition in the extracellular matrix by fibroblasts. Mouse embryonic fibroblasts defi...

  11. Nasal Physiology

    Science.gov (United States)

    ... Caregivers Contact ARS HOME ANATOMY Nasal Anatomy Sinus Anatomy Nasal Physiology Nasal Endoscopy Skull Base Anatomy Virtual Anatomy Disclosure ... Patient Education About this Website Font Size + - Home > ANATOMY > Nasal Physiology Nasal Anatomy Sinus Anatomy Nasal Physiology Nasal Endoscopy ...

  12. Assessing human variability in kinetics for exposures to multiple environmental chemicals: a physiologically based pharmacokinetic modeling case study with dichloromethane, benzene, toluene, ethylbenzene, and m-xylene.

    Science.gov (United States)

    Valcke, Mathieu; Haddad, Sami

    2015-01-01

    The objective of this study was to compare the magnitude of interindividual variability in internal dose for inhalation exposure to single versus multiple chemicals. Physiologically based pharmacokinetic models for adults (AD), neonates (NEO), toddlers (TODD), and pregnant women (PW) were used to simulate inhalation exposure to "low" (RfC-like) or "high" (AEGL-like) air concentrations of benzene (Bz) or dichloromethane (DCM), along with various levels of toluene alone or toluene with ethylbenzene and xylene. Monte Carlo simulations were performed and distributions of relevant internal dose metrics of either Bz or DCM were computed. Area under the blood concentration of parent compound versus time curve (AUC)-based variability in AD, TODD, and PW rose for Bz when concomitant "low" exposure to mixtures of increasing complexities occurred (coefficient of variation (CV) = 16-24%, vs. 12-15% for Bz alone), but remained unchanged considering DCM. Conversely, AUC-based CV in NEO fell (15 to 5% for Bz; 12 to 6% for DCM). Comparable trends were observed considering production of metabolites (AMET), except for NEO's CYP2E1-mediated metabolites of Bz, where an increased CV was observed (20 to 71%). For "high" exposure scenarios, Cmax-based variability of Bz and DCM remained unchanged in AD and PW, but decreased in NEO (CV= 11-16% to 2-6%) and TODD (CV= 12-13% to 7-9%). Conversely, AMET-based variability for both substrates rose in every subpopulation. This study analyzed for the first time the impact of multiple exposures on interindividual variability in toxicokinetics. Evidence indicates that this impact depends upon chemical concentrations and biochemical properties, as well as the subpopulation and internal dose metrics considered.

  13. The physiological role of orexin/hypocretin neurons in the regulation of sleep/wakefulness and neuroendocrine functions

    Directory of Open Access Journals (Sweden)

    Ayumu eInutsuka

    2013-03-01

    Full Text Available The hypothalamus monitors body homeostasis and regulates various behaviors such as feeding, thermogenesis, and sleeping. Orexins (also known as hypocretins were identified as endogenous ligands for two orphan G-protein-coupled receptors in the lateral hypothalamic area. They were initially recognized as regulators of feeding behavior, but they are mainly regarded as key modulators of the sleep/wakefulness cycle. Orexins activate orexin neurons, monoaminergic and cholinergic neurons in the hypothalamus/brainstem regions, to maintain a long, consolidated awake period. Anatomical studies of neural projections from/to orexin neurons and phenotypic characterization of transgenic mice revealed various roles for orexin neurons in the coordination of emotion, energy homeostasis, reward system, and arousal. For example, orexin neurons are regulated by peripheral metabolic cues, including ghrelin, leptin, and glucose concentration. This suggests that they may provide a link between energy homeostasis and arousal states. A link between the limbic system and orexin neurons might be important for increasing vigilance during emotional stimuli. Orexins are also involved in reward systems and the mechanisms of drug addiction. These findings suggest that orexin neurons sense the outer and inner environment of the body and maintain the proper wakefulness level of animals for survival. This review discusses the mechanism by which orexins maintain sleep/wakefulness states and how this mechanism relates to other systems that regulate emotion, reward, and energy homeostasis.

  14. Fructose 1-phosphate is the one and only physiological effector of the Cra (FruR) regulator of Pseudomonas putida.

    Science.gov (United States)

    Chavarría, Max; Durante-Rodríguez, Gonzalo; Krell, Tino; Santiago, César; Brezovsky, Jan; Damborsky, Jiri; de Lorenzo, Víctor

    2014-01-01

    Fructose-1-phosphate (F1P) is the preferred effector of the catabolite repressor/activator (Cra) protein of the soil bacterium Pseudomonas putida but its ability to bind other metabolic intermediates in vivo is unclear. The Cra protein of this microorganism (Cra(PP)) was submitted to mobility shift assays with target DNA sequences (the PfruB promoter) and candidate effectors fructose-1,6-bisphosphate (FBP), glucose 6-phosphate (G6P), and fructose-6-phosphate (F6P). 1 mM F1P was sufficient to release most of the Cra protein from its operators but more than 10 mM of FBP or G6P was required to free the same complex. However, isothermal titration microcalorimetry failed to expose any specific interaction between Cra(PP) and FBP or G6P. To solve this paradox, transcriptional activity of a PfruB-lacZ fusion was measured in wild-type and ΔfruB cells growing on substrates that change the intracellular concentrations of F1P and FBP. The data indicated that PfruB activity was stimulated by fructose but not by glucose or succinate. This suggested that Cra(PP) represses expression in vivo of the cognate fruBKA operon in a fashion dependent just on F1P, ruling out any other physiological effector. Molecular docking and dynamic simulations of the Cra-agonist interaction indicated that both metabolites can bind the repressor, but the breach in the relative affinity of Cra(PP) for F1P vs FBP is three orders of magnitude larger than the equivalent distance in the Escherichia coli protein. This assigns the Cra protein of P. putida the sole role of transducing the presence of fructose in the medium into a variety of direct and indirect physiological responses.

  15. Aging and Intermittent Fasting Impact on Transcriptional Regulation and Physiological Responses of Adult Drosophila Neuronal and Muscle Tissues.

    Science.gov (United States)

    Zhang, Sharon; Ratliff, Eric P; Molina, Brandon; El-Mecharrafie, Nadja; Mastroianni, Jessica; Kotzebue, Roxanne W; Achal, Madhulika; Mauntz, Ruth E; Gonzalez, Arysa; Barekat, Ayeh; Bray, William A; Macias, Andrew M; Daugherty, Daniel; Harris, Greg L; Edwards, Robert A; Finley, Kim D

    2018-04-10

    The progressive decline of the nervous system, including protein aggregate formation, reflects the subtle dysregulation of multiple functional pathways. Our previous work has shown intermittent fasting (IF) enhances longevity, maintains adult behaviors and reduces aggregates, in part, by promoting autophagic function in the aging Drosophila brain. To clarify the impact that IF-treatment has upon aging, we used high throughput RNA-sequencing technology to examine the changing transcriptome in adult Drosophila tissues. Principle component analysis (PCA) and other analyses showed ~1200 age-related transcriptional differences in head and muscle tissues, with few genes having matching expression patterns. Pathway components showing age-dependent expression differences were involved with stress response, metabolic, neural and chromatin remodeling functions. Middle-aged tissues also showed a significant increase in transcriptional drift-variance (TD), which in the CNS included multiple proteolytic pathway components. Overall, IF-treatment had a demonstrably positive impact on aged transcriptomes, partly ameliorating both fold and variance changes. Consistent with these findings, aged IF-treated flies displayed more youthful metabolic, behavioral and basal proteolytic profiles that closely correlated with transcriptional alterations to key components. These results indicate that even modest dietary changes can have therapeutic consequences, slowing the progressive decline of multiple cellular systems, including proteostasis in the aging nervous system.

  16. Aging and Intermittent Fasting Impact on Transcriptional Regulation and Physiological Responses of Adult Drosophila Neuronal and Muscle Tissues

    Directory of Open Access Journals (Sweden)

    Sharon Zhang

    2018-04-01

    Full Text Available The progressive decline of the nervous system, including protein aggregate formation, reflects the subtle dysregulation of multiple functional pathways. Our previous work has shown intermittent fasting (IF enhances longevity, maintains adult behaviors and reduces aggregates, in part, by promoting autophagic function in the aging Drosophila brain. To clarify the impact that IF-treatment has upon aging, we used high throughput RNA-sequencing technology to examine the changing transcriptome in adult Drosophila tissues. Principle component analysis (PCA and other analyses showed ~1200 age-related transcriptional differences in head and muscle tissues, with few genes having matching expression patterns. Pathway components showing age-dependent expression differences were involved with stress response, metabolic, neural and chromatin remodeling functions. Middle-aged tissues also showed a significant increase in transcriptional drift-variance (TD, which in the CNS included multiple proteolytic pathway components. Overall, IF-treatment had a demonstrably positive impact on aged transcriptomes, partly ameliorating both fold and variance changes. Consistent with these findings, aged IF-treated flies displayed more youthful metabolic, behavioral and basal proteolytic profiles that closely correlated with transcriptional alterations to key components. These results indicate that even modest dietary changes can have therapeutic consequences, slowing the progressive decline of multiple cellular systems, including proteostasis in the aging nervous system.

  17. An experimental investigation of a liquid cooling scheme for the low dropout voltage regulators of the multiplicity and vertex detector

    International Nuclear Information System (INIS)

    Bernardin, J.D.; Bosze, E.

    1997-10-01

    This report presents a summary of an experimental investigation of a liquid cooling system for the low dropout voltage regulators in the multiplicity and vertex detector (MVD), a device used to determine and characterize the collision location of two accelerated heavy ions. The coolant temperatures and flow rates as well as the voltage regulator operating temperatures were used to assess and optimize the performance of the proposed cooling system, identify potential assembly problems and system limitations, and provide the necessary information for designing and sizing the final MVD cooling system components. The MVD is part of the PHENIX experiment at Brookhaven RHIC

  18. Application of Physiological Self-Regulation and Adaptive Task Allocation Techniques for Controlling Operator Hazardous States of Awareness

    Science.gov (United States)

    Prinzel, Lawrence J., III; Pope, Alan T.; Freeman, Frederick G.

    2001-01-01

    Prinzel, Hadley, Freeman, and Mikulka found that adaptive task allocation significantly enhanced performance only when used at the endpoints of the task workload continuum (i.e., very low or high workload), but that the technique degraded performance if invoked during other levels of task demand. These researchers suggested that other techniques should be used in conjunction with adaptive automation to help minimize the onset of hazardous states of awareness (HSA) and keep the operator 'in-the-loop.' The paper reports on such a technique that uses psychophysiological self-regulation to modulate the level of task engagement. Eighteen participants were assigned to three groups (self-regulation, false feedback, and control) and performed a compensatory tracking task that was cycled between three levels of task difficulty on the basis of the electroencephalogram (EEG) record. Those participants who had received self-regulation training performed significantly better and reported lower NASA-TLX scores than participants in the false feedback and control groups. Furthermore, the false feedback and control groups had significantly more task allocations resulting in return-to-manual performance decrements and higher EEG difference scores. Theoretical and practical implications of these results for adaptive automation are discussed.

  19. Early Prediction of Student Self-Regulation Strategies by Combining Multiple Models

    Science.gov (United States)

    Sabourin, Jennifer L.; Mott, Bradford W.; Lester, James C.

    2012-01-01

    Self-regulated learning behaviors such as goal setting and monitoring have been found to be crucial to students' success in computer-based learning environments. Consequently, understanding students' self-regulated learning behavior has been the subject of increasing interest. Unfortunately, monitoring these behaviors in real-time has proven…

  20. Several Hfq-dependent alterations in physiology of Yersinia enterocolitica O:3 are mediated by derepression of the transcriptional regulator RovM.

    Science.gov (United States)

    Leskinen, Katarzyna; Pajunen, Maria I; Varjosalo, Markku; Fernández-Carrasco, Helena; Bengoechea, José A; Skurnik, Mikael

    2017-03-01

    In bacteria, the RNA chaperone Hfq enables pairing of small regulatory RNAs with their target mRNAs and therefore is a key player of post-transcriptional regulation network. As a global regulator, Hfq is engaged in the adaptation to external environment, regulation of metabolism and bacterial virulence. In this study we used RNA-sequencing and quantitative proteomics (LC-MS/MS) to elucidate the role of this chaperone in the physiology and virulence of Yersinia enterocolitica serotype O:3. This global approach revealed the profound impact of Hfq on gene and protein expression. Furthermore, the role of Hfq in the cell morphology, metabolism, cell wall integrity, resistance to external stresses and pathogenicity was evaluated. Importantly, our results revealed that several alterations typical for the hfq-negative phenotype were due to derepression of the transcriptional factor RovM. The overexpression of RovM caused by the loss of Hfq chaperone resulted in extended growth defect, alterations in the lipid A structure, motility and biofilm formation defects, as well as changes in mannitol utilization. Furthermore, in Y. enterocolitica RovM only in the presence of Hfq affected the abundance of RpoS. Finally, the impact of hfq and rovM mutations on the virulence was assessed in the mouse infection model. © 2016 John Wiley & Sons Ltd.

  1. Physiological Regulation of Gut Peptide Hormone (PYY) Levels by Age, Sex, Hormonal and Nutritional Status in Rats

    International Nuclear Information System (INIS)

    Hebashy, M.I.A.; Mazen, G.M.A.

    2007-01-01

    Peptide YY hormone (PYY) was recently appreciated as an important gut hormonal regulator of appetite. PYY is produced by the gut and released into the circulation after food intake and is found to decrease appetite. The main form of PYY, both stored and circulated, is PYY(3-36), the N-terminal truncated form of the full length peptide so, peripheral injections of PYY(3-36) in rats inhibit food intake in experimental animals as well as in lean and obese human subjects. Also, this hormone has been suggested to be an attractive therapeutic option for obesity. PYY levels are influenced by age and the highest hormone level is achieved in early postnatal life (day 30) and is decreased thereafter. PYY levels were also dependent on thyroid hormone status and being decreased in hyperthyroid rats. The PYY levels observed in acute and chronic food restricted rats indicated that, in situations of decreased energy intake, the lower PYY levels could serve to regulate central pathways and facilitate food intake. Contrary, in pregnant rats, PYY levels were enhanced at late gestation. The aim of this study was to assess the influence of age, sex, thyroid status, pregnancy and food restriction on PYY levels in rats. The underling mechanisms through which PYY levels alternated as a result of sex, age, pregnancy, thyroidal and nutritional status were discussed in the light of recent research outcomes

  2. Tif1γ regulates the TGF-β1 receptor and promotes physiological aging of hematopoietic stem cells.

    Science.gov (United States)

    Quéré, Ronan; Saint-Paul, Laetitia; Carmignac, Virginie; Martin, Romain Z; Chrétien, Marie-Lorraine; Largeot, Anne; Hammann, Arlette; Pais de Barros, Jean-Paul; Bastie, Jean-Noël; Delva, Laurent

    2014-07-22

    The hematopoietic system declines with age. Myeloid-biased differentiation and increased incidence of myeloid malignancies feature aging of hematopoietic stem cells (HSCs), but the mechanisms involved remain uncertain. Here, we report that 4-mo-old mice deleted for transcription intermediary factor 1γ (Tif1γ) in HSCs developed an accelerated aging phenotype. To reinforce this result, we also show that Tif1γ is down-regulated in HSCs during aging in 20-mo-old wild-type mice. We established that Tif1γ controls TGF-β1 receptor (Tgfbr1) turnover. Compared with young HSCs, Tif1γ(-/-) and old HSCs are more sensitive to TGF-β signaling. Importantly, we identified two populations of HSCs specifically discriminated by Tgfbr1 expression level and provided evidence of the capture of myeloid-biased (Tgfbr1(hi)) and myeloid-lymphoid-balanced (Tgfbr1(lo)) HSCs. In conclusion, our data provide a new paradigm for Tif1γ in regulating the balance between lymphoid- and myeloid-derived HSCs through TGF-β signaling, leading to HSC aging.

  3. Inhibition of host extracellular signal-regulated kinase (ERK) activation decreases new world alphavirus multiplication in infected cells

    Energy Technology Data Exchange (ETDEWEB)

    Voss, Kelsey; Amaya, Moushimi [National Center for Biodefense and Infectious Diseases, School of Systems Biology, George Mason University, 10650 Pyramid Place, Manassas, VA (United States); Mueller, Claudius [Center for Applied Proteomics and Personalized Medicine, George Mason University, 10900 University Boulevard, Manassas, VA (United States); Roberts, Brian [Leidos Health Life Sciences, 5202 Presidents Court, Suite 110, Frederick, MD (United States); Kehn-Hall, Kylene; Bailey, Charles [National Center for Biodefense and Infectious Diseases, School of Systems Biology, George Mason University, 10650 Pyramid Place, Manassas, VA (United States); Petricoin, Emanuel [Center for Applied Proteomics and Personalized Medicine, George Mason University, 10900 University Boulevard, Manassas, VA (United States); Narayanan, Aarthi, E-mail: anaraya1@gmu.edu [National Center for Biodefense and Infectious Diseases, School of Systems Biology, George Mason University, 10650 Pyramid Place, Manassas, VA (United States)

    2014-11-15

    New World alphaviruses belonging to the family Togaviridae are classified as emerging infectious agents and Category B select agents. Our study is focused on the role of the host extracellular signal-regulated kinase (ERK) in the infectious process of New World alphaviruses. Infection of human cells by Venezuelan equine encephalitis virus (VEEV) results in the activation of the ERK-signaling cascade. Inhibition of ERK1/2 by the small molecule inhibitor Ag-126 results in inhibition of viral multiplication. Ag-126-mediated inhibition of VEEV was due to potential effects on early and late stages of the infectious process. While expression of viral proteins was down-regulated in Ag-126 treated cells, we did not observe any influence of Ag-126 on the nuclear distribution of capsid. Finally, Ag-126 exerted a broad-spectrum inhibitory effect on New World alphavirus multiplication, thus indicating that the host kinase, ERK, is a broad-spectrum candidate for development of novel therapeutics against New World alphaviruses. - Highlights: • VEEV infection activated multiple components of the ERK signaling cascade. • Inhibition of ERK activation using Ag-126 inhibited VEEV multiplication. • Activation of ERK by Ceramide C6 increased infectious titers of TC-83. • Ag-126 inhibited virulent strains of all New World alphaviruses. • Ag-126 treatment increased percent survival of infected cells.

  4. Inhibition of host extracellular signal-regulated kinase (ERK) activation decreases new world alphavirus multiplication in infected cells

    International Nuclear Information System (INIS)

    Voss, Kelsey; Amaya, Moushimi; Mueller, Claudius; Roberts, Brian; Kehn-Hall, Kylene; Bailey, Charles; Petricoin, Emanuel; Narayanan, Aarthi

    2014-01-01

    New World alphaviruses belonging to the family Togaviridae are classified as emerging infectious agents and Category B select agents. Our study is focused on the role of the host extracellular signal-regulated kinase (ERK) in the infectious process of New World alphaviruses. Infection of human cells by Venezuelan equine encephalitis virus (VEEV) results in the activation of the ERK-signaling cascade. Inhibition of ERK1/2 by the small molecule inhibitor Ag-126 results in inhibition of viral multiplication. Ag-126-mediated inhibition of VEEV was due to potential effects on early and late stages of the infectious process. While expression of viral proteins was down-regulated in Ag-126 treated cells, we did not observe any influence of Ag-126 on the nuclear distribution of capsid. Finally, Ag-126 exerted a broad-spectrum inhibitory effect on New World alphavirus multiplication, thus indicating that the host kinase, ERK, is a broad-spectrum candidate for development of novel therapeutics against New World alphaviruses. - Highlights: • VEEV infection activated multiple components of the ERK signaling cascade. • Inhibition of ERK activation using Ag-126 inhibited VEEV multiplication. • Activation of ERK by Ceramide C6 increased infectious titers of TC-83. • Ag-126 inhibited virulent strains of all New World alphaviruses. • Ag-126 treatment increased percent survival of infected cells

  5. Culture medium and growth regulators on in vitro multiplication of Psidium guajava L.

    Directory of Open Access Journals (Sweden)

    Jorge Vilchez

    2014-01-01

    Full Text Available Guava (Psidium guajava L. cultivar `Dwarf Cuban Red 18-40 EEA' has high yields. For large-scale propagation, micropropagation is a possible solution. The aim of this study was to determine the effect of two culture media, two cytokinins and an analog brasinoesteoides (DI-31 in the in vitro multiplication of this cultivar. Two culture media (MS and WPM, three concentrations of benzylaminopurine (BAP (0.5, 1.0, 1.5 mg l-1, three of kinetin (0.5, 1.0, 1.5 mg l-1 and two DI-31 (0.01 and 0.02 mg l-1 were evaluated. The variables evaluated were: number of shoots, number of leaves, shoot length and multiplication coefficient. It was found that the type of culture medium influenced the shoot multiplication of guava. The number of shoots, shoot length and multiplication coefficient were determined by the type and concentration of cytokinin added to the culture medium. With the use of WPM culture medium with 1 mg l-1 BAP It was obtained the highest values of the variables evaluated. The use of DI-31 promoted the shoot growth without affecting the multiplication coefficient. Key words: benzylaminopurine, DI-31, kinetin, guava, micropropagation, multiplication phase

  6. Transcriptional regulation of the outer membrane porin gene ompW reveals its physiological role during the transition from the aerobic to the anaerobic lifestyle of Escherichia coli

    Directory of Open Access Journals (Sweden)

    Minfeng eXiao

    2016-05-01

    Full Text Available Understanding bacterial physiology relies on elucidating the regulatory mechanisms and cellular functions of those differentially expressed genes in response to environmental changes. A widespread Gram-negative bacterial outer membrane protein OmpW has been implicated in the adaptation to stresses in various species. It is recently found to be present in the regulon of the global anaerobic transcription factor FNR and ArcA in E. coli. However, little is known about the physiological implications of this regulatory disposition. In this study, we demonstrate that transcription of ompW is indeed mediated by a series of global regulators involved in the anaerobiosis of E. coli. We show that FNR can both activate and repress the expression of ompW through its direct binding to two distinctive sites, -81.5 and -126.5 bp respectively, on ompW promoter. ArcA also participates in repression of ompW under anaerobic condition, but in an FNR dependent manner. Additionally, ompW is also subject to the regulation by CRP and NarL which senses the availability and types of carbon sources and respiration electron acceptors in the environment respectively, implying a role of OmpW in the carbon and energy metabolism of E. coli during its anaerobic adaptation. Molecular docking reveals that OmpW can bind fumarate, an alternative electron acceptor in anaerobic respiration, with sufficient affinity. Moreover, supplement of fumarate or succinate which belongs to the C4-dicarboxylates family of metabolite, to E. coli culture rescues OmpW-mediated colicin S4 killing. Taken together, we propose that OmpW is involved in anaerobic carbon and energy metabolism to mediate the transition from aerobic to anaerobic lifestyle in E. coli.

  7. Changes in the physiological regulation of transpiration caused by the effects of industrial air pollution. [Cucumis sativus

    Energy Technology Data Exchange (ETDEWEB)

    Kozinka, V; Klasova, A; Niznansky, A

    1963-01-01

    Through Hygen's method of quantitative analysis of transpiration curves, the authors studied the intensity of stomatal and cuticular transpiration of germinating leaves of Cucumis sativus which were experimentally exposed to solid impurities containing F. The difference between the control and experimental plants shows that the impurities not only blocked the regulating system of breathing but also caused increased cuticular transpiration. Numerous lesions were observed; cuticle damage also spread to the inner tissues. A direct relationship between microscopic and macroscopic symptoms was not proven. The creation of conditions adverse to the normal development of the water balance was intensified when the impurities were dropped onto the surface of the leaves. The possible protective function of trichomes is mentioned, but applies only when the impurities settle on a dry surface.

  8. Physiological studies in heterozygous calcium sensing receptor (CaSR gene-ablated mice confirm that the CaSR regulates calcitonin release in vivo

    Directory of Open Access Journals (Sweden)

    Kovacs Christopher S

    2004-04-01

    Full Text Available Abstract Background The calcium sensing receptor (CaSR regulates serum calcium by suppressing secretion of parathyroid hormone; it also regulates renal tubular calcium excretion. Inactivating mutations of CaSR raise serum calcium and reduce urine calcium excretion. Thyroid C-cells (which make calcitonin express CaSR and may, therefore, be regulated by it. Since calcium stimulates release of calcitonin, the higher blood calcium caused by inactivation of CaSR should increase serum calcitonin, unless CaSR mutations alter the responsiveness of calcitonin to calcium. To demonstrate regulatory effects of CaSR on calcitonin release, we studied calcitonin responsiveness to calcium in normal and CaSR heterozygous-ablated (Casr+/- mice. Casr+/- mice have hypercalcemia and hypocalciuria, and live normal life spans. Each mouse received either 500 μl of normal saline or one of two doses of elemental calcium (500 μmol/kg or 5 mmol/kg by intraperitoneal injection. Ionized calcium was measured at baseline and 10 minutes, and serum calcitonin was measured on the 10 minute sample. Results At baseline, Casr+/- mice had a higher blood calcium, and in response to the two doses of elemental calcium, had greater increments and peak levels of ionized calcium than their wild type littermates. Despite significantly higher ionized calcium levels, the calcitonin levels of Casr+/- mice were consistently lower than wild type at any ionized calcium level, indicating that the dose-response curve of calcitonin to increases in ionized calcium had been significantly blunted or shifted to the right in Casr+/- mice. Conclusions These results confirm that the CaSR is a physiological regulator of calcitonin; therefore, in response to increases in ionized calcium, the CaSR inhibits parathyroid hormone secretion and stimulates calcitonin secretion.

  9. Carotenoid Biosynthetic Pathways Are Regulated by a Network of Multiple Cascades of Alternative Sigma Factors in Azospirillum brasilense Sp7.

    Science.gov (United States)

    Rai, Ashutosh Kumar; Dubey, Ashutosh Prakash; Kumar, Santosh; Dutta, Debashis; Mishra, Mukti Nath; Singh, Bhupendra Narain; Tripathi, Anil Kumar

    2016-11-01

    Carotenoids constitute an important component of the defense system against photooxidative stress in bacteria. In Azospirillum brasilense Sp7, a nonphotosynthetic rhizobacterium, carotenoid synthesis is controlled by a pair of extracytoplasmic function sigma factors (RpoEs) and their cognate zinc-binding anti-sigma factors (ChrRs). Its genome harbors two copies of the gene encoding geranylgeranyl pyrophosphate synthase (CrtE), the first critical step in the carotenoid biosynthetic pathway in bacteria. Inactivation of each of two crtE paralogs found in A. brasilense caused reduction in carotenoid content, suggesting their involvement in carotenoid synthesis. However, the effect of crtE1 deletion was more pronounced than that of crtE2 deletion. Out of the five paralogs of rpoH in A. brasilense, overexpression of rpoH1 and rpoH2 enhanced carotenoid synthesis. Promoters of crtE2 and rpoH2 were found to be dependent on RpoH2 and RpoE1, respectively. Using a two-plasmid system in Escherichia coli, we have shown that the crtE2 gene of A. brasilense Sp7 is regulated by two cascades of sigma factors: one consisting of RpoE1and RpoH2 and the other consisting of RpoE2 and RpoH1. In addition, expression of crtE1 was upregulated indirectly by RpoE1 and RpoE2. This study shows, for the first time in any carotenoid-producing bacterium, that the regulation of carotenoid biosynthetic pathway involves a network of multiple cascades of alternative sigma factors. Carotenoids play a very important role in coping with photooxidative stress in prokaryotes and eukaryotes. Although extracytoplasmic function (ECF) sigma factors are known to directly regulate the expression of carotenoid biosynthetic genes in bacteria, regulation of carotenoid biosynthesis by one or multiple cascades of sigma factors had not been reported. This study provides the first evidence of the involvement of multiple cascades of sigma factors in the regulation of carotenoid synthesis in any bacterium by showing the

  10. A gene expression system offering multiple levels of regulation: the Dual Drug Control (DDC) system.

    Science.gov (United States)

    Sudomoina, Marina; Latypova, Ekaterina; Favorova, Olga O; Golemis, Erica A; Serebriiskii, Ilya G

    2004-04-29

    Whether for cell culture studies of protein function, construction of mouse models to enable in vivo analysis of disease epidemiology, or ultimately gene therapy of human diseases, a critical enabling step is the ability to achieve finely controlled regulation of gene expression. Previous efforts to achieve this goal have explored inducible drug regulation of gene expression, and construction of synthetic promoters based on two-hybrid paradigms, among others. In this report, we describe the combination of dimerizer-regulated two-hybrid and tetracycline regulatory elements in an ordered cascade, placing expression of endpoint reporters under the control of two distinct drugs. In this Dual Drug Control (DDC) system, a first plasmid expresses fusion proteins to DBD and AD, which interact only in the presence of a small molecule dimerizer; a second plasmid encodes a cassette transcriptionally responsive to the first DBD, directing expression of the Tet-OFF protein; and a third plasmid encodes a reporter gene transcriptionally responsive to binding by Tet-OFF. We evaluate the dynamic range and specificity of this system in comparison to other available systems. This study demonstrates the feasibility of combining two discrete drug-regulated expression systems in a temporally sequential cascade, without loss of dynamic range of signal induction. The efficient layering of control levels allowed by this combination of elements provides the potential for the generation of complex control circuitry that may advance ability to regulate gene expression in vivo.

  11. A gene expression system offering multiple levels of regulation: the Dual Drug Control (DDC system

    Directory of Open Access Journals (Sweden)

    Golemis Erica A

    2004-04-01

    Full Text Available Abstract Background Whether for cell culture studies of protein function, construction of mouse models to enable in vivo analysis of disease epidemiology, or ultimately gene therapy of human diseases, a critical enabling step is the ability to achieve finely controlled regulation of gene expression. Previous efforts to achieve this goal have explored inducible drug regulation of gene expression, and construction of synthetic promoters based on two-hybrid paradigms, among others. Results In this report, we describe the combination of dimerizer-regulated two-hybrid and tetracycline regulatory elements in an ordered cascade, placing expression of endpoint reporters under the control of two distinct drugs. In this Dual Drug Control (DDC system, a first plasmid expresses fusion proteins to DBD and AD, which interact only in the presence of a small molecule dimerizer; a second plasmid encodes a cassette transcriptionally responsive to the first DBD, directing expression of the Tet-OFF protein; and a third plasmid encodes a reporter gene transcriptionally responsive to binding by Tet-OFF. We evaluate the dynamic range and specificity of this system in comparison to other available systems. Conclusion This study demonstrates the feasibility of combining two discrete drug-regulated expression systems in a temporally sequential cascade, without loss of dynamic range of signal induction. The efficient layering of control levels allowed by this combination of elements provides the potential for the generation of complex control circuitry that may advance ability to regulate gene expression in vivo.

  12. Enterobacter asburiae KE17 association regulates physiological changes and mitigates the toxic effects of heavy metals in soybean.

    Science.gov (United States)

    Kang, S-M; Radhakrishnan, R; You, Y-H; Khan, A-L; Lee, K-E; Lee, J-D; Lee, I-J

    2015-09-01

    This study aimed to elucidate the role played by Enterobacter asburiae KE17 in the growth and metabolism of soybeans during copper (100 μm Cu) and zinc (100 μm Zn) toxicity. When compared to controls, plants grown under Cu and Zn stress exhibited significantly lower growth rates, but inoculation with E. asburiae KE17 increased growth rates of stressed plants. The concentrations of plant hormones (abscisic acid and salicylic acid) and rates of lipid peroxidation were higher in plants under heavy metal stress, while total chlorophyll, carotenoid content and total polyphenol concentration were lower. While the bacterial treatment reduced the abscisic acid and salicylic acid content and lipid peroxidation rate of Cu-stressed plants, it also increased the concentration of photosynthetic pigments and total polyphenol. Moreover, the heavy metals induced increased accumulation of free amino acids such as aspartic acid, threonine, serine, glycine, alanine, leucine, isoleucine, tyrosine, proline and gamma-aminobutyric acid, while E. asburiae KE17 significantly reduced concentrations of free amino acids in metal-affected plants. Co-treatment with E. asburiae KE17 regulated nutrient uptake by enhancing nitrogen content and inhibiting Cu and Zn accumulation in soybean plants. The results of this study suggest that E. asburiae KE17 mitigates the effects of Cu and Zn stress by reprogramming plant metabolic processes. © 2015 German Botanical Society and The Royal Botanical Society of the Netherlands.

  13. Effects of regulated deficit irrigation on physiology, yield and fruit quality in apricot trees under Mediterranean conditions

    Directory of Open Access Journals (Sweden)

    Francisco Pérez-Sarmiento

    2016-12-01

    Full Text Available Scarce water resources mainly in arid and semi-arid areas have caused an increasing interest for applying irrigation protocols aiming to reduce water spends. The effects of regulated deficit irrigation (RDI on the performance of apricot trees (Prunus armeniaca L. cv. “Búlida” were assessed in Murcia (SE Spain, during three consecutive growing seasons (2008-2010. The hypothesis was that RDI would not restrict yield but increase fruit quality while saving water. Two irrigation treatments were established: i control, irrigated to fully satisfy crop water requirements (100% ETc and ii RDI, that reduced the amount of applied water to: a 40% of ETc at flowering and stage I of fruit growth; b 60% of ETc during the stage II of fruit growth and c 50% and 25% of ETc during the late postharvest period (from 60 days after harvest. Stem water potential, gas exchanges, trunk cross-sectional area (TCSA, fruit diameter, yield and fruit quality traits were determined. Vegetative growth was decreased by the use of RDI (12% less TCSA on average for the three years, whereas yield was unaffected. In addition, some qualitative characteristics of the fruits, such as the level of soluble solids, sweetness/acidity relation and fruit colour, were improved by the use of RDI. These results and average water savings of approximately 30%, lead us to conclude that RDI strategies are a possible solution for irrigation management in areas with water shortages, such as arid and semi-arid environments.

  14. Are mechanically sensitive regulators involved in the function and (patho)physiology of cerebral palsy-related contractures?

    Science.gov (United States)

    Pingel, Jessica; Suhr, Frank

    2017-08-01

    Skeletal muscle tissue is mechanosensitive, as it is able to sense mechanical impacts and to translate these into biochemical signals making the tissue adapt. Among its mechanosensitive nature, skeletal muscle tissue is the largest metabolic organ of the human body. Disturbances in skeletal muscle mechanosensing and metabolism cause and contribute to many diseases, i.e. muscular dystrophies/myopathies, cardiovascular diseases, COPD or diabetes mellitus type 2. A less commonly focused muscle-related disorder is clinically known as muscle contractures that derive from cerebral palsy (CP) conditions in young and adults. Muscle contractures are characterized by gradually increasing passive muscle stiffness resulting in complete fixation of joints. Different mechanisms have been identified in CP-related contractures, i.e. altered calcium handling, altered metabolism or altered titin regulation. The muscle-related extracellular matrix (ECM), specifically collagens, plays a role in CP-related contractures. Herein, we focus on mechanically sensitive complexes, known as costameres (Cstms), and discuss their potential role in CP-related contractures. We extend our discussion to the ECM due to the limited knowledge of its role in CP-related contractures. The aims of this review are (1) to summarize CP-related contracture mechanisms, (2) to raise novel hypotheses on the genesis of contractures with a focus on Cstms, and (3) to stimulate novel approaches to study CP-related contractures.

  15. Effects of regulated deficit irrigation on physiology, yield and fruit quality in apricot trees under Mediterranean conditions

    International Nuclear Information System (INIS)

    Pérez-Sarmiento, F.; Mirás-Avalos, J.M.; Alcobendas, R.; Alarcón, J.J.; Mounzer, O.; Nicolas, E.

    2016-01-01

    Scarce water resources mainly in arid and semi-arid areas have caused an increasing interest for applying irrigation protocols aiming to reduce water spends. The effects of regulated deficit irrigation (RDI) on the performance of apricot trees (Prunus armeniaca L. cv. “Búlida”) were assessed in Murcia (SE Spain), during three consecutive growing seasons (2008-2010). The hypothesis was that RDI would not restrict yield but increase fruit quality while saving water. Two irrigation treatments were established: i) control, irrigated to fully satisfy crop water requirements (100% ETc) and ii) RDI, that reduced the amount of applied water to: a) 40% of ETc at flowering and stage I of fruit growth; b) 60% of ETc during the stage II of fruit growth and c) 50% and 25% of ETc during the late postharvest period (from 60 days after harvest). Stem water potential, gas exchanges, trunk cross-sectional area (TCSA), fruit diameter, yield and fruit quality traits were determined. Vegetative growth was decreased by the use of RDI (12% less TCSA on average for the three years), whereas yield was unaffected. In addition, some qualitative characteristics of the fruits, such as the level of soluble solids, sweetness/acidity relation and fruit colour, were improved by the use of RDI. These results and average water savings of approximately 30%, lead us to conclude that RDI strategies are a possible solution for irrigation management in areas with water shortages, such as arid and semi-arid environments.

  16. Effects of regulated deficit irrigation on physiology, yield and fruit quality in apricot trees under Mediterranean conditions

    Energy Technology Data Exchange (ETDEWEB)

    Pérez-Sarmiento, F.; Mirás-Avalos, J.M.; Alcobendas, R.; Alarcón, J.J.; Mounzer, O.; Nicolas, E.

    2016-07-01

    Scarce water resources mainly in arid and semi-arid areas have caused an increasing interest for applying irrigation protocols aiming to reduce water spends. The effects of regulated deficit irrigation (RDI) on the performance of apricot trees (Prunus armeniaca L. cv. “Búlida”) were assessed in Murcia (SE Spain), during three consecutive growing seasons (2008-2010). The hypothesis was that RDI would not restrict yield but increase fruit quality while saving water. Two irrigation treatments were established: i) control, irrigated to fully satisfy crop water requirements (100% ETc) and ii) RDI, that reduced the amount of applied water to: a) 40% of ETc at flowering and stage I of fruit growth; b) 60% of ETc during the stage II of fruit growth and c) 50% and 25% of ETc during the late postharvest period (from 60 days after harvest). Stem water potential, gas exchanges, trunk cross-sectional area (TCSA), fruit diameter, yield and fruit quality traits were determined. Vegetative growth was decreased by the use of RDI (12% less TCSA on average for the three years), whereas yield was unaffected. In addition, some qualitative characteristics of the fruits, such as the level of soluble solids, sweetness/acidity relation and fruit colour, were improved by the use of RDI. These results and average water savings of approximately 30%, lead us to conclude that RDI strategies are a possible solution for irrigation management in areas with water shortages, such as arid and semi-arid environments.

  17. Huntingtin-associated protein-1 (HAP1) regulates endocytosis and interacts with multiple trafficking-related proteins.

    Science.gov (United States)

    Mackenzie, Kimberly D; Lim, Yoon; Duffield, Michael D; Chataway, Timothy; Zhou, Xin-Fu; Keating, Damien J

    2017-07-01

    Huntingtin-associated protein 1 (HAP1) was initially identified as a binding partner of huntingtin, mutations in which underlie Huntington's disease. Subcellular localization and protein interaction data indicate that HAP1 may be important in vesicle trafficking, cell signalling and receptor internalization. In this study, a proteomics approach was used for the identification of novel HAP1-interacting partners to attempt to shed light on the physiological function of HAP1. Using affinity chromatography with HAP1-GST protein fragments bound to Sepharose columns, this study identified a number of trafficking-related proteins that bind to HAP1. Interestingly, many of the proteins that were identified by mass spectrometry have trafficking-related functions and include the clathrin light chain B and Sec23A, an ER to Golgi trafficking vesicle coat component. Using co-immunoprecipitation and GST-binding assays the association between HAP1 and clathrin light chain B has been validated in vitro. This study also finds that HAP1 co-localizes with clathrin light chain B. In line with a physiological function of the HAP1-clathrin interaction this study detected a dramatic reduction in vesicle retrieval and endocytosis in adrenal chromaffin cells. Furthermore, through examination of transferrin endocytosis in HAP1 -/- cortical neurons, this study has determined that HAP1 regulates neuronal endocytosis. In this study, the interaction between HAP1 and Sec23A was also validated through endogenous co-immunoprecipitation in rat brain homogenate. Through the identification of novel HAP1 binding partners, many of which have putative trafficking roles, this study provides us with new insights into the mechanisms underlying the important physiological function of HAP1 as an intracellular trafficking protein through its protein-protein interactions. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. RhoGDI: multiple functions in the regulation of Rho family GTPase activities

    DEFF Research Database (Denmark)

    Dovas, Athanassios; Couchman, John R

    2005-01-01

    necessary for the correct targeting and regulation of Rho activities by conferring cues for spatial restriction, guidance and availability to effectors. These potential functions are discussed in the context of RhoGDI-associated multimolecular complexes, the newly emerged shuttling capability...... insight as to how RhoGDI exerts its effects on nucleotide binding, the membrane association-dissociation cycling of the GTPase and how these activities are controlled. Despite the initial negative roles attributed to RhoGDI, recent evidence has come to suggest that it may also act as a positive regulator...... of activities....

  19. Diurnal Regulation of Cellular Processes in the Cyanobacterium Synechocystis sp. Strain PCC 6803: Insights from Transcriptomic, Fluxomic, and Physiological Analyses

    Directory of Open Access Journals (Sweden)

    Rajib Saha

    2016-05-01

    Full Text Available Synechocystis sp. strain PCC 6803 is the most widely studied model cyanobacterium, with a well-developed omics level knowledgebase. Like the lifestyles of other cyanobacteria, that of Synechocystis PCC 6803 is tuned to diurnal changes in light intensity. In this study, we analyzed the expression patterns of all of the genes of this cyanobacterium over two consecutive diurnal periods. Using stringent criteria, we determined that the transcript levels of nearly 40% of the genes in Synechocystis PCC 6803 show robust diurnal oscillating behavior, with a majority of the transcripts being upregulated during the early light period. Such transcripts corresponded to a wide array of cellular processes, such as light harvesting, photosynthetic light and dark reactions, and central carbon metabolism. In contrast, transcripts of membrane transporters for transition metals involved in the photosynthetic electron transport chain (e.g., iron, manganese, and copper were significantly upregulated during the late dark period. Thus, the pattern of global gene expression led to the development of two distinct transcriptional networks of coregulated oscillatory genes. These networks help describe how Synechocystis PCC 6803 regulates its metabolism toward the end of the dark period in anticipation of efficient photosynthesis during the early light period. Furthermore, in silico flux prediction of important cellular processes and experimental measurements of cellular ATP, NADP(H, and glycogen levels showed how this diurnal behavior influences its metabolic characteristics. In particular, NADPH/NADP+ showed a strong correlation with the majority of the genes whose expression peaks in the light. We conclude that this ratio is a key endogenous determinant of the diurnal behavior of this cyanobacterium.

  20. CCR5 in Multiple Sclerosis : expression, regulation, and modulation by statins

    NARCIS (Netherlands)

    Kuipers, Hedwich Fardau

    2007-01-01

    Activation of microglia, the macrophages of the central nervous system, is a key element in multiple sclerosis (MS) lesion development and is characterized by enhanced expression of both classes of major histocompatibility complex (MHC) molecules. This enhanced expression results from increased

  1. Estrogens regulate the hepatic effects of growth hormone, a hormonal interplay with multiple fates

    DEFF Research Database (Denmark)

    Fernández-Pérez, Leandro; Guerra, Borja; Díaz-Chico, Juan C

    2013-01-01

    The liver responds to estrogens and growth hormone (GH) which are critical regulators of body growth, gender-related hepatic functions, and intermediate metabolism. The effects of estrogens on liver can be direct, through the direct actions of hepatic ER, or indirect, which include the crosstalk...

  2. Multiple diguanylate cyclase-coordinated regulation of pyoverdine synthesis in Pseudomonas aeruginosa

    DEFF Research Database (Denmark)

    Chen, Yicai; Yuan, Mingjun; Mohanty, Anee

    2015-01-01

    The nucleotide signalling molecule bis-(3'-5')-cyclic dimeric guanosine monophosphate (c-di-GMP) plays an essential role in regulating microbial virulence and biofilm formation. C-di-GMP is synthesized by diguanylate cyclase (DGC) enzymes and degraded by phosphodiesterase (PDE) enzymes. One...

  3. 26 CFR 1.167(l)-3 - Multiple regulation, asset acquisitions, reorganizations, etc.

    Science.gov (United States)

    2010-04-01

    ... not using, such method of regulated accounting only with respect to property subject to the... treatment of certain property as “pre-1970 public utility property” and § 1.167(l)-1(e)(4)(ii) for...) Property not entirely subject to jurisdiction of one regulatory body—(1) In general. If a taxpayer which...

  4. Systems analysis of multiple regulator perturbations allows discovery of virulence factors in Salmonella

    Energy Technology Data Exchange (ETDEWEB)

    Yoon, Hyunjin; Ansong, Charles; McDermott, Jason E.; Gritsenko, Marina A.; Smith, Richard D.; Heffron, Fred; Adkins, Joshua N.

    2011-06-28

    Background: Systemic bacterial infections are highly regulated and complex processes that are orchestrated by numerous virulence factors. Genes that are coordinately controlled by the set of regulators required for systemic infection are potentially required for pathogenicity. Results: In this study we present a systems biology approach in which sample-matched multi-omic measurements of fourteen virulence-essential regulator mutants were coupled with computational network analysis to efficiently identify Salmonella virulence factors. Immunoblot experiments verified network-predicted virulence factors and a subset was determined to be secreted into the host cytoplasm, suggesting that they are virulence factors directly interacting with host cellular components. Two of these, SrfN and PagK2, were required for full mouse virulence and were shown to be translocated independent of either of the type III secretion systems in Salmonella or the type III injectisome-related flagellar mechanism. Conclusions: Integrating multi-omic datasets from Salmonella mutants lacking virulence regulators not only identified novel virulence factors but also defined a new class of translocated effectors involved in pathogenesis. The success of this strategy at discovery of known and novel virulence factors suggests that the approach may have applicability for other bacterial pathogens.

  5. Rice Physiology

    Science.gov (United States)

    P.A. Counce; Davidi R. Gealy; Shi-Jean Susana Sung

    2002-01-01

    Physiology occurs tn physical space through chemical reactions constrained by anatomy and morphology, yet guided by genetics. Physiology has been called the logic of life. Genes encode structural and fimcdonal proteins. These proteins are subsequently processed to produce enzymes that direct and govern the biomechanical processes involved in the physiology of the...

  6. Renal phosphate handling: Physiology

    Directory of Open Access Journals (Sweden)

    Narayan Prasad

    2013-01-01

    Full Text Available Phosphorus is a common anion. It plays an important role in energy generation. Renal phosphate handling is regulated by three organs parathyroid, kidney and bone through feedback loops. These counter regulatory loops also regulate intestinal absorption and thus maintain serum phosphorus concentration in physiologic range. The parathyroid hormone, vitamin D, Fibrogenic growth factor 23 (FGF23 and klotho coreceptor are the key regulators of phosphorus balance in body.

  7. Living high training low induces physiological cardiac hypertrophy accompanied by down-regulation and redistribution of the renin-angiotensin system

    Science.gov (United States)

    Shi, Wei; Meszaros, J Gary; Zeng, Shao-ju; Sun, Ying-yu; Zuo, Ming-xue

    2013-01-01

    Aim: Living high training low” (LHTL) is an exercise-training protocol that refers living in hypoxia stress and training at normal level of O2. In this study, we investigated whether LHTL caused physiological heart hypertrophy accompanied by changes of biomarkers in renin-angiotensin system in rats. Methods: Adult male SD rats were randomly assigned into 4 groups, and trained on living low-sedentary (LLS, control), living low-training low (LLTL), living high-sedentary (LHS) and living high-training low (LHTL) protocols, respectively, for 4 weeks. Hematological parameters, hemodynamic measurement, heart hypertrophy and plasma angiotensin II (Ang II) level of the rats were measured. The gene and protein expression of angiotensin-converting enzyme (ACE), angiotensinogen (AGT) and angiotensin II receptor I (AT1) in heart tissue was assessed using RT-PCR and immunohistochemistry, respectively. Results: LLTL, LHS and LHTL significantly improved cardiac function, increased hemoglobin concentration and RBC. At the molecular level, LLTL, LHS and LHTL significantly decreased the expression of ACE, AGT and AT1 genes, but increased the expression of ACE and AT1 proteins in heart tissue. Moreover, ACE and AT1 protein expression was significantly increased in the endocardium, but unchanged in the epicardium. Conclusion: LHTL training protocol suppresses ACE, AGT and AT1 gene expression in heart tissue, but increases ACE and AT1 protein expression specifically in the endocardium, suggesting that the physiological heart hypertrophy induced by LHTL is regulated by region-specific expression of renin-angiotensin system components. PMID:23377552

  8. Brd4 and HEXIM1: Multiple Roles in P-TEFb Regulation and Cancer

    Directory of Open Access Journals (Sweden)

    Ruichuan Chen

    2014-01-01

    Full Text Available Bromodomain-containing protein 4 (Brd4 and hexamethylene bisacetamide (HMBA inducible protein 1 (HEXIM1 are two opposing regulators of the positive transcription elongation factor b (P-TEFb, which is the master modulator of RNA polymerase II during transcriptional elongation. While Brd4 recruits P-TEFb to promoter-proximal chromatins to activate transcription, HEXIM1 sequesters P-TEFb into an inactive complex containing the 7SK small nuclear RNA. Besides regulating P-TEFb’s transcriptional activity, recent evidence demonstrates that both Brd4 and HEXIM1 also play novel roles in cell cycle progression and tumorigenesis. Here we will discuss the current knowledge on Brd4 and HEXIM1 and their implication as novel therapeutic options against cancer.

  9. Cell-cycle regulation in green algae dividing by multiple fission

    Czech Academy of Sciences Publication Activity Database

    Bišová, Kateřina; Zachleder, Vilém

    2014-01-01

    Roč. 65, č. 10 (2014), s. 2585-2602 ISSN 0022-0957 R&D Projects: GA ČR M200201205; GA MŠk LH12145 Grant - others:Centre for Algal Biotechnologies (Algatech)(CZ) CZ.1.05/2.1.00/03.0110 Institutional support: RVO:61388971 Keywords : cell cycle * regulation * growth * light Subject RIV: EE - Microbiology, Virology Impact factor: 5.526, year: 2014

  10. An Integrated Cell Purification and Genomics Strategy Reveals Multiple Regulators of Pancreas Development

    Science.gov (United States)

    Benitez, Cecil M.; Qu, Kun; Sugiyama, Takuya; Pauerstein, Philip T.; Liu, Yinghua; Tsai, Jennifer; Gu, Xueying; Ghodasara, Amar; Arda, H. Efsun; Zhang, Jiajing; Dekker, Joseph D.; Tucker, Haley O.; Chang, Howard Y.; Kim, Seung K.

    2014-01-01

    The regulatory logic underlying global transcriptional programs controlling development of visceral organs like the pancreas remains undiscovered. Here, we profiled gene expression in 12 purified populations of fetal and adult pancreatic epithelial cells representing crucial progenitor cell subsets, and their endocrine or exocrine progeny. Using probabilistic models to decode the general programs organizing gene expression, we identified co-expressed gene sets in cell subsets that revealed patterns and processes governing progenitor cell development, lineage specification, and endocrine cell maturation. Purification of Neurog3 mutant cells and module network analysis linked established regulators such as Neurog3 to unrecognized gene targets and roles in pancreas development. Iterative module network analysis nominated and prioritized transcriptional regulators, including diabetes risk genes. Functional validation of a subset of candidate regulators with corresponding mutant mice revealed that the transcription factors Etv1, Prdm16, Runx1t1 and Bcl11a are essential for pancreas development. Our integrated approach provides a unique framework for identifying regulatory genes and functional gene sets underlying pancreas development and associated diseases such as diabetes mellitus. PMID:25330008

  11. An integrated cell purification and genomics strategy reveals multiple regulators of pancreas development.

    Directory of Open Access Journals (Sweden)

    Cecil M Benitez

    2014-10-01

    Full Text Available The regulatory logic underlying global transcriptional programs controlling development of visceral organs like the pancreas remains undiscovered. Here, we profiled gene expression in 12 purified populations of fetal and adult pancreatic epithelial cells representing crucial progenitor cell subsets, and their endocrine or exocrine progeny. Using probabilistic models to decode the general programs organizing gene expression, we identified co-expressed gene sets in cell subsets that revealed patterns and processes governing progenitor cell development, lineage specification, and endocrine cell maturation. Purification of Neurog3 mutant cells and module network analysis linked established regulators such as Neurog3 to unrecognized gene targets and roles in pancreas development. Iterative module network analysis nominated and prioritized transcriptional regulators, including diabetes risk genes. Functional validation of a subset of candidate regulators with corresponding mutant mice revealed that the transcription factors Etv1, Prdm16, Runx1t1 and Bcl11a are essential for pancreas development. Our integrated approach provides a unique framework for identifying regulatory genes and functional gene sets underlying pancreas development and associated diseases such as diabetes mellitus.

  12. Protein arginine methyltransferase 5 regulates multiple signaling pathways to promote lung cancer cell proliferation

    International Nuclear Information System (INIS)

    Sheng, Xiumei; Wang, Zhengxin

    2016-01-01

    Protein arginine methyltransferase 5 (PRMT5) catalyzes the formation of symmetrical dimethylation of arginine residues in proteins. WD repeat domain 77 (WDR77), also known as p44, MEP50, or WD45, forms a stoichiometric complex with PRMT5. The PRMT5/p44 complex is required for cellular proliferation of lung and prostate epithelial cells during earlier stages of development and is re-activated during prostate and lung tumorigenesis. The molecular mechanisms by which PRMT5 and p44 promote cellular proliferation are unknown. Expression of PRMT5 and p44 in lung and prostate cancer cells was silenced and their target genes were identified. The regulation of target genes was validated in various cancer cells during lung development and tumorigenesis. Altered expression of target genes was achieved by ectopic cDNA expression and shRNA-mediated silencing. PRMT5 and p44 regulate expression of a specific set of genes encoding growth and anti-growth factors, including receptor tyrosine kinases and antiproliferative proteins. Genes whose expression was suppressed by PRMT5 and p44 encoded anti-growth factors and inhibited cell growth when ectopically expressed. In contrast, genes whose expression was enhanced by PRMT5 and p44 encoded growth factors and increased cell growth when expressed. Altered expression of target genes is associated with re-activation of PRMT5 and p44 during lung tumorigenesis. Our data provide the molecular basis by which PRMT5 and p44 regulate cell growth and lay a foundation for further investigation of their role in lung tumor initiation. The online version of this article (doi:10.1186/s12885-016-2632-3) contains supplementary material, which is available to authorized users

  13. Disorders of Transcriptional Regulation: An Emerging Category of Multiple Malformation Syndromes

    Science.gov (United States)

    Izumi, Kosuke

    2016-01-01

    Some genetic disorders caused by mutations in genes encoding components of the transcriptional machinery as well as proteins involved in epigenetic modification of the genome share many overlapping features, such as facial dysmorphisms, growth problems and developmental delay/intellectual disability. As a basis for some shared phenotypic characteristics in these syndromes, a similar transcriptome disturbance, characterized by global transcriptional dysregulation, is believed to play a major role. In this review article, a general overview of gene transcription is provided, and the current knowledge of the mechanisms underlying some disorders of transcriptional regulation, such as Rubinstein- Taybi, Coffin-Siris, Cornelia de Lange, and CHOPS syndromes, are discussed. PMID:27867341

  14. Multiple Signaling Pathways Coordinately Regulate Forgetting of Olfactory Adaptation through Control of Sensory Responses in Caenorhabditis elegans.

    Science.gov (United States)

    Kitazono, Tomohiro; Hara-Kuge, Sayuri; Matsuda, Osamu; Inoue, Akitoshi; Fujiwara, Manabi; Ishihara, Takeshi

    2017-10-18

    invertebrates. We found that in Caenorhabditis elegans hermaphrodite, the noncell autonomous regulations of forgetting of olfactory adaptation is regulated by three conserved proteins: a membrane protein, MACO-1; a receptor tyrosine kinase, SCD-2: and its ligand, HEN-1. MACO-1 and SCD-2/HEN-1, working in coordination, accelerate forgetting by controlling sensory responses in parallel. Furthermore, temporal regulation of neuronal activity is important for proper forgetting. We suggest that multiple pathways may coordinately and temporally regulate forgetting through control of sensory responses. This study should lead to a better understanding of forgetting in higher organisms. Copyright © 2017 the authors 0270-6474/17/3710240-12$15.00/0.

  15. Multiple ketolases involved in light regulation of canthaxanthin biosynthesis in Nostoc punctiforme PCC 73102.

    Science.gov (United States)

    Schöpf, Lotte; Mautz, Jürgen; Sandmann, Gerhard

    2013-05-01

    In the genome of Nostoc punctiforme PCC 73102, three functional β-carotene ketolase genes exist, one of the crtO and two of the crtW type. They were all expressed and their corresponding enzymes were functional inserting 4-keto groups into β-carotene as shown by functional pathway complementation in Escherichia coli. They all synthesized canthaxanthin but with different efficiencies. Canthaxanthin is the photoprotective carotenoid of N. punctiforme PCC 73102. Under high-light stress, its synthesis was enhanced. This was caused by up-regulation of the transcripts of two genes in combination. The first crtB-encoding phytoene synthase is the gate way enzyme of carotenogenesis resulting in an increased inflow into the pathway. The second was the ketolase gene crtW148 which in high light takes over β-carotene conversion into canthaxanthin from the other ketolases. The other ketolases were down-regulated under high-light conditions. CrtW148 was also exclusively responsible for the last step in 4-keto-myxoxanthophyll synthesis.

  16. Environmental emergency response plans (EERPs): A single plan approach to satisfy multiple regulations

    International Nuclear Information System (INIS)

    Muzyka, L.

    1995-01-01

    Conrail is a freight railroad operating in twelve northeast and midwestern states transporting goods and materials over 11,700 miles of railroad. To repair, maintain, rebuild, and manufacture locomotives and rail cars, and to maintain the track, right of way, bridges, tunnels and other structures, Conrail uses petroleum products, solvents and cleaners. These products are stored in hundreds of storage tanks in and around the yards and right of way. To power the trains, locomotives are fueled with diesel fuel. With large volumes of fuel, lubricants, solvents and cleaners, safe and efficient handling of petroleum and chemicals is crucial to avoid negative impacts on the environment. Conrail recently revisited the issue of environmental emergency response planning. In an attempt to assure full compliance with a myriad of federal, state, and local regulation, a ''single plan approach'' was chosen. Single plans for each facility, coined EERPs, were decided on after careful review of the regulations, and evaluation of the company's operational and organizational needs

  17. A Nonlinear Dynamic Approach Reveals a Long-Term Stroke Effect on Cerebral Blood Flow Regulation at Multiple Time Scales

    Science.gov (United States)

    Hu, Kun; Lo, Men-Tzung; Peng, Chung-Kang; Liu, Yanhui; Novak, Vera

    2012-01-01

    Cerebral autoregulation (CA) is an important vascular control mechanism responsible for relatively stable cerebral blood flow despite changes of systemic blood pressure (BP). Impaired CA may leave brain tissue unprotected against potentially harmful effects of BP fluctuations. It is generally accepted that CA is less effective or even inactive at frequencies >∼0.1 Hz. Without any physiological foundation, this concept is based on studies that quantified the coupling between BP and cerebral blood flow velocity (BFV) using transfer function analysis. This traditional analysis assumes stationary oscillations with constant amplitude and period, and may be unreliable or even invalid for analysis of nonstationary BP and BFV signals. In this study we propose a novel computational tool for CA assessment that is based on nonlinear dynamic theory without the assumption of stationary signals. Using this method, we studied BP and BFV recordings collected from 39 patients with chronic ischemic infarctions and 40 age-matched non-stroke subjects during baseline resting conditions. The active CA function in non-stroke subjects was associated with an advanced phase in BFV oscillations compared to BP oscillations at frequencies from ∼0.02 to 0.38 Hz. The phase shift was reduced in stroke patients even at > = 6 months after stroke, and the reduction was consistent at all tested frequencies and in both stroke and non-stroke hemispheres. These results provide strong evidence that CA may be active in a much wider frequency region than previously believed and that the altered multiscale CA in different vascular territories following stroke may have important clinical implications for post-stroke recovery. Moreover, the stroke effects on multiscale cerebral blood flow regulation could not be detected by transfer function analysis, suggesting that nonlinear approaches without the assumption of stationarity are more sensitive for the assessment of the coupling of nonstationary

  18. Shaping long-term primate development: Telomere length trajectory as an indicator of early maternal maltreatment and predictor of future physiologic regulation.

    Science.gov (United States)

    Drury, Stacy S; Howell, Brittany R; Jones, Christopher; Esteves, Kyle; Morin, Elyse; Schlesinger, Reid; Meyer, Jerrold S; Baker, Kate; Sanchez, Mar M

    2017-12-01

    The molecular, neurobiological, and physical health impacts of child maltreatment are well established, yet mechanistic pathways remain inadequately defined. Telomere length (TL) decline is an emerging molecular indicator of stress exposure with definitive links to negative health outcomes in maltreated individuals. The multiple confounders endemic to human maltreatment research impede the identification of causal pathways. This study leverages a unique randomized, cross-foster, study design in a naturalistic translational nonhuman primate model of infant maltreatment. At birth, newborn macaques were randomly assigned to either a maltreating or a competent control mother, balancing for sex, biological mother parenting history, and social rank. Offspring TL was measured longitudinally across the first 6 months of life (infancy) from peripheral blood. Hair cortisol accumulation was also determined at 6, 12, and 18 months of age. TL decline was greater in animals randomized to maltreatment, but also interacted with biological mother group. Shorter TL at 6 months was associated with higher mean cortisol levels through 18 months (juvenile period) when controlling for relevant covariates. These results suggest that even under the equivalent social, nutritional, and environmental conditions feasible in naturalistic translational nonhuman primate models, early adverse caregiving results in lasting molecular scars that foreshadow elevated health risk and physiologic dysregulation.

  19. High efficiency cell-recycle continuous sodium gluconate production by Aspergillus niger using on-line physiological parameters association analysis to regulate feed rate rationally.

    Science.gov (United States)

    Lu, Fei; Li, Chao; Wang, Zejian; Zhao, Wei; Chu, Ju; Zhuang, Yingping; Zhang, Siliang

    2016-11-01

    In this paper, a system of cell-recycle continuous fermentation for sodium gluconate (SG) production by Aspergillus niger (A. niger) was established. Based on initial continuous fermentation result (100.0h) with constant feed rate, an automatic feedback strategy to regulate feed rate using on-line physiological parameters (OUR and DO) was proposed and applied successfully for the first time in the improved continuous fermentation (240.5h). Due to less auxiliary time, highest SG production rate (31.05±0.29gL(-1)h(-1)) and highest yield (0.984±0.067molmol(-1)), overall SG production capacity (975.8±5.8gh(-1)) in 50-L fermentor of improved continuous fermentation increased more than 300.0% compared to that of batch fermentation. Improvement of mass transfer and dispersed mycelia morphology were the two major reasons responsible for the high SG production rate. This system had been successfully applied to industrial fermentation and SG production was greatly improved. Copyright © 2016 Elsevier Ltd. All rights reserved.

  20. Spatial heterogeneity regulates plant-pollinator networks across multiple landscape scales.

    Directory of Open Access Journals (Sweden)

    Eduardo Freitas Moreira

    Full Text Available Mutualistic plant-pollinator interactions play a key role in biodiversity conservation and ecosystem functioning. In a community, the combination of these interactions can generate emergent properties, e.g., robustness and resilience to disturbances such as fluctuations in populations and extinctions. Given that these systems are hierarchical and complex, environmental changes must have multiple levels of influence. In addition, changes in habitat quality and in the landscape structure are important threats to plants, pollinators and their interactions. However, despite the importance of these phenomena for the understanding of biological systems, as well as for conservation and management strategies, few studies have empirically evaluated these effects at the network level. Therefore, the objective of this study was to investigate the influence of local conditions and landscape structure at multiple scales on the characteristics of plant-pollinator networks. This study was conducted in agri-natural lands in Chapada Diamantina, Bahia, Brazil. Pollinators were collected in 27 sampling units distributed orthogonally along a gradient of proportion of agriculture and landscape diversity. The Akaike information criterion was used to select models that best fit the metrics for network characteristics, comparing four hypotheses represented by a set of a priori candidate models with specific combinations of the proportion of agriculture, the average shape of the landscape elements, the diversity of the landscape and the structure of local vegetation. The results indicate that a reduction of habitat quality and landscape heterogeneity can cause species loss and decrease of networks nestedness. These structural changes can reduce robustness and resilience of plant-pollinator networks what compromises the reproductive success of plants, the maintenance of biodiversity and the pollination service stability. We also discuss the possible explanations for

  1. Spatial heterogeneity regulates plant-pollinator networks across multiple landscape scales.

    Science.gov (United States)

    Moreira, Eduardo Freitas; Boscolo, Danilo; Viana, Blandina Felipe

    2015-01-01

    Mutualistic plant-pollinator interactions play a key role in biodiversity conservation and ecosystem functioning. In a community, the combination of these interactions can generate emergent properties, e.g., robustness and resilience to disturbances such as fluctuations in populations and extinctions. Given that these systems are hierarchical and complex, environmental changes must have multiple levels of influence. In addition, changes in habitat quality and in the landscape structure are important threats to plants, pollinators and their interactions. However, despite the importance of these phenomena for the understanding of biological systems, as well as for conservation and management strategies, few studies have empirically evaluated these effects at the network level. Therefore, the objective of this study was to investigate the influence of local conditions and landscape structure at multiple scales on the characteristics of plant-pollinator networks. This study was conducted in agri-natural lands in Chapada Diamantina, Bahia, Brazil. Pollinators were collected in 27 sampling units distributed orthogonally along a gradient of proportion of agriculture and landscape diversity. The Akaike information criterion was used to select models that best fit the metrics for network characteristics, comparing four hypotheses represented by a set of a priori candidate models with specific combinations of the proportion of agriculture, the average shape of the landscape elements, the diversity of the landscape and the structure of local vegetation. The results indicate that a reduction of habitat quality and landscape heterogeneity can cause species loss and decrease of networks nestedness. These structural changes can reduce robustness and resilience of plant-pollinator networks what compromises the reproductive success of plants, the maintenance of biodiversity and the pollination service stability. We also discuss the possible explanations for these relationships and

  2. [HSP90 Inhibitor 17-AAG Inhibits Multiple Myeloma Cell Proliferation by Down-regulating Wnt/β-Catenin Signaling Pathway].

    Science.gov (United States)

    Chen, Kan-Kan; He, Zheng-Mei; Ding, Bang-He; Chen, Yue; Zhang, Li-Juan; Yu, Liang; Gao, Jian

    2016-02-01

    To investigate the inhibitory effect of HSP90 inhibitory 17-AAG on proliferation of multiple myeloma cells and its main mechanism. The multiple myeloma cells U266 were treated with 17-AAG of different concentrations (200, 400, 600 and 800 nmol/L) for 24, 48, and 72 hours respectively, then the proliferation rate, expression levels of β-catenin and C-MYC protein, as well as cell cycle of U266 cells were treated with 17-AAG and were detected by MTT method, Western blot and flow cytometry, respectively. The 17-AAG showed inhibitory effect on the proliferation of U266 cells in dose- and time-depetent manners (r = -0.518, P AAG displayed no inhibitory effect on proliferation of U266 cells (P > 0.05). The result of culturing U266 cells for 72 hours by 17-AAG of different concentrations showed that the more high of 17-AAG concentration, the more low level of β-catenin and C-MYC proteins (P AAG concentration, the more high of cell ratio in G1 phase (P AAG, the more long time of culture, the more high of cell ratio in G1 phase (P AAG can inhibit the proliferation of multiple myeloma cells, the down-regulation of Wnt/β-catenin signaling pathway and inhibition of HSP90 expression may be the main mechnisms of 17-AAG effect.

  3. Regulation of an Autoimmune Model for Multiple Sclerosis in Th2-Biased GATA3 Transgenic Mice

    Directory of Open Access Journals (Sweden)

    Viromi Fernando

    2014-01-01

    Full Text Available T helper (Th2 cells have been proposed to play a neuroprotective role in multiple sclerosis (MS. This is mainly based on “loss-of-function” studies in an animal model for MS, experimental autoimmune encephalomyelitis (EAE, using blocking antibodies against Th2 related cytokines, and knockout mice lacking Th2-related molecules. We tested whether an increase of Th2 responses (“gain-of-function” approach could alter EAE, the approach of novel GATA binding protein 3 (GATA3-transgenic (tg mice that overexpress GATA3, a transcription factor required for Th2 differentiation. In EAE induced with myelin oligodendrocyte glycoprotein (MOG35−55 peptide, GATA3-tg mice had a significantly delayed onset of disease and a less severe maximum clinical score, compared with wild-type C57BL/6 mice. Histologically, GATA3-tg mice had decreased levels of meningitis and demyelination in the spinal cord, and anti-inflammatory cytokine profiles immunologically, however both groups developed similar levels of MOG-specific lymphoproliferative responses. During the early stage, we detected higher levels of interleukin (IL-4 and IL-10, with MOG and mitogen stimulation of regional lymph node cells in GATA3-tg mice. During the late stage, only mitogen stimulation induced higher IL-4 and lower interferon-γ and IL-17 production in GATA3-tg mice. These results suggest that a preexisting bias toward a Th2 immune response may reduce the severity of inflammatory demyelinating diseases, including MS.

  4. Model of the regulation of the rate of multiplication of the stem cells of the bone marrow. [X radiation, gamma radiation

    Energy Technology Data Exchange (ETDEWEB)

    Gruzdev, G P; Monichev, A Ya

    1975-01-01

    A mathematical model of regulation of the rate of multiplication of the stem cells of the bone marrow has been constructed and investigated. Two possible variants of regulation of the proliferative activity of the irradiated stem cells are compared: at the level of tissue and subtissue units. Comparison of the results of modeling with the results of experimental investigations supports the latter mechanism of regulation of the proliferation of the stem cells.

  5. Multiple cone pathways are involved in photic regulation of retinal dopamine.

    Science.gov (United States)

    Qiao, Sheng-Nan; Zhang, Zhijing; Ribelayga, Christophe P; Zhong, Yong-Mei; Zhang, Dao-Qi

    2016-06-30

    Dopamine is a key neurotransmitter in the retina and plays a central role in the light adaptive processes of the visual system. The sole source of retinal dopamine is dopaminergic amacrine cells (DACs). We and others have previously demonstrated that DACs are activated by rods, cones, and intrinsically photosensitive retinal ganglion cells (ipRGCs) upon illumination. However, it is still not clear how each class of photosensitive cells generates light responses in DACs. We genetically isolated cone function in mice to specifically examine the cone-mediated responses of DACs and their neural pathways. In addition to the reported excitatory input to DACs from light-increment (ON) bipolar cells, we found that cones alternatively signal to DACs via a retrograde signalling pathway from ipRGCs. Cones also produce ON and light-decrement (OFF) inhibitory responses in DACs, which are mediated by other amacrine cells, likely driven by type 1 and type 2/3a OFF bipolar cells, respectively. Dye injections indicated that DACs had similar morphological profiles with or without ON/OFF inhibition. Our data demonstrate that cones utilize specific parallel excitatory and inhibitory circuits to modulate DAC activity and efficiently regulate dopamine release and the light-adaptive state of the retina.

  6. Insulin regulates multiple signaling pathways leading to monocyte/macrophage chemotaxis into the wound tissue

    Directory of Open Access Journals (Sweden)

    Yan Liu

    2018-01-01

    Full Text Available Wound healing is a complex process that involves sequential phases that overlap in time and space and affect each other dynamically at the gene and protein levels. We previously showed that insulin accelerates wound healing by stimulating faster and regenerative healing. One of the processes that insulin stimulates is an increase in monocyte/macrophage chemotaxis. In this study, we performed experiments in vivo and in vitro to elucidate the signaling transduction pathways that are involved in insulin-induced monocyte/macrophage chemotaxis. We found that insulin stimulates THP-1 cell chemotaxis in a dose-dependent and insulin receptor-dependent manner. We also show that the kinases PI3K-Akt, SPAK/JNK, and p38 MAPK are key molecules in the insulin-induced signaling pathways that lead to chemoattraction of the THP-1 cell. Furthermore, both PI3K-Akt and SPAK/JNK signaling involve Rac1 activation, an important molecule in regulating cell motility. Indeed, topical application of Rac1 inhibitor at an early stage during the healing process caused delayed and impaired healing even in the presence of insulin. These results delineate cell and molecular mechanisms involved in insulin-induced chemotaxis of monocyte/macrophage, cells that are critical for proper healing.

  7. Trafficking of plant plasma membrane aquaporins: multiple regulation levels and complex sorting signals.

    Science.gov (United States)

    Chevalier, Adrien S; Chaumont, François

    2015-05-01

    Aquaporins are small channel proteins which facilitate the diffusion of water and small neutral molecules across biological membranes. Compared with animals, plant genomes encode numerous aquaporins, which display a large variety of subcellular localization patterns. More specifically, plant aquaporins of the plasma membrane intrinsic protein (PIP) subfamily were first described as plasma membrane (PM)-resident proteins, but recent research has demonstrated that the trafficking and subcellular localization of these proteins are complex and highly regulated. In the past few years, PIPs emerged as new model proteins to study subcellular sorting and membrane dynamics in plant cells. At least two distinct sorting motifs (one cytosolic, the other buried in the membrane) are required to direct PIPs to the PM. Hetero-oligomerization and interaction with SNAREs (soluble N-ethylmaleimide-sensitive factor protein attachment protein receptors) also influence the subcellular trafficking of PIPs. In addition to these constitutive processes, both the progression of PIPs through the secretory pathway and their dynamics at the PM are responsive to changing environmental conditions. © The Author 2014. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  8. Small leucine rich proteoglycan family regulates multiple signalling pathways in neural development and maintenance.

    Science.gov (United States)

    Dellett, Margaret; Hu, Wanzhou; Papadaki, Vasiliki; Ohnuma, Shin-ichi

    2012-04-01

    The small leucine-rich repeat proteoglycan (SLRPs) family of proteins currently consists of five classes, based on their structural composition and chromosomal location. As biologically active components of the extracellular matrix (ECM), SLRPs were known to bind to various collagens, having a role in regulating fibril assembly, organization and degradation. More recently, as a function of their diverse proteins cores and glycosaminoglycan side chains, SLRPs have been shown to be able to bind various cell surface receptors, growth factors, cytokines and other ECM components resulting in the ability to influence various cellular functions. Their involvement in several signaling pathways such as Wnt, transforming growth factor-β and epidermal growth factor receptor also highlights their role as matricellular proteins. SLRP family members are expressed during neural development and in adult neural tissues, including ocular tissues. This review focuses on describing SLRP family members involvement in neural development with a brief summary of their role in non-neural ocular tissues and in response to neural injury. © 2012 The Authors Development, Growth & Differentiation © 2012 Japanese Society of Developmental Biologists.

  9. Multiple structure-intrinsic disorder interactions regulate and coordinate Hox protein function

    Science.gov (United States)

    Bondos, Sarah

    During animal development, Hox transcription factors determine fate of developing tissues to generate diverse organs and appendages. Hox proteins are famous for their bizarre mutant phenotypes, such as replacing antennae with legs. Clearly, the functions of individual Hox proteins must be distinct and reliable in vivo, or the organism risks malformation or death. However, within the Hox protein family, the DNA-binding homeodomains are highly conserved and the amino acids that contact DNA are nearly invariant. These observations raise the question: How do different Hox proteins correctly identify their distinct target genes using a common DNA binding domain? One possible means to modulate DNA binding is through the influence of the non-homeodomain protein regions, which differ significantly among Hox proteins. However genetic approaches never detected intra-protein interactions, and early biochemical attempts were hindered because the special features of ``intrinsically disordered'' sequences were not appreciated. We propose the first-ever structural model of a Hox protein to explain how specific contacts between distant, intrinsically disordered regions of the protein and the homeodomain regulate DNA binding and coordinate this activity with other Hox molecular functions.

  10. Novel energy-saving strategies to multiple stressors in birds: the ultradian regulation of body temperature.

    Science.gov (United States)

    Tattersall, Glenn J; Roussel, Damien; Voituron, Yann; Teulier, Loïc

    2016-09-28

    This study aimed to examine thermoregulatory responses in birds facing two commonly experienced stressors, cold and fasting. Logging devices allowing long-term and precise access to internal body temperature were placed within the gizzards of ducklings acclimated to cold (CA) (5°C) or thermoneutrality (TN) (25°C). The animals were then examined under three equal 4-day periods: ad libitum feeding, fasting and re-feeding. Through the analysis of daily as well as short-term, or ultradian, variations of body temperature, we showed that while ducklings at TN show only a modest decline in daily thermoregulatory parameters when fasted, they exhibit reduced surface temperatures from key sites of vascular heat exchange during fasting. The CA birds, on the other hand, significantly reduced their short-term variations of body temperature while increasing long-term variability when fasting. This phenomenon would allow the CA birds to reduce the energetic cost of body temperature maintenance under fasting. By analysing ultradian regulation of body temperature, we describe a means by which an endotherm appears to lower thermoregulatory costs in response to the combined stressors of cold and fasting. © 2016 The Author(s).

  11. REGULATION OF EXPRESSION OF MULTIPLE BETA- GLUCOSIDASES OF ASPERGILLUS TERREUS AND THEIR PURIFICATION AND CHARACTERIZATION

    Directory of Open Access Journals (Sweden)

    Asiya Nazir

    2009-02-01

    Full Text Available This study reports the regulation and purification of -glucosidases from a thermotolerant Aspergillus terreus AN1 strain, previously reported for efficient deinking of composite paper waste. The differential expression of four -glucosidase isoforms, in response to carbon sources in production medium, was studied by electrophoretically resolving proteins by polyacrylamide gel electro-phoresis analysis (PAGE and developing zymograms using methylum-belliferyl -D glucoside as substrate. Three -glucosidases (GI, GII & GIII were purified using chromatographic techniques. SDS-PAGE revealed the respective molecular masses of GI, GII, and GIII, as 29, 43, and 98 KDa, and isoelectric point (pI to be 2.8, 3.7, and 3.0. The -glucosidases exhibited diverse pH and temperature optima as well as stability. -Glucosidase I (GI specifically recog-nized pNP--glucopyranoside (pNPG as a substrate, whereas, -glucosidase II (GII and III (GIII also showed activities against cellobiose and salicin. In contrast to GII and GIII, the activity of GI was positively influenced in the presence of hexoses/pentoses and alcohols. Km and Vmax for hydrolysis of pNPG by GI, GII, andGIII were found to be 14.2 mM and 166.9 µmol -1mg protein -1, 4.37 mM, and 34.7 µmol -1mg proteins -1, and 11.1 mM and 378.7µ mol -1 mg protein -1, respectively.

  12. Improving anxiety regulation in patients with breast cancer at the beginning of the survivorship period: a randomized clinical trial comparing the benefits of single-component and multiple-component group interventions.

    Science.gov (United States)

    Merckaert, Isabelle; Lewis, Florence; Delevallez, France; Herman, Sophie; Caillier, Marie; Delvaux, Nicole; Libert, Yves; Liénard, Aurore; Nogaret, Jean-Marie; Ogez, David; Scalliet, Pierre; Slachmuylder, Jean-Louis; Van Houtte, Paul; Razavi, Darius

    2017-08-01

    To compare in a multicenter randomized controlled trial the benefits in terms of anxiety regulation of a 15-session single-component group intervention (SGI) based on support with those of a 15-session multiple-component structured manualized group intervention (MGI) combining support with cognitive-behavioral and hypnosis components. Patients with nonmetastatic breast cancer were randomly assigned at the beginning of the survivorship period to the SGI (n = 83) or MGI (n = 87). Anxiety regulation was assessed, before and after group interventions, through an anxiety regulation task designed to assess their ability to regulate anxiety psychologically (anxiety levels) and physiologically (heart rates). Questionnaires were used to assess psychological distress, everyday anxiety regulation, and fear of recurrence. Group allocation was computer generated and concealed till baseline completion. Compared with patients in the SGI group (n = 77), patients attending the MGI group (n = 82) showed significantly reduced anxiety after a self-relaxation exercise (P = .006) and after exposure to anxiety triggers (P = .013) and reduced heart rates at different time points throughout the task (P = .001 to P = .047). The MGI participants also reported better everyday anxiety regulation (P = .005), greater use of fear of recurrence-related coping strategies (P = .022), and greater reduction in fear of recurrence-related psychological distress (P = .017) compared with the SGI group. This study shows that an MGI combining support with cognitive-behavioral techniques and hypnosis is more effective than an SGI based only on support in improving anxiety regulation in patients with breast cancer. Copyright © 2016 John Wiley & Sons, Ltd.

  13. Vital Recorder—a free research tool for automatic recording of high-resolution time-synchronised physiological data from multiple anaesthesia devices

    OpenAIRE

    Lee, Hyung-Chul; Jung, Chul-Woo

    2018-01-01

    The current anaesthesia information management system (AIMS) has limited capability for the acquisition of high-quality vital signs data. We have developed a Vital Recorder program to overcome the disadvantages of AIMS and to support research. Physiological data of surgical patients were collected from 10 operating rooms using the Vital Recorder. The basic equipment used were a patient monitor, the anaesthesia machine, and the bispectral index (BIS) monitor. Infusion pumps, cardiac output mon...

  14. Modeling the effector - regulatory T cell cross-regulation reveals the intrinsic character of relapses in Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    Torrealdea Javier

    2011-07-01

    Full Text Available Abstract Background The relapsing-remitting dynamics is a hallmark of autoimmune diseases such as Multiple Sclerosis (MS. Although current understanding of both cellular and molecular mechanisms involved in the pathogenesis of autoimmune diseases is significant, how their activity generates this prototypical dynamics is not understood yet. In order to gain insight about the mechanisms that drive these relapsing-remitting dynamics, we developed a computational model using such biological knowledge. We hypothesized that the relapsing dynamics in autoimmunity can arise through the failure in the mechanisms controlling cross-regulation between regulatory and effector T cells with the interplay of stochastic events (e.g. failure in central tolerance, activation by pathogens that are able to trigger the immune system. Results The model represents five concepts: central tolerance (T-cell generation by the thymus, T-cell activation, T-cell memory, cross-regulation (negative feedback between regulatory and effector T-cells and tissue damage. We enriched the model with reversible and irreversible tissue damage, which aims to provide a comprehensible link between autoimmune activity and clinical relapses and active lesions in the magnetic resonances studies in patients with Multiple Sclerosis. Our analysis shows that the weakness in this negative feedback between effector and regulatory T-cells, allows the immune system to generate the characteristic relapsing-remitting dynamics of autoimmune diseases, without the need of additional environmental triggers. The simulations show that the timing at which relapses appear is highly unpredictable. We also introduced targeted perturbations into the model that mimicked immunotherapies that modulate effector and regulatory populations. The effects of such therapies happened to be highly dependent on the timing and/or dose, and on the underlying dynamic of the immune system. Conclusion The relapsing dynamic in MS

  15. Vital Recorder-a free research tool for automatic recording of high-resolution time-synchronised physiological data from multiple anaesthesia devices.

    Science.gov (United States)

    Lee, Hyung-Chul; Jung, Chul-Woo

    2018-01-24

    The current anaesthesia information management system (AIMS) has limited capability for the acquisition of high-quality vital signs data. We have developed a Vital Recorder program to overcome the disadvantages of AIMS and to support research. Physiological data of surgical patients were collected from 10 operating rooms using the Vital Recorder. The basic equipment used were a patient monitor, the anaesthesia machine, and the bispectral index (BIS) monitor. Infusion pumps, cardiac output monitors, regional oximeter, and rapid infusion device were added as required. The automatic recording option was used exclusively and the status of recording was frequently checked through web monitoring. Automatic recording was successful in 98.5% (4,272/4,335) cases during eight months of operation. The total recorded time was 13,489 h (3.2 ± 1.9 h/case). The Vital Recorder's automatic recording and remote monitoring capabilities enabled us to record physiological big data with minimal effort. The Vital Recorder also provided time-synchronised data captured from a variety of devices to facilitate an integrated analysis of vital signs data. The free distribution of the Vital Recorder is expected to improve data access for researchers attempting physiological data studies and to eliminate inequalities in research opportunities due to differences in data collection capabilities.

  16. Physiology Flies with Time.

    Science.gov (United States)

    Sehgal, Amita

    2017-11-30

    The 2017 Nobel Prize in Medicine or Physiology has been awarded to Jeffrey Hall, Michael Rosbash, and Michael Young for elucidating molecular mechanisms of the circadian clock. From studies beginning in fruit flies, we now know that circadian regulation pervades most biological processes and has strong ties to human health and disease. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. IVF policy and global/local politics: the making of multiple-embryo transfer regulation in Taiwan.

    Science.gov (United States)

    Wu, Chia-Ling

    2012-08-01

    This paper analyzes the regulatory trajectory of multiple-embryo transfer in in-vitro fertilization (IVF) in Taiwan. Taking a latecomer to policy-making as the case, it argues the importance of conceptualizing the global/local dynamics in policy-making for assisted reproductive technology (ART). The conceptual framework is built upon recent literature on standardization, science policy, and global assemblage. I propose three interrelated features that reveal the "global in the local": (1) the power relationships among stakeholders, (2) the selected global form that involved actors drew upon, and (3) the re-contextualized assemblage made of local networks. Data included archives, interviews, and participant observation. In different historical periods the specific stakeholders selected different preferred global forms for Taiwan, such as Britain's code of ethics in the 1990s, the American guideline in the early 2000s, and the European trend in the mid-2000s. The global is heterogeneous. The failure to transfer the British regulation, the revision of the American guideline by adding one more embryo than it specified, and the gap between the cited European trend and the "no more than four" in Taiwan's 2007 Human Reproduction Law all show that the local network further transforms the selected global form, confining it to rhetoric only or tailoring it to local needs. Overall, Taiwanese practitioners successfully maintained their medical autonomy to build a 'flexible standardization'. Multiple pregnancy remains the most common health risk of IVF in Taiwan. Copyright © 2012 Elsevier Ltd. All rights reserved.

  18. Nontranscriptional regulation of SYK by the coactivator OCA-B is required at multiple stages of B cell development.

    Science.gov (United States)

    Siegel, Rachael; Kim, Unkyu; Patke, Alina; Yu, Xin; Ren, Xiaodi; Tarakhovsky, Alexander; Roeder, Robert G

    2006-05-19

    OCA-B was originally identified as a nuclear transcriptional coactivator that is essential for antigen-driven immune responses. The later identification of a membrane bound, myristoylated form of OCA-B suggested additional, unique functions in B cell signaling pathways. This study has shown that OCA-B also functions in the pre-B1-to-pre-B2 cell transition and, most surprisingly, that it directly interacts with SYK, a tyrosine kinase critical for pre-BCR and BCR signaling. This unprecedented type of interaction-a transcriptional coactivator with a signaling kinase-occurs in the cytoplasm and directly regulates SYK stability. This study indicates that OCA-B is required for pre-BCR and BCR signaling at multiple stages of B cell development through its nontranscriptional regulation of SYK. Combined with the deregulation of OCA-B target genes, this may help explain the multitude of defects observed in B cell development and immune responses of Oca-b-/- mice.

  19. In Vitro Effect of Malachite Green on Candida albicans Involves Multiple Pathways and Transcriptional Regulators UPC2 and STP2

    Science.gov (United States)

    Dhamgaye, Sanjiveeni; Devaux, Frederic; Manoharlal, Raman; Vandeputte, Patrick; Shah, Abdul Haseeb; Singh, Ashutosh; Blugeon, Corinne; Sanglard, Dominique

    2012-01-01

    In this study, we show that a chemical dye, malachite green (MG), which is commonly used in the fish industry as an antifungal, antiparasitic, and antibacterial agent, could effectively kill Candida albicans and non-C. albicans species. We have demonstrated that Candida cells are susceptible to MG at a very low concentration (MIC that reduces growth by 50% [MIC50], 100 ng ml−1) and that the effect of MG is independent of known antifungal targets, such as ergosterol metabolism and major drug efflux pump proteins. Transcriptional profiling in response to MG treatment of C. albicans cells revealed that of a total of 207 responsive genes, 167 genes involved in oxidative stress, virulence, carbohydrate metabolism, heat shock, amino acid metabolism, etc., were upregulated, while 37 genes involved in iron acquisition, filamentous growth, mitochondrial respiration, etc., were downregulated. We confirmed experimentally that Candida cells exposed to MG resort to a fermentative mode of metabolism, perhaps due to defective respiration. In addition, we showed that MG triggers depletion of intracellular iron pools and enhances reactive oxygen species (ROS) levels. These effects could be reversed by the addition of iron or antioxidants, respectively. We provided evidence that the antifungal effect of MG is exerted through the transcription regulators UPC2 (regulating ergosterol biosynthesis and azole resistance) and STP2 (regulating amino acid permease genes). Taken together, our transcriptome, genetic, and biochemical results allowed us to decipher the multiple mechanisms by which MG exerts its anti-Candida effects, leading to a metabolic shift toward fermentation, increased generation of ROS, labile iron deprivation, and cell necrosis. PMID:22006003

  20. Connections Between Future Time Perspectives and Self-Regulated Learning for Mid-Year Engineering Students: A Multiple Case Study

    Science.gov (United States)

    Chasmar, Justine

    This dissertation presents multiple studies with the purpose of understanding the connections between undergraduate engineering students' motivations, specifically students' Future Time Perspectives (FTPs) and Self-Regulated Learning (SRL). FTP refers to the views students hold about the future and how their perceptions of current tasks are affected by these views. SRL connects the behaviors, metacognition, and motivation of students in their learning. The goals of this research project were to 1) qualitatively describe and document engineering students' SRL strategies, 2) examine interactions between engineering students' FTPs and SRL strategy use, and 3) explore goal-setting as a bridge between FTP and SRL. In an exploratory qualitative study with mid-year industrial engineering students to examine the SRL strategies used before and after an SRL intervention, results showed that students intended to use more SRL strategies than they attempted. However, students self-reported using new SRL strategies from the intervention. Students in this population also completed a survey and a single interview about FTP and SRL. Results showed perceptions of instrumentality of coursework and skills as motivation for using SRL strategies, and a varied use of SRL strategies for students with different FTPs. Overall, three types of student FTP were seen: students with a single realistic view of the future, conflicting ideal and realistic future views, or open views of the future. A sequential explanatory mixed methods study was conducted with mid-year students from multiple engineering majors. First a cluster analysis of survey results of FTP items compared to FTP interview responses was used for participant selection. Then a multiple case study was conducted with data collected through surveys, journal entries, course performance, and two interviews. Results showed that students with a well-defined FTP self-regulated in the present based on their varied perceptions of

  1. Autonomous and controlled motivational regulations for multiple health-related behaviors: between- and within-participants analyses

    Science.gov (United States)

    Hagger, M.S.; Hardcastle, S.J.; Chater, A.; Mallett, C.; Pal, S.; Chatzisarantis, N.L.D.

    2014-01-01

    Self-determination theory has been applied to the prediction of a number of health-related behaviors with self-determined or autonomous forms of motivation generally more effective in predicting health behavior than non-self-determined or controlled forms. Research has been confined to examining the motivational predictors in single health behaviors rather than comparing effects across multiple behaviors. The present study addressed this gap in the literature by testing the relative contribution of autonomous and controlling motivation to the prediction of a large number of health-related behaviors, and examining individual differences in self-determined motivation as a moderator of the effects of autonomous and controlling motivation on health behavior. Participants were undergraduate students (N = 140) who completed measures of autonomous and controlled motivational regulations and behavioral intention for 20 health-related behaviors at an initial occasion with follow-up behavioral measures taken four weeks later. Path analysis was used to test a process model for each behavior in which motivational regulations predicted behavior mediated by intentions. Some minor idiosyncratic findings aside, between-participants analyses revealed significant effects for autonomous motivational regulations on intentions and behavior across the 20 behaviors. Effects for controlled motivation on intentions and behavior were relatively modest by comparison. Intentions mediated the effect of autonomous motivation on behavior. Within-participants analyses were used to segregate the sample into individuals who based their intentions on autonomous motivation (autonomy-oriented) and controlled motivation (control-oriented). Replicating the between-participants path analyses for the process model in the autonomy- and control-oriented samples did not alter the relative effects of the motivational orientations on intention and behavior. Results provide evidence for consistent effects

  2. Physiological parameters

    International Nuclear Information System (INIS)

    Natera, E.S.

    1998-01-01

    The physiological characteristics of man depend on the intake, metabolism and excretion of stable elements from food, water, and air. The physiological behavior of natural radionuclides and radionuclides from nuclear weapons testing and from the utilization of nuclear energy is believed to follow the pattern of stable elements. Hence information on the normal physiological processes occurring in the human body plays an important role in the assessment of the radiation dose received by man. Two important physiological parameters needed for internal dose determination are the pulmonary function and the water balance. In the Coordinated Research Programme on the characterization of Asian population, five participants submitted data on these physiological characteristics - China, India, Japan, Philippines and Viet Nam. During the CRP, data on other pertinent characteristics such as physical and dietary were simultaneously being collected. Hence, the information on the physiological characteristics alone, coming from the five participants were not complete and are probably not sufficient to establish standard values for the Reference Asian Man. Nonetheless, the data collected is a valuable contribution to this research programme

  3. Iterative use of nuclear receptor Nr5a2 regulates multiple stages of liver and pancreas development

    Science.gov (United States)

    Nissim, Sahar; Weeks, Olivia; Talbot, Jared C.; Hedgepeth, John W.; Wucherpfennig, Julia; Schatzman-Bone, Stephanie; Swinburne, Ian; Cortes, Mauricio; Alexa, Kristen; Megason, Sean; North, Trista E.; Amacher, Sharon L.; Goessling, Wolfram

    2016-01-01

    The stepwise progression of common endoderm progenitors into differentiated liver and pancreas organs is regulated by a dynamic array of signals that are not well understood. The nuclear receptor subfamily 5, group A, member 2 gene nr5a2, also known as Liver receptor homolog-1 (Lrh-1) is expressed in several tissues including the developing liver and pancreas. Here, we interrogate the role of Nr5a2 at multiple developmental stages using genetic and chemical approaches and uncover novel pleiotropic requirements during zebrafish liver and pancreas development. Zygotic loss of nr5a2 in a targeted genetic null mutant disrupted the development of the exocrine pancreas and liver, while leaving the endocrine pancreas intact. Loss of nr5a2 abrogated exocrine pancreas markers such as trypsin, while pancreas progenitors marked by ptf1a or pdx1 remained unaffected, suggesting a role for Nr5a2 in regulating pancreatic acinar cell differentiation. In the developing liver, Nr5a2 regulates hepatic progenitor outgrowth and differentiation, as nr5a2 mutants exhibited reduced hepatoblast markers hnf4α and prox1 as well as differentiated hepatocyte marker fabp10a. Through the first in vivo use of Nr5a2 chemical antagonist Cpd3, the iterative requirement for Nr5a2 for exocrine pancreas and liver differentiation was temporally elucidated: chemical inhibition of Nr5a2 function during hepatopancreas progenitor specification was sufficient to disrupt exocrine pancreas formation and enhance the size of the embryonic liver, suggesting that Nr5a2 regulates hepatic versus pancreatic progenitor fate choice. Chemical inhibition of Nr5a2 at a later time during pancreas and liver differentiation was sufficient to block the formation of mature acinar cells and hepatocytes. These findings define critical iterative and pleiotropic roles for Nr5a2 at distinct stages of pancreas and liver organogenesis, and provide novel perspectives for interpreting the role of Nr5a2 in disease. PMID:27474396

  4. Personalized physiological medicine.

    Science.gov (United States)

    Ince, Can

    2017-12-28

    This paper introduces the concept of personalized physiological medicine that is specifically directed at the needs of the critically ill patient. This differs from the conventional view of personalized medicine, characterized by biomarkers and gene profiling, instead focusing on time-variant changes in the pathophysiology and regulation of various organ systems and their cellular and subcellular constituents. I propose that personalized physiological medicine is composed of four pillars relevant to the critically ill patient. Pillar 1 is defined by the frailty and fitness of the patient and their physiological reserve to cope with the stress of critical illness and therapy. Pillar 2 involves monitoring of the key physiological variables of the different organ systems and their response to disease and therapy. Pillar 3 concerns the evaluation of the success of resuscitation by assessment of the hemodynamic coherence between the systemic and microcirculation and parenchyma of the organ systems. Finally, pillar 4 is defined by the integration of the physiological and clinical data into a time-learning adaptive model of the patient to provide feedback about the function of organ systems and to guide and assess the response to disease and therapy. I discuss each pillar and describe the challenges to research and development that will allow the realization of personalized physiological medicine to be practiced at the bedside for critically ill patients.

  5. Regulating multiple externalities

    DEFF Research Database (Denmark)

    Waldo, Staffan; Jensen, Frank; Nielsen, Max

    2016-01-01

    Open access is a well-known externality problem in fisheries causing excess capacity and overfishing. Due to global warming, externality problems from CO2 emissions have gained increased interest. With two externality problems, a first-best optimum can be achieved by using two regulatory instrume......Open access is a well-known externality problem in fisheries causing excess capacity and overfishing. Due to global warming, externality problems from CO2 emissions have gained increased interest. With two externality problems, a first-best optimum can be achieved by using two regulatory...

  6. Multiple length peptide-pheromone variants produced by Streptococcus pyogenes directly bind Rgg proteins to confer transcriptional regulation.

    Science.gov (United States)

    Aggarwal, Chaitanya; Jimenez, Juan Cristobal; Nanavati, Dhaval; Federle, Michael J

    2014-08-08

    Streptococcus pyogenes, a human-restricted pathogen, accounts for substantial mortality related to infections worldwide. Recent studies indicate that streptococci produce and respond to several secreted peptide signaling molecules (pheromones), including those known as short hydrophobic peptides (SHPs), to regulate gene expression by a quorum-sensing mechanism. Upon transport into the bacterial cell, pheromones bind to and modulate activity of receptor proteins belonging to the Rgg family of transcription factors. Previously, we reported biofilm regulation by the Rgg2/3 quorum-sensing circuit in S. pyogenes. The aim of this study was to identify the composition of mature pheromones from cell-free culture supernatants that facilitate biofilm formation. Bioluminescent reporters were employed to detect active pheromones in culture supernatants fractionated by reverse-phase chromatography, and mass spectrometry was used to characterize their properties. Surprisingly, multiple SHPs that varied by length were detected. Synthetic peptides of each variant were tested individually using bioluminescence reporters and biofilm growth assays, and although activities differed widely among the group, peptides comprising the C-terminal eight amino acids of the full-length native peptide were most active. Direct Rgg/SHP interactions were determined using a fluorescence polarization assay that utilized FITC-labeled peptide ligands. Peptide receptor affinities were seen to be as low as 500 nm and their binding affinities directly correlated with observed bioactivity. Revelation of naturally produced pheromones along with determination of their affinity for cognate receptors are important steps forward in designing compounds whose purpose is positioned for future therapeutics aimed at treating infections through the interference of bacterial communication. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  7. Regulatory Physiology

    Science.gov (United States)

    Lane, Helen W.; Whitson, Peggy A.; Putcha, Lakshmi; Baker, Ellen; Smith, Scott M.; Stewart, Karen; Gretebeck, Randall; Nimmagudda, R. R.; Schoeller, Dale A.; Davis-Street, Janis

    1999-01-01

    As noted elsewhere in this report, a central goal of the Extended Duration Orbiter Medical Project (EDOMP) was to ensure that cardiovascular and muscle function were adequate to perform an emergency egress after 16 days of spaceflight. The goals of the Regulatory Physiology component of the EDOMP were to identify and subsequently ameliorate those biochemical and nutritional factors that deplete physiological reserves or increase risk for disease, and to facilitate the development of effective muscle, exercise, and cardiovascular countermeasures. The component investigations designed to meet these goals focused on biochemical and physiological aspects of nutrition and metabolism, the risk of renal (kidney) stone formation, gastrointestinal function, and sleep in space. Investigations involved both ground-based protocols to validate proposed methods and flight studies to test those methods. Two hardware tests were also completed.

  8. Mathematical physiology

    CERN Document Server

    Sneyd, James

    2009-01-01

    There has been a long history of interaction between mathematics and physiology. This book looks in detail at a wide selection of mathematical models in physiology, showing how physiological problems can be formulated and studied mathematically, and how such models give rise to interesting and challenging mathematical questions. With its coverage of many recent models it gives an overview of the field, while many older models are also discussed, to put the modern work in context. In this second edition the coverage of basic principles has been expanded to include such topics as stochastic differential equations, Markov models and Gibbs free energy, and the selection of models has also been expanded to include some of the basic models of fluid transport, respiration/perfusion, blood diseases, molecular motors, smooth muscle, neuroendrocine cells, the baroreceptor loop, turboglomerular oscillations, blood clotting and the retina. Owing to this extensive coverage, the second edition is published in two volumes. ...

  9. Physiological pseudomyopia.

    Science.gov (United States)

    Jones, R

    1990-08-01

    Objective refraction through plus fogging lenses and base-in prisms revealed that normally accommodation is not completely relaxed when the stimulus to accommodation is zero. The myopic shift in the refractive error due to this focus error of accommodation was defined as physiological pseudomyopia. Two previously established features of accommodation are responsible for this behavior: (1) accommodation acts as a proportional control system for steady-state responses; and (2) the rest focus of accommodation is nonzero. It is proposed that the hyperopic shift in refraction observed in cycloplegia is the result of elimination of physiological pseudomyopia.

  10. Transforming growth factor alpha (TGFα regulates granulosa cell tumor (GCT cell proliferation and migration through activation of multiple pathways.

    Directory of Open Access Journals (Sweden)

    Cheng Wang

    Full Text Available Granulosa cell tumors (GCTs are the most common ovarian estrogen producing tumors, leading to symptoms of excessive estrogen such as endometrial hyperplasia and endometrial adenocarcinoma. These tumors have malignant potential and often recur. The etiology of GCT is unknown. TGFα is a potent mitogen for many different cells. However, its function in GCT initiation, progression and metastasis has not been determined. The present study aims to determine whether TGFα plays a role in the growth of GCT cells. KGN cells, which are derived from an invasive GCT and have many features of normal granulosa cells, were used as the cellular model. Immunohistochemistry, Western blot and RT-PCR results showed that the ErbB family of receptors is expressed in human GCT tissues and GCT cell lines. RT-PCR results also indicated that TGFα and EGF are expressed in the human granulosa cells and the GCT cell lines, suggesting that TGFα might regulate GCT cell function in an autocrine/paracrine manner. TGFα stimulated KGN cell DNA synthesis, cell proliferation, cell viability, cell cycle progression, and cell migration. TGFα rapidly activated EGFR/PI3K/Akt and mTOR pathways, as indicated by rapid phosphorylation of Akt, TSC2, Rictor, mTOR, P70S6K and S6 proteins following TGFα treatment. TGFα also rapidly activated the EGFR/MEK/ERK pathway, and P38 MAPK pathways, as indicated by the rapid phosphorylation of EGFR, MEK, ERK1/2, P38, and CREB after TGFα treatment. Whereas TGFα triggered a transient activation of Akt, it induced a sustained activation of ERK1/2 in KGN cells. Long-term treatment of KGN cells with TGFα resulted in a significant increase in cyclin D2 and a decrease in p27/Kip1, two critical regulators of granulosa cell proliferation and granulosa cell tumorigenesis. In conclusion, TGFα, via multiple signaling pathways, regulates KGN cell proliferation and migration and may play an important role in the growth and metastasis of GCTs.

  11. Study of physiological properties of some probiotics in multiple cultures with mesophilic lactic acid bacteria by Flora Danica Ch. Hansen commercial starter

    Directory of Open Access Journals (Sweden)

    DANIELA PARASCHIV

    2011-12-01

    Full Text Available The aim of this study was to establish the growth ability and stability of probiotic strains Lactobacillus acidophilus (commercial code La-5®, Lactobacillus casei ssp. paracasei (commercial code L. casei 431® and Bifidobacterium bifidus (commercial code BB-12® in multiple cultures with mesophilic lactic bacteria, Lactococcus lactis ssp. cremoris, Lactococcus lactis ssp. lactis, Lactococcus lactis ssp. diacetylactis and Leuconostoc mesenteroides spp. cremoris, as Flora Danica Chr. Hansen commercial starters. Under the controlled fermentative conditions described below, a good starter combination, for the high rate of cells multiplication and for the good viability during storage, was identified in the mixture of L. casei 431®, BB-12® and Flora Danica, in ratio of 1:1:1 (9 log CFU/mL for each starter culture.

  12. Study of physiological properties of some probiotics in multiple cultures with mesophilic lactic acid bacteria by Flora Danica Ch. Hansen commercial starter

    OpenAIRE

    DANIELA PARASCHIV; AIDA VASILE; MADALINA CONSTANTIN; ALEXANDRU CIOBANU; GABRIELA BAHRIM

    2011-01-01

    The aim of this study was to establish the growth ability and stability of probiotic strains Lactobacillus acidophilus (commercial code La-5®), Lactobacillus casei ssp. paracasei (commercial code L. casei 431®) and Bifidobacterium bifidus (commercial code BB-12®) in multiple cultures with mesophilic lactic bacteria, Lactococcus lactis ssp. cremoris, Lactococcus lactis ssp. lactis, Lactococcus lactis ssp. diacetylactis and Leuconostoc mesenteroides spp. cremoris, as Flora Danica Chr. Hansen co...

  13. Multiple functions of the crustacean gill: osmotic/ionic regulation, acid-base balance, ammonia excretion, and bioaccumulation of toxic metals

    Science.gov (United States)

    Henry, Raymond P.; Lucu, Čedomil; Onken, Horst; Weihrauch, Dirk

    2012-01-01

    The crustacean gill is a multi-functional organ, and it is the site of a number of physiological processes, including ion transport, which is the basis for hemolymph osmoregulation; acid-base balance; and ammonia excretion. The gill is also the site by which many toxic metals are taken up by aquatic crustaceans, and thus it plays an important role in the toxicology of these species. This review provides a comprehensive overview of the ecology, physiology, biochemistry, and molecular biology of the mechanisms of osmotic and ionic regulation performed by the gill. The current concepts of the mechanisms of ion transport, the structural, biochemical, and molecular bases of systemic physiology, and the history of their development are discussed. The relationship between branchial ion transport and hemolymph acid-base regulation is also treated. In addition, the mechanisms of ammonia transport and excretion across the gill are discussed. And finally, the toxicology of heavy metal accumulation via the gill is reviewed in detail. PMID:23162474

  14. Exercise physiology

    DEFF Research Database (Denmark)

    Kiens, Bente; Richter, Erik; Wojtaszewski, Jørgen

    2014-01-01

    The passing of Professor Bengt Saltin on September 12, 2014 truly marks the end of an era. As editor of the Journal of Applied Physiology and one of Bengt’s many collaborators and colleagues, I wanted the Journal to celebrate his many seminal contributions by means of an Editorial. Professor Bent...

  15. Assessments at multiple levels of biological organization allow for an integrative determination of physiological tolerances to turbidity in an endangered fish species.

    Science.gov (United States)

    Hasenbein, Matthias; Fangue, Nann A; Geist, Juergen; Komoroske, Lisa M; Truong, Jennifer; McPherson, Rina; Connon, Richard E

    2016-01-01

    Turbidity can influence trophic levels by altering species composition and can potentially affect fish feeding strategies and predator-prey interactions. The estuarine turbidity maximum, described as an area of increased suspended particles, phytoplankton and zooplankton, generally represents a zone with higher turbidity and enhanced food sources important for successful feeding and growth in many fish species. The delta smelt (Hypomesus transpacificus) is an endangered, pelagic fish species endemic to the San Francisco Estuary and Sacramento-San Joaquin River Delta, USA, where it is associated with turbid waters. Turbidity is known to play an important role for the completion of the species' life cycle; however, turbidity ranges in the Delta are broad, and specific requirements for this fish species are still unknown. To evaluate turbidity requirements for early life stages, late-larval delta smelt were maintained at environmentally relevant turbidity levels ranging from 5 to 250 nephelometric turbidity units (NTU) for 24 h, after which a combination of physiological endpoints (molecular biomarkers and cortisol), behavioural indices (feeding) and whole-organism measures (survival) were determined. All endpoints delivered consistent results and identified turbidities between 25 and 80 NTU as preferential. Delta smelt survival rates were highest between 12 and 80 NTU and feeding rates were highest between 25 and 80 NTU. Cortisol levels indicated minimal stress between 35 and 80 NTU and were elevated at low turbidities (5, 12 and 25 NTU). Expression of stress-related genes indicated significant responses for gst, hsp70 and glut2 in high turbidities (250 NTU), and principal component analysis on all measured genes revealed a clustering of 25, 35, 50 and 80 NTU separating the medium-turbidity treatments from low- and high-turbidity treatments. Taken together, these data demonstrate that turbidity levels that are either too low or too high affect delta

  16. Plant aquaporins: roles in plant physiology.

    Science.gov (United States)

    Li, Guowei; Santoni, Véronique; Maurel, Christophe

    2014-05-01

    Aquaporins are membrane channels that facilitate the transport of water and small neutral molecules across biological membranes of most living organisms. Here, we present comprehensive insights made on plant aquaporins in recent years, pointing to their molecular and physiological specificities with respect to animal or microbial counterparts. In plants, aquaporins occur as multiple isoforms reflecting a high diversity of cellular localizations and various physiological substrates in addition to water. Of particular relevance for plants is the transport by aquaporins of dissolved gases such as carbon dioxide or metalloids such as boric or silicic acid. The mechanisms that determine the gating and subcellular localization of plant aquaporins are extensively studied. They allow aquaporin regulation in response to multiple environmental and hormonal stimuli. Thus, aquaporins play key roles in hydraulic regulation and nutrient transport in roots and leaves. They contribute to several plant growth and developmental processes such as seed germination or emergence of lateral roots. Plants with genetically altered aquaporin functions are now tested for their ability to improve plant resistance to stresses. This article is part of a Special Issue entitled Aquaporins. Copyright © 2013 Elsevier B.V. All rights reserved.

  17. Profiles of self-concept, goal orientation, and self-regulation in students with physical, intellectual, and multiple disabilities: Implications for instructional support.

    Science.gov (United States)

    Varsamis, Panagiotis; Agaliotis, Ioannis

    2011-01-01

    The present study explored physical self-concept, goal orientation in sport, and self-regulation in regard to a motor task, in 75 secondary students with physical, intellectual, and multiple disabilities, who were educated in the same special education units. It was found that students with intellectual disabilities generally presented a positive profile in all three psychosocial constructs, whereas students with physical disabilities presented low scores in most measures. Students with multiple disabilities did not differ essentially from students with intellectual disability in regard to physical self-concept and goal orientation; however, they compared unfavorably to them regarding self-regulation. The delineation of a distinct and defendable profile of self-concept, goal orientation, and self-regulation for each disability group allows the formulation of proposals for the implementation of appropriate instructional programs for students belonging to the above mentioned categories. Copyright © 2011 Elsevier Ltd. All rights reserved.

  18. Environmental physiology

    International Nuclear Information System (INIS)

    Anon.

    1979-01-01

    Summaries of research projects conducted during 1978 and 1979 are presented. Subject areas include: the effects of environmental pollutants on homeostasis of the hematopoietic system; pollutant effects on steroid metabolism; pollutant effects on pulmonary macrophages; effects of toxic gases on lung cells; the development of immunological methods for assessing lung damage at the cellular level; the response of erythropoietin concentration to various physiological changes; and the study of actinide metabolism in monkey skeletons

  19. Variation in regulator of G-protein signaling 17 gene (RGS17 is associated with multiple substance dependence diagnoses

    Directory of Open Access Journals (Sweden)

    Zhang Huiping

    2012-05-01

    Full Text Available Abstract Background RGS17 and RGS20 encode two members of the regulator of G-protein signaling RGS-Rz subfamily. Variation in these genes may alter their transcription and thereby influence the function of G protein-coupled receptors, including opioid receptors, and modify risk for substance dependence. Methods The association of 13 RGS17 and eight RGS20 tag single nucleotide polymorphisms (SNPs was examined with four substance dependence diagnoses (alcohol (AD, cocaine (CD, opioid (OD or marijuana (MjD] in 1,905 African Americans (AAs: 1,562 cases and 343 controls and 1,332 European Americans (EAs: 981 cases and 351 controls. Analyses were performed using both χ2 tests and logistic regression analyses that covaried sex, age, and ancestry proportion. Correlation of genotypes and mRNA expression levels was assessed by linear regression analyses. Results Seven RGS17 SNPs showed a significant association with at least one of the four dependence traits after a permutation-based correction for multiple testing (0.003≤Pempirical≤0.037. The G allele of SNP rs596359, in the RGS17 promoter region, was associated with AD, CD, OD, or MjD in both populations (0.005≤Pempirical≤0.019. This allele was also associated with significantly lower mRNA expression levels of RGS17 in YRI subjects (P = 0.002 and non-significantly lower mRNA expression levels of RGS17 in CEU subjects (P = 0.185. No RGS20 SNPs were associated with any of the four dependence traits in either population. Conclusions This study demonstrated that variation in RGS17 was associated with risk for substance dependence diagnoses in both AA and EA populations.

  20. Physiologically based pharmacokinetic and pharmacodynamic modeling of an antagonist (SM-406/AT-406) of multiple inhibitor of apoptosis proteins (IAPs) in a mouse xenograft model of human breast cancer.

    Science.gov (United States)

    Zhang, Tao; Li, Yanyan; Zou, Peng; Yu, Jing-yu; McEachern, Donna; Wang, Shaomeng; Sun, Duxin

    2013-09-01

    The inhibitors of apoptosis proteins (IAPs) are a class of key apoptosis regulators overexpressed or dysregulated in cancer. SM-406/AT-406 is a potent and selective small molecule mimetic of Smac that antagonizes the inhibitor of apoptosis proteins (IAPs). A physiologically based pharmacokinetic and pharmacodynamic (PBPK-PD) model was developed to predict the tissue concentration-time profiles of SM-406, the related onco-protein levels in tumor, and the tumor growth inhibition in a mouse model bearing human breast cancer xenograft. In the whole body physiologically based pharmacokinetic (PBPK) model for pharmacokinetics characterization, a well stirred (perfusion rate-limited) model was used to describe SM-406 pharmacokinetics in the lung, heart, kidney, intestine, liver and spleen, and a diffusion rate-limited (permeability limited) model was used for tumor. Pharmacodynamic (PD) models were developed to correlate the SM-406 concentration in tumor to the cIAP1 degradation, pro-caspase 8 decrease, CL-PARP accumulation and tumor growth inhibition. The PBPK-PD model well described the experimental pharmacokinetic data, the pharmacodynamic biomarker responses and tumor growth. This model may be helpful to predict tumor and plasma SM-406 concentrations in the clinic. Copyright © 2013 John Wiley & Sons, Ltd.

  1. A Carbonic Anhydrase Serves as an Important Acid-Base Regulator in Pacific Oyster Crassostrea gigas Exposed to Elevated CO2: Implication for Physiological Responses of Mollusk to Ocean Acidification.

    Science.gov (United States)

    Wang, Xiudan; Wang, Mengqiang; Jia, Zhihao; Qiu, Limei; Wang, Lingling; Zhang, Anguo; Song, Linsheng

    2017-02-01

    Carbonic anhydrases (CAs) have been demonstrated to play an important role in acid-base regulation in vertebrates. However, the classification and modulatory function of CAs in marine invertebrates, especially their responses to ocean acidification remain largely unknown. Here, a cytosolic α-CA (designated as CgCAII-1) was characterized from Pacific oyster Crassostrea gigas and its molecular activities against CO 2 exposure were investigated. CgCAII-1 possessed a conserved CA catalytic domain, with high similarity to invertebrate cytoplasmic or mitochondrial α-CAs. Recombinant CgCAII-1 could convert CO 2 to HCO 3 - with calculated activity as 0.54 × 10 3  U/mg, which could be inhibited by acetazolamide (AZ). The mRNA transcripts of CgCAII-1 in muscle, mantle, hepatopancreas, gill, and hemocytes increased significantly after exposure to elevated CO 2 . CgCAII-1 could interact with the hemocyte membrane proteins and the distribution of CgCAII-1 protein became more concentrated and dense in gill and mantle under CO 2 exposure. The intracellular pH (pHi) of hemocytes under CO 2 exposure increased significantly (p ocean acidification and participate in acid-base regulation. Such cytoplasmic CA-based physiological regulation mechanism might explain other physiological responses of marine organisms to OA.

  2. The physiology of ex vitro pineapple (Ananas comosus L. Merr. var MD-2) as CAM or C3 is regulated by the environmental conditions.

    Science.gov (United States)

    Aragón, C; Carvalho, L; González, J; Escalona, M; Amancio, S

    2012-04-01

    Many plant species grown under in vitro controlled conditions can be used as models for the study of physiological processes. Adult pineapple can display CAM physiology while in vitro it functions as a C3 plant. Ex vitro Ananas comosus has plastic morphology and physiology, both easy to modify from C3 to CAM by changing the environmental conditions. The yield of survival for a rentable propagation protocol of pineapple is closely related with the C3/CAM shift and the associated physiological characteristics. In the present work, ex vitro pineapple plants were divided in two sets and subjected to C3 and CAM-inducing environmental conditions, determined by light intensity and relative humidity, respectively, 40 μmol m(-2) s(-1)/85% and 260 μmol m(-2) s(-1)/50%. The results demonstrated that the stress imposed by the environmental conditions switched pineapple plants from C3 to CAM behavior. Comparing to CAM induced, C3-induced pineapple plants showed substandard growth parameters and morphological leaf characteristics but a better rooting process and a higher ABA production, a phenotype closer to adult plants, which are expected to produce fruits in a normal production cycle. We conclude that the upholding of these characteristics is conditioned by low light intensity plus high relative humidity, especially during the first 8 weeks of ex vitro growth. It is expected that the better understanding of pineapple acclimatization will contribute to the design of a protocol to apply as a rentable tool in the pineapple agronomic industry. © Springer-Verlag 2011

  3. Physiological age at harvest regulates the variability in postharvest ripening, sensory and nutritional characteristics of mango (Mangifera indica L.) cv. Coghshall due to growing conditions.

    Science.gov (United States)

    Joas, Jacques; Vulcain, Emmanuelle; Desvignes, Claire; Morales, Emeline; Léchaudel, Mathieu

    2012-04-01

    Climacteric fruits are harvested at the green-mature stage and ripen during their marketing cycle. However, growing conditions induce variability into the maturity stage of mangoes at harvest, with an impact on their final quality. Assuming that the physiological age can be correctly evaluated by a criterion based on the variable chlorophyll fluorescence of the skin (F(v)) and that differences in physiological age depend on growing conditions, controlled stress experiments were carried out on mango fruit by manipulating either the leaf/fruit ratio or the light environment. Delays from 9 to 30 days were observed, depending on stress level and harvest stage, to obtain the same F(v) value. For moderate stress, fruit composition after ripening was partially compensated for, with little or no difference in sugar, dry matter, carotenoid and aroma contents. For more pronounced stress, the major metabolites were not particularly affected, but the synthesis capacity of carotenoids and aromas was lower after maturity. The ripening ability of a fruit is acquired on the tree and defines its postharvest changes. Control of the physiological age at harvest can minimise the variability observed under natural conditions and guarantee fruit batches whose postharvest changes will be relatively homogeneous. Copyright © 2011 Society of Chemical Industry.

  4. Occupational physiology

    CERN Document Server

    Toomingas, Allan; Tornqvist, Ewa Wigaeus

    2011-01-01

    In a clear and accessible presentation, Occupational Physiology focuses on important issues in the modern working world. Exploring major public health problems-such as musculoskeletal disorders and stress-this book explains connections between work, well-being, and health based on up-to-date research in the field. It provides useful methods for risk assessment and guidelines on arranging a good working life from the perspective of the working individual, the company, and society as a whole.The book focuses on common, stressful situations in different professions. Reviewing bodily demands and r

  5. Structured association analysis leads to insight into Saccharomyces cerevisiae gene regulation by finding multiple contributing eQTL hotspots associated with functional gene modules.

    Science.gov (United States)

    Curtis, Ross E; Kim, Seyoung; Woolford, John L; Xu, Wenjie; Xing, Eric P

    2013-03-21

    Association analysis using genome-wide expression quantitative trait locus (eQTL) data investigates the effect that genetic variation has on cellular pathways and leads to the discovery of candidate regulators. Traditional analysis of eQTL data via pairwise statistical significance tests or linear regression does not leverage the availability of the structural information of the transcriptome, such as presence of gene networks that reveal correlation and potentially regulatory relationships among the study genes. We employ a new eQTL mapping algorithm, GFlasso, which we have previously developed for sparse structured regression, to reanalyze a genome-wide yeast dataset. GFlasso fully takes into account the dependencies among expression traits to suppress false positives and to enhance the signal/noise ratio. Thus, GFlasso leverages the gene-interaction network to discover the pleiotropic effects of genetic loci that perturb the expression level of multiple (rather than individual) genes, which enables us to gain more power in detecting previously neglected signals that are marginally weak but pleiotropically significant. While eQTL hotspots in yeast have been reported previously as genomic regions controlling multiple genes, our analysis reveals additional novel eQTL hotspots and, more interestingly, uncovers groups of multiple contributing eQTL hotspots that affect the expression level of functional gene modules. To our knowledge, our study is the first to report this type of gene regulation stemming from multiple eQTL hotspots. Additionally, we report the results from in-depth bioinformatics analysis for three groups of these eQTL hotspots: ribosome biogenesis, telomere silencing, and retrotransposon biology. We suggest candidate regulators for the functional gene modules that map to each group of hotspots. Not only do we find that many of these candidate regulators contain mutations in the promoter and coding regions of the genes, in the case of the Ribi group

  6. Regulation

    International Nuclear Information System (INIS)

    Ballereau, P.

    1999-01-01

    The different regulations relative to nuclear energy since the first of January 1999 are given here. Two points deserve to be noticed: the decree of the third august 1999 authorizing the national Agency for the radioactive waste management to install and exploit on the commune of Bures (Meuse) an underground laboratory destined to study the deep geological formations where could be stored the radioactive waste. The second point is about the uranium residues and the waste notion. The judgment of the administrative tribunal of Limoges ( 9. july 1998) forbidding the exploitation of a storage installation of depleted uranium considered as final waste and qualifying it as an industrial waste storage facility has been annulled bu the Court of Appeal. It stipulated that, according to the law number 75663 of the 15. july 1965, no criteria below can be applied to depleted uranium: production residue (possibility of an ulterior enrichment), abandonment of a personal property or simple intention to do it ( future use aimed in the authorization request made in the Prefecture). This judgment has devoted the primacy of the waste notion on this one of final waste. (N.C.)

  7. Complex Interplay between FleQ, Cyclic Diguanylate and Multiple σ Factors Coordinately Regulates Flagellar Motility and Biofilm Development in Pseudomonas putida.

    Directory of Open Access Journals (Sweden)

    Alicia Jiménez-Fernández

    Full Text Available Most bacteria alternate between a free living planktonic lifestyle and the formation of structured surface-associated communities named biofilms. The transition between these two lifestyles requires a precise and timely regulation of the factors involved in each of the stages that has been likened to a developmental process. Here we characterize the involvement of the transcriptional regulator FleQ and the second messenger cyclic diguanylate in the coordinate regulation of multiple functions related to motility and surface colonization in Pseudomonas putida. Disruption of fleQ caused strong defects in flagellar motility, biofilm formation and surface attachment, and the ability of this mutation to suppress multiple biofilm-related phenotypes associated to cyclic diguanylate overproduction suggests that FleQ mediates cyclic diguanylate signaling critical to biofilm growth. We have constructed a library containing 94 promoters potentially involved in motility and biofilm development fused to gfp and lacZ, screened this library for FleQ and cyclic diguanylate regulation, and assessed the involvement of alternative σ factors σN and FliA in the transcription of FleQ-regulated promoters. Our results suggest a dual mode of action for FleQ. Low cyclic diguanylate levels favor FleQ interaction with σN-dependent promoters to activate the flagellar cascade, encompassing the flagellar cluster and additional genes involved in cyclic diguanylate metabolism, signal transduction and gene regulation. On the other hand, characterization of the FleQ-regulated σN- and FliA-independent PlapA and PbcsD promoters revealed two disparate regulatory mechanisms leading to a similar outcome: the synthesis of biofilm matrix components in response to increased cyclic diguanylate levels.

  8. Physiological Acoustics

    Science.gov (United States)

    Young, Eric D.

    The analysis of physiological sound in the peripheral auditory system solves three important problems. First, sound energy impinging on the head must be captured and presented to the transduction apparatus in the ear as a suitable mechanical signal; second, this mechanical signal needs to be transduced into a neural representation that can be used by the brain; third, the resulting neural representation needs to be analyzed by central neurons to extract information useful to the animal. This chapter provides an overview of some aspects of the first two of these processes. The description is entirely focused on the mammalian auditory system, primarily on human hearing and on the hearing of a few commonly used laboratory animals (mainly rodents and carnivores). Useful summaries of non-mammalian hearing are available [1]. Because of the large size of the literature, review papers are referenced wherever possible.

  9. Canonical transient receptor potential channel 2 (TRPC2): old name-new games. Importance in regulating of rat thyroid cell physiology.

    Science.gov (United States)

    Törnquist, Kid; Sukumaran, Pramod; Kemppainen, Kati; Löf, Christoffer; Viitanen, Tero

    2014-11-01

    In addition to the TSH-cyclic AMP signalling pathway, calcium signalling is of crucial importance in thyroid cells. Although the importance of calcium signalling has been thoroughly investigated for several decades, the nature of the calcium channels involved in signalling is unknown. In a recent series of investigations using the well-studied rat thyroid FRTL-5 cell line, we showed that these cells exclusively express the transient receptor potential canonical 2 (TRPC2) channel. Our results suggested that the TRPC2 channel is of significant importance in regulating thyroid cell function. These investigations were the first to show that thyroid cells express a member of the TRPC family of ion channels. In this review, we will describe the importance of the TRPC2 channel in regulating TSH receptor expression, thyroglobulin maturation, intracellular calcium and iodide homeostasis and that the channel also regulates thyroid cell proliferation.

  10. Acute and chronic glucocorticoid treatments regulate astrocyte-enriched mRNAs in multiple brain regions in vivo

    Directory of Open Access Journals (Sweden)

    Bradley S. Carter

    2013-08-01

    Full Text Available Previous studies have primarily interpreted gene expression regulation by glucocorticoids in the brain in terms of impact on neurons; however, less is known about the corresponding impact of glucocorticoids on glia and specifically astrocytes in vivo. Recent microarray experiments have identified glucocorticoid-sensitive mRNAs in primary astrocyte cell culture, including a number of mRNAs that have reported astrocyte-enriched expression patterns relative to other brain cell types. Here, we have tested whether elevations of glucocorticoids regulate a subset of these mRNAs in vivo following acute and chronic corticosterone exposure in adult mice. Acute corticosterone exposure was achieved by a single injection of 10 mg/kg corticosterone, and tissue samples were harvested two hours post-injection. Chronic corticosterone exposure was achieved by administering 10 mg/mL corticosterone via drinking water for two weeks. Gene expression was then assessed in two brain regions associated with glucocorticoid action (prefrontal cortex and hippocampus by qPCR and by in situ hybridization. The majority of measured mRNAs regulated by glucocorticoids in astrocytes in vitro were similarly regulated by acute and/or chronic glucocorticoid exposure in vivo. In addition, the expression levels for mRNAs regulated in at least one corticosterone exposure condition (acute/chronic demonstrated moderate positive correlation between the two conditions by brain region. In situ hybridization analyses suggest that select mRNAs are regulated by chronic corticosterone exposure specifically in astroctyes based on (1 similar general expression patterns between corticosterone-treated and vehicle-treated animals and (2 similar expression patterns to the pan-astrocyte marker Aldh1l1. Our findings demonstrate that glucocorticoids regulate astrocyte-enriched mRNAs in vivo and suggest that glucocorticoids regulate gene expression in the brain in a cell type-dependent fashion.

  11. Chloroplasts as source and target of cellular redox regulation: a discussion on chloroplast redox signals in the context of plant physiology.

    Science.gov (United States)

    Baier, Margarete; Dietz, Karl-Josef

    2005-06-01

    During the evolution of plants, chloroplasts have lost the exclusive genetic control over redox regulation and antioxidant gene expression. Together with many other genes, all genes encoding antioxidant enzymes and enzymes involved in the biosynthesis of low molecular weight antioxidants were transferred to the nucleus. On the other hand, photosynthesis bears a high risk for photo-oxidative damage. Concomitantly, an intricate network for mutual regulation by anthero- and retrograde signals has emerged to co-ordinate the activities of the different genetic and metabolic compartments. A major focus of recent research in chloroplast regulation addressed the mechanisms of redox sensing and signal transmission, the identification of regulatory targets, and the understanding of adaptation mechanisms. In addition to redox signals communicated through signalling cascades also used in pathogen and wounding responses, specific chloroplast signals control nuclear gene expression. Signalling pathways are triggered by the redox state of the plastoquinone pool, the thioredoxin system, and the acceptor availability at photosystem I, in addition to control by oxolipins, tetrapyrroles, carbohydrates, and abscisic acid. The signalling function is discussed in the context of regulatory circuitries that control the expression of antioxidant enzymes and redox modulators, demonstrating the principal role of chloroplasts as the source and target of redox regulation.

  12. Space Physiology within an Exercise Physiology Curriculum

    Science.gov (United States)

    Carter, Jason R.; West, John B.

    2013-01-01

    Compare and contrast strategies remain common pedagogical practices within physiological education. With the support of an American Physiological Society Teaching Career Enhancement Award, we have developed a junior- or senior-level undergraduate curriculum for exercise physiology that compares and contrasts the physiological adaptations of…

  13. Low empathy-like behaviour in male mice associates with impaired sociability, emotional memory, physiological stress reactivity and variations in neurobiological regulations.

    Science.gov (United States)

    Laviola, Giovanni; Zoratto, Francesca; Ingiosi, Danilo; Carito, Valentina; Huzard, Damien; Fiore, Marco; Macrì, Simone

    2017-01-01

    Deficits in empathy have been proposed to constitute a hallmark of several psychiatric disturbances like conduct disorder, antisocial and narcissistic personality disorders. Limited sensitivity to punishment, shallow or deficient affect and reduced physiological reactivity to environmental stressors have been often reported to co-occur with limited empathy and contribute to the onset of antisocial phenotypes. Empathy in its simplest form (i.e. emotional contagion) is addressed in preclinical models through the evaluation of the social transmission of emotional states: mice exposed to a painful stimulus display a higher response if in the presence of a familiar individual experiencing a higher degree of discomfort, than in isolation. In the present study, we investigated whether a reduction of emotional contagion can be considered a predictor of reduced sociality, sensitivity to punishment and physiological stress reactivity. To this aim, we first evaluated emotional contagion in a group of Balb/cJ mice and then discretised their values in four quartiles. The upper (i.e. Emotional Contagion Prone, ECP) and the lower (i.e. Emotional Contagion Resistant, ECR) quartiles constituted the experimental groups. Our results indicate that mice in the lower quartile are characterized by reduced sociability, impaired memory of negative events and dampened hypothalamic-pituitary-adrenocortical reactivity to external stressors. Furthermore, in the absence of changes in oxytocin receptor density, we show that these mice exhibit elevated concentrations of oxytocin and vasopressin and reduced density of BDNF receptors in behaviourally-relevant brain areas. Thus, not only do present results translate to the preclinical investigation of psychiatric disturbances, but also they can contribute to the study of emotional contagion in terms of its adaptive significance.

  14. Low empathy-like behaviour in male mice associates with impaired sociability, emotional memory, physiological stress reactivity and variations in neurobiological regulations.

    Directory of Open Access Journals (Sweden)

    Giovanni Laviola

    Full Text Available Deficits in empathy have been proposed to constitute a hallmark of several psychiatric disturbances like conduct disorder, antisocial and narcissistic personality disorders. Limited sensitivity to punishment, shallow or deficient affect and reduced physiological reactivity to environmental stressors have been often reported to co-occur with limited empathy and contribute to the onset of antisocial phenotypes. Empathy in its simplest form (i.e. emotional contagion is addressed in preclinical models through the evaluation of the social transmission of emotional states: mice exposed to a painful stimulus display a higher response if in the presence of a familiar individual experiencing a higher degree of discomfort, than in isolation. In the present study, we investigated whether a reduction of emotional contagion can be considered a predictor of reduced sociality, sensitivity to punishment and physiological stress reactivity. To this aim, we first evaluated emotional contagion in a group of Balb/cJ mice and then discretised their values in four quartiles. The upper (i.e. Emotional Contagion Prone, ECP and the lower (i.e. Emotional Contagion Resistant, ECR quartiles constituted the experimental groups. Our results indicate that mice in the lower quartile are characterized by reduced sociability, impaired memory of negative events and dampened hypothalamic-pituitary-adrenocortical reactivity to external stressors. Furthermore, in the absence of changes in oxytocin receptor density, we show that these mice exhibit elevated concentrations of oxytocin and vasopressin and reduced density of BDNF receptors in behaviourally-relevant brain areas. Thus, not only do present results translate to the preclinical investigation of psychiatric disturbances, but also they can contribute to the study of emotional contagion in terms of its adaptive significance.

  15. Effects of potentially acidic air pollutants on the intracellular distribution and transport of plant growth regulators in mesophyll cells of leaves. Consequences on stress- and developmental physiology

    Energy Technology Data Exchange (ETDEWEB)

    Kremer, H.; Pfanz, H.; Hartung, W.

    1987-07-11

    The influence of SO/sub 2/ on the intracellular distribution of abscisic acid (ABA) and indole-acetic acid (IAA) in mesophyll cells of Picea abies, Tsuga americana and Hordeum vulgare was investigated. The compartmentation of ABA and IAA depends on intracellular pH-gradients. The hydrophilic anions ABA and IAA are accumulated in the alkaline cell compartments cytosol and chloroplasts, which act as anion traps for weak acids. Uptake of sulfur dioxide into leaves leads to an acidification of alkaline cell compartments, thus decreasing intracellular pH-gradients. Consequently this results in an increased release of plant growth regulators from the cell interior into the apoplast. Therefore the target cells of plant hormones i.e. meristems and stomates are exposed to altered hormone concentrations. Obviously this influences the regulation of cellular metabolism plant development and growth.

  16. Hindsight regulates photoreceptor axon targeting through transcriptional control of jitterbug/Filamin and multiple genes involved in axon guidance in Drosophila.

    Science.gov (United States)

    Oliva, Carlos; Molina-Fernandez, Claudia; Maureira, Miguel; Candia, Noemi; López, Estefanía; Hassan, Bassem; Aerts, Stein; Cánovas, José; Olguín, Patricio; Sierralta, Jimena

    2015-09-01

    During axon targeting, a stereotyped pattern of connectivity is achieved by the integration of intrinsic genetic programs and the response to extrinsic long and short-range directional cues. How this coordination occurs is the subject of intense study. Transcription factors play a central role due to their ability to regulate the expression of multiple genes required to sense and respond to these cues during development. Here we show that the transcription factor HNT regulates layer-specific photoreceptor axon targeting in Drosophila through transcriptional control of jbug/Filamin and multiple genes involved in axon guidance and cytoskeleton organization.Using a microarray analysis we identified 235 genes whose expression levels were changed by HNT overexpression in the eye primordia. We analyzed nine candidate genes involved in cytoskeleton regulation and axon guidance, six of which displayed significantly altered gene expression levels in hnt mutant retinas. Functional analysis confirmed the role of OTK/PTK7 in photoreceptor axon targeting and uncovered Tiggrin, an integrin ligand, and Jbug/Filamin, a conserved actin- binding protein, as new factors that participate of photoreceptor axon targeting. Moreover, we provided in silico and molecular evidence that supports jbug/Filamin as a direct transcriptional target of HNT and that HNT acts partially through Jbug/Filamin in vivo to regulate axon guidance. Our work broadens the understanding of how HNT regulates the coordinated expression of a group of genes to achieve the correct connectivity pattern in the Drosophila visual system. © 2015 Wiley Periodicals, Inc. Develop Neurobiol 75: 1018-1032, 2015. © 2015 Wiley Periodicals, Inc.

  17. Effects of exercise on tumor physiology and metabolism.

    Science.gov (United States)

    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.

  18. Role of physiological ClC-1 Cl- ion channel regulation for the excitability and function of working skeletal muscle

    DEFF Research Database (Denmark)

    Pedersen, Thomas Holm; Riisager, Anders; de Paoli, Frank Vincenzo

    2016-01-01

    Electrical membrane properties of skeletal muscle fibers have been thoroughly studied over the last five to six decades. This has shown that muscle fibers from a wide range of species, including fish, amphibians, reptiles, birds, and mammals, are all characterized by high resting membrane...... temporal resolution in action potential firing muscle fibers. These and other techniques have revealed that ClC-1 function is controlled by multiple cellular signals during muscle activity. Thus, onset of muscle activity triggers ClC-1 inhibition via protein kinase C, intracellular acidosis, and lactate...

  19. Reexamination of the Physiological Role of PykA in Escherichia coli Revealed that It Negatively Regulates the Intracellular ATP Levels under Anaerobic Conditions.

    Science.gov (United States)

    Zhao, Chunhua; Lin, Zhao; Dong, Hongjun; Zhang, Yanping; Li, Yin

    2017-06-01

    Pyruvate kinase is one of the three rate-limiting glycolytic enzymes that catalyze the last step of glycolysis, conversion of phosphoenolpyruvate (PEP) into pyruvate, which is associated with ATP generation. Two isozymes of pyruvate kinase, PykF and PykA, are identified in Escherichia coli PykF is considered important, whereas PykA has a less-defined role. Prior studies inactivated the pykA gene to increase the level of its substrate, PEP, and thereby increased the yield of end products derived from PEP. We were surprised when we found a pykA ::Tn 5 mutant in a screen for increased yield of an end product derived from pyruvate ( n -butanol), suggesting that the role of PykA needs to be reexamined. We show that the pykA mutant exhibited elevated intracellular ATP levels, biomass concentrations, glucose consumption, and n -butanol production. We also discovered that the pykA mutant expresses higher levels of a presumed pyruvate transporter, YhjX, permitting the mutant to recapture and metabolize excreted pyruvate. Furthermore, we demonstrated that the nucleotide diphosphate kinase activity of PykA leads to negative regulation of the intracellular ATP levels. Taking the data together, we propose that inactivation of pykA can be considered a general strategy to enhance the production of pyruvate-derived metabolites under anaerobic conditions. IMPORTANCE This study showed that knocking out pykA significantly increased the intracellular ATP level and thus significantly increased the levels of glucose consumption, biomass formation, and pyruvate-derived product formation under anaerobic conditions. pykA was considered to be encoding a dispensable pyruvate kinase; here we show that pykA negatively regulates the anaerobic glycolysis rate through regulating the energy distribution. Thus, knocking out pykA can be used as a general strategy to increase the level of pyruvate-derived fermentative products. Copyright © 2017 American Society for Microbiology.

  20. Global Kinetic Analysis of Mammalian E3 Reveals pH-dependent NAD+/NADH Regulation, Physiological Kinetic Reversibility, and Catalytic Optimum*

    Science.gov (United States)

    Moxley, Michael A.; Beard, Daniel A.; Bazil, Jason N.

    2016-01-01

    Mammalian E3 is an essential mitochondrial enzyme responsible for catalyzing the terminal reaction in the oxidative catabolism of several metabolites. E3 is a key regulator of metabolic fuel selection as a component of the pyruvate dehydrogenase complex (PDHc). E3 regulates PDHc activity by altering the affinity of pyruvate dehydrogenase kinase, an inhibitor of the enzyme complex, through changes in reduction and acetylation state of lipoamide moieties set by the NAD+/NADH ratio. Thus, an accurate kinetic model of E3 is needed to predict overall mammalian PDHc activity. Here, we have combined numerous literature data sets and new equilibrium spectroscopic experiments with a multitude of independently collected forward and reverse steady-state kinetic assays using pig heart E3. The latter kinetic assays demonstrate a pH-dependent transition of NAD+ activation to inhibition, shown here, to our knowledge, for the first time in a single consistent data set. Experimental data were analyzed to yield a thermodynamically constrained four-redox-state model of E3 that simulates pH-dependent activation/inhibition and active site redox states for various conditions. The developed model was used to determine substrate/product conditions that give maximal E3 rates and show that, due to non-Michaelis-Menten behavior, the maximal flux is different compared with the classically defined kcat. PMID:26644471

  1. GABA receptors in the region of the dorsomedial hypothalamus of rats regulate anxiety in the elevated plus-maze test. II. Physiological measures.

    Science.gov (United States)

    Shekhar, A; Sims, L S; Bowsher, R R

    1993-11-05

    In the previous report, we had shown that blockade and enhancement of GABAA receptors in the DMH of rats increased or decreased the level of anxiety, respectively, as measured by the elevated plus-maze test. The present study was conducted to assess the effects of enhancing GABAA neurotransmission in the DMH of rats on the physiological concomitants of anxiety such as increases in heart rate (HR), blood pressure (BP) and plasma norepinephrine (NE) levels while the animals were placed on the elevated plus-maze. Male Sprague-Dawley rats were equipped with arterial and venous catheters and stereotaxically implanted with microinjection cannulae in the cardiostimulatory region of the DMH where injection of bicuculline methiodide (BMI) elicited increases in heart rate under anesthesia. After recovery, rats were injected with either saline or the GABAA agonist muscimol and their HR, BP and plasma NE responses were measured when confined in the open or the closed arm of the elevated plus-maze. Injection of muscimol into the DMH reduced the increases seen in HR, BP and plasma NE when the rats were confined to either the closed or the open arms in addition to decreasing 'anxiety' in the plus-maze. Injection of muscimol into the areas of the hypothalamus surrounding the DMH did not significantly affect the changes in HR, BP and plasma NE in the plus-maze. Blocking the changes in HR and BP elicited by microinjecting GABAergic drugs into the DMH of rats, with systemic injections of a combination of atropine and the beta-blocker atenolol, did not block the behavioral effects of the GABAergic drugs in the plus-maze test.

  2. Interleukin-6 counteracts therapy-induced cellular oxidative stress in multiple myeloma by up-regulating manganese superoxide dismutase

    OpenAIRE

    Brown, Charles O.; Salem, Kelley; Wagner, Brett A.; Bera, Soumen; Singh, Neeraj; Tiwari, Ajit; Choudhury, Amit; Buettner, Garry R.; Goel, Apollina

    2012-01-01

    IL (interleukin)-6, an established growth factor for multiple myeloma cells, induces myeloma therapy resistance, but the resistance mechanisms remain unclear. The present study determines the role of IL-6 in re-establishing intracellular redox homoeostasis in the context of myeloma therapy. IL-6 treatment increased myeloma cell resistance to agents that induce oxidative stress, including IR (ionizing radiation) and Dex (dexamethasone). Relative to IR alone, myeloma cells treated with IL-6 plu...

  3. Repair of steam generator heating tubes by roll-expanded plugs: approach to cover multiple national regulations

    Energy Technology Data Exchange (ETDEWEB)

    Beck, J.; Ziegler, B.; Schoenheit, N. [AREVA NP Gmbh, Erlangen (Germany); Kostroun, F. [AREVA NP Canada Ltd., Pickering, ON (Canada)

    2012-07-01

    During operation, steam generators in nuclear power plants are subject to degradation mechanisms which have an impact on the component life-time. Most affected are the heating tubes which constitute the barrier of the contaminated primary cycle to the secondary side. Various corrosive attacks may cause wall thinning which requires tube repair. A common repair method is to plug the tubes by roll expanded plugs. This is a fast method, easily applicable and requires less equipment or personnel qualification as needed for weld plugs. After insertion, the plugs act as a pressure boundary from primary to secondary side. Although the function of the roll plug is simple, the different national regulations define the requirements which need to be fulfilled by a roll plug differently. In order to reduce the tooling as well as the plug types to a minimum, an approach according to one common design for different regulations and steam generator types is profitable. It was found, that the regulations according to the ASME Boiler and Pressure Vessel code in combination with the German Safety Standards of the German Nuclear Safety Standards Commission covers the regulations of the majority of utilities. To develop a roll plug which suits the different regulatory demands, efforts were made to consider all technical and regulatory boundary conditions implied on roll expanded plugs. This covering approach had an impact on the plug design, which was required to be Helium tight after installation and suitable for a 40 year component lifetime also in accident and emergency conditions. To prove the suitability of the plug design a comprehensive testing programme of the mechanical and chemical properties of the designed roll-expanded plug was launched. A summary of the plug design and testing as well as the main test results are described. (author)

  4. Repair of steam generator heating tubes by roll-expanded plugs: approach to cover multiple national regulations

    International Nuclear Information System (INIS)

    Beck, J.; Ziegler, B.; Schoenheit, N.; Kostroun, F.

    2012-01-01

    During operation, steam generators in nuclear power plants are subject to degradation mechanisms which have an impact on the component life-time. Most affected are the heating tubes which constitute the barrier of the contaminated primary cycle to the secondary side. Various corrosive attacks may cause wall thinning which requires tube repair. A common repair method is to plug the tubes by roll expanded plugs. This is a fast method, easily applicable and requires less equipment or personnel qualification as needed for weld plugs. After insertion, the plugs act as a pressure boundary from primary to secondary side. Although the function of the roll plug is simple, the different national regulations define the requirements which need to be fulfilled by a roll plug differently. In order to reduce the tooling as well as the plug types to a minimum, an approach according to one common design for different regulations and steam generator types is profitable. It was found, that the regulations according to the ASME Boiler and Pressure Vessel code in combination with the German Safety Standards of the German Nuclear Safety Standards Commission covers the regulations of the majority of utilities. To develop a roll plug which suits the different regulatory demands, efforts were made to consider all technical and regulatory boundary conditions implied on roll expanded plugs. This covering approach had an impact on the plug design, which was required to be Helium tight after installation and suitable for a 40 year component lifetime also in accident and emergency conditions. To prove the suitability of the plug design a comprehensive testing programme of the mechanical and chemical properties of the designed roll-expanded plug was launched. A summary of the plug design and testing as well as the main test results are described. (author)

  5. SuhB Is a Regulator of Multiple Virulence Genes and Essential for Pathogenesis of Pseudomonas aeruginosa

    Science.gov (United States)

    Li, Kewei; Xu, Chang; Jin, Yongxin; Sun, Ziyu; Liu, Chang; Shi, Jing; Chen, Gukui; Chen, Ronghao; Jin, Shouguang; Wu, Weihui

    2013-01-01

    ABSTRACT During initial colonization and chronic infection, pathogenic bacteria encounter distinct host environments. Adjusting gene expression accordingly is essential for the pathogenesis. Pseudomonas aeruginosa has evolved complicated regulatory networks to regulate different sets of virulence factors to facilitate colonization and persistence. The type III secretion system (T3SS) and motility are associated with acute infections, while biofilm formation and the type VI secretion system (T6SS) are associated with chronic persistence. To identify novel regulatory genes required for pathogenesis, we screened a P. aeruginosa transposon (Tn) insertion library and found suhB to be an essential gene for the T3SS gene expression. The expression of suhB was upregulated in a mouse acute lung infection model, and loss of suhB resulted in avirulence. Suppression of T3SS gene expression in the suhB mutant is linked to a defective translation of the T3SS master regulator, ExsA. Further studies demonstrated that suhB mutation led to the upregulation of GacA and its downstream small RNAs, RsmY and RsmZ, triggering T6SS expression and biofilm formation while inhibiting the T3SS. Our results demonstrate that an in vivo-inducible gene, suhB, reciprocally regulates genes associated with acute and chronic infections and plays an essential role in the pathogenesis of P. aeruginosa. PMID:24169572

  6. Young Human Cholinergic Neurons Respond to Physiological Regulators and Improve Cognitive Symptoms in an Animal Model of Alzheimer’s Disease

    Directory of Open Access Journals (Sweden)

    Annamaria Morelli

    2017-10-01

    Full Text Available The degeneration of cholinergic neurons of the nucleus basalis of Meynert (NBM in the basal forebrain (BF is associated to the cognitive decline of Alzheimer’s disease (AD patients. To date no resolutive therapies exist. Cell-based replacement therapy is a strategy currently under consideration, although the mechanisms underlying the generation of stem cell-derived NBM cholinergic neurons able of functional integration remain to be clarified. Since fetal brain is an optimal source of neuronal cells committed towards a specific phenotype, this study is aimed at isolating cholinergic neurons from the human fetal NBM (hfNBMs in order to study their phenotypic, maturational and functional properties. Extensive characterization confirmed the cholinergic identity of hfNBMs, including positivity for specific markers (such as choline acetyltransferase and acetylcholine (Ach release. Electrophysiological measurements provided the functional validation of hfNBM cells, which exhibited the activation of peculiar sodium (INa and potassium (IK currents, as well as the presence of functional cholinergic receptors. Accordingly, hfNBMs express both nicotinic and muscarinic receptors, which were activated by Ach. The hfNBMs cholinergic phenotype was regulated by the nerve growth factor (NGF, through the activation of the high-affinity NGF receptor TrkA, as well as by 17-β-estradiol through a peculiar recruitment of its own receptors. When intravenously administered in NBM-lesioned rats, hfNBMs determined a significant improvement in memory functions. Histological examination of brain sections showed that hfNBMs (labeled with PKH26 fluorescent dye prior to administration reached the damaged brain areas. The study provides a useful model to study the ontogenetic mechanisms regulating the development and maintenance of the human brain cholinergic system and to assess new lines of research, including disease modeling, drug discovery and cell-based therapy for AD.

  7. Significance of adipose tissue-derived stem cells regulate CD4+ T cell immune in the treatment of multiple sclerosis

    Directory of Open Access Journals (Sweden)

    Yong-lin XIE

    2014-10-01

    Full Text Available Adipose tissue-derived stem cells (ADSCs are genetically engineered seed cells with immunomodulatory effects, widely used in the treatment of autoimmune diseases. This article focuses on the immunomodulatory effects of adipose tissue-derived stem cells on CD4+ T cell subsets, including T helper cell (Th 1, 2, 17 and regulatory T cell (Treg, and its clinical significance in the treatment of multiple sclerosis. doi: 10.3969/j.issn.1672-6731.2014.10.005

  8. Regulation of the CD56 promoter and its association with proliferation, anti-apoptosis and clinical factors in multiple myeloma

    DEFF Research Database (Denmark)

    Damgaard, Tina; Knudsen, Lene M; Dahl, Inger Marie S

    2009-01-01

    the regulation of the CD56 promoter in relation to typical clinical factors. We used qPCR and FACS to measure the expression levels of CD56, and potential regulatory factors in patients with MM and related these with MM progression/prognosis. The transcription factors BTBD3, Pax5, RUNX1 and MMSET were positively...... associated with CD56 expression, as was CYCLIN D1, which is involved in disease progression, anti-apoptosis and proliferation. RUNX1 was negatively associated with the survival of stem-cell transplanted patients. Our findings propose four potential activators of the CD56 promoter and for CD56 to be involved...

  9. Physiological function of gastrin-releasing peptide and neuromedin B receptors in regulating itch scratching behavior in the spinal cord of mice.

    Directory of Open Access Journals (Sweden)

    Devki D Sukhtankar

    Full Text Available Pruritus (itch is a severe side effect associated with the use of drugs as well as hepatic and hematological disorders. Previous studies in rodents suggest that bombesin receptor subtypes i.e. receptors for gastrin-releasing peptide (GRPr and neuromedin B (NMBr differentially regulate itch scratching. However, to what degree spinal GRPr and NMBr regulate scratching evoked by intrathecally administered bombesin-related peptides is not known. The first aim of this study was to pharmacologically compare the dose-response curves for scratching induced by intrathecally administered bombesin-related peptides versus morphine, which is known to elicit itch in humans. The second aim was to determine if spinal GRPr and NMBr selectively or generally mediate scratching behavior. Mice received intrathecal injection of bombesin (0.01-0.3 nmol, GRP (0.01-0.3 nmol, NMB (0.1-1 nmol or morphine (0.3-3 nmol and were observed for one hour for scratching activity. Bombesin elicited most profound scratching over one hour followed by GRP and NMB, whereas morphine failed to evoke scratching response indicating the insensitivity of mouse models to intrathecal opioid-induced itch. Intrathecal pretreatment with GRPr antagonist RC-3095 (0.03-0.1 nmol produced a parallel rightward shift in the dose response curve of GRP-induced scratching but not NMB-induced scratching. Similarly, PD168368 (1-3 nmol only attenuated NMB but not GRP-induced scratching. Individual or co-administration of RC-3095 and PD168368 failed to alter bombesin-evoked scratching. A higher dose of RC-3095 (0.3 nmol generally suppressed scratching induced by all three peptides but also compromised motor function in the rotarod test. Together, these data indicate that spinal GRPr and NMBr independently drive itch neurotransmission in mice and may not mediate bombesin-induced scratching. GRPr antagonists at functionally receptor-selective doses only block spinal GRP-elicited scratching but the suppression of

  10. A viral microRNA down-regulates multiple cell cycle genes through mRNA 5'UTRs.

    Directory of Open Access Journals (Sweden)

    Finn Grey

    2010-06-01

    Full Text Available Global gene expression data combined with bioinformatic analysis provides strong evidence that mammalian miRNAs mediate repression of gene expression primarily through binding sites within the 3' untranslated region (UTR. Using RNA induced silencing complex immunoprecipitation (RISC-IP techniques we have identified multiple cellular targets for a human cytomegalovirus (HCMV miRNA, miR-US25-1. Strikingly, this miRNA binds target sites primarily within 5'UTRs, mediating significant reduction in gene expression. Intriguingly, many of the genes targeted by miR-US25-1 are associated with cell cycle control, including cyclin E2, BRCC3, EID1, MAPRE2, and CD147, suggesting that miR-US25-1 is targeting genes within a related pathway. Deletion of miR-US25-1 from HCMV results in over expression of cyclin E2 in the context of viral infection. Our studies demonstrate that a viral miRNA mediates translational repression of multiple cellular genes by targeting mRNA 5'UTRs.

  11. The physiology of ex vitro pineapple (Ananas comosus L. Merr. var MD-2) as CAM or C3 is regulated by the environmental conditions: proteomic and transcriptomic profiles.

    Science.gov (United States)

    Aragón, C; Pascual, P; González, J; Escalona, M; Carvalho, L; Amancio, S

    2013-11-01

    Proteomic and transcriptomic profiles of key enzymes were monitored in pineapple plants propagated under C3 and CAM-inducing metabolisms to obtain insight into the CAM-facultative metabolism and the relationship of CAM plants with oxidative stress. Pineapple is one of the most important tropical crops worldwide. The use of temporary immersion bioreactors for the first stages of pineapple propagation enables precise control of plant growth, increases the rate of plant multiplication, decreases space, energy and labor requirements for pineapple plants in commercial micropropagation. Once the plantlets are ready to be taken from the reactors, they are carefully acclimatized to natural environmental conditions, and a facultative C3/CAM metabolism in the first 2 months of growth is the characteristic of pineapple plants, depending on environmental conditions. We subjected two sets of micropropagated pineapple plants to C3 and CAM-inducing environmental conditions, determined by light intensity/relative humidity (respectively 40 μmol m−2 s−1/85 % and 260 μmol m−2 s−1/50 %). Leaves of pineapple plants grown under CAM-inducing conditions showed higher leaf thickness and more developed cuticles and hypodermic tissue. Proteomic profiles of several proteins, isoenzyme patterns and transcriptomic profiles were also measured. Five major spots were isolated and identified, two of them for the first time in Ananas comosus (OEE 1; OEE 2) and the other three corresponding to small fragments of the large subunit of Rubisco (LSU). PEPC and PEPCK were also detected by immunobloting of 2DE at the end of both ex vitro treatments (C3/CAM) during the dark period. Isoenzymes of SOD and CAT were identified by electrophoresis and the transcript levels of OEE 1 and CAT were associated with CAM metabolism in pineapple plants.

  12. Alterations in glutathione levels and apoptotic regulators are associated with acquisition of arsenic trioxide resistance in multiple myeloma.

    Directory of Open Access Journals (Sweden)

    Shannon M Matulis

    Full Text Available Arsenic trioxide (ATO has been tested in relapsed/refractory multiple myeloma with limited success. In order to better understand drug mechanism and resistance pathways in myeloma we generated an ATO-resistant cell line, 8226/S-ATOR05, with an IC50 that is 2-3-fold higher than control cell lines and significantly higher than clinically achievable concentrations. Interestingly we found two parallel pathways governing resistance to ATO in 8226/S-ATOR05, and the relevance of these pathways appears to be linked to the concentration of ATO used. We found changes in the expression of Bcl-2 family proteins Bfl-1 and Noxa as well as an increase in cellular glutathione (GSH levels. At low, clinically achievable concentrations, resistance was primarily associated with an increase in expression of the anti-apoptotic protein Bfl-1 and a decrease in expression of the pro-apoptotic protein Noxa. However, as the concentration of ATO increased, elevated levels of intracellular GSH in 8226/S-ATOR05 became the primary mechanism of ATO resistance. Removal of arsenic selection resulted in a loss of the resistance phenotype, with cells becoming sensitive to high concentrations of ATO within 7 days following drug removal, indicating changes associated with high level resistance (elevated GSH are dependent upon the presence of arsenic. Conversely, not until 50 days without arsenic did cells once again become sensitive to clinically relevant doses of ATO, coinciding with a decrease in the expression of Bfl-1. In addition we found cross-resistance to melphalan and doxorubicin in 8226/S-ATOR05, suggesting ATO-resistance pathways may also be involved in resistance to other chemotherapeutic agents used in the treatment of multiple myeloma.

  13. Catabolite regulation analysis of Escherichia coli for acetate overflow mechanism and co-consumption of multiple sugars based on systems biology approach using computer simulation.

    Science.gov (United States)

    Matsuoka, Yu; Shimizu, Kazuyuki

    2013-10-20

    It is quite important to understand the basic principle embedded in the main metabolism for the interpretation of the fermentation data. For this, it may be useful to understand the regulation mechanism based on systems biology approach. In the present study, we considered the perturbation analysis together with computer simulation based on the models which include the effects of global regulators on the pathway activation for the main metabolism of Escherichia coli. Main focus is the acetate overflow metabolism and the co-fermentation of multiple carbon sources. The perturbation analysis was first made to understand the nature of the feed-forward loop formed by the activation of Pyk by FDP (F1,6BP), and the feed-back loop formed by the inhibition of Pfk by PEP in the glycolysis. Those together with the effect of transcription factor Cra caused by FDP level affected the glycolysis activity. The PTS (phosphotransferase system) acts as the feed-back system by repressing the glucose uptake rate for the increase in the glucose uptake rate. It was also shown that the increased PTS flux (or glucose consumption rate) causes PEP/PYR ratio to be decreased, and EIIA-P, Cya, cAMP-Crp decreased, where cAMP-Crp in turn repressed TCA cycle and more acetate is formed. This was further verified by the detailed computer simulation. In the case of multiple carbon sources such as glucose and xylose, it was shown that the sequential utilization of carbon sources was observed for wild type, while the co-consumption of multiple carbon sources with slow consumption rates were observed for the ptsG mutant by computer simulation, and this was verified by experiments. Moreover, the effect of a specific gene knockout such as Δpyk on the metabolic characteristics was also investigated based on the computer simulation. Copyright © 2013 Elsevier B.V. All rights reserved.

  14. The Drosophila nerfin-1 mRNA requires multiple microRNAs to regulate its spatial and temporal translation dynamics in the developing nervous system.

    Science.gov (United States)

    Kuzin, Alexander; Kundu, Mukta; Brody, Thomas; Odenwald, Ward F

    2007-10-01

    The mRNA encoding the Drosophila Zn-finger transcription factor Nerfin-1, required for CNS axon pathfinding events, is subject to post-transcriptional silencing. Although nerfin-1 mRNA is expressed in many neural precursor cells including all early delaminating CNS neuroblasts, the encoded Nerfin-1 protein is detected only in the nuclei of neural precursors that divide just once to generate neurons and then only transiently in nascent neurons. Using a nerfin-1 promoter-controlled reporter transgene, replacement of the nerfin-1 3' UTR with the viral SV-40 3' UTR releases the neuroblast translational block and prolongs reporter protein expression in neurons. Comparative genomics analysis reveals that the nerfin-1 mRNA 3' UTR contains multiple highly conserved sequence blocks that either harbor and/or overlap 21 predicted binding sites for 18 different microRNAs. To determine the functional significance of these microRNA-binding sites and less conserved microRNA target sites, we have studied their ability to block or limit the expression of reporter protein in nerfin-1-expressing cells during embryonic development. Our results indicate that no single microRNA is sufficient to fully inhibit protein expression but rather multiple microRNAs that target different binding sites are required to block ectopic protein expression in neural precursor cells and temporally restrict expression in neurons. Taken together, these results suggest that multiple microRNAs play a cooperative role in the post-transcriptional regulation of nerfin-1 mRNA, and the high degree of microRNA-binding site evolutionary conservation indicates that all members of the Drosophila genus employ a similar strategy to regulate the onset and extinction dynamics of Nerfin-1 expression.

  15. Multiple R2R3-MYB transcription factors involved in the regulation of anthocyanin accumulation in peach flower

    Directory of Open Access Journals (Sweden)

    Hui Zhou

    2016-10-01

    Full Text Available Anthocyanin accumulation is responsible for flower coloration in peach. Here, we report the identification and functional characterization of eight flavonoid-related R2R3-MYB transcription factors, designated PpMYB10.2, PpMYB9, PpMYBPA1, Peace, PpMYB17, PpMYB18, PpMYB19 and PpMYB20, respectively, in peach flower transcriptome. PpMYB10.2 and PpMYB9 are able to activate transcription of anthocyanin biosynthetic genes, whilst PpMYBPA1 and Peace have a strong activation on the promoters of proanthocyanin (PA biosynthetic genes. PpMYB17-20 show a strong repressive effect on transcription of flavonoid pathway genes such as DFR. These results indicate that anthocyanin accumulation in peach flower is coordinately regulated by a set of R2R3-MYB genes. In addition, PpMYB9 and PpMYB10.2 are closely related but separated into two groups, designated MYB9 and MYB10, respectively. PpMYB9 shows a strong activation on the PpUGT78A2 promoter, but with no effect on the promoter of PpUGT78B (commonly called PpUFGT in previous studies. In contrast, PpMYB10.2 is able to activate the PpUFGT promoter, but not for the PpUGT78A2 promoter. Unlike the MYB10 gene that is universally present in plants, the MYB9 gene is lost in most dicot species. Therefore, the PpMYB9 gene represents a novel group of anthocyanin-related MYB activators, which may have diverged in function from the MYB10 genes. Our study will aid in understanding the complex mechanism regulating floral pigmentation in peach and functional divergence of the R2R3-MYB gene family in plants.

  16. Epigenetic regulation of multiple tumor-related genes leads to suppression of breast tumorigenesis by dietary genistein.

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    Yuanyuan Li

    Full Text Available Breast cancer is one of the most lethal diseases in women; however, the precise etiological factors are still not clear. Genistein (GE, a natural isoflavone found in soybean products, is believed to be a potent chemopreventive agent for breast cancer. One of the most important mechanisms for GE inhibition of breast cancer may involve its potential in impacting epigenetic processes allowing reversal of aberrant epigenetic events during breast tumorigenesis. To investigate epigenetic regulation for GE impedance of breast tumorigenesis, we monitored epigenetic alterations of several key tumor-related genes in an established breast cancer transformation system. Our results show that GE significantly inhibited cell growth in a dose-dependent manner in precancerous breast cells and breast cancer cells, whereas it exhibited little effect on normal human mammary epithelial cells. Furthermore, GE treatment increased expression of two crucial tumor suppressor genes, p21(WAF1 (p21 and p16(INK4a (p16, although it decreased expression of two tumor promoting genes, BMI1 and c-MYC. GE treatment led to alterations of histone modifications in the promoters of p21 and p16 as well as the binding ability of the c-MYC-BMI1 complex to the p16 promoter contributing to GE-induced epigenetic activation of these tumor suppressor genes. In addition, an orally-fed GE diet prevented breast tumorigenesis and inhibited breast cancer development in breast cancer mice xenografts. Our results suggest that genistein may repress early breast tumorigenesis by epigenetic regulation of p21 and p16 by impacting histone modifications as well as the BMI1-c-MYC complex recruitment to the regulatory region in the promoters of these genes. These studies will facilitate more effective use of soybean product in breast cancer prevention and also help elucidate the mechanisms during the process of early breast tumorigenesis.

  17. Epigenetic regulation of multiple tumor-related genes leads to suppression of breast tumorigenesis by dietary genistein.

    Science.gov (United States)

    Li, Yuanyuan; Chen, Huaping; Hardy, Tabitha M; Tollefsbol, Trygve O

    2013-01-01

    Breast cancer is one of the most lethal diseases in women; however, the precise etiological factors are still not clear. Genistein (GE), a natural isoflavone found in soybean products, is believed to be a potent chemopreventive agent for breast cancer. One of the most important mechanisms for GE inhibition of breast cancer may involve its potential in impacting epigenetic processes allowing reversal of aberrant epigenetic events during breast tumorigenesis. To investigate epigenetic regulation for GE impedance of breast tumorigenesis, we monitored epigenetic alterations of several key tumor-related genes in an established breast cancer transformation system. Our results show that GE significantly inhibited cell growth in a dose-dependent manner in precancerous breast cells and breast cancer cells, whereas it exhibited little effect on normal human mammary epithelial cells. Furthermore, GE treatment increased expression of two crucial tumor suppressor genes, p21(WAF1) (p21) and p16(INK4a) (p16), although it decreased expression of two tumor promoting genes, BMI1 and c-MYC. GE treatment led to alterations of histone modifications in the promoters of p21 and p16 as well as the binding ability of the c-MYC-BMI1 complex to the p16 promoter contributing to GE-induced epigenetic activation of these tumor suppressor genes. In addition, an orally-fed GE diet prevented breast tumorigenesis and inhibited breast cancer development in breast cancer mice xenografts. Our results suggest that genistein may repress early breast tumorigenesis by epigenetic regulation of p21 and p16 by impacting histone modifications as well as the BMI1-c-MYC complex recruitment to the regulatory region in the promoters of these genes. These studies will facilitate more effective use of soybean product in breast cancer prevention and also help elucidate the mechanisms during the process of early breast tumorigenesis.

  18. Regulation of unbalanced electromagnetic moment in mutual loading systems of electric machines of traction rolling stock and multiple unit of mainline and industrial transport

    Directory of Open Access Journals (Sweden)

    A. M. Afanasov

    2014-12-01

    Full Text Available Purpose. The research data are aimed to identify the regulatory principles of unbalanced electromagnetic moment of mutually loaded electric machines of traction rolling stock and multiple unit of main and industrial transport. The purpose of this study is energy efficiency increase of the testing of traction electric machines of direct and pulse current using the improvement methods of their mutual loading, including the principles of automatic regulation of mutual loading system. Methodology. The general theoretical provisions and principles of system approach to the theoretical electric engineering, the theory of electric machines and theoretical mechanics are the methodological basis of this research. The known methods of analysis of electromagnetic and electromechanical processes in electrical machines of direct and pulse current are used in the study. Methods analysis of loading modes regulation of traction electric machines was conducted using the generalized scheme of mutual loading. It is universal for all known methods to cover the losses of idling using the electric power. Findings. The general management principles of mutual loading modes of the traction electric machines of direct and pulse current by regulating their unbalanced electric magnetic moment were developed. Regulatory options of unbalanced electromagnetic moment are examined by changing the difference of the magnetic fluxes of mutually loaded electric machines, the current difference of electric machines anchors, the difference of the angular velocities of electric machines shafts. Originality. It was obtained the scientific basis development to improve the energy efficiency test methods of traction electric machines of direct and pulse current. The management principles of mutual loading modes of traction electric machines were formulated. For the first time it is introduced the concept and developed the principles of regulation of unbalanced electromagnetic moment in

  19. Prohibitin( PHB) roles in granulosa cell physiology.

    Science.gov (United States)

    Chowdhury, Indrajit; Thomas, Kelwyn; Thompson, Winston E

    2016-01-01

    Ovarian granulosa cells (GC) play an important role in the growth and development of the follicle in the process known as folliculogenesis. In the present review, we focus on recent developments in prohibitin (PHB) research in relation to GC physiological functions. PHB is a member of a highly conserved eukaryotic protein family containing the repressor of estrogen activity (REA)/stomatin/PHB/flotillin/HflK/C (SPFH) domain (also known as the PHB domain) found in diverse species from prokaryotes to eukaryotes. PHB is ubiquitously expressed in a circulating free form or is present in multiple cellular compartments including mitochondria, nucleus and plasma membrane. In mitochondria, PHB is anchored to the mitochondrial inner membrane and forms complexes with the ATPases associated with proteases having diverse cellular activities. PHB continuously shuttles between the mitochondria, cytosol and nucleus. In the nucleus, PHB interacts with various transcription factors and modulates transcriptional activity directly or through interactions with chromatin remodeling proteins. Many functions have been attributed to the mitochondrial and nuclear PHB complexes such as cellular differentiation, anti-proliferation, morphogenesis and maintenance of the functional integrity of the mitochondria. However, to date, the regulation of PHB expression patterns and GC physiological functions are not completely understood.

  20. Physiology of bile secretion.

    Science.gov (United States)

    Esteller, Alejandro

    2008-10-07

    The formation of bile depends on the structural and functional integrity of the bile-secretory apparatus and its impairment, in different situations, results in the syndrome of cholestasis. The structural bases that permit bile secretion as well as various aspects related with its composition and flow rate in physiological conditions will first be reviewed. Canalicular bile is produced by polarized hepatocytes that hold transporters in their basolateral (sinusoidal) and apical (canalicular) plasma membrane. This review summarizes recent data on the molecular determinants of this primary bile formation. The major function of the biliary tree is modification of canalicular bile by secretory and reabsorptive processes in bile-duct epithelial cells (cholangiocytes) as bile passes through bile ducts. The mechanisms of fluid and solute transport in cholangiocytes will also be discussed. In contrast to hepatocytes where secretion is constant and poorly controlled, cholangiocyte secretion is regulated by hormones and nerves. A short section dedicated to these regulatory mechanisms of bile secretion has been included. The aim of this revision was to set the bases for other reviews in this series that will be devoted to specific issues related with biliary physiology and pathology.

  1. Identifying and quantifying main components of physiological noise in functional near infrared spectroscopy on prefrontal cortex

    Directory of Open Access Journals (Sweden)

    Evgeniya eKirilina

    2013-12-01

    Full Text Available Functional Near-Infrared Spectroscopy (fNIRS is a promising method to study functional organization of the prefrontal cortex. However, in order to realize the high potential of fNIRS, effective discrimination between physiological noise originating from forehead skin haemodynamic and cerebral signals is required. Main sources of physiological noise are global and local blood flow regulation processes on multiple time scales. The goal of the present study was to identify the main physiological noise contributions in fNIRS forehead signals and to develop a method for physiological de-noising of fNIRS data. To achieve this goal we combined concurrent time-domain fNIRS and peripheral physiology recordings with wavelet coherence analysis. Depth selectivity was achieved by analyzing moments of photon time-of-flight distributions provided by time-domain fNIRS. Simultaneously, mean arterial blood pressure (MAP, heart rate (HR, and skin blood flow (SBF on the forehead were recorded. Wavelet coherence analysis was employed to quantify the impact of physiological processes on fNIRS signals separately for different time scales. We identified three main processes contributing to physiological noise in fNIRS signals on the forehead. The first process with the period of about 3 s is induced by respiration. The second process is highly correlated with time lagged MAP and HR fluctuations with a period of about 10 s often referred as Mayer waves. The third process is local regulation of the facial skin blood flow time locked to the task-evoked fNIRS signals. All processes affect oxygenated haemoglobin concentration more strongly than that of deoxygenated haemoglobin. Based on these results we developed a set of physiological regressors, which were used for physiological de-noising of fNIRS signals. Our results demonstrate that proposed de-noising method can significantly improve the sensitivity of fNIRS to cerebral signals.

  2. Use of the SSHAC methodology within regulated environments: Cost-effective application for seismic characterization at multiple sites

    International Nuclear Information System (INIS)

    Coppersmith, Kevin J.; Bommer, Julian J.

    2012-01-01

    Highlights: ► SSHAC processes provide high levels of regulatory assurance in hazard assessments for purposes of licensing and safety review. ► SSHAC projects provide structure to the evaluation of available data, models, and methods for building hazard input models. ► Experience on several nuclear projects in the past 15 years leads to the identification of key essential procedural steps. ► Conducting a regional SSHAC Level 3 study, followed by Level 2 site-specific studies can be time and cost effective. - Abstract: Essential elements of license applications and safety reviews for nuclear facilities are quantifications of earthquake and other natural hazards. A Senior Seismic Hazard Analysis Committee (SSHAC) Level 3 or 4 process provides regulatory assurance that the hazard assessment considers all data and models proposed by members of the technical community and the associated uncertainties have been properly quantified. The SSHAC process has been endorsed as an acceptable hazard assessment methodology in US NRC regulatory guidance. Where hazard studies are required for multiple sites, regional SSHAC Level 3 or 4 studies followed by site-specific Level 2 refinements can provide major benefits in cost and duration.

  3. Somatostatin and opioid receptors do not regulate proliferation or apoptosis of the human multiple myeloma U266 cells

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    Allouche Stéphane

    2009-06-01

    Full Text Available Abstract Background opioid and somatostatin receptors (SSTRs that can assemble as heterodimer were individually reported to modulate malignant cell proliferation and to favour apoptosis. Materials and methods: SSTRs and opioid receptors expression were examined by RT-PCR, western-blot and binding assays, cell proliferation was studied by XTT assay and propidium iodide (PI staining and apoptosis by annexin V-PI labelling. Results almost all human malignant haematological cell lines studied here expressed the five SSTRs. Further experiments were conducted on the human U266 multiple myeloma cells, which express also μ-opioid receptors (MOP-R. XTT assays and cell cycle studies provide no evidence for a significant effect upon opioid or somatostatin receptors stimulation. Furthermore, neither direct effect nor potentiation of the Fas-receptor pathway was detected on apoptosis after these treatments. Conclusion these data suggest that SSTRs or opioid receptors expression is not a guaranty for an anti-tumoral action in U266 cell line.

  4. The Imipridone ONC201 Induces Apoptosis and Overcomes Chemotherapy Resistance by Up-Regulation of Bim in Multiple Myeloma.

    Science.gov (United States)

    Tu, Yong-Sheng; He, Jin; Liu, Huan; Lee, Hans C; Wang, Hua; Ishizawa, Jo; Allen, Joshua E; Andreeff, Michael; Orlowski, Robert Z; Davis, Richard E; Yang, Jing

    2017-10-01

    In multiple myeloma, despite recent improvements offered by new therapies, disease relapse and drug resistance still occur in the majority of patients. Therefore, there is an urgent need for new drugs that can overcome drug resistance and prolong patient survival after failure of standard therapies. The imipridone ONC201 causes downstream inactivation of ERK1/2 signaling and has tumoricidal activity against a variety of tumor types, while its efficacy in preclinical models of myeloma remains unclear. In this study, we treated human myeloma cell lines and patient-derived tumor cells with ONC201. Treatment decreased cellular viability and induced apoptosis in myeloma cell lines, with IC50 values of 1 to 1.5 μM, even in those with high risk features or TP53 loss. ONC201 increased levels of the pro-apoptotic protein Bim in myeloma cells, resulting from decreased phosphorylation of degradation-promoting Bim Ser69 by ERK1/2. In addition, myeloma cell lines made resistant to several standard-of-care agents (by chronic exposure) were equally sensitive to ONC201 as their drug-naïve counterparts, and combinations of ONC201 with proteasome inhibitors had synergistic anti-myeloma activity. Overall, these findings demonstrate that ONC201 kills myeloma cells regardless of resistance to standard-of-care therapies, making it promising for clinical testing in relapsed/refractory myeloma. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  5. The Imipridone ONC201 Induces Apoptosis and Overcomes Chemotherapy Resistance by Up-Regulation of Bim in Multiple Myeloma

    Directory of Open Access Journals (Sweden)

    Yong-sheng Tu

    2017-10-01

    Full Text Available In multiple myeloma, despite recent improvements offered by new therapies, disease relapse and drug resistance still occur in the majority of patients. Therefore, there is an urgent need for new drugs that can overcome drug resistance and prolong patient survival after failure of standard therapies. The imipridone ONC201 causes downstream inactivation of ERK1/2 signaling and has tumoricidal activity against a variety of tumor types, while its efficacy in preclinical models of myeloma remains unclear. In this study, we treated human myeloma cell lines and patient-derived tumor cells with ONC201. Treatment decreased cellular viability and induced apoptosis in myeloma cell lines, with IC50 values of 1 to 1.5 μM, even in those with high risk features or TP53 loss. ONC201 increased levels of the pro-apoptotic protein Bim in myeloma cells, resulting from decreased phosphorylation of degradation-promoting Bim Ser69 by ERK1/2. In addition, myeloma cell lines made resistant to several standard-of-care agents (by chronic exposure were equally sensitive to ONC201 as their drug-naïve counterparts, and combinations of ONC201 with proteasome inhibitors had synergistic anti-myeloma activity. Overall, these findings demonstrate that ONC201 kills myeloma cells regardless of resistance to standard-of-care therapies, making it promising for clinical testing in relapsed/refractory myeloma.

  6. P2X7 receptors regulate multiple types of membrane trafficking responses and non-classical secretion pathways.

    Science.gov (United States)

    Qu, Yan; Dubyak, George R

    2009-06-01

    Activation of the P2X7 receptor (P2X7R) triggers a remarkably diverse array of membrane trafficking responses in leukocytes and epithelial cells. These responses result in altered profiles of cell surface lipid and protein composition that can modulate the direct interactions of P2X7R-expressing cells with other cell types in the circulation, in blood vessels, at epithelial barriers, or within sites of immune and inflammatory activation. Additionally, these responses can result in the release of bioactive proteins, lipids, and large membrane complexes into extracellular compartments for remote communication between P2X7R-expressing cells and other cells that amplify or modulate inflammation, immunity, and responses to tissue damages. This review will discuss P2X7R-mediated effects on membrane composition and trafficking in the plasma membrane (PM) and intracellular organelles, as well as actions of P2X7R in controlling various modes of non-classical secretion. It will review P2X7R regulation of: (1) phosphatidylserine distribution in the PM outer leaflet; (2) shedding of PM surface proteins; (3) release of PM-derived microvesicles or microparticles; (4) PM blebbing; (5) cell-cell fusion resulting in formation of multinucleate cells; (6) phagosome maturation and fusion with lysosomes; (7) permeability of endosomes with internalized pathogen-associated molecular patterns; (8) permeability/integrity of mitochondria; (9) exocytosis of secretory lysosomes; and (10) release of exosomes from multivesicular bodies.

  7. Drosophila Pumilio protein contains multiple autonomous repression domains that regulate mRNAs independently of Nanos and brain tumor.

    Science.gov (United States)

    Weidmann, Chase A; Goldstrohm, Aaron C

    2012-01-01

    Drosophila melanogaster Pumilio is an RNA-binding protein that potently represses specific mRNAs. In developing embryos, Pumilio regulates a key morphogen, Hunchback, in collaboration with the cofactor Nanos. To investigate repression by Pumilio and Nanos, we created cell-based assays and found that Pumilio inhibits translation and enhances mRNA decay independent of Nanos. Nanos robustly stimulates repression through interactions with the Pumilio RNA-binding domain. We programmed Pumilio to recognize a new binding site, which garners repression of new target mRNAs. We show that cofactors Brain Tumor and eIF4E Homologous Protein are not obligatory for Pumilio and Nanos activity. The conserved RNA-binding domain of Pumilio was thought to be sufficient for its function. Instead, we demonstrate that three unique domains in the N terminus of Pumilio possess the major repressive activity and can function autonomously. The N termini of insect and vertebrate Pumilio and Fem-3 binding factors (PUFs) are related, and we show that corresponding regions of human PUM1 and PUM2 have repressive activity. Other PUF proteins lack these repression domains. Our findings suggest that PUF proteins have evolved new regulatory functions through protein sequences appended to their conserved PUF repeat RNA-binding domains.

  8. Transcriptome Profiling Reveals the Negative Regulation of Multiple Plant Hormone Signaling Pathways Elicited by Overexpression of C-Repeat Binding Factors

    Directory of Open Access Journals (Sweden)

    Aixin Li

    2017-09-01

    Full Text Available C-repeat binding factors (CBF are a subfamily of AP2 transcription factors that play critical roles in the regulation of plant cold tolerance and growth in low temperature. In the present work, we sought to perform a detailed investigation into global transcriptional regulation of plant hormone signaling associated genes in transgenic plants engineered with CBF genes. RNA samples from Arabidopsis thaliana plants overexpressing two CBF genes, CBF2 and CBF3, were subjected to Illumina HiSeq 2000 RNA sequencing (RNA-Seq. Our results showed that more than half of the hormone associated genes that were differentially expressed in CBF2 or CBF3 transgenic plants were related to auxin signal transduction and metabolism. Most of these alterations in gene expression could lead to repression of auxin signaling. Accordingly, the IAA content was significantly decreased in young tissues of plants overexpressing CBF2 and CBF3 compared with wild type. In addition, genes associated with the biosynthesis of Jasmonate (JA and Salicylic acid (SA, as well as the signal sensing of Brassinolide (BR and SA, were down-regulated, while genes associated with Gibberellin (GA deactivation were up-regulated. In general, overexpression of CBF2 and CBF3 negatively affects multiple plant hormone signaling pathways in Arabidopsis. The transcriptome analysis using CBF2 and CBF3 transgenic plants provides novel and integrated insights into the interaction between CBFs and plant hormones, particularly the modulation of auxin signaling, which may contribute to the improvement of crop yields under abiotic stress via molecular engineering using CBF genes.

  9. Comparison of two-concentration with multi-concentration linear regressions: Retrospective data analysis of multiple regulated LC-MS bioanalytical projects.

    Science.gov (United States)

    Musuku, Adrien; Tan, Aimin; Awaiye, Kayode; Trabelsi, Fethi

    2013-09-01

    Linear calibration is usually performed using eight to ten calibration concentration levels in regulated LC-MS bioanalysis because a minimum of six are specified in regulatory guidelines. However, we have previously reported that two-concentration linear calibration is as reliable as or even better than using multiple concentrations. The purpose of this research is to compare two-concentration with multiple-concentration linear calibration through retrospective data analysis of multiple bioanalytical projects that were conducted in an independent regulated bioanalytical laboratory. A total of 12 bioanalytical projects were randomly selected: two validations and two studies for each of the three most commonly used types of sample extraction methods (protein precipitation, liquid-liquid extraction, solid-phase extraction). When the existing data were retrospectively linearly regressed using only the lowest and the highest concentration levels, no extra batch failure/QC rejection was observed and the differences in accuracy and precision between the original multi-concentration regression and the new two-concentration linear regression are negligible. Specifically, the differences in overall mean apparent bias (square root of mean individual bias squares) are within the ranges of -0.3% to 0.7% and 0.1-0.7% for the validations and studies, respectively. The differences in mean QC concentrations are within the ranges of -0.6% to 1.8% and -0.8% to 2.5% for the validations and studies, respectively. The differences in %CV are within the ranges of -0.7% to 0.9% and -0.3% to 0.6% for the validations and studies, respectively. The average differences in study sample concentrations are within the range of -0.8% to 2.3%. With two-concentration linear regression, an average of 13% of time and cost could have been saved for each batch together with 53% of saving in the lead-in for each project (the preparation of working standard solutions, spiking, and aliquoting). Furthermore

  10. Interleukin-6 counteracts therapy-induced cellular oxidative stress in multiple myeloma by up-regulating manganese superoxide dismutase.

    Science.gov (United States)

    Brown, Charles O; Salem, Kelley; Wagner, Brett A; Bera, Soumen; Singh, Neeraj; Tiwari, Ajit; Choudhury, Amit; Buettner, Garry R; Goel, Apollina

    2012-06-15

    IL (interleukin)-6, an established growth factor for multiple myeloma cells, induces myeloma therapy resistance, but the resistance mechanisms remain unclear. The present study determines the role of IL-6 in re-establishing intracellular redox homoeostasis in the context of myeloma therapy. IL-6 treatment increased myeloma cell resistance to agents that induce oxidative stress, including IR (ionizing radiation) and Dex (dexamethasone). Relative to IR alone, myeloma cells treated with IL-6 plus IR demonstrated reduced annexin/propidium iodide staining, caspase 3 activation, PARP [poly(ADP-ribose) polymerase] cleavage and mitochondrial membrane depolarization with increased clonogenic survival. IL-6 combined with IR or Dex increased early intracellular pro-oxidant levels that were causally related to activation of NF-κB (nuclear factor κB) as determined by the ability of N-acetylcysteine to suppress both pro-oxidant levels and NF-κB activation. In myeloma cells, upon combination with hydrogen peroxide treatment, relative to TNF (tumour necrosis factor)-α, IL-6 induced an early perturbation in reduced glutathione level and increased NF-κB-dependent MnSOD (manganese superoxide dismutase) expression. Furthermore, knockdown of MnSOD suppressed the IL-6-induced myeloma cell resistance to radiation. MitoSOX Red staining showed that IL-6 treatment attenuated late mitochondrial oxidant production in irradiated myeloma cells. The present study provides evidence that increases in MnSOD expression mediate IL-6-induced resistance to Dex and radiation in myeloma cells. The results of the present study indicate that inhibition of antioxidant pathways could enhance myeloma cell responses to radiotherapy and/or chemotherapy.

  11. Biallelic germline and somatic mutations in malignant mesothelioma: multiple mutations in transcription regulators including mSWI/SNF genes.

    Science.gov (United States)

    Yoshikawa, Yoshie; Sato, Ayuko; Tsujimura, Tohru; Otsuki, Taiichiro; Fukuoka, Kazuya; Hasegawa, Seiki; Nakano, Takashi; Hashimoto-Tamaoki, Tomoko

    2015-02-01

    We detected low levels of acetylation for histone H3 tail lysines in malignant mesothelioma (MM) cell lines resistant to histone deacetylase inhibitors. To identify the possible genetic causes related to the low histone acetylation levels, whole-exome sequencing was conducted with MM cell lines established from eight patients. A mono-allelic variant of BRD1 was common to two MM cell lines with very low acetylation levels. We identified 318 homozygous protein-damaging variants/mutations (18-78 variants/mutations per patient); annotation analysis showed enrichment of the molecules associated with mammalian SWI/SNF (mSWI/SNF) chromatin remodeling complexes and co-activators that facilitate initiation of transcription. In seven of the patients, we detected a combination of variants in histone modifiers or transcription factors/co-factors, in addition to variants in mSWI/SNF. Direct sequencing showed that homozygous mutations in SMARCA4, PBRM1 and ARID2 were somatic. In one patient, homozygous germline variants were observed for SMARCC1 and SETD2 in chr3p22.1-3p14.2. These exhibited extended germline homozygosity and were in regions containing somatic mutations, leading to a loss of BAP1 and PBRM1 expression in MM cell line. Most protein-damaging variants were heterozygous in normal tissues. Heterozygous germline variants were often converted into hemizygous variants by mono-allelic deletion, and were rarely homozygous because of acquired uniparental disomy. Our findings imply that MM might develop through the somatic inactivation of mSWI/SNF complex subunits and/or histone modifiers, including BAP1, in subjects that have rare germline variants of these transcription regulators and/or transcription factors/co-factors, and in regions prone to mono-allelic deletion during oncogenesis. © 2014 UICC.

  12. Structural characterization of a novel full-length transcript promoter from Horseradish Latent Virus (HRLV) and its transcriptional regulation by multiple stress responsive transcription factors.

    Science.gov (United States)

    Khan, Ahamed; Shrestha, Ankita; Bhuyan, Kashyap; Maiti, Indu B; Dey, Nrisingha

    2018-01-01

    The promoter fragment described in this study can be employed for strong transgene expression under both biotic and abiotic stress conditions. Plant-infecting Caulimoviruses have evolved multiple regulatory mechanisms to address various environmental stimuli during the course of evolution. One such mechanism involves the retention of discrete stress responsive cis-elements which are required for their survival and host-specificity. Here we describe the characterization of a novel Caulimoviral promoter isolated from Horseradish Latent Virus (HRLV) and its regulation by multiple stress responsive Transcription factors (TFs) namely DREB1, AREB1 and TGA1a. The activity of full length transcript (Flt-) promoter from HRLV (- 677 to + 283) was investigated in both transient and transgenic assays where we identified H12 (- 427 to + 73) as the highest expressing fragment having ~ 2.5-fold stronger activity than the CaMV35S promoter. The H12 promoter was highly active and near-constitutive in the vegetative and reproductive parts of both Tobacco and Arabidopsis transgenic plants. Interestingly, H12 contains a distinct cluster of cis-elements like dehydration-responsive element (DRE-core; GCCGAC), an ABA-responsive element (ABRE; ACGTGTC) and as-1 element (TGACG) which are known to be induced by cold, drought and pathogen/SA respectively. The specific binding of DREB1, AREB1 and TGA1a to DRE, ABRE and as-1 elements respectively were confirmed by the gel-binding assays using H12 promoter-specific probes. Detailed mutational analysis of the H12 promoter suggested that the presence of DRE-core and as-1 element was indispensable for its activity which was further confirmed by the transactivation assays. Our studies imply that H12 could be a valuable genetic tool for regulated transgene expression under diverse environmental conditions.

  13. Grass Carp Laboratory of Genetics and Physiology 2 Serves As a Negative Regulator in Retinoic Acid-Inducible Gene I- and Melanoma Differentiation-Associated Gene 5-Mediated Antiviral Signaling in Resting State and Early Stage of Grass Carp Reovirus Infection

    OpenAIRE

    Rao, Youliang; Wan, Quanyuan; Yang, Chunrong; Su, Jianguo

    2017-01-01

    Laboratory of genetics and physiology 2 (LGP2) is a key component of RIG-I-like receptors (RLRs). However, the lack of the caspase recruitment domains (CARDs) results in its controversial functional performance as a negative or positive regulator in antiviral responses. Especially, no sufficient evidence uncovers the functional mechanisms of LGP2 in RLR signaling pathways in teleost. Here, negative regulation mechanism of LGP2 in certain situations in retinoic acid-inducible gene I (RIG-I) an...

  14. SHP2 sails from physiology to pathology.

    Science.gov (United States)

    Tajan, Mylène; de Rocca Serra, Audrey; Valet, Philippe; Edouard, Thomas; Yart, Armelle

    2015-10-01

    Over the two past decades, mutations of the PTPN11 gene, encoding the ubiquitous protein tyrosine phosphatase SHP2 (SH2 domain-containing tyrosine phosphatase 2), have been identified as the causal factor of several developmental diseases (Noonan syndrome (NS), Noonan syndrome with multiple lentigines (NS-ML), and metachondromatosis), and malignancies (juvenile myelomonocytic leukemia). SHP2 plays essential physiological functions in organism development and homeostasis maintenance by regulating fundamental intracellular signaling pathways in response to a wide range of growth factors and hormones, notably the pleiotropic Ras/Mitogen-Activated Protein Kinase (MAPK) and the Phosphoinositide-3 Kinase (PI3K)/AKT cascades. Analysis of the biochemical impacts of PTPN11 mutations first identified both loss-of-function and gain-of-function mutations, as well as more subtle defects, highlighting the major pathophysiological consequences of SHP2 dysregulation. Then, functional genetic studies provided insights into the molecular dysregulations that link SHP2 mutants to the development of specific traits of the diseases, paving the way for the design of specific therapies for affected patients. In this review, we first provide an overview of SHP2's structure and regulation, then describe its molecular roles, notably its functions in modulating the Ras/MAPK and PI3K/AKT signaling pathways, and its physiological roles in organism development and homeostasis. In the second part, we describe the different PTPN11 mutation-associated pathologies and their clinical manifestations, with particular focus on the biochemical and signaling outcomes of NS and NS-ML-associated mutations, and on the recent advances regarding the pathophysiology of these diseases. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  15. Personality and Emotion Regulation Strategies

    Directory of Open Access Journals (Sweden)

    Esti Hayu Purnamaningsih

    2017-01-01

    Full Text Available The emotions has many important functions in our life such as in relation of interpersonal communication, and health. In interpersonal communicative function aimed to signal to other information about internal state. Emotions manifests in specific cognitive, behavioural, and physiological reactions, thus closely related to health. There is wide variety of ways for individuals to regulate their emotion. In this regard, there are two kinds of emotion regulation strategy; first Antecedent-focused emotion regulation consisting of situation selection, situation modification, attentional deployment, cognitive change and second, Response-focused emotion regulation consisting of suppression. The purpose of this research is to investigate personality factors relate with emotion regulation strategies. 339 students from Faculty of Psychology, Universitas Gadjah Mada were participating in this study and given The Big Five Personality Factors (Ramdhani, 2012, adaptation, and the modified version of the Emotion Regulation Scale was used, Emotion Regulation Questionnaire (John & Gross, 2004 which measure personality and emotion regulation respectively. Using multiple regression analysis, the study indicated that personality predicts emotion regulation strategies.

  16. Rice bacterial blight pathogen Xanthomonas oryzae pv. oryzae produces multiple DSF-family signals in regulation of virulence factor production

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    Cha Jae-Soon

    2010-07-01

    Full Text Available Abstract Background Xanthomonas oryzae pv. oryzae (Xoo is the causal agent of rice bacterial blight disease. Xoo produces a range of virulence factors, including EPS, extracellular enzyme, iron-chelating siderophores, and type III-secretion dependent effectors, which are collectively essential for virulence. Genetic and genomics evidence suggest that Xoo might use the diffusible signal factor (DSF type quorum sensing (QS system to regulate the virulence factor production. However, little is known about the chemical structure of the DSF-like signal(s produced by Xoo and the factors influencing the signal production. Results Xoo genome harbours an rpf cluster comprising rpfB, rpfF, rpfC and rpfG. The proteins encoded by these genes are highly homologous to their counterparts in X. campestris pv. campestris (Xcc, suggesting that Xcc and Xoo might use similar mechanisms for DSF biosynthesis and autoregulation. Consistent with in silico analysis, the rpfF mutant was DSF-deficient and the rpfC mutant produced about 25 times higher DSF-like activity than the wild type Xoo strain KACC10331. From the supernatants of rpfC mutant, we purified three compounds showing strong DSF-like activity. Mass spectrometry and NMR analysis revealed that two of them were the previously characterized DSF and BDSF; the third one was a novel unsaturated fatty acid with 2 double bonds and was designated as CDSF in this study. Further analysis showed that all the three DSF-family signals were synthesized via the enzyme RpfF encoded by Xoo2868. DSF and BDSF at a final concentration of 3 μM to the rpfF mutant could fully restore its extracellular xylanase activity and EPS production to the wild type level, but CDSF was less active than DSF and BDSF in induction of EPS and xylanase. DSF and CDSF shared a similar cell density-dependent production time course with the maximum production being detected at 42 h after inoculation, whereas the maximum production of BDSF was observed

  17. Smolt physiology and endocrinology

    Science.gov (United States)

    McCormick, Stephen D.; McCormick, Stephen D.; Farrell, Anthony Peter; Brauner, Colin J.

    2013-01-01

    Hormones play a critical role in maintaining body fluid balance in euryhaline fishes during changes in environmental salinity. The neuroendocrine axis senses osmotic and ionic changes, then signals and coordinates tissue-specific responses to regulate water and ion fluxes. Rapid-acting hormones, e.g. angiotensins, cope with immediate challenges by controlling drinking rate and the activity of ion transporters in the gill, gut, and kidney. Slow-acting hormones, e.g. prolactin and growth hormone/insulin-like growth factor-1, reorganize the body for long-term acclimation by altering the abundance of ion transporters and through cell proliferation and differentiation of ionocytes and other osmoregulatory cells. Euryhaline species exist in all groups of fish, including cyclostomes, and cartilaginous and teleost fishes. The diverse strategies for responding to changes in salinity have led to differential regulation and tissue-specific effects of hormones. Combining traditional physiological approaches with genomic, transcriptomic, and proteomic analyses will elucidate the patterns and diversity of the endocrine control of euryhalinity.

  18. Overexpression of NtPR-Q Up-Regulates Multiple Defense-Related Genes in Nicotiana tabacum and Enhances Plant Resistance to Ralstonia solanacearum

    Directory of Open Access Journals (Sweden)

    Yuanman Tang

    2017-11-01

    Full Text Available Various classes of plant pathogenesis-related proteins have been identified in the past several decades. PR-Q, a member of the PR3 family encoding chitinases, has played an important role in regulating plant resistance and preventing pathogen infection. In this paper, we functionally characterized NtPR-Q in tobacco plants and found that the overexpression of NtPR-Q in tobacco Yunyan87 resulted in higher resistance to Ralstonia solanacearum inoculation. Surprisingly, overexpression of NtPR-Q led to the activation of many defense-related genes, such as salicylic acid (SA-responsive genes NtPR1a/c, NtPR2 and NtCHN50, JA-responsive gene NtPR1b and ET production-associated genes NtACC Oxidase and NtEFE26. Consistent with the role of NtPR-Q in multiple stress responses, NtPR-Q transcripts were induced by the exogenous hormones SA, ethylene and methyl jasmonate, which could enhance the resistance of tobacco to R. solanacearum. Collectively, our results suggested that NtPR-Q overexpression led to the up-regulation of defense-related genes and enhanced plant resistance to R. solanacearum infection.

  19. Physiological control of behaviour in tephritid fruit flies

    International Nuclear Information System (INIS)

    Jang, Eric B.

    2000-01-01

    Studies on the behaviour of tephritid fruit flies have historically focused on the interaction of external stimuli such as temperature, semiochemicals, seasonality, etc., or the interactions of flies between and among species for a number of observed behaviours such as mating, pheromone calling and oviposition. While descriptive behaviour represent much of what we know about these pest species, less is known about the underlying physiological mechanisms which function in priming or modulation of the observed behaviour. Central to our understanding of tephritid behaviour are the multiple and often complex internal factors which are involved, and the path/mechanisms by which external stimuli result in observed behaviour. Tephritid fruit fly physiology is a vastly understudied research area which may provide important information on how peripheral receptors receive information, the transduction and coding of information centrally and how behaviour is regulated biochemically. The integration of physiology disciplines to help explain behaviour is central to the goal of developing new technology which may be useful in fruit fly control. In our laboratory, we have been studying the mechanisms of chemoreception and its link to behaviour in tephritids in such areas as olfaction, feeding, mating and oviposition. Our approach has been that tephritid behaviour can be largely influenced by their peripheral receptors which are responsible for receiving olfactory, gustatory, visual and tactile information inputs and their physiological state which controls internal modulation of behaviour. Thus, differences in behaviour between species might be explained on the basis of differences in their peripheral receptors, and the plasticity in which observed behaviour vary between the same species could very well be attributed to changes in their physiological state that are not readily apparent merely from visual observation. The importance of the physiological state in behavioural

  20. Multiple Myeloma-Derived Exosomes Regulate the Functions of Mesenchymal Stem Cells Partially via Modulating miR-21 and miR-146a

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    Qian Cheng

    2017-01-01

    Full Text Available Exosomes derived from cancer cells can affect various functions of mesenchymal stem cells (MSCs via conveying microRNAs (miRs. miR-21 and miR-146a have been demonstrated to regulate MSC proliferation and transformation. Interleukin-6 (IL-6 secreted from transformed MSCs in turn favors the survival of multiple myeloma (MM cells. However, the effects of MM exosomes on MSC functions remain largely unclear. In this study, we investigated the effects of OPM2 (a MM cell line exosomes (OPM2-exo on regulating the proliferation, cancer-associated fibroblast (CAF transformation, and IL-6 secretion of MSCs and determined the role of miR-21 and miR-146a in these effects. We found that OPM2-exo harbored high levels of miR-21 and miR-146a and that OPM2-exo coculture significantly increased MSC proliferation with upregulation of miR-21 and miR-146a. Moreover, OPM2-exo induced CAF transformation of MSCs, which was evidenced by increased fibroblast-activated protein (FAP, α-smooth muscle actin (α-SMA, and stromal-derived factor 1 (SDF-1 expressions and IL-6 secretion. Inhibition of miR-21 or miR-146a reduced these effects of OPM2-exo on MSCs. In conclusion, MM could promote the proliferation, CAF transformation, and IL-6 secretion of MSCs partially through regulating miR21 and miR146a.

  1. Regulators of Slc4 bicarbonate transporter activity

    Directory of Open Access Journals (Sweden)

    Ian M. Thornell

    2015-06-01

    Full Text Available The Slc4 family of transporters is comprised of anion exchangers (AE1-4, Na-coupled bicarbonate transporters (NCBTs including electrogenic Na/bicarbonate cotransporters (NBCe1 and NBCe2, electroneutral Na/bicarbonate cotransporters (NBCn1 and NBCn2, and the electroneutral Na-driven Cl-bicarbonate exchanger (NDCBE, as well as a borate transporter (BTR1. These transporters regulate intracellular pH (pHi and contribute to steady-state pHi, but are also involved in other physiological processes including CO2 carriage by red blood cells and solute secretion/reabsorption across epithelia. Acid-base transporters function as either acid extruders or acid loaders, with the Slc4 proteins moving HCO3– either into or out of cells. According to results from both molecular and functional studies, multiple Slc4 proteins and/or associated splice variants with similar expected effects on pHi are often found in the same tissue or cell. Such apparent redundancy is likely to be physiologically important. In addition to regulating pHi, a HCO3– transporter contributes to a cell’s ability to fine tune the intracellular regulation of the cotransported/exchanged ion(s (e.g., Na+ or Cl–. In addition, functionally similar transporters or splice variants with different regulatory profiles will optimize pH physiology and solute transport under various conditions or within subcellular domains. Such optimization will depend on activated signaling pathways and transporter expression profiles. In this review, we will summarize and discuss both classical and more recently identified regulators of the Slc4 proteins. Some of these regulators include traditional second messengers, lipids, binding proteins, autoregulatory domains, and less conventional regulators. The material presented will provide insight into the diversity and physiological significance of multiple members within the Slc4 gene family.

  2. Interacción entre proteínas y glicanos en la regulación fisiológica de las células T How do protein-glycan interactions regulate T-cell physiology?

    Directory of Open Access Journals (Sweden)

    Marta A. Toscano

    2006-08-01

    Full Text Available Las interacciones entre proteínas y glicanos juegan un papel fundamental en numerosos eventos de la regulación de la fisiología del sistema inmune, como maduración tímica, activación, migración y apoptosis de células T. Los carbohidratos son capaces de modular la fisiología linfocitaria a través de la interacción específica con lectinas endógenas como selectinas y galectinas. Estas lectinas endógenas son capaces de reconocer estructuras sacarídicas localizadas en glicoproteínas de la superficie celular y regular procesos tan diversos como proliferación, diferenciación y ciclo celular. Existen diversos niveles de control de la interacción entre lectinas y azúcares; en primer lugar podemos mencionar la expresión regulada de estas lectinas durante el desarrollo de una respuesta inmune, y en segundo lugar la regulación espacio-temporal de la actividad de glicosiltranferasas y glicosidasas cuya función es crear y modificar los azúcares específicos para estas lectinas. Existen evidencias de que la expresión y actividad de estas enzimas se regulan en forma positiva o negativa durante diferentes eventos del desarrollo, ejecución y finalización de la respuesta inmune. En este artículo se analizarán los mecanismos a través de los cuales las interacciones entre lectinas con sus carbohidratos específicos modulan en forma específica diversos procesos fisiológicos, como maduración de timocitos, migración linfocitaria, activación y diferenciación de células T y apoptosis.Recent evidence indicates that protein-glycan interactions play a critical role in different events associated with the physiology of T-cell responses including thymocyte maturation, T-cell activation, lymphocyte migration and T-cell apoptosis. Glycans decorating T-cell surface glycoproteins can modulate T-cell physiology by specifically interacting with endogenous lectins including selectins and galectins. These endogenous lectins are capable of

  3. Multilevel functional genomics data integration as a tool for understanding physiology: a network biology perspective.

    Science.gov (United States)

    Davidsen, Peter K; Turan, Nil; Egginton, Stuart; Falciani, Francesco

    2016-02-01

    The overall aim of physiological research is to understand how living systems function in an integrative manner. Consequently, the discipline of physiology has since its infancy attempted to link multiple levels of biological organization. Increasingly this has involved mathematical and computational approaches, typically to model a small number of components spanning several levels of biological organization. With the advent of "omics" technologies, which can characterize the molecular state of a cell or tissue (intended as the level of expression and/or activity of its molecular components), the number of molecular components we can quantify has increased exponentially. Paradoxically, the unprecedented amount of experimental data has made it more difficult to derive conceptual models underlying essential mechanisms regulating mammalian physiology. We present an overview of state-of-the-art methods currently used to identifying biological networks underlying genomewide responses. These are based on a data-driven approach that relies on advanced computational methods designed to "learn" biology from observational data. In this review, we illustrate an application of these computational methodologies using a case study integrating an in vivo model representing the transcriptional state of hypoxic skeletal muscle with a clinical study representing muscle wasting in chronic obstructive pulmonary disease patients. The broader application of these approaches to modeling multiple levels of biological data in the context of modern physiology is discussed. Copyright © 2016 the American Physiological Society.

  4. Chewing Over Physiology Integration

    Science.gov (United States)

    Abdulkader, Fernando; Azevedo-Martins, Anna Karenina; de Arcisio Miranda, Manoel; Brunaldi, Kellen

    2005-01-01

    An important challenge for both students and teachers of physiology is to integrate the differentareas in which physiological knowledge is didactically divided. In developing countries, such an issue is even more demanding, because budget restrictions often affect the physiology program with laboratory classes being the first on the list when it…

  5. Plant Physiology in Greenhouses

    NARCIS (Netherlands)

    Heuvelink, E.; Kierkels, T.

    2015-01-01

    Since 2004 Ep Heuvelink and Tijs Kierkels have been writing a continuing series of plant physiology articles for the Dutch horticultural journal Onder Glas and the international edition In Greenhouses. The book Plant Physiology in Greenhouses consists of 50 of their plant physiology articles. The

  6. Effects of insemination quantity on honey bee queen physiology.

    Directory of Open Access Journals (Sweden)

    Freddie-Jeanne Richard

    2007-10-01

    Full Text Available Mating has profound effects on the physiology and behavior of female insects, and in honey bee (Apis mellifera queens, these changes are permanent. Queens mate with multiple males during a brief period in their early adult lives, and shortly thereafter they initiate egg-laying. Furthermore, the pheromone profiles of mated queens differ from those of virgins, and these pheromones regulate many different aspects of worker behavior and colony organization. While it is clear that mating causes dramatic changes in queens, it is unclear if mating number has more subtle effects on queen physiology or queen-worker interactions; indeed, the effect of multiple matings on female insect physiology has not been broadly addressed. Because it is not possible to control the natural mating behavior of queens, we used instrumental insemination and compared queens inseminated with semen from either a single drone (single-drone inseminated, or SDI or 10 drones (multi-drone inseminated, or MDI. We used observation hives to monitor attraction of workers to SDI or MDI queens in colonies, and cage studies to monitor the attraction of workers to virgin, SDI, and MDI queen mandibular gland extracts (the main source of queen pheromone. The chemical profiles of the mandibular glands of virgin, SDI, and MDI queens were characterized using GC-MS. Finally, we measured brain expression levels in SDI and MDI queens of a gene associated with phototaxis in worker honey bees (Amfor. Here, we demonstrate for the first time that insemination quantity significantly affects mandibular gland chemical profiles, queen-worker interactions, and brain gene expression. Further research will be necessary to elucidate the mechanistic bases for these effects: insemination volume, sperm and seminal protein quantity, and genetic diversity of the sperm may all be important factors contributing to this profound change in honey bee queen physiology, queen behavior, and social interactions in the

  7. Narrowing the gap between eye care needs and service provision: a model to dynamically regulate the flow of personnel through a multiple entry and exit training programme

    Directory of Open Access Journals (Sweden)

    Masnick Keith

    2009-05-01

    Full Text Available Abstract Background The purpose of this paper is to present a complex yet transparent, computable model to simulate the regulation of the flow of personnel through a previously described multiple-entry, multiple-exit eye care training scheme linked to the health workforce. This methodology should be a useful tool for the planner; it can address changes and feedbacks over time and be sensitive to any unexpected consequences of the interactions. The same model template can be applied to calculate the finances associated with the personnel flow. Presentation of the hypothesis The worth of any model or set of concepts of human resources for health is considerably enhanced by actual field application. However, implementation involves the selection of one set of parameters and a large, long-term commitment of resources. A far less expensive and time-consuming, yet still effective, method of testing assumptions and ideas would be to simulate their application using a variety of possible inputs, structural configurations and/or desired outcomes. To that end, this paper presents a computable, dynamic model of personnel flows within a health system. Testing the hypothesis Some testing of the model has been demonstrated in a previous paper. However, the value of the model is that all stakeholders can enter their own data and parameter assumptions and readily review the outcomes. Implications of the hypothesis The complex yet easy-to-use model presented in this paper opens the debate on current and future policy to any stakeholder. A very wide range of scenarios can be considered and a selected option can be monitored and changed dynamically over time.

  8. Multiple conformational states of DnaA protein regulate its interaction with DnaA boxes in the initiation of DNA replication.

    Science.gov (United States)

    Patel, Meera J; Bhatia, Lavesh; Yilmaz, Gulden; Biswas-Fiss, Esther E; Biswas, Subhasis B

    2017-09-01

    DnaA protein is the initiator of genomic DNA replication in prokaryotes. It binds to specific DNA sequences in the origin of DNA replication and unwinds small AT-rich sequences downstream for the assembly of the replisome. The mechanism of activation of DnaA that enables it to bind and organize the origin DNA and leads to replication initiation remains unclear. In this study, we have developed double-labeled fluorescent DnaA probes to analyze conformational states of DnaA protein upon binding DNA, nucleotide, and Soj sporulation protein using Fluorescence Resonance Energy Transfer (FRET). Our studies demonstrate that DnaA protein undergoes large conformational changes upon binding to substrates and there are multiple distinct conformational states that enable it to initiate DNA replication. DnaA protein adopted a relaxed conformation by expanding ~15Å upon binding ATP and DNA to form the ATP·DnaA·DNA complex. Hydrolysis of bound ATP to ADP led to a contraction of DnaA within the complex. The relaxed conformation of DnaA is likely required for the formation of the multi-protein ATP·DnaA·DNA complex. In the initiation of sporulation, Soj binding to DnaA prevented relaxation of its conformation. Soj·ADP appeared to block the activation of DnaA, suggesting a mechanism for Soj·ADP in switching initiation of DNA replication to sporulation. Our studies demonstrate that multiple conformational states of DnaA protein regulate its binding to DNA in the initiation of DNA replication. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Doppler radar physiological sensing

    CERN Document Server

    Lubecke, Victor M; Droitcour, Amy D; Park, Byung-Kwon; Singh, Aditya

    2016-01-01

    Presents a comprehensive description of the theory and practical implementation of Doppler radar-based physiological monitoring. This book includes an overview of current physiological monitoring techniques and explains the fundamental technology used in remote non-contact monitoring methods. Basic radio wave propagation and radar principles are introduced along with the fundamentals of physiological motion and measurement. Specific design and implementation considerations for physiological monitoring radar systems are then discussed in detail. The authors address current research and commercial development of Doppler radar based physiological monitoring for healthcare and other applications.

  10. An index-based framework for assessing patterns and trends in river fragmentation and flow regulation by global dams at multiple scales

    International Nuclear Information System (INIS)

    Grill, Günther; Lehner, Bernhard; Lumsdon, Alexander E; Zarfl, Christiane; MacDonald, Graham K; Reidy Liermann, Catherine

    2015-01-01

    The global number of dam constructions has increased dramatically over the past six decades and is forecast to continue to rise, particularly in less industrialized regions. Identifying development pathways that can deliver the benefits of new infrastructure while also maintaining healthy and productive river systems is a great challenge that requires understanding the multifaceted impacts of dams at a range of scales. New approaches and advanced methodologies are needed to improve predictions of how future dam construction will affect biodiversity, ecosystem functioning, and fluvial geomorphology worldwide, helping to frame a global strategy to achieve sustainable dam development. Here, we respond to this need by applying a graph-based river routing model to simultaneously assess flow regulation and fragmentation by dams at multiple scales using data at high spatial resolution. We calculated the cumulative impact of a set of 6374 large existing dams and 3377 planned or proposed dams on river connectivity and river flow at basin and subbasin scales by fusing two novel indicators to create a holistic dam impact matrix for the period 1930–2030. Static network descriptors such as basin area or channel length are of limited use in hierarchically nested and dynamic river systems, so we developed the river fragmentation index and the river regulation index, which are based on river volume. These indicators are less sensitive to the effects of network configuration, offering increased comparability among studies with disparate hydrographies as well as across scales. Our results indicate that, on a global basis, 48% of river volume is moderately to severely impacted by either flow regulation, fragmentation, or both. Assuming completion of all dams planned and under construction in our future scenario, this number would nearly double to 93%, largely due to major dam construction in the Amazon Basin. We provide evidence for the importance of considering small to medium

  11. Nitric oxide: a physiologic messenger.

    Science.gov (United States)

    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.

  12. Human physiological models of insomnia.

    Science.gov (United States)

    Richardson, Gary S

    2007-12-01

    Despite the wide prevalence and important consequences of insomnia, remarkably little is known about its pathophysiology. Available models exist primarily in the psychological domain and derive from the demonstrated efficacy of behavioral treatment approaches to insomnia management. However, these models offer little specific prediction about the anatomic or physiological foundation of chronic primary insomnia. On the other hand, a growing body of data on the physiology of sleep supports a reasonably circumscribed overview of possible pathophysiological mechanisms, as well as the development of physiological models of insomnia to guide future research. As a pragmatic step, these models focus on primary insomnia, as opposed to comorbid insomnias, because the latter is by its nature a much more heterogeneous presentation, reflecting the effects of the distinct comorbid condition. Current understanding of the regulation of sleep and wakefulness in mammalian brain supports four broad candidate areas: 1) disruption of the sleep homeostat; 2) disruption of the circadian clock; 3) disruption of intrinsic systems responsible for the expression of sleep states; or 4) disruption (hyperactivity) of extrinsic systems capable of over-riding normal sleep-wake regulation. This review examines each of the four candidate pathophysiological mechanisms and the available data in support of each. While studies that directly test the viability of each model are not yet available, descriptive data on primary insomnia favor the involvement of dysfunctional extrinsic stress-response systems in the pathology of primary chronic insomnia.

  13. Physiology of free radicals

    Directory of Open Access Journals (Sweden)

    Stevanović Jelka

    2011-01-01

    Full Text Available Free radicals imply that every atom, molecule, ion, group of atoms, or molecules with one or several non-paired electrons in outer orbital. Among these are: nitrogenoxide (NO•, superoxide-anion-radical (O2•-, hydroxyl radical (OH•, peroxyl radical (ROO•, alcoxyl radical (RO• and hydroperoxyl radical (HO2•. However, reactive oxygen species also include components without non-paired electrons in outer orbital (so-called reactive non-radical agents, such as: singlet oxygen (1O2, peroxynitrite (ONOO-, hydrogen-peroxide (H2O2, hypochloric acid (eg. HOCl and ozone (O3. High concentrations of free radicals lead to the development of oxidative stress which is a precondition for numerous pathological effects. However, low and moderate concentrations of these matter, which occur quite normally during cell metabolic activity, play multiple significant roles in many reactions. Some of these are: regulation of signal pathways within the cell and between cells, the role of chemoattractors and leukocyte activators, the role in phagocytosis, participation in maintaining, changes in the position and shape of the cell, assisting the cell during adaption and recovery from damage (e.g.caused by physical effort, the role in normal cell growth, programmed cell death (apoptosis and cell ageing, in the synthesis of essential biological compounds and energy production, as well as the contribution to the regulation of the vascular tone, actually, tissue vascularization.

  14. Which Feedback Is More Effective for Pursuing Multiple Goals of Differing Importance? The Interaction Effects of Goal Importance and Performance Feedback Type on Self-Regulation and Task Achievement

    Science.gov (United States)

    Lee, Hyunjoo

    2016-01-01

    This study examined how performance feedback type (progress vs. distance) affects Korean college students' self-regulation and task achievement according to relative goal importance in the pursuit of multiple goals. For this study, 146 students participated in a computerised task. The results showed the interaction effects of goal importance and…

  15. Metabolic effects of physiological levels of caffeine in myotubes.

    Science.gov (United States)

    Schnuck, Jamie K; Gould, Lacey M; Parry, Hailey A; Johnson, Michele A; Gannon, Nicholas P; Sunderland, Kyle L; Vaughan, Roger A

    2018-02-01

    Caffeine has been shown to stimulate multiple major regulators of cell energetics including AMP-activated protein kinase (AMPK) and Ca 2+ /calmodulin-dependent protein kinase II (CaMKII). Additionally, caffeine induces peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) and mitochondrial biogenesis. While caffeine enhances oxidative metabolism, experimental concentrations often exceed physiologically attainable concentrations through diet. This work measured the effects of low-level caffeine on cellular metabolism and gene expression in myotubes, as well as the dependence of caffeine's effects on the nuclear receptor peroxisome proliferator-activated receptor beta/delta (PPARβ/δ). C2C12 myotubes were treated with various doses of caffeine for up to 24 h. Gene and protein expression were measured via qRT-PCR and Western blot, respectively. Cellular metabolism was determined via oxygen consumption and extracellular acidification rate. Caffeine significantly induced regulators of mitochondrial biogenesis and oxidative metabolism. Mitochondrial staining was suppressed in PPARβ/δ-inhibited cells which was rescued by concurrent caffeine treatment. Caffeine-treated cells also displayed elevated peak oxidative metabolism which was partially abolished following PPARβ/δ inhibition. Similar to past observations, glucose uptake and GLUT4 content were elevated in caffeine-treated cells, however, glycolytic metabolism was unaltered following caffeine treatment. Physiological levels of caffeine appear to enhance cell metabolism through mechanisms partially dependent on PPARβ/δ.

  16. Multiple garlic (Allium sativum L.) microRNAs regulate the immunity against the basal rot fungus Fusarium oxysporum f. sp. Cepae.

    Science.gov (United States)

    Chand, Subodh Kumar; Nanda, Satyabrata; Mishra, Rukmini; Joshi, Raj Kumar

    2017-04-01

    The basal plate rot fungus, Fusarium oxysporum f. sp. cepae (FOC), is the most devastating pathogen posing a serious threat to garlic (Allium sativum L.) production worldwide. MicroRNAs (miRNAs) are key modulators of gene expression related to development and defense responses in eukaryotes. However, the miRNA species associated with garlic immunity against FOC are yet to be explored. In the present study, a small RNA library developed from FOC infected resistant garlic line was sequenced to identify immune responsive miRNAs. Forty-five miRNAs representing 39 conserved and six novel sequences responsive to FOC were detected. qRT-PCR analyses further classified them into three classes based on their expression patterns in susceptible line CBT-As11 and in the resistant line CBT-As153. North-blot analyses of six selective miRNAs confirmed the qRT-PCR results. Expression studies on a selective set of target genes revealed a negative correlation with the complementary miRNAs. Furthermore, transgenic garlic plant overexpresing miR164a, miR168a and miR393 showed enhanced resistance to FOC, as revealed by decreased fungal growth and up-regulated expression of defense-responsive genes. These results indicate that multiple miRNAs are involved in garlic immunity against FOC and that the overexpression of miR164a, miR168a and miR393 can augment garlic resistance to Fusarium basal rot infection. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. Enzyme-regulated the changes of pH values for assembling a colorimetric and multistage interconnection logic network with multiple readouts

    Energy Technology Data Exchange (ETDEWEB)

    Huang, Yanyan; Ran, Xiang; Lin, Youhui [Laboratory of Chemical Biology, Division of Biological Inorganic Chemistry, State Key Laboratory of Rare Earth Resource Utilization, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, Jilin 130022 (China); Graduate School of University of Chinese Academy of Sciences, Beijing 100039 (China); Ren, Jinsong, E-mail: jren@ciac.ac.cn [Laboratory of Chemical Biology, Division of Biological Inorganic Chemistry, State Key Laboratory of Rare Earth Resource Utilization, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, Jilin 130022 (China); Qu, Xiaogang [Laboratory of Chemical Biology, Division of Biological Inorganic Chemistry, State Key Laboratory of Rare Earth Resource Utilization, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, Jilin 130022 (China)

    2015-04-22

    Highlights: • A colorimetric and multistage biological network has been developed. • This system was on the basis of the enzyme-regulated changes of pH values. • This enzyme-based system could assemble large biological circuit. • Two signal transducers (DNA/AuNPs and acid–base indicators) were used. • The compositions of samples could be detected through visual output signals. - Abstract: Based on enzymatic reactions-triggered changes of pH values and biocomputing, a novel and multistage interconnection biological network with multiple easy-detectable signal outputs has been developed. Compared with traditional chemical computing, the enzyme-based biological system could overcome the interference between reactions or the incompatibility of individual computing gates and offer a unique opportunity to assemble multicomponent/multifunctional logic circuitries. Our system included four enzyme inputs: β-galactosidase (β-gal), glucose oxidase (GOx), esterase (Est) and urease (Ur). With the assistance of two signal transducers (gold nanoparticles and acid–base indicators) or pH meter, the outputs of the biological network could be conveniently read by the naked eyes. In contrast to current methods, the approach present here could realize cost-effective, label-free and colorimetric logic operations without complicated instrument. By designing a series of Boolean logic operations, we could logically make judgment of the compositions of the samples on the basis of visual output signals. Our work offered a promising paradigm for future biological computing technology and might be highly useful in future intelligent diagnostics, prodrug activation, smart drug delivery, process control, and electronic applications.

  18. Enzyme-regulated the changes of pH values for assembling a colorimetric and multistage interconnection logic network with multiple readouts

    International Nuclear Information System (INIS)

    Huang, Yanyan; Ran, Xiang; Lin, Youhui; Ren, Jinsong; Qu, Xiaogang

    2015-01-01

    Highlights: • A colorimetric and multistage biological network has been developed. • This system was on the basis of the enzyme-regulated changes of pH values. • This enzyme-based system could assemble large biological circuit. • Two signal transducers (DNA/AuNPs and acid–base indicators) were used. • The compositions of samples could be detected through visual output signals. - Abstract: Based on enzymatic reactions-triggered changes of pH values and biocomputing, a novel and multistage interconnection biological network with multiple easy-detectable signal outputs has been developed. Compared with traditional chemical computing, the enzyme-based biological system could overcome the interference between reactions or the incompatibility of individual computing gates and offer a unique opportunity to assemble multicomponent/multifunctional logic circuitries. Our system included four enzyme inputs: β-galactosidase (β-gal), glucose oxidase (GOx), esterase (Est) and urease (Ur). With the assistance of two signal transducers (gold nanoparticles and acid–base indicators) or pH meter, the outputs of the biological network could be conveniently read by the naked eyes. In contrast to current methods, the approach present here could realize cost-effective, label-free and colorimetric logic operations without complicated instrument. By designing a series of Boolean logic operations, we could logically make judgment of the compositions of the samples on the basis of visual output signals. Our work offered a promising paradigm for future biological computing technology and might be highly useful in future intelligent diagnostics, prodrug activation, smart drug delivery, process control, and electronic applications

  19. Small interfering RNA-mediated silencing of nicotinamide phosphoribosyltransferase (NAMPT and lysosomal trafficking regulator (LYST induce growth inhibition and apoptosis in human multiple myeloma cells: A preliminary study

    Directory of Open Access Journals (Sweden)

    Ivyna Pau Ni Bong

    2016-11-01

    Full Text Available Multiple myeloma (MM is a malignancy of B lymphocytes or plasma cells. Our array-based comparative genomic hybridization findings revealed chromosomal gains at 7q22.3 and 1q42.3, where nicotinamide (NAM phosphoribosyltransferase (NAMPT and lysosomal trafficking regulator (LYST genes are localized, respectively. This led us to further study the functions of these genes in myeloma cells. NAMPT is a key enzyme involved in nicotinamide adenine dinucleotide salvage pathway, and it is frequently overexpressed in human cancers. In contrast, little is known about the function of LYST in cancer. The expression of LYST is shown to affect lysosomal size, granule size, and autophagy in human cells. In this study, the effects of small interfering RNA (siRNA-mediated silencing of NAMPT and LYST on cell proliferation and apoptosis were evaluated in RPMI 8226 myeloma cells. Transfection efficiencies were determined by quantitative real time reverse transcriptase PCR. Cell proliferation was determined using MTT assay, while apoptosis was analyzed with flow cytometry using Annexin V-fluorescein isothiocyanate/propidium iodide assay. The NAMPT protein expression in siRNA-treated cells was estimated by enzyme-linked immunosorbent assay. Our results showed that NAMPT and LYST were successfully knockdown by siRNA transfection (p < 0.05. NAMPT or LYST gene silencing significantly inhibited cell proliferation and induced apoptosis in RPMI 8226 cells (p < 0.05. Silencing of NAMPT gene also decreased NAMPT protein levels (p < 0.01. Our study demonstrated that NAMPT and LYST play pivotal roles in the molecular pathogenesis of MM. This is the first report describing the possible functions of LYST in myelomagenesis and its potential role as a therapeutic target in MM.

  20. Small interfering RNA-mediated silencing of nicotinamide phosphoribosyltransferase (NAMPT) and lysosomal trafficking regulator (LYST) induce growth inhibition and apoptosis in human multiple myeloma cells: A preliminary study

    Science.gov (United States)

    Bong, Ivyna Pau Ni; Ng, Ching Ching; Fakiruddin, Shaik Kamal; Lim, Moon Nian; Zakaria, Zubaidah

    2016-01-01

    Multiple myeloma (MM) is a malignancy of B lymphocytes or plasma cells. Our array-based comparative genomic hybridization findings revealed chromosomal gains at 7q22.3 and 1q42.3, where nicotinamide (NAM) phosphoribosyltransferase (NAMPT) and lysosomal trafficking regulator (LYST) genes are localized, respectively. This led us to further study the fprotein expression in unctions of these genes in myeloma cells. NAMPT is a key enzyme involved in nicotinamide adenine dinucleotide salvage pathway, and it is frequently overexpressed in human cancers. In contrast, little is known about the function of LYST in cancer. The expression of LYST is shown to affect lysosomal size, granule size, and autophagy in human cells. In this study, the effects of small interfering RNA (siRNA)-mediated silencing of NAMPT and LYST on cell proliferation and apoptosis were evaluated in RPMI 8226 myeloma cells. Transfection efficiencies were determined by quantitative real time reverse transcriptase PCR. Cell proliferation was determined using MTT assay, while apoptosis was analyzed with flow cytometry using Annexin V-fluorescein isothiocyanate/propidium iodide assay. The NAMPT protein expression in siRNA-treated cells was estimated by enzyme-linked immunosorbent assay. Our results showed that NAMPT and LYST were successfully knockdown by siRNA transfection (p < 0.05). NAMPT or LYST gene silencing significantly inhibited cell proliferation and induced apoptosis in RPMI 8226 cells (p < 0.05). Silencing of NAMPT gene also decreased NAMPT protein levels (p < 0.01). Our study demonstrated that NAMPT and LYST play pivotal roles in the molecular pathogenesis of MM. This is the first report describing the possible functions of LYST in myelomagenesis and its potential role as a therapeutic target in MM. PMID:27754828

  1. Advances in physiological computing

    CERN Document Server

    Fairclough, Stephen H

    2014-01-01

    This edited collection will provide an overview of the field of physiological computing, i.e. the use of physiological signals as input for computer control. It will cover a breadth of current research, from brain-computer interfaces to telemedicine.

  2. Phun Week: Understanding Physiology

    Science.gov (United States)

    Limson, Mel; Matyas, Marsha Lakes

    2009-01-01

    Topics such as sports, exercise, health, and nutrition can make the science of physiology relevant and engaging for students. In addition, many lessons on these topics, such as those on the cardiovascular, respiratory, and digestive systems, align with national and state life science education standards. Physiology Understanding Week (PhUn…

  3. PHYSIOLOGICAL RESPONSES OF DWARF COCONUT PLANTS UNDER WATER DEFICIT IN SALT - AFFECTED SOILS

    Directory of Open Access Journals (Sweden)

    ALEXANDRE REUBER ALMEIDA DA SILVA

    2017-01-01

    Full Text Available The objective of this study was to characterize the physiological acclimation responses of young plants of the dwarf coconut cultivar ̳Jiqui Green‘ associated with tolerance to conditions of multiple abiotic stresses (drought and soil salinity, acting either independently or in combination. The study was conducted under controlled conditions and evaluated the following parameters: leaf gas exchange, quantum yield of chlorophyll a fluorescence, and relative contents of total chlorophyll (SPAD index. The experiment was conducted under a randomized block experimental design, in a split plot arrangement. In the plots, plants were exposed to different levels of water stress, by imposing potential crop evapotranspiration replacement levels equivalent to 100%, 80%, 60%, 40%, and 20%, whereas in subplots, plants were exposed to different levels of soil salinity (1.72, 6.25, 25.80, and 40.70 dS m - 1 . Physiological mechanisms were effectively limited when water deficit and salinity acted separately and/or together. Compared with soil salinity, water stress was more effective in reducing the measured physiological parameters. The magnitudes of the responses of plants to water supply and salinity depended on the intensity of stress and evaluation period. The physiological acclimation responses of plants were mainly related to stomatal regulation. The coconut tree has a number of physiological adjustment mechanisms that give the species partial tolerance to drought stress and/or salt, thereby enabling it to revegetate salinated areas, provided that its water requirements are at least partially met.

  4. Spatiotemporal characteristics of physiological gastroesophageal reflux

    NARCIS (Netherlands)

    Weusten, B. L.; Akkermans, L. M.; vanBerge-Henegouwen, G. P.; Smout, A. J.

    1994-01-01

    Recent technological developments have made it possible to measure intraluminal pH simultaneously at multiple sites using one single small-caliber catheter. The aim of this study was to investigate the dynamics of physiological gastroesophageal reflux in eight ambulatory healthy volunteers (age

  5. The Effect of 12 Weeks Individualized Combined Exercise Rehabilitation Training on Physiological Cost Index (PCI and Walking Speed in Patients with Multiple Sclerosis at all Levels of Physical Disability

    Directory of Open Access Journals (Sweden)

    M Narimani

    2016-11-01

    Full Text Available Background & aim: Most research on the effects of exercise on people with MS rehabilitation exercises sclerosis (MS  have been carried out on patients with low to moderate disability, but research on patients with different severity of disability (physical disability scale of zero to 10 still has to be carefully considered. The aim of this study was to investigate the effects of twelve weeks of rehabilitation exercises personalized compound exercise on physiological cost index (PCI and average speed walking in patients with MS at various levels of disability. Methods: The present research was a semi-experimental practical study. Thus among female patients admitted to the MS Association of Shahrekord city, 96 people were chosen on the basis of physical disability scores and divided into three groups. The first group consisted of less than 5/4 a total of 44 people, the second group between 5/65 and 5/6 up third of each 26 patients were then randomly assigned to an experimental group and a control group. Afterwards each group was divided randomly into an experimental group and a control group. The first group (the scale of disability less than 4.5, N= 44. The second group (the scale of disability 5 - 6.5, N=26. Also 26 patients were in the third group (the scale of disability 6.5 and above. In addition, they were divided into 6 experimental and control groups. Training programs for experimental groups were 12 weeks, three sessions per week and one hour for each session. Factors such as physiological cost index and walking speed were measured with the appropriate tools before and after training. The experimental groups of 1, 2 and 3 each did their own intervention, while the control groups received only stretching exercises. Analysis of data obtained from 96 patients studied was done using descriptive statistics and the analysis of covariance and paired comparing of the adjusted means (P<0.05. ‌‌‌ Results: A significant difference in walking

  6. Reproduction, physiology and biochemistry

    Science.gov (United States)

    This chapter summarizes fundamental knowledge and recent discoveries about the reproduction, physiology and biochemistry of plant-parasitic nematodes. Various types of reproduction are reviewed, including sexual reproduction and mitotic and meiotic parthenogenesis. Although much is known about the p...

  7. Endogenous Pyrogen Physiology.

    Science.gov (United States)

    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)

  8. Biophysics and cell physiology

    International Nuclear Information System (INIS)

    Mazur, P.

    1975-01-01

    Progress is reported on research activities in the fields of physiology and low-temperature biology of mammalian embryos; effects of sub-zero temperatures on eggs and embryos of sea urchins; survival of frozen-thawed human red cells; effects of radiation on physiology of Escherichia coli; transfer of triplet electronic energy in dinucleotides; effects of x radiation on DNA degradation; energy deposition by neutrons; photosynthesis; excision repair of uv-induced pyrimidine dimers in DNA of plant cells

  9. Physiology of Ramadan fasting

    OpenAIRE

    Shokoufeh Bonakdaran

    2016-01-01

    Considering the emphasis of Islam on the importance of fasting, Muslims attempt to fast from dawn until sunset during the holy month of Ramadan. Fasting is associated with several benefits for normal and healthy individuals. However, it could pose high risks to the health of diabetic patients due to certain physiological changes. This study aimed to compare the physiological changes associated with fasting in healthy individuals and diabetic patients during Ramadan. Furthermore, we reviewed t...

  10. Human physiology in space

    Science.gov (United States)

    Vernikos, J.

    1996-01-01

    The universality of gravity (1 g) in our daily lives makes it difficult to appreciate its importance in morphology and physiology. Bone and muscle support systems were created, cellular pumps developed, neurons organised and receptors and transducers of gravitational force to biologically relevant signals evolved under 1g gravity. Spaceflight provides the only microgravity environment where systematic experimentation can expand our basic understanding of gravitational physiology and perhaps provide new insights into normal physiology and disease processes. These include the surprising extent of our body's dependence on perceptual information, and understanding the effect and importance of forces generated within the body's weightbearing structures such as muscle and bones. Beyond this exciting prospect is the importance of this work towards opening the solar system for human exploration. Although both appear promising, we are only just beginning to taste what lies ahead.

  11. Plant Physiology and Development

    DEFF Research Database (Denmark)

    Taiz, Lincoln; Zeiger, Eduardo; Møller, Ian Max

    Throughout its twenty-two year history, the authors of Plant Physiology have continually updated the book to incorporate the latest advances in plant biology and implement pedagogical improvements requested by adopters. This has made Plant Physiology the most authoritative, comprehensive......, and widely used upper-division plant biology textbook. In the Sixth Edition, the Growth and Development section (Unit III) has been reorganized and expanded to present the complete life cycle of seed plants from germination to senescence. In recognition of this enhancement, the text has been renamed Plant...... Physiology and Development. As before, Unit III begins with updated chapters on Cell Walls and Signals and Signal Transduction. The latter chapter has been expanded to include a discussion of major signaling molecules, such as calcium ions and plant hormones. A new, unified chapter entitled Signals from...

  12. The interacting Cra and KdpE regulators are involved in the expression of multiple virulence factors in enterohemorrhagic Escherichia coli.

    Science.gov (United States)

    Njoroge, Jacqueline W; Gruber, Charley; Sperandio, Vanessa

    2013-06-01

    The human pathogen enterohemorrhagic Escherichia coli (EHEC) O157:H7 codes for two interacting DNA binding proteins, Cra and KdpE, that coregulate expression of the locus of enterocyte effacement (LEE) genes in a metabolite-dependent manner. Cra is a transcription factor that uses fluctuations in the concentration of carbon metabolism intermediates to positively regulate virulence of EHEC. KdpE is a response regulator that activates the transcription of homeostasis genes in response to salt-induced osmolarity and virulence genes in response to changes in metabolite concentrations. Here, we probed the transcriptional profiles of the Δcra, ΔkdpE, and Δcra ΔkdpE mutant strains and show that Cra and KdpE share several targets besides the LEE, but both Cra and KdpE also have independent targets. Several genes within O-islands (genomic islands present in EHEC but absent from E. coli K-12), such as Z0639, Z0640, Z3388, Z4267, and espFu (encoding an effector necessary for formation of attaching and effacing lesions on epithelial cells), were directly regulated by both Cra and KdpE, while Z2077 was only regulated by Cra. These studies identified and confirmed new direct targets for Cra and KdpE that included putative virulence factors as well as characterized virulence factors, such as EspFu and EspG. These results map out the role of the two interacting regulators, Cra and KdpE, in EHEC pathogenesis and global gene regulation.

  13. Nigerian Journal of Physiological Sciences

    African Journals Online (AJOL)

    Nigerian Journal of Physiological Sciences (Niger. J. Physiol. Sci.) is a biannual publication of the Physiological Society of Nigeria. It covers diverse areas of research in physiological sciences, publishing reviews in current research areas and original laboratory and clinical research in physiological sciences. Other websites ...

  14. Physiological desensitization of carbohydrate permeases and adenylate cyclase to regulation by the phosphoenolpyruvate:sugar phosphotransferase system in Escherichia coli and Salmonella typhimurium. Involvement of adenosine cyclic 3',5'-phosphate and inducer.

    Science.gov (United States)

    Saier, M H; Keeler, D K; Feucht, B U

    1982-03-10

    Adenylate cyclase and a number of carbohydrate transport systems are subject to regulation by the phosphoenolpyruvate:sugar phosphotransferase system. These sensitive carbohydrate transport systems are desensitized to regulation by the phosphotransferase system, and adenylate cyclase is deactivated when cells are grown in medium containing cyclic AMP. These effects are specific for cyclic AMP and are potentiated by the genetic loss of cyclic AMP phosphodiesterase. Inclusion in the growth medium of an inducer of a sensitive transport system also promotes desensitization of that particular transport system. Inducer-promoted desensitization is specific for the particular target transport system, while cyclic AMP-promoted desensitization is general and affects several systems. Desensitization of the permeases to regulation, and inactivation of adenylate cyclase, are slow processes which are blocked by chloramphenicol and are therefore presumably dependent on protein synthesis. Several sugar substrates of the phosphotransferase system are capable of regulating the sensitive carbohydrate transport systems. The evidence suggests that desensitization to this regulation does not result from a direct effect on the functioning of Enzyme I, a small heat-stable protein of the phosphotransferase system, HPr, or an Enzyme II of the phosphotransferase system, but specifically uncouples the permease systems from regulation.

  15. Simulated Exercise Physiology Laboratories.

    Science.gov (United States)

    Morrow, James R., Jr.; Pivarnik, James M.

    This book consists of a lab manual and computer disks for either Apple or IBM hardware. The lab manual serves as "tour guide" for the learner going through the various lab experiences. The manual contains definitions, proper terminology, and other basic information about physiological principles. It is organized so a step-by-step procedure may be…

  16. Personalized physiological medicine

    NARCIS (Netherlands)

    Ince, Can

    2017-01-01

    This paper introduces the concept of personalized physiological medicine that is specifically directed at the needs of the critically ill patient. This differs from the conventional view of personalized medicine, characterized by biomarkers and gene profiling, instead focusing on time-variant

  17. Physiological responses to hypothermia.

    Science.gov (United States)

    Wood, Thomas; Thoresen, Marianne

    2015-04-01

    Therapeutic hypothermia is the only treatment currently recommended for moderate or severe encephalopathy of hypoxic‒ischaemic origin in term neonates. Though the effects of hypothermia on human physiology have been explored for many decades, much of the data comes from animal or adult studies; the latter originally after accidental hypothermia, followed by application of controlled hypothermia after cardiac arrest or trauma, or during cardiopulmonary bypass. Though this work is informative, the effects of hypothermia on neonatal physiology after perinatal asphyxia must be considered in the context of a prolonged hypoxic insult that has already induced a number of significant physiological sequelae. This article reviews the effects of therapeutic hypothermia on respiratory, cardiovascular, and metabolic parameters, including glycaemic control and feeding requirements. The potential pitfalls of blood‒gas analysis and overtreatment of physiological changes in cardiovascular parameters are also discussed. Finally, the effects of hypothermia on drug metabolism are covered, focusing on how the pharmacokinetics, pharmacodynamics, and dosing requirements of drugs frequently used in neonatal intensive care may change during therapeutic hypothermia. Copyright © 2014 Elsevier Ltd. All rights reserved.

  18. The Face of Physiology

    Directory of Open Access Journals (Sweden)

    Paul White

    2008-10-01

    Full Text Available This article explores the relationship between the physiology of the emotions and the display of character in Victorian Britain. Charles Bell and others had begun to link certain physiological functions, such as respiration, with the expression of feelings such as fear, regarding the heart and other internal organs as instruments by which the emotions were made visible. But a purely functional account of the emotions, which emerged through the development of reflex physiology during the second half of the century, would dramatically alter the nature of feelings and the means of observing them. At the same time, instinctual or acquired sympathy, which had long underpinned the accurate reading of expressions, became a problem to be surmounted by new 'objectively'. Graphic recording instruments measuring a variety of physiological functions and used with increasing frequency in clinical diagnostics became of fundamental importance for tracing the movement of feelings during the period prior to the development of cinematography. They remained, in the form of devices such as the polygraph, a crucial and controversial means of measuring affective states, beneath the potentially deceptive surface of the body.

  19. Natural variation in germination responses of Arabidopsis to seasonal cues and their associated physiological mechanisms

    Science.gov (United States)

    Barua, Deepak; Butler, Colleen; Tisdale, Tracy E.; Donohue, Kathleen

    2012-01-01

    Background and Aims Despite the intense interest in phenological adaptation to environmental change, the fundamental character of natural variation in germination is almost entirely unknown. Specifically, it is not known whether different genotypes within a species are germination specialists to particular conditions, nor is it known what physiological mechanisms of germination regulation vary in natural populations and how they are associated with responses to particular environmental factors. Methods We used a set of recombinant inbred genotypes of Arabidopsis thaliana, in which linkage disequilibrium has been disrupted over seven generations, to test for genetic variation and covariation in germination responses to distinct environmental factors. We then examined physiological mechanisms associated with those responses, including seed-coat permeability and sensitivity to the phytohormones gibberellic acid (GA) and abscisic acid (ABA). Key Results Genetic variation for germination was environment-dependent, but no evidence for specialization of germination to different conditions was found. Hormonal sensitivities also exhibited significant genetic variation, but seed-coat properties did not. GA sensitivity was associated with germination responses to multiple environmental factors, but seed-coat permeability and ABA sensitivity were associated with specific germination responses, suggesting that an evolutionary change in GA sensitivity could affect germination in multiple environments, but that of ABA sensitivity may affect germination under more restricted conditions. Conclusions The physiological mechanisms of germination responses to specific environmental factors therefore can influence the ability to adapt to diverse seasonal environments encountered during colonization of new habitats or with future predicted climate change. PMID:22012958

  20. Application of meta-transcriptomics and –proteomics to analysis of in situ physiological state

    Directory of Open Access Journals (Sweden)

    Allan eKonopka

    2012-05-01

    Full Text Available Analysis of the growth-limiting factor or environmental stressors affecting microbes in situ is of fundamental importance but analytically difficult. Microbes can reduce in situ limiting nutrient concentrations to sub-micromolar levels, and contaminated ecosystems may contain multiple stressors. The patterns of gene or protein expression by microbes in nature can be used to infer growth limitations, because they are regulated in response to environmental conditions. Experimental studies under controlled conditions in the laboratory provide the physiological underpinnings for developing these physiological indicators. Although regulatory networks may differ among specific microbes, there are some broad principles that can be applied, related to limiting nutrient acquisition, resource allocation, and stress responses. As technologies for transcriptomics and proteomics mature, the capacity to apply these approaches to complex microbial communities will accelerate. In particular, global proteomics reflect expressed catalytic activities. Furthermore, the high mass accuracy of some proteomic approaches allows mapping back to specific microbial strains. For example, at the Rifle IFRC field site in Western Colorado, the physiological status of Fe(III-reducing populations has been tracked over time. Members of a subsurface clade within the Geobacter predominated during carbon amendment to the subsurface environment. At the functional level, proteomic identifications produced inferences regarding (i temporal changes in anabolism and catabolism of acetate, (ii the onset of N2 fixation when N became limiting, and (iii expression of phosphate transporters during periods of intense growth. The application of these approaches in situ can lead to discovery of novel physiological adaptations.

  1. Decorin is down-regulated in multiple myeloma and MGUS bone marrow plasma and inhibits HGF-induced myeloma plasma cell viability and migration

    DEFF Research Database (Denmark)

    Kristensen, Ida Bruun; Pedersen, Lise Mariager; Rø, Torstein Baade

    2013-01-01

    pathway in multiple myeloma (MM). METHODS: Decorin levels in paired peripheral blood and bone marrow plasma samples from healthy volunteers (HV) (n=23), and patients with monoclonal gammopathy of undetermined significance (MGUS) (n=41) and MM (n=19) were determined by ELISA. Further, the ability...

  2. Multiple uses and regulation: elements for the sustain of the water resource systems; Usos multiplos e regulacao: elementos para a sustentabilidade dos sistemas de recursos hidricos

    Energy Technology Data Exchange (ETDEWEB)

    Salles, Lauriberto S. [Secretaria de Estado de Meio Ambiente, Sao Paulo, SP (Brazil). Dept. de Uso do Solo Metropolitano; Bermann, Celio [Sao Paulo Univ., SP (Brazil). Programa Interunidades de Pos-Graduacao em Energia

    1998-12-31

    National and State water resource management plans demand new patterns of relationships between water users and the society. Regarding water resources sustainability, this work appraises some aspects of the water Committee Basins policies related to multiple water uses, within the frame of the regulatory agencies proposed. (author) 4 refs.

  3. Socioeconomic Status, Subjective Social Status, and Perceived Stress: Associations with Stress Physiology and Executive Functioning.

    Science.gov (United States)

    Ursache, Alexandra; Noble, Kimberly G; Blair, Clancy

    2015-01-01

    Several studies have investigated associations between socioeconomic status (SES) and indicators of children's physiological and cognitive self-regulation. Although objective measures of family SES may be good proxies for families' experiences of disadvantage, less is known about subjective aspects of families' experiences. We hypothesize that subjective social status (SSS) and perceived stress may be important independent predictors of children's stress physiology and executive functioning (EF). Eighty-two children from diverse SES backgrounds were administered EF measures and provided saliva samples for cortisol assay. Caregivers reported on objective SES, SSS, and perceived stress. Results suggest that SES and SSS are both independently and positively related to EF. In models predicting stress physiology, higher perceived stress was associated with lower baseline cortisol. Moreover, SES and age interacted to predict cortisol levels such that among younger children, lower SES was associated with higher cortisol, whereas among older children, lower SES was associated with lower cortisol. Results highlight the importance of considering both objective and subjective indicators of families' SES and stressful experiences in relation to multiple aspects of children's self-regulation.

  4. Avian reproductive physiology

    Science.gov (United States)

    Gee, G.F.; Gibbons, Edward F.; Durrant, Barbara S.; Demarest, Jack

    1995-01-01

    Knowledge of the many physiological factors associated with egg production , fertility, incubation, and brooding in nondomestic birds is limited. Science knows even less about reproduction in most of the 238 endangered or threatened birds. This discussion uses studies of nondomestic and, when necessary, domestic birds to describe physiological control of reproduction. Studies of the few nondomestic avian species show large variation in physiological control of reproduction. Aviculturists, in order to successfully propagate an endangered bird, must understand the bird's reproductive peculiarities. First, investigators can do studies with carefully chosen surrogate species, but eventually they need to confirm the results in the target endangered bird. Studies of reproduction in nondomestic birds increased in the last decade. Still, scientists need to do more comparative studies to understand the mechanisms that control reproduction in birds. New technologies are making it possible to study reproductive physiology of nondomestic species in less limiting ways. These technologies include telemetry to collect information without inducing stress on captives (Howey et al., 1987; Klugman, 1987), new tests for most of the humoral factors associated with reproduction, and the skill to collect small samples and manipulate birds without disrupting the physiological mechanisms (Bercovitz et al., 1985). Managers are using knowledge from these studies to improve propagation in zoological parks, private and public propagation facilities, and research institutions. Researchers need to study the control of ovulation, egg formation, and oviposition in the species of nondomestic birds that lay very few eggs in a season, hold eggs in the oviduct for longer intervals, or differ in other ways from the more thoroughly studied domestic birds. Other techniques that would enhance propagation for nondomestlc birds include tissue culture of cloned embryonic cells, cryopreservation of embryos

  5. SPG7 Variant Escapes Phosphorylation-Regulated Processing by AFG3L2, Elevates Mitochondrial ROS, and Is Associated with Multiple Clinical Phenotypes

    Directory of Open Access Journals (Sweden)

    Naif A.M. Almontashiri

    2014-05-01

    Full Text Available Mitochondrial production of reactive oxygen species (ROS affects many processes in health and disease. SPG7 assembles with AFG3L2 into the mAAA protease at the inner membrane of mitochondria, degrades damaged proteins, and regulates the synthesis of mitochondrial ribosomes. SPG7 is cleaved and activated by AFG3L2 upon assembly. A variant in SPG7 that replaces arginine 688 with glutamine (Q688 is associated with several phenotypes, including toxicity of chemotherapeutic agents, type 2 diabetes mellitus, and (as reported here coronary artery disease. We demonstrate that SPG7 processing is regulated by tyrosine phosphorylation of AFG3L2. Carriers of Q688 bypass this regulation and constitutively process and activate SPG7 mAAA protease. Cells expressing Q688 produce higher ATP levels and ROS, promoting cell proliferation. Our results thus reveal an unexpected link between the phosphorylation-dependent regulation of the mitochondria mAAA protease affecting ROS production and several clinical phenotypes.

  6. Multiple transcription factors directly regulate Hox gene lin-39 expression in ventral hypodermal cells of the C. elegans embryo and larva, including the hypodermal fate regulators LIN-26 and ELT-6.

    Science.gov (United States)

    Liu, Wan-Ju; Reece-Hoyes, John S; Walhout, Albertha J M; Eisenmann, David M

    2014-05-13

    Hox genes encode master regulators of regional fate specification during early metazoan development. Much is known about the initiation and regulation of Hox gene expression in Drosophila and vertebrates, but less is known in the non-arthropod invertebrate model system, C. elegans. The C. elegans Hox gene lin-39 is required for correct fate specification in the midbody region, including the Vulval Precursor Cells (VPCs). To better understand lin-39 regulation and function, we aimed to identify transcription factors necessary for lin-39 expression in the VPCs, and in particular sought factors that initiate lin-39 expression in the embryo. We used the yeast one-hybrid (Y1H) method to screen for factors that bound to 13 fragments from the lin-39 region: twelve fragments contained sequences conserved between C. elegans and two other nematode species, while one fragment was known to drive reporter gene expression in the early embryo in cells that generate the VPCs. Sixteen transcription factors that bind to eight lin-39 genomic fragments were identified in yeast, and we characterized several factors by verifying their physical interactions in vitro, and showing that reduction of their function leads to alterations in lin-39 levels and lin-39::GFP reporter expression in vivo. Three factors, the orphan nuclear hormone receptor NHR-43, the hypodermal fate regulator LIN-26, and the GATA factor ELT-6 positively regulate lin-39 expression in the embryonic precursors to the VPCs. In particular, ELT-6 interacts with an enhancer that drives GFP expression in the early embryo, and the ELT-6 site we identified is necessary for proper embryonic expression. These three factors, along with the factors ZTF-17, BED-3 and TBX-9, also positively regulate lin-39 expression in the larval VPCs. These results significantly expand the number of factors known to directly bind and regulate lin-39 expression, identify the first factors required for lin-39 expression in the embryo, and hint at a

  7. Agreeableness, Extraversion, Stressor and Physiological Stress Response

    OpenAIRE

    Xiaoyuan Chu; Zhentao Ma; Yuan Li; Jing Han

    2015-01-01

    Based on the theoretical analysis, with first-hand data collection and using multiple regression models, this study explored the relationship between agreeableness, extraversion, stressor and stress response and figured out interactive effect of agreeableness, extraversion, and stressor on stress response. We draw on the following conclusions: (1) the interaction term of stressor (work) and agreeableness can negatively predict physiological stress response; (2) the interaction term of stresso...

  8. The Physiology of Adventitious Roots1

    Science.gov (United States)

    Steffens, Bianka; Rasmussen, Amanda

    2016-01-01

    Adventitious roots are plant roots that form from any nonroot tissue and are produced both during normal development (crown roots on cereals and nodal roots on strawberry [Fragaria spp.]) and in response to stress conditions, such as flooding, nutrient deprivation, and wounding. They are important economically (for cuttings and food production), ecologically (environmental stress response), and for human existence (food production). To improve sustainable food production under environmentally extreme conditions, it is important to understand the adventitious root development of crops both in normal and stressed conditions. Therefore, understanding the regulation and physiology of adventitious root formation is critical for breeding programs. Recent work shows that different adventitious root types are regulated differently, and here, we propose clear definitions of these classes. We use three case studies to summarize the physiology of adventitious root development in response to flooding (case study 1), nutrient deficiency (case study 2), and wounding (case study 3). PMID:26697895

  9. Price regulation to remove EE-DSM disincentives and pressure for increased energy sales in monopoly segments of restructured electricity and gas markets: the multiple drivers target (MDT) tariff scheme

    International Nuclear Information System (INIS)

    Pagliano, L.; Alari, P.; Ruggieri, G.; Irrek, W.; Thomas, S.; Leprich, U.

    2002-01-01

    Even in restructured markets a part of the energy business remains a monopoly and should be correctly regulated. We present an analysis which reveals common structures in schemes enacted in UK, Norway, Portugal and recently (on the basis of this study) in Italy. The identified structure, which we named Multiple Driver Target (MDT) regulation is a performance-based regulation scheme, which provides incentives for greater economic efficiency, without creating biases against environmental efficiency. The method relies on a statistical analysis of the correlation of utility costs and a few 'cost drivers' (e.g. number of customers served, grid length, sold or transported energy). We discuss how MDT can be used to set price levels and price changes in the regulatory period in such a way to correctly match the evolution of costs and avoid awarding unwanted signals to utilities. At the opposite, pure Price Cap regulation provides artificial incentives to utilities to increase energy sales (even if this is not economic for the customers nor for society ) beyond the predicted levels foreseen in the price fixing Rate Cases. We show that Under MDT regulation the reduction in profits due to reduced sales as a consequence of DSM is minimised. In so doing this procedure removes the most important disincentive for utilities to implement DSM programmes since lost profits due to reduced sales can be substantially higher than direct costs of DSM programmes; once MDT regulation is in place, also these direct costs can be recovered through a small part of the tariff. We also discuss how MDT can be implemented with a moderate effort by regulatory authorities. (author)

  10. Circadian physiology of metabolism.

    Science.gov (United States)

    Panda, Satchidananda

    2016-11-25

    A majority of mammalian genes exhibit daily fluctuations in expression levels, making circadian expression rhythms the largest known regulatory network in normal physiology. Cell-autonomous circadian clocks interact with daily light-dark and feeding-fasting cycles to generate approximately 24-hour oscillations in the function of thousands of genes. Circadian expression of secreted molecules and signaling components transmits timing information between cells and tissues. Such intra- and intercellular daily rhythms optimize physiology both by managing energy use and by temporally segregating incompatible processes. Experimental animal models and epidemiological data indicate that chronic circadian rhythm disruption increases the risk of metabolic diseases. Conversely, time-restricted feeding, which imposes daily cycles of feeding and fasting without caloric reduction, sustains robust diurnal rhythms and can alleviate metabolic diseases. These findings highlight an integrative role of circadian rhythms in physiology and offer a new perspective for treating chronic diseases in which metabolic disruption is a hallmark. Copyright © 2016, American Association for the Advancement of Science.

  11. Intracellular pH in sperm physiology.

    Science.gov (United States)

    Nishigaki, Takuya; José, Omar; González-Cota, Ana Laura; Romero, Francisco; Treviño, Claudia L; Darszon, Alberto

    2014-08-01

    Intracellular pH (pHi) regulation is essential for cell function. Notably, several unique sperm ion transporters and enzymes whose elimination causes infertility are either pHi dependent or somehow related to pHi regulation. Amongst them are: CatSper, a Ca(2+) channel; Slo3, a K(+) channel; the sperm-specific Na(+)/H(+) exchanger and the soluble adenylyl cyclase. It is thus clear that pHi regulation is of the utmost importance for sperm physiology. This review briefly summarizes the key components involved in pHi regulation, their characteristics and participation in fundamental sperm functions such as motility, maturation and the acrosome reaction. Copyright © 2014 Elsevier Inc. All rights reserved.

  12. Multiple C-terminal tail Ca(2+)/CaMs regulate Ca(V)1.2 function but do not mediate channel dimerization.

    Science.gov (United States)

    Kim, Eun Young; Rumpf, Christine H; Van Petegem, Filip; Arant, Ryan J; Findeisen, Felix; Cooley, Elizabeth S; Isacoff, Ehud Y; Minor, Daniel L

    2010-12-01

    Interactions between voltage-gated calcium channels (Ca(V)s) and calmodulin (CaM) modulate Ca(V) function. In this study, we report the structure of a Ca(2+)/CaM Ca(V)1.2 C-terminal tail complex that contains two PreIQ helices bridged by two Ca(2+)/CaMs and two Ca(2+)/CaM-IQ domain complexes. Sedimentation equilibrium experiments establish that the complex has a 2:1 Ca(2+)/CaM:C-terminal tail stoichiometry and does not form higher order assemblies. Moreover, subunit-counting experiments demonstrate that in live cell membranes Ca(V)1.2s are monomers. Thus, contrary to previous proposals, the crystallographic dimer lacks physiological relevance. Isothermal titration calorimetry and biochemical experiments show that the two Ca(2+)/CaMs in the complex have different properties. Ca(2+)/CaM bound to the PreIQ C-region is labile, whereas Ca(2+)/CaM bound to the IQ domain is not. Furthermore, neither of lobes of apo-CaM interacts strongly with the PreIQ domain. Electrophysiological studies indicate that the PreIQ C-region has a role in calcium-dependent facilitation. Together, the data show that two Ca(2+)/CaMs can bind the Ca(V)1.2 tail simultaneously and indicate a functional role for Ca(2+)/CaM at the C-region site.

  13. Applied physiology of triathlon.

    Science.gov (United States)

    O'Toole, M L; Douglas, P S

    1995-04-01

    The triathlon is a 3-event endurance sport in which athletes compete sequentially in swimming, cycling and running. The primary determinant of success is the ability to sustain a high rate of energy expenditure for prolonged periods of time. Exercise training-induced physiological adaptations in virtually all systems of the body allow the athlete to accomplish this. Aerobic capacity (measured as maximal oxygen uptake, VO2max), economy of motion (submaximal VO2) and fractional utilisation of maximal capacity (%VO2max) reflect the integrated responses of these physiological adaptations. Numerous studies have reported relatively high mean VO2max values for various groups of triathletes that are comparable to those reported for athletes in single-event endurance sports and clearly above those reported for untrained individuals. In shorter distance triathlons and in studies using recreational (rather than elite) triathletes, VO2max is related to performance in the corresponding event of the triathlon (e.g. tethered swimming VO2max with swim time). In longer events and with more elite triathletes, VO2max correlates less well with performance. The physiological adaptations that correspond to and facilitate improved VO2max occur centrally in the cardiovascular system, centred on increased maximal cardiac output, and peripherally in the metabolic systems, centred around increased arterio-venous O2 (a-v O2) difference. While a high VO2max in individuals is clearly of importance to triathlon performance, energy output must be sustained for long periods of time, making economy of motion also very important. Studies suggests that competitive swimmers have better swimming economy than triathletes. However, since many triathletes have previously been competitive swimmers this finding is questionable. The finding suggests that triathletes from nonswimming backgrounds would benefit from improving swimming technique rather than concentrating training workouts solely on distance. In

  14. Suppressor of cytokine signalling (SOCS)-3 protects beta cells against IL-1beta-mediated toxicity through inhibition of multiple nuclear factor-kappaB-regulated proapoptotic pathways

    DEFF Research Database (Denmark)

    Karlsen, Allan Ertman; Heding, P E; Frobøse, H

    2004-01-01

    The proinflammatory cytokine IL-1beta induces apoptosis in pancreatic beta cells via pathways dependent on nuclear factor-kappaB (NF-kappaB), mitogen-activated protein kinase, and protein kinase C. We recently showed suppressor of cytokine signalling (SOCS)-3 to be a natural negative feedback reg...... regulator of IL-1beta- and IFN-gamma-mediated signalling in rat islets and beta cell lines, preventing their deleterious effects. However, the mechanisms underlying SOCS-3 inhibition of IL-1beta signalling and prevention against apoptosis remain unknown....

  15. Altered serotonin physiology in human breast cancers favors paradoxical growth and cell survival.

    Science.gov (United States)

    Pai, Vaibhav P; Marshall, Aaron M; Hernandez, Laura L; Buckley, Arthur R; Horseman, Nelson D

    2009-01-01

    The breast microenvironment can either retard or accelerate the events associated with progression of latent cancers. However, the actions of local physiological mediators in the context of breast cancers are poorly understood. Serotonin (5-HT) is a critical local regulator of epithelial homeostasis in the breast and other organs. Herein, we report complex alterations in the intrinsic mammary gland serotonin system of human breast cancers. Serotonin biosynthetic capacity was analyzed in human breast tumor tissue microarrays using immunohistochemistry for tryptophan hydroxylase 1 (TPH1). Serotonin receptors (5-HT1-7) were analyzed in human breast tumors using the Oncomine database. Serotonin receptor expression, signal transduction, and 5-HT effects on breast cancer cell phenotype were compared in non-transformed and transformed human breast cells. In the context of the normal mammary gland, 5-HT acts as a physiological regulator of lactation and involution, in part by favoring growth arrest and cell death. This tightly regulated 5-HT system is subverted in multiple ways in human breast cancers. Specifically, TPH1 expression undergoes a non-linear change during progression, with increased expression during malignant progression. Correspondingly, the tightly regulated pattern of 5-HT receptors becomes dysregulated in human breast cancer cells, resulting in both ectopic expression of some isoforms and suppression of others. The receptor expression change is accompanied by altered downstream signaling of 5-HT receptors in human breast cancer cells, resulting in resistance to 5-HT-induced apoptosis, and stimulated proliferation. Our data constitutes the first report of direct involvement of 5-HT in human breast cancer. Increased 5-HT biosynthetic capacity accompanied by multiple changes in 5-HT receptor expression and signaling favor malignant progression of human breast cancer cells (for example, stimulated proliferation, inappropriate cell survival). This occurs

  16. The emergence of Applied Physiology within the discipline of Physiology.

    Science.gov (United States)

    Tipton, Charles M

    2016-08-01

    Despite the availability and utilization of the physiology textbooks authored by Albrecht von Haller during the 18th century that heralded the modern age of physiology, not all physicians or physiologists were satisfied with its presentation, contents, or application to medicine. Initial reasons were fundamental disagreements between the "mechanists," represented by Boerhaave, Robinson, and von Haller, and the "vitalists," represented by the faculty and graduates of the Montpellier School of Medicine in France, notably, Bordeu and Barthez. Subsequently, objections originated from Europe, United Kingdom, and the United States in publications that focused not only on the teaching of physiology to medical and secondary students, but on the specific applications of the content of physiology to medicine, health, hygiene, pathology, and chronic diseases. At the turn of the 20th century, texts began to appear with applied physiology in their titles and in 1926, physician Samson Wright published a textbook entitled Applied Physiology that was intended for both medical students and the medical profession. Eleven years later, physicians Best and Taylor published The Physiological Basis of Medical Practice: A University of Toronto Texbook in Applied Physiology Although both sets of authors defined the connection between applied physiology and physiology, they failed to define the areas of physiology that were included within applied physiology. This was accomplished by the American Physiological Society (APS) Publications Committee in 1948 with the publication of the Journal of Appplied Physiology, that stated the word "applied" would broadly denote human physiology whereas the terms stress and environment would broadly include work, exercise, plus industrial, climatic and social factors. NIH established a study section (SS) devoted to applied physiology in 1964 which remained active until 2001 when it became amalgamated into other SSs. Before the end of the 20th century when

  17. Targeted genome regulation via synthetic programmable transcriptional regulators

    KAUST Repository

    Piatek, Agnieszka Anna

    2016-04-19

    Regulation of gene transcription controls cellular functions and coordinates responses to developmental, physiological and environmental cues. Precise and efficient molecular tools are needed to characterize the functions of single and multiple genes in linear and interacting pathways in a native context. Modular DNA-binding domains from zinc fingers (ZFs) and transcriptional activator-like proteins (TALE) are amenable to bioengineering to bind DNA target sequences of interest. As a result, ZF and TALE proteins were used to develop synthetic programmable transcription factors. However, these systems are limited by the requirement to re-engineer proteins for each new target sequence. The clustered regularly interspaced palindromic repeats (CRISPR)/CRISPR associated 9 (Cas9) genome editing tool was recently repurposed for targeted transcriptional regulation by inactivation of the nuclease activity of Cas9. Due to the facile engineering, simplicity, precision and amenability to library construction, the CRISPR/Cas9 system is poised to revolutionize the functional genomics field across diverse eukaryotic species. In this review, we discuss the development of synthetic customizable transcriptional regulators and provide insights into their current and potential applications, with special emphasis on plant systems, in characterization of gene functions, elucidation of molecular mechanisms and their biotechnological applications. © 2016 Informa UK Limited, trading as Taylor & Francis Group

  18. Physiology of woody plants

    CERN Document Server

    Hazewinkel, Michiel; Pallardy, Stephen G

    1996-01-01

    This completely revised classic volume is an up-to-date synthesis of the intensive research devoted to woody plants. Intended primarily as a text for students and a reference for researchers, this interdisciplinary book should be useful to a broad range of scientists from agroforesters, agronomists, and arborists to plant pathologists, ecophysiologists, and soil scientists. Anyone interested in plant physiology will find this text invaluable. Key Features * Includes supplementary chapter summaries and lists of general references * Provides a solid foundation of reference information * Thoroughly updated classic text/reference.

  19. Cross-cultural generality and specificity in self-regulation: avoidance personal goals and multiple aspects of well-being in the United States and Japan.

    Science.gov (United States)

    Elliot, Andrew J; Sedikides, Constantine; Murayama, Kou; Tanaka, Ayumi; Thrash, Todd M; Mapes, Rachel R

    2012-10-01

    The authors examined avoidance personal goals as concurrent (Study 1) and longitudinal (Study 2) predictors of multiple aspects of well-being in the United States and Japan. In both studies, participants adopted more avoidance personal goals in Japan relative to the United States. Both studies also demonstrated that avoidance personal goals were significant negative predictors of the most relevant aspects of well-being in each culture. Specifically, avoidance personal goals were negative predictors of intrapersonal and eudaimonic well-being in the United States and were negative predictors of interpersonal and eudaimonic well-being in Japan. The findings clarify and extend puzzling findings from prior empirical work in this area, and raise provocative possibilities about the nature of avoidance goal pursuit.

  20. Multiple layers of temporal and spatial control regulate accumulation of the fruiting body-specific protein APP in Sordaria macrospora and Neurospora crassa.

    Science.gov (United States)

    Nowrousian, Minou; Piotrowski, Markus; Kück, Ulrich

    2007-07-01

    During fungal fruiting body development, specialized cell types differentiate from vegetative mycelium. We have isolated a protein from the ascomycete Sordaria macrospora that is not present during vegetative growth but accumulates in perithecia. The protein was sequenced by mass spectrometry and the corresponding gene was termed app (abundant perithecial protein). app transcript occurs only after the onset of sexual development; however, the formation of ascospores is not a prerequisite for APP accumulation. The transcript of the Neurospora crassa ortholog is present prior to fertilization, but the protein accumulates only after fertilization. In crosses of N. crassa Deltaapp strains with the wild type, APP accumulates when the wild type serves as female parent, but not in the reciprocal cross; thus, the presence of a functional female app allele is necessary and sufficient for APP accumulation. These findings highlight multiple layers of temporal and spatial control of gene expression during fungal development.

  1. Multiple Perspectives / Multiple Readings

    Directory of Open Access Journals (Sweden)

    Simon Biggs

    2005-01-01

    Full Text Available People experience things from their own physical point of view. What they see is usually a function of where they are and what physical attitude they adopt relative to the subject. With augmented vision (periscopes, mirrors, remote cameras, etc we are able to see things from places where we are not present. With time-shifting technologies, such as the video recorder, we can also see things from the past; a time and a place we may never have visited.In recent artistic work I have been exploring the implications of digital technology, interactivity and internet connectivity that allow people to not so much space/time-shift their visual experience of things but rather see what happens when everybody is simultaneously able to see what everybody else can see. This is extrapolated through the remote networking of sites that are actual installation spaces; where the physical movements of viewers in the space generate multiple perspectives, linked to other similar sites at remote locations or to other viewers entering the shared data-space through a web based version of the work.This text explores the processes involved in such a practice and reflects on related questions regarding the non-singularity of being and the sense of self as linked to time and place.

  2. Multiple cis-acting elements involved in up-regulation of a cytochrome P450 gene conferring resistance to deltamethrin in smal brown planthopper, Laodelphax striatellus (Fallén).

    Science.gov (United States)

    Pu, Jian; Sun, Haina; Wang, Jinda; Wu, Min; Wang, Kangxu; Denholm, Ian; Han, Zhaojun

    2016-11-01

    As well as arising from single point mutations in binding sites or detoxifying enzymes, it is likely that insecticide resistance mechanisms are frequently controlled by multiple genetic factors, resulting in resistance being inherited as a quantitative trait. However, empirical evidence for this is still rare. Here we analyse the causes of up-regulation of CYP6FU1, a monoxygenase implicated in resistance to deltamethrin in the rice pest Laodelphax striatellus. The 5'-flanking region of this gene was cloned and sequenced from individuals of a susceptible and a resistant strain. A luminescent reporter assay was used to evaluate different 5'-flanking regions and their fragments for promoter activity. Mutations enhancing promoter activity in various fragments were characterized, singly and in combination, by site mutation recovery. Nucleotide diversity in flanking sequences was greatly reduced in deltamethrin-resistant insects compared to susceptible ones. Phylogenetic sequence analysis found that CYP6FU1 had five different types of 5'-flanking region. All five types were present in a susceptible strain but only a single type showing the highest promoter activity was present in a resistant strain. Four cis-acting elements were identified whose influence on up-regulation was much more pronounced in combination than when present singly. Of these, two were new transcription factor (TF) binding sites produced by mutations, another one was also a new TF binding site alternated from an existing one, and the fourth was a unique transcription start site. These results demonstrate that multiple cis-acting elements are involved in up-regulating CYP6FU1 to generate a resistance phenotype. Copyright © 2016 Elsevier Ltd. All rights reserved.

  3. Physiological Actions of Fibroblast Growth Factor-23

    Directory of Open Access Journals (Sweden)

    Reinhold G. Erben

    2018-05-01

    Full Text Available Fibroblast growth factor-23 (FGF23 is a bone-derived hormone suppressing phosphate reabsorption and vitamin D hormone synthesis in the kidney. At physiological concentrations of the hormone, the endocrine actions of FGF23 in the kidney are αKlotho-dependent, because high-affinity binding of FGF23 to FGF receptors requires the presence of the co-receptor αKlotho on target cells. It is well established that excessive concentrations of intact FGF23 in the blood lead to phosphate wasting in patients with normal kidney function. Based on the importance of diseases associated with gain of FGF23 function such as phosphate-wasting diseases and chronic kidney disease, a large body of literature has focused on the pathophysiological consequences of FGF23 excess. Less emphasis has been put on the role of FGF23 in normal physiology. Nevertheless, during recent years, lessons we have learned from loss-of-function models have shown that besides the paramount physiological roles of FGF23 in the control of 1α-hydroxylase expression and of apical membrane expression of sodium-phosphate co-transporters in proximal renal tubules, FGF23 also is an important stimulator of calcium and sodium reabsorption in distal renal tubules. In addition, there is an emerging role of FGF23 as an auto-/paracrine regulator of alkaline phosphatase expression and mineralization in bone. In contrast to the renal actions of FGF23, the FGF23-mediated suppression of alkaline phosphatase in bone is αKlotho-independent. Moreover, FGF23 may be a physiological suppressor of differentiation of hematopoietic stem cells into the erythroid lineage in the bone microenvironment. At present, there is little evidence for a physiological role of FGF23 in organs other than kidney and bone. The purpose of this mini-review is to highlight the current knowledge about the complex physiological functions of FGF23.

  4. Interleukin-34 Regulates Th1 and Th17 Cytokine Production by Activating Multiple Signaling Pathways through CSF-1R in Chicken Cell Lines

    Directory of Open Access Journals (Sweden)

    Anh Duc Truong

    2018-06-01

    Full Text Available Interleukin-34 (IL-34 is a newly recognized cytokine with functions similar to macrophage colony-stimulating factor 1. It is expressed in macrophages and fibroblasts, where it induces cytokine production; however, the mechanism of chicken IL-34 (chIL-34 signaling has not been identified to date. The aim of this study was to analyze the signal transduction pathways and specific biological functions associated with chIL-34 in chicken macrophage (HD11 and fibroblast (OU2 cell lines. We found that IL-34 is a functional ligand for the colony-stimulating factor receptor (CSF-1R in chicken cell lines. Treatment with chIL-34 increased the expression of Th1 and Th17 cytokines through phosphorylation of tyrosine and serine residues in Janus kinase (JAK 2, tyrosine kinase 2 (TYK2, signal transducer and activator of transcription (STAT 1, STAT3, and Src homology 2-containing tyrosine phosphatase 2 (SHP-2, which also led to phosphorylation of NF-κB1, p-mitogen-activated protein kinase kinase kinase 7 (TAK1, MyD88, suppressor of cytokine signaling 1 (SOCS1, and extracellular signal-regulated kinase 1 and 2 (ERK1/2. Taken together, these results suggest that chIL-34 functions by binding to CSF-1R and activating the JAK/STAT, nuclear factor κ B (NF-κB, and mitogen-activated protein kinase signaling pathways; these signaling events regulate cytokine expression and suggest roles for chIL-34 in innate and adaptive immunity.

  5. Multiple Copies of a Simple MYB-Binding Site Confers Trans-regulation by Specific Flavonoid-Related R2R3 MYBs in Diverse Species

    Directory of Open Access Journals (Sweden)

    Cyril Brendolise

    2017-10-01

    Full Text Available In apple, the MYB transcription factor MYB10 controls the accumulation of anthocyanins. MYB10 is able to auto-activate its expression by binding its own promoter at a specific motif, the R1 motif. In some apple accessions a natural mutation, termed R6, has more copies of this motif within the MYB10 promoter resulting in stronger auto-activation and elevated anthocyanins. Here we show that other anthocyanin-related MYBs selected from apple, pear, strawberry, petunia, kiwifruit and Arabidopsis are able to activate promoters containing the R6 motif. To examine the specificity of this motif, members of the R2R3 MYB family were screened against a promoter harboring the R6 mutation. Only MYBs from subgroups 5 and 6 activate expression by binding the R6 motif, with these MYBs sharing conserved residues in their R2R3 DNA binding domains. Insertion of the apple R6 motif into orthologous promoters of MYB10 in pear (PcMYB10 and Arabidopsis (AtMY75 elevated anthocyanin levels. Introduction of the R6 motif into the promoter region of an anthocyanin biosynthetic enzyme F3′5′H of kiwifruit imparts regulation by MYB10. This results in elevated levels of delphinidin in both tobacco and kiwifruit. Finally, an R6 motif inserted into the promoter the vitamin C biosynthesis gene GDP-L-Gal phosphorylase increases vitamin C content in a MYB10-dependent manner. This motif therefore provides a tool to re-engineer novel MYB-regulated responses in plants.

  6. Krogh’s principle or a multiple fish model approach to phosphate balance: is there a centrally regulated intestinal-skeletal-renal axis?

    Directory of Open Access Journals (Sweden)

    Pedro Miguel Guerreiro

    2015-10-01

    Full Text Available Inorganic phosphate (Pi is a crucial ion for vertebrate life. In addition to many physiological roles it is, together with calcium, the major element forming the internal skeleton and Pi balance has been considered a secondary consequence of calciotropic endocrine factors. However, contrary to calcium which can be readily obtained from even Ca-poor environments, Pi is not available in water, and fish can only obtain it via the food. Intestinal absorption drives Pi into the blood stream, but a central part of Pi balance is renal excretion and conservation. Recently, several Pi specific regulatory factors have been brought to light, and we use fish models to investigate their role and the hypothesis of a centrally controlled intestinal-skeletal-renal Pi axis. Using tissues mounted in Ussing chambers under symmetrical and asymmetrical short-circuited conditions we measure unidirectional 33Pi fluxes and test PTHrP, but also STC and FGF23 as regulatory factors, as well as specific drugs to unveil the functional transporting mechanisms. Pi absorption is modified in starved and fed sea bass, an effect dependent on Pi availability in diet, which modifies gene expression of uptake mechanisms. Phosphate secretion across flounder primary renal cell cultures is increased by PTHrP, which reduces the expression of reabsorption mechanisms such as NaPiII and evokes an increase in GFR in cannulated fish, thus resulting in net Pi excretion. A similar effect occurs in the toadfish urinary bladder, which displays moderate Pi transport that is abolished by the drug ouabain and modified by endocrines. Finally we used the shark choroid plexus (CP to show active CSF-to-blood transport with biochemical properties consistent with PiT Na+-dependent transporters. RT-PCR revealed the PiT1/2, but no NaPiII gene expression and we localized PiT2 in CP apical membranes while PiT1 occurred in vascular endothelial cells. Shark CP expresses both PTHrP and its receptor. Could

  7. Fusing Multiple Sensor Modalities for Complex Physiological State Monitoring

    Science.gov (United States)

    2012-12-01

    STDLAT has been correlated to the Karolinska Sleepiness Scale (KSS), with a chi-squared value of 11 (p < 0.001) (17). For this study, we look at the...width at half maximum GAZEDIS gaze distribution HRED Human Research and Engineering Directorate KSS Karolinska Sleepiness Scale NTSB National

  8. Starting physiology: bioelectrogenesis.

    Science.gov (United States)

    Baptista, Vander

    2015-12-01

    From a Cartesian perspective of rational analysis, the electric potential difference across the cell membrane is one of the fundamental concepts for the study of physiology. Unfortunately, undergraduate students often struggle to understand the genesis of this energy gradient, which makes the teaching activity a hard task for the instructor. The topic of bioelectrogenesis encompasses multidisciplinary concepts, involves several mechanisms, and is a dynamic process, i.e., it never turns off during the lifetime of the cell. Therefore, to improve the transmission and acquisition of knowledge in this field, I present an alternative didactic model. The design of the model assumes that it is possible to build, in a series of sequential steps, an assembly of proteins within the membrane of an isolated cell in a simulated electrophysiology experiment. Initially, no proteins are inserted in the membrane and the cell is at a baseline energy state; the extracellular and intracellular fluids are at thermodynamic equilibrium. Students are guided through a sequence of four steps that add key membrane transport proteins to the model cell. The model is simple at the start and becomes progressively more complex, finally producing transmembrane chemical and electrical gradients. I believe that this didactic approach helps instructors with a more efficient tool for the teaching of the mechanisms of resting membrane potential while helping students avoid common difficulties that may be encountered when learning this topic. Copyright © 2015 The American Physiological Society.

  9. Ozone Damages to Mediterranean Crops: Physiological Responses

    Directory of Open Access Journals (Sweden)

    Albino Maggio

    2008-03-01

    Full Text Available In this brief review we analyzed some aspects of tropospheric ozone damages to crop plants. Specifically, we addressed this issue to Mediterranean environments, where plant response to multiple stresses may either exacerbate or counteract deleterious ozone effects. After discussing the adequacy of current models to predict ozone damages to Mediterranean crops, we present a few examples of physiological responses to drought and salinity stress that generally overlap with seasonal ozone peaks in Southern Italy. The co-existence of multiple stresses is then analyzed in terms of stomatal vs. non-stomatal control of ozone damages. Recent results on osmoprotectant feeding experiments, as a non-invasive strategy to uncouple stomatal vs. non stomatal contribution to ozone protection, are also presented. In the final section, we discuss critical needs in ozone research and the great potential of plant model systems to unravel multiple stress responses in agricultural crops.

  10. Ozone Damages to Mediterranean Crops: Physiological Responses

    Directory of Open Access Journals (Sweden)

    Massimo Fagnano

    2011-02-01

    Full Text Available In this brief review we analyzed some aspects of tropospheric ozone damages to crop plants. Specifically, we addressed this issue to Mediterranean environments, where plant response to multiple stresses may either exacerbate or counteract deleterious ozone effects. After discussing the adequacy of current models to predict ozone damages to Mediterranean crops, we present a few examples of physiological responses to drought and salinity stress that generally overlap with seasonal ozone peaks in Southern Italy. The co-existence of multiple stresses is then analyzed in terms of stomatal vs. non-stomatal control of ozone damages. Recent results on osmoprotectant feeding experiments, as a non-invasive strategy to uncouple stomatal vs. non stomatal contribution to ozone protection, are also presented. In the final section, we discuss critical needs in ozone research and the great potential of plant model systems to unravel multiple stress responses in agricultural crops.

  11. Teaching physics in a physiologically meaningful manner

    Directory of Open Access Journals (Sweden)

    Michael Plomer

    2010-09-01

    Full Text Available The learning outcome of a physics laboratory course for medical students was examined in an interdisciplinary field study and discussed for the electrical physiology (“Propagation of Excitation and Nerve Cells”. At the Ludwig-Maximilians-University of Munich (LMU at a time about 300 medicine students were assessed in two successive years. Students from the control group worked with standard experiments, while students from the treatment group performed newly developed “addressee-specific” experiments, designed to guide students to transfer physics knowledge to physiological problems. The assessment took place within the laboratory course on physiology, after the students had finished their laboratory classes in physics, and consisted of the construction of a concept map with additional multiple choice questions. The results showed that standard physics experiments are not adequate for teaching students to transfer physical principles to physiology. Introducing new addressee-specific experiments enriched the physics laboratory course by improving student attitudes toward physics and demonstrating better ability of students to relate concepts of physics and medicine, and overall to improve their understanding of the physics taught in the course.

  12. Eliminating animal facility light-at-night contamination and its effect on circadian regulation of rodent physiology, tumor growth, and metabolism: a challenge in the relocation of a cancer research laboratory.

    Science.gov (United States)

    Dauchy, Robert T; Dupepe, Lynell M; Ooms, Tara G; Dauchy, Erin M; Hill, Cody R; Mao, Lulu; Belancio, Victoria P; Slakey, Lauren M; Hill, Steven M; Blask, David E

    2011-05-01

    Appropriate laboratory animal facility lighting and lighting protocols are essential for maintaining the health and wellbeing of laboratory animals and ensuring the credible outcome of scientific investigations. Our recent experience in relocating to a new laboratory facility illustrates the importance of these considerations. Previous studies in our laboratory demonstrated that animal room contamination with light-at-night (LAN) of as little as 0.2 lx at rodent eye level during an otherwise normal dark-phase disrupted host circadian rhythms and stimulated the metabolism and proliferation of human cancer xenografts in rats. Here we examined how simple improvements in facility design at our new location completely eliminated dark-phase LAN contamination and restored normal circadian rhythms in nontumor-bearing rats and normal tumor metabolism and growth in host rats bearing tissue-isolated MCF7(SR(-)) human breast tumor xenografts or 7288CTC rodent hepatomas. Reducing LAN contamination in the animal quarters from 24.5 ± 2.5 lx to nondetectable levels (complete darkness) restored normal circadian regulation of rodent arterial blood melatonin, glucose, total fatty and linoleic acid concentrations, tumor uptake of O(2), glucose, total fatty acid and CO(2) production and tumor levels of cAMP, triglycerides, free fatty acids, phospholipids, and cholesterol esters, as well as extracellular-signal-regulated kinase, mitogen-activated protein kinase, serine-threonine protein kinase, glycogen synthase kinase 3β, γ-histone 2AX, and proliferating cell nuclear antigen.

  13. [Anatomy and physiology of sexuality].

    Science.gov (United States)

    Cour, F; Droupy, S; Faix, A; Methorst, C; Giuliano, F

    2013-07-01

    Knowledge of the physiology of male and female sexuality has advanced considerably. Initially there is always desire with its biological neuroendocrine components and its emotional field which is particularly marked in women. There is a distinction between "spontaneous" sexual desire related to intrinsic affective, cognitive stimuli, and fantasies, and "reactive" sexual desire in response to physical arousal. There are similarities between men and women concerning the activation of cerebral zones in sexual arousal contexts in laboratory conditions. The neural pathways for sexual arousal are similar between men and women, bringing into play the sympathetic centres of the thoracic and lumbar spinal cord and, at the sacral level, the parasympathetic center and the motoneurons controlling the muscular contractions of the pelviperineal striated muscles. Genital sensitivity is mainly transmitted by the pudendal nerve in both men and women. Sexual arousal in men consists of penile erection, and ejaculation accompanied with orgasm. In women, sexual arousal causes increase in blood to flow to the vagina leading to lubrication and to the vulva leading to the erection of the clitoris and vulvar hyperaemia. The orgasm which can be multiple in women is accompanied by contractions of the striated perineal muscles. Several neurotransmitters are closely involved in the control of sexuality at the central level: dopamine, ocytocin, serotonin, and peripheral: nitric oxide and noradrenaline in men, vasoactive intestinal peptide and neuropeptide Y in women. Copyright © 2012. Published by Elsevier Masson SAS.

  14. Soluble Receptor for Advanced Glycation End Products (sRAGE is Up-Regulated in Multiple Sclerosis Patients Treated with Interferon β-1a

    Directory of Open Access Journals (Sweden)

    Mahnoosh Rahimi

    2018-03-01

    Full Text Available Background/Aims: Multiple sclerosis (MS is a chronic inflammatory disorder of the central nervous system. Considering the role of immune system in its pathogenesis, researchers have focused on evaluation of the expression of immune-related genes or proteins in MS patients. Among proteins whose participation in inflammatory process has been documented is the receptor for advanced glycation end products (RAGE. Methods: In the present study, we compared RAGE transcript levels by means of quantitative real-time PCR as well as the serum level of soluble RAGE (sRAGE by means of enzyme- linked immunosorbent assay (ELISA in 50 IFNβ-1a responsive relapsing-remitting MS patients when compared with age and sex-matched healthy subjects. Results: Elevated expression of RAGE as well as higher levels of sRAGE were detected in IFN-β responsive MS patients compared with the controls. A significant inverse correlation between sRAGE plasma concentrations and the expanded disability status scale (EDSS was also detected in which each unit of increase in sRAGE level resulted in a 0.308 unit decrease in EDSS. Conclusion: Considering the stable clinical state of the MS patients in this study and their response to IFNβ-1a, the elevated levels of sRAGE in patients compared with healthy subjects could be related to the effects of this kind of treatment.

  15. Enzyme-regulated the changes of pH values for assembling a colorimetric and multistage interconnection logic network with multiple readouts.

    Science.gov (United States)

    Huang, Yanyan; Ran, Xiang; Lin, Youhui; Ren, Jinsong; Qu, Xiaogang

    2015-04-22

    Based on enzymatic reactions-triggered changes of pH values and biocomputing, a novel and multistage interconnection biological network with multiple easy-detectable signal outputs has been developed. Compared with traditional chemical computing, the enzyme-based biological system could overcome the interference between reactions or the incompatibility of individual computing gates and offer a unique opportunity to assemble multicomponent/multifunctional logic circuitries. Our system included four enzyme inputs: β-galactosidase (β-gal), glucose oxidase (GOx), esterase (Est) and urease (Ur). With the assistance of two signal transducers (gold nanoparticles and acid-base indicators) or pH meter, the outputs of the biological network could be conveniently read by the naked eyes. In contrast to current methods, the approach present here could realize cost-effective, label-free and colorimetric logic operations without complicated instrument. By designing a series of Boolean logic operations, we could logically make judgment of the compositions of the samples on the basis of visual output signals. Our work offered a promising paradigm for future biological computing technology and might be highly useful in future intelligent diagnostics, prodrug activation, smart drug delivery, process control, and electronic applications. Copyright © 2015 Elsevier B.V. All rights reserved.

  16. DP IV/CD26, APN/CD13 and related enzymes as regulators of T cell immunity: implications for experimental encephalomyelitis and multiple sclerosis.

    Science.gov (United States)

    Reinhold, Dirk; Bank, Ute; Täger, Michael; Ansorge, Siegfried; Wrenger, Sabine; Thielitz, Anja; Lendeckel, Uwe; Faust, Jürgen; Neubert, Klaus; Brocke, Stefan

    2008-01-01

    Multiple sclerosis (MS) is the most frequent demyelinating disease of the central nervous system. Peptidases like dipeptidyl peptidase IV (DP IV, CD26) and aminopeptidase N (APN, CD13) play a regulatory role in T cell activation and represent potential targets for the treatment of inflammatory disorders. Synthetic inhibitors of DP IV and/or APN enzymatic activity induce production of the immunosuppressive cytokine TGF-beta1 and subsequently suppress DNA synthesis and Th1 cytokine production of activated human T cells. Compelling evidence has demonstrated that IL-17-producing CD4 cells (Th17) are a major contributor to the pathogenesis of autoimmune inflammation. Here, we report that inhibitors of DP IV-like activity as well as of APN activity inhibit IL-17 production in activated human and mouse T cells. Combining inhibitors of DP IV and APN increases the suppressive effect on T cell specific IL-17 production in vitro compared to a single peptidase inhibitor. In the following, we summarize the evidence for the role of both ectoenzymes in T cell activation in vitro and in vivo and provide a rationale for the use of combined or dual ectopeptidase inhibitors to treat autoimmune diseases like MS.

  17. Robust Selection Algorithm (RSA) for Multi-Omic Biomarker Discovery; Integration with Functional Network Analysis to Identify miRNA Regulated Pathways in Multiple Cancers.

    Science.gov (United States)

    Sehgal, Vasudha; Seviour, Elena G; Moss, Tyler J; Mills, Gordon B; Azencott, Robert; Ram, Prahlad T

    2015-01-01

    MicroRNAs (miRNAs) play a crucial role in the maintenance of cellular homeostasis by regulating the expression of their target genes. As such, the dysregulation of miRNA expression has been frequently linked to cancer. With rapidly accumulating molecular data linked to patient outcome, the need for identification of robust multi-omic molecular markers is critical in order to provide clinical impact. While previous bioinformatic tools have been developed to identify potential biomarkers in cancer, these methods do not allow for rapid classification of oncogenes versus tumor suppressors taking into account robust differential expression, cutoffs, p-values and non-normality of the data. Here, we propose a methodology, Robust Selection Algorithm (RSA) that addresses these important problems in big data omics analysis. The robustness of the survival analysis is ensured by identification of optimal cutoff values of omics expression, strengthened by p-value computed through intensive random resampling taking into account any non-normality in the data and integration into multi-omic functional networks. Here we have analyzed pan-cancer miRNA patient data to identify functional pathways involved in cancer progression that are associated with selected miRNA identified by RSA. Our approach demonstrates the way in which existing survival analysis techniques can be integrated with a functional network analysis framework to efficiently identify promising biomarkers and novel therapeutic candidates across diseases.

  18. Multiple Roles for UV RESISTANCE LOCUS8 in Regulating Gene Expression and Metabolite Accumulation in Arabidopsis under Solar Ultraviolet Radiation1[W][OA

    Science.gov (United States)

    Morales, Luis O.; Brosché, Mikael; Vainonen, Julia; Jenkins, Gareth I.; Wargent, Jason J.; Sipari, Nina; Strid, Åke; Lindfors, Anders V.; Tegelberg, Riitta; Aphalo, Pedro J.

    2013-01-01

    Photomorphogenic responses triggered by low fluence rates of ultraviolet B radiation (UV-B; 280–315 nm) are mediated by the UV-B photoreceptor UV RESISTANCE LOCUS8 (UVR8). Beyond our understanding of the molecular mechanisms of UV-B perception by UVR8, there is still limited information on how the UVR8 pathway functions under natural sunlight. Here, wild-type Arabidopsis (Arabidopsis thaliana) and the uvr8-2 mutant were used in an experiment outdoors where UV-A (315–400 nm) and UV-B irradiances were attenuated using plastic films. Gene expression, PYRIDOXINE BIOSYNTHESIS1 (PDX1) accumulation, and leaf metabolite signatures were analyzed. The results show that UVR8 is required for transcript accumulation of genes involved in UV protection, oxidative stress, hormone signal transduction, and defense against herbivores under solar UV. Under natural UV-A irradiance, UVR8 is likely to interact with UV-A/blue light signaling pathways to moderate UV-B-driven transcript and PDX1 accumulation. UVR8 both positively and negatively affects UV-A-regulated gene expression and metabolite accumulation but is required for the UV-B induction of phenolics. Moreover, UVR8-dependent UV-B acclimation during the early stages of plant development may enhance normal growth under long-term exposure to solar UV. PMID:23250626

  19. The MAPKK FgMkk1 of Fusarium graminearum regulates vegetative differentiation, multiple stress response, and virulence via the cell wall integrity and high-osmolarity glycerol signaling pathways.

    Science.gov (United States)

    Yun, Yingzi; Liu, Zunyong; Zhang, Jingze; Shim, Won-Bo; Chen, Yun; Ma, Zhonghua

    2014-07-01

    Mitogen-activated protein (MAP) kinases play crucial roles in regulating fungal development, growth and pathogenicity, and in responses to the environment. In this study, we characterized a MAP kinase kinase FgMkk1 in Fusarium graminearum, the causal agent of wheat head blight. Phenotypic analyses of the FgMKK1 mutant (ΔFgMKK1) showed that FgMkk1 is involved in the regulation of hyphal growth, pigmentation, conidiation, deoxynivalenol biosynthesis and virulence of F. graminearum. ΔFgMKK1 also showed increased sensitivity to cell wall-damaging agents, and to osmotic and oxidative stresses, but exhibited decreased sensitivity to the fungicides iprodione and fludioxonil. In addition, the mutant revealed increased sensitivity to a biocontrol agent, Trichoderma atroviride. Western blot assays revealed that FgMkk1 positively regulates phosphorylation of the MAP kinases Mgv1 and FgOs-2, the key component in the cell wall integrity (CWI) and high-osmolarity glycerol (HOG) signalling pathway respectively. Yeast two-hybrid assay indicated that Mgv1 interacts with a transcription factor FgRlm1. The FgRLM1 mutant (ΔFgRLM1) showed increased sensitivity to cell wall-damaging agents and exhibited decreased virulence. Taken together, our data indicated that FgMkk1 is an upstream component of Mgv1, and regulates vegetative differentiation, multiple stress response and virulence via the CWI and HOG signalling pathways. FgRlm1 may be a downstream component of Mgv1 in the CWI pathway in F. graminearum. © 2013 Society for Applied Microbiology and John Wiley & Sons Ltd.

  20. Interorgan Communication Pathways in Physiology: Focus on Drosophila

    OpenAIRE

    Droujinine, Ilia A.; Perrimon, Norbert

    2016-01-01

    Studies in mammals and Drosophila have demonstrated the existence and significance of secreted factors involved in communication between distal organs. In this review, primarily focusing on Drosophila, we examine the known interorgan communication factors and their functions, physiological inducers, and integration in regulating physiology. Moreover, we describe how organ-sensing screens in Drosophila can systematically identify novel conserved interorgan communication factors. Finally, we di...

  1. miR-320a regulates cell proliferation and apoptosis in multiple myeloma by targeting pre-B-cell leukemia transcription factor 3

    Energy Technology Data Exchange (ETDEWEB)

    Lu, Yinghao [Jiangsu Institute of Hematology, First Affiliated Hospital of Soochow University, Key Laboratory of Thrombosis and Hemostasis Under Ministry of Health, Collaborative Innovation Center of Hematology, Suzhou, 215006 (China); Department of Hematology, Affiliated Hospital of Guizhou Medical University, The Hematopoietic Stem Cell Transplant Center of Guizhou Province, Blood Diseases Diagnosis and Treatment Center of Guizhou Province, Guiyang, 550004, Guizhou Province (China); Wu, Depei, E-mail: wudepei@medmail.com.cn [Jiangsu Institute of Hematology, First Affiliated Hospital of Soochow University, Key Laboratory of Thrombosis and Hemostasis Under Ministry of Health, Collaborative Innovation Center of Hematology, Suzhou, 215006 (China); Wang, Jishi, E-mail: lgylhlyh@aliyun.com [Department of Hematology, Affiliated Hospital of Guizhou Medical University, The Hematopoietic Stem Cell Transplant Center of Guizhou Province, Blood Diseases Diagnosis and Treatment Center of Guizhou Province, Guiyang, 550004, Guizhou Province (China); Li, Yan; Chai, Xiao; Kang, Qian [Department of Hematology, Affiliated Hospital of Guizhou Medical University, The Hematopoietic Stem Cell Transplant Center of Guizhou Province, Blood Diseases Diagnosis and Treatment Center of Guizhou Province, Guiyang, 550004, Guizhou Province (China)

    2016-05-13

    Aberrant expression of microRNAs (miRNAs) is implicated in cancer development and progression. While miR-320a is reported to be deregulated in many malignancy types, its biological role in multiple myeloma (MM) remains unclear. Here, we observed reduced expression of miR-320a in MM samples and cell lines. Ectopic expression of miR-320a dramatically suppressed cell viability and clonogenicity and induced apoptosis in vitro. Mechanistic investigation led to the identification of Pre-B-cellleukemia transcription factor 3 (PBX3) as a novel and direct downstream target of miR-320a. Interestingly, reintroduction of PBX3 abrogated miR-320a-induced MM cell growth inhibition and apoptosis. In a mouse xenograft model, miR-320a overexpression inhibited tumorigenicity and promoted apoptosis. Our findings collectively indicate that miR-320a inhibits cell proliferation and induces apoptosis in MM cells by directly targeting PBX3, supporting its utility as a novel and potential therapeutic agent for miRNA-based MM therapy. -- Highlights: •Expression of miR-320a in MM cell induces apoptosis in vitro. •miR-320a represses PBX3 via targeting specific sequences in the 3′UTR region. •Exogenous expression of PBX3 reverses the effects of miR-320a in inhibiting MM cell growth and promoting apoptosis. •Overexpression of miR-320a inhibits tumor growth and increases apoptosis in vivo.

  2. Perichondrium phenotype and border function are regulated by Ext1 and heparan sulfate in developing long bones: a mechanism likely deranged in Hereditary Multiple Exostoses.

    Science.gov (United States)

    Huegel, Julianne; Mundy, Christina; Sgariglia, Federica; Nygren, Patrik; Billings, Paul C; Yamaguchi, Yu; Koyama, Eiki; Pacifici, Maurizio

    2013-05-01

    During limb skeletogenesis the cartilaginous long bone anlagen and their growth plates become delimited by perichondrium with which they interact functionally. Yet, little is known about how, despite being so intimately associated with cartilage, perichondrium acquires and maintains its distinct phenotype and exerts its border function. Because perichondrium becomes deranged and interrupted by cartilaginous outgrowths in Hereditary Multiple Exostoses (HME), a pediatric disorder caused by EXT mutations and consequent heparan sulfate (HS) deficiency, we asked whether EXT genes and HS normally have roles in establishing its phenotype and function. Indeed, conditional Ext1 ablation in perichondrium and lateral chondrocytes flanking the epiphyseal region of mouse embryo long bone anlagen - a region encompassing the groove of Ranvier - caused ectopic cartilage formation. A similar response was observed when HS function was disrupted in long bone anlagen explants by genetic, pharmacological or enzymatic means, a response preceded by ectopic BMP signaling within perichondrium. These treatments also triggered excess chondrogenesis and cartilage nodule formation and overexpression of chondrogenic and matrix genes in limb bud mesenchymal cells in micromass culture. Interestingly, the treatments disrupted the peripheral definition and border of the cartilage nodules in such a way that many nodules overgrew and fused with each other into large amorphous cartilaginous masses. Interference with HS function reduced the physical association and interactions of BMP2 with HS and increased the cell responsiveness to endogenous and exogenous BMP proteins. In sum, Ext genes and HS are needed to establish and maintain perichondrium's phenotype and border function, restrain pro-chondrogenic signaling proteins including BMPs, and restrict chondrogenesis. Alterations in these mechanisms may contribute to exostosis formation in HME, particularly at the expense of regions rich in progenitor

  3. Spearfishing regulation benefits artisanal fisheries: the ReGS indicator and its application to a multiple-use Mediterranean marine protected area.

    Science.gov (United States)

    Rocklin, Delphine; Tomasini, Jean-Antoine; Culioli, Jean-Michel; Pelletier, Dominique; Mouillot, David

    2011-01-01

    The development of fishing efficiency coupled with an increase of fishing effort led to the overexploitation of numerous natural marine resources. In addition to this commercial pressure, the impact of recreational activities on fish assemblages remains barely known. Here we examined the impact of spearfishing limitation on resources in a marine protected area (MPA) and the benefit it provides for the local artisanal fishery through the use of a novel indicator. We analysed trends in the fish assemblage composition using artisanal fisheries data collected in the Bonifacio Strait Natural Reserve (BSNR), a Mediterranean MPA where the spearfishing activity has been forbidden over 15% of its area. Fish species were pooled into three response groups according to their target level by spearfishing. We developed the new flexible ReGS indicator reflecting shifts in species assemblages according to the relative abundance of each response group facing external pressure. The catch per unit effort (CPUE) increased by ca. 60% in the BSNR between 2000 and 2007, while the MPA was established in 1999. The gain of CPUE strongly depended on the considered response group: for the highly targeted group, the CPUE doubled while the CPUE of the untargeted group increased by only 15.5%. The ReGS value significantly increased from 0.31 to 0.45 (on a scale between 0 and 1) in the general perimeter of this MPA while it has reached a threshold of 0.43, considered as a reference point, in the area protected from spearfishing since 1982. Our results demonstrated that limiting recreational fishing by appropriate zoning in multiple-use MPAs represents a real benefit for artisanal fisheries. More generally we showed how our new indicator may reveal a wide range of impacts on coastal ecosystems such as global change or habitat degradation.

  4. Spearfishing regulation benefits artisanal fisheries: the ReGS indicator and its application to a multiple-use Mediterranean marine protected area.

    Directory of Open Access Journals (Sweden)

    Delphine Rocklin

    Full Text Available The development of fishing efficiency coupled with an increase of fishing effort led to the overexploitation of numerous natural marine resources. In addition to this commercial pressure, the impact of recreational activities on fish assemblages remains barely known. Here we examined the impact of spearfishing limitation on resources in a marine protected area (MPA and the benefit it provides for the local artisanal fishery through the use of a novel indicator. We analysed trends in the fish assemblage composition using artisanal fisheries data collected in the Bonifacio Strait Natural Reserve (BSNR, a Mediterranean MPA where the spearfishing activity has been forbidden over 15% of its area. Fish species were pooled into three response groups according to their target level by spearfishing. We developed the new flexible ReGS indicator reflecting shifts in species assemblages according to the relative abundance of each response group facing external pressure. The catch per unit effort (CPUE increased by ca. 60% in the BSNR between 2000 and 2007, while the MPA was established in 1999. The gain of CPUE strongly depended on the considered response group: for the highly targeted group, the CPUE doubled while the CPUE of the untargeted group increased by only 15.5%. The ReGS value significantly increased from 0.31 to 0.45 (on a scale between 0 and 1 in the general perimeter of this MPA while it has reached a threshold of 0.43, considered as a reference point, in the area protected from spearfishing since 1982. Our results demonstrated that limiting recreational fishing by appropriate zoning in multiple-use MPAs represents a real benefit for artisanal fisheries. More generally we showed how our new indicator may reveal a wide range of impacts on coastal ecosystems such as global change or habitat degradation.

  5. Home geriatric physiological measurements.

    Science.gov (United States)

    Tamura, Toshiyo

    2012-10-01

    In an ageing society, the elderly can be monitored with numerous physiological, physical and passive devices. Sensors can be installed in the home for continuous mobility assistance and unobtrusive disease prevention. This review presents several modern sensors, which improve the quality of life and assist the elderly, disabled people and their caregivers. The main concept of geriatric sensors is that they are capable of providing assistance without limiting or disturbing the subject's daily routine, giving him or her greater comfort, pleasure and well-being. Furthermore, this review includes associated technologies of wearable/implantable monitoring systems and the 'smart-house' project. This review concludes by discussing future challenges of the future aged society.

  6. Home geriatric physiological measurements

    International Nuclear Information System (INIS)

    Tamura, Toshiyo

    2012-01-01

    In an ageing society, the elderly can be monitored with numerous physiological, physical and passive devices. Sensors can be installed in the home for continuous mobility assistance and unobtrusive disease prevention. This review presents several modern sensors, which improve the quality of life and assist the elderly, disabled people and their caregivers. The main concept of geriatric sensors is that they are capable of providing assistance without limiting or disturbing the subject's daily routine, giving him or her greater comfort, pleasure and well-being. Furthermore, this review includes associated technologies of wearable/implantable monitoring systems and the ‘smart-house’ project. This review concludes by discussing future challenges of the future aged society. (topical review)

  7. Physiology for engineers applying engineering methods to physiological systems

    CERN Document Server

    Chappell, Michael

    2016-01-01

    This book provides an introduction to qualitative and quantitative aspects of human physiology. It looks at biological and physiological processes and phenomena, including a selection of mathematical models, showing how physiological problems can be mathematically formulated and studied. It also illustrates how a wide range of engineering and physics topics, including electronics, fluid dynamics, solid mechanics and control theory can be used to describe and understand physiological processes and systems. Throughout the text there are introductions to measuring and quantifying physiological processes using both signal and imaging technologies. Physiology for Engineers describes the basic structure and models of cellular systems, the structure and function of the cardiovascular system, the electrical and mechanical activity of the heart and provides an overview of the structure and function of the respiratory and nervous systems. It also includes an introduction to the basic concepts and applications of reacti...

  8. Evidence that multiple genetic variants of MC4R play a functional role in the regulation of energy expenditure and appetite in Hispanic children1234

    Science.gov (United States)

    Cole, Shelley A; Voruganti, V Saroja; Cai, Guowen; Haack, Karin; Kent, Jack W; Blangero, John; Comuzzie, Anthony G; McPherson, John D; Gibbs, Richard A

    2010-01-01

    Background: Melanocortin-4-receptor (MC4R) haploinsufficiency is the most common form of monogenic obesity; however, the frequency of MC4R variants and their functional effects in general populations remain uncertain. Objective: The aim was to identify and characterize the effects of MC4R variants in Hispanic children. Design: MC4R was resequenced in 376 parents, and the identified single nucleotide polymorphisms (SNPs) were genotyped in 613 parents and 1016 children from the Viva la Familia cohort. Measured genotype analysis (MGA) tested associations between SNPs and phenotypes. Bayesian quantitative trait nucleotide (BQTN) analysis was used to infer the most likely functional polymorphisms influencing obesity-related traits. Results: Seven rare SNPs in coding and 18 SNPs in flanking regions of MC4R were identified. MGA showed suggestive associations between MC4R variants and body size, adiposity, glucose, insulin, leptin, ghrelin, energy expenditure, physical activity, and food intake. BQTN analysis identified SNP 1704 in a predicted micro-RNA target sequence in the downstream flanking region of MC4R as a strong, probable functional variant influencing total, sedentary, and moderate activities with posterior probabilities of 1.0. SNP 2132 was identified as a variant with a high probability (1.0) of exerting a functional effect on total energy expenditure and sleeping metabolic rate. SNP rs34114122 was selected as having likely functional effects on the appetite hormone ghrelin, with a posterior probability of 0.81. Conclusion: This comprehensive investigation provides strong evidence that MC4R genetic variants are likely to play a functional role in the regulation of weight, not only through energy intake but through energy expenditure. PMID:19889825

  9. Multiple sclerosis

    Science.gov (United States)

    ... indwelling catheter Osteoporosis or thinning of the bones Pressure sores Side effects of medicines used to treat the ... Daily bowel care program Multiple sclerosis - discharge Preventing pressure ulcers Swallowing problems Images Multiple sclerosis MRI of the ...

  10. Deconstructing the superorganism: social physiology, groundplans, and sociogenomics

    DEFF Research Database (Denmark)

    Johnson, Brian R; Linksvayer, Timothy A

    2010-01-01

    changes in the regulation of ancestral gene sets affecting reproductive physiology and behavior, and we argue that this hypothesis is explanatory for the evolution of division of labor (social anatomy) but not for the regulatory systems that ensure group-level coordination of action (social physiology...... to a truly integrative approach remains, as social physiology--the basis of group-level coordination--has generally been neglected by geneticists. In this paper, we begin a synthesis of these fields by first reviewing three classes of social insect organization that mark major transitions in increasing...

  11. Dramatic variability of the carbonate system at a temperate coastal ocean site (Beaufort, North Carolina, USA is regulated by physical and biogeochemical processes on multiple timescales.

    Directory of Open Access Journals (Sweden)

    Zackary I Johnson

    Full Text Available Increasing atmospheric carbon dioxide (CO2 from anthropogenic sources is acidifying marine environments resulting in potentially dramatic consequences for the physical, chemical and biological functioning of these ecosystems. If current trends continue, mean ocean pH is expected to decrease by ~0.2 units over the next ~50 years. Yet, there is also substantial temporal variability in pH and other carbon system parameters in the ocean resulting in regions that already experience change that exceeds long-term projected trends in pH. This points to short-term dynamics as an important layer of complexity on top of long-term trends. Thus, in order to predict future climate change impacts, there is a critical need to characterize the natural range and dynamics of the marine carbonate system and the mechanisms responsible for observed variability. Here, we present pH and dissolved inorganic carbon (DIC at time intervals spanning 1 hour to >1 year from a dynamic, coastal, temperate marine system (Beaufort Inlet, Beaufort NC USA to characterize the carbonate system at multiple time scales. Daily and seasonal variation of the carbonate system is largely driven by temperature, alkalinity and the balance between primary production and respiration, but high frequency change (hours to days is further influenced by water mass movement (e.g. tides and stochastic events (e.g. storms. Both annual (~0.3 units and diurnal (~0.1 units variability in coastal ocean acidity are similar in magnitude to 50 year projections of ocean acidity associated with increasing atmospheric CO2. The environmental variables driving these changes highlight the importance of characterizing the complete carbonate system rather than just pH. Short-term dynamics of ocean carbon parameters may already exert significant pressure on some coastal marine ecosystems with implications for ecology, biogeochemistry and evolution and this shorter term variability layers additive effects and

  12. Multiple levels of epigenetic control for bone biology and pathology.

    Science.gov (United States)

    Montecino, Martin; Stein, Gary; Stein, Janet; Zaidi, Kaleem; Aguilar, Rodrigo

    2015-12-01

    Multiple dimensions of epigenetic control contribute to regulation of gene expression that governs bone biology and pathology. Once confined to DNA methylation and a limited number of post-translational modifications of histone proteins, the definition of epigenetic mechanisms is expanding to include contributions of non-coding RNAs and mitotic bookmarking, a mechanism for retaining phenotype identity during cell proliferation. Together these different levels of epigenetic control of physiological processes and their perturbations that are associated with compromised gene expression during the onset and progression of disease, have contributed to an unprecedented understanding of the activities (operation) of the genomic landscape. Here, we address general concepts that explain the contribution of epigenetic control to the dynamic regulation of gene expression during eukaryotic transcription. This article is part of a Special Issue entitled Epigenetics and Bone. Copyright © 2015 Elsevier Inc. All rights reserved.

  13. Insulin signaling regulates fatty acid catabolism at the level of CoA activation.

    Directory of Open Access Journals (Sweden)

    Xiaojun Xu

    2012-01-01

    Full Text Available The insulin/IGF signaling pathway is a highly conserved regulator of metabolism in flies and mammals, regulating multiple physiological functions including lipid metabolism. Although insulin signaling is known to regulate the activity of a number of enzymes in metabolic pathways, a comprehensive understanding of how the insulin signaling pathway regulates metabolic pathways is still lacking. Accepted knowledge suggests the key regulated step in triglyceride (TAG catabolism is the release of fatty acids from TAG via the action of lipases. We show here that an additional, important regulated step is the activation of fatty acids for beta-oxidation via Acyl Co-A synthetases (ACS. We identify pudgy as an ACS that is transcriptionally regulated by direct FOXO action in Drosophila. Increasing or reducing pudgy expression in vivo causes a decrease or increase in organismal TAG levels respectively, indicating that pudgy expression levels are important for proper lipid homeostasis. We show that multiple ACSs are also transcriptionally regulated by insulin signaling in mammalian cells. In sum, we identify fatty acid activation onto CoA as an important, regulated step in triglyceride catabolism, and we identify a mechanistic link through which insulin regulates lipid homeostasis.

  14. Protein kinase FgSch9 serves as a mediator of the target of rapamycin and high osmolarity glycerol pathways and regulates multiple stress responses and secondary metabolism in Fusarium graminearum.

    Science.gov (United States)

    Gu, Qin; Zhang, Chengqi; Yu, Fangwei; Yin, Yanni; Shim, Won-Bo; Ma, Zhonghua

    2015-08-01

    Saccharomyces cerevisiae protein kinase Sch9 is one of the downstream effectors of the target of rapamycin (TOR) complex 1 and plays multiple roles in stress resistance, longevity and nutrient sensing. However, the functions of Sch9 orthologs in filamentous fungi, particularly in pathogenic species, have not been characterized to date. Here, we investigated biological and genetic functions of FgSch9 in Fusarium graminearum. The FgSCH9 deletion mutant (ΔFgSch9) was defective in aerial hyphal growth, hyphal branching and conidial germination. The mutant exhibited increased sensitivity to osmotic and oxidative stresses, cell wall-damaging agents, and to rapamycin, while showing increased thermal tolerance. We identified FgMaf1 as one of the FgSch9-interacting proteins that plays an important role in regulating mycotoxin biosynthesis and virulence of F. graminearum. Co-immunoprecipitation and affinity capture-mass spectrometry assays showed that FgSch9 also interacts with FgTor and FgHog1. More importantly, both ΔFgSch9 and FgHog1 null mutant (ΔFgHog1) exhibited increased sensitivity to osmotic and oxidative stresses. This defect was more severe in the FgSch9/FgHog1 double mutant. Taken together, we propose that FgSch9 serves as a mediator of the TOR and high osmolarity glycerol pathways, and regulates vegetative differentiation, multiple stress responses and secondary metabolism in F. graminearum. © 2014 Society for Applied Microbiology and John Wiley & Sons Ltd.

  15. A genome-wide association meta-analysis of circulating sex hormone-binding globulin reveals multiple Loci implicated in sex steroid hormone regulation.

    Directory of Open Access Journals (Sweden)

    Andrea D Coviello

    Full Text Available Sex hormone-binding globulin (SHBG is a glycoprotein responsible for the transport and biologic availability of sex steroid hormones, primarily testosterone and estradiol. SHBG has been associated with chronic diseases including type 2 diabetes (T2D and with hormone-sensitive cancers such as breast and prostate cancer. We performed a genome-wide association study (GWAS meta-analysis of 21,791 individuals from 10 epidemiologic studies and validated these findings in 7,046 individuals in an additional six studies. We identified twelve genomic regions (SNPs associated with circulating SHBG concentrations. Loci near the identified SNPs included SHBG (rs12150660, 17p13.1, p = 1.8 × 10(-106, PRMT6 (rs17496332, 1p13.3, p = 1.4 × 10(-11, GCKR (rs780093, 2p23.3, p = 2.2 × 10(-16, ZBTB10 (rs440837, 8q21.13, p = 3.4 × 10(-09, JMJD1C (rs7910927, 10q21.3, p = 6.1 × 10(-35, SLCO1B1 (rs4149056, 12p12.1, p = 1.9 × 10(-08, NR2F2 (rs8023580, 15q26.2, p = 8.3 × 10(-12, ZNF652 (rs2411984, 17q21.32, p = 3.5 × 10(-14, TDGF3 (rs1573036, Xq22.3, p = 4.1 × 10(-14, LHCGR (rs10454142, 2p16.3, p = 1.3 × 10(-07, BAIAP2L1 (rs3779195, 7q21.3, p = 2.7 × 10(-08, and UGT2B15 (rs293428, 4q13.2, p = 5.5 × 10(-06. These genes encompass multiple biologic pathways, including hepatic function, lipid metabolism, carbohydrate metabolism and T2D, androgen and estrogen receptor function, epigenetic effects, and the biology of sex steroid hormone-responsive cancers including breast and prostate cancer. We found evidence of sex-differentiated genetic influences on SHBG. In a sex-specific GWAS, the loci 4q13.2-UGT2B15 was significant in men only (men p = 2.5 × 10(-08, women p = 0.66, heterogeneity p = 0.003. Additionally, three loci showed strong sex-differentiated effects: 17p13.1-SHBG and Xq22.3-TDGF3 were stronger in men, whereas 8q21.12-ZBTB10 was stronger in women. Conditional analyses identified additional signals at the SHBG gene that together almost double the proportion

  16. Procedures of Exercise Physiology Laboratories

    Science.gov (United States)

    Bishop, Phillip A.; Fortney, Suzanne; Greenisen, Michael; Siconolfi, Steven F.; Bamman, Marcas M.; Moore, Alan D., Jr.; Squires, William

    1998-01-01

    This manual describes the laboratory methods used to collect flight crew physiological performance data at the Johnson Space Center. The Exercise Countermeasures Project Laboratory is a standard physiology laboratory; only the application to the study of human physiological adaptations to spaceflight is unique. In the absence of any other recently published laboratory manual, this manual should be a useful document staffs and students of other laboratories.

  17. Conservation physiology of marine fishes

    DEFF Research Database (Denmark)

    Jørgensen, Christian; Peck, Myron A.; Antognarelli, Fabio

    2012-01-01

    At the end of May, 17 scientists involved in an EU COST Action on Conservation Physiology of Marine Fishes met in Oristano, Sardinia, to discuss how physiology can be better used in modelling tools to aid in management of marine ecosystems. Current modelling approaches incorporate physiology...... to different extents, ranging from no explicit consideration to detailed physiological mechanisms, and across scales from a single fish to global fishery resources. Biologists from different sub-disciplines are collaborating to rise to the challenge of projecting future changes in distribution and productivity...

  18. MULTIPLE OBJECTS

    Directory of Open Access Journals (Sweden)

    A. A. Bosov

    2015-04-01

    Full Text Available Purpose. The development of complicated techniques of production and management processes, information systems, computer science, applied objects of systems theory and others requires improvement of mathematical methods, new approaches for researches of application systems. And the variety and diversity of subject systems makes necessary the development of a model that generalizes the classical sets and their development – sets of sets. Multiple objects unlike sets are constructed by multiple structures and represented by the structure and content. The aim of the work is the analysis of multiple structures, generating multiple objects, the further development of operations on these objects in application systems. Methodology. To achieve the objectives of the researches, the structure of multiple objects represents as constructive trio, consisting of media, signatures and axiomatic. Multiple object is determined by the structure and content, as well as represented by hybrid superposition, composed of sets, multi-sets, ordered sets (lists and heterogeneous sets (sequences, corteges. Findings. In this paper we study the properties and characteristics of the components of hybrid multiple objects of complex systems, proposed assessments of their complexity, shown the rules of internal and external operations on objects of implementation. We introduce the relation of arbitrary order over multiple objects, we define the description of functions and display on objects of multiple structures. Originality.In this paper we consider the development of multiple structures, generating multiple objects.Practical value. The transition from the abstract to the subject of multiple structures requires the transformation of the system and multiple objects. Transformation involves three successive stages: specification (binding to the domain, interpretation (multiple sites and particularization (goals. The proposed describe systems approach based on hybrid sets

  19. Polyamines in plant physiology

    Science.gov (United States)

    Galston, A. W.; Sawhney, R. K.

    1990-01-01

    The diamine putrescine, the triamine spermidine, and the tetramine spermine are ubiquitous in plant cells, while other polyamines are of more limited occurrence. Their chemistry and pathways of biosynthesis and metabolism are well characterized. They occur in the free form as cations, but are often conjugated to small molecules like phenolic acids and also to various macromolecules. Their titer varies from approximately micromolar to more than millimolar, and depends greatly on environmental conditions, especially stress. In cereals, the activity of one of the major polyamine biosynthetic enzymes, arginine decarboxylase, is rapidly and dramatically increased by almost every studied external stress, leading to 50-fold or greater increases in putrescine titer within a few hours. The physiological significance of this increase is not yet clear, although most recent work suggests an adaptive, protective role. Polyamines produced through the action of ornithine decarboxylase, by contrast, seem essential for DNA replication and cell division. The application of exogenous polyamines produces effects on patterns of senescence and morphogenesis, suggesting but not proving a regulatory role for polyamines in these processes. The evidence for such a regulatory role is growing.

  20. Clinical physiology grand rounds.

    Science.gov (United States)

    Richards, Jeremy; Schwartzstein, Richard; Irish, Julie; Almeida, Jacqueline; Roberts, David

    2013-04-01

    Clinical Physiology Grand Rounds (CPGR) is an interactive, case-based conference for medical students designed to: (1) integrate preclinical and clinical learning; (2) promote inductive clinical reasoning; and (3) emphasise students as peer teachers. CPGR specifically encourages mixed learning level student interactions and emphasises the use of concept mapping. We describe the theoretical basis and logistical considerations for an interactive, integrative, mixed-learner environment such as CPGR. In addition, we report qualitative data regarding students' attitudes towards and perceptions of CPGR. Medical students from first to fourth year participate in a monthly, interactive conference. The CPGR was designed to bridge gaps and reinforce linkages between basic science and clinical concepts, and to incorporate interactive vertical integration between preclinical and clinical students. Medical education and content experts use Socratic, interactive teaching methods to develop real-time concept maps to emphasise the presence and importance of linkages across curricula. Student focus groups were held to assess attitudes towards and perceptions of the mixed-learner environment and concept maps in CPGR. Qualitative analyses of focus group transcripts were performed to develop themes and codes describing the students' impressions of CPGR. CPGR is a case-based, interactive conference designed to help students gain an increased appreciation of linkages between basic science and clinical medicine concepts, and an increased awareness of clinical reasoning thought processes. Success is dependent upon explicit attention being given to goals for students' integrated learning. © Blackwell Publishing Ltd 2013.

  1. Conjoined twins: scientific cinema and Pavlovian physiology.

    Science.gov (United States)

    Krementsov, Nikolai

    2015-01-01

    Through the lens of a 1957 documentary film, "Neural and humoral factors in the regulation of bodily functions (research on conjoined twins)," produced by the USSR Academy of Medical Sciences, this essay traces the entwined histories of Soviet physiology, studies of conjoined twins and scientific cinema. It examines the role of Ivan Pavlov and his students, including Leonid Voskresenkii, Dmitrii Fursikov and Petr Anokhin, in the development of "scientific film" as a particular cinematographic genre in Soviet Russia and explores numerous puzzles hidden behind the film's striking visuals. Crown Copyright © 2015. Published by Elsevier Ltd. All rights reserved.

  2. Molecular physiology of seeds

    International Nuclear Information System (INIS)

    Hajduch, M.

    2014-05-01

    Plant development is well described. However, full understanding of the regulation of processes associated with plant development is still missing. Present Dr.Sc. thesis advances our understanding of the regulation of plant development by quantitative proteomics analyses of seed development of soybean, canola, castor, flax, and model plant arabidopsis in control and environmentally challenged environments. The analysis of greenhouse-grown soybean, canola, castor, and arabidospis provided complex characterization of metabolic processes during seed development, for instance, of carbon assimilation into fatty acids. Furthermore, the analyses of soybean and flax grown in Chernobyl area provided in-depth characterization of seed development in radio-contaminated environment. Soybean and flax were altered by radio-contaminated environment in different way. However, these alterations resulted into modifications in seed oil content. Further analyses showed that soybean and flax possess alterations of carbon metabolism in cytoplasm and plastids along with increased activity of photosynthetic apparatus. Our present experiments are focused on further characterization of molecular bases that might be responsible for alterations of seed oil content in Chernobyl grown plants. (author)

  3. Physiologic effects of bowel preparation

    DEFF Research Database (Denmark)

    Holte, Kathrine; Nielsen, Kristine Grubbe; Madsen, Jan Lysgård

    2004-01-01

    PURPOSE: Despite the universal use of bowel preparation before colonoscopy and colorectal surgery, the physiologic effects have not been described in a standardized setting. This study was designed to investigate the physiologic effects of bowel preparation. METHODS: In a prospective study, 12...

  4. VEGFR2 Trafficking, Signaling and Proteolysis is Regulated by the Ubiquitin Isopeptidase USP8.

    Science.gov (United States)

    Smith, Gina A; Fearnley, Gareth W; Abdul-Zani, Izma; Wheatcroft, Stephen B; Tomlinson, Darren C; Harrison, Michael A; Ponnambalam, Sreenivasan

    2016-01-01

    Vascular endothelial growth factor A (VEGF-A) regulates many aspects of vascular function. VEGF-A binding to vascular endothelial growth factor receptor 2 (VEGFR2) stimulates endothelial signal transduction and regulates multiple cellular responses. Activated VEGFR2 undergoes ubiquitination but the enzymes that regulate this post-translational modification are unclear. In this study, the de-ubiquitinating enzyme, USP8, is shown to regulate VEGFR2 trafficking, de-ubiquitination, proteolysis and signal transduction. USP8-depleted endothelial cells displayed altered VEGFR2 ubiquitination and production of a unique VEGFR2 extracellular domain proteolytic fragment caused by VEGFR2 accumulation in the endosome-lysosome system. In addition, perturbed VEGFR2 trafficking impaired VEGF-A-stimulated signal transduction in USP8-depleted cells. Thus, regulation of VEGFR2 ubiquitination and de-ubiquitination has important consequences for the endothelial cell response and vascular physiology. © 2015 The Authors. Traffic published by John Wiley & Sons Ltd.

  5. Rationally designed chimeric peptide of met-enkephalin and FMRFa-[D-Ala2,p-Cl-Phe4]YFa induce multiple opioid receptors mediated antinociception and up-regulate their expression.

    Science.gov (United States)

    Vats, Ishwar Dutt; Chaudhary, Snehlata; Sharma, Ahuti; Nath, Mahendra; Pasha, Santosh

    2010-07-25

    The physiological role of NPFF/FMRFa family of peptides appears to be complex and exact mechanism of action of these peptides is not yet completely understood. In same line of scrutiny, another analog of YGGFMKKKFMRFamide (YFa), a chimeric peptide of met-enkephalin and FMRFamide, was rationally designed and synthesized which contain D-alanine and p-Cl-phenylalanine residues at 2nd and 4th positions, respectively i.e., Y-(D-Ala)-G-(p-Cl-Phe)-MKKKFMRFamide ([D-Ala(2), p-Cl-Phe(4)]YFa) in order to achieve improved bioavailability and blood brain barrier penetration. Therefore, present study investigates the possible antinociceptive effect of [D-Ala(2), p-Cl-Phe(4)]YFa on intra-peritoneal (i.p.) administration using tail-flick test in rats followed by its opioid receptor(s) specificity using mu, delta and kappa receptor antagonists. Further, its antinociceptive effect was examined during 6 days of chronic i.p. treatment and assessed effect of this treatment on differential expression of opioid receptors. [D-Ala(2), p-Cl-Phe(4)]YFa in comparison to parent peptide YFa, induce significantly higher dose dependent antinociception in rats which was mediated by all three opioid receptors (mu, delta and kappa). Importantly, it induced comparable antinociception in rats throughout the chronic i.p. treatment and significantly up-regulated the overall expression (mRNA and protein) of mu, delta and kappa opioid receptors. Therefore, pharmacological and molecular behavior of [D-Ala(2), p-Cl-Phe(4)]YFa demonstrate that incorporation of D-alanine and p-Cl-phenylalanine residues at appropriate positions in chimeric peptide leads to altered opioid receptor selectivity and enhanced antinociceptive potency, relative to parent peptide. (c) 2010 Elsevier B.V. All rights reserved.

  6. Adropin – physiological and pathophysiological role

    Directory of Open Access Journals (Sweden)

    Natalia Marczuk

    2016-09-01

    Full Text Available Adropin is a peptide hormone that was discovered in 2008 by Kumar et al. This protein consists of 76 amino acids, and it was originally described as a secreted peptide, with residues 1-33 encoding a secretory signal peptide sequence. The amino acid sequence of this protein in humans, mice and rats is identical. While our knowledge of the exact physiological roles of this poorly understood peptide continues to evolve, recent data suggest a role in energy homeostasis and the control of glucose and fatty acid metabolism. This protein is encoded by the Enho gene, which is expressed primarily in the liver and the central nervous system. The regulation of adropin secretion is controversial. Adropin immunoreactivity has been reported by several laboratories in the circulation of humans, non-human primates and rodents. However, more recently it has been suggested that adropin is a membrane-bound protein that modulates cell-cell communication. Moreover, adropin has been detected in various tissues and body fluids, such as brain, cerebellum, liver, kidney, heart, pancreas, small intestine, endothelial cells, colostrum, cheese whey and milk. The protein level, as shown by previous research, changes in various physiological and pathophysiological conditions. Adropin is involved in carbohydrate-lipid metabolism, metabolic diseases, central nervous system function, endothelial function and cardiovascular disease. The knowledge of this interesting protein, its exact role and mechanism of action is insufficient. This article provides an overview of the existing literature about the role of adropin, both in physiological and pathophysiological conditions.

  7. New concepts in white adipose tissue physiology

    International Nuclear Information System (INIS)

    Proença, A.R.G.; Sertié, R.A.L.; Oliveira, A.C.; Campaãa, A.B.; Caminhotto, R.O.; Chimin, P.; Lima, F.B.

    2014-01-01

    Numerous studies address the physiology of adipose tissue (AT). The interest surrounding the physiology of AT is primarily the result of the epidemic outburst of obesity in various contemporary societies. Briefly, the two primary metabolic activities of white AT include lipogenesis and lipolysis. Throughout the last two decades, a new model of AT physiology has emerged. Although AT was considered to be primarily an abundant energy source, it is currently considered to be a prolific producer of biologically active substances, and, consequently, is now recognized as an endocrine organ. In addition to leptin, other biologically active substances secreted by AT, generally classified as cytokines, include adiponectin, interleukin-6, tumor necrosis factor-alpha, resistin, vaspin, visfatin, and many others now collectively referred to as adipokines. The secretion of such biologically active substances by AT indicates its importance as a metabolic regulator. Cell turnover of AT has also recently been investigated in terms of its biological role in adipogenesis. Consequently, the objective of this review is to provide a comprehensive critical review of the current literature concerning the metabolic (lipolysis, lipogenesis) and endocrine actions of AT

  8. New concepts in white adipose tissue physiology

    Energy Technology Data Exchange (ETDEWEB)

    Proença, A.R.G. [Universidade Estadual de Campinas, Laboratório de Biotecnologia, Faculdade de Ciências Aplicadas, Limeira, SP, Brasil, Laboratório de Biotecnologia, Faculdade de Ciências Aplicadas, Universidade Estadual de Campinas, Limeira, SP (Brazil); Sertié, R.A.L. [Universidade de São Paulo, Instituto de Ciências Biomédicas, Departamento de Fisiologia e Biofísica, São Paulo, SP, Brasil, Departamento de Fisiologia e Biofísica, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, SP (Brazil); Oliveira, A.C. [Universidade Estadual do Ceará, Instituto Superior de Ciências Biomédicas, Fortaleza, CE, Brasil, Instituto Superior de Ciências Biomédicas, Universidade Estadual do Ceará, Fortaleza, CE (Brazil); Campaãa, A.B.; Caminhotto, R.O.; Chimin, P.; Lima, F.B. [Universidade de São Paulo, Instituto de Ciências Biomédicas, Departamento de Fisiologia e Biofísica, São Paulo, SP, Brasil, Departamento de Fisiologia e Biofísica, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, SP (Brazil)

    2014-03-03

    Numerous studies address the physiology of adipose tissue (AT). The interest surrounding the physiology of AT is primarily the result of the epidemic outburst of obesity in various contemporary societies. Briefly, the two primary metabolic activities of white AT include lipogenesis and lipolysis. Throughout the last two decades, a new model of AT physiology has emerged. Although AT was considered to be primarily an abundant energy source, it is currently considered to be a prolific producer of biologically active substances, and, consequently, is now recognized as an endocrine organ. In addition to leptin, other biologically active substances secreted by AT, generally classified as cytokines, include adiponectin, interleukin-6, tumor necrosis factor-alpha, resistin, vaspin, visfatin, and many others now collectively referred to as adipokines. The secretion of such biologically active substances by AT indicates its importance as a metabolic regulator. Cell turnover of AT has also recently been investigated in terms of its biological role in adipogenesis. Consequently, the objective of this review is to provide a comprehensive critical review of the current literature concerning the metabolic (lipolysis, lipogenesis) and endocrine actions of AT.

  9. Two component systems: physiological effect of a third component.

    Directory of Open Access Journals (Sweden)

    Baldiri Salvado

    Full Text Available Signal transduction systems mediate the response and adaptation of organisms to environmental changes. In prokaryotes, this signal transduction is often done through Two Component Systems (TCS. These TCS are phosphotransfer protein cascades, and in their prototypical form they are composed by a kinase that senses the environmental signals (SK and by a response regulator (RR that regulates the cellular response. This basic motif can be modified by the addition of a third protein that interacts either with the SK or the RR in a way that could change the dynamic response of the TCS module. In this work we aim at understanding the effect of such an additional protein (which we call "third component" on the functional properties of a prototypical TCS. To do so we build mathematical models of TCS with alternative designs for their interaction with that third component. These mathematical models are analyzed in order to identify the differences in dynamic behavior inherent to each design, with respect to functionally relevant properties such as sensitivity to changes in either the parameter values or the molecular concentrations, temporal responsiveness, possibility of multiple steady states, or stochastic fluctuations in the system. The differences are then correlated to the physiological requirements that impinge on the functioning of the TCS. This analysis sheds light on both, the dynamic behavior of synthetically designed TCS, and the conditions under which natural selection might favor each of the designs. We find that a third component that modulates SK activity increases the parameter space where a bistable response of the TCS module to signals is possible, if SK is monofunctional, but decreases it when the SK is bifunctional. The presence of a third component that modulates RR activity decreases the parameter space where a bistable response of the TCS module to signals is possible.

  10. Distinguish self- and hetero-perceived stress through behavioral imaging and physiological features.

    Science.gov (United States)

    Spodenkiewicz, Michel; Aigrain, Jonathan; Bourvis, Nadège; Dubuisson, Séverine; Chetouani, Mohamed; Cohen, David

    2018-03-02

    Stress reactivity is a complex phenomenon associated to multiple and multimodal expressions. Response to stressors has an obvious survival function and may be seen as an internal regulation to adapt to threat or danger. The intensity of this internal response can be assessed as the self-perception of the stress response. In species with social organization, this response also serves a communicative function, so-called hetero-perception. Our study presents multimodal stress detection assessment - a new methodology combining behavioral imaging and physiological monitoring for analyzing stress from these two perspectives. The system is based on automatic extraction of 39 behavioral (2D+3D video recording) and 62 physiological (Nexus-10 recording) features during a socially evaluated mental arithmetic test. The analysis with machine learning techniques for automatic classification using Support Vector Machine (SVM) show that self-perception and hetero-perception of social stress are both close but different phenomena: self-perception was significantly correlated with hetero-perception but significantly differed from it. Also, assessing stress with SVM through multimodality gave excellent classification results (F1 score values: 0.9±0.012 for hetero-perception and 0.87±0.021 for self-perception). In the best selected feature subsets, we found some common behavioral and physiological features that allow classification of both self- and hetero-perceived stress. However, we also found the contributing features for automatic classifications had opposite distributions: self-perception classification was mainly based on physiological features and hetero-perception was mainly based on behavioral features. Copyright © 2017. Published by Elsevier Inc.

  11. Cassava biology and physiology.

    Science.gov (United States)

    El-Sharkawy, Mabrouk A

    2004-11-01

    Cassava or manioc (Manihot esculenta Crantz), a perennial shrub of the New World, currently is the sixth world food crop for more than 500 million people in tropical and sub-tropical Africa, Asia and Latin America. It is cultivated mainly by resource-limited small farmers for its starchy roots, which are used as human food either fresh when low in cyanogens or in many processed forms and products, mostly starch, flour, and for animal feed. Because of its inherent tolerance to stressful environments, where other food crops would fail, it is often considered a food-security source against famine, requiring minimal care. Under optimal environmental conditions, it compares favorably in production of energy with most other major staple food crops due to its high yield potential. Recent research at the Centro Internacional de Agricultura Tropical (CIAT) in Colombia has demonstrated the ability of cassava to assimilate carbon at very high rates under high levels of humidity, temperature and solar radiation,which correlates with productivity across all environments whether dry or humid. When grown on very poor soils under prolonged drought for more than 6 months, the crop reduce both its leaf canopy and transpiration water loss, but its attached leaves remain photosynthetically active, though at greatly reduced rates. The main physiological mechanism underlying such a remarkable tolerance to drought was rapid stomatal closure under both atmospheric and edaphic water stress, protecting the leaf against dehydration while the plant depletes available soil water slowly during long dry periods. This drought tolerance mechanism leads to high crop water use efficiency values. Although the cassava fine root system is sparse, compared to other crops, it can penetrate below 2 m soil,thus enabling the crop to exploit deep water if available. Leaves of cassava and wild Manihot possess elevated activities of the C4 enzyme PEP carboxylase but lack the leaf Kranz anatomy typical of C4

  12. Multiple sclerosis

    International Nuclear Information System (INIS)

    Grunwald, I.Q.; Kuehn, A.L.; Backens, M.; Papanagiotou, P.; Shariat, K.; Kostopoulos, P.

    2008-01-01

    Multiple sclerosis is the most common chronic inflammatory disease of myelin with interspersed lesions in the white matter of the central nervous system. Magnetic resonance imaging (MRI) plays a key role in the diagnosis and monitoring of white matter diseases. This article focuses on key findings in multiple sclerosis as detected by MRI. (orig.) [de

  13. Common Student Misconceptions in Exercise Physiology and Biochemistry

    Science.gov (United States)

    Morton, James P.; Doran, Dominic A.; MacLaren, Don P. M.

    2008-01-01

    The present study represents a preliminary investigation designed to identify common misconceptions in students' understanding of physiological and biochemical topics within the academic domain of sport and exercise sciences. A specifically designed misconception inventory (consisting of 10 multiple-choice questions) was administered to a cohort…

  14. Principles and applications of TAL effectors for plant physiology and metabolism.

    Science.gov (United States)

    Bogdanove, Adam J

    2014-06-01

    Recent advances in DNA targeting allow unprecedented control over gene function and expression. Targeting based on TAL effectors is arguably the most promising for systems biology and metabolic engineering. Multiple, orthogonal TAL-effector reagents of different types can be used in the same cell. Furthermore, variation in base preferences of the individual structural repeats that make up the TAL effector DNA recognition domain makes targeting stringency tunable. Realized applications range from genome editing to epigenome modification to targeted gene regulation to chromatin labeling and capture. The principles that govern TAL effector DNA recognition make TAL effectors well suited for applications relevant to plant physiology and metabolism. TAL effector targeting has merits that are distinct from those of the RNA-based DNA targeting CRISPR/Cas9 system. Copyright © 2014 Elsevier Ltd. All rights reserved.

  15. The Emergence of Physiology and Form: Natural Selection Revisited

    Science.gov (United States)

    Torday, John S.

    2016-01-01

    Natural Selection describes how species have evolved differentially, but it is descriptive, non-mechanistic. What mechanisms does Nature use to accomplish this feat? One known way in which ancient natural forces affect development, phylogeny and physiology is through gravitational effects that have evolved as mechanotransduction, seen in the lung, kidney and bone, linking as molecular homologies to skin and brain. Tracing the ontogenetic and phylogenetic changes that have facilitated mechanotransduction identifies specific homologous cell-types and functional molecular markers for lung homeostasis that reveal how and why complex physiologic traits have evolved from the unicellular to the multicellular state. Such data are reinforced by their reverse-evolutionary patterns in chronic degenerative diseases. The physiologic responses of model organisms like Dictyostelium and yeast to gravity provide deep comparative molecular phenotypic homologies, revealing mammalian Target of Rapamycin (mTOR) as the final common pathway for vertical integration of vertebrate physiologic evolution; mTOR integrates calcium/lipid epistatic balance as both the proximate and ultimate positive selection pressure for vertebrate physiologic evolution. The commonality of all vertebrate structure-function relationships can be reduced to calcium/lipid homeostatic regulation as the fractal unit of vertebrate physiology, demonstrating the primacy of the unicellular state as the fundament of physiologic evolution. PMID:27534726

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

    Science.gov (United States)

    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

  17. Physiological response of carnation to radiation and some other factors

    International Nuclear Information System (INIS)

    Abdel - Baky, M.M.

    1986-01-01

    This study was carried out to investigate the physiological response of carnation plant (Dianthus caryophyllus c v. William sim) to gamma rays irradiation and some other factors namely: gibberellic acid and alar (B - 9 or daminozide) as growth regulators and potassium and boron as nutrients. The obtained results would be summarized

  18. Physiological impacts of elevated carbon dioxide and ocean acidification on fish.

    Science.gov (United States)

    Heuer, Rachael M; Grosell, Martin

    2014-11-01

    Most fish studied to date efficiently compensate for a hypercapnic acid-base disturbance; however, many recent studies examining the effects of ocean acidification on fish have documented impacts at CO2 levels predicted to occur before the end of this century. Notable impacts on neurosensory and behavioral endpoints, otolith growth, mitochondrial function, and metabolic rate demonstrate an unexpected sensitivity to current-day and near-future CO2 levels. Most explanations for these effects seem to center on increases in Pco2 and HCO3- that occur in the body during pH compensation for acid-base balance; however, few studies have measured these parameters at environmentally relevant CO2 levels or directly related them to reported negative endpoints. This compensatory response is well documented, but noted variation in dynamic regulation of acid-base transport pathways across species, exposure levels, and exposure duration suggests that multiple strategies may be utilized to cope with hypercapnia. Understanding this regulation and changes in ion gradients in extracellular and intracellular compartments during CO2 exposure could provide a basis for predicting sensitivity and explaining interspecies variation. Based on analysis of the existing literature, the present review presents a clear message that ocean acidification may cause significant effects on fish across multiple physiological systems, suggesting that pH compensation does not necessarily confer tolerance as downstream consequences and tradeoffs occur. It remains difficult to assess if acclimation responses during abrupt CO2 exposures will translate to fitness impacts over longer timescales. Nonetheless, identifying mechanisms and processes that may be subject to selective pressure could be one of many important components of assessing adaptive capacity. Copyright © 2014 the American Physiological Society.

  19. Multiple homicides.

    Science.gov (United States)

    Copeland, A R

    1989-09-01

    A study of multiple homicides or multiple deaths involving a solitary incident of violence by another individual was performed on the case files of the Office of the Medical Examiner of Metropolitan Dade County in Miami, Florida, during 1983-1987. A total of 107 multiple homicides were studied: 88 double, 17 triple, one quadruple, and one quintuple. The 236 victims were analyzed regarding age, race, sex, cause of death, toxicologic data, perpetrator, locale of the incident, and reason for the incident. This article compares this type of slaying with other types of homicide including those perpetrated by serial killers. Suggestions for future research in this field are offered.

  20. Multiple Sclerosis

    Science.gov (United States)

    Multiple sclerosis (MS) is a nervous system disease that affects your brain and spinal cord. It damages the myelin sheath, the material that surrounds and protects your nerve cells. This damage slows down ...

  1. Multiple myeloma.

    LENUS (Irish Health Repository)

    Collins, Conor D

    2012-02-01

    Advances in the imaging and treatment of multiple myeloma have occurred over the past decade. This article summarises the current status and highlights how an understanding of both is necessary for optimum management.

  2. Multiple mononeuropathy

    Science.gov (United States)

    ... with multiple mononeuropathy are prone to new nerve injuries at pressure points such as the knees and elbows. They should avoid putting pressure on these areas, for example, by not leaning on the elbows, crossing the knees, ...

  3. The Arabidopsis gene DIG6 encodes a large 60S subunit nuclear export GTPase 1 that is involved in ribosome biogenesis and affects multiple auxin-regulated development processes

    KAUST Repository

    Zhao, Huayan

    2015-08-13

    The circularly permuted GTPase large subunit GTPase 1 (LSG1) is involved in the maturation step of the 60S ribosome and is essential for cell viability in yeast. Here, an Arabidopsis mutant dig6 (drought inhibited growth of lateral roots) was isolated. The mutant exhibited multiple auxin-related phenotypes, which included reduced lateral root number, altered leaf veins, and shorter roots. Genetic mapping combined with next-generation DNA sequencing identified that the mutation occurred in AtLSG1-2. This gene was highly expressed in regions of auxin accumulation. Ribosome profiling revealed that a loss of function of AtLSG1-2 led to decreased levels of monosomes, further demonstrating its role in ribosome biogenesis. Quantitative proteomics showed that the expression of certain proteins involved in ribosome biogenesis was differentially regulated, indicating that ribosome biogenesis processes were impaired in the mutant. Further investigations showed that an AtLSG1-2 deficiency caused the alteration of auxin distribution, response, and transport in plants. It is concluded that AtLSG1-2 is integral to ribosome biogenesis, consequently affecting auxin homeostasis and plant development.

  4. Hypermethylation of MIR21 in CD4+ T cells from patients with relapsing-remitting multiple sclerosis associates with lower miRNA-21 levels and concomitant up-regulation of its target genes

    KAUST Repository

    Ruhrmann, Sabrina

    2017-08-02

    Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system caused by genetic and environmental factors. DNA methylation, an epigenetic mechanism that controls genome activity, may provide a link between genetic and environmental risk factors.We sought to identify DNA methylation changes in CD4+ T cells in patients with relapsing-remitting (RR-MS) and secondary-progressive (SP-MS) disease and healthy controls (HC).We performed DNA methylation analysis in CD4+ T cells from RR-MS, SP-MS, and HC and associated identified changes with the nearby risk allele, smoking, age, and gene expression.We observed significant methylation differences in the VMP1/MIR21 locus, with RR-MS displaying higher methylation compared to SP-MS and HC. VMP1/MIR21 methylation did not correlate with a known MS risk variant in VMP1 or smoking but displayed a significant negative correlation with age and the levels of mature miR-21 in CD4+ T cells. Accordingly, RR-MS displayed lower levels of miR-21 compared to SP-MS, which might reflect differences in age between the groups, and healthy individuals and a significant enrichment of up-regulated miR-21 target genes.Disease-related changes in epigenetic marking of MIR21 in RR-MS lead to differences in miR-21 expression with a consequence on miR-21 target genes.

  5. The Arabidopsis gene DIG6 encodes a large 60S subunit nuclear export GTPase 1 that is involved in ribosome biogenesis and affects multiple auxin-regulated development processes

    KAUST Repository

    Zhao, Huayan; Lü , Shiyou; Li, Ruixi; Chen, Tao; Zhang, Huoming; Cui, Peng; Ding, Feng; Liu, Pei; Wang, Guangchao; Xia, Yiji; Running, Mark P.; Xiong, Liming

    2015-01-01

    The circularly permuted GTPase large subunit GTPase 1 (LSG1) is involved in the maturation step of the 60S ribosome and is essential for cell viability in yeast. Here, an Arabidopsis mutant dig6 (drought inhibited growth of lateral roots) was isolated. The mutant exhibited multiple auxin-related phenotypes, which included reduced lateral root number, altered leaf veins, and shorter roots. Genetic mapping combined with next-generation DNA sequencing identified that the mutation occurred in AtLSG1-2. This gene was highly expressed in regions of auxin accumulation. Ribosome profiling revealed that a loss of function of AtLSG1-2 led to decreased levels of monosomes, further demonstrating its role in ribosome biogenesis. Quantitative proteomics showed that the expression of certain proteins involved in ribosome biogenesis was differentially regulated, indicating that ribosome biogenesis processes were impaired in the mutant. Further investigations showed that an AtLSG1-2 deficiency caused the alteration of auxin distribution, response, and transport in plants. It is concluded that AtLSG1-2 is integral to ribosome biogenesis, consequently affecting auxin homeostasis and plant development.

  6. Nest predation, clutch size, and physiological costs of egg production in the song sparrow (Melospiza melodia)

    OpenAIRE

    Travers, Marc Simon

    2009-01-01

    We examined the effects of nest predation on both clutch size and the physiological cost of egg production using a clutch removal experiment in free-living song sparrows (Melospiza melodia), inducing “high nest predation” (HNP) females to produce many replacement clutches compared to “low nest predation” (LNP) females. In a preliminary analysis we investigated the utility of multiple measures to assess “physiological condition”, including inter-correlations between physiological traits, sex d...

  7. Regulation of reproduction by the circadian rhythms.

    Science.gov (United States)

    Zhang, Wen-Xiang; Chen, Si-Yu; Liu, Chang

    2016-12-25

    Mammals synchronize their circadian activity primarily to the cycles of light and darkness in the environment. Circadian rhythm is controlled by the central clock in the hypothalamic suprachiasmatic nucleus (SCN) and the peripheral clocks in various tissues. More importantly, the central clock can integrate photic/nonphotic signals to generate rhythmic outputs, and then drive the slave oscillators in peripheral tissues through neuroendocrine and behavioral signals. Human reproductive activities, as some other physiological functions, are controlled by the biological clocks. Accumulating lines of epidemiological and genetic evidence indicate that disruption of circadian clock can be directly involved in multiple pathological processes, including infertility. In this review, we mainly discuss the presence of a circadian clock in reproductive tissues and its roles in follicles development, ovulation, spermatogenesis, fertilization and embryo implantation, etc. As the increased shift work and assisted reproductive technologies possibly disrupt circadian rhythmicity to impact reproduction, the importance of circadian rhythms should be highlighted in the regulation of reproductive process.

  8. Multimodal Regulation of Circadian Glucocorticoid Rhythm by Central and Adrenal Clocks.

    Science.gov (United States)

    Son, Gi Hoon; Cha, Hyo Kyeong; Chung, Sooyoung; Kim, Kyungjin

    2018-05-01

    Adrenal glucocorticoids (GCs) control a wide range of physiological processes, including metabolism, cardiovascular and pulmonary activities, immune and inflammatory responses, and various brain functions. During stress responses, GCs are secreted through activation of the hypothalamic-pituitary-adrenal axis, whereas circulating GC levels in unstressed states follow a robust circadian oscillation with a peak around the onset of the active period of a day. A recent advance in chronobiological research has revealed that multiple regulatory mechanisms, along with classical neuroendocrine regulation, underlie this GC circadian rhythm. The hierarchically organized circadian system, with a central pacemaker in the suprachiasmatic nucleus of the hypothalamus and local oscillators in peripheral tissues, including the adrenal gland, mediates periodicities in physiological processes in mammals. In this review, we primarily focus on our understanding of the circadian regulation of adrenal GC rhythm, with particular attention to the cooperative actions of the suprachiasmatic nucleus central and adrenal local clocks, and the clinical implications of this rhythm in human diseases.

  9. The Regulation of Mammalian Circadian Physiology by Light

    National Research Council Canada - National Science Library

    Foster, Russel

    1997-01-01

    .... Our work studies on retinally degenerate mammals have shown that visual blindness need not mean circadian blindness, and that two functionally distinct systems for processing light information must...

  10. Impact of regulated deficit irrigation on the physiological ...

    African Journals Online (AJOL)

    2011

    2012-03-22

    Mar 22, 2012 ... in plant response to water deficit under field conditions ... firstly related to the reduction in photosynthesis and CO2 ... However, varieties with the highest osmotic ... Indeed, the high potassium consumption in both stressed.

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

    Science.gov (United States)

    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.

  12. [Multiple meningiomas].

    Science.gov (United States)

    Terrier, L-M; François, P

    2016-06-01

    Multiple meningiomas (MMs) or meningiomatosis are defined by the presence of at least 2 lesions that appear simultaneously or not, at different intracranial locations, without the association of neurofibromatosis. They present 1-9 % of meningiomas with a female predominance. The occurrence of multiple meningiomas is not clear. There are 2 main hypotheses for their development, one that supports the independent evolution of these tumors and the other, completely opposite, that suggests the propagation of tumor cells of a unique clone transformation, through cerebrospinal fluid. NF2 gene mutation is an important intrinsic risk factor in the etiology of multiple meningiomas and some exogenous risk factors have been suspected but only ionizing radiation exposure has been proven. These tumors can grow anywhere in the skull but they are more frequently observed in supratentorial locations. Their histologic types are similar to unique meningiomas of psammomatous, fibroblastic, meningothelial or transitional type and in most cases are benign tumors. The prognosis of these tumors is eventually good and does not differ from the unique tumors except for the cases of radiation-induced multiple meningiomas, in the context of NF2 or when diagnosed in children where the outcome is less favorable. Each meningioma lesion should be dealt with individually and their multiple character should not justify their resection at all costs. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  13. Conservation physiology of animal migration

    Science.gov (United States)

    Lennox, Robert J.; Chapman, Jacqueline M.; Souliere, Christopher M.; Tudorache, Christian; Wikelski, Martin; Metcalfe, Julian D.; Cooke, Steven J.

    2016-01-01

    Migration is a widespread phenomenon among many taxa. This complex behaviour enables animals to exploit many temporally productive and spatially discrete habitats to accrue various fitness benefits (e.g. growth, reproduction, predator avoidance). Human activities and global environmental change represent potential threats to migrating animals (from individuals to species), and research is underway to understand mechanisms that control migration and how migration responds to modern challenges. Focusing on behavioural and physiological aspects of migration can help to provide better understanding, management and conservation of migratory populations. Here, we highlight different physiological, behavioural and biomechanical aspects of animal migration that will help us to understand how migratory animals interact with current and future anthropogenic threats. We are in the early stages of a changing planet, and our understanding of how physiology is linked to the persistence of migratory animals is still developing; therefore, we regard the following questions as being central to the conservation physiology of animal migrations. Will climate change influence the energetic costs of migration? Will shifting temperatures change the annual clocks of migrating animals? Will anthropogenic influences have an effect on orientation during migration? Will increased anthropogenic alteration of migration stopover sites/migration corridors affect the stress physiology of migrating animals? Can physiological knowledge be used to identify strategies for facilitating the movement of animals? Our synthesis reveals that given the inherent challenges of migration, additional stressors derived from altered environments (e.g. climate change, physical habitat alteration, light pollution) or interaction with human infrastructure (e.g. wind or hydrokinetic turbines, dams) or activities (e.g. fisheries) could lead to long-term changes to migratory phenotypes. However, uncertainty remains

  14. Contributions of Child's Physiology and Maternal Behavior to Children's Trajectories of Temperamental Reactivity

    Science.gov (United States)

    Blandon, Alysia Y.; Calkins, Susan D.; Keane, Susan P.; O'brien, Marion

    2010-01-01

    Trajectories of children's temperamental reactivity (negative affectivity and surgency) were examined in a community sample of 370 children across the ages of 4 to 7 with hierarchical linear modeling. Children's physiological reactivity (respiratory sinus arrhythmia [RSA]), physiological regulation ([delta]RSA), and maternal parenting behavior…

  15. [An overview on the physiological and ecological adaptation mechanisms of the overwinter ticks].

    Science.gov (United States)

    Yu, Zhi-jun; Yang, Xiao-long; Chen, Jie; Liu, Jing-ze

    2014-10-01

    The current paper introduces the recent research and development on the cryobiology of ticks, based on their overwinter behavior strategy and biochemical and physiological adaptation mechanisms, and provides detail information on the cold hardiness, biochemical and physiological mechanisms, the relationship between cold hardiness and diapause, which will give theoretical clues for subsequent research on the molecular regulation of cold hardiness of ticks.

  16. GABA signalling modulates plant growth by directly regulating the activity of plant-specific anion transporters.

    Science.gov (United States)

    Ramesh, Sunita A; Tyerman, Stephen D; Xu, Bo; Bose, Jayakumar; Kaur, Satwinder; Conn, Vanessa; Domingos, Patricia; Ullah, Sana; Wege, Stefanie; Shabala, Sergey; Feijó, José A; Ryan, Peter R; Gilliham, Matthew; Gillham, Matthew

    2015-07-29

    The non-protein amino acid, gamma-aminobutyric acid (GABA) rapidly accumulates in plant tissues in response to biotic and abiotic stress, and regulates plant growth. Until now it was not known whether GABA exerts its effects in plants through the regulation of carbon metabolism or via an unidentified signalling pathway. Here, we demonstrate that anion flux through plant aluminium-activated malate transporter (ALMT) proteins is activated by anions and negatively regulated by GABA. Site-directed mutagenesis of selected amino acids within ALMT proteins abolishes GABA efficacy but does not alter other transport properties. GABA modulation of ALMT activity results in altered root growth and altered root tolerance to alkaline pH, acid pH and aluminium ions. We propose that GABA exerts its multiple physiological effects in plants via ALMT, including the regulation of pollen tube and root growth, and that GABA can finally be considered a legitimate signalling molecule in both the plant and animal kingdoms.

  17. Multiple sclerosis

    DEFF Research Database (Denmark)

    Stenager, Egon; Stenager, E N; Knudsen, Lone

    1994-01-01

    In a cross-sectional study of 117 randomly selected patients (52 men, 65 women) with definite multiple sclerosis, it was found that 76 percent were married or cohabitant, 8 percent divorced. Social contacts remained unchanged for 70 percent, but outgoing social contacts were reduced for 45 percent......, need for structural changes in home and need for pension became greater with increasing physical handicap. No significant differences between gender were found. It is concluded that patients and relatives are under increased social strain, when multiple sclerosis progresses to a moderate handicap...

  18. Physiology of fish endocrine pancreas.

    Science.gov (United States)

    Plisetskaya, E M

    1989-06-01

    From the very beginning of physiological studies on the endocine pancreas, fish have been used as experimental subjects. Fish insulin was one of the first vertebrate insulins isolated and one of the first insulins whose primary and then tertiary structures were reported. Before a second pancreatic hormone, glucagon, was characterized, a physiologically active 'impurity', similar to that in mammalian insulin preparations, was found in fish insulins.Fish have become the most widely used model for studies of biosynthesis and processing of the pancreatic hormones. It seems inconceivable, therefore, that until the recent past cod and tuna insulins have been the only purified piscine islet hormones available for physiological experiments. The situation has changed remarkably during the last decade.In this review the contemporary status of physiological studies on the fish pancreas is outlined with an emphasis on the following topics: 1) contents of pancreatic peptides in plasma and in islet tissue; 2) actions of piscine pancreatic hormones in fish; 3) specific metabolic consequences of an acute insufficiency of pancreatic peptides; 4) functional interrelations among pancreatic peptides which differ from those of mammals. The pitfalls, lacunae and the perspectives of contemporary physiological studies on fish endocrine pancreas are outlined.

  19. Interorgan Communication Pathways in Physiology: Focus on Drosophila.

    Science.gov (United States)

    Droujinine, Ilia A; Perrimon, Norbert

    2016-11-23

    Studies in mammals and Drosophila have demonstrated the existence and significance of secreted factors involved in communication between distal organs. In this review, primarily focusing on Drosophila, we examine the known interorgan communication factors and their functions, physiological inducers, and integration in regulating physiology. Moreover, we describe how organ-sensing screens in Drosophila can systematically identify novel conserved interorgan communication factors. Finally, we discuss how interorgan communication enabled and evolved as a result of specialization of organs. Together, we anticipate that future studies will establish a model for metazoan interorgan communication network (ICN) and how it is deregulated in disease.

  20. Hypoxic regulation of the noncoding genome and NEAT1

    Science.gov (United States)

    Choudhry, Hani

    2016-01-01

    Activation of hypoxia pathways is both associated with and contributes to an aggressive phenotype across multiple types of solid cancers. The regulation of gene transcription by hypoxia-inducible factor (HIF) is a key element in this response. HIF directly upregulates the expression of many hundreds of protein-coding genes, which act to both improve oxygen delivery and to reduce oxygen demand. However, it is now becoming apparent that many classes of noncoding RNAs are also regulated by hypoxia, with sev