Activities and Effects of Ergot Alkaloids on Livestock Physiology and Production

PubMed Central

Klotz, James L.

2015-01-01

Consumption of feedstuffs contaminated with ergot alkaloids has a broad impact on many different physiological mechanisms that alters the homeostasis of livestock. This change in homeostasis causes an increased sensitivity in livestock to perturbations in the ambient environment, resulting in an increased sensitivity to such stressors. This ultimately results in large financial losses in the form of production losses to livestock producers around the world. This review will focus on the underlying physiological mechanisms that are affected by ergot alkaloids that lead to decreases in livestock production. PMID:26226000

Exercise-Induced Changes in Glucose Metabolism Promote Physiological Cardiac Growth

PubMed Central

Gibb, Andrew A.; Epstein, Paul N.; Uchida, Shizuka; Zheng, Yuting; McNally, Lindsey A.; Obal, Detlef; Katragadda, Kartik; Trainor, Patrick; Conklin, Daniel J.; Brittian, Kenneth R.; Tseng, Michael T.; Wang, Jianxun; Jones, Steven P.; Bhatnagar, Aruni

2017-01-01

Background: Exercise promotes metabolic remodeling in the heart, which is associated with physiological cardiac growth; however, it is not known whether or how physical activity–induced changes in cardiac metabolism cause myocardial remodeling. In this study, we tested whether exercise-mediated changes in cardiomyocyte glucose metabolism are important for physiological cardiac growth. Methods: We used radiometric, immunologic, metabolomic, and biochemical assays to measure changes in myocardial glucose metabolism in mice subjected to acute and chronic treadmill exercise. To assess the relevance of changes in glycolytic activity, we determined how cardiac-specific expression of mutant forms of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase affect cardiac structure, function, metabolism, and gene programs relevant to cardiac remodeling. Metabolomic and transcriptomic screenings were used to identify metabolic pathways and gene sets regulated by glycolytic activity in the heart. Results: Exercise acutely decreased glucose utilization via glycolysis by modulating circulating substrates and reducing phosphofructokinase activity; however, in the recovered state following exercise adaptation, there was an increase in myocardial phosphofructokinase activity and glycolysis. In mice, cardiac-specific expression of a kinase-deficient 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase transgene (GlycoLo mice) lowered glycolytic rate and regulated the expression of genes known to promote cardiac growth. Hearts of GlycoLo mice had larger myocytes, enhanced cardiac function, and higher capillary-to-myocyte ratios. Expression of phosphatase-deficient 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase in the heart (GlycoHi mice) increased glucose utilization and promoted a more pathological form of hypertrophy devoid of transcriptional activation of the physiological cardiac growth program. Modulation of phosphofructokinase activity was sufficient to regulate the glucose–fatty acid cycle in the heart; however, metabolic inflexibility caused by invariantly low or high phosphofructokinase activity caused modest mitochondrial damage. Transcriptomic analyses showed that glycolysis regulates the expression of key genes involved in cardiac metabolism and remodeling. Conclusions: Exercise-induced decreases in glycolytic activity stimulate physiological cardiac remodeling, and metabolic flexibility is important for maintaining mitochondrial health in the heart. PMID:28860122

Neo-Darwinism, the Modern Synthesis and selfish genes: are they of use in physiology?

PubMed Central

Noble, Denis

2011-01-01

This article argues that the gene-centric interpretations of evolution, and more particularly the selfish gene expression of those interpretations, form barriers to the integration of physiological science with evolutionary theory. A gene-centred approach analyses the relationships between genotypes and phenotypes in terms of differences (change the genotype and observe changes in phenotype). We now know that, most frequently, this does not correctly reveal the relationships because of extensive buffering by robust networks of interactions. By contrast, understanding biological function through physiological analysis requires an integrative approach in which the activity of the proteins and RNAs formed from each DNA template is analysed in networks of interactions. These networks also include components that are not specified by nuclear DNA. Inheritance is not through DNA sequences alone. The selfish gene idea is not useful in the physiological sciences, since selfishness cannot be defined as an intrinsic property of nucleotide sequences independently of gene frequency, i.e. the ‘success’ in the gene pool that is supposed to be attributable to the ‘selfish’ property. It is not a physiologically testable hypothesis. PMID:21135048

Neo-Darwinism, the modern synthesis and selfish genes: are they of use in physiology?

PubMed

Noble, Denis

2011-03-01

This article argues that the gene-centric interpretations of evolution, and more particularly the selfish gene expression of those interpretations, form barriers to the integration of physiological science with evolutionary theory. A gene-centred approach analyses the relationships between genotypes and phenotypes in terms of differences (change the genotype and observe changes in phenotype). We now know that, most frequently, this does not correctly reveal the relationships because of extensive buffering by robust networks of interactions. By contrast, understanding biological function through physiological analysis requires an integrative approach in which the activity of the proteins and RNAs formed from each DNA template is analysed in networks of interactions. These networks also include components that are not specified by nuclear DNA. Inheritance is not through DNA sequences alone. The selfish gene idea is not useful in the physiological sciences, since selfishness cannot be defined as an intrinsic property of nucleotide sequences independently of gene frequency, i.e. the 'success' in the gene pool that is supposed to be attributable to the 'selfish' property. It is not a physiologically testable hypothesis.

Endothelium and Its Alterations in Cardiovascular Diseases: Life Style Intervention

PubMed Central

Paganelli, Corrado; Buffoli, Barbara; Rodella, Luigi Fabrizio; Rezzani, Rita

2014-01-01

The endothelium, which forms the inner cellular lining of blood vessels and lymphatics, is a highly metabolically active organ that is involved in many physiopathological processes, including the control of vasomotor tone, barrier function, leukocyte adhesion, and trafficking and inflammation. In this review, we summarized and described the following: (i) endothelial cell function in physiological conditions and (ii) endothelial cell activation and dysfunction in the main cardiovascular diseases (such as atherosclerosis, and hypertension) and to diabetes, cigarette smoking, and aging physiological process. Finally, we presented the currently available evidence that supports the beneficial effects of physical activity and various dietary compounds on endothelial functions. PMID:24719887

Subtype-specific control of P2X receptor channel signaling by ATP and Mg2+.

PubMed

Li, Mufeng; Silberberg, Shai D; Swartz, Kenton J

2013-09-03

The identity and forms of activating ligands for ion channels are fundamental to their physiological roles in rapid electrical signaling. P2X receptor channels are ATP-activated cation channels that serve important roles in sensory signaling and inflammation, yet the active forms of the nucleotide are unknown. In physiological solutions, ATP is ionized and primarily found in complex with Mg(2+). Here we investigated the active forms of ATP and found that the action of MgATP(2-) and ATP(4-) differs between subtypes of P2X receptors. The slowly desensitizing P2X2 receptor can be activated by free ATP, but MgATP(2-) promotes opening with very low efficacy. In contrast, both free ATP and MgATP(2-) robustly open the rapidly desensitizing P2X3 subtype. A further distinction between these two subtypes is the ability of Mg(2+) to regulate P2X3 through a distinct allosteric mechanism. Importantly, heteromeric P2X2/3 channels present in sensory neurons exhibit a hybrid phenotype, characterized by robust activation by MgATP(2-) and weak regulation by Mg(2+). These results reveal the existence of two classes of homomeric P2X receptors with differential sensitivity to MgATP(2-) and regulation by Mg(2+), and demonstrate that both restraining mechanisms can be disengaged in heteromeric channels to form fast and sensitive ATP signaling pathways in sensory neurons.

Subtype-specific control of P2X receptor channel signaling by ATP and Mg2+

PubMed Central

Li, Mufeng; Silberberg, Shai D.; Swartz, Kenton J.

2013-01-01

The identity and forms of activating ligands for ion channels are fundamental to their physiological roles in rapid electrical signaling. P2X receptor channels are ATP-activated cation channels that serve important roles in sensory signaling and inflammation, yet the active forms of the nucleotide are unknown. In physiological solutions, ATP is ionized and primarily found in complex with Mg2+. Here we investigated the active forms of ATP and found that the action of MgATP2− and ATP4− differs between subtypes of P2X receptors. The slowly desensitizing P2X2 receptor can be activated by free ATP, but MgATP2− promotes opening with very low efficacy. In contrast, both free ATP and MgATP2− robustly open the rapidly desensitizing P2X3 subtype. A further distinction between these two subtypes is the ability of Mg2+ to regulate P2X3 through a distinct allosteric mechanism. Importantly, heteromeric P2X2/3 channels present in sensory neurons exhibit a hybrid phenotype, characterized by robust activation by MgATP2− and weak regulation by Mg2+. These results reveal the existence of two classes of homomeric P2X receptors with differential sensitivity to MgATP2− and regulation by Mg2+, and demonstrate that both restraining mechanisms can be disengaged in heteromeric channels to form fast and sensitive ATP signaling pathways in sensory neurons. PMID:23959888

Membrane lipid-protein interactions modify the regulatory role of adenosine-deaminase complexing protein: a phase fluorometry study of a malignancy marker

NASA Astrophysics Data System (ADS)

Parola, Abraham H.; Porat, Nurith; Caiolfa, Valeria R.; Gill, David; Kiesow, Lutz A.; Weisman, Mathew; Nemschitz, S.; Yaron, Dahlia; Singer, Karen; Solomon, Ethel

1990-05-01

The role of membrane lipid-protein interactions in malignant cell transformation was examined with adenosine deaminase (ADA) as a representative membrane protein. ADA's activity changes dramatically in transformed cells and accordingly it is a malignancy marker. Yet, the mechanisms controlling its variable activity are unknown. We undertook the spectroscopic deciphering of its interactions with its lipidic environment in normal and malignant cells. ADA exists in two interconvertible forms, small (45 KD) and large (21OKD). The large form consists of two small catalytic subunits (55-ADA) and a dimeric complexing protein ADCP. The physiological role of ADCP was not known either. Our studies were carried out at three levels.: 1. Solution enzyme kinetics, 2. The interaction of 55-ADA with ADCP reconstituted in liposomes: Effect of cholesterol and 3. Multifrequency phase modulation spectrofluorometry of pyrene-labeled 55-ADA bound to ADCP on the membranes of normal and RSV or RSV Ts68 transformed chick embryo fibroblasts. We found: 1. ADCP has an allosteric regulatory role on 55-ADA, which may be of physiological relevance: It inhibits 55-ADA activity at low physiological adenosine concentrations but accelerates deamination at high substrate concentration. 2. When reconstituted in DMPC liposomes, it retains 55-ADA activity (in its absence the activity is lost) and upon rigidification with cholesterol, a three fold increase in 55-ADA activity is attained, contrary to ADCP's regulatory activity when free of lipids. 3. The reduced ADA activity in transformed chick embryo fibroblasts is associated with increased membrane lipid fluidity (reduced order parameter), reduced accessibility of ADCP and increase rotational dynamics of the complex. We thus obtained spectroscopic deciphering of the vertical motion of ADCP, controlled by lipid-protein interaction, resulting in variable activity of this malignancy marker.

In silico, in vitro and antifungal activity of the surface layers formed on zinc during this biomaterial degradation

NASA Astrophysics Data System (ADS)

Alves, Marta M.; Marques, Luísa M.; Nogueira, Isabel; Santos, Catarina F.; Salazar, Sara B.; Eugénio, Sónia; Mira, Nuno P.; Montemor, M. F.

2018-07-01

Zinc (Zn) has been proposed as an alternative metallic biodegradable material to support transient wound-healing processes. Once a Zn piece is implanted inside the organism the degradation will depend upon the physiological surrounding environment. This, by modulating the composition of the surface layers formed on Zn devices, will govern the subsequent interactions with the surrounding living cells (e.g. biocompatibility and/or antifungal behaviour). In silico simulation of an implanted Zn piece at bone-muscle interface or inside the bone yielded the preferential precipitation of simonkolleite or zincite, respectively. To study the impact of these surface layers in the in vitro behaviour of Zn biomaterials, simonkolleite and zincite where synthesised. The successful production of simonkolleite or zincite was confirmed by an extensive physicochemical characterization. An in vitro layer formed on the top of these surface layers revealed that simonkolleite was rather inert, while zincite yielded a complex matrix containing hydroxyapatite, an important bone analogue. When analysing the "anti-biofilm" activity simonkolleite stood out for its activity against an important pathogenic fungi involved in implant-device infections, Candida albicans. The possible physiological implications of these findings are discussed.

Syndecan-4 Signaling Is Required for Exercise-Induced Cardiac Hypertrophy

PubMed Central

Xie, Jun; He, Guixin; Chen, Qinhua; Sun, Jiayin; Dai, Qin; Lu, Jianrong; Li, Guannan; Wu, Han; Li, Ran; Chen, Jianzhou; Xu, Wei; Xu, Biao

2016-01-01

Cardiac hypertrophy can be broadly classified as either physiological or pathological. Physiological stimuli such as exercise cause adaptive cardiac hypertrophy and normal heart function. Pathological stimuli including hypertension and aortic valvular stenosis cause maladaptive cardiac remodeling and ultimately heart failure. Syndecan-4 (synd4) is a transmembrane proteoglycan identified as being involved in cardiac adaptation after injury, but whether it takes part in physiological cardiac hypertrophy is unclear. We observed upregulation of synd4 in exercise-induced hypertrophic myocardium. To evaluate the role of synd4 in the physiological form of cardiac hypertrophy, mice lacking synd4 (synd4–/–) were exercised by swimming for 4 wks. Ultrasonic cardiogram (UCG) and histological analysis revealed that swimming induced the hypertrophic phenotype but was blunted in synd4–/– compared with wild-type (WT) mice. The swimming-induced activation of Akt, a key molecule in physiological hypertrophy was also more decreased than in WT controls. In cultured cardiomyocytes, synd4 overexpression could induce cell enlargement, protein synthesis and distinct physiological molecular alternation. Akt activation also was observed in synd4-overexpressed cardiomyocytes. Furthermore, inhibition of protein kinase C (PKC) prevented the synd4-induced hypertrophic phenotype and Akt phosphorylation. This study identified an essential role of synd4 in mediation of physiological cardiac hypertrophy. PMID:26835698

Partial biochemical characterization of a metalloproteinase from the bloodstream forms of Trypanosoma brucei brucei parasites.

PubMed

de Sousa, Karina Pires; Atouguia, Jorge; Silva, Marcelo Sousa

2010-05-01

Metalloproteinases (MMP) belong to the family of cation dependent endopeptidases that degrade matrices at physiological pH and to cleave extracellular matrix proteins. They play an important role in diverse physiological and pathological processes; not only there diverse types of MMP differ in structure and functionally, but also their enzymatic activity is regulated at multiple levels. Trying to shed some light over the processes that govern the pathology of African Trypanosomiasis, the aim of the present study was to examine the proteolytic activity of the crude trypanosome protein extract obtained from the bloodstream forms of Trypanosoma brucei brucei parasites. We hereby report the partial biochemical characterization of a neutral Trypanosoma brucei-metalloproteinase that displays marked proteolytic activities on gelatin and casein, with a molecular mass of approximately 40 kDa, whose activity is strongly dependent of pH and temperature. Furthermore, we show that this activity can be inhibited by classical MMP inhibitors such as EDTA, EGTA, phenantroline, and also by tetracycline and derivatives. This study has a relevant role in the search for new therapeutical targets, for the use of metalloproteinases inhibitors as treatment strategies, or as enhancement to trypanocidal drugs used in the treatment of the disease.

AmTAR2: Functional characterization of a honeybee tyramine receptor stimulating adenylyl cyclase activity.

PubMed

Reim, Tina; Balfanz, Sabine; Baumann, Arnd; Blenau, Wolfgang; Thamm, Markus; Scheiner, Ricarda

2017-01-01

The biogenic monoamines norepinephrine and epinephrine regulate important physiological functions in vertebrates. Insects such as honeybees do not synthesize these neuroactive substances. Instead, they employ octopamine and tyramine for comparable physiological functions. These biogenic amines activate specific guanine nucleotide-binding (G) protein-coupled receptors (GPCRs). Based on pharmacological data obtained on heterologously expressed receptors, α- and β-adrenergic-like octopamine receptors are better activated by octopamine than by tyramine. Conversely, GPCRs forming the type 1 tyramine receptor clade (synonymous to octopamine/tyramine receptors) are better activated by tyramine than by octopamine. More recently, receptors were characterized which are almost exclusively activated by tyramine, thus forming an independent type 2 tyramine receptor clade. Functionally, type 1 tyramine receptors inhibit adenylyl cyclase activity, leading to a decrease in intracellular cAMP concentration ([cAMP] i ). Type 2 tyramine receptors can mediate Ca 2+ signals or both Ca 2+ signals and effects on [cAMP] i . We here provide evidence that the honeybee tyramine receptor 2 (AmTAR2), when heterologously expressed in flpTM cells, exclusively causes an increase in [cAMP] i . The receptor displays a pronounced preference for tyramine over octopamine. Its activity can be blocked by a series of established antagonists, of which mianserin and yohimbine are most efficient. The functional characterization of two tyramine receptors from the honeybee, AmTAR1 (previously named AmTYR1) and AmTAR2, which respond to tyramine by changing cAMP levels in opposite direction, is an important step towards understanding the actions of tyramine in honeybee behavior and physiology, particularly in comparison to the effects of octopamine. Copyright © 2016 Elsevier Ltd. All rights reserved.

The Impact of Continuous and Interval Cycle Exercise on Affect and Enjoyment

ERIC Educational Resources Information Center

Kilpatrick, Marcus W.; Greeley, Samuel J.; Collins, Larry H.

2015-01-01

Rates of physical activity remain low despite public health efforts. One form of physical activity that provides significant physiological benefit but has not been evaluated in terms of affective and enjoyment responses is interval exercise. Purpose: The purpose of this study was to compare affect and enjoyment assessed before, during, and after…

Physiological Parameters for Oral Delivery and In vitro Testing

PubMed Central

Mudie, Deanna M.; Amidon, Gordon L.; Amidon, Gregory E.

2010-01-01

Pharmaceutical solid oral dosage forms must undergo dissolution in the intestinal fluids of the gastrointestinal tract before they can be absorbed and reach the systemic circulation. Therefore, dissolution is a critical part of the drug-delivery process. The rate and extent of drug dissolution and absorption depend on the characteristics of the active ingredient as well as properties of the dosage form. Just as importantly, characteristics of the physiological environment such as buffer species, pH, bile salts, gastric emptying rate, intestinal motility, and hydrodynamics can significantly impact dissolution and absorption. While significant progress has been made since 1970 when the first compendial dissolution test was introduced (USP Apparatus 1), current dissolution testing does not take full advantage of the extensive physiologic information that is available. For quality control purposes, where the question is one of lot-to-lot consistency in performance, using nonphysiologic test conditions that match drug and dosage form properties with practical dissolution media and apparatus may be appropriate. However, where in vitro – in vivo correlations are desired, it is logical to consider and utilize knowledge of the in vivo condition. This publication critically reviews the literature that is relevant to oral human drug delivery. Physiologically relevant information must serve as a basis for the design of dissolution test methods and systems that are more representative of the human condition. As in vitro methods advance in their physiological relevance, better in vitro - in vivo correlations will be possible. This will, in turn, lead to in vitro systems that can be utilized to more effectively design dosage forms that have improved and more consistent oral bioperformance. PMID:20822152

Immunohistochemical detection of active transforming growth factor-beta in situ using engineered tissue

NASA Technical Reports Server (NTRS)

Barcellos-Hoff, M. H.; Ehrhart, E. J.; Kalia, M.; Jirtle, R.; Flanders, K.; Tsang, M. L.; Chatterjee, A. (Principal Investigator)

1995-01-01

The biological activity of transforming growth factor-beta 1 (TGF-beta) is governed by dissociation from its latent complex. Immunohistochemical discrimination of active and latent TGF-beta could provide insight into TGF-beta activation in physiological and pathological processes. However, evaluation of immunoreactivity specificity in situ has been hindered by the lack of tissue in which TGF-beta status is known. To provide in situ analysis of antibodies to differentiate between these functional forms, we used xenografts of human tumor cells modified by transfection to overexpress latent TGF-beta or constitutively active TGF-beta. This comparison revealed that, whereas most antibodies did not differentiate between TGF-beta activation status, the immunoreactivity of some antibodies was activation dependent. Two widely used peptide antibodies to the amino-terminus of TGF-beta, LC(1-30) and CC(1-30) showed marked preferential immunoreactivity with active TGF-beta versus latent TGF-beta in cryosections. However, in formalin-fixed, paraffin-embedded tissue, discrimination of active TGF-beta by CC(1-30) was lost and immunoreactivity was distinctly extracellular, as previously reported for this antibody. Similar processing-dependent extracellular localization was found with a neutralizing antibody raised to recombinant TGF-beta. Antigen retrieval recovered cell-associated immunoreactivity of both antibodies. Two antibodies to peptides 78-109 showed mild to moderate preferential immunoreactivity with active TGF-beta only in paraffin sections. LC(1-30) was the only antibody tested that discriminated active from latent TGF-beta in both frozen and paraffin-embedded tissue. Thus, in situ discrimination of active versus latent TGF-beta depends on both the antibody and tissue preparation. We propose that tissues engineered to express a specific form of a given protein provide a physiological setting in which to evaluate antibody reactivity with specific functional forms of a protein.

Optogenetics and pharmacogenetics: principles and applications.

PubMed

Jiang, Jingwei; Cui, Huxing; Rahmouni, Kamal

2017-12-01

Remote and selective spatiotemporal control of the activity of neurons to regulate behavior and physiological functions has been a long-sought goal in system neuroscience. Identification and subsequent bioengineering of light-sensitive ion channels (e.g., channelrhodopsins, halorhodopsin, and archaerhodopsins) from the bacteria have made it possible to use light to artificially modulate neuronal activity, namely optogenetics. Recent advance in genetics has also allowed development of novel pharmacological tools to selectively and remotely control neuronal activity using engineered G protein-coupled receptors, which can be activated by otherwise inert drug-like small molecules such as the designer receptors exclusively activated by designer drug, a form of chemogenetics. The cutting-edge optogenetics and pharmacogenetics are powerful tools in neuroscience that allow selective and bidirectional modulation of the activity of defined populations of neurons with unprecedented specificity. These novel toolboxes are enabling significant advances in deciphering how the nervous system works and its influence on various physiological processes in health and disease. Here, we discuss the fundamental elements of optogenetics and chemogenetics approaches and some of the applications that yielded significant advances in various areas of neuroscience and beyond. Copyright © 2017 the American Physiological Society.

Saccharomyces cerevisiae Differential Functionalization of Presumed ScALT1 and ScALT2 Alanine Transaminases Has Been Driven by Diversification of Pyridoxal Phosphate Interactions

PubMed Central

Rojas-Ortega, Erendira; Aguirre-López, Beatriz; Reyes-Vivas, Horacio; González-Andrade, Martín; Campero-Basaldúa, Jose C.; Pardo, Juan P.; González, Alicia

2018-01-01

Saccharomyces cerevisiae arose from an interspecies hybridization (allopolyploidiza-tion), followed by Whole Genome Duplication. Diversification analysis of ScAlt1/ScAlt2 indicated that while ScAlt1 is an alanine transaminase, ScAlt2 lost this activity, constituting an example in which one of the members of the gene pair lacks the apparent ancestral physiological role. This paper analyzes structural organization and pyridoxal phosphate (PLP) binding properties of ScAlt1 and ScAlt2 indicating functional diversification could have determined loss of ScAlt2 alanine transaminase activity and thus its role in alanine metabolism. It was found that ScAlt1 and ScAlt2 are dimeric enzymes harboring 67% identity and intact conservation of the catalytic residues, with very similar structures. However, tertiary structure analysis indicated that ScAlt2 has a more open conformation than that of ScAlt1 so that under physiological conditions, while PLP interaction with ScAlt1 allows the formation of two tautomeric PLP isomers (enolimine and ketoenamine) ScAlt2 preferentially forms the ketoenamine PLP tautomer, indicating a modified polarity of the active sites which affect the interaction of PLP with these proteins, that could result in lack of alanine transaminase activity in ScAlt2. The fact that ScAlt2 forms a catalytically active Schiff base with PLP and its position in an independent clade in “sensu strictu” yeasts suggests this protein has a yet undiscovered physiological function. PMID:29867852

Insights into the mechanism and catalysis of oxime coupling chemistry at physiological pH.

PubMed

Wang, Shujiang; Gurav, Deepanjali; Oommen, Oommen P; Varghese, Oommen P

2015-04-07

The dynamic covalent-coupling reaction involving α-effect nucleophiles has revolutionized bioconjugation approaches, due to its ease and high efficiency. Key to its success is the discovery of aniline as a nucleophilic catalyst, which made this reaction feasible under physiological conditions. Aniline however, is not so effective for keto substrates. Here, we investigate the mechanism of aniline activation in the oxime reaction with aldehyde and keto substrates. We also present carboxylates as activating agents that can promote the oxime reaction with both aldehyde and keto substrates at physiological pH. This rate enhancement circumvents the influence of α-effect by forming H-bonds with the rate-limiting intermediate, which drives the reaction to completion. The combination of aniline and carboxylates had a synergistic effect, resulting in a ∼14-31-fold increase in reaction rate at pD 7.4 with keto substrates. The biocompatibility and efficiency of carboxylate as an activating agent is demonstrated by performing cell-surface oxime labeling at physiological pH using acetate, which showed promising results that were comparable with aniline. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

A Futile Redox Cycle Involving Neuroglobin Observed at Physiological Temperature.

PubMed

Liu, Anyang; Brittain, Thomas

2015-08-24

Previous studies identifying the potential anti-apoptotic role of neuroglobin raise the question as to how cells might employ neuroglobin to avoid the apoptotic impact of acute hypoxia whilst also avoiding chronic enhancement of tumour formation. We show that under likely physiological conditions neuroglobin can take part in a futile redox cycle. Determination of the rate constants for each of the steps in the cycle allows us to mathematically model the steady state concentration of the active anti-apoptotic ferrous form of neuroglobin under various conditions. Under likely normal physiological conditions neuroglobin is shown to be present in the ferrous state at approximately 30% of its total cellular concentration. Under hypoxic conditions this rapidly rises to approximately 80%. Temporal analysis of this model indicates that the transition from low concentrations to high concentration of ferrous neuroglobin occurs on the seconds time scale. These findings indicate a potential control model for the anti-apoptotic activity of neuroglobin, under likely physiological conditions, whereby, in normoxic conditions, the anti-apoptotic activity of neuroglobin is maintained at a low level, whilst immediately a transition occurs to a hypoxic situation, as might arise during stroke, the anti-apoptotic activity is drastically increased. In this way the cell avoids unwanted increased oncogenic potential under normal conditions, but the rapid activation of neuroglobin provides anti-apoptotic protection in times of acute hypoxia.

Home-Based vs. Laboratory-Based Practical Activities in the Learning of Human Physiology: The Perception of Students

ERIC Educational Resources Information Center

Neves, Ben-Hur S.; Altermann, Caroline; Gonçalves, Rithiele; Lara, Marcus Vinícius; Mello-Carpes, Pâmela B.

2017-01-01

Different tools have been used to facilitate the teaching and learning process in different areas of knowledge. Practical activities represent a form of teaching in which students not only listen to theoretical concepts but are also able to link theory and practice, and their importance in the biological sciences is notable. Sometimes, however,…

Modeling activated states of GPCRs: the rhodopsin template.

PubMed

Niv, Masha Y; Skrabanek, Lucy; Filizola, Marta; Weinstein, Harel

2006-01-01

Activation of G Protein-Coupled Receptors (GPCRs) is an allosteric mechanism triggered by ligand binding and resulting in conformational changes transduced by the transmembrane domain. Models of the activated forms of GPCRs have become increasingly necessary for the development of a clear understanding of signal propagation into the cell. Experimental evidence points to a multiplicity of conformations related to the activation of the receptor, rendered important physiologically by the suggestion that different conformations may be responsible for coupling to different signaling pathways. In contrast to the inactive state of rhodopsin (RHO) for which several high quality X-ray structures are available, the structure-related information for the active states of rhodopsin and all other GPCRs is indirect. We have collected and stored such information in a repository we maintain for activation-specific structural data available for rhodopsin-like GPCRs, http://www.physiology.med.cornell.edu/GPCRactivation/gpcrindex.html . Using these data as structural constraints, we have applied Simulated Annealing Molecular Dynamics to construct a number of different active state models of RHO starting from the known inactive structure. The common features of the models indicate that TM3 and TM5 play an important role in activation, in addition to the well-established rearrangement of TM6. Some of the structural changes observed in these models occur in regions that were not involved in the constraints, and have not been previously tested experimentally; they emerge as interesting candidates for further experimental exploration of the conformational space of activated GPCRs. We show that none of the normal modes calculated from the inactive structure has a dominant contribution along the path of conformational rearrangement from inactive to the active forms of RHO in the models. This result may differentiate rhodopsin from other GPCRs, and the reasons for this difference are discussed in the context of the structural properties and the physiological function of the protein.

The mechanism of formation, structure and physiological relevance of covalent hemoglobin attachment to the erythrocyte membrane.

PubMed

Welbourn, Elizabeth M; Wilson, Michael T; Yusof, Ashril; Metodiev, Metodi V; Cooper, Chris E

2017-02-01

Covalent hemoglobin binding to membranes leads to band 3 (AE1) clustering and the removal of erythrocytes from the circulation; it is also implicated in blood storage lesions. Damaged hemoglobin, with the heme being in a redox and oxygen-binding inactive hemichrome form, has been implicated as the binding species. However, previous studies used strong non-physiological oxidants. In vivo hemoglobin is constantly being oxidised to methemoglobin (ferric), with around 1% of hemoglobin being in this form at any one time. In this study we tested the ability of the natural oxidised form of hemoglobin (methemoglobin) in the presence or absence of the physiological oxidant hydrogen peroxide to initiate membrane binding. The higher the oxidation state of hemoglobin (from Fe(III) to Fe(V)) the more binding was observed, with approximately 50% of this binding requiring reactive sulphydryl groups. The hemoglobin bound was in a high molecular weight complex containing spectrin, ankyrin and band 4.2, which are common to one of the cytoskeletal nodes. Unusually, we showed that hemoglobin bound in this way was redox active and capable of ligand binding. It can initiate lipid peroxidation showing the potential to cause cell damage. In vivo oxidative stress studies using extreme endurance exercise challenges showed an increase in hemoglobin membrane binding, especially in older cells with lower levels of antioxidant enzymes. These are then targeted for destruction. We propose a model where mild oxidative stress initiates the binding of redox active hemoglobin to the membrane. The maximum lifetime of the erythrocyte is thus governed by the redox activity of the cell; from the moment of its release into the circulation the timer is set. Copyright © 2016. Published by Elsevier Inc.

Of channels and pumps: different ways to boost the aldosterone?

PubMed

Bandulik, S

2017-07-01

The mineralocorticoid aldosterone is a major factor controlling the salt and water balance and thereby also the arterial blood pressure. Accordingly, primary aldosteronism (PA) characterized by an inappropriately high aldosterone secretion is the most common form of secondary hypertension. The physiological stimulation of aldosterone synthesis in adrenocortical glomerulosa cells by angiotensin II and an increased plasma K + concentration depends on a membrane depolarization and an increase in the cytosolic Ca 2+ activity. Recurrent gain-of-function mutations of ion channels and transporters have been identified in a majority of cases of aldosterone-producing adenomas and in familial forms of PA. In this review, the physiological role of these genes in the regulation of aldosterone synthesis and the altered function of the mutant proteins as well are described. The specific changes of the membrane potential and the cellular ion homoeostasis in adrenal cells expressing the different mutants are compared, and their impact on autonomous aldosterone production and proliferation is discussed. © 2016 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.

Specialised sympathetic neuroeffector associations in immature rat iris arterioles

PubMed Central

SANDOW, SHAUN L.; HILL, CARYL E.

1999-01-01

Sympathetic nerve-mediated vasoconstriction in iris arterioles of mature rats occurs via the activation of α1B-adrenoceptors alone, while in immature rat iris arterioles, vasoconstriction occurs via activation of both α1- and α2-adrenoceptors. In mature rats the vast majority of sympathetic varicosities form close neuroeffector junctions. Serial section electron microscopy of 14 d iris arterioles has been used to determine whether restriction in physiological receptor types with age may result from the establishment of these close neuroeffector junctions. Ninety varicosities which lay within 4 μm of arteriolar smooth muscle were followed for their entire length. Varicosities rarely contained dense cored vesicles even after treatment with 5-hydroxydopamine. 47% of varicosities formed close associations with muscle cells and 88% formed close associations with muscle cells or melanocytes. Varicosities in bundles were as likely as single varicosities to form close associations with vascular smooth muscle cells, although the distribution of synaptic vesicles in single varicosities did not show the asymmetric accumulation towards the smooth muscle cells seen in the varicosities in bundles which were frequently clustered together. We conclude that restriction of physiological receptor types during development does not appear to correlate with the establishment of close neuroeffector junctions, although changes in presynaptic structures may contribute to the refinement of postsynaptic responses. PMID:10529061

Stability of dendriplexes formed by anti-HIV genetic material and poly(propylene imine) dendrimers in the presence of glucosaminoglycans.

PubMed

Szewczyk, Michal; Drzewinska, Joanna; Dzmitruk, Volha; Shcharbin, Dzmitry; Klajnert, Barbara; Appelhans, Dietmar; Bryszewska, Maria

2012-12-20

There are several barriers to the application of dendriplexes formed by poly(propylene imine) dendrimers and genetic material for gene therapy. One limitation is their interaction with extracellular matrix components such as glucosaminoglycans. These can displace the genetic material from the dendriplexes, affecting their transfection activity. In this study, we analyzed the interaction between dendriplexes and the four main glucosaminoglycans (heparin, heparan sulfate, chondroitin sulfate, and hyaluronic acid) by fluorescence polarization and gel electrophoresis. Dendriplexes were formed by combining three anti-HIV antisense oligodeoxynucleotides with three poly(propylene imine) dendrimers of the fourth generation: unmodified and partially modified with maltose and maltotriose (open shell glycodendrimers). The data showed that the effect of glucosaminoglycans on dendriplexes depends on the glucosaminoglycan type and the oligosaccharide serving as the surface group of the dendrimer. Heparin at physiological concentrations destroys dendriplexes formed by open shell glycodendrimers, but dendriplexes based on unmodified poly(propylene imine) dendrimers are stable in its presence. The other glucosaminoglycans at physiological concentrations cannot destroy dendriplexes formed by any of the dendrimers studied.

Immunochemical approach to the problem of differential determination of natural forms of abscisic acid.

PubMed

Blintsov, A N; Gussakovskaya, M A

2004-10-01

An original modification of the standard ELISA procedure for differential determination of different forms of abscisic acid (ABA) is proposed. It is shown that endogenous forms of ABA may be quantitatively determined in plant tissues subjected to minimal treatment, without purification of the hormones and their chemical modification. The modification has been approved when analyzing changes in the content of different ABA forms in plant tissues differing in physiological activity. Quantitative differential determination of changes in the content of different ABA forms has been performed in ovaries of Triticum aestivum L. and Taraxacum officinale Web. in the period of activity of the ovule (from the moment of its activation to the beginning of division). It is shown that, despite the different types of reproduction in the species studied (amphimixis and apomixis), the time course of changes in the content of different forms of ABA in ovaries is similar, which is suggestive of a correlation between the activity of endogenous hormonal system and chronology of main events (e.g., the beginning of endospermogenesis) of the reproductive cycle.

Fermentation pH influences the physiological-state dynamics of Lactobacillus bulgaricus CFL1 during pH-controlled culture.

PubMed

Rault, Aline; Bouix, Marielle; Béal, Catherine

2009-07-01

This study aims at better understanding the effects of fermentation pH and harvesting time on Lactobacillus bulgaricus CFL1 cellular state in order to improve knowledge of the dynamics of the physiological state and to better manage starter production. The Cinac system and multiparametric flow cytometry were used to characterize and compare the progress of the physiological events that occurred during pH 6 and pH 5 controlled cultures. Acidification activity, membrane damage, enzymatic activity, cellular depolarization, intracellular pH, and pH gradient were determined and compared during growing conditions. Strong differences in the time course of viability, membrane integrity, and acidification activity were displayed between pH 6 and pH 5 cultures. As a main result, the pH 5 control during fermentation allowed the cells to maintain a more robust physiological state, with high viability and stable acidification activity throughout growth, in opposition to a viability decrease and fluctuation of activity at pH 6. This result was mainly explained by differences in lactate concentration in the culture medium and in pH gradient value. The elevated content of the ionic lactate form at high pH values damaged membrane integrity that led to a viability decrease. In contrast, the high pH gradient observed throughout pH 5 cultures was associated with an increased energetic level that helped the cells maintain their physiological state. Such results may benefit industrial starter producers and fermented-product manufacturers by allowing them to better control the quality of their starters, before freezing or before using them for food fermentation.

[18F]-FDG positron emission tomography--an established clinical tool opening a new window into exercise physiology.

PubMed

Rudroff, Thorsten; Kindred, John H; Kalliokoski, Kari K

2015-05-15

Positron emission tomography (PET) with [(18)F]-fluorodeoxyglucose (FDG) is an established clinical tool primarily used to diagnose and evaluate disease status in patients with cancer. PET imaging using FDG can be a highly valuable tool to investigate normal human physiology by providing a noninvasive, quantitative measure of glucose uptake into various cell types. Over the past years it has also been increasingly used in exercise physiology studies to identify changes in glucose uptake, metabolism, and muscle activity during different exercise modalities. Metabolically active cells transport FDG, an (18)fluorine-labeled glucose analog tracer, from the blood into the cells where it is then phosphorylated but not further metabolized. This metabolic trapping process forms the basis of this method's use during exercise. The tracer is given to a participant during an exercise task, and the actual PET imaging is performed immediately after the exercise. Provided the uptake period is of sufficient duration, and the imaging is performed shortly after the exercise; the captured image strongly reflects the metabolic activity of the cells used during the task. When combined with repeated blood sampling to determine tracer blood concentration over time, also known as the input function, glucose uptake rate of the tissues can be quantitatively calculated. This synthesis provides an accounting of studies using FDG-PET to measure acute exercise-induced skeletal muscle activity, describes the advantages and limitations of this imaging technique, and discusses its applications to the field of exercise physiology. Copyright © 2015 the American Physiological Society.

Class IA phosphoinositide 3-kinase regulates heart size and physiological cardiac hypertrophy.

PubMed

Luo, Ji; McMullen, Julie R; Sobkiw, Cassandra L; Zhang, Li; Dorfman, Adam L; Sherwood, Megan C; Logsdon, M Nicole; Horner, James W; DePinho, Ronald A; Izumo, Seigo; Cantley, Lewis C

2005-11-01

Class I(A) phosphoinositide 3-kinases (PI3Ks) are activated by growth factor receptors, and they regulate, among other processes, cell growth and organ size. Studies using transgenic mice overexpressing constitutively active and dominant negative forms of the p110alpha catalytic subunit of class I(A) PI3K have implicated the role of this enzyme in regulating heart size and physiological cardiac hypertrophy. To further understand the role of class I(A) PI3K in controlling heart growth and to circumvent potential complications from the overexpression of dominant negative and constitutively active proteins, we generated mice with muscle-specific deletion of the p85alpha regulatory subunit and germ line deletion of the p85beta regulatory subunit of class I(A) PI3K. Here we show that mice with cardiac deletion of both p85 subunits exhibit attenuated Akt signaling in the heart, reduced heart size, and altered cardiac gene expression. Furthermore, exercise-induced cardiac hypertrophy is also attenuated in the p85 knockout hearts. Despite such defects in postnatal developmental growth and physiological hypertrophy, the p85 knockout hearts exhibit normal contractility and myocardial histology. Our results therefore provide strong genetic evidence that class I(A) PI3Ks are critical regulators for the developmental growth and physiological hypertrophy of the heart.

Generator for ionic gallium-68 based on column chromatography

DOEpatents

Neirinckx, Rudi D.; Davis, Michael A.

1981-01-01

A physiologically acceptable solution of gallium-68 fluorides, having an activity of 0.1 to 50 millicuries per milliliter of solution is provided. The solution is obtained from a generator comprising germanium-68 hexafluoride bound to a column of an anion exchange resin which forms gallium-68 in situ by eluting the column with an acid solution to form a solution containing .sup.68 Ga-fluorides. The solution then is neutralized prior to administration.

Radiopharmaceutical composition containing tantalum-178 and process therefor

DOEpatents

Neirinckx, Rudi D.; Holman, B. Leonard; Davis, Michael A.; Harris, Gale I.

1989-05-16

A physiologically acceptable solution of tantalum-178 having an activity of 0.1 to 200 millicuries per milliliter of tantalum-178 solution is provided. The solution is obtained from tungsten-178 bound to a column of an anion exchange resin which forms tantalum-178 in situ by eluting the column with a hydrochloric acid solution containing hydrogen peroxide to form an acidic solution of tantalum-178. The acidic solution of tantalum-178 then is neutralized.

Effect of a puzzle on the process of students' learning about cardiac physiology.

PubMed

Cardozo, Lais Tono; Miranda, Aline Soares; Moura, Maria José Costa Sampaio; Marcondes, Fernanda Klein

2016-09-01

The aim of the present study was to evaluate the effects of using a puzzle to learn about cardiac physiology. Students were divided into control and game groups. In class 1, the control group had a 2-h theoretical class about cardiac physiology, including a detailed description of the phases of the cardiac cycle, whereas the game group had a 50-min theoretical class without the description of the cardiac cycle. In class 2, the control group did an assessment exercise before an activity with the cardiac puzzle and the game group answered questions after the above-mentioned activity. While solving the puzzle, the students had to describe the cardiac cycle by relating the concepts of heart morphology and physiology. To evaluate short-term learning, the number of wrong answers and grades in the assessment exercise were compared between the control and game groups. To evaluate medium-term learning, we compared the grades obtained by students of the control and game groups in questions about cardiac physiology that formed part of the academic exam. In the assessment exercise, the game group presented a lower number of errors and higher score compared with the control group. In the academic exam, applied after both groups had used the puzzle, there was no difference in the scores obtained by the control and game groups in questions about cardiac physiology. These results showed a positive effect of the puzzle on students' learning about cardiac physiology compared with those not using the puzzle. Copyright © 2016 The American Physiological Society.

Worker honeybee sterility: a proteomic analysis of suppressed ovary activation.

PubMed

Cardoen, Dries; Ernst, Ulrich R; Boerjan, Bart; Bogaerts, Annelies; Formesyn, Ellen; de Graaf, Dirk C; Wenseleers, Tom; Schoofs, Liliane; Verleyen, Peter

2012-05-04

Eusocial behavior is extensively studied in the honeybee, Apis mellifera, as it displays an extreme form of altruism. Honeybee workers are generally obligatory sterile in a bee colony headed by a queen, but the inhibition of ovary activation is lifted upon the absence of queen and larvae. Worker bees are then able to develop mature, viable eggs. The detailed repressive physiological mechanisms that are responsible for this remarkable phenomenon are as of yet largely unknown. Physiological studies today mainly focus on the transcriptome, while the proteome stays rather unexplored. Here, we present a quantitative 2-dimensional differential gel electrophoresis comparison between activated and inactivated worker ovaries and brains of reproductive and sterile worker bees, including a spot map of ovaries, containing 197 identified spots. Our findings suggest that suppression of ovary activation might involve a constant interplay between primordial oogenesis and subsequent degradation, which is probably mediated through steroid and neuropeptide hormone signaling. Additionally, the observation of higher viral protein loads in both the brains and ovaries of sterile workers is particularly noteworthy. This data set will be of great value for future research unraveling the physiological mechanisms underlying the altruistic sterility in honeybee workers.

Physiology of Hyperuricemia and Urate-Lowering Treatments.

PubMed

Benn, Caroline L; Dua, Pinky; Gurrell, Rachel; Loudon, Peter; Pike, Andrew; Storer, R Ian; Vangjeli, Ciara

2018-01-01

Gout is the most common form of inflammatory arthritis and is a multifactorial disease typically characterized by hyperuricemia and monosodium urate crystal deposition predominantly in, but not limited to, the joints and the urinary tract. The prevalence of gout and hyperuricemia has increased in developed countries over the past two decades and research into the area has become progressively more active. We review the current field of knowledge with emphasis on active areas of hyperuricemia research including the underlying physiology, genetics and epidemiology, with a focus on studies which suggest association of hyperuricemia with common comorbidities including cardiovascular disease, renal insufficiency, metabolic syndrome and diabetes. Finally, we discuss current therapies and emerging drug discovery efforts aimed at delivering an optimized clinical treatment strategy.

How consumer physical activity monitors could transform human physiology research.

PubMed

Wright, Stephen P; Hall Brown, Tyish S; Collier, Scott R; Sandberg, Kathryn

2017-03-01

A sedentary lifestyle and lack of physical activity are well-established risk factors for chronic disease and adverse health outcomes. Thus, there is enormous interest in measuring physical activity in biomedical research. Many consumer physical activity monitors, including Basis Health Tracker, BodyMedia Fit, DirectLife, Fitbit Flex, Fitbit One, Fitbit Zip, Garmin Vivofit, Jawbone UP, MisFit Shine, Nike FuelBand, Polar Loop, Withings Pulse O 2 , and others have accuracies similar to that of research-grade physical activity monitors for measuring steps. This review focuses on the unprecedented opportunities that consumer physical activity monitors offer for human physiology and pathophysiology research because of their ability to measure activity continuously under real-life conditions and because they are already widely used by consumers. We examine current and potential uses of consumer physical activity monitors as a measuring or monitoring device, or as an intervention in strategies to change behavior and predict health outcomes. The accuracy, reliability, reproducibility, and validity of consumer physical activity monitors are reviewed, as are limitations and challenges associated with using these devices in research. Other topics covered include how smartphone apps and platforms, such as the Apple ResearchKit, can be used in conjunction with consumer physical activity monitors for research. Lastly, the future of consumer physical activity monitors and related technology is considered: pattern recognition, integration of sleep monitors, and other biosensors in combination with new forms of information processing. Copyright © 2017 the American Physiological Society.

Porcine CD38 exhibits prominent secondary NAD(+) cyclase activity.

PubMed

Ting, Kai Yiu; Leung, Christina F P; Graeff, Richard M; Lee, Hon Cheung; Hao, Quan; Kotaka, Masayo

2016-03-01

Cyclic ADP-ribose (cADPR) mobilizes intracellular Ca(2+) stores and activates Ca(2+) influx to regulate a wide range of physiological processes. It is one of the products produced from the catalysis of NAD(+) by the multifunctional CD38/ADP-ribosyl cyclase superfamily. After elimination of the nicotinamide ring by the enzyme, the reaction intermediate of NAD(+) can either be hydrolyzed to form linear ADPR or cyclized to form cADPR. We have previously shown that human CD38 exhibits a higher preference towards the hydrolysis of NAD(+) to form linear ADPR while Aplysia ADP-ribosyl cyclase prefers cyclizing NAD(+) to form cADPR. In this study, we characterized the enzymatic properties of porcine CD38 and revealed that it has a prominent secondary NAD(+) cyclase activity producing cADPR. We also determined the X-ray crystallographic structures of porcine CD38 and were able to observe conformational flexibility at the base of the active site of the enzyme which allow the NAD(+) reaction intermediate to adopt conformations resulting in both hydrolysis and cyclization forming linear ADPR and cADPR respectively. © 2016 The Protein Society.

Drawing on student knowledge in human anatomy and physiology

NASA Astrophysics Data System (ADS)

Slominski, Tara Nicole

Prior to instruction, students may have developed alternative conceptions about the mechanics behind human physiology. To help students re-shape these ideas into correct reasoning, the faulty characteristics reinforcing the alternative conceptions need to made explicit. This study used student-generated drawings to expose alternative conceptions Human Anatomy and Physiology students had prior to instruction on neuron physiology. Specifically, we investigated how students thought about neuron communication across a synapse (n=355) and how neuron activity can be modified (n=311). When asked to depict basic communication between two neurons, at least 80% of students demonstrated incorrect ideas about synaptic transmission. When targeting spatial and temporal summation, only eleven students (3.5%) were able to accurately depict at least one form of summation. In response to both drawing questions, student drawings revealed multiple alternative conceptions that resulted in a deeper analysis and characterization of the wide variation of student ideas.

Mechanisms of action of light on circadian rhythms in the monkey

NASA Technical Reports Server (NTRS)

Winget, C. M.; Rosenblatt, L. S.; DeRoshia, C. W.; Hetherington, N. W.

1970-01-01

Light is considered by many investigators to be the primary Zeitgeber for most physiologic rhythms. In order to study the effects on biorhythms of changing photoperiods and to provide information on the nature of the wave forms and the mechanisms of entrainment, unrestrained male monkeys (Cebus albifrons, Macaca nemestrina) were maintained in a sound-proofed environmental chamber. The Cebus was initially maintained on a 12L:12D schedule; it was subjected to a 180 degrees phase shift for 14 days, then returned to the original photoperiod. In two experiments (24 days; 27 days each) the same monkey was again maintained on a 12L:12D schedule which was gradually altered to a constant light environment. Deep body temperature (DBT) data were obtained with miniature radiotransmitters. Locomotor activity (LMA) was measured by strain gauges. Under the 12L:12D regimens the Macaca DBT cycles were uniform as to phase and wave form for over 60 weeks. These wave forms were analyzed by the use of periodogram and correlogram analyses and by fitting to the Volterra Integro-Differential Equation. Phase angle relationships between Zeitgeber and physiologic parameters were characterized. After the photoperiod phase shift the DBT cycle rephased in about 9 days. During the rephasing process the wave form changed. The shapes of the wave forms of DBT and activity were maintained with increasing light until an 18L:6D photoperiod was reached. The rhythms were entrained to the onset of darkness rather than lights on. Major and minor periods of LMA were detected. Hysteresis diagrams showed that DBT led the onset of major LA by 6 hr and the end of major activity by 2 hr.

The Temporal Dynamics of Two Response-Focused Forms of Emotion Regulation: Experiential, Expressive, and Autonomic Consequences

PubMed Central

Dan-Glauser, Elise S.; Gross, James J.

2011-01-01

This study examines the early affective consequences of two close forms of suppression. Participants (N=37) were shown negative, positive, and neutral pictures and cued either to attend to the pictures, or to perform expressive or physiological suppression (i.e. reduce body reactions). Continuous measures of experience, expressivity, and autonomic responses showed that both suppression strategies produced rapid response modulation. Common effects of the two strategies included a transient increase in negative feeling, a durable decrease in positive feeling, and a decrease in expressivity, cardiovascular activity, and oxygenation. The two strategies were significantly different only in response to positive stimuli, with physiological suppression showing a larger decrease in experience intensity and blood pressure. These results suggest a strong overlap between the two suppression strategies in terms of their early impact on emotional responses. PMID:21361967

Separation of active and inactive fractions from starved culture of Vibrio parahaemolyticus by density dependent cell sorting.

PubMed

Nayak, Binaya Bhusan; Kamiya, Eriko; Nishino, Tomohiko; Wada, Minoru; Nishimura, Masahiko; Kogure, Kazuhiro

2005-01-01

The co-existence of physiologically different cells in bacterial cultures is a general phenomenon. We have examined the applicability of the density dependent cell sorting (DDCS) method to separate subpopulations from a long-term starvation culture of Vibrio parahaemolyticus. The cells were subjected to Percoll density gradient and separated into 12 fractions of different buoyant densities, followed by measuring the cell numbers, culturability, respiratory activity and leucine incorporation activity. While more than 78% of cells were in lighter fractions, about 95% of culturable cells were present in heavier fractions. The high-density subpopulations also had high proportion of cells capable of forming formazan granules. Although this was accompanied by the cell specific INT-reduction rate, both leucine incorporation rates and INT-reduction rates per cell had a peak at mid-density fraction. The present results indicated that DDCS could be used to separate subpopulations of different physiological conditions.

Vasomotor Symptoms Monitoring with a Commercial Activity Tracking Watch

DTIC Science & Technology

2017-12-31

volunteers wearing physiological monitors. The study protocol and written consent form were...available, but similar devices with EDA/GSR sensors are available. Vasomotor symptoms started disrupting the sleep of a woman volunteer on...November 23, 2015, calling attention to their occurrence. After November 23, 2015, the volunteer started personally logging the occurrence of

Short-Latency Median-Nerve Somatosensory-Evoked Potentials and Induced Gamma-Oscillations in Humans

ERIC Educational Resources Information Center

Fukuda, Miho; Nishida, Masaaki; Juhasz, Csaba; Muzik, Otto; Sood, Sandeep; Chugani, Harry T.; Asano, Eishi

2008-01-01

Recent studies have suggested that cortical gamma-oscillations are tightly linked with various forms of physiological activity. In the present study, the dynamic changes of intracranially recorded median-nerve somatosensory-evoked potentials (SEPs) and somatosensory-induced gamma-oscillations were animated on a three-dimensional MR image, and the…

Innate Immune Activation in Obesity

PubMed Central

Lumeng, Carey N.

2014-01-01

The innate immune system is a prewired set of cellular and humoral components that has developed to sense perturbations in normal physiology and trigger responses to restore the system back to baseline. It is now understood that many of these components can also sense the physiologic changes that occur with obesity and be activated. While the exact reasons for this chronic immune response to obesity are unclear, there is strong evidence to suggest that innate inflammatory systems link obesity and disease. Based on this, anti-inflammatory therapies for diseases like type 2 diabetes and metabolic syndrome may form the core of future treatment plans. This review will highlight the components involved in the innate immune response and discuss the evidence that they contribute to the pathogenesis of obesity-associated diseases. PMID:23068074

Identification of a probable pore-forming domain in the multimeric vacuolar anion channel AtALMT9.

PubMed

Zhang, Jingbo; Baetz, Ulrike; Krügel, Undine; Martinoia, Enrico; De Angeli, Alexis

2013-10-01

Aluminum-activated malate transporters (ALMTs) form an important family of anion channels involved in fundamental physiological processes in plants. Because of their importance, the role of ALMTs in plant physiology is studied extensively. In contrast, the structural basis of their functional properties is largely unknown. This lack of information limits the understanding of the functional and physiological differences between ALMTs and their impact on anion transport in plants. This study aimed at investigating the structural organization of the transmembrane domain of the Arabidopsis (Arabidopsis thaliana) vacuolar channel AtALMT9. For that purpose, we performed a large-scale mutagenesis analysis and found two residues that form a salt bridge between the first and second putative transmembrane α-helices (TMα1 and TMα2). Furthermore, using a combination of pharmacological and mutagenesis approaches, we identified citrate as an "open channel blocker" of AtALMT9 and used this tool to examine the inhibition sensitivity of different point mutants of highly conserved amino acid residues. By this means, we found a stretch within the cytosolic moiety of the TMα5 that is a probable pore-forming domain. Moreover, using a citrate-insensitive AtALMT9 mutant and biochemical approaches, we could demonstrate that AtALMT9 forms a multimeric complex that is supposedly composed of four subunits. In summary, our data provide, to our knowledge, the first evidence about the structural organization of an ion channel of the ALMT family. We suggest that AtALMT9 is a tetramer and that the TMα5 domains of the subunits contribute to form the pore of this anion channel.

Structures of human thymidylate synthase R163K with dUMP, FdUMP and glutathione show asymmetric ligand binding

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

Gibson, Lydia M.; Celeste, Lesa R.; Lovelace, Leslie L.

Thymidylate synthase (TS) is a well validated target in cancer chemotherapy. Here, a new crystal form of the R163K variant of human TS (hTS) with five subunits per asymmetric part of the unit cell, all with loop 181-197 in the active conformation, is reported. This form allows binding studies by soaking crystals in artificial mother liquors containing ligands that bind in the active site. Using this approach, crystal structures of hTS complexes with FdUMP and dUMP were obtained, indicating that this form should facilitate high-throughput analysis of hTS complexes with drug candidates. Crystal soaking experiments using oxidized glutathione revealed thatmore » hTS binds this ligand. Interestingly, the two types of binding observed are both asymmetric. In one subunit of the physiological dimer covalent modification of the catalytic nucleophile Cys195 takes place, while in another dimer a noncovalent adduct with reduced glutathione is formed in one of the active sites.« less

Soil microbial community structure and function responses to successive planting of Eucalyptus.

PubMed

Chen, Falin; Zheng, Hua; Zhang, Kai; Ouyang, Zhiyun; Li, Huailin; Wu, Bing; Shi, Qian

2013-10-01

Many studies have shown soil degradation after the conversion of native forests to exotic Eucalyptus plantations. However, few studies have investigated the long-term impacts of short-rotation forestry practices on soil microorganisms. The impacts of Eucalyptus successive rotations on soil microbial communities were evaluated by comparing phospholipid fatty acid (PLFA) abundances, compositions, and enzyme activities of native Pinus massoniana plantations and adjacent 1st, 2nd, 3rd, 4th generation Eucalyptus plantations. The conversion from P. massoniana to Eucalyptus plantations significantly decreased soil microbial community size and enzyme activities, and increased microbial physiological stress. However, the PLFA abundances formed "u" shaped quadratic functions with Eucalyptus plantation age. Alternatively, physiological stress biomarkers, the ratios of monounsaturated to saturated fatty acid and Gram+ to Gram- bacteria, formed "n"' shaped quadratic functions, and the ratio of cy17:0 to 16:1omega7c decreased with plantation age. The activities of phenol oxidase, peroxidase, and acid phosphatase increased with Eucalyptus plantation age, while the cellobiohydrolase activity formed "u" shaped quadratic functions. Soil N:P, alkaline hydrolytic nitrogen, soil organic carbon, and understory cover largely explained the variation in PLFA profiles while soil N:P, alkaline hydrolytic nitrogen, and understory cover explained most of the variability in enzyme activity. In conclusion, soil microbial structure and function under Eucalyptus plantations were strongly impacted by plantation age. Most of the changes could be explained by altered soil resource availability and understory cover associated with successive planting of Eucalyptus. Our results highlight the importance of plantation age for assessing the impacts of plantation conversion as well as the importance of reducing disturbance for plantation management.

Systems analysis in Cellvibrio japonicus resolves predicted redundancy of β-glucosidases and determines essential physiological functions: Functional analysis of C. japonicus β-glucosidases

DOE PAGES

Nelson, Cassandra E.; Rogowski, Artur; Morland, Carl; ...

2017-02-28

Degradation of polysaccharides forms an essential arc in the carbon cycle, provides a percentage of our daily caloric intake, and is a major driver in the renewable chemical industry. Microorganisms proficient at degrading insoluble polysaccharides possess large numbers of carbohydrate active enzymes, many of which have been categorized as functionally redundant. Here we present data that suggests that carbohydrate active enzymes that have overlapping enzymatic activities can have unique, non-overlapping biological functions in the cell. Our comprehensive study to understand cellodextrin utilization in the soil saprophyte Cellvibrio japonicus found that only one of four predicted β-glucosidases is required in amore » physiological context. Gene deletion analysis indicated that only the cel3B gene product is essential for efficient cellodextrin utilization in C. japonicus and is constitutively expressed at high levels. Interestingly, expression of individual β-glucosidases in Escherichia coli K-12 enabled this non-cellulolytic bacterium to be fully capable of using cellobiose as a sole carbon source. Furthermore, enzyme kinetic studies indicated that the Cel3A enzyme is significantly more active than the Cel3B enzyme on the oligosaccharides but not disaccharides. Finally, our approach for parsing related carbohydrate active enzymes to determine actual physiological roles in the cell can be applied to other polysaccharide-degradation systems.« less

Targeting physiological activities to modify the ecology and functionality of rumen and gastrointestinal ecosystems, prototypical anaerobic digester

USDA-ARS?s Scientific Manuscript database

The rumen microbial ecosystem is highly regarded for its ability to digest and transform low quality plant material into chemical forms of use by the host. However, less than 35% of the dietary energy consumed by the ruminant is conserved by the host. Methane production within the rumen contribute...

Tissue-specific expression of transgenic secreted ACE in vasculature can restore normal kidney functions, but not blood pressure, of Ace-/- mice.

PubMed

Chattopadhyay, Saurabh; Kessler, Sean P; Colucci, Juliana Almada; Yamashita, Michifumi; Senanayake, Preenie deS; Sen, Ganes C

2014-01-01

Angiotensin-converting enzyme (ACE) regulates normal blood pressure and fluid homeostasis through its action in the renin-angiotensin-system (RAS). Ace-/- mice are smaller in size, have low blood pressure and defective kidney structure and functions. All of these defects are cured by transgenic expression of somatic ACE (sACE) in vascular endothelial cells of Ace-/- mice. sACE is expressed on the surface of vascular endothelial cells and undergoes a natural cleavage secretion process to generate a soluble form in the body fluids. Both the tissue-bound and the soluble forms of ACE are enzymatically active, and generate the vasoactive octapeptide Angiotensin II (Ang II) with equal efficiency. To assess the relative physiological roles of the secreted and the cell-bound forms of ACE, we expressed, in the vascular endothelial cells of Ace-/- mice, the ectodomain of sACE, which corresponded to only the secreted form of ACE. Our results demonstrated that the secreted form of ACE could normalize kidney functions and RAS integrity, growth and development of Ace-/- mice, but not their blood pressure. This study clearly demonstrates that the secreted form of ACE cannot replace the tissue-bound ACE for maintaining normal blood pressure; a suitable balance between the tissue-bound and the soluble forms of ACE is essential for maintaining all physiological functions of ACE.

Tissue-Specific Expression of Transgenic Secreted ACE in Vasculature Can Restore Normal Kidney Functions, but Not Blood Pressure, of Ace-/- Mice

PubMed Central

Chattopadhyay, Saurabh; Kessler, Sean P.; Colucci, Juliana Almada; Yamashita, Michifumi; Senanayake, Preenie deS; Sen, Ganes C.

2014-01-01

Angiotensin-converting enzyme (ACE) regulates normal blood pressure and fluid homeostasis through its action in the renin-angiotensin-system (RAS). Ace-/- mice are smaller in size, have low blood pressure and defective kidney structure and functions. All of these defects are cured by transgenic expression of somatic ACE (sACE) in vascular endothelial cells of Ace-/- mice. sACE is expressed on the surface of vascular endothelial cells and undergoes a natural cleavage secretion process to generate a soluble form in the body fluids. Both the tissue-bound and the soluble forms of ACE are enzymatically active, and generate the vasoactive octapeptide Angiotensin II (Ang II) with equal efficiency. To assess the relative physiological roles of the secreted and the cell-bound forms of ACE, we expressed, in the vascular endothelial cells of Ace-/- mice, the ectodomain of sACE, which corresponded to only the secreted form of ACE. Our results demonstrated that the secreted form of ACE could normalize kidney functions and RAS integrity, growth and development of Ace-/- mice, but not their blood pressure. This study clearly demonstrates that the secreted form of ACE cannot replace the tissue-bound ACE for maintaining normal blood pressure; a suitable balance between the tissue-bound and the soluble forms of ACE is essential for maintaining all physiological functions of ACE. PMID:24475296

Comparison of biological activities of human antithrombins with high-mannose or complex-type nonfucosylated N-linked oligosaccharides

PubMed Central

Yamada, Tsuyoshi; Kanda, Yutaka; Takayama, Makoto; Hashimoto, Akitoshi; Sugihara, Tsutomu; Satoh-Kubota, Ai; Suzuki-Takanami, Eri; Yano, Keiichi; Iida, Shigeru; Satoh, Mitsuo

2016-01-01

The structure of the N-linked oligosaccharides attached to antithrombin (AT) has been shown to affect its anticoagulant activity and pharmacokinetics. Human AT has biantennary complex-type oligosaccharides with the unique feature of lacking a core fucose, which affects its biological activities by changing its heparin-binding affinity. In human plasma, AT circulates as a mixture of the α-form bearing four oligosaccharides and the β-form lacking an oligosaccharide at Asn135. However, it remains unclear how the immature high-mannose-type oligosaccharides produced by mammalian cells affect biological activities of AT. Here, we succeeded in directly comparing the activities between the high-mannose and complex types. Interestingly, although there were no substantial differences in thrombin inhibitory activity, the high-mannose type showed higher heparin-binding affinity. The anticoagulant activities were increased by heparin and correlated with the heparin-binding affinity, resulting in the strongest anticoagulant activity being displayed in the β-form with the high-mannose type. In pharmacokinetic profiling, the high-mannose type showed a much shorter plasma half-life than the complex type. The β-form was found to have a prolonged plasma half-life compared with the α-form for the high-mannose type; conversely, the α-form showed a longer half-life than the β-form for the complex-type. The present study highlights that AT physiological activities are strictly controlled not only by a core fucose at the reducing end but also by the high-mannose-type structures at the nonreducing end. The β-form with the immature high-mannose type appears to function as a more potent anticoagulant than the AT typically found in human plasma, once it emerges in the blood. PMID:26747427

Comparison of biological activities of human antithrombins with high-mannose or complex-type nonfucosylated N-linked oligosaccharides.

PubMed

Yamada, Tsuyoshi; Kanda, Yutaka; Takayama, Makoto; Hashimoto, Akitoshi; Sugihara, Tsutomu; Satoh-Kubota, Ai; Suzuki-Takanami, Eri; Yano, Keiichi; Iida, Shigeru; Satoh, Mitsuo

2016-05-01

The structure of the N-linked oligosaccharides attached to antithrombin (AT) has been shown to affect its anticoagulant activity and pharmacokinetics. Human AT has biantennary complex-type oligosaccharides with the unique feature of lacking a core fucose, which affects its biological activities by changing its heparin-binding affinity. In human plasma, AT circulates as a mixture of the α-form bearing four oligosaccharides and the β-form lacking an oligosaccharide at Asn135. However, it remains unclear how the immature high-mannose-type oligosaccharides produced by mammalian cells affect biological activities of AT. Here, we succeeded in directly comparing the activities between the high-mannose and complex types. Interestingly, although there were no substantial differences in thrombin inhibitory activity, the high-mannose type showed higher heparin-binding affinity. The anticoagulant activities were increased by heparin and correlated with the heparin-binding affinity, resulting in the strongest anticoagulant activity being displayed in the β-form with the high-mannose type. In pharmacokinetic profiling, the high-mannose type showed a much shorter plasma half-life than the complex type. The β-form was found to have a prolonged plasma half-life compared with the α-form for the high-mannose type; conversely, the α-form showed a longer half-life than the β-form for the complex-type. The present study highlights that AT physiological activities are strictly controlled not only by a core fucose at the reducing end but also by the high-mannose-type structures at the nonreducing end. The β-form with the immature high-mannose type appears to function as a more potent anticoagulant than the AT typically found in human plasma, once it emerges in the blood. © The Author 2016. Published by Oxford University Press.

Loss of HMG-CoA reductase in C. elegans causes defects in protein prenylation and muscle mitochondria.

PubMed

Ranji, Parmida; Rauthan, Manish; Pitot, Christophe; Pilon, Marc

2014-01-01

HMG-CoA reductase is the rate-limiting enzyme in the mevalonate pathway and the target of cholesterol-lowering statins. We characterized the C. elegans hmgr-1(tm4368) mutant, which lacks HMG-CoA reductase, and show that its phenotypes recapitulate that of statin treatment, though in a more severe form. Specifically, the hmgr-1(tm4368) mutant has defects in growth, reproduction and protein prenylation, is rescued by exogenous mevalonate, exhibits constitutive activation of the UPRer and requires less mevalonate to be healthy when the UPRmt is activated by a constitutively active form of ATFS-1. We also show that different amounts of mevalonate are required for different physiological processes, with reproduction requiring the highest levels. Finally, we provide evidence that the mevalonate pathway is required for the activation of the UPRmt.

Nuclear localization of matrix metalloproteinases.

PubMed

Mannello, Ferdinando; Medda, Virginia

2012-03-01

Matrix metalloproteinases (MMPs) were originally identified as matrixin proteases that act in the extracellular matrix. Recent works have uncovered nontraditional roles for MMPs in the extracellular space as well as in the cytosol and nucleus. There is strong evidence that subspecialized and compartmentalized matrixins participate in many physiological and pathological cellular processes, in which they can act as both degradative and regulatory proteases. In this review, we discuss the transcriptional and translational control of matrixin expression, their regulation of intracellular sorting, and the structural basis of activation and inhibition. In particular, we highlight the emerging roles of various matrixin forms in diseases. The activity of matrix metalloproteinases is regulated at several levels, including enzyme activation, inhibition, complex formation and compartmentalization. Most MMPs are secreted and have their function in the extracellular environment. MMPs are also found inside cells, both in the nucleus, cytosol and organelles. The role of intracellular located MMPs is still poorly understood, although recent studies have unraveled some of their functions. The localization, activation and activity of MMPs are regulated by their interactions with other proteins, proteoglycan core proteins and / or their glycosaminoglycan chains, as well as other molecules. Complexes formed between MMPs and various molecules may also include interactions with noncatalytic sites. Such exosites are regions involved in substrate processing, localized outside the active site, and are potential binding sites of specific MMP inhibitors. Knowledge about regulation of MMP activity is essential for understanding various physiological processes and pathogenesis of diseases, as well as for the development of new MMP targeting drugs. Copyright © 2011 Elsevier GmbH. All rights reserved.

Cleavage of Disulfide Bonds in Mouse Spermatogenic Cell-Specific Type 1 Hexokinase Isozyme Is Associated with Increased Hexokinase Activity and Initiation of Sperm Motility1

PubMed Central

Nakamura, Noriko; Miranda-Vizuete, Antonio; Miki, Kiyoshi; Mori, Chisato; Eddy, Edward M.

2008-01-01

During epididymal transit, sperm acquire the ability to initiate rapid forward progressive motility on release into the female reproductive tract or physiological media. Glycolysis is the primary source of the ATP necessary for this motility in the mouse, and several novel glycolytic enzymes have been identified that are localized to the principal piece region of the flagellum. One of these is the spermatogenic cell-specific type 1 hexokinase isozyme (HK1S), the only member of the hexokinase enzyme family detected in sperm. Hexokinase activity was found to be lower in immotile sperm immediately after removal from the cauda epididymis (quiescent) than in sperm incubated in physiological medium for 5 min and showing rapid forward progressive motility (activated). However, incubating sperm in medium containing diamide, an inhibitor of disulfide bond reduction, resulted in lower motility and HK activity than in controls. HK1S was present in dimer and monomer forms in extracts of quiescent sperm but mainly as a monomer in motile sperm. A dimer-size band detected in quiescent sperm with phosphotyrosine antibody was not detected in activated sperm, and the monomer-size band was enhanced. In addition, the general protein oxido-reductase thioredoxin-1 was able to catalyze the in vitro conversion of HK1S dimers to the monomeric form. These results strongly suggest that cleavage of disulfide bonds in HK1S dimers contributes to the increases in HK activity and motility that occur when mouse sperm become activated. PMID:18509164

Cognitive and physiological dissociations in response to emotional pictures in patients with anorexia.

PubMed

Nandrino, Jean-Louis; Berna, Guillaume; Hot, Pascal; Dodin, Vincent; Latrée, Julie; Decharles, Sandra; Sequeira, Henrique

2012-01-01

Recent studies suggest that patients with anorexia may express dissociated cognitive and physiological reactivities to emotional stimuli. The present research aimed to compare subjective and autonomic responses to pleasant, unpleasant and neutral scenes during a categorization task and an activation rating task in anorexic (AN), alexithymic (AL), depressed (DEP) and control participants (CONT). The participants first categorized pictures according to their emotional valence, followed by a rating of their activation level, concomitant with the recording of skin conductance responses (SCRs). Main findings showed that the AN patients presented major difficulty in categorizing pictures, particularly neutral ones. Contrary to the AL participants, this difficulty did not induce significant increases of SCR amplitude in the AN patients. In the second task, the AN patients rated the intensity of activation of unpleasant pictures higher than the AL participants and that of pleasant ones higher than the AL and CONT participants. In addition, no significant linear correlation was observed between the intensity of activation ratings and SCR amplitude in the AN, AL or DEP participants contrarily to what was observed for control participants. This lack of relation suggests a non-specific disconnection between physiological and cognitive self-reported responses to emotional stimuli. Our results highlight a specific form of emotional processing in the AN patients distinct from that observed in alexithymia or depression and characterized by a dissociation between cognitive and physiological responses. This kind of disconnection could be associated with emotional regulation processes and may benefit the AN patients by lowering the psychological stress response. Copyright © 2011 Elsevier Inc. All rights reserved.

Hemodynamic and Thermal Responses to Head and Neck Cooling in Men and Women

NASA Technical Reports Server (NTRS)

Ku, Yu-Tsuan E.; Montgomery, Leslie D.; Carbo, Jorge E.; Webbon, Bruce W.

1995-01-01

Personal cooling systems are used to alleviate symptoms of multiple sclerosis and to prevent increased core temperature during daily activities. Configurations of these systems include passive ice vests and circulating liquid cooling garments (LCGs) in the forms of vests, cooling caps and combined head and neck cooling systems. However, little information is available oil the amount or heat that can be extracted from the body with these systems or the physiologic changes produced by routine operation of these systems. The objective of this study was to determine the operating characteristics and the physiologic change, produced by short term use of one commercially available thermal control system.

Physiological controls of large‐scale patterning in planarian regeneration: a molecular and computational perspective on growth and form

PubMed Central

Durant, Fallon; Lobo, Daniel; Hammelman, Jennifer

2016-01-01

Abstract Planaria are complex metazoans that repair damage to their bodies and cease remodeling when a correct anatomy has been achieved. This model system offers a unique opportunity to understand how large‐scale anatomical homeostasis emerges from the activities of individual cells. Much progress has been made on the molecular genetics of stem cell activity in planaria. However, recent data also indicate that the global pattern is regulated by physiological circuits composed of ionic and neurotransmitter signaling. Here, we overview the multi‐scale problem of understanding pattern regulation in planaria, with specific focus on bioelectric signaling via ion channels and gap junctions (electrical synapses), and computational efforts to extract explanatory models from functional and molecular data on regeneration. We present a perspective that interprets results in this fascinating field using concepts from dynamical systems theory and computational neuroscience. Serving as a tractable nexus between genetic, physiological, and computational approaches to pattern regulation, planarian pattern homeostasis harbors many deep insights for regenerative medicine, evolutionary biology, and engineering. PMID:27499881

A new insight into the physiological role of bile salt hydrolase among intestinal bacteria from the genus Bifidobacterium.

PubMed

Jarocki, Piotr; Podleśny, Marcin; Glibowski, Paweł; Targoński, Zdzisław

2014-01-01

This study analyzes the occurrence of bile salt hydrolase in fourteen strains belonging to the genus Bifidobacterium. Deconjugation activity was detected using a plate test, two-step enzymatic reaction and activity staining on a native polyacrylamide gel. Subsequently, bile salt hydrolases from B. pseudocatenulatum and B. longum subsp. suis were purified using a two-step chromatographic procedure. Biochemical characterization of the bile salt hydrolases showed that the purified enzymes hydrolyzed all of the six major human bile salts under the pH and temperature conditions commonly found in the human gastrointestinal tract. Next, the dynamic rheometry was applied to monitor the gelation process of deoxycholic acid under different conditions. The results showed that bile acids displayed aqueous media gelating properties. Finally, gel-forming abilities of bifidobacteria exhibiting bile salt hydrolase activity were analyzed. Our investigations have demonstrated that the release of deconjugated bile acids led to the gelation phenomenon of the enzymatic reaction solution containing purified BSH. The presented results suggest that bile salt hydrolase activity commonly found among intestinal microbiota increases hydrogel-forming abilities of certain bile salts. To our knowledge, this is the first report showing that bile salt hydrolase activity among Bifidobacterium is directly connected with the gelation process of bile salts. In our opinion, if such a phenomenon occurs in physiological conditions of human gut, it may improve bacterial ability to colonize the gastrointestinal tract and their survival in this specific ecological niche.

Doing peer review and receiving feedback: impact on scientific literacy and writing skills.

PubMed

Geithner, Christina A; Pollastro, Alexandria N

2016-03-01

Doing peer review has been effectively implemented to help students develop critical reading and writing skills; however, its application in Human Physiology programs is limited. The purpose of the present study was to determine the impact of peer review on Human Physiology majors' perceptions of their scientific literacy and writing skills. Students enrolled in the Scientific Writing course completed multiple writing assignments, including three revisions after receiving peer and instructor feedback. Students self-assessed their knowledge, skills, and attitudes related to science and writing in pre- and postcourse surveys (n = 26 with complete data). Seven survey items related to scientific literacy and writing skills impacted by peer review were selected for analysis. Scores on these survey items were summed to form a composite self-rating score. Responses to two questions regarding the most useful learning activities were submitted to frequency analysis. Mean postcourse scores for individual survey items and composite self-rating scores were significantly higher than precourse means (P < 0.05). Peer review was the most frequently noted among 21 learning activities for increasing scientific literacy and in the top 5 for improving writing skills. In conclusion, peer review is an effective teaching/learning approach for improving undergraduate Human Physiology majors' knowledge, skills, and attitudes regarding science and scientific writing. Copyright © 2016 The American Physiological Society.

Physiological Responses to Arm Activity in Individuals With Chronic Obstructive Pulmonary Disease Compared With Healthy Controls: A SYSTEMATIC REVIEW.

PubMed

Lima, Vanessa Pereira; Iamonti, Vinicius C; Velloso, Marcelo; Janaudis-Ferreira, Tania

The mechanisms underlying physiological limitations during arm activity in individuals with chronic obstructive pulmonary disease (COPD) are unknown. The objective of this systematic review was to describe cardiorespiratory responses, symptoms, chest wall kinematics, muscle activity, and lung volumes during arm activity in individuals with COPD relative to the responses of healthy controls. Original research articles that compared cardiorespiratory responses, symptoms, muscle activity, chest wall kinematics, and lung function during arm activity between individuals with COPD and healthy controls were identified after searches of 5 electronic databases and reference lists of pertinent articles. Two reviewers performed the electronic and manual searches with 1 screening title and abstracts. Two investigators screened the full texts to determine eligibility for inclusion. One reviewer performed the data extraction and tabulation using a standardized form with a second reviewer double-checking the data extracted. Of the 54 full-text articles assessed for eligibility, 6 met the inclusion criteria. Reduced cardiorespiratory responses during peak arm exercise in individuals with COPD compared with healthy controls were evident. Compared with healthy controls, individuals with COPD had increased dyspnea and hyperinflation during peak arm exercise. Increased effort of the trapezius muscle during arm activities was also found in persons with COPD compared with healthy controls. There is limited evidence describing physiological responses during arm activity in individuals with COPD. Findings of this systematic review suggest that individuals with COPD have decreased cardiorespiratory responses during peak arm exercise compared with controls but increased dyspnea, hyperinflation, and arm muscle effort.

Are plants sentient?

PubMed

Calvo, Paco; Sahi, Vaidurya Pratap; Trewavas, Anthony

2017-11-01

Feelings in humans are mental states representing groups of physiological functions that usually have defined behavioural purposes. Feelings, being evolutionarily ancient, are thought to be coordinated in the brain stem of animals. One function of the brain is to prioritise between competing mental states and, thus, groups of physiological functions and in turn behaviour. Plants use groups of coordinated physiological activities to deal with defined environmental situations but currently have no known mental state to prioritise any order of response. Plants do have a nervous system based on action potentials transmitted along phloem conduits but which in addition, through anastomoses and other cross-links, forms a complex network. The emergent potential for this excitable network to form a mental state is unknown, but it might be used to distinguish between different and even contradictory signals to the individual plant and thus determine a priority of response. This plant nervous system stretches throughout the whole plant providing the potential for assessment in all parts and commensurate with its self-organising, phenotypically plastic behaviour. Plasticity may, in turn, depend heavily on the instructive capabilities of local bioelectric fields enabling both a degree of behavioural independence but influenced by the condition of the whole plant. © 2017 John Wiley & Sons Ltd.

Cx43-hemichannel function and regulation in physiology and pathophysiology: insights from the bovine corneal endothelial cell system and beyond

PubMed Central

D'hondt, Catheleyne; Iyyathurai, Jegan; Himpens, Bernard; Leybaert, Luc; Bultynck, Geert

2014-01-01

Intercellular communication in primary bovine corneal endothelial cells (BCECs) is mainly driven by the release of extracellular ATP through Cx43 hemichannels. Studying the characteristics of Ca2+-wave propagation in BCECs, an important form of intercellular communication, in response to physiological signaling events has led to the discovery of important insights in the functional properties and regulation of native Cx43 hemichannels. Together with ectopic expression models for Cx43 hemichannels and truncated/mutated Cx43 versions, it became very clear that loop/tail interactions play a key role in controlling the activity of Cx43 hemichannels. Interestingly, the negative regulation of Cx43 hemichannels by enhanced actin/myosin contractility seems to impinge upon loss of these loop/tail interactions essential for opening Cx43 hemichannels. Finally, these molecular insights have spurred the development of novel peptide tools that can selectively inhibit Cx43 hemichannels, but neither Cx43 gap junctions nor hemichannels formed by other Cx isoforms. These tools now set the stage to hunt for novel physiological functions for Cx43 hemichannels in primary cells and tissues and to tackle disease conditions associated with excessive, pathological Cx43-hemichannel openings. PMID:25309448

A physiology-based model describing heterogeneity in glucose metabolism: the core of the Eindhoven Diabetes Education Simulator (E-DES).

PubMed

Maas, Anne H; Rozendaal, Yvonne J W; van Pul, Carola; Hilbers, Peter A J; Cottaar, Ward J; Haak, Harm R; van Riel, Natal A W

2015-03-01

Current diabetes education methods are costly, time-consuming, and do not actively engage the patient. Here, we describe the development and verification of the physiological model for healthy subjects that forms the basis of the Eindhoven Diabetes Education Simulator (E-DES). E-DES shall provide diabetes patients with an individualized virtual practice environment incorporating the main factors that influence glycemic control: food, exercise, and medication. The physiological model consists of 4 compartments for which the inflow and outflow of glucose and insulin are calculated using 6 nonlinear coupled differential equations and 14 parameters. These parameters are estimated on 12 sets of oral glucose tolerance test (OGTT) data (226 healthy subjects) obtained from literature. The resulting parameter set is verified on 8 separate literature OGTT data sets (229 subjects). The model is considered verified if 95% of the glucose data points lie within an acceptance range of ±20% of the corresponding model value. All glucose data points of the verification data sets lie within the predefined acceptance range. Physiological processes represented in the model include insulin resistance and β-cell function. Adjusting the corresponding parameters allows to describe heterogeneity in the data and shows the capabilities of this model for individualization. We have verified the physiological model of the E-DES for healthy subjects. Heterogeneity of the data has successfully been modeled by adjusting the 4 parameters describing insulin resistance and β-cell function. Our model will form the basis of a simulator providing individualized education on glucose control. © 2014 Diabetes Technology Society.

Physiological integration modifies δ15N in the clonal plant Fragaria vesca, suggesting preferential transport of nitrogen to water-stressed offspring.

PubMed

Roiloa, S R; Antelo, B; Retuerto, R

2014-08-01

One of the most striking attributes of clonal plants is their capacity for physiological integration, which enables movement of essential resources between connected ramets. This study investigated the capacity of physiological integration to buffer differences in resource availability experienced by ramets of the clonal wild strawberry plant, Fragaria vesca. Specifically, a study was made of the responses of connected and severed offspring ramets growing in environments with different water availability conditions (well watered or water stressed) and nitrogen forms (nitrate or ammonium). The experimental design consisted of three factors, 'integration' (connected, severed) 'water status' (well watered, water stressed) and 'nitrogen form' (nitrate, ammonium), applied in a pot experiment. The effects of physiological integration were studied by analysing photochemical efficiency, leaf spectral reflectance, photosynthesis and carbon and nitrogen isotope discrimination, the last of which has been neglected in previous studies. Physiological integration buffered the stress caused by water deprivation. As a consequence, survival was improved in water-stressed offspring ramets that remained connected to their parent plants. The nitrogen isotope composition (δ(15)N) values in the connected water-stressed ramets were similar to those in ramets in the ammonium treatment; however, δ(15)N values in connected well-watered ramets were similar to those in the nitrate treatment. The results also demonstrated the benefit of integration for offspring ramets in terms of photochemical activity and photosynthesis. This is the first study in which carbon and nitrogen isotopic discrimination has been used to detect physiological integration in clonal plants. The results for nitrogen isotope composition represent the first evidence of preferential transport of a specific form of nitrogen to compensate for stressful conditions experienced by a member clone. Water consumption was lower in plants supplied with ammonium than in plants supplied with nitrate, and therefore preferential transport of ammonium from parents to water-stressed offspring could potentially optimize the water use of the whole clone. © The Author 2014. Published by Oxford University Press on behalf of the Annals of Botany Company. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

On the Evolution of the Mammalian Brain.

PubMed

Torday, John S; Miller, William B

2016-01-01

Hobson and Friston have hypothesized that the brain must actively dissipate heat in order to process information (Hobson et al., 2014). This physiologic trait is functionally homologous with the first instantation of life formed by lipids suspended in water forming micelles- allowing the reduction in entropy (heat dissipation). This circumvents the Second Law of Thermodynamics permitting the transfer of information between living entities, enabling them to perpetually glean information from the environment, that is felt by many to correspond to evolution per se. The next evolutionary milestone was the advent of cholesterol, embedded in the cell membranes of primordial eukaryotes, facilitating metabolism, oxygenation and locomotion, the triadic basis for vertebrate evolution. Lipids were key to homeostatic regulation of calcium, forming calcium channels. Cell membrane cholesterol also fostered metazoan evolution by forming lipid rafts for receptor-mediated cell-cell signaling, the origin of the endocrine system. The eukaryotic cell membrane exapted to all complex physiologic traits, including the lung and brain, which are molecularly homologous through the function of neuregulin, mediating both lung development and myelinization of neurons. That cooption later exapted as endothermy during the water-land transition (Torday, 2015a), perhaps being the functional homolog for brain heat dissipation and conscious/mindful information processing. The skin and brain similarly share molecular homologies through the "skin-brain" hypothesis, giving insight to the cellular-molecular "arc" of consciousness from its unicellular origins to integrated physiology. This perspective on the evolution of the central nervous system clarifies self-organization, reconciling thermodynamic and informational definitions of the underlying biophysical mechanisms, thereby elucidating relations between the predictive capabilities of the brain and self-organizational processes.

Isozymes of lignin peroxidase and manganese(II) peroxidase from the white-rot basidiomycete Trametes versicolor. I. Isolation of enzyme forms and characterization of physical and catalytic properties.

PubMed

Johansson, T; Nyman, P O

1993-01-01

The basidiomycete Trametes versicolor is a white-rot fungus and a potent degrader of lignin. The development of extracellular enzyme activities in the fungal culture under physiological conditions of secondary metabolism was investigated. Using the culture medium as starting material a large number of peroxidase forms were purified by the use of chromatographic techniques. Sixteen forms of lignin peroxidase and five forms of manganese(II) peroxidase were separated and the majority of these enzymes was characterized with respect to isoelectric point, molecular mass, and specific enzyme activity. The manganese(II) peroxidases showed a lower isoelectric point (pI 3.2-2.9) and a slightly higher molecular mass (44-45 kDa) than the lignin peroxidases (pI 3.7-3.1, and 41-43 kDa). Specific enzyme activities for the forms of lignin peroxidase, using veratryl alcohol as the substrate, were found to differ considerably. Certain differences in the specific enzyme activity were also observed among the forms of manganese(II) peroxidase. A multitude of peroxidase forms has previously been encountered in another white-rot fungus, Phanerochaete chrysosporium. The discovery that it also occurs in T. versicolor would suggest that this multiplicity could be a common feature among white-rot fungi and may be essential for the biodegradation of lignin.

Who Perceives They Are Smarter? Exploring the Influence of Student Characteristics on Student Academic Self-Concept in Physiology

ERIC Educational Resources Information Center

Cooper, Katelyn M.; Krieg, Anna; Brownell, Sara E.

2018-01-01

Academic self-concept is one's perception of his or her ability in an academic domain and is formed by comparing oneself to other students. As college biology classrooms transition from lecturing to active learning, students interact more with each other and are likely comparing themselves more to other students in the class. Student…

Effect of Eight-Week Exercise Program on Social Physique Anxiety Conditions in Adult Males

ERIC Educational Resources Information Center

Akyüz, Öznur

2017-01-01

Physiological changes occurring with physical activity have played role in appearance of a different field of study. Thus, examination of the effect of eight-week exercise program on SPA in adult males forms the purpose of the study. 20 sedentary males aged 18-25 voluntarily participated in the research. Volunteers were applied resistance exercise…

Spinal atypical protein kinase C activity is necessary to stabilize inactivity-induced phrenic motor facilitation

PubMed Central

Strey, K.A.; Nichols, N.L.; Baertsch, N.A.; Broytman, O.; Baker-Herman, T.L.

2012-01-01

The neural network controlling breathing must establish rhythmic motor output at a level adequate to sustain life. Reduced respiratory neural activity elicits a novel form of plasticity in circuits driving the diaphragm known as inactivity-induced phrenic motor facilitation (iPMF), a rebound increase in phrenic inspiratory output observed once respiratory neural drive is restored. The mechanisms underlying iPMF are unknown. Here, we demonstrate in anesthetized rats that spinal mechanisms give rise to iPMF, and that iPMF consists of at least two mechanistically distinct phases: 1) an early, labile phase that requires atypical PKC (PKCζ and/or PKCΙ/λ) activity to transition to a 2) late, stable phase. Early (but not late) iPMF is associated with increased interactions between PKCζ/Ι and the scaffolding protein ZIP/p62 in spinal regions associated with the phrenic motor pool. Although PKCζ/Ι activity is necessary for iPMF, spinal aPKC activity is not necessary for phrenic long-term facilitation (pLTF) following acute intermittent hypoxia, an activity-independent form of spinal respiratory plasticity. Thus, while iPMF and pLTF both manifest as prolonged increases in phrenic burst amplitude, they arise from distinct spinal cellular pathways. Our data are consistent with the hypotheses that: 1) local mechanisms sense and respond to reduced respiratory-related activity in the phrenic motor pool, and 2) inactivity-induced increases in phrenic inspiratory output require local PKCζ/Ι activity to stabilize into a long-lasting iPMF. Although the physiological role of iPMF is unknown, we suspect that iPMF represents a compensatory mechanism, assuring adequate motor output in a physiological system where prolonged inactivity ends life. PMID:23152633

Role of pattern recognition receptors of the neurovascular unit in inflamm-aging.

PubMed

Wilhelm, Imola; Nyúl-Tóth, Ádám; Kozma, Mihály; Farkas, Attila E; Krizbai, István A

2017-11-01

Aging is associated with chronic inflammation partly mediated by increased levels of damage-associated molecular patterns, which activate pattern recognition receptors (PRRs) of the innate immune system. Furthermore, many aging-related disorders are associated with inflammation. PRRs, such as Toll-like receptors (TLRs) and nucleotide-binding oligomerization domain-like receptors (NLRs), are expressed not only in cells of the innate immune system but also in other cells, including cells of the neurovascular unit and cerebral vasculature forming the blood-brain barrier. In this review, we summarize our present knowledge about the relationship between activation of PRRs expressed by cells of the neurovascular unit-blood-brain barrier, chronic inflammation, and aging-related pathologies of the brain. The most important damage-associated molecular pattern-sensing PRRs in the brain are TLR2, TLR4, and NLR family pyrin domain-containing protein-1 and pyrin domain-containing protein-3, which are activated during physiological and pathological aging in microglia, neurons, astrocytes, and possibly endothelial cells and pericytes. Copyright © 2017 the American Physiological Society.

Loss of HMG-CoA Reductase in C. elegans Causes Defects in Protein Prenylation and Muscle Mitochondria

PubMed Central

Ranji, Parmida; Rauthan, Manish; Pitot, Christophe; Pilon, Marc

2014-01-01

HMG-CoA reductase is the rate-limiting enzyme in the mevalonate pathway and the target of cholesterol-lowering statins. We characterized the C. elegans hmgr-1(tm4368) mutant, which lacks HMG-CoA reductase, and show that its phenotypes recapitulate that of statin treatment, though in a more severe form. Specifically, the hmgr-1(tm4368) mutant has defects in growth, reproduction and protein prenylation, is rescued by exogenous mevalonate, exhibits constitutive activation of the UPRer and requires less mevalonate to be healthy when the UPRmt is activated by a constitutively active form of ATFS-1. We also show that different amounts of mevalonate are required for different physiological processes, with reproduction requiring the highest levels. Finally, we provide evidence that the mevalonate pathway is required for the activation of the UPRmt. PMID:24918786

Characterization of plasma cholinesterase in rabbit and evaluation of the inhibitory potential of diazinon.

PubMed

Oropesa, Ana Lourdes; Pérez-López, Marcos; Soler, Francisco

2014-02-01

Several studies indicate that more than one cholinesterase form may be present in the blood of mammals. In this study the predominant plasma cholinesterase activity, the physiological cholinesterase activity as well as cholinesterase sex-dependent changes in non-exposed individuals of rabbit have been established. Plasma cholinesterase was characterized using three substrates (acetylthiocholine iodide, propionylthiocholine iodide, and S-butyrylthiocholine iodide) and three cholinesterase inhibitors (eserine sulfate, BW284C51 and iso-OMPA). The results indicated that propionylthiocholine was the preferred substrate by plasma cholinesterase followed by acetylthiocholine and butyrylthiocholine, and the predominant enzymatic activity was acetylcholinesterase. Physiological plasma cholinesterase activity was 198.9 ± 5.8 nmol/min/ml for male and 205.2 ± 5.0 nmol/min/ml for female using acetylthiocholine as substrate. Thus, sex had no significant effect on the physiological cholinesterase activity (p>0.05). In addition, the in vivo and in vitro sensitivity of plasma cholinesterase to diazinon was also investigated. In rabbits exposed to single doses of diazinon (25 or 125 mg/kg) the higher inhibitions of plasma cholinesterase were reached 9h after oral administration (53% and 87% inhibition, respectively). Cholinesterase activity significantly recovered up to values similar to pre-administration between 3 and 7d depending on the administered dose and sex of the animals. Plasma cholinesterase activity decreased to 24%, 53% and 74% of the initial activity at 9h of in vitro exposure to 1.25, 3.13 and 6.25mg/l of diazinon, respectively, and it remained steadily depressed throughout the experimental period (10d). This study has demonstrated the sensitivity of cholinesterase activity in plasma of rabbits following both in vivo and in vitro exposure to sub-lethal concentrations of diazinon. © 2013 Published by Elsevier Inc.

Nitric oxide-mediated pathogenesis during nicotine and alcohol consumption.

PubMed

Cooper, R G; Magwere, T

2008-01-01

Nitric oxide (NO) is formed by different cell types in response to a variety of physiological and patho-physiological stimuli. The intake of nicotine and/or alcohol has patho-physiological effects on organ function, and the progression of alcohol-/tobacco-related diseases seem to be directly influenced by NO-mediated mechanisms. Nicotine has an adverse influence on blood vessel functionality, repair and maintenance. Chronic nicotine exposure augments atherosclerosis by enhancing the production of proinflammatory cytokines by macrophages which then activate atherogenic NF-kB target genes in aortic lesions. Alcohol produces NO which speeds up the apoptosis of neutrophils. Alcohol sensitizes the liver to endotoxemic shock. Nitrosative stress and increased basal levels of NO contribute to tumour growth. The progression of disease seems to be directed via a definite NO-mediated mechanism. This review gives an insight into how intake of tobacco and alcohol may affect quality of life.

Interviewing Suspects with Avatars: Avatars Are More Effective When Perceived as Human

PubMed Central

Ströfer, Sabine; Ufkes, Elze G.; Bruijnes, Merijn; Giebels, Ellen; Noordzij, Matthijs L.

2016-01-01

It has been consistently demonstrated that deceivers generally can be discriminated from truth tellers by monitoring an increase in their physiological response. But is this still the case when deceivers interact with a virtual avatar? The present research investigated whether the mere “belief” that the virtual avatar is computer or human operated forms a crucial factor for eliciting physiological cues to deception. Participants were interviewed about a transgression they had been seduced to commit, by a human-like virtual avatar. In a between-subject design, participants either deceived or told the truth about this transgression. During the interviews, we measured the physiological responses assessing participants' electrodermal activity (EDA). In line with our hypothesis, EDA differences between deceivers and truth tellers only were significant for participants who believed they interacted with a human operated (compared to a computer operated) avatar. These results have theoretical as well as practical implications which we will discuss. PMID:27148150

Advances in Our Understanding of Oxylipins Derived from Dietary PUFAs12

PubMed Central

Gabbs, Melissa; Leng, Shan; Devassy, Jessay G; Monirujjaman, Md; Aukema, Harold M

2015-01-01

Oxylipins formed from polyunsaturated fatty acids (PUFAs) are the main mediators of PUFA effects in the body. They are formed via cyclooxygenase, lipoxygenase, and cytochrome P450 pathways, resulting in the formation of prostaglandins, thromboxanes, mono-, di-, and tri-hydroxy fatty acids (FAs), epoxy FAs, lipoxins, eoxins, hepoxilins, resolvins, protectins (also called neuroprotectins in the brain), and maresins. In addition to the well-known eicosanoids derived from arachidonic acid, recent developments in lipidomic methodologies have raised awareness of and interest in the large number of oxylipins formed from other PUFAs, including those from the essential FAs and the longer-chain n–3 (ω-3) PUFAs. Oxylipins have essential roles in normal physiology and function, but can also have detrimental effects. Compared with the oxylipins derived from n–3 PUFAs, oxylipins from n–6 PUFAs generally have greater activity and more inflammatory, vasoconstrictory, and proliferative effects, although there are notable exceptions. Because PUFA composition does not necessarily reflect oxylipin composition, comprehensive analysis of the oxylipin profile is necessary to understand the overall physiologic effects of PUFAs mediated through their oxylipins. These analyses should include oxylipins derived from linoleic and α-linolenic acids, because these largely unexplored bioactive oxylipins constitute more than one-half of oxylipins present in tissues. Because collated information on oxylipins formed from different PUFAs is currently unavailable, this review provides a detailed compilation of the main oxylipins formed from PUFAs and describes their functions. Much remains to be elucidated in this emerging field, including the discovery of more oxylipins, and the understanding of the differing biological potencies, kinetics, and isomer-specific activities of these novel PUFA metabolites. PMID:26374175

Piezo proteins are pore-forming subunits of mechanically activated channels.

PubMed

Coste, Bertrand; Xiao, Bailong; Santos, Jose S; Syeda, Ruhma; Grandl, Jörg; Spencer, Kathryn S; Kim, Sung Eun; Schmidt, Manuela; Mathur, Jayanti; Dubin, Adrienne E; Montal, Mauricio; Patapoutian, Ardem

2012-02-19

Mechanotransduction has an important role in physiology. Biological processes including sensing touch and sound waves require as-yet-unidentified cation channels that detect pressure. Mouse Piezo1 (MmPiezo1) and MmPiezo2 (also called Fam38a and Fam38b, respectively) induce mechanically activated cationic currents in cells; however, it is unknown whether Piezo proteins are pore-forming ion channels or modulate ion channels. Here we show that Drosophila melanogaster Piezo (DmPiezo, also called CG8486) also induces mechanically activated currents in cells, but through channels with remarkably distinct pore properties including sensitivity to the pore blocker ruthenium red and single channel conductances. MmPiezo1 assembles as a ∼1.2-million-dalton homo-oligomer, with no evidence of other proteins in this complex. Purified MmPiezo1 reconstituted into asymmetric lipid bilayers and liposomes forms ruthenium-red-sensitive ion channels. These data demonstrate that Piezo proteins are an evolutionarily conserved ion channel family involved in mechanotransduction.

Inactivity-induced respiratory plasticity: Protecting the drive to breathe in disorders that reduce respiratory neural activity☆

PubMed Central

Strey, K.A.; Baertsch, N.A.; Baker-Herman, T.L.

2013-01-01

Multiple forms of plasticity are activated following reduced respiratory neural activity. For example, in ventilated rats, a central neural apnea elicits a rebound increase in phrenic and hypoglossal burst amplitude upon resumption of respiratory neural activity, forms of plasticity called inactivity-induced phrenic and hypoglossal motor facilitation (iPMF and iHMF), respectively. Here, we provide a conceptual framework for plasticity following reduced respiratory neural activity to guide future investigations. We review mechanisms giving rise to iPMF and iHMF, present new data suggesting that inactivity-induced plasticity is observed in inspiratory intercostals (iIMF) and point out gaps in our knowledge. We then survey conditions relevant to human health characterized by reduced respiratory neural activity and discuss evidence that inactivity-induced plasticity is elicited during these conditions. Understanding the physiological impact and circumstances in which inactivity-induced respiratory plasticity is elicited may yield novel insights into the treatment of disorders characterized by reductions in respiratory neural activity. PMID:23816599

Molecular crowding overcomes the destabilizing effects of mutations in a bacterial ribozyme

DOE PAGES

Lee, Hui-Ting; Kilburn, D.; Behrouzi, R.; ...

2014-12-05

The native structure of the Azoarcus group I ribozyme is stabilized by the cooperative formation of tertiary interactions between double helical domains. Thus, even single mutations that break this network of tertiary interactions reduce ribozyme activity in physiological Mg2+ concentrations. Here, we report that molecular crowding comparable to that in the cell compensates for destabilizing mutations in the Azoarcus ribozyme. Small angle X-ray scattering, native polyacrylamide gel electrophoresis and activity assays were used to compare folding free energies in dilute and crowded solutions containing 18% PEG1000. Crowder molecules allowed the wild-type and mutant ribozymes to fold at similarly low Mg2+more » concentrations and stabilized the active structure of the mutant ribozymes under physiological conditions. This compensation helps explains why ribozyme mutations are often less deleterious in the cell than in the test tube. Nevertheless, crowding did not rescue the high fraction of folded but less active structures formed by double and triple mutants. We conclude that crowding broadens the fitness landscape by stabilizing compact RNA structures without improving the specificity of self-assembly.« less

Molecular crowding overcomes the destabilizing effects of mutations in a bacterial ribozyme

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

Lee, Hui-Ting; Kilburn, D.; Behrouzi, R.

The native structure of the Azoarcus group I ribozyme is stabilized by the cooperative formation of tertiary interactions between double helical domains. Thus, even single mutations that break this network of tertiary interactions reduce ribozyme activity in physiological Mg2+ concentrations. Here, we report that molecular crowding comparable to that in the cell compensates for destabilizing mutations in the Azoarcus ribozyme. Small angle X-ray scattering, native polyacrylamide gel electrophoresis and activity assays were used to compare folding free energies in dilute and crowded solutions containing 18% PEG1000. Crowder molecules allowed the wild-type and mutant ribozymes to fold at similarly low Mg2+more » concentrations and stabilized the active structure of the mutant ribozymes under physiological conditions. This compensation helps explains why ribozyme mutations are often less deleterious in the cell than in the test tube. Nevertheless, crowding did not rescue the high fraction of folded but less active structures formed by double and triple mutants. We conclude that crowding broadens the fitness landscape by stabilizing compact RNA structures without improving the specificity of self-assembly.« less

PHYSIOLOGY OF ION TRANSPORT ACROSS THE TONOPLAST OF HIGHER PLANTS.

PubMed

Barkla, Bronwyn J.; Pantoja, Omar

1996-06-01

The vacuole of plant cells plays an important role in the homeostasis of the cell. It is involved in the regulation of cytoplasmic pH, sequestration of toxic ions and xenobiotics, regulation of cell turgor, storage of amino acids, sugars and CO2 in the form of malate, and possibly as a source for elevating cytoplasmic calcium. All these activities are driven by two primary active transport mechanisms present in the vacuolar membrane (tonoplast). These two mechanisms employ high-energy metabolites to pump protons into the vacuole, establishing a proton electrochemical potential that mediates the transport of a diverse range of solutes. Within the past few years, great advances at the molecular and functional levels have been made on the characterization and identification of these mechanisms. The aim of this review is to summarize these studies in the context of the physiology of the plant cell.

Physiological relaxation induced by horticultural activity: transplanting work using flowering plants.

PubMed

Lee, Min-sun; Park, Bum-jin; Lee, Juyoung; Park, Kun-tae; Ku, Ja-hyeong; Lee, Jun-woo; Oh, Kyung-ok; Miyazaki, Yoshifumi

2013-10-10

Despite increasing attention and a growing volume of research data, little physiological evidence is available on the benefits of horticultural activity and the different effects on individuals. Therefore, the aim of the present study was to investigate the physiological effects of horticultural activity and to examine how differences in personality alter these effects. The effects of transplanting real flowers (horticultural activity) and handling artificial flowers (control activity) on human physiological activity were compared. On the first day, eight participants engaged in horticultural activity and another eight in the control activity. On the second day, participants switched roles. Participants' physiological conditions during each activity were assessed by measuring the heart rate and heart rate variability (HRV). Psychological responses, which were measured using a semantic differential rating scale, showed that the horticultural activity promoted comfortable, soothed, and natural feelings, compared to the control activity. Analysis of physiological responses using two-way repeated measures analysis of variance (ANOVA) revealed that sympathetic nervous activity significantly decreased in the late time period (11 to 15 minutes) of horticultural activity only in the type A group. This study supports the fact that the horticultural activity can enhance psychological and physiological relaxation effects, although these physiological effects can differ among individuals with different personalities.

Physiological relaxation induced by horticultural activity: transplanting work using flowering plants

PubMed Central

2013-01-01

Background Despite increasing attention and a growing volume of research data, little physiological evidence is available on the benefits of horticultural activity and the different effects on individuals. Therefore, the aim of the present study was to investigate the physiological effects of horticultural activity and to examine how differences in personality alter these effects. Results The effects of transplanting real flowers (horticultural activity) and handling artificial flowers (control activity) on human physiological activity were compared. On the first day, eight participants engaged in horticultural activity and another eight in the control activity. On the second day, participants switched roles. Participants’ physiological conditions during each activity were assessed by measuring the heart rate and heart rate variability (HRV). Psychological responses, which were measured using a semantic differential rating scale, showed that the horticultural activity promoted comfortable, soothed, and natural feelings, compared to the control activity. Analysis of physiological responses using two-way repeated measures analysis of variance (ANOVA) revealed that sympathetic nervous activity significantly decreased in the late time period (11 to 15 minutes) of horticultural activity only in the type A group. Conclusions This study supports the fact that the horticultural activity can enhance psychological and physiological relaxation effects, although these physiological effects can differ among individuals with different personalities. PMID:24112302

S-acylation dependent post-translational cross-talk regulates large conductance calcium- and voltage- activated potassium (BK) channels

PubMed Central

Shipston, Michael J.

2014-01-01

Mechanisms that control surface expression and/or activity of large conductance calcium-activated potassium (BK) channels are important determinants of their (patho)physiological function. Indeed, BK channel dysfunction is associated with major human disorders ranging from epilepsy to hypertension and obesity. S-acylation (S-palmitoylation) represents a major reversible, post-translational modification controlling the properties and function of many proteins including ion channels. Recent evidence reveals that both pore-forming and regulatory subunits of BK channels are S-acylated and control channel trafficking and regulation by AGC-family protein kinases. The pore-forming α-subunit is S-acylated at two distinct sites within the N- and C-terminus, each site being regulated by different palmitoyl acyl transferases (zDHHCs) and acyl thioesterases (APTs). S-acylation of the N-terminus controls channel trafficking and surface expression whereas S-acylation of the C-terminal domain determines regulation of channel activity by AGC-family protein kinases. S-acylation of the regulatory β4-subunit controls ER exit and surface expression of BK channels but does not affect ion channel kinetics at the plasma membrane. Furthermore, a significant number of previously identified BK-channel interacting proteins have been shown, or are predicted to be, S-acylated. Thus, the BK channel multi-molecular signaling complex may be dynamically regulated by this fundamental post-translational modification and thus S-acylation likely represents an important determinant of BK channel physiology in health and disease. PMID:25140154

A capillary zone electrophoresis method to detect conformers and dimers of antithrombin in therapeutic preparations.

PubMed

Marie, Anne-Lise; Tran, Nguyet Thuy; Saller, François; Abdou, Youmna Mohamed; Zeau, Pascal; Plantier, Jean-Luc; Urbain, Rémi; Borgel, Delphine; Taverna, Myriam

2016-07-01

Antithrombin (AT) is a human plasma glycoprotein that possesses anticoagulant and anti-inflammatory properties. However, the native (active) form of AT is unstable and undergoes conformational changes, leading to latent, cleaved, and heterodimeric forms. The presence of these alternative forms mostly inactive can highly impact the quality and therapeutic activity of pharmaceutical AT preparations. We developed a capillary zone electrophoresis method, based on a neutral polyethylene oxide-coated capillary and a buffer close to physiological conditions, enabling the separation of more than eight forms of AT. Several peaks were identified as native, latent, and heterodimeric forms. The CZE method was reproducible with intraday relative standard deviations less than 0.5 and 2% for migration times and peak areas, respectively. The method was applied to the comparison of AT preparations produced by five competitive pharmaceutical companies, and statistical tests were performed. Important differences in the proportion of each form were highlighted. In particular, one AT preparation was shown to contain a high quantity of heterodimer, and two preparations contained high quantities of latent form. In addition, one AT preparation exhibited additional forms, not yet identified. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

A new Drosophila octopamine receptor responds to serotonin.

PubMed

Qi, Yi-Xiang; Xu, Gang; Gu, Gui-Xiang; Mao, Fen; Ye, Gong-Yin; Liu, Weiwei; Huang, Jia

2017-11-01

As the counterparts of the vertebrate adrenergic transmitters, octopamine and tyramine are important physiological regulators in invertebrates. They control and modulate many physiological and behavioral functions in insects. In this study, we reported the pharmacological properties of a new α2-adrenergic-like octopamine receptor (CG18208) from Drosophila melanogaster, named DmOctα2R. This new receptor gene encodes two transcripts by alternative splicing. The long isoform DmOctα2R-L differs from the short isoform DmOctα2R-S by the presence of an additional 29 amino acids within the third intracellular loop. When heterologously expressed in mammalian cell lines, both receptors were activated by octopamine, tyramine, epinephrine and norepinephrine, resulting in the inhibition of cAMP production in a dose-dependent manner. The long form is more sensitive to the above ligands than the short form. The adrenergic agonists naphazoline, tolazoline and clonidine can stimulate DmOctα2R as full agonists. Surprisingly, serotonin and serotoninergic agonists can also activate DmOctα2R. Several tested adrenergic antagonists and serotonin antagonists blocked the action of octopamine or serotonin on DmOctα2R. The data presented here reported an adrenergic-like G protein-coupled receptor activated by serotonin, suggesting that the neurotransmission and neuromodulation in the nervous system could be more complex than previously thought. Copyright © 2017 Elsevier Ltd. All rights reserved.

Pulsed 86Sr-labeling and NanoSIMS imaging to study coral biomineralization at ultra-structural length scales

NASA Astrophysics Data System (ADS)

Brahmi, C.; Domart-Coulon, I.; Rougée, L.; Pyle, D. G.; Stolarski, J.; Mahoney, J. J.; Richmond, R. H.; Ostrander, G. K.; Meibom, A.

2012-09-01

A method to label marine biocarbonates is developed based on a concentration enrichment of a minor stable isotope of a trace element that is a natural component of seawater, resulting in the formation of biocarbonate with corresponding isotopic enrichments. This biocarbonate is subsequently imaged with a NanoSIMS ion microprobe to visualize the locations of the isotopic marker on sub-micrometric length scales, permitting resolution of all ultra-structural details. In this study, a scleractinian coral, Pocillopora damicornis, was labeled 3 times with 86Sr-enhanced seawater for a period of 48 h with 5 days under normal seawater conditions separating each labeling event. Two non-specific cellular stress biomarkers, glutathione-S-transferase activity and porphyrin concentration plus carbonic anhydrase, an enzymatic marker involved in the physiology of carbonate biomineralization, as well as unchanged levels of zooxanthellae photosynthesis efficiency indicate that coral physiological processes are not affected by the 86Sr-enhancement. NanoSIMS images of the 86Sr/44Ca ratio in skeleton formed during the experiment allow for a determination of the average extension rate of the two major ultra-structural components of the coral skeleton: Rapid Accretion Deposits are found to form on average about 4.5 times faster than Thickening Deposits. The method opens up new horizons in the study of biocarbonate formation because it holds the potential to observe growth of calcareous structures such as skeletons, shells, tests, spines formed by a wide range of organisms under essentially unperturbed physiological conditions.

Cardiac and renal upregulation of Nox2 and NF-κB and repression of Nox4 and Nrf2 in season- and diabetes-mediated models of vascular oxidative stress in guinea-pig and rat.

PubMed

Gajos-Draus, Anna; Duda, Monika; Beręsewicz, Andrzej

2017-11-01

The superoxide-forming NADPH oxidase homologues, Nox1, Nox2, and Nox5, seem to mediate the pro-atherosclerotic vascular phenotype. The hydrogen peroxide-forming Nox4 afforded vascular protection, likely via NF-E2-related factor-2 (Nrf2) activation and/or Nox2 downregulation in transgenic mice. We hypothesized that oxidative stress in the intact vasculature involves, aside from the upregulation of the superoxide-forming Noxs, the downregulation of the Nox4/Nrf2 pathway. Guinea-pigs and rats were studied either in winter or in summer, and the streptozotocin diabetic rats in winter. Plasma nitrite, and superoxide production by isolated hearts were measured, while frozen tissues served in biochemical analyses. Summer in both species and diabetes in rats downregulated myocardial Nox4 while reciprocally upregulating Nox2 and Nox5 in guinea-pigs, and Nox2 in rats. Simultaneously, myocardial Nrf2 activity and the expression of the Nrf2-directed heme oxygenase-1 and endothelial NO synthase were reduced while activity of the nuclear factor κ B (NF- κ B) and the expression of NF- κ B-directed inducible NO synthase and the vascular cell adhesion molecule-1 were increased. Cardiac superoxide production was increased while plasma nitrite was decreased reciprocally. Analogous disregulation of Noxs, Nrf2, and NF- κ B, occurred in diabetic rat kidneys. Given the diversity of the experimental settings and the uniform pattern of the responses, we speculate that: (1) chronic vascular oxidative stress is a nonspecific (model-, species-, organ-independent) response involving the induction of Nox2 (and Nox5 in guinea-pigs) and the NF- κ B pathway, and the repression of Nox4 and the Nrf2 pathway; and (2) the systems Nox2-NF- κ B and Nox4-Nrf2 regulate each other negatively. © 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

New physiologically-relevant liver tissue model based on hierarchically cocultured primary rat hepatocytes with liver endothelial cells.

PubMed

Xiao, Wenjin; Perry, Guillaume; Komori, Kikuo; Sakai, Yasuyuki

2015-11-01

To develop an in vitro liver tissue equivalent, hepatocytes should be cocultured with liver non-parenchymal cells to mimic the in vivo physiological microenvironments. In this work, we describe a physiologically-relevant liver tissue model by hierarchically organizing layers of primary rat hepatocytes and human liver sinusoidal endothelial cells (TMNK-1) on an oxygen-permeable polydimethylsiloxane (PDMS) membrane, which facilitates direct oxygenation by diffusion through the membrane. This in vivo-mimicking hierarchical coculture was obtained by simply proceeding the overlay of TMNK-1 cells on the hepatocyte layer re-formed on the collagen immobilized PDMS membranes. The comparison of hepatic functionalities was achieved between coculture and sandwich culture with Matrigel, in the presence and absence of direct oxygenation. A complete double-layered structure of functional liver cells with vertical contact between hepatocytes and TMNK-1 was successfully constructed in the coculture with direct oxygen supply and was well-maintained for 14 days. The hepatocytes in this hierarchical culture exhibited improved survival, functional bile canaliculi formation, cellular level polarization and maintenance of metabolic activities including Cyp1A1/2 activity and albumin production. By contrast, the two cell populations formed discontinuous monolayers on the same surfaces in the non-oxygen-permeable cultures. These results demonstrate that (i) the direct oxygenation through the PDMS membranes enables very simple formation of a hierarchical structure consisting of a hepatocyte layer and a layer of TMNK-1 and (ii) we may include other non-parenchymal cells in this format easily, which can be widely applicable to other epithelial organs.

Naturally occurring alkaline amino acids function as efficient catalysts on Knoevenagel condensation at physiological pH: a mechanistic elucidation.

PubMed

Li, Weina; Fedosov, Sergey; Tan, Tianwei; Xu, Xuebing; Guo, Zheng

2014-05-01

To maintain biological functions, thousands of different reactions take place in human body at physiological pH (7.0) and mild conditions, which is associated with health and disease. Therefore, to examine the catalytic function of the intrinsically occurring molecules, such as amino acids at neutral pH, is of fundamental interests. Natural basic α-amino acid of L-lysine, L-arginine, and L-histidine neutralized to physiological pH as salts were investigated for their ability to catalyze Knoevenagel condensation of benzaldehyde and ethyl cyanoacetate. Compared with their free base forms, although neutralized alkaline amino acid salts reduced the catalytic activity markedly, they were still capable to perform an efficient catalysis at physiological pH as porcine pancreatic lipase (PPL), one of the best enzymes that catalyze Knoevenagel condensation. In agreement with the fact that the three basic amino acids were well neutralized, stronger basic amino acid Arg and Lys showed more obvious variation in NH bend peak from the FTIR spectroscopy study. Study of ethanol/water system and quantitative kinetic analysis suggested that the microenvironment in the vicinity of amino acid salts and protonability/deprotonability of the amine moiety may determine their catalytic activity and mechanism. The kinetic study of best approximation suggested that the random binding might be the most probable catalytic mechanism for the neutralized alkaline amino acid salt-catalyzed Knoevenagel condensation.

Influence of elevated CO2 concentrations on cell division and nitrogen fixation rates in the bloom-forming cyanobacterium Nodularia spumigena

NASA Astrophysics Data System (ADS)

Czerny, J.; Ramos, J. Barcelos E.; Riebesell, U.

2009-09-01

The surface ocean absorbs large quantities of the CO2 emitted to the atmosphere from human activities. As this CO2 dissolves in seawater, it reacts to form carbonic acid. While this phenomenon, called ocean acidification, has been found to adversely affect many calcifying organisms, some photosynthetic organisms appear to benefit from increasing [CO2]. Among these is the cyanobacterium Trichodesmium, a predominant diazotroph (nitrogen-fixing) in large parts of the oligotrophic oceans, which responded with increased carbon and nitrogen fixation at elevated pCO2. With the mechanism underlying this CO2 stimulation still unknown, the question arises whether this is a common response of diazotrophic cyanobacteria. In this study we therefore investigate the physiological response of Nodularia spumigena, a heterocystous bloom-forming diazotroph of the Baltic Sea, to CO2-induced changes in seawater carbonate chemistry. N. spumigena reacted to seawater acidification/carbonation with reduced cell division rates and nitrogen fixation rates, accompanied by significant changes in carbon and phosphorus quota and elemental composition of the formed biomass. Possible explanations for the contrasting physiological responses of Nodularia compared to Trichodesmium may be found in the different ecological strategies of non-heterocystous (Trichodesmium) and heterocystous (Nodularia) cyanobacteria.

Unraveling the role of dark septate endophyte (DSE) colonizing maize (Zea mays) under cadmium stress: physiological, cytological and genic aspects.

PubMed

Wang, Jun-ling; Li, Tao; Liu, Gao-yuan; Smith, Joshua M; Zhao, Zhi-wei

2016-02-25

A growing body of evidence suggests that plant root-associated fungi such as dark septate endophytes (DSE) can help plants overcome many biotic and abiotic stresses, of great interest is DSE-plant metal tolerance and alleviation capabilities on contaminated soils. However, the tolerance and alleviation mechanisms involved have not yet been elucidated. In the current study, the regulation and physiological response of Zea mays to its root-associated DSE, Exophiala pisciphila was analyzed under increased soil Cd stress (0, 10, 50, 100 mg kg(-1)). Under Cd stress, DSE inoculation significantly enhanced the activities of antioxidant enzymes and low-molecular weight antioxidants, while also inducing increased Cd accumulation in the cell wall and conversion of Cd into inactive forms by shoot and root specific regulation of genes related to metal uptake, translocation and chelation. Our results showed that DSE colonization resulted in a marked tolerance to Cd, with a significant decrease in cadmium phytotoxicity and a significant increase in maize growth by triggering antioxidant systems, altering metal chemical forms into inactive Cd, and repartitioning subcellular Cd into the cell wall. These results provide comprehensive evidence for the mechanisms by which DSE colonization bioaugments Cd tolerance in maize at physiological, cytological and molecular levels.

Humor, laughter, learning, and health! A brief review.

PubMed

Savage, Brandon M; Lujan, Heidi L; Thipparthi, Raghavendar R; DiCarlo, Stephen E

2017-09-01

Human emotions, such as anxiety, depression, fear, joy, and laughter, profoundly affect psychological and physiological processes. These emotions form a set of basic, evolved functions that are shared by all humans. Laughter is part of a universal language of basic emotions that all humans recognize. Health care providers and educators may utilize the power of laughter to improve health and enhance teaching and learning. This is an important consideration because teaching is not just about content: it is also about forming relationships and strengthening human connections. In this context, when used effectively, humor is documented to build relationships and enhance performance. Specifically, humor improves student performance by attracting and sustaining attention, reducing anxiety, enhancing participation, and increasing motivation. Moreover, humor stimulates multiple physiological systems that decrease levels of stress hormones, such as cortisol and epinephrine, and increase the activation of the mesolimbic dopaminergic reward system. To achieve these benefits, it is important to use humor that is relevant to the course content and not disparaging toward others. Self-effacing humor illustrates to students that the teacher is comfortable making mistakes and sharing these experiences with the classroom. In this brief review, we discuss the history and relationship between humor, laughing, learning, and health with an emphasis on the powerful, universal language of laughter. Copyright © 2017 the American Physiological Society.

Unraveling the role of dark septate endophyte (DSE) colonizing maize (Zea mays) under cadmium stress: physiological, cytological and genic aspects

NASA Astrophysics Data System (ADS)

Wang, Jun-Ling; Li, Tao; Liu, Gao-Yuan; Smith, Joshua M.; Zhao, Zhi-Wei

2016-02-01

A growing body of evidence suggests that plant root-associated fungi such as dark septate endophytes (DSE) can help plants overcome many biotic and abiotic stresses, of great interest is DSE-plant metal tolerance and alleviation capabilities on contaminated soils. However, the tolerance and alleviation mechanisms involved have not yet been elucidated. In the current study, the regulation and physiological response of Zea mays to its root-associated DSE, Exophiala pisciphila was analyzed under increased soil Cd stress (0, 10, 50, 100 mg kg-1). Under Cd stress, DSE inoculation significantly enhanced the activities of antioxidant enzymes and low-molecular weight antioxidants, while also inducing increased Cd accumulation in the cell wall and conversion of Cd into inactive forms by shoot and root specific regulation of genes related to metal uptake, translocation and chelation. Our results showed that DSE colonization resulted in a marked tolerance to Cd, with a significant decrease in cadmium phytotoxicity and a significant increase in maize growth by triggering antioxidant systems, altering metal chemical forms into inactive Cd, and repartitioning subcellular Cd into the cell wall. These results provide comprehensive evidence for the mechanisms by which DSE colonization bioaugments Cd tolerance in maize at physiological, cytological and molecular levels.

Supra-physiological folic acid concentrations induce aberrant DNA methylation in normal human cells in vitro.

PubMed

Charles, Michelle A; Johnson, Ian T; Belshaw, Nigel J

2012-07-01

The micronutrients folate and selenium may modulate DNA methylation patterns by affecting intracellular levels of the methyl donor S-adenosylmethionine (SAM) and/or the product of methylation reactions S-adenosylhomocysteine (SAH). WI-38 fibroblasts and FHC colon epithelial cells were cultured in the presence of two forms of folate or four forms of selenium at physiologically-relevant doses, and their effects on LINE-1 methylation, gene-specific CpG island (CGI) methylation and intracellular SAM:SAH were determined. At physiologically-relevant doses the forms of folate or selenium had no effect on LINE-1 or CGI methylation, nor on intracellular SAM:SAH. However the commercial cell culture media used for the selenium studies, containing supra-physiological concentrations of folic acid, induced LINE-1 hypomethylation, CGI hypermethylation and decreased intracellular SAM:SAH in both cell lines. We conclude that the exposure of normal human cells to supra-physiological folic acid concentrations present in commercial cell culture media perturbs the intracellular SAM:SAH ratio and induces aberrant DNA methylation.

RUTBC1 Functions as a GTPase-activating Protein for Rab32/38 and Regulates Melanogenic Enzyme Trafficking in Melanocytes*

PubMed Central

Marubashi, Soujiro; Shimada, Hikaru; Fukuda, Mitsunori; Ohbayashi, Norihiko

2016-01-01

Two cell type-specific Rab proteins, Rab32 and Rab38 (Rab32/38), have been proposed as regulating the trafficking of melanogenic enzymes, including tyrosinase and tyrosinase-related protein 1 (Tyrp1), to melanosomes in melanocytes. Like other GTPases, Rab32/38 function as switch molecules that cycle between a GDP-bound inactive form and a GTP-bound active form; the cycle is thought to be regulated by an activating enzyme, guanine nucleotide exchange factor (GEF), and an inactivating enzyme, GTPase-activating protein (GAP), which stimulates the GTPase activity of Rab32/38. Although BLOC-3 has already been identified as a Rab32/38-specific GEF that regulates the trafficking of tyrosinase and Tyrp1, no physiological GAP for Rab32/38 in melanocytes has ever been identified, and it has remained unclear whether Rab32/38 is involved in the trafficking of dopachrome tautomerase, another melanogenic enzyme, in mouse melanocytes. In this study we investigated RUTBC1, which was originally characterized as a Rab9-binding protein and GAP for Rab32 and Rab33B in vitro, and the results demonstrated that RUTBC1 functions as a physiological GAP for Rab32/38 in the trafficking of all three melanogenic enzymes in mouse melanocytes. The results of this study also demonstrated the involvement of Rab9A in the regulation of the RUTBC1 localization and in the trafficking of all three melanogenic enzymes. We discovered that either excess activation or inactivation of Rab32/38 achieved by manipulating RUTBC1 inhibits the trafficking of all three melanogenic enzymes. These results collectively indicate that proper spatiotemporal regulation of Rab32/38 is essential for the trafficking of all three melanogenic enzymes in mouse melanocytes. PMID:26620560

[Methuosis: a novel type of cell death].

PubMed

Cai, Hongbing; Liu, Jinkun; Fan, Qin; Li, Xin

2013-12-01

Cell death is a major physiological or pathological phenomenon in life activities. The classic forms of cell death include apoptosis, necrosis, and autophagy. Recently, a novel type of cell death has been observed and termed as methuosis, in which excessive stimuli can induce cytoplasmic uptake and accumulation of small bubbles that gradually merge into giant vacuoles, eventually leading to decreased cellular metabolic activity, cell membrane rupture and cell death. In this article, we describe the nomenclature, morphological characteristics and underlying mechanisms of methuosis, compare methuosis with autophagy, oncosis and paraptosis, and review the related researches.

[Cardiac rhythm variability as an index of vegetative heart regulation in a situation of psychoemotional tension].

PubMed

Revina, N E

2006-01-01

Differentiated role of segmental and suprasegmental levels of cardiac rhythm variability regulation in dynamics of motivational human conflict was studied for the first time. The author used an original method allowing simultaneous analysis of psychological and physiological parameters of human activity. The study demonstrates that will and anxiety, as components of motivational activity spectrum, form the "energetic" basis of voluntary-constructive and involuntary-affective behavioral strategies, selectively uniting various levels of suprasegmental and segmental control of human heart functioning in a conflict situation.

Generator for gallium-68 and compositions obtained therefrom

DOEpatents

Neirinckx, Rudi D.; Davis, Michael A.

1981-01-01

A generator for obtaining radioactive gallium-68 from germanium-68 bound in a resin containing unsubstituted phenolic hydroxyl groups. The germanium-68 is loaded into the resin from an aqueous solution of the germanium-68. A physiologically acceptable solution of gallium-68 having an activity of 0.1 to 50 millicuries per milliliter of gallium-68 solution is obtained. The solution is obtained from the bound germanium-68 which forms gallium-68 in situ by eluting the column with a hydrochloric acid solution to form an acidic solution of gallium-68. The acidic solution of gallium-68 can be neutralized.

Venom Protein C activators as diagnostic agents for defects of protein C System.

PubMed

Ramzan, Faiqah; Asmat, Andleeb

2018-06-18

Background Protein C is a vitamin K dependent plasma zymogen. It prevents clotting by inhibiting clotting by inactivating factor V and factor VIII. Protein C activation pathway involves three steps: (i) Activation of protein C; (ii) Inhibition of coagulation through inactivating factor V and VIII by activated protein C and (iii) Inhibition of activated protein C by plasma protease inhibitors specific for this enzyme. Proteinases converts the zymogen Protein C (PC) of vertebrates into activated PC, which has been detected in several snake venoms. Most PC activators have been purified from venom of snake species belonging to the genera of the Agkistrodon complex. Unlike the physiological thrombin-catalyzed PC activation reaction which requires thrombomodulin as a cofactor, most snake venom activators directly convert the zymogen PC into the catalytically active form which can easily be determined by means of coagulation or chromogenic substrate techniques. Conclusion The fast-acting PC activator Protac® from Agkistrodon contortrix (southern copperhead snake) venom has been found to have broad application in diagnostic practice for the determination of disorders in the PC pathway. Recently, screening assays for the PC pathway have been introduced, based on the observation that the PC pathway is probably the most important physiological barrier against thrombosis. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Daily Physical Activity and Hot Flashes in the Study of Women's Health Across the Nation FLASHES Study

PubMed Central

Gibson, Carolyn; Matthews, Karen; Thurston, Rebecca

2014-01-01

Objective To examine the role of physical activity in menopausal hot flashes. Competing models conceptualize physical activity as a risk or protective factor for hot flashes. Few studies have examined this relationship prospectively using physiologic measures of hot flashes and physical activity. Design Over two 48 hour-periods, 51 participants wore a physiologic hot flash monitor and activity monitor, and reported their hot flashes in an electronic diary. Physiologic hot flashes, reported hot flashes and reported hot flashes without physiological corroboration were related to activity changes using hierarchical generalized linear modeling, adjusting for potential confounders. Setting Community. Patients Midlife women. Interventions None. Main Outcome Measures Physiologically-detected hot flashes and reported hot flashes with and without physiologic corroboration. Results Hot flash reports without physiologic corroboration were more likely after activity increases (OR 1.04, 95% CI: 1.00-1.10, p=.01), particularly among women with higher levels of depressive symptoms (interaction p=.02). No other types of hot flashes were related to physical activity. Conclusion Acute increases in physical activity were associated with increased reporting of hot flashes lacking physiologic corroboration, particularly among women with depressive symptoms. Clinicians should consider the role of symptom perception and reporting in relations between physical activity and hot flashes. PMID:24491454

Preparation of Single-cohort Colonies and Hormone Treatment of Worker Honeybees to Analyze Physiology Associated with Role and/or Endocrine System.

PubMed

Ueno, Takayuki; Kawasaki, Kiyoshi; Kubo, Takeo

2016-09-06

Honeybee workers are engaged in various tasks related to maintaining colony activity. The tasks of the workers change according to their age (age-related division of labor). Young workers are engaged in nursing the brood (nurse bees), while older workers are engaged in foraging for nectar and pollen (foragers). The physiology of the workers changes in association with this role shift. For example, the main function of the hypopharyngeal glands (HPGs) changes from the secretion of major royal jelly proteins (MRJPs) to the secretion of carbohydrate-metabolizing enzymes. Because worker tasks change as the workers age in typical colonies, it is difficult to discriminate the physiological changes that occur with aging from those that occur with the role shift. To study the physiological changes in worker tissues, including the HPGs, in association with the role shift, it would be useful to manipulate the honeybee colony population by preparing single-cohort colonies in which workers of almost the same age perform different tasks. Here we describe a detailed protocol for preparing single-cohort colonies for this analysis. Six to eight days after single-cohort colony preparation, precocious foragers that perform foraging tasks earlier than usual appear in the colony. Representative results indicated role-associated changes in HPG gene expression, suggesting role-associated HPG function. In addition to manipulating the colony population, analysis of the endocrine system is important for investigating role-associated physiology. Here, we also describe a detailed protocol for treating workers with 20-hydroxyecdysone (20E), an active form of ecdysone, and methoprene, a juvenile hormone analogue. The survival rate of treated bees was sufficient to examine gene expression in the HPGs. Gene expression changes were observed in response to 20E- and/or methoprene-treatment, suggesting that hormone treatments induce physiological changes of the HPGs. The protocol for hormone treatment described here is appropriate for examining hormonal effects on worker physiology.

Physiology of man and animals in the Tenth Five-Year Plan: Proceedings of the Thirteenth Congress of the I. P. Pavlov All-Union Physiological Society

NASA Technical Reports Server (NTRS)

Lange, K. A.

1980-01-01

Research in the field of animal and human physiology is reviewed. The following topics on problems of physiological science and related fields of knowledge are discussed: neurophysiology and higher nervous activity, physiology of sensory systems, physiology of visceral systems, evolutionary and ecological physiology, physiological cybernetics, computer application in physiology, information support of physiological research, history and theory of development of physiology. Also discussed were: artificial intelligence, physiological problems of reflex therapy, correlation of structure and function of the brain, adaptation and activity, microcirculation, and physiological studies in nerve and mental diseases.

Seamless Integration of Detection and Therapy for Breast Cancer using Targeted Engineered Nanoparticles

DTIC Science & Technology

2007-06-01

Quantum Electronics Conference, Snowbird, UT, January 2007. 20. “Nanophotonics: the next Big Thing”, Invited talk, CINT Annual Workshop, Los ...affinity, bac- terial, diarrheagenic, heat-stable enterotoxins (STs) and the lower affinity endogenous ligands guanylin and uro - guanylin, which induce...metabolic, and lo - comotor) were compared to explore whether the deficiency of APN altered physiology (Fig. 4). First, activity tests were per- formed in

Sugar for the brain: the role of glucose in physiological and pathological brain function

PubMed Central

Mergenthaler, Philipp; Lindauer, Ute; Dienel, Gerald A.; Meisel, Andreas

2013-01-01

The mammalian brain depends upon glucose as its main source of energy, and tight regulation of glucose metabolism is critical for brain physiology. Consistent with its critical role for physiological brain function, disruption of normal glucose metabolism as well as its interdependence with cell death pathways forms the pathophysiological basis for many brain disorders. Here, we review recent advances in understanding how glucose metabolism sustains basic brain physiology. We aim at synthesizing these findings to form a comprehensive picture of the cooperation required between different systems and cell types, and the specific breakdowns in this cooperation which lead to disease. PMID:23968694

A primer on clothing systems for cold-weather field work

USGS Publications Warehouse

Denner, Jon

1990-01-01

Conducting field work in cold weather is a demanding task. The most important safety consideration for field personnel is to maintain normal body temperature and avoid hypothermia.The human body adjusts to cold temperatures through different physiological processes. Heat production is enhanced by increases in the rates of basal metabolism, specific dynamic action, and physical exercise, and heat loss is reduced by vasoconstriction.Physiological adaptations alone are inadequate to stop rapid heat loss in cold temperatures. Additional insulation in the form of cold-weather clothing is necessary to retain heat.The most practical method of dressing for winter conditions is the layering system. Wearing multiple thin layers allows one to fine tune the insulation needed for different temperatures and activity levels.

Performance in physiology evaluation: possible improvement by active learning strategies.

PubMed

Montrezor, Luís H

2016-12-01

The evaluation process is complex and extremely important in the teaching/learning process. Evaluations are constantly employed in the classroom to assist students in the learning process and to help teachers improve the teaching process. The use of active methodologies encourages students to participate in the learning process, encourages interaction with their peers, and stimulates thinking about physiological mechanisms. This study examined the performance of medical students on physiology over four semesters with and without active engagement methodologies. Four activities were used: a puzzle, a board game, a debate, and a video. The results show that engaging in activities with active methodologies before a physiology cognitive monitoring test significantly improved student performance compared with not performing the activities. We integrate the use of these methodologies with classic lectures, and this integration appears to improve the teaching/learning process in the discipline of physiology and improves the integration of physiology with cardiology and neurology. In addition, students enjoy the activities and perform better on their evaluations when they use them. Copyright © 2016 The American Physiological Society.

The small GTPase Arf6 regulates sea urchin morphogenesis

PubMed Central

Stepicheva, Nadezda A.; Dumas, Megan; Kobi, Priscilla; Donaldson, Julie G.; Song, Jia L.

2017-01-01

The small GTPase Arf6 is a conserved protein that is expressed in all metazoans. Arf6 remodels cytoskeletal actin and mediates membrane protein trafficking between the plasma membrane in its active form and endosomal compartments in its inactive form. While a rich knowledge exists for the cellular functions of Arf6, relatively little is known about its physiological role in development. This study examines the function of Arf6 in mediating cellular morphogenesis in early development. We dissect the function of Arf6 with a loss-of-function morpholino and constitutively active Arf6-Q67L construct. We focus on the two cell types that undergo active directed migration: the primary mesenchyme cells (PMCs) that give rise to the sea urchin skeleton and endodermal cells that form the gut. Our results indicate that Arf6 plays an important role in skeleton formation and PMC migration, in part due to its ability to remodel actin. We also found that embryos injected with Arf6 morpholino have gastrulation defects and embryos injected with constitutively active Arf6 have endodermal cells detached from the gut epithelium with decreased junctional cadherin staining, indicating that Arf6 may mediate the recycling of cadherin. Thus, Arf6 impacts cells that undergo coordinated movement to form embryonic structures in the developing embryo. PMID:28188999

Biomass conversion inhibitors furfural and 5-hydroxymethylfurfural induce formation of messenger RNP granules and attenuate translation activity in Saccharomyces cerevisiae.

PubMed

Iwaki, Aya; Kawai, Takao; Yamamoto, Yosuke; Izawa, Shingo

2013-03-01

Various forms of stress can cause an attenuation of bulk translation activity and the accumulation of nontranslating mRNAs into cytoplasmic messenger RNP (mRNP) granules termed processing bodies (P-bodies) and stress granules (SGs) in eukaryotic cells. Furfural and 5-hydroxymethylfurfural (HMF), derived from lignocellulosic biomass, inhibit yeast growth and fermentation as stressors. Since there is no report regarding their effects on the formation of cytoplasmic mRNP granules, here we investigated whether furfural and HMF cause the assembly of yeast P-bodies and SGs accompanied by translational repression. We found that furfural and HMF cause the attenuation of bulk translation activity and the assembly of cytoplasmic mRNP granules in Saccharomyces cerevisiae. Notably, a combination of furfural and HMF induced the remarkable repression of translation initiation and SG formation. These findings provide new information about the physiological effects of furfural and HMF on yeast cells, and also suggest the potential usefulness of cytoplasmic mRNP granules as a warning sign or index of the deterioration of cellular physiological status in the fermentation of lignocellulosic hydrolysates.

Biomass Conversion Inhibitors Furfural and 5-Hydroxymethylfurfural Induce Formation of Messenger RNP Granules and Attenuate Translation Activity in Saccharomyces cerevisiae

PubMed Central

Iwaki, Aya; Kawai, Takao; Yamamoto, Yosuke

2013-01-01

Various forms of stress can cause an attenuation of bulk translation activity and the accumulation of nontranslating mRNAs into cytoplasmic messenger RNP (mRNP) granules termed processing bodies (P-bodies) and stress granules (SGs) in eukaryotic cells. Furfural and 5-hydroxymethylfurfural (HMF), derived from lignocellulosic biomass, inhibit yeast growth and fermentation as stressors. Since there is no report regarding their effects on the formation of cytoplasmic mRNP granules, here we investigated whether furfural and HMF cause the assembly of yeast P-bodies and SGs accompanied by translational repression. We found that furfural and HMF cause the attenuation of bulk translation activity and the assembly of cytoplasmic mRNP granules in Saccharomyces cerevisiae. Notably, a combination of furfural and HMF induced the remarkable repression of translation initiation and SG formation. These findings provide new information about the physiological effects of furfural and HMF on yeast cells, and also suggest the potential usefulness of cytoplasmic mRNP granules as a warning sign or index of the deterioration of cellular physiological status in the fermentation of lignocellulosic hydrolysates. PMID:23275506

Triple-aspect monism: physiological, mental unconscious and conscious aspects of brain activity.

PubMed

Pereira, Alfredo

2014-06-01

Brain activity contains three fundamental aspects: (a) The physiological aspect, covering all kinds of processes that involve matter and/or energy; (b) the mental unconscious aspect, consisting of dynamical patterns (i.e., frequency, amplitude and phase-modulated waves) embodied in neural activity. These patterns are variously operated (transmitted, stored, combined, matched, amplified, erased, etc), forming cognitive and emotional unconscious processes and (c) the mental conscious aspect, consisting of feelings experienced in the first-person perspective and cognitive functions grounded in feelings, as memory formation, selection of the focus of attention, voluntary behavior, aesthetical appraisal and ethical judgment. Triple-aspect monism (TAM) is a philosophical theory that provides a model of the relation of the three aspects. Spatially distributed neuronal dendritic potentials generate amplitude-modulated waveforms transmitted to the extracellular medium and adjacent astrocytes, prompting the formation of large waves in the astrocyte network, which are claimed to both integrate distributed information and instantiate feelings. According to the valence of the feeling, the large wave feeds back on neuronal synapses, modulating (reinforcing or depressing) cognitive and behavioral functions.

Divalent cations and molecular crowding buffers stabilize G-triplex at physiologically relevant temperatures

PubMed Central

Jiang, Hong-Xin; Cui, Yunxi; Zhao, Ting; Fu, Hai-Wei; Koirala, Deepak; Punnoose, Jibin Abraham; Kong, De-Ming; Mao, Hanbin

2015-01-01

G-triplexes are non-canonical DNA structures formed by G-rich sequences with three G-tracts. Putative G-triplex-forming sequences are expected to be more prevalent than putative G-quadruplex-forming sequences. However, the research on G-triplexes is rare. In this work, the effects of molecular crowding and several physiologically important metal ions on the formation and stability of G-triplexes were examined using a combination of circular dichroism, thermodynamics, optical tweezers and calorimetry techniques. We determined that molecular crowding conditions and cations, such as Na+, K+, Mg2+ and Ca2+, promote the formation of G-triplexes and stabilize these structures. Of these four metal cations, Ca2+ has the strongest stabilizing effect, followed by K+, Mg2+, and Na+ in a decreasing order. The binding of K+ to G-triplexes is accompanied by exothermic heats, and the binding of Ca2+ with G-triplexes is characterized by endothermic heats. G-triplexes formed from two G-triad layers are not stable at physiological temperatures; however, G-triplexes formed from three G-triads exhibit melting temperatures higher than 37°C, especially under the molecular crowding conditions and in the presence of K+ or Ca2+. These observations imply that stable G-triplexes may be formed under physiological conditions. PMID:25787838

Network properties of interstitial cells of Cajal affect intestinal pacemaker activity and motor patterns, according to a mathematical model of weakly coupled oscillators.

PubMed

Wei, Ruihan; Parsons, Sean P; Huizinga, Jan D

2017-03-01

What is the central question of this study? What are the effects of interstitial cells of Cajal (ICC) network perturbations on intestinal pacemaker activity and motor patterns? What is the main finding and its importance? Two-dimensional modelling of the ICC pacemaker activity according to a phase model of weakly coupled oscillators showed that network properties (coupling strength between oscillators, frequency gradient and frequency noise) strongly influence pacemaker network activity and subsequent motor patterns. The model explains motor patterns observed in physiological conditions and provides predictions and testable hypotheses for effects of ICC loss and frequency modulation on the motor patterns. Interstitial cells of Cajal (ICC) are the pacemaker cells of gut motility and are associated with motility disorders. Interstitial cells of Cajal form a network, but the contributions of its network properties to gut physiology and dysfunction are poorly understood. We modelled an ICC network as a two-dimensional network of weakly coupled oscillators with a frequency gradient and showed changes over time in video and graphical formats. Model parameters were obtained from slow-wave-driven contraction patterns in the mouse intestine and pacemaker slow-wave activities from the cat intestine. Marked changes in propagating oscillation patterns (including changes from propagation to non-propagating) were observed by changing network parameters (coupling strength between oscillators, the frequency gradient and frequency noise), which affected synchronization, propagation velocity and occurrence of dislocations (termination of an oscillation). Complete uncoupling of a circumferential ring of oscillators caused the proximal and distal section to desynchronize, but complete synchronization was maintained with only a single oscillator connecting the sections with high enough coupling. The network of oscillators could withstand loss; even with 40% of oscillators lost randomly within the network, significant synchronization and anterograde propagation remained. A local increase in pacemaker frequency diminished anterograde propagation; the effects were strongly dependent on location, frequency gradient and coupling strength. In summary, the model puts forth the hypothesis that fundamental changes in oscillation patterns (ICC slow-wave activity or circular muscle contractions) can occur through physiological modulation of network properties. Strong evidence is provided to accept the ICC network as a system of coupled oscillators. © 2016 The Authors. Experimental Physiology © 2016 The Physiological Society.

The effect of xanthine oxidase and hypoxanthine on the permeability of red cells from patients with sickle cell anemia.

PubMed

Al Balushi, Halima W M; Rees, David C; Brewin, John N; Hannemann, Anke; Gibson, John S

2018-03-01

Red cells from patients with sickle cell anemia (SCA) are under greater oxidative challenge than those from normal individuals. We postulated that oxidants generated by xanthine oxidase (XO) and hypoxanthine (HO) contribute to the pathogenesis of SCA through altering solute permeability. Sickling, activities of the main red cell dehydration pathways (P sickle , Gardos channel, and KCl cotransporter [KCC]), and cell volume were measured at 100, 30, and 0 mmHg O 2 , together with deoxygenation-induced nonelectrolyte hemolysis. Unexpectedly, XO/HO mixtures had mainly inhibitory effects on sickling, P sickle , and Gardos channel activities, while KCC activity and nonelectrolyte hemolysis were increased. Gardos channel activity was significantly elevated in red cells pharmacologically loaded with Ca 2+ using the ionophore A23187, consistent with an effect on the transport system per se as well as via Ca 2+ entry likely via the P sickle pathway. KCC activity is controlled by several pairs of conjugate protein kinases and phosphatases. Its activity, however, was also stimulated by XO/HO mixtures in red cells pretreated with N-ethylmaleimide (NEM), which is thought to prevent regulation via changes in protein phosphorylation, suggesting that the oxidants formed could also have direct effects on this transporter. In the presence of XO/HO, red cell volume was better maintained in deoxygenated red cells. Overall, the most notable effect of XO/HO mixtures was an increase in red cell fragility. These findings increase our understanding of the effects of oxidative challenge in SCA patients and are relevant to the behavior of red cells in vivo. © 2018 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

Relative roles of different mechanisms of depression at the mouse endbulb of Held

PubMed Central

Yang, Hua; Xu-Friedman, Matthew A.

2010-01-01

Several mechanisms can underlie short-term synaptic depression, including vesicle depletion, receptor desensitization, and changes in presynaptic release probability. To determine which mechanisms affect depression under physiological conditions, we studied the synapse formed by auditory nerve fibers onto bushy cells in the anteroventral cochlear nucleus (the “endbulb of Held”) using voltage-clamp recordings of brain slices from P15–21 mice near physiological temperatures. Depression of both AMPA and NMDA EPSCs showed two phases of recovery. The fast component of depression for the AMPA EPSC was eliminated by cyclothiazide and aniracetam, suggesting it results from desensitization. The fast component of depression for the NMDA EPSC was reduced by the low-affinity antagonist L-AP5, suggesting it results from saturation. The remaining depression in AMPA and NMDA components is identical and therefore presynaptic in origin. It is likely to result from presynaptic vesicle depletion. Recovery from depression after trains of activity was slowed by the application of EGTA-AM, suggesting that the endbulb has a residual-calcium-dependent form of recovery. We developed a model that incorporates depletion, desensitization, and calcium-dependent recovery. This model replicated experimental findings over a range of experimental conditions. The model further indicated that desensitization plays only a minor role during prolonged activity, in large part because presynaptic release is so depleted. Thus, depletion appears to be the dominant mechanism of depression at the endbulb during normal activity. Furthermore, calcium-dependent recovery at the endbulb is critical to prevent complete run-down during high activity and to preserve the reliability of information transmission. PMID:18367696

Intrinsic circannual regulation of brown adipose tissue form and function in tune with hibernation

PubMed Central

Hindle, Allyson G.

2013-01-01

Winter hibernators repeatedly cycle between cold torpor and rewarming supported by nonshivering thermogenesis in brown adipose tissue (BAT). In contrast, summer animals are homeotherms, undergoing reproduction, growth, and fattening. This life history confers variability to BAT recruitment and activity. To address the components underlying prewinter enhancement and winter activation, we interrogated the BAT proteome in 13-lined ground squirrels among three summer and five winter states. We also examined mixed physiology in fall and spring individuals to test for ambient temperature and seasonal effects, as well as the timing of seasonal transitions. BAT form and function differ circannually in these animals, as evidenced by morphology and proteome dynamics. This intrinsic pattern distinguished homeothermic groups and early vs. late winter hibernators. Homeothermic variation derived from postemergence delay in growth and substrate biosynthesis. The heterothermic proteome varied less despite extreme winter physiological shifts and was optimized to exploit lipids by enhanced fatty acid binding, β-oxidation, and mitochondrial protein translocation. Surprisingly, ambient temperature did not affect the BAT proteome during transition seasons; rather, the pronounced summer-winter shift preceded environmental changes and phenotypic progression. During fall transition, differential regulation of two fatty acid binding proteins provides further evidence of recruitment and separates proteomic preparation from successful hibernation. Abundance of FABP4 correlates with torpor bout length throughout the year, clarifying its potential function in hibernation. Metabolically active BAT is a target for treating human obesity and metabolic disorders. Understanding the hibernator's extreme and seasonally distinct recruitment and activation control strategies offers untapped potential to identify novel, therapeutically relevant regulatory pathways. PMID:24326419

[The clinical biochemistry of hypo-lipedemic therapy and mechanisms of action of statins: the fatty acids, statins and diabetes mellitus].

PubMed

Titov, V N

2014-02-01

In liver statins inhibit synthesis of specific pool of cholesterol which is formed de novo by hepatocytes for monolayer of polar lipids at the surface of forming lipoproteins of very low density. The statins, decreasing content of non-esterified cholesterol in monolayer, activate hydrolysis of triglycerides in lipoproteins of very low density, formation of lipoproteins of low density and their absorption by cells through apoB-100 receptors. The statins, activating absorption of lipoproteins of low density, restore functional action of essential polyenoic fatty acids. The essential polyenoic fatty acids, fibrates and glitazones form in cells effective oleic version of metabolism when mitochondrions predominantly oxidize oleic fatty acid. The statins, non-activating oxidation in peroxisomes and inhibiting activity of stearil-KoA-desaturase, form in cells less effective palmitic variant of metabolism of fatty acids under oxidation of palmitic fatty acid in mitochondrions. The fatty acids are not enough under hydrolysis of exogenous triglycerides to synthesize optimal amount of ATP. The fatty acids accumulated in adipocytes are to be used. This is the cause of formation by statins the resistance to insulin. Functionally, lipoproteins of very low density and lipoproteins of low density are phylogenetically different. The former ones transfer fatty acids to cells in the form of triglycerides and the latter ones--in the form of ethers with alcohol cholesterol. The statins normalize absorption of essential polyenoic fatty acids by cells which manifest a physiological action named a pleotropic one.

Activity of 3-Ketosteroid 9α-Hydroxylase (KshAB) Indicates Cholesterol Side Chain and Ring Degradation Occur Simultaneously in Mycobacterium tuberculosis*

PubMed Central

Capyk, Jenna K.; Casabon, Israël; Gruninger, Robert; Strynadka, Natalie C.; Eltis, Lindsay D.

2011-01-01

Mycobacterium tuberculosis (Mtb), a significant global pathogen, contains a cholesterol catabolic pathway. Although the precise role of cholesterol catabolism in Mtb remains unclear, the Rieske monooxygenase in this pathway, 3-ketosteroid 9α-hydroxylase (KshAB), has been identified as a virulence factor. To investigate the physiological substrate of KshAB, a rhodococcal acyl-CoA synthetase was used to produce the coenzyme A thioesters of two cholesterol derivatives: 3-oxo-23,24-bisnorchol-4-en-22-oic acid (forming 4-BNC-CoA) and 3-oxo-23,24-bisnorchola-1,4-dien-22-oic acid (forming 1,4-BNC-CoA). The apparent specificity constant (kcat/Km) of KshAB for the CoA thioester substrates was 20–30 times that for the corresponding 17-keto compounds previously proposed as physiological substrates. The apparent KmO2 was 90 ± 10 μm in the presence of 1,4-BNC-CoA, consistent with the value for two other cholesterol catabolic oxygenases. The Δ1 ketosteroid dehydrogenase KstD acted with KshAB to cleave steroid ring B with a specific activity eight times greater for a CoA thioester than the corresponding ketone. Finally, modeling 1,4-BNC-CoA into the KshA crystal structure suggested that the CoA moiety binds in a pocket at the mouth of the active site channel and could contribute to substrate specificity. These results indicate that the physiological substrates of KshAB are CoA thioester intermediates of cholesterol side chain degradation and that side chain and ring degradation occur concurrently in Mtb. This finding has implications for steroid metabolites potentially released by the pathogen during infection and for the design of inhibitors for cholesterol-degrading enzymes. The methodologies and rhodococcal enzymes used to generate thioesters will facilitate the further study of cholesterol catabolism. PMID:21987574

Activity of 3-ketosteroid 9α-hydroxylase (KshAB) indicates cholesterol side chain and ring degradation occur simultaneously in Mycobacterium tuberculosis.

PubMed

Capyk, Jenna K; Casabon, Israël; Gruninger, Robert; Strynadka, Natalie C; Eltis, Lindsay D

2011-11-25

Mycobacterium tuberculosis (Mtb), a significant global pathogen, contains a cholesterol catabolic pathway. Although the precise role of cholesterol catabolism in Mtb remains unclear, the Rieske monooxygenase in this pathway, 3-ketosteroid 9α-hydroxylase (KshAB), has been identified as a virulence factor. To investigate the physiological substrate of KshAB, a rhodococcal acyl-CoA synthetase was used to produce the coenzyme A thioesters of two cholesterol derivatives: 3-oxo-23,24-bisnorchol-4-en-22-oic acid (forming 4-BNC-CoA) and 3-oxo-23,24-bisnorchola-1,4-dien-22-oic acid (forming 1,4-BNC-CoA). The apparent specificity constant (k(cat)/K(m)) of KshAB for the CoA thioester substrates was 20-30 times that for the corresponding 17-keto compounds previously proposed as physiological substrates. The apparent K(m)(O(2)) was 90 ± 10 μM in the presence of 1,4-BNC-CoA, consistent with the value for two other cholesterol catabolic oxygenases. The Δ(1) ketosteroid dehydrogenase KstD acted with KshAB to cleave steroid ring B with a specific activity eight times greater for a CoA thioester than the corresponding ketone. Finally, modeling 1,4-BNC-CoA into the KshA crystal structure suggested that the CoA moiety binds in a pocket at the mouth of the active site channel and could contribute to substrate specificity. These results indicate that the physiological substrates of KshAB are CoA thioester intermediates of cholesterol side chain degradation and that side chain and ring degradation occur concurrently in Mtb. This finding has implications for steroid metabolites potentially released by the pathogen during infection and for the design of inhibitors for cholesterol-degrading enzymes. The methodologies and rhodococcal enzymes used to generate thioesters will facilitate the further study of cholesterol catabolism.

An "enigmatic" L-carnosine (β-alanyl-L-histidine)? Cell proliferative activity as a fundamental property of a natural dipeptide inherent to traditional antioxidant, anti-aging biological activities: balancing and a hormonally correct agent, novel patented oral therapy dosage formulation for mobility, skeletal muscle power and functional performance, hypothalamic-pituitary- brain relationship in health, aging and stress studies.

PubMed

Babizhayev, Mark A; Yegorov, Yegor E

2015-01-01

Hypothalamic releasing and inhibiting hormones are major neuroendocrine regulators of human body metabolism being driven directly to the anterior pituitary gland via hypothalamic-hypophyseal portal veins. The alternative physiological or therapeutic interventions utilizing the pharmaco-nutritional boost of imidazole-containing dipeptides (non-hydrolized oral form of carnosine, carcinine, N-acetylcarnosine lubricant eye drops) can maintain health, enhance physical exercise performance and prevent ageing. Carnosine (β-alanyl-L-histidine) is synthesized in mammalian skeletal muscle. There is an evidence that the release of carnosine from the skeletal muscle sarcomeres moieties during physical exercise affects autonomic neurotransmission and physiological functions. Carnosine released from skeletal muscle during exercise acts as a powerful afferent physiological signaling stimulus for hypothalamus, may be transported into the hypothalamic tuberomammillary nucleus (TMN), specifically to TMN-histamine neurons and hydrolyzed herewith via activities of carnosine-degrading enzyme (carnosinase 2) localized in situ. Through the colocalized enzymatic activity of Histidine decarboxylase in the histaminergic neurons, the resulting L-histidine may subsequently be converted into histamine, which could be responsible for the effects of carnosine on neurotransmission and physiological function. Carnosine and its imidazole-containing dipeptide derivatives are renowned for their anti-aging, antioxidant, membrane protective, metal ion chelating, buffering, anti-glycation/ transglycating activities used to prevent and treat a spectrum of age-related and metabolic diseases, such as neurodegenerative disease, sight threatening eye diseases, Diabetes mellitus and its complications, cancers and other disorders due to their wide spectrum biological activities. The precursor of carnosine (and related imidazole containing compounds) synthesis in skeletal muscles beta-alanine is used as the oral supplement by athletes to achieve the fine sporting art results due to the buffering activities of carnosine and its related imidazole- containing compounds which contribute to the maintenance of the acid-base balance in the acting muscles. This work originally emphasizes that overall data indicate the signaling activities of carnosine in skeletal and cardiac muscles switching on the mechanisms of exercise-induced telomere protection and point to the stress response and growth/cellular proliferation pathways as high-priority candidates for the ongoing studies and therapeutic concepts. The therapeutic interventions utilizing the specific oral formulation (Can-C Plus), timing dosing and pharmaco-nutritional boost of imidazolecontaining dipeptides can maintain health, enhance physical exercise performance and prevent aging. The patented therapeutic concept protects the existence of the interesting physiological major activities, better controls and therapeutic treatments for aging/age-related disorders (including age-related loss of muscle mass and muscle function) using carnosine dipeptide for cellular rejuvenation and manipulating telomeres and enzyme telomerase activity that may reduce some of the physiological declines that accompany aging.

Requirement for tyrosine phosphatase during serotonergic neuromodulation by protein kinase C.

PubMed

Catarsi, S; Drapeau, P

1997-08-01

Tyrosine kinases and phosphatases are abundant in the nervous system, where they signal cellular differentiation, mediate the responses to growth factors, and direct neurite outgrowth during development. Tyrosine phosphorylation can also alter ion channel activity, but its physiological significance remains unclear. In an identified leech mechanosensory neuron, the ubiquitous neuromodulator serotonin increases the activity of a cation channel by activating protein kinase C (PKC), resulting in membrane depolarization and modulation of the receptive field properties. We observed that the effects on isolated neurons and channels were blocked by inhibiting tyrosine phosphatases. Serotonergic stimulation of PKC thus activates a tyrosine phosphatase activity associated with the channels, which reverses their constitutive inhibition by tyrosine phosphorylation, representing a novel form of neuromodulation.

Multifunctional enzymes from reduced genomes - model proteins for simple primordial metabolism?

PubMed

Seelig, Burckhard

2017-08-01

Billions of years of evolution have yielded today's complex metabolic networks driven by efficient and highly specialized enzymes. In contrast, the metabolism of the earliest cellular life forms was likely much simpler with only a few enzymes of comparatively low activity. It has been speculated that these early enzymes had low specificities and in turn were able to perform multiple functions. In this issue of Molecular Microbiology, Ferla et al. describe examples of enzymes that catalyze chemically distinct reactions while using the same active site. Most importantly, the authors demonstrated that the comparatively weak activities of these multifunctional enzymes are each physiologically relevant. These findings contrast with simply promiscuous enzyme activities, which have been described numerous times but are not physiologically relevant. Ferla et al. elegantly combined initial bioinformatics searches for enzyme candidates with sound kinetic measurements, evolutionary considerations and even structural discussions. The phenomenon of multifunctionality appears to be a mechanism for bacteria with reduced genomes to compensate for their lack of certain enzymes. In the broader context of evolution, these organisms could be considered living model systems to study features of long-extinct early cellular life. © 2017 John Wiley & Sons Ltd.

Long-Chain Metabolites of Vitamin E: Metabolic Activation as a General Concept for Lipid-Soluble Vitamins?

PubMed

Schubert, Martin; Kluge, Stefan; Schmölz, Lisa; Wallert, Maria; Galli, Francesco; Birringer, Marc; Lorkowski, Stefan

2018-01-12

Vitamins E, A, D and K comprise the class of lipid-soluble vitamins. For vitamins A and D, a metabolic conversion of precursors to active metabolites has already been described. During the metabolism of vitamin E, the long-chain metabolites (LCMs) 13'-hydroxychromanol (13'-OH) and 13'-carboxychromanol (13'-COOH) are formed by oxidative modification of the side-chain. The occurrence of these metabolites in human serum indicates a physiological relevance. Indeed, effects of the LCMs on lipid metabolism, apoptosis, proliferation and inflammatory actions as well as tocopherol and xenobiotic metabolism have been shown. Interestingly, there are several parallels between the actions of the LCMs of vitamin E and the active metabolites of vitamin A and D. The recent findings that the LCMs exert effects different from that of their precursors support their putative role as regulatory metabolites. Hence, it could be proposed that the mode of action of the LCMs might be mediated by a mechanism similar to vitamin A and D metabolites. If the physiological relevance and this concept of action of the LCMs can be confirmed, a general concept of activation of lipid-soluble vitamins via their metabolites might be deduced.

Nitric oxide (NO), the only nitrogen monoxide redox form capable of activating soluble guanylyl cyclase.

PubMed

Dierks, E A; Burstyn, J N

1996-06-28

In the present study, we determined that of the redox forms of nitrogen monoxide, NO-, NO and NO+, only NO significantly activates soluble guanylyl cyclase (GTP pyrophosphate-lyase cyclizing, EC 4.6.1.2). Neither of the NO-donors tested, Angeli's salt (Na2N2O3) or Piloty's acid (C6H5SO2NHOH), caused a change in the guanylyl cyclase activity relative to the basal activity level. Interference by other reaction products was eliminated as a possible explanation for the lack of activation. To the extent that NO+ could be stabilized in aqueous solution, by dissolution of the nitrosonium salt NOPF6 in dry organic solvent prior to addition to the enzyme in buffer, NO+ had no effect on the activity of soluble guanylyl cyclase. The counter-ion, PF6-, had a minimal effect on the enzyme activity and, therefore was, not responsible for the lack of activation by NO+. These observations suggest that NO- is the natural activator of soluble guanylyl cyclase and is reasonably identical with endothelium-derived relaxing factor, the physiological regulator of soluble guanylyl cyclase activity.

DNA methylation mediates neural processing after odor learning in the honeybee

PubMed Central

Biergans, Stephanie D.; Claudianos, Charles; Reinhard, Judith; Galizia, C. Giovanni

2017-01-01

DNA methyltransferases (Dnmts) - epigenetic writers catalyzing the transfer of methyl-groups to cytosine (DNA methylation) – regulate different aspects of memory formation in many animal species. In honeybees, Dnmt activity is required to adjust the specificity of olfactory reward memories and bees’ relearning capability. The physiological relevance of Dnmt-mediated DNA methylation in neural networks, however, remains unknown. Here, we investigated how Dnmt activity impacts neuroplasticity in the bees’ primary olfactory center, the antennal lobe (AL) an equivalent of the vertebrate olfactory bulb. The AL is crucial for odor discrimination, an indispensable process in forming specific odor memories. Using pharmacological inhibition, we demonstrate that Dnmt activity influences neural network properties during memory formation in vivo. We show that Dnmt activity promotes fast odor pattern separation in trained bees. Furthermore, Dnmt activity during memory formation increases both the number of responding glomeruli and the response magnitude to a novel odor. These data suggest that Dnmt activity is necessary for a form of homoeostatic network control which might involve inhibitory interneurons in the AL network. PMID:28240742

The Biochemistry, Chemistry and Physiology of the Isoflavones in Soybeans and their Food Products

PubMed Central

2010-01-01

Abstract In this review of the chemistry, absorption, metabolism, and mechanisms of action of plant isoflavones, emphasis is placed on the isoflavones in soy and the food products derived from them. Soybeans have been part of food history in Asia for several millennia but did not reach the Americas and Europe until the eighteenth century. In the twentieth century, there was a tremendous increase in the cultivation of soybeans in the United States and more recently in South America. Soy foods have entered the U.S. food supply in ever-increasing amounts both in the form of traditional products (soy milk, tofu) and in more subtle ways in dairy and bread/cake products. The isoflavones in non-fermented foods are for the most part in the form of glycoside conjugates. These undergo changes due to different processing procedures. Isoflavones and their metabolites are well absorbed and undergo an enterohepatic circulation. They are often termed phytoestrogens because they bind to the estrogen receptors although weakly compared to physiologic estrogens. This estrogenicity is not the only mechanism by which isoflavones may have bioactivity—they inhibit tyrosine kinases, have antioxidant activity, bind to and activate peroxisome proliferator regulators α and γ, inhibit enzymes in steroid biosynthesis, strongly influence natural killer cell function and the activation of specific T-cell subsets, and inhibit metastasis. These various properties may explain the much lower incidence of hormonally-dependent breast cancer in Asian populations compared to Americans and Europeans. PMID:20235891

Establishment, characterization and immortalization of a fibroblast cell line from the Chinese red belly toad Bombina maxima skin.

PubMed

Xiang, Yang; Gao, Qian; Su, Weiting; Zeng, Lin; Wang, Jinhuan; Hu, Yi; Nie, Wenhui; Ma, Xutong; Zhang, Yong; Lee, Wenhui; Zhang, Yun

2012-01-01

The skin of the amphibian Bombina maxima is rich in biologically active proteins and peptides, most of which have mammalian analogues. The physiological functions of most of the mammalian analogues are still unknown. Thus, Bombina maxima skin may be a promising model to reveal the physiological role of these proteins and peptides because of their large capacity for secretion. To investigate the physiological role of these proteins and peptides in vitro, a fibroblast cell line was successfully established from Bombina maxima tadpole skin. The cell line grew to form a monolayer with cells of a uniform shape and abundant rough endoplasmic reticulum, which are typical characteristics of fibroblasts. Further identification at a molecular level revealed that they strongly expressed the fibroblast marker protein vimentin. The chromosome number of these cells is 2n = 28, and most of them were diploid. Growth property analysis showed that they grew well for 14 passages. However, cells showed decreased proliferative ability after passage 15. Thus, we tried to immortalize the cells through the overexpression of SV40 T antigen. After selecting by G418, cells stably expressed SV40 large T antigen and showed enhanced proliferative ability and increased telomerase activity. Signal transduction analysis revealed functional p42 mitogen-activated protein (MAP) kinase in immortalized Bombina maxima dermal fibroblasts. Primary fibroblast cells and the immortalized fibroblast cells from Bombina maxima cultured in the present study can be used to investigate the physiological role of Bombina maxima skin-secreted proteins and peptides. In addition, the methods for primary cell culturing and cell immortalization will be useful for culturing and immortalizing cells from other types of amphibians.

Store-operated Ca2+ entry in muscle physiology and diseases

PubMed Central

Pan, Zui; Brotto, Marco; Ma, Jianjie

2014-01-01

Ca2+ release from intracellular stores and influx from extracellular reservoir regulate a wide range of physiological functions including muscle contraction and rhythmic heartbeat. One of the most ubiquitous pathways involved in controlled Ca2+ influx into cells is store-operated Ca2+ entry (SOCE), which is activated by the reduction of Ca2+ concentration in the lumen of endoplasmic or sarcoplasmic reticulum (ER/SR). Although SOCE is pronounced in non-excitable cells, accumulating evidences highlight its presence and important roles in skeletal muscle and heart. Recent discovery of STIM proteins as ER/SR Ca2+ sensors and Orai proteins as Ca2+ channel pore forming unit expedited the mechanistic understanding of this pathway. This review focuses on current advances of SOCE components, regulation and physiologic and pathophysiologic roles in muscles. The specific property and the dysfunction of this pathway in muscle diseases, and new directions for future research in this rapidly growing field are discussed. [BMB Reports 2014; 47(2): 69-79] PMID:24411466

Physiological patterns during practice of the Transcendental Meditation technique compared with patterns while reading Sanskrit and a modern language.

PubMed

Travis, F; Olson, T; Egenes, T; Gupta, H K

2001-07-01

This study tested the prediction that reading Vedic Sanskrit texts, without knowledge of their meaning, produces a distinct physiological state. We measured EEG, breath rate, heart rate, and skin conductance during: (1) 15-min Transcendental Meditation (TM) practice; (2) 15-min reading verses of the Bhagavad Gita in Sanskrit; and (3) 15-min reading the same verses translated in German, Spanish, or French. The two reading conditions were randomly counterbalanced, and subjects filled out experience forms between each block to reduce carryover effects. Skin conductance levels significantly decreased during both reading Sanskrit and TM practice, and increased slightly during reading a modern language. Alpha power and coherence were significantly higher when reading Sanskrit and during TM practice, compared to reading modern languages. Similar physiological patterns when reading Sanskrit and during practice of the TM technique suggests that the state gained during TM practice may be integrated with active mental processes by reading Sanskrit.

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

PubMed

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.

The Sensorium: Psychophysiological Evaluation of Responses to a Multimodal Neurofeedback Environment.

PubMed

Hinterberger, Thilo; Fürnrohr, Elena

2016-09-01

The Sensorium is a multimodal neurofeedback environment that reflects a person's physiological state by presenting physiological signals via orchestral sounds from a speaker and multi-coloured lights projected onto a white surface. The software manages acquisition, real-time processing, storage, and sonification of various physiological signals such as the electroencephalogram (EEG) or electrocardiogram (ECG). Each of the 36 participants completed 6 interventional conditions consisting of three different Sensorium-phases with EEG and ECG feedback, a mindfulness meditation, a guided body scan exercise, and a Pseudo-Sensorium using pre-recorded data that did not reflect the subject's own physiology. During all phases EEG, ECG, skin conductance, and respiration were recorded. A feedback questionnaire assessed the participants' subjective reports of changes in well-being, perception, and life-spirit. The results indicate that the Sensorium sessions were not statistically inferior compared to their corresponding active control conditions with respect to improvements in subjective reports concerning well-being and perception. Additionally, the Sensorium was rated as being a more extraordinary experience, as compared to meditation. During the Sensorium conditions the EEG showed lower levels of theta2 (7-8.5 Hz), alpha (9-12 Hz) and beta (12.5-25 Hz) activity. Since participants reported benefit from the Sensorium experience regardless of any prior experience with meditation, we propose this novel method of meditative and extraordinary self-experience to be utilized as a modern alternative to more traditional forms of meditation.

Partial purification of histone H3 proteolytic activity from the budding yeast Saccharomyces cerevisiae.

PubMed

Azad, Gajendra Kumar; Tomar, Raghuvir Singh

2016-06-01

The proteolytic clipping of histone tails has recently emerged as a novel form of irreversible post-translational modification (PTM) of histones. Histone clipping has been implicated as a regulatory process leading to the permanent removal of PTMs from histone proteins. However, there is scarcity of literature that describes the identification and characterization of histone-specific proteases. Here, we employed various biochemical methods to report histone H3-specific proteolytic activity from budding yeast. Our results demonstrate that H3 proteolytic activity was associated with sepharose bead matrices and activity was not affected by a variety of stress conditions. We have also identified the existence of an unknown protein that acts as a physiological inhibitor of the H3-clipping activity of yeast H3 protease. Moreover, through protease inhibition assays, we have also characterized yeast H3 protease as a serine protease. Interestingly, unlike glutamate dehydrogenase (GDH), yeast H3 proteolytic activity was not inhibited by Stefin B. Together, our findings suggest the existence of a novel H3 protease in yeast that is different from other reported histone H3 proteases. The presence of histone H3 proteolytic activity, along with the physiological inhibitor in yeast, suggests an interesting molecular mechanism that regulates the activity of histone proteases. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Processing of metacaspase 2 from Trypanosoma brucei (TbMCA2) broadens its substrate specificity.

PubMed

Gilio, Joyce M; Marcondes, Marcelo F; Ferrari, Débora; Juliano, Maria A; Juliano, Luiz; Oliveira, Vitor; Machado, Maurício F M

2017-04-01

Metacaspases are members of the cysteine peptidase family and may be implicated in programmed cell death in plants and lower eukaryotes. These proteases exhibit calcium-dependent activity and specificity for arginine residues at P 1 . In contrast to caspases, they do not require processing or dimerization for activity. Indeed, unprocessed metacaspase-2 of Trypanosoma brucei (TbMCA2) is active; however, it has been shown that cleavages at Lys 55 and Lys 268 increase TbMCA2 hydrolytic activity on synthetic substrates. The processed TbMCA2 comprises 3 polypeptide chains that remain attached by non-covalent bonds. Replacement of Lys 55 and Lys 268 with Gly via site-directed mutagenesis results in non-processed but enzymatically active mutant, TbMCA2 K55/268G. To investigate the importance of this processing for the activity and specificity of TbMCA2, we performed activity assays comparing the non-processed mutant (TbMCA2 K55/268G) with the processed TbMCA2 form. Significant differences between TbMCA2 WT (processed form) and TbMCA2 K55/268G (non-processed form) were observed. Specifically, we verified that although non-processed TbMCA2 is active when assayed with small synthetic substrates, the TbMCA2 form does not exhibit hydrolytic activity on large substrates such as azocasein, while processed TbMCA2 is able to readily digest this protein. Such differences can be relevant for understanding the physiological regulation and function of TbMCA2. Copyright © 2017 Elsevier B.V. All rights reserved.

Form Factor Evaluation of Open Body Area Network (OBAN) Physiological Status Monitoring (PSM) System Prototype Designs

DTIC Science & Technology

2018-05-11

SYSTEM PROTOTYPE DESIGNS DISCLAIMERS The opinions or assertions contained herein are the private views of the author(s) and are not to be construed as...FORM FACTOR EVALUATION OF OPEN BODY AREA NETWORK (OBAN) PHYSIOLOGICAL STATUS MONITORING (PSM) SYSTEM PROTOTYPE DESIGNS William J...security; and is designed to function for 72 hours or more. The test described in this report assesses proposed form-factor designs . Feedback using

c-di-GMP can form remarkably stable G-quadruplexes at physiological conditions in the presence of some planar intercalators.

PubMed

Nakayama, Shizuka; Kelsey, Ilana; Wang, Jingxin; Sintim, Herman O

2011-04-28

The ubiquitous bacterial biofilm regulator, c-di-GMP can form G-quadruplexes at physiological conditions in the presence of some aromatic compounds, such as acriflavine and proflavine. The fluorescence of these compounds is quenched upon c-di-GMP binding and some of the formed c-di-GMP G-quadruplexes are stable even at 75 °C. © The Royal Society of Chemistry 2011

Carbonylation as a Key Reaction in Anaerobic Acetone Activation by Desulfococcus biacutus

PubMed Central

Gutiérrez Acosta, Olga B.; Hardt, Norman

2013-01-01

Acetone is activated by aerobic and nitrate-reducing bacteria via an ATP-dependent carboxylation reaction to form acetoacetate as the first reaction product. In the activation of acetone by sulfate-reducing bacteria, acetoacetate has not been found to be an intermediate. Here, we present evidence of a carbonylation reaction as the initial step in the activation of acetone by the strictly anaerobic sulfate reducer Desulfococcus biacutus. In cell suspension experiments, CO was found to be a far better cosubstrate for acetone activation than CO2. The hypothetical reaction product, acetoacetaldehyde, is extremely reactive and could not be identified as a free intermediate. However, acetoacetaldehyde dinitrophenylhydrazone was detected by mass spectrometry in cell extract experiments as a reaction product of acetone, CO, and dinitrophenylhydrazine. In a similar assay, 2-amino-4-methylpyrimidine was formed as the product of a reaction between acetoacetaldehyde and guanidine. The reaction depended on ATP as a cosubstrate. Moreover, the specific activity of aldehyde dehydrogenase (coenzyme A [CoA] acylating) tested with the putative physiological substrate was found to be 153 ± 36 mU mg−1 protein, and its activity was specifically induced in extracts of acetone-grown cells. Moreover, acetoacetyl-CoA was detected (by mass spectrometry) after the carbonylation reaction as the subsequent intermediate after acetoacetaldehyde was formed. These results together provide evidence that acetoacetaldehyde is an intermediate in the activation of acetone by sulfate-reducing bacteria. PMID:23913429

Carbonylation as a key reaction in anaerobic acetone activation by Desulfococcus biacutus.

PubMed

Gutiérrez Acosta, Olga B; Hardt, Norman; Schink, Bernhard

2013-10-01

Acetone is activated by aerobic and nitrate-reducing bacteria via an ATP-dependent carboxylation reaction to form acetoacetate as the first reaction product. In the activation of acetone by sulfate-reducing bacteria, acetoacetate has not been found to be an intermediate. Here, we present evidence of a carbonylation reaction as the initial step in the activation of acetone by the strictly anaerobic sulfate reducer Desulfococcus biacutus. In cell suspension experiments, CO was found to be a far better cosubstrate for acetone activation than CO2. The hypothetical reaction product, acetoacetaldehyde, is extremely reactive and could not be identified as a free intermediate. However, acetoacetaldehyde dinitrophenylhydrazone was detected by mass spectrometry in cell extract experiments as a reaction product of acetone, CO, and dinitrophenylhydrazine. In a similar assay, 2-amino-4-methylpyrimidine was formed as the product of a reaction between acetoacetaldehyde and guanidine. The reaction depended on ATP as a cosubstrate. Moreover, the specific activity of aldehyde dehydrogenase (coenzyme A [CoA] acylating) tested with the putative physiological substrate was found to be 153 ± 36 mU mg(-1) protein, and its activity was specifically induced in extracts of acetone-grown cells. Moreover, acetoacetyl-CoA was detected (by mass spectrometry) after the carbonylation reaction as the subsequent intermediate after acetoacetaldehyde was formed. These results together provide evidence that acetoacetaldehyde is an intermediate in the activation of acetone by sulfate-reducing bacteria.

Sugar for the brain: the role of glucose in physiological and pathological brain function.

PubMed

Mergenthaler, Philipp; Lindauer, Ute; Dienel, Gerald A; Meisel, Andreas

2013-10-01

The mammalian brain depends upon glucose as its main source of energy, and tight regulation of glucose metabolism is critical for brain physiology. Consistent with its critical role for physiological brain function, disruption of normal glucose metabolism as well as its interdependence with cell death pathways forms the pathophysiological basis for many brain disorders. Here, we review recent advances in understanding how glucose metabolism sustains basic brain physiology. We synthesize these findings to form a comprehensive picture of the cooperation required between different systems and cell types, and the specific breakdowns in this cooperation that lead to disease. Copyright © 2013 Elsevier Ltd. All rights reserved.

Distinct generation, pharmacology, and distribution of sphingosine 1-phosphate and dihydro-sphingosine 1-phosphate in human neural progenitor cells

USDA-ARS?s Scientific Manuscript database

In-vivo and in-vitro studies suggest a crucial role for Sphingosine 1-phosphate (S1P) and its receptors in the development of the nervous system. Dihydrosphingosine 1-phosphate (dhS1P), a reduced form of S1P, is an active ligand at S1P receptors, but the pharmacology and physiology of dhS1P has not...

Non Linear Assessment of Musical Consonance

NASA Astrophysics Data System (ADS)

Trulla, Lluis Lligoña; Guiliani, Alessandro; Zimatore, Giovanna; Colosimo, Alfredo; Zbilut, Joseph P.

2005-12-01

The position of intervals and the degree of musical consonance can be objectively explained by temporal series formed by mixing two pure sounds covering an octave. This result is achieved by means of Recurrence Quantification Analysis (RQA) without considering neither overtones nor physiological hypotheses. The obtained prediction of a consonance can be considered a novel solution to Galileo's conjecture on the nature of consonance. It constitutes an objective link between musical performance and listeners' hearing activity..

Promotion of endocytosis efficiency through an ATP-independent mechanism at rat calyx of Held terminals.

PubMed

Yue, Hai-Yuan; Bieberich, Erhard; Xu, Jianhua

2017-08-01

At rat calyx of Held terminals, ATP was required not only for slow endocytosis, but also for rapid phase of compensatory endocytosis. An ATP-independent form of endocytosis was recruited to accelerate membrane retrieval at increased activity and temperature. ATP-independent endocytosis primarily involved retrieval of pre-existing membrane, which depended on Ca 2+ and the activity of neutral sphingomyelinase but not clathrin-coated pit maturation. ATP-independent endocytosis represents a non-canonical mechanism that can efficiently retrieve membrane at physiological conditions without competing for the limited ATP at elevated neuronal activity. Neurotransmission relies on membrane endocytosis to maintain vesicle supply and membrane stability. Endocytosis has been generally recognized as a major ATP-dependent function, which efficiently retrieves more membrane at elevated neuronal activity when ATP consumption within nerve terminals increases drastically. This paradox raises the interesting question of whether increased activity recruits ATP-independent mechanism(s) to accelerate endocytosis at the same time as preserving ATP availability for other tasks. To address this issue, we studied ATP requirement in three typical forms of endocytosis at rat calyx of Held terminals by whole-cell membrane capacitance measurements. At room temperature, blocking ATP hydrolysis effectively abolished slow endocytosis and rapid endocytosis but only partially inhibited excess endocytosis following intense stimulation. The ATP-independent endocytosis occurred at calyces from postnatal days 8-15, suggesting its existence before and after hearing onset. This endocytosis was not affected by a reduction of exocytosis using the light chain of botulinum toxin C, nor by block of clathrin-coat maturation. It was abolished by EGTA, which preferentially blocked endocytosis of retrievable membrane pre-existing at the surface, and was impaired by oxidation of cholesterol and inhibition of neutral sphingomyelinase. ATP-independent endocytosis became more significant at 34-35°C, and recovered membrane by an amount that, on average, was close to exocytosis. The results of the present study suggest that activity and temperature recruit ATP-independent endocytosis of pre-existing membrane (in addition to ATP-dependent endocytosis) to efficiently retrieve membrane at nerve terminals. This less understood endocytosis represents a non-canonical mechanism regulated by lipids such as cholesterol and sphingomyelinase. © 2017 The Authors. The Journal of Physiology © 2017 The Physiological Society.

Pituitary hyperplasia and gigantism in mice caused by a cholera toxin transgene.

PubMed

Burton, F H; Hasel, K W; Bloom, F E; Sutcliffe, J G

1991-03-07

Cyclic AMP is thought to act as an intracellular second messenger, mediating the physiological response of many cell types to extracellular signals. In the pituitary, growth hormone (GH)-producing cells (somatotrophs) proliferate and produce GH in response to hypothalamic GH-releasing factor, which binds a receptor that stimulates Gs protein activation of adenylyl cyclase. We have now determined whether somatotroph proliferation and GH production are stimulated by cAMP alone, or require concurrent, non-Gs-mediated induction of other regulatory molecules by designing a transgene to induce chronic supraphysiological concentrations of cAMP in somatotrophs. The rat GH promoter was used to express an intracellular form of cholera toxin, a non-cytotoxic and irreversible activator of Gs. Introduction of this transgene into mice caused gigantism, elevated serum GH levels, somatotroph proliferation and pituitary hyperplasia. These results support the direct triggering of these events by cAMP, and illustrate the utility of cholera toxin transgenes as a tool for physiological engineering.

[Biological activity evaluation of porous HA ceramics using NH4 HCO3/PVA as pore-creating agents].

PubMed

Wang, Songquan; Zhang, Dekun

2010-12-01

Porous HA ceramics were prepared by using NH4 HCO3/PVA as pore-formed material along with biological glass as intensifier, and these ceramics were immersed in Locke's Physiological Saline and Simulate Body Fluid (SBF). The changes of phase composition, grain size and crystallinity of porous HA ceramics before and after immersion were investigated by X-Ray Diffraction (XRD) and Scanning Electron Microscopy (SEM). The biological activity was evaluated. The porous HA ceramics showed various degrees of decomposition after immersion in the two solution systems, but there was no evident change in respect to crystallinity. Besides, the impact of different degrees of solution systems on the change of grain size and planar preferred orientation was observed. The TCP phase of the ceramics immersed in Locke's Physiological Saline decomposed and there was no crystal growth on the surface of ceramics; however, the grain size of ceramics immersed in SBF became refined in certain degree and the surface of ceramics took on the new crystal growth.

Touch increases autonomic coupling between romantic partners

PubMed Central

Chatel-Goldman, Jonas; Congedo, Marco; Jutten, Christian; Schwartz, Jean-Luc

2014-01-01

Interpersonal touch is of paramount importance in human social bonding and close relationships, allowing a unique channel for affect communication. So far the effect of touch on human physiology has been studied at an individual level. The present study aims at extending the study of affective touch from isolated individuals to truly interacting dyads. We have designed an ecological paradigm where romantic partners interact only via touch and we manipulate their empathic states. Simultaneously, we collected their autonomic activity (skin conductance, pulse, respiration). Fourteen couples participated to the experiment. We found that interpersonal touch increased coupling of electrodermal activity between the interacting partners, regardless the intensity and valence of the emotion felt. In addition, physical touch induced strong and reliable changes in physiological states within individuals. These results support an instrumental role of interpersonal touch for affective support in close relationships. Furthermore, they suggest that touch alone allows the emergence of a somatovisceral resonance between interacting individuals, which in turn is likely to form the prerequisites for emotional contagion and empathy. PMID:24734009

How consumer physical activity monitors could transform human physiology research

PubMed Central

Hall Brown, Tyish S.; Collier, Scott R.; Sandberg, Kathryn

2017-01-01

A sedentary lifestyle and lack of physical activity are well-established risk factors for chronic disease and adverse health outcomes. Thus, there is enormous interest in measuring physical activity in biomedical research. Many consumer physical activity monitors, including Basis Health Tracker, BodyMedia Fit, DirectLife, Fitbit Flex, Fitbit One, Fitbit Zip, Garmin Vivofit, Jawbone UP, MisFit Shine, Nike FuelBand, Polar Loop, Withings Pulse O2, and others have accuracies similar to that of research-grade physical activity monitors for measuring steps. This review focuses on the unprecedented opportunities that consumer physical activity monitors offer for human physiology and pathophysiology research because of their ability to measure activity continuously under real-life conditions and because they are already widely used by consumers. We examine current and potential uses of consumer physical activity monitors as a measuring or monitoring device, or as an intervention in strategies to change behavior and predict health outcomes. The accuracy, reliability, reproducibility, and validity of consumer physical activity monitors are reviewed, as are limitations and challenges associated with using these devices in research. Other topics covered include how smartphone apps and platforms, such as the Apple ResearchKit, can be used in conjunction with consumer physical activity monitors for research. Lastly, the future of consumer physical activity monitors and related technology is considered: pattern recognition, integration of sleep monitors, and other biosensors in combination with new forms of information processing. PMID:28052867

Protease-Activated Receptors and other G-Protein-Coupled Receptors: the Melanoma Connection

PubMed Central

Rosero, Rebecca A.; Villares, Gabriel J.; Bar-Eli, Menashe

2016-01-01

The vast array of G-protein-coupled receptors (GPCRs) play crucial roles in both physiological and pathological processes, including vision, coagulation, inflammation, autophagy, and cell proliferation. GPCRs also affect processes that augment cell proliferation and metastases in many cancers including melanoma. Melanoma is the deadliest form of skin cancer, yet limited therapeutic modalities are available to patients with metastatic melanoma. Studies have found that both chemokine receptors and protease-activated receptors, both of which are GPCRs, are central to the metastatic melanoma phenotype and may serve as potential targets in novel therapies against melanoma and other cancers. PMID:27379162

Protease-Activated Receptors and other G-Protein-Coupled Receptors: the Melanoma Connection.

PubMed

Rosero, Rebecca A; Villares, Gabriel J; Bar-Eli, Menashe

2016-01-01

The vast array of G-protein-coupled receptors (GPCRs) play crucial roles in both physiological and pathological processes, including vision, coagulation, inflammation, autophagy, and cell proliferation. GPCRs also affect processes that augment cell proliferation and metastases in many cancers including melanoma. Melanoma is the deadliest form of skin cancer, yet limited therapeutic modalities are available to patients with metastatic melanoma. Studies have found that both chemokine receptors and protease-activated receptors, both of which are GPCRs, are central to the metastatic melanoma phenotype and may serve as potential targets in novel therapies against melanoma and other cancers.

Pedagogical effectiveness of innovative teaching methods initiated at the Department of Physiology, Government Medical College, Chandigarh.

PubMed

Nageswari, K Sri; Malhotra, Anita S; Kapoor, Nandini; Kaur, Gurjit

2004-12-01

Modern teaching trends in medical education exhibit a paradigm shift from the conventional classroom teaching methods adopted in the past to nonconventional teaching aids so as to encourage interactive forms of learning in medical students through active participation and integrative reasoning where the relationship of the teacher and the taught has undergone tremendous transformation. Some of the nonconventional teaching methods adopted at our department are learning through active participation by the students through computer-assisted learning (CD-ROMs), Web-based learning (undergraduate projects), virtual laboratories, seminars, audiovisual aids (video-based demonstrations), and "physioquiz."

Immune and Inflammatory Role in Renal Disease

PubMed Central

Ryan, Michael J.

2013-01-01

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

In-vitro Drug Dissolution Studies in Medicinal Compounds.

PubMed

Bozal-Palabiyik, Burcin; Uslu, Bengi; Ozkan, Yalcin; Ozkan, Sibel A

2018-03-22

After oral administration, drug absorption from solid dosage forms depend on the release of the drug active compounds from the dosage form, the dissolution or solubilization of the drug under physiological conditions, and the permeability across the gastrointestinal tract. Dissolution testing is an essential part of designing more effective solid dosage forms in pharmaceutical industry. Moreover dissolution testing contributes to the selection of appropriate formulation excipients for improving the dosage form efficiency. This study aims to analyze in-vitro drug dissolution testing in solid dosage forms since 2010 in order to present a comprehensive outlook of recent trends. In doing that the previous studies in the literature are summarized in the form of a table to demonstrate the apparatuses used for dissolution testing, the media in which the solid dosage form is dissolved, the method preferred for analysis from dissolution media, the conditions of analyses and the results obtained. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

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

Nelson, Cassandra E.; Rogowski, Artur; Morland, Carl

Degradation of polysaccharides forms an essential arc in the carbon cycle, provides a percentage of our daily caloric intake, and is a major driver in the renewable chemical industry. Microorganisms proficient at degrading insoluble polysaccharides possess large numbers of carbohydrate active enzymes, many of which have been categorized as functionally redundant. Here we present data that suggests that carbohydrate active enzymes that have overlapping enzymatic activities can have unique, non-overlapping biological functions in the cell. Our comprehensive study to understand cellodextrin utilization in the soil saprophyte Cellvibrio japonicus found that only one of four predicted β-glucosidases is required in amore » physiological context. Gene deletion analysis indicated that only the cel3B gene product is essential for efficient cellodextrin utilization in C. japonicus and is constitutively expressed at high levels. Interestingly, expression of individual β-glucosidases in Escherichia coli K-12 enabled this non-cellulolytic bacterium to be fully capable of using cellobiose as a sole carbon source. Furthermore, enzyme kinetic studies indicated that the Cel3A enzyme is significantly more active than the Cel3B enzyme on the oligosaccharides but not disaccharides. Finally, our approach for parsing related carbohydrate active enzymes to determine actual physiological roles in the cell can be applied to other polysaccharide-degradation systems.« less

Isolation of a latent polyphenol oxidase from loquat fruit (Eriobotrya japonica Lindl.): kinetic characterization and comparison with the active form.

PubMed

Sellés-Marchart, Susana; Casado-Vela, Juan; Bru-Martínez, Roque

2006-02-15

Polyphenol oxidase (PPO) has been extracted from both soluble and particulate fractions of loquat fruit (Eriobotrya japonica Lindl. cv. Algerie). The soluble PPO (20% of total activity) was partially purified 3.3-fold after ammonium sulfate fractionation being in its active state. The particulate PPO fraction (80% of total activity) was purified to homogeneity in a latent form being activable by sodium dodecyl sulfate (SDS). The enzyme was purified 40.0-fold with a total yield of 15.3% after extraction by phase partitioning in Triton X-114 followed by three chromatographic steps. The molecular weight was estimated to be about 59.2 and 61.2 kDa by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and gel filtration chromatography, respectively, indicating that latent PPO is a monomer. Latent PPO catalyzed the oxidation of chlorogenic acid (CA) at a rate 50-fold faster than that of 4-tert-butylcatechol (TBC) but the soluble active counterpart only twice. Both PPOs exhibited similar Km values for TBC but Km for CA was 5-fold higher for the latent than for the active soluble PPO. Other kinetic characteristics, including sensitivity to inhibitors, substrate specificity, thermal stability, temperature, and pH profiles, were quite different between both PPOs. These results provide strong evidences that the soluble active and the particulate latent are different forms of PPO in loquat fruit flesh. The results suggest that the major PPO form for the oxidation of CA, leading to enzymatic browning under physiological conditions, is the latent one.

Crew activities, science, and hazards of manned missions to Mars

NASA Technical Reports Server (NTRS)

Clark, Benton C.

1988-01-01

The crew scientific and nonscientific activities that will occur at each stage of a mission to Mars are examined. Crew activities during the interplanetary flight phase will include simulations, maintenance and monitoring, communications, upgrading procedures and operations, solar activity monitoring, cross-training and sharpening of skills, physical conditioning, and free-time activities. Scientific activities will address human physiology, human psychology, sociology, astronomy, space environment effects, manufacturing, and space agriculture. Crew activities on the Martian surface will include exploration, construction, manufacturing, food production, maintenance and training, and free time. Studies of Martian geology and atmosphere, of the life forms that may exist there, and of the Martian moons will occur on the planet's surface. Crew activities and scientific studies that will occur in Mars orbit, and the hazards relevant to each stage of the mission, are also addressed.

Unusual 4-hydroxybenzaldehyde synthase activity from tissue cultures of the vanilla orchid Vanilla planifolia.

PubMed

Podstolski, Andrzej; Havkin-Frenkel, Daphna; Malinowski, Jacek; Blount, Jack W; Kourteva, Galina; Dixon, Richard A

2002-11-01

Tissue cultures of the vanilla orchid, Vanilla planifolia, produce the flavor compound vanillin (4-hydroxy-3-methoxybenzaldehyde) and vanillin precursors such as 4-hydroxybenzaldehyde. A constitutively expressed enzyme activity catalyzing chain shortening of a hydroxycinnamic acid, believed to be the first reaction specific for formation of vanilla flavor compounds, was identified in these cultures. The enzyme converts 4-coumaric acid non-oxidatively to 4-hydroxybenzaldehyde in the presence of a thiol reagent but with no co-factor requirement. Several forms of this 4-hydroxybenzaldehyde synthase (4HBS) were resolved and partially purified by a combination of hydrophobic interaction, ion exchange and gel filtration chromatography. These forms appear to be interconvertible. The unusual properties of the 4HBS, and its appearance in different protein fractions, raise questions as to its physiological role in vanillin biosynthesis in vivo.

Discrete coding of stimulus value, reward expectation, and reward prediction error in the dorsal striatum.

PubMed

Oyama, Kei; Tateyama, Yukina; Hernádi, István; Tobler, Philippe N; Iijima, Toshio; Tsutsui, Ken-Ichiro

2015-11-01

To investigate how the striatum integrates sensory information with reward information for behavioral guidance, we recorded single-unit activity in the dorsal striatum of head-fixed rats participating in a probabilistic Pavlovian conditioning task with auditory conditioned stimuli (CSs) in which reward probability was fixed for each CS but parametrically varied across CSs. We found that the activity of many neurons was linearly correlated with the reward probability indicated by the CSs. The recorded neurons could be classified according to their firing patterns into functional subtypes coding reward probability in different forms such as stimulus value, reward expectation, and reward prediction error. These results suggest that several functional subgroups of dorsal striatal neurons represent different kinds of information formed through extensive prior exposure to CS-reward contingencies. Copyright © 2015 the American Physiological Society.

Cocaine Effects on Dopaminergic Transmission Depend on a Balance between Sigma-1 and Sigma-2 Receptor Expression.

PubMed

Aguinaga, David; Medrano, Mireia; Vega-Quiroga, Ignacio; Gysling, Katia; Canela, Enric I; Navarro, Gemma; Franco, Rafael

2018-01-01

Sigma σ 1 and σ 2 receptors are targets of cocaine. Despite sharing a similar name, the two receptors are structurally unrelated and their physiological role is unknown. Cocaine increases the level of dopamine, a key neurotransmitter in CNS motor control and reward areas. While the drug also affects dopaminergic signaling by allosteric modulations exerted by σ 1 R interacting with dopamine D 1 and D 2 receptors, the potential regulation of dopaminergic transmission by σ 2 R is also unknown. We here demonstrate that σ 2 R may form heteroreceptor complexes with D 1 but not with D 2 receptors. Remarkably σ 1 , σ 2 , and D 1 receptors may form heterotrimers with particular signaling properties. Determination of cAMP levels, MAP kinase activation and label-free assays demonstrate allosteric interactions within the trimer. Importantly, the presence of σ 2 R induces bias in signal transduction as σ 2 R ligands increase cAMP signaling whereas reduce MAP kinase activation. These effects, which are opposite to those exerted via σ 1 R, suggest that the D 1 receptor-mediated signaling depends on the degree of trimer formation and the differential balance of sigma receptor and heteroreceptor expression in acute versus chronic cocaine consumption. Although the physiological role is unknown, the heteroreceptor complex formed by σ 1 , σ 2 , and D 1 receptors arise as relevant to convey the cocaine actions on motor control and reward circuits and as a key factor in acquisition of the addictive habit.

Cocaine Effects on Dopaminergic Transmission Depend on a Balance between Sigma-1 and Sigma-2 Receptor Expression

PubMed Central

Aguinaga, David; Medrano, Mireia; Vega-Quiroga, Ignacio; Gysling, Katia; Canela, Enric I.; Navarro, Gemma; Franco, Rafael

2018-01-01

Sigma σ1 and σ2 receptors are targets of cocaine. Despite sharing a similar name, the two receptors are structurally unrelated and their physiological role is unknown. Cocaine increases the level of dopamine, a key neurotransmitter in CNS motor control and reward areas. While the drug also affects dopaminergic signaling by allosteric modulations exerted by σ1R interacting with dopamine D1 and D2 receptors, the potential regulation of dopaminergic transmission by σ2R is also unknown. We here demonstrate that σ2R may form heteroreceptor complexes with D1 but not with D2 receptors. Remarkably σ1, σ2, and D1 receptors may form heterotrimers with particular signaling properties. Determination of cAMP levels, MAP kinase activation and label-free assays demonstrate allosteric interactions within the trimer. Importantly, the presence of σ2R induces bias in signal transduction as σ2R ligands increase cAMP signaling whereas reduce MAP kinase activation. These effects, which are opposite to those exerted via σ1R, suggest that the D1 receptor-mediated signaling depends on the degree of trimer formation and the differential balance of sigma receptor and heteroreceptor expression in acute versus chronic cocaine consumption. Although the physiological role is unknown, the heteroreceptor complex formed by σ1, σ2, and D1 receptors arise as relevant to convey the cocaine actions on motor control and reward circuits and as a key factor in acquisition of the addictive habit. PMID:29483862

Mechanism for pH-dependent gene regulation by amino-terminus-mediated homooligomerization of Bacillus subtilis anti-trp RNA-binding attenuation protein

PubMed Central

Sachleben, Joseph R.; McElroy, Craig A.; Gollnick, Paul; Foster, Mark P.

2010-01-01

Anti-TRAP (AT) is a small zinc-binding protein that regulates tryptophan biosynthesis in Bacillus subtilis by binding to tryptophan-bound trp RNA-binding attenuation protein (TRAP), thereby preventing it from binding RNA, and allowing transcription and translation of the trpEDCFBA operon. Crystallographic and sedimentation studies have shown that AT can homooligomerize to form a dodecamer, AT12, composed of a tetramer of trimers, AT3. Structural and biochemical studies suggest that only trimeric AT is active for binding to TRAP. Our chromatographic and spectroscopic data revealed that a large fraction of recombinantly overexpressed AT retains the N-formyl group (fAT), presumably due to incomplete N-formyl-methionine processing by peptide deformylase. Hydrodynamic parameters from NMR relaxation and diffusion measurements showed that fAT is exclusively trimeric (AT3), while (deformylated) AT exhibits slow exchange between both trimeric and dodecameric forms. We examined this equilibrium using NMR spectroscopy and found that oligomerization of active AT3 to form inactive AT12 is linked to protonation of the amino terminus. Global analysis of the pH dependence of the trimer-dodecamer equilibrium revealed a near physiological pKa for the N-terminal amine of AT and yielded a pH-dependent oligomerization equilibrium constant. Estimates of excluded volume effects due to molecular crowding suggest the oligomerization equilibrium may be physiologically important. Because deprotonation favors “active” trimeric AT and protonation favors “inactive” dodecameric AT, our findings illuminate a possible mechanism for sensing and responding to changes in cellular pH. PMID:20713740

Role of hepsin in factor VII activation in zebrafish.

PubMed

Khandekar, Gauri; Jagadeeswaran, Pudur

2014-01-01

Factor VII, the initiator of the extrinsic coagulation cascade, circulates in human plasma mainly in its zymogen form, factor VII and in small amounts in its activated form, factor VIIa. However, the mechanism of initial generation of factor VIIa is not known despite intensive research using currently available model systems. Earlier findings suggested serine proteases factor VII activating protease and hepsin play a role in activating factor VII, however, it has remained controversial. In this paper we estimated the levels of factor VIIa and factor VII for the first time in zebrafish adult population and also reevaluated the role of the above two serine proteases in activating factor VII in vivo using zebrafish as a model system. Knockdown of factor VII activating protease and hepsin was performed followed by assaying for their effect on factor VIIa concentration and extrinsic coagulation as measured by the kinetic prothrombin time. Factor VII activating protease knockdown showed no change in kinetic prothrombin time and no effect on factor VIIa levels while hepsin knockdown increased the kinetic prothrombin time and significantly reduced the factor VIIa plasma levels. Our results thus indicate that hepsin plays a physiologically important role in factor VII activation and hemostasis in zebrafish. © 2013.

Molecular basis of activation of endopeptidase activity of botulinum neurotoxin type E.

PubMed

Kukreja, Roshan V; Sharma, Shashi K; Singh, Bal Ram

2010-03-23

Botulinum neurotoxins (BoNTs) are a group of large proteins that are responsible for the clinical syndrome of botulism. The seven immunologically distinct serotypes of BoNTs (A-G), each produced by various strains of Clostridium botulinum, act on the neuromuscular junction by blocking the release of the neurotransmitter acetylcholine, thereby resulting in flaccid muscle paralysis. BoNTs are synthesized as single inactive polypeptide chains that are cleaved by endogenous or exogenous proteases to generate the active dichain form of the toxin. Nicking of the single chain BoNT/E to the dichain form is associated with 100-fold increase in toxicity. Here we investigated the activation mechanism of botulinum neurotoxin type E upon nicking and subsequent reduction of disulfide bond. It was observed that nicking of BoNT/E significantly enhances its endopeptidase activity and that at the physiological temperature of 37 degrees C the reduced form of nicked BoNT/E adopts a dynamically flexible conformation resulting from the exposure of hydrophobic segments and facilitating optimal cleavage of its substrate SNAP-25. Such reduction-induced increase in the flexibility of the polypeptide folding provides a rationale for the mechanism of BoNT/E endopeptidase against its intracellular substrate, SNAP-25, and complements current understanding of the mechanistics of interaction between the substrate and BoNT endopeptidase.

Structural network heterogeneities and network dynamics: a possible dynamical mechanism for hippocampal memory reactivation.

NASA Astrophysics Data System (ADS)

Jablonski, Piotr; Poe, Gina; Zochowski, Michal

2007-03-01

The hippocampus has the capacity for reactivating recently acquired memories and it is hypothesized that one of the functions of sleep reactivation is the facilitation of consolidation of novel memory traces. The dynamic and network processes underlying such a reactivation remain, however, unknown. We show that such a reactivation characterized by local, self-sustained activity of a network region may be an inherent property of the recurrent excitatory-inhibitory network with a heterogeneous structure. The entry into the reactivation phase is mediated through a physiologically feasible regulation of global excitability and external input sources, while the reactivated component of the network is formed through induced network heterogeneities during learning. We show that structural changes needed for robust reactivation of a given network region are well within known physiological parameters.

Structural network heterogeneities and network dynamics: A possible dynamical mechanism for hippocampal memory reactivation

NASA Astrophysics Data System (ADS)

Jablonski, Piotr; Poe, Gina R.; Zochowski, Michal

2007-01-01

The hippocampus has the capacity for reactivating recently acquired memories and it is hypothesized that one of the functions of sleep reactivation is the facilitation of consolidation of novel memory traces. The dynamic and network processes underlying such a reactivation remain, however, unknown. We show that such a reactivation characterized by local, self-sustained activity of a network region may be an inherent property of the recurrent excitatory-inhibitory network with a heterogeneous structure. The entry into the reactivation phase is mediated through a physiologically feasible regulation of global excitability and external input sources, while the reactivated component of the network is formed through induced network heterogeneities during learning. We show that structural changes needed for robust reactivation of a given network region are well within known physiological parameters.

Midi-maxi computer interaction in the interpretation of nuclear medicine procedures

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

Schlapper, G.A.

1977-01-01

A study of renal function with an Anger Gamma Camera coupled with a Digital Equipment Corporation Gamma-11 System and an IBM System 370 demonstrates the potential of quantitative determinations of physiological function through the application of midi-maxi computer interaction in the interpretation of nuclear medicine procedures. It is shown that radiotracers can provide an opportunity to assess physiological processes of renal function by noninvasively following the path of a tracer as a function of time. Time-activity relationships obtained over seven anatomically defined regions are related to parameters of a seven compartment model employed to describe the renal clearance process. Themore » values obtained for clinically significant parameters agree with known renal pathophysiology. Differentiation of failure of acute, chronic, and obstructive forms is indicated.« less

Physiological and Psychological Effects of Viewing a Kiwifruit (Actinidia deliciosa ‘Hayward’) Orchard Landscape in Summer in Japan

PubMed Central

Igarashi, Miho; Miwa, Masayuki; Ikei, Harumi; Song, Chorong; Takagaki, Michiko; Miyazaki, Yoshifumi

2015-01-01

The physiological and psychological relaxation effects of viewing a kiwifruit (Actinidia deliciosa ‘Hayward’) orchard landscape were investigated. Seventeen Japanese adult females (46.1 ± 8.2 years) viewed a kiwifruit orchard landscape or a building site (control) for 10 min. The heart rate variability and heart rate were determined. The modified semantic differential method and the short-form Profile of Mood States were used to assess the psychological effects. Compared with viewing the building site, viewing the kiwifruit orchard landscape resulted in a significant increase in the parasympathetic activity, a marginally significant decrease in the heart rate, a significant increase in “comfortable”, “relaxed” and “natural” feelings and a significant improvement in mood states. PMID:26110331

[An increase in efficiency of adaptations and a weakening of organism protective reactions in the process of biological evolution].

PubMed

Ivanov, K P

2014-01-01

The main direction of evolution of living organisms is development of the central nervous system and sense organ, an increase of energy exchange development of homoiothermia, development of the more and more complex forms of behavior, an increase in energy expenditure in connection with an increase of the organism activity, and development of adaptation to the habitat. Such fundamental processes were subjected and have been subjected to numerous studies and discussions. However, in different animals there exist different species peculiarities of evolution of physiological functions, from which finally formed are fundamental evolutionary processes. We studied some of these specific processes by dividing them into two categories. The first category is "Increase of efficiency of adaptation" in development of biological evolution. By this term we mean development of amazing by perfection specific physiological mechanisms of adaptive character. The second category is "Weakening of protective organism reactions". By this we understand disturbance of protective mechanisms of the organism immune system, discoordination of movement of leukocytes along microvessels, the absence of efficient collateral circulation in brain and in heart, etc.

Paradoxical activation of the sodium chloride cotransporter (NCC) without hypertension in kidney deficient in a regulatory subunit of Na,K-ATPase, FXYD2.

PubMed

Arystarkhova, Elena; Ralph, Donna L; Liu, Yi Bessie; Bouley, Richard; McDonough, Alicia A; Sweadner, Kathleen J

2014-12-01

Na,K-ATPase generates the driving force for sodium reabsorption in the kidney. Na,K-ATPase functional properties are regulated by small proteins belonging to the FXYD family. In kidney FXYD2 is the most abundant: it is an inhibitory subunit expressed in almost every nephron segment. Its absence should increase sodium pump activity and promote Na(+) retention, however, no obvious renal phenotype was detected in mice with global deletion of FXYD2 (Arystarkhova et al. 2013). Here, increased total cortical Na,K-ATPase activity was documented in the Fxyd2(-/-) mouse, without increased α1β1 subunit expression. We tested the hypothesis that adaptations occur in distal convoluted tubule (DCT), a major site of sodium adjustments. Na,K-ATPase immunoreactivity in DCT was unchanged, and there was no DCT hypoplasia. There was a marked activation of thiazide-sensitive sodium chloride cotransporter (NCC; Slc12a3) in DCT, predicted to increase Na(+) reabsorption in this segment. Specifically, NCC total increased 30% and NCC phosphorylated at T53 and S71, associated with activation, increased 4-6 fold. The phosphorylation of the closely related thick ascending limb (TAL) apical NKCC2 (Slc12a1) increased at least twofold. Abundance of the total and cleaved (activated) forms of ENaC α-subunit was not different between genotypes. Nonetheless, no elevation of blood pressure was evident despite the fact that NCC and NKCC2 are in states permissive for Na(+) retention. Activation of NCC and NKCC2 may reflect an intracellular linkage to elevated Na,K-ATPase activity or a compensatory response to Na(+) loss proximal to the TAL and DCT. © 2014 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

Cardiac vagal flexibility and accurate personality impressions: Examining a physiological correlate of the good judge.

PubMed

Human, Lauren J; Mendes, Wendy Berry

2018-02-23

Research has long sought to identify which individuals are best at accurately perceiving others' personalities or are good judges, yet consistent predictors of this ability have been difficult to find. In the current studies, we revisit this question by examining a novel physiological correlate of social sensitivity, cardiac vagal flexibility, which reflects dynamic modulation of cardiac vagal control. We examined whether greater cardiac vagal flexibility was associated with forming more accurate personality impressions, defined as viewing targets more in line with their distinctive self-reported profile of traits, in two studies, including a thin-slice video perceptions study (N = 109) and a dyadic interaction study (N = 175). Across studies, we found that individuals higher in vagal flexibility formed significantly more accurate first impressions of others' more observable personality traits (e.g., extraversion, creativity, warmth). These associations held while including a range of relevant covariates, including cardiac vagal tone, sympathetic activation, and gender. In sum, social sensitivity as indexed by cardiac vagal flexibility is linked to forming more accurate impressions of others' observable traits, shedding light on a characteristic that may help to identify the elusive good judge and providing insight into its neurobiological underpinnings. © 2018 Wiley Periodicals, Inc.

Antibiofilm Activities of a Novel Chimeolysin against Streptococcus mutans under Physiological and Cariogenic Conditions

PubMed Central

Yang, Hang; Bi, Yongli; Shang, Xiaoran; Wang, Mengyue; Linden, Sara B.; Li, Yunpeng

2016-01-01

Streptococcus mutans often survives as a biofilm on the tooth surface and contributes to the development of dental caries. We investigated the efficacy of ClyR, an engineered chimeolysin, against S. mutans biofilms under physiological and cariogenic conditions. Susceptibility tests showed that ClyR was active against all clinical S. mutans isolates tested as well as S. mutans biofilms that displayed resistance to penicillin. The S. mutans biofilms that formed on hydroxyapatite discs under physiological sugar conditions and cariogenic conditions were reduced ∼2 logs and 3 logs after treatment with 100 μg/ml ClyR, respectively. In comparison, only a 1-log reduction was observed in the chlorhexidine gluconate (ChX)-treated group, and no killing effect was observed in the NaF-treated group. A mouse dental colonization model showed that repeated use of ClyR for 3 weeks (5 μg/day) reduced the number of colonized S. mutans cells in the dental plaques significantly (P < 0.05) and had no harmful effects on the mice. Furthermore, toxicity was not noted at concentrations exceeding those used for the in vitro and in vivo studies, and ClyR-specific antibodies could not be detected in mouse saliva after repeated use of ClyR in the oral cavity. Our data collectively demonstrate that ClyR is active against S. mutans biofilms both in vitro and in vivo, thus representing a preventative or therapeutic agent for use against dental caries. PMID:27736755

A student-centered approach for developing active learning: the construction of physical models as a teaching tool in medical physiology.

PubMed

Rezende-Filho, Flávio Moura; da Fonseca, Lucas José Sá; Nunes-Souza, Valéria; Guedes, Glaucevane da Silva; Rabelo, Luiza Antas

2014-09-15

Teaching physiology, a complex and constantly evolving subject, is not a simple task. A considerable body of knowledge about cognitive processes and teaching and learning methods has accumulated over the years, helping teachers to determine the most efficient way to teach, and highlighting student's active participation as a means to improve learning outcomes. In this context, this paper describes and qualitatively analyzes an experience of a student-centered teaching-learning methodology based on the construction of physiological-physical models, focusing on their possible application in the practice of teaching physiology. After having Physiology classes and revising the literature, students, divided in small groups, built physiological-physical models predominantly using low-cost materials, for studying different topics in Physiology. Groups were followed by monitors and guided by teachers during the whole process, finally presenting the results in a Symposium on Integrative Physiology. Along the proposed activities, students were capable of efficiently creating physiological-physical models (118 in total) highly representative of different physiological processes. The implementation of the proposal indicated that students successfully achieved active learning and meaningful learning in Physiology while addressing multiple learning styles. The proposed method has proved to be an attractive, accessible and relatively simple approach to facilitate the physiology teaching-learning process, while facing difficulties imposed by recent requirements, especially those relating to the use of experimental animals and professional training guidelines. Finally, students' active participation in the production of knowledge may result in a holistic education, and possibly, better professional practices.

Functional Groups Based on Leaf Physiology: Are they Spatially and Temporally Robust?

NASA Technical Reports Server (NTRS)

Foster, Tammy E.; Brooks, J. Renee

2004-01-01

The functional grouping hypothesis, which suggests that complexity in ecosystem function can be simplified by grouping species with similar responses, was tested in the Florida scrub habitat. Functional groups were identified based on how species in fire maintained Florida scrub regulate exchange of carbon and water with the atmosphere as indicated by both instantaneous gas exchange measurements and integrated measures of function (%N, delta C-13, delta N-15, C-N ratio). Using cluster analysis, five distinct physiologically-based functional groups were identified in the fire maintained scrub. These functional groups were tested to determine if they were robust spatially, temporally, and with management regime. Analysis of Similarities (ANOSIM), a non-parametric multivariate analysis, indicated that these five physiologically-based groupings were not altered by plot differences (R = -0.115, p = 0.893) or by the three different management regimes; prescribed burn, mechanically treated and burn, and fire-suppressed (R = 0.018, p = 0.349). The physiological groupings also remained robust between the two climatically different years 1999 and 2000 (R = -0.027, p = 0.725). Easy-to-measure morphological characteristics indicating functional groups would be more practical for scaling and modeling ecosystem processes than detailed gas-exchange measurements, therefore we tested a variety of morphological characteristics as functional indicators. A combination of non-parametric multivariate techniques (Hierarchical cluster analysis, non-metric Multi-Dimensional Scaling, and ANOSIM) were used to compare the ability of life form, leaf thickness, and specific leaf area classifications to identify the physiologically-based functional groups. Life form classifications (ANOSIM; R = 0.629, p 0.001) were able to depict the physiological groupings more adequately than either specific leaf area (ANOSIM; R = 0.426, p = 0.001) or leaf thickness (ANOSIM; R 0.344, p 0.001). The ability of life forms to depict the physiological groupings was improved by separating the parasitic Ximenia americana from the shrub category (ANOSIM; R = 0.794, p = 0.001). Therefore, a life form classification including parasites was determined to be a good indicator of the physiological processes of scrub species, and would be a useful method of grouping for scaling physiological processes to the ecosystem level.

Factor XII (Hageman factor) is a missing link between stress and hypercoagulability and plays an important role in the pathophysiology of ischemic stroke.

PubMed

Eggers, Arnold E

2006-01-01

A new hypothesis is presented on the function of factor XII, which is postulated to be a "missing link" between acute stress and transient hypercoagulability. The implications of this idea are developed to show how chronic stress, which involves activation of hypertension and migraine as well as hypercoagulability, can cause of cerebrovascular disease. "Acute stress" is defined as "the normal short-term physiological response to the perception of major threats or demands". "Chronic stress" is "the abnormal ongoing physiological response to the continuing perception of unresolvable major threats or demands". The factor XII hypothesis is as follows: Acute stress includes release of epinephrine by the adrenal medulla. Epinephrine activates platelets by binding to alpha-2A adrenergic receptors. Activated platelets convert pre-bound factor XII to its active form, which then initiates the intrinsic coagulation cascade. This can be called the "activated platelet initiation pathway" for coagulation. Neither tissue factor nor pre-formed thrombin is required. Thrombosis proceeds to completion, but only a minute amount of thrombin is formed, and the process normally stops at this point. In people who lapse into a state of chronic stress, essential hypertension, which is also a manifestation of stress, synergizes with hypercoagulability: there is both a baseline rise in blood pressure and systemic platelet activation as well as superimposed labile rises of both. Upregulation of these two stress parameters is atherogenic: epinephrine-activated platelets stimulating thrombin formation interact with endothelial cells activated by angiotensin II to cause, first, smooth muscle cell proliferation, which is a histological hallmark of atherosclerosis, and, lastly, a symptomatic thrombotic occlusion-the stroke. The migraine symptoms which often accompany this process are a marker of chronic stress and ongoing pathophysiologic damage. Therapeutic predictions are made regarding novel ways of blocking stress-induced hypercoagulability and hypertension. Hypercoagulability could be targeted by monoclonal antibodies directed against the platelet-specific alpha-2 adrenergic receptor or the (putative) platelet receptor for Factor XII; hypertension could be treated with monoclonal antibodies directed against the beta-adrenergic receptor in the juxtaglomerular apparatus or by surgical denervation of the kidneys, either of which would decrease the renin release which helps drive the hypertension.

Neuroserpin Differentiates Between Forms of Tissue Type Plasminogen Activator via pH Dependent Deacylation

PubMed Central

Carlson, Karen-Sue B.; Nguyen, Lan; Schwartz, Kat; Lawrence, Daniel A.; Schwartz, Bradford S.

2016-01-01

Tissue-type plasminogen activator (t-PA), initially characterized for its critical role in fibrinolysis, also has key functions in both physiologic and pathologic processes in the CNS. Neuroserpin (NSP) is a t-PA specific serine protease inhibitor (serpin) found almost exclusively in the CNS that regulates t-PA’s proteolytic activity and protects against t-PA mediated seizure propagation and blood–brain barrier disruption. This report demonstrates that NSP inhibition of t-PA varies profoundly as a function of pH within the biologically relevant pH range for the CNS, and reflects the stability, rather than the formation of NSP: t-PA acyl-enzyme complexes. Moreover, NSP differentiates between the zymogen-like single chain form (single chain t-PA, sct-PA) and the mature protease form (two chain t-PA, tct-PA) of t-PA, demonstrating different pH profiles for protease inhibition, different pH ranges over which catalytic deacylation occurs, and different pH dependent profiles of deacylation rates for each form of t-PA. NSP’s pH dependent inhibition of t-PA is not accounted for by differential acylation, and is specific for the NSP-t-PA serpin-protease pair. These results demonstrate a novel mechanism for the differential regulation of the two forms of t-PA in the CNS, and suggest a potential specific regulatory role for CNS pH in controlling t-PA proteolytic activity. PMID:27378851

Exercise Physiology. Basic Stuff Series I. I.

ERIC Educational Resources Information Center

Svoboda, Milan; And Others

The fundamentals of exercise physiology (the study of the physiological effects of bodily exertion) form the basis for this booklet designed for teachers of physical education. The scientific principles underlying the building of muscular strength and flexibility are described and illustrated. Topics covered include: (1) muscular strength,…

Relationship of plasma nonesterified fatty acids and walking activity in postpartum dairy cows.

PubMed

Adewuyi, A A; Roelofs, J B; Gruys, E; Toussaint, M J M; van Eerdenburg, F J C M

2006-08-01

To survive and produce milk, postpartum dairy cows use their reserves through lipolysis. If the negative energy balance is severe, nonesterified fatty acids (NEFA) are formed that can impair several physiological processes. A pilot study suggested that increased walking activity after calving may be related to a reduced serum concentration of NEFA. The objective of this study was to determine the relationship between plasma concentrations of NEFA and walking activity in dairy cattle during the postpartum period. Data were collected from 33 multiparous Holstein-Friesian dairy cows. Walking activities were quantified using pedometry, and blood samples were collected for determination of NEFA. Results of this study indicated that a negative relationship existed between walking activity and plasma NEFA concentrations in postpartum dairy cows.

Monomeric Alpha-Synuclein Exerts a Physiological Role on Brain ATP Synthase

PubMed Central

Ludtmann, Marthe H.R.; Angelova, Plamena R.; Ninkina, Natalia N.; Gandhi, Sonia

2016-01-01

Misfolded α-synuclein is a key factor in the pathogenesis of Parkinson's disease (PD). However, knowledge about a physiological role for the native, unfolded α-synuclein is limited. Using brains of mice lacking α-, β-, and γ-synuclein, we report that extracellular monomeric α-synuclein enters neurons and localizes to mitochondria, interacts with ATP synthase subunit α, and modulates ATP synthase function. Using a combination of biochemical, live-cell imaging and mitochondrial respiration analysis, we found that brain mitochondria of α-, β-, and γ-synuclein knock-out mice are uncoupled, as characterized by increased mitochondrial respiration and reduced mitochondrial membrane potential. Furthermore, synuclein deficiency results in reduced ATP synthase efficiency and lower ATP levels. Exogenous application of low unfolded α-synuclein concentrations is able to increase the ATP synthase activity that rescues the mitochondrial phenotypes observed in synuclein deficiency. Overall, the data suggest that α-synuclein is a previously unrecognized physiological regulator of mitochondrial bioenergetics through its ability to interact with ATP synthase and increase its efficiency. This may be of particular importance in times of stress or PD mutations leading to energy depletion and neuronal cell toxicity. SIGNIFICANCE STATEMENT Misfolded α-synuclein aggregations in the form of Lewy bodies have been shown to be a pathological hallmark in histological staining of Parkinson's disease (PD) patient brains. It is known that misfolded α-synuclein is a key driver in PD pathogenesis, but the physiological role of unfolded monomeric α-synuclein remains unclear. Using neuronal cocultures and isolated brain mitochondria of α-, β-, and γ-synuclein knock-out mice and monomeric α-synuclein, this current study shows that α-synuclein in its unfolded monomeric form improves ATP synthase efficiency and mitochondrial function. The ability of monomeric α-synuclein to enhance ATP synthase efficiency under physiological conditions may be of importance when α-synuclein undergoes the misfolding and aggregation reported in PD. PMID:27733604

[The 2009 Nobel Prize in Medicine and its surprising message: lifestyle is associated with telomerase activity].

PubMed

Falus, András; Marton, István; Borbényi, Erika; Tahy, Adám; Karádi, Pál; Aradi, János; Stauder, Adrienne; Kopp, Mária

2010-06-13

The 2009 Nobel Prize in Physiology and Medicine was awarded to three scientists for their pioneer research on telomeres - and the enzyme that forms them - telomerase. Their work highlighted the considerable connection between the length of telomeres and intensive changes in lifestyle and nutrition (Ornish method) as well as behavioral and psychological factors. In this review the various elements of molecular, cell biological, nutritional and lifestyle changes are introduced and discussed.

[Carbohydrate transport in the cestode Triaenophorus nodulosus].

PubMed

Izvekova, G I

1989-01-01

The data demonstrating the presence of the glucose active transport system in the cestode T. nodulosus are obtained. Kinetic characteristics of the transport are estimated and their dependence on the incubation temperature are shown. Heterogeneity of the worm body in respect to transport processes and their dependence on the physiological state of cestodes are discovered. The absorption of different forms of glucose is studied and the similarity of digestion processes in parasites and their hosts is shown.

The Hungry Stomach: Physiology, Disease, and Drug Development Opportunities

PubMed Central

Sanger, Gareth J.; Hellström, Per M.; Näslund, Erik

2010-01-01

During hunger, a series of high-amplitude contractions of the stomach and small intestine (phase III), which form part of a cycle of quiescence and contractions (known as the migrating motor complex, MMC), play a “housekeeping” role prior to the next meal, and may contribute toward the development of hunger. Several gastrointestinal (GI) hormones are associated with phase III MMC activity, but currently the most prominent is motilin, thought to at least partly mediate phase III contractions of the gastric MMC. Additional GI endocrine and neuronal systems play even more powerful roles in the development of hunger. In particular, the ghrelin-precursor gene is proving to have a complex physiology, giving rise to three different products: ghrelin itself, which is formed from a post-translational modification of des-acyl-ghrelin, and obestatin. The receptors acted on by des-acyl-ghrelin and by obestatin are currently unknown but both these peptides seem able to exert actions which oppose that of ghrelin, either indirectly or directly. An increased understanding of the actions of these peptides is helping to unravel a number of different eating disorders and providing opportunities for the discovery of new drugs to regulate dysfunctional gastric behaviors and appetite. To date, ghrelin and motilin receptor agonists and antagonists have been described. The most advanced are compounds which activate the ghrelin and motilin receptors which are being progressed for disorders associated with gastric hypomotility. PMID:21927604

Role of the protective antigen octamer in the molecular mechanism of anthrax lethal toxin stabilization in plasma

PubMed Central

Kintzer, Alexander F.; Sterling, Harry J.; Tang, Iok I.; Abdul-Gader, Ali; Miles, Andrew J.; Wallace, B. A.; Williams, Evan R.; Krantz, Bryan A.

2010-01-01

Anthrax is caused by strains of Bacillus anthracis that produce two key virulence factors, anthrax toxin (Atx) and a poly-γ-D-glutamic acid capsule. Atx is comprised of three-proteins: protective antigen (PA) and two enzymes, lethal factor (LF) and edema factor (EF). To disrupt cell function, these components must assemble into holotoxin complexes, which contain either a ring-shaped homooctameric or homoheptameric PA oligomer bound to multiple copies of either LF and/or EF, producing lethal toxin (LT), edema toxin, or mixtures thereof. Once a host cell endocytoses these complexes, PA converts into a membrane-inserted channel that translocates LF and EF into the cytosol. LT may assemble on host cell surfaces or extracellularly in plasma. We show that under physiological conditions in bovine plasma that LT complexes containing heptameric PA aggregate and inactivate more readily than LT complexes containing octameric PA. LT complexes containing octameric PA possess enhanced stability, channel forming activity, and macrophage cytotoxicity relative to those containing heptameric PA. Under physiological conditions, multiple biophysical probes reveal that heptameric PA can prematurely adopt the channel conformation, but octameric PA complexes remain in their soluble prechannel configuration allowing them to resist aggregation and inactivation. We conclude that PA may form an octameric oligomeric state as a means to produce a more stable and active LT complex that may circulate freely in the blood. PMID:20433851

High aryl acylamidase activity associated with cobra venom acetylcholinesterase: biological significance.

PubMed

Rajesh, Ramanna V; Layer, Paul G; Boopathy, Rathanam

2009-01-01

Investigation of the non-classical functions of cholinesterases (ChEs) has been the subject of interest in the past three decades. One of which is aryl acylamidase (AAA) activity associated with ChEs, but characterized in in vitro, as an enzyme, splitting the artificial substrate o-nitroacetanilide with unknown physiological function. In the present study, we have compared levels of AAA activity of AChE from different sources like goat brain, electric eel organ and from venoms of different snakes. Remarkably cobra venom showed the highest AAA activity and also high AAA/AChE ratio. Both serotonergenic and cholinergic inhibitors inhibited the cobra venom AAA activity in a concentration dependent manner, which also underlines the association of AAA with AChE of cobra venom. The study becomes interesting because of i) the cobra venom AChE exists in monomeric globular forms; ii) in Alzheimer's disease too the most abundant forms of cholinesterases are monomeric globular forms, thought to be involved in the pathogenesis of Alzheimer's disease; iii) the effect of Alzheimer's disease drugs on the AAA activity of cobra venom, indicated that AAA activity of cobra venom was more sensitive than AChE and iv) Huperzine and Tacrine showed more pronounced effect on AAA. Thus, this study elucidates the high AAA associated with cobra venom AChE may serve as one of the prominent activity to test the pharmacological effect of AD drugs, as other sources were found to have lower activity.

A controlled comparison of emotional reactivity and physiological response in masticatory muscle pain patients.

PubMed

Schmidt, John E; Carlson, Charles R

2009-01-01

To investigate (1) differences in heart rate variability (HRV) indices between masticatory muscle pain (MMP) patients and pain-free controls at rest, during a stressor condition, and during a post-stressor recovery period, and (2) factors including psychological distress, social environment, and family-of-origin characteristics in the MMP sample compared to a pain-free matched control sample. Physiological activation and emotional reactivity were assessed in 22 MMP patients and 23 controls during baseline, stressor, and recovery periods. Physiological activity was assessed with frequency domain HRV indices. Emotional reactivity was assessed with the Emotional Assessment Scale. Analytic strategy began with overall 2 x 3 multivariate analyses of variance on physiological data followed by focused contrasts to test specific hypotheses regarding physiological and emotional status. Hypothesized differences between study groups on psychological and social-environmental variables were compared with univariate analyses of variance. The MMP patients showed physiological activation during the baseline period and significantly more physiological activation during the recovery period compared to the controls. This pattern was also present in emotional reactivity between the groups. The emotional and physiological differences between the groups across study periods were more pronounced in pain patients reporting a traumatic stressor. These results provide further evidence of physiological activation and emotional responding in MMP patients that differentiates them from matched pain-free controls. The use of HRV indices to measure physiological functioning quantifies the degree of sympathetic and parasympathetic activation. Study results suggest the use of these HRV indices may improve understanding of the role of excitatory and inhibitory mechanisms in patients with MMP conditions.

Comparison of the postural and physiological effects of two dynamic workstations to conventional sitting and standing workstations.

PubMed

Botter, Juliane; Ellegast, Rolf P; Burford, Eva-Maria; Weber, Britta; Könemann, Reinier; Commissaris, Dianne A C M

2016-03-01

Increasing evidence is being found for the association of health risk factors with work-related physical inactivity. An increasing number of people are being exposed to this form of inactivity, and as a result, various interventions aimed at increasing physical activity during working hours are being developed. This study aims to investigate the differences in postural, muscular and physical activities resulting from two dynamic workstations, namely an elliptical trainer and a treadmill workstation, compared with a conventional sitting and standing workstation. Twelve participants completed five standardised office tasks in a laboratory setting at all workstations. No significant effect was found regarding changes in posture and the muscular activity was only significantly higher for the trapezius muscle (50th percentile: 8.1 %MVC) at the dynamic workstations. For the dynamic workstations, physical activity ranged from 4.0 to 14.9 × 10(-2) g, heart rate from 14.3 to 27.5 %HRR and energy expenditure from 1.8 to 3.1 METs. Practitioner Summary: Work-related physical inactivity is associated with health risk factors. In this study, physiological and postural effects of dynamic workstations were assessed in comparison to conventional workstations. No significant effects were found regarding changes in posture and muscular activity. Physical activity, heart rate and energy expenditure increased for the dynamic workstations.

Application of Acceleration Sensors in Physiological Experiments

NASA Astrophysics Data System (ADS)

Vavrinský, Erik; Moskal'vá, Daniela; Darříček, Martin; Donoval, Martin; Horínek, František; Popovič, Marían; Miklovič, Peter

2014-09-01

This paper illustrates a promising application of an accelerometer sensor in physiological research, we demonstrated use of accelerometers for monitoring the standard proband physical activity (PA) and also in special applications like respiration and mechanical heart activity, the so-called seismocardiography (SCG) monitoring, physiological activation monitoring and mechanomyography (MMG)

WAVE2 forms a complex with PKA and is involved in PKA enhancement of membrane protrusions.

PubMed

Yamashita, Hiroshi; Ueda, Kazumitsu; Kioka, Noriyuki

2011-02-04

PKA contributes to many physiological processes, including glucose homeostasis and cell migration. The substrate specificity of PKA is low compared with other kinases; thus, complex formation with A-kinase-anchoring proteins is important for the localization of PKA in specific subcellular regions and the phosphorylation of specific substrates. Here, we show that PKA forms a complex with WAVE2 (Wiskott-Aldrich syndrome protein family verprolin-homologous protein 2) in MDA-MB-231 breast cancer cells and mouse brain extracts. Two separate regions of WAVE2 are involved in WAVE2-PKA complex formation. This complex localizes to the leading edge of MDA-MB-231 cells. PKA activation results in enlargement of the membrane protrusion. WAVE2 depletion impairs PKA localization at membrane protrusions and the enlargement of membrane protrusion induced by PKA activation. Together, these results suggest that WAVE2 works as an A-kinase-anchoring protein that recruits PKA at membrane protrusions and plays a role in the enlargement of membrane protrusions induced by PKA activation.

A Review of Disintegration Mechanisms and Measurement Techniques.

PubMed

Markl, Daniel; Zeitler, J Axel

2017-05-01

Pharmaceutical solid dosage forms (tablets or capsules) are the predominant form to administer active pharmaceutical ingredients (APIs) to the patient. Tablets are typically powder compacts consisting of several different excipients in addition to the API. Excipients are added to a formulation in order to achieve the desired fill weight of a dosage form, to improve the processability or to affect the drug release behaviour in the body. These complex porous systems undergo different mechanisms when they come in contact with physiological fluids. The performance of a drug is primarily influenced by the disintegration and dissolution behaviour of the powder compact. The disintegration process is specifically critical for immediate-release dosage forms. Its mechanisms and the factors impacting disintegration are discussed and methods used to study the disintegration in-situ are presented. This review further summarises mathematical models used to simulate disintegration phenomena and to predict drug release kinetics.

Channel function reconstitution and re-animation: a single-channel strategy in the postcrystal age.

PubMed

Oiki, Shigetoshi

2015-06-15

The most essential properties of ion channels for their physiologically relevant functions are ion-selective permeation and gating. Among the channel species, the potassium channel is primordial and the most ubiquitous in the biological world, and knowledge of this channel underlies the understanding of features of other ion channels. The strategy applied to studying channels changed dramatically after the crystal structure of the potassium channel was resolved. Given the abundant structural information available, we exploited the bacterial KcsA potassium channel as a simple model channel. In the postcrystal age, there are two effective frameworks with which to decipher the functional codes present in the channel structure, namely reconstitution and re-animation. Complex channel proteins are decomposed into essential functional components, and well-examined parts are rebuilt for integrating channel function in the membrane (reconstitution). Permeation and gating are dynamic operations, and one imagines the active channel by breathing life into the 'frozen' crystal (re-animation). Capturing the motion of channels at the single-molecule level is necessary to characterize the behaviour of functioning channels. Advanced techniques, including diffracted X-ray tracking, lipid bilayer methods and high-speed atomic force microscopy, have been used. Here, I present dynamic pictures of the KcsA potassium channel from the submolecular conformational changes to the supramolecular collective behaviour of channels in the membrane. These results form an integrated picture of the active channel and offer insights into the processes underlying the physiological function of the channel in the cell membrane. © 2015 The Authors. The Journal of Physiology © 2015 The Physiological Society.

Scale-Free Neural and Physiological Dynamics in Naturalistic Stimuli Processing

PubMed Central

Lin, Amy

2016-01-01

Abstract Neural activity recorded at multiple spatiotemporal scales is dominated by arrhythmic fluctuations without a characteristic temporal periodicity. Such activity often exhibits a 1/f-type power spectrum, in which power falls off with increasing frequency following a power-law function: P(f)∝1/fβ, which is indicative of scale-free dynamics. Two extensively studied forms of scale-free neural dynamics in the human brain are slow cortical potentials (SCPs)—the low-frequency (<5 Hz) component of brain field potentials—and the amplitude fluctuations of α oscillations, both of which have been shown to carry important functional roles. In addition, scale-free dynamics characterize normal human physiology such as heartbeat dynamics. However, the exact relationships among these scale-free neural and physiological dynamics remain unclear. We recorded simultaneous magnetoencephalography and electrocardiography in healthy subjects in the resting state and while performing a discrimination task on scale-free dynamical auditory stimuli that followed different scale-free statistics. We observed that long-range temporal correlation (captured by the power-law exponent β) in SCPs positively correlated with that of heartbeat dynamics across time within an individual and negatively correlated with that of α-amplitude fluctuations across individuals. In addition, across individuals, long-range temporal correlation of both SCP and α-oscillation amplitude predicted subjects’ discrimination performance in the auditory task, albeit through antagonistic relationships. These findings reveal interrelations among different scale-free neural and physiological dynamics and initial evidence for the involvement of scale-free neural dynamics in the processing of natural stimuli, which often exhibit scale-free dynamics. PMID:27822495

Physiological stimuli evoke two forms of endocytosis in bovine chromaffin cells.

PubMed

Chan, S A; Smith, C

2001-12-15

1. Exocytosis and endocytosis were measured following single, or trains of, simulated action potentials (sAP) in bovine adrenal chromaffin cells. Catecholamine secretion was measured by oxidative amperometry and cell membrane turnover was measured by voltage clamp cell capacitance measurements. 2. The sAPs evoked inward Na(+) and Ca(2+) currents that were statistically identical to those evoked by native action potential waveforms. On average, a single secretory granule underwent fusion following sAP stimulation. An equivalent amount of membrane was then quickly internalised (tau = 560 ms). 3. Stimulation with sAP trains revealed a biphasic relationship between cell firing rate and endocytic activity. At basal stimulus frequencies (single to 0.5 Hz) cells exhibited a robust membrane internalisation that then diminished as firing increased to intermediate levels (1.9 and 6 Hz). However at the higher stimulation rates (10 and 16 Hz) endocytic activity rebounded and was again able to effectively maintain cell surface near pre-stimulus levels. 4. Treatment with cyclosporin A and FK506, inhibitors of the phosphatase calcineurin, left endocytosis characteristics unaltered at the lower basal stimulus levels, but blocked the resurgence in endocytosis seen in control cells at higher sAP frequencies. 5. Based on these findings we propose that, under physiological electrical stimulation, chromaffin cells internalise membrane via two distinct pathways that are separable. One is prevalent at basal stimulus frequencies, is lessened with increased firing, and is insensitive to cyclosporin A and FK506. A second endocytic form is activated by increased firing frequencies, and is selectively blocked by cyclosporin A and FK506.

Physiological stimuli evoke two forms of endocytosis in bovine chromaffin cells

PubMed Central

Chan, Shyue-An; Smith, Corey

2001-01-01

Exocytosis and endocytosis were measured following single, or trains of, simulated action potentials (sAP) in bovine adrenal chromaffin cells. Catecholamine secretion was measured by oxidative amperometry and cell membrane turnover was measured by voltage clamp cell capacitance measurements. The sAPs evoked inward Na+ and Ca2+ currents that were statistically identical to those evoked by native action potential waveforms. On average, a single secretory granule underwent fusion following sAP stimulation. An equivalent amount of membrane was then quickly internalised (τ = 560 ms). Stimulation with sAP trains revealed a biphasic relationship between cell firing rate and endocytic activity. At basal stimulus frequencies (single to 0.5 Hz) cells exhibited a robust membrane internalisation that then diminished as firing increased to intermediate levels (1.9 and 6 Hz). However at the higher stimulation rates (10 and 16 Hz) endocytic activity rebounded and was again able to effectively maintain cell surface near pre-stimulus levels. Treatment with cyclosporin A and FK506, inhibitors of the phosphatase calcineurin, left endocytosis characteristics unaltered at the lower basal stimulus levels, but blocked the resurgence in endocytosis seen in control cells at higher sAP frequencies. Based on these findings we propose that, under physiological electrical stimulation, chromaffin cells internalise membrane via two distinct pathways that are separable. One is prevalent at basal stimulus frequencies, is lessened with increased firing, and is insensitive to cyclosporin A and FK506. A second endocytic form is activated by increased firing frequencies, and is selectively blocked by cyclosporin A and FK506. PMID:11744761

Transient diabetes insipidus in a post-partum woman with pre-eclampsia associated with residual placental vasopressinase activity.

PubMed

Rodrigo, Natassia; Hocking, Samantha

2018-01-01

This case illustrates the exceedingly rare phenomenon of transient diabetes insipidus, in association with pre-eclampsia, occurring in the post-partum period following an in vitro fertilisation pregnancy, in an otherwise well 48-year-old lady. Diabetes insipidus can manifest during pregnancy, induced by increased vasopressinase activity secreted by placental trophoblasts and usually manifests in the third trimester. This presentation elucidates not only the intricate balance between the physiology of pregnancy and hormonal homeostasis, but also the importance of post-partum care as the physiological changes of pregnancy still hold pathological potential in the weeks immediately following delivery. Diabetes insipidus (DI) is a rare complication of pregnancy occurring in 1 in 30 000 pregnancies.It is associated with excessive vasopressinase activity, secreted by placental trophoblasts, which increases the rate of degradation of anti-diuretic hormone.It is responsive to synthetic desmopressin 1-deanimo-8-d-arginine vasopressin as this form is not degraded by placental vasopressinase.Vasopressinase is proportional to placental weight, which is increased in pregnancies conceived with assisted reproductive techniques including in vitro fertilisation.Vasopressinase-induced DI is associated with pre-eclampsia.

RUTBC1 Functions as a GTPase-activating Protein for Rab32/38 and Regulates Melanogenic Enzyme Trafficking in Melanocytes.

PubMed

Marubashi, Soujiro; Shimada, Hikaru; Fukuda, Mitsunori; Ohbayashi, Norihiko

2016-01-15

Two cell type-specific Rab proteins, Rab32 and Rab38 (Rab32/38), have been proposed as regulating the trafficking of melanogenic enzymes, including tyrosinase and tyrosinase-related protein 1 (Tyrp1), to melanosomes in melanocytes. Like other GTPases, Rab32/38 function as switch molecules that cycle between a GDP-bound inactive form and a GTP-bound active form; the cycle is thought to be regulated by an activating enzyme, guanine nucleotide exchange factor (GEF), and an inactivating enzyme, GTPase-activating protein (GAP), which stimulates the GTPase activity of Rab32/38. Although BLOC-3 has already been identified as a Rab32/38-specific GEF that regulates the trafficking of tyrosinase and Tyrp1, no physiological GAP for Rab32/38 in melanocytes has ever been identified, and it has remained unclear whether Rab32/38 is involved in the trafficking of dopachrome tautomerase, another melanogenic enzyme, in mouse melanocytes. In this study we investigated RUTBC1, which was originally characterized as a Rab9-binding protein and GAP for Rab32 and Rab33B in vitro, and the results demonstrated that RUTBC1 functions as a physiological GAP for Rab32/38 in the trafficking of all three melanogenic enzymes in mouse melanocytes. The results of this study also demonstrated the involvement of Rab9A in the regulation of the RUTBC1 localization and in the trafficking of all three melanogenic enzymes. We discovered that either excess activation or inactivation of Rab32/38 achieved by manipulating RUTBC1 inhibits the trafficking of all three melanogenic enzymes. These results collectively indicate that proper spatiotemporal regulation of Rab32/38 is essential for the trafficking of all three melanogenic enzymes in mouse melanocytes. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Long-Chain Metabolites of Vitamin E: Metabolic Activation as a General Concept for Lipid-Soluble Vitamins?

PubMed Central

Schubert, Martin; Kluge, Stefan; Schmölz, Lisa; Wallert, Maria

2018-01-01

Vitamins E, A, D and K comprise the class of lipid-soluble vitamins. For vitamins A and D, a metabolic conversion of precursors to active metabolites has already been described. During the metabolism of vitamin E, the long-chain metabolites (LCMs) 13′-hydroxychromanol (13′-OH) and 13′-carboxychromanol (13′-COOH) are formed by oxidative modification of the side-chain. The occurrence of these metabolites in human serum indicates a physiological relevance. Indeed, effects of the LCMs on lipid metabolism, apoptosis, proliferation and inflammatory actions as well as tocopherol and xenobiotic metabolism have been shown. Interestingly, there are several parallels between the actions of the LCMs of vitamin E and the active metabolites of vitamin A and D. The recent findings that the LCMs exert effects different from that of their precursors support their putative role as regulatory metabolites. Hence, it could be proposed that the mode of action of the LCMs might be mediated by a mechanism similar to vitamin A and D metabolites. If the physiological relevance and this concept of action of the LCMs can be confirmed, a general concept of activation of lipid-soluble vitamins via their metabolites might be deduced. PMID:29329238

Coral Carbonic Anhydrases: Regulation by Ocean Acidification.

PubMed

Zoccola, Didier; Innocenti, Alessio; Bertucci, Anthony; Tambutté, Eric; Supuran, Claudiu T; Tambutté, Sylvie

2016-06-03

Global change is a major threat to the oceans, as it implies temperature increase and acidification. Ocean acidification (OA) involving decreasing pH and changes in seawater carbonate chemistry challenges the capacity of corals to form their skeletons. Despite the large number of studies that have investigated how rates of calcification respond to ocean acidification scenarios, comparatively few studies tackle how ocean acidification impacts the physiological mechanisms that drive calcification itself. The aim of our paper was to determine how the carbonic anhydrases, which play a major role in calcification, are potentially regulated by ocean acidification. For this we measured the effect of pH on enzyme activity of two carbonic anhydrase isoforms that have been previously characterized in the scleractinian coral Stylophora pistillata. In addition we looked at gene expression of these enzymes in vivo. For both isoforms, our results show (1) a change in gene expression under OA (2) an effect of OA and temperature on carbonic anhydrase activity. We suggest that temperature increase could counterbalance the effect of OA on enzyme activity. Finally we point out that caution must, thus, be taken when interpreting transcriptomic data on carbonic anhydrases in ocean acidification and temperature stress experiments, as the effect of these stressors on the physiological function of CA will depend both on gene expression and enzyme activity.

Heterotrophic bacteria in soils of Larsemann Oasis of East Antarctica

NASA Astrophysics Data System (ADS)

Churilin, Nikita; Soina, Vera

2015-04-01

The study of diversity and functional state of microorganisms in subsurface rocks layers, their participation in the biochemical weathering and formation of organic horizons of soils is important for understanding ecology and microorganisms in Antarctic soils. The study of cultured forms of microorganisms and their potential viability is still relevant to characterize the physiological state, biological activity and resilience of microorganisms involved in the initial soil formation. Improvement of isolation techniques of viable bacteria from the extreme habitats has a particular importance for rising the efficiency of environmental monitoring. The aim of the study was to investigate the viable heterotrophic bacteria involved in the formation of soils from wet valleys Larsemann Oasis, which is one of the warmest ice-free space of East Antarctica. Soil samples were taken from the intermountain humid valleys, where silt-gravelly substrates formed moss, algae, lichen cover. We used nutrient solutions (trypticase soy, R2A and glucose-peptone) to isolate cultured bacteria and study their morphological types in the light microscope. The total number of microorganisms was determined by fluorescent microscopy with acridine orange. SEM was used for morphological studies of bacterial communities in situ. To activate the growth processes we added into nutrient solutions various regulatory metabolites that have dose-dependence and operate at the community level. Physiological and functional conditions were determined by the duration of the lag phase and specific growth rate of bacterial communities in nutrient solutions containing various organic substrates. Soils form under protection of «stone pavement» and organisms leave the surface, so the forming organo-mineral horizon occurs inside of rock, thus the microprofile can form on both sides of the organic horizons. UV radiation, lack of moisture and strong wind are main limiting factors for microorganisms' growth in Antarctic soils. Primitive soils and permafrost layer have a great unevenness in the number of cultivated and potentially viable cells in different horizons. This phenomenon is characteristic for habitats with stable and alternating negative temperatures that can be attributed to the irregular migration of cells during freezing and heterogeneity of microbial populations along the depth of dormancy. One of the identified features was the lack of correlation with the organic content. SEM study of microbial communities in native Antarctic soils revealed the presence of biofilms, which can play an important role in weathering of rocks and primary soil formation, by forming organic horizon and protecting cells from environmental impact. Biofilms can also influence on distribution of bacterial cells in forming soils. Growth regulators (indoleacetic acid, wheat germ agglutinin, alkylhydroxybenzenes, pyruvate Na and serotonin) were used in experiments on the growth reactivation using soil samples with low number of microorganisms. The results obtained by this analysis can be used for further research to develop methods of the most complete selection of viable bacteria from Antarctic soils. We also determined the physiological condition of bacterial populations and their maximum specific growth rate. This method determines the functional (trophic) diversity of microbial communities and the maximum specific growth rate that reflects the environmental strategy of bacterial growth. In spite of the extreme conditions, a variety of physiological and metabolic willingness to consume polymers hydrolytic bacterial associations of endolithic soil is highest in the surface horizon and sharply decreases in the mineral horizon.

In vivo Magnetic Resonance Imaging of Tumor Protease Activity

PubMed Central

Haris, Mohammad; Singh, Anup; Mohammed, Imran; Ittyerah, Ranjit; Nath, Kavindra; Nanga, Ravi Prakash Reddy; Debrosse, Catherine; Kogan, Feliks; Cai, Kejia; Poptani, Harish; Reddy, Damodar; Hariharan, Hari; Reddy, Ravinder

2014-01-01

Increased expression of cathepsins has diagnostic as well as prognostic value in several types of cancer. Here, we demonstrate a novel magnetic resonance imaging (MRI) method, which uses poly-L-glutamate (PLG) as an MRI probe to map cathepsin expression in vivo, in a rat brain tumor model. This noninvasive, high-resolution and non-radioactive method exploits the differences in the CEST signals of PLG in the native form and cathepsin mediated cleaved form. The method was validated in phantoms with known physiological concentrations, in tumor cells and in an animal model of brain tumor along with immunohistochemical analysis. Potential applications in tumor diagnosis and evaluation of therapeutic response are outlined. PMID:25124082

Back to the future! Revisiting the physiological cost of negative work as a team-based activity for exercise physiology students.

PubMed

Kilgas, Matthew A; Elmer, Steven J

2017-03-01

We implemented a team-based activity in our exercise physiology teaching laboratory that was inspired from Abbott et al.'s classic 1952 Journal of Physiology paper titled "The physiological cost of negative work." Abbott et al. connected two bicycles via one chain. One person cycled forward (muscle shortening contractions, positive work) while the other resisted the reverse moving pedals (muscle lengthening contractions, negative work), and the cost of work was compared. This study was the first to link human whole body energetics with isolated muscle force-velocity characteristics. The laboratory activity for our students ( n = 35) was designed to reenact Abbott et al.'s experiment, integrate previously learned techniques, and illustrate differences in physiological responses to muscle shortening and lengthening contractions. Students (11-12 students/laboratory section) were split into two teams (positive work vs. negative work). One student from each team volunteered to cycle against the other for ~10 min. The remaining students in each team were tasked with measuring: 1 ) O 2 consumption, 2 ) heart rate, 3 ) blood lactate, and 4 ) perceived exertion. Students discovered that O 2 consumption during negative work was about one-half that of positive work and all other physiological parameters were also substantially lower. Muscle lengthening contractions were discussed and applied to rehabilitation and sport training. The majority of students (>90%) agreed or strongly agreed that they stayed engaged during the activity and it improved their understanding of exercise physiology. All students recommended the activity be performed again. This activity was engaging, emphasized teamwork, yielded clear results, was well received, and preserved the history of classic physiological experiments. Copyright © 2017 the American Physiological Society.

Conformational ensemble of human α-synuclein physiological form predicted by molecular simulations.

PubMed

Rossetti, G; Musiani, F; Abad, E; Dibenedetto, D; Mouhib, H; Fernandez, C O; Carloni, P

2016-02-17

We perform here enhanced sampling simulations of N-terminally acetylated human α-synuclein, an intrinsically disordered protein involved in Parkinson's disease. The calculations, consistent with experiments, suggest that the post-translational modification leads to the formation of a transient amphipathic α-helix. The latter, absent in the non-physiological form, alters protein dynamics at the N-terminal and intramolecular interactions.

Amplification and oscillations in the FAK/Src kinase system during integrin signaling.

PubMed

Caron-Lormier, G; Berry, H

2005-01-21

Integrin signaling is a major pathway of cell adhesion to extracellular matrices that regulates many physiological cell behaviors such as cell proliferation, migration or differentiation and is implied in pathologies such as tumor invasion. In this paper, we focused on the molecular system formed by the two kinases FAK (focal adhesion kinase) and Src, which undergo auto- and co-activation during early steps of integrin signaling. The system is modelled using classical kinetic equations and yields a set of three nonlinear ordinary differential equations describing the dynamics of the different phosphorylation forms of FAK. Analytical and numerical analysis of these equations show that this system may in certain cases amplify incoming signals from the integrins. A quantitative condition is obtained, which indicates that the total FAK charge in the system acts as a critical mass that must be exceeded for amplification to be effective. Furthermore, we show that when FAK activity is lower than Src activity, spontaneous oscillations of FAK phosphorylation forms may appear. The oscillatory behavior is studied using bifurcation and stability diagrams. We finally discuss the significance of this behavior with respect to recent experimental results evidencing FAK dynamics.

Effects of Dimerization of Serratia marcescens Endonuclease on Water Dynamics.

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

Chen, Chuanying; Beck, Brian W.; Krause, Kurt

2007-02-15

The research described in this product was performed in part in the Environmental Molecular Sciences Laboratory, a national scientific user facility sponsored by the Department of Energy's Office of Biological and Environmental Research and located at Pacific Northwest National Laboratory. The dynamics and structure of Serratia marcescens endonuclease and its neighboring solvent are investigated by molecular dynamics (MD). Comparisons are made with structural and biochemical experiments. The dimer form is physiologic and functions more processively than the monomer. We previously found a channel formed by connected clusters of waters from the active site to the dimer interface. Here, we showmore » that dimerization clearly changes correlations in the water structure and dynamics in the active site not seen in the monomer. Our results indicate that water at the active sites of the dimer is less affected compared with bulk solvent than in the monomer where it has much slower characteristic relaxation times. Given that water is a required participant in the reaction, this gives a clear advantage to dimerization in the absence of an apparent ability to use both active sites simultaneously.« less

Influence of elevated CO2 concentrations on cell division and nitrogen fixation rates in the bloom-forming cyanobacterium Nodularia spumigena

NASA Astrophysics Data System (ADS)

Czerny, J.; Ramos, J. Barcelos E.; Riebesell, U.

2009-04-01

The surface ocean currently absorbs about one-fourth of the CO2 emitted to the atmosphere from human activities. As this CO2 dissolves in seawater, it reacts with seawater to form carbonic acid, increasing ocean acidity and shifting the partitioning of inorganic carbon species towards increased CO2 at the expense of CO32- concentrations. While the decrease in [CO32-] and/or increase in [H+] has been found to adversely affect many calcifying organisms, some photosynthetic organisms appear to benefit from increasing [CO2]. Among these is the cyanobacterium Trichodesmium, a predominant diazotroph (nitrogen-fixing) in large parts of the oligotrophic oceans, which responded with increased carbon and nitrogen fixation at elevated pCO2. With the mechanism underlying this CO2 stimulation still unknown, the question arises whether this is a common response of diazotrophic cyanobacteria. In this study we therefore investigate the physiological response of Nodularia spumigena, a heterocystous bloom-forming diazotroph of the Baltic Sea, to CO2-induced changes in seawater carbonate chemistry. N. spumigena reacted to seawater acidification/carbonation with reduced cell division rates and nitrogen fixation rates, accompanied by significant changes in carbon and phosphorus quota and elemental composition of the formed biomass. Possible explanations for the contrasting physiological responses of Nodularia compared to Trichodesmium may be found in the different ecological strategies of non-heterocystous (Trichodesmium) and heterocystous (Nodularia) cyanobacteria.

The protein corona of circulating PEGylated liposomes.

PubMed

Palchetti, Sara; Colapicchioni, Valentina; Digiacomo, Luca; Caracciolo, Giulio; Pozzi, Daniela; Capriotti, Anna Laura; La Barbera, Giorgia; Laganà, Aldo

2016-02-01

Following systemic administration, liposomes are covered by a 'corona' of proteins, and preserving the surface functionality is challenging. Coating the liposome surface with polyethylene glycol (PEG) is the most widely used anti-opsonization strategy, but it cannot fully preclude protein adsorption. To date, protein binding has been studied following in vitro incubation to predict the fate of liposomes in vivo, while dynamic incubation mimicking in vivo conditions remains largely unexplored. The main aim of this investigation was to determine whether shear stress, produced by physiologically relevant dynamic flow, could influence the liposome-protein corona. The corona of circulating PEGylated liposome was thoroughly compared with that formed by incubation in vitro. Systematic comparison in terms of size, surface charge and quantitative composition was made by dynamic light scattering, microelectrophoresis and nano-liquid chromatography tandem mass spectrometry (nanoLC-MS/MS). Size of coronas formed under static vs. dynamic incubation did not appreciably differ from each other. On the other side, the corona of circulating liposomes was more negatively charged than its static counterpart. Of note, the variety of protein species in the corona formed in a dynamic flow was significantly wider. Collectively, these results demonstrated that the corona of circulating PEGylated liposomes can be considerably different from that formed in a static fluid. This seems to be a key factor to predict the biological activity of a liposomal formulation in a physiological environment. Copyright © 2015 Elsevier B.V. All rights reserved.

Acquisition of pro-oxidant activity of fALS-linked SOD1 mutants as revealed using circular dichroism and UV-resonance Raman spectroscopy

NASA Astrophysics Data System (ADS)

Fujimaki, Nobuhiro; Nishiya, Ken; Miura, Takashi; Nakabayashi, Takakazu

2016-11-01

The acquisition of pro-oxidant activity of the mutated form of human Cu, Zn-superoxide dismutase (SOD1) has been investigated to clarify the relationship between mutations in SOD1 and the pathogenesis of amyotrophic lateral sclerosis (ALS). Ala4 → Val (A4V) and Gly93 → Ala (G93A) mutants, which are representative ALS-linked SOD1 mutants, have been found to exhibit both the denaturation and the gain of pro-oxidant activity after incubation in the apo-form at a physiological condition of 37 °C and pH 7.4 and the rebinding of Cu2+. These characteristics are similar to those previously reported for the His43 → Arg (H43R) mutant. UV-resonance Raman spectra indicated that the coordination structure of the Cu-binding site catalyzing the oxidation reaction is the same among the denatured A4V, G93A, and H43R. Since wild-type SOD1 does not exhibit the denaturation in its apo-form at 37 °C and pH 7.4, the instability of the protein structure due to mutation can be considered as a significant factor that induces the denaturation and the subsequent pro-oxidant activity.

Active Rehabilitation of Concussion and Post-concussion Syndrome.

PubMed

Leddy, John J; Baker, John G; Willer, Barry

2016-05-01

Concussion is a physiological brain injury with physical, cognitive, and emotional sequelae. The macrophysiological insult to the brain affects the autonomic nervous system and its control of cerebral blood flow. Most patients recover within 2 weeks, but some do not. Persistence of symptoms beyond the generally accepted time frame for recovery is called post-concussion syndrome (PCS). PCS is not a single entity; it is a group of disorders that requires specific forms of therapy. Rest has been the mainstay of the treatment for concussion and PCS. This article discusses the rationale for the active treatment of concussion and PCS. Copyright © 2016 Elsevier Inc. All rights reserved.

Iminoboronate Formation Leads to Fast and Reversible Conjugation Chemistry of α-Nucleophiles at Neutral pH

PubMed Central

Bandyopadhyay, Anupam

2015-01-01

Bioorthogonal reactions that are fast and reversible under physiologic conditions are in high demand for biological applications. Herein, we show that an ortho boronic acid substituent makes aryl ketones to rapidly conjugate with α-nucleophiles at neutral pH. Specifically, 2-acetylphenylboronic acid and derivatives were found to conjugate with phenylhydrazine with rate constants of 102 to 103 M−1 s−1, comparable to the fastest bioorthogonal conjugations known to date. 11B-NMR analysis reveals varied extent of iminoboronate formation of the conjugates, in which the imine nitrogen forms a dative bond with boron. The iminoboronate formation activates the imines for hydrolysis and exchange, rendering these oxime/hydrazone conjugations reversible and dynamic under physiologic conditions. The fast and dynamic nature of the iminoboronate chemistry should find wide applications in biology. PMID:26311464

ATM activation in normal human tissues and testicular cancer.

PubMed

Bartkova, Jirina; Bakkenist, Christopher J; Rajpert-De Meyts, Ewa; Skakkebaek, Niels E; Sehested, Maxwell; Lukas, Jiri; Kastan, Michael B; Bartek, Jiri

2005-06-01

The ATM kinase is a tumor suppressor and key regulator of biological responses to DNA damage. Cultured cells respond to genotoxic insults that induce DNA double-strand breaks by prompt activation of ATM through its autophosphorylation on serine 1981. However, whether ATM-S1981 becomes phosphorylated in vivo, for example during physiological processes that generate DSBs, is unknown. Here we produced phospho-specific monoclonal antibodies against S1981-phosphorylated ATM (pS-ATM), and applied them to immunohistochemical analyses of a wide range of normal human tissues and testicular tumors. Our data show that regardless of proliferation and differentiation, most human tissues contain only the S1981-nonphosphorylated, inactive form of ATM. In contrast, nuclear staining for pS-ATM was detected in subsets of bone-marrow lymphocytes and primary spermatocytes in the adult testes, cell types in which DSBs are generated during physiological V(D)J recombination and meiotic recombination, respectively. Among testicular germ-cell tumors, an aberrant constitutive pS-ATM was observed especially in embryonal carcinomas, less in seminomas, and only modestly in teratomas and the pre-invasive carcinoma-in-situ stage. Compared with pS-ATM, phosphorylated histone H2AX (gammaH2AX), another DNA damage marker and ATM substrate, was detected in a higher proportion of cancer cells, and also in normal fetal gonocytes, and a wider range of adult spermatocyte differentiation stages. Collectively, our results strongly support the physiological relevance of the recently proposed model of ATM autoactivation, and provide further evidence for constitutive activation of the DNA damage machinery during cancer development. The new tools characterized here should facilitate monitoring of ATM activation in clinical specimens, and help develop future treatment strategies.

[P. K. Anokhin--creator of the theory of the functional system].

PubMed

Golubeva, E L

1997-01-01

Memories about scientific activities of P. K. Anokhin cover "Gorbi" period of his work, pre-war work in VIEM in (All-Union Institute of Experimental Medicine) Moscow, renew of researches the war (1944-1952), stress the losses, caused by scientific session, devoted to problems of I. P. Pavlov physiological doctrine in 1950. Indicated roots and ways of forming of functional system theory and system genesis conception. Overview of scientific works, belong to academics, headed by P. K. Anokhin.

Measuring a Journey without Goal: Meditation, Spirituality, and Physiology

PubMed Central

2015-01-01

The secular practice of meditation is associated with a range of physiological and cognitive effects, including lower blood pressure, lower cortisol, cortical thickening, and activation of areas of the brain associated with attention and emotion regulation. However, in the context of spiritual practice, these benefits are secondary gains, as the primary aim is spiritual transformation. Despite obvious difficulties in trying to measure a journey without goal, spiritual aspects involved in the practice of meditation should also be addressed by experimental study. This review starts by considering meditation in the form of the relaxation response (a counterpart to the stress response), before contrasting mindfulness research that emphasizes the role of attention and alertness in meditation. This contrast demonstrates how reference to traditional spiritual texts (in this case Buddhist) can be used to guide research questions involving meditation. Further considerations are detailed, along with the proposal that research should triangulate spiritual textual sources, first person accounts (i.e., neurophenomenology), and physiological/cognitive measures in order to aid our understanding of meditation, not only in the secular context of health benefits, but also in the context of spiritual practice. PMID:26137495

Does flavor impact function? Potential consequences of polyphenol-protein interactions in delivery and bioactivity of flavan-3-ols from foods.

PubMed

Ferruzzi, Mario G; Bordenave, Nicolas; Hamaker, Bruce R

2012-11-05

Astringency is a component of the overall flavor experienced when consuming polyphenol rich foods and beverages such as tea, wine, cocoa and select fruits. Following consumption, the astringent sensation results from the well documented ability of polyphenols to bind to salivary proline rich proteins (PRP) and facilitate their precipitation in the oral cavity. In a similar fashion, polyphenols are also known to non-specifically bind food and other biological proteins. While much is known regarding the polyphenol-protein interactions leading to astringency, significantly less information is available regarding the impact of these polyphenol-protein interactions with food or other biological proteins on relevant physiological outcomes. This paper focuses on the interactions between flavan-3-ols, one of the most abundant dietary polyphenol forms, with proteins in food, salivary PRP and other physiological proteins. The physiological implications of these interactions in food and through the gut will be discussed in relation to manipulation of flavan-3-ol bioavailability, metabolism and biological activities including inhibition of digestive enzymes in the gut. Copyright © 2012 Elsevier Inc. All rights reserved.

Insights into Host Cell Modulation and Induction of New Cells by the Corn Smut Ustilago maydis.

PubMed

Redkar, Amey; Matei, Alexandra; Doehlemann, Gunther

2017-01-01

Many filamentous fungal pathogens induce drastic modulation of host cells causing abnormal infectious structures such as galls, or tumors that arise as a result of re-programming in the original developmental cell fate of a colonized host cell. Developmental consequences occur predominantly with biotrophic phytopathogens. This suggests that these host structures result as an outcome of efficient defense suppression and intimate fungal-host interaction to suit the pathogen's needs for completion of its infection cycle. This mini-review mainly summarizes host cell re-programming that occurs in the Ustilago maydis - maize interaction, in which the pathogen deploys cell-type specific effector proteins with varying activities. The fungus senses the physiological status and identity of colonized host cells and re-directs the endogenous developmental program of its host. The disturbance of host cell physiology and cell fate leads to novel cell shapes, increased cell size, and/or the number of host cells. We particularly highlight the strategies of U. maydis to induce physiologically varied host organs to form the characteristic tumors in both vegetative and floral parts of maize.

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

PubMed

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 that l-DOPA administration at 1.0 μmol shrimp -1 can mediate the transient regulation of neuroendocrinological, immunological, and physiologic responses resulting in immunosuppression, which in turn promoted the susceptibility of L. vannamei to V. alginolyticus. Copyright © 2018 Elsevier Ltd. All rights reserved.

Physiological Role of Gap-Junctional Hemichannels

PubMed Central

Quist, Arjan Pieter; Rhee, Seung Keun; Lin, Hai; Lal, Ratneshwar

2000-01-01

Hemichannels in the overlapping regions of apposing cells plasma membranes join to form gap junctions and provide an intercellular communication pathway. Hemichannels are also present in the nonjunctional regions of individual cells and their activity is gated by several agents, including calcium. However, their physiological roles are unknown. Using techniques of atomic force microscopy (AFM), fluorescent dye uptake assay, and laser confocal immunofluorescence imaging, we have examined the extracellular calcium-dependent modulation of cell volume. In response to a change in the extracellular physiological calcium concentration (1.8 to ≤1.6 mM) in an otherwise isosmotic condition, real-time AFM imaging revealed a significant and reversible increase in the volume of cells expressing gap-junctional proteins (connexins). Volume change did not occur in cells that were not expressing connexins. However, after the transient or stable transfection of connexin43, volume change did occur. The volume increase was accompanied by cytochalasin D-sensitive higher cell stiffness, which helped maintain cell integrity. These cellular physical changes were prevented by gap-junctional blockers, oleamide and β-glycyrrhetinic acid, or were reversed by returning extracellular calcium to the normal level. We conclude that nongap-junctional hemichannels regulate cell volume in response to the change in extracellular physiological calcium in an otherwise isosmotic situation. PMID:10704454

Detection of cardiac activity changes from human speech

NASA Astrophysics Data System (ADS)

Tovarek, Jaromir; Partila, Pavol; Voznak, Miroslav; Mikulec, Martin; Mehic, Miralem

2015-05-01

Impact of changes in blood pressure and pulse from human speech is disclosed in this article. The symptoms of increased physical activity are pulse, systolic and diastolic pressure. There are many methods of measuring and indicating these parameters. The measurements must be carried out using devices which are not used in everyday life. In most cases, the measurement of blood pressure and pulse following health problems or other adverse feelings. Nowadays, research teams are trying to design and implement modern methods in ordinary human activities. The main objective of the proposal is to reduce the delay between detecting the adverse pressure and to the mentioned warning signs and feelings. Common and frequent activity of man is speaking, while it is known that the function of the vocal tract can be affected by the change in heart activity. Therefore, it can be a useful parameter for detecting physiological changes. A method for detecting human physiological changes by speech processing and artificial neural network classification is described in this article. The pulse and blood pressure changes was induced by physical exercises in this experiment. The set of measured subjects was formed by ten healthy volunteers of both sexes. None of the subjects was a professional athlete. The process of the experiment was divided into phases before, during and after physical training. Pulse, systolic, diastolic pressure was measured and voice activity was recorded after each of them. The results of this experiment describe a method for detecting increased cardiac activity from human speech using artificial neural network.

Recommended level of physical activity and health-related quality of life among Japanese adults

PubMed Central

Shibata, Ai; Oka, Koichiro; Nakamura, Yoshio; Muraoka, Isao

2007-01-01

Background The benefits of a recommended level of physical activity on physiological health indicators such as morbidity and mortality are well-accepted, but less research has addressed whether or not the association between the recommended level of physical activity and a health-related quality of life (HRQOL) exists in the Japanese population. Thus, the present study examined whether the recommended physical activity would be associated with HRQOL in the general Japanese middle-aged population. Methods Data were obtained from 1211 male and female respondents (39.4 ± 10.9 year, mean ± SD) from an Internet-based survey of registrants of an Internet research service. Physical activity level was estimated from the short form of the International Physical Activity Questionnaire. HRQOL was assessed with the Medical Outcomes Survey Short Form-8 questionnaire (SF-8). Based on the current national guidelines for exercise in Japan, respondents were divided into a recommended group, an insufficient group, and an inactive group according to their estimated weekly physical activity level. Multivariate analyses of covariance were utilized. Results Across both genders, the recommended group had significantly higher physical functioning (PF) scores than the inactive group (p < .05). Additionally, across both genders, the recommended group had significantly higher general health perception scores than the insufficient and inactive groups (p < .05). The recommended group had significantly higher vitality scores than the insufficient and inactive groups in males, and higher than only the inactive group in females (p < .05). The insufficient group had significantly higher PF scores than the inactive group across both genders (p < .05). The recommended group had significantly higher physical component scores than the inactive group (p = .001). Conclusion Individuals who attained the recommended level of physical activity had better scores on some dimensions of HRQOL than those who did not, suggesting that the recommended level of physical activity may be applicable not only to the physiological objective outcomes but also to some dimensions in both the physical and mental aspects of HRQOL. PMID:18042301

Characterization of [4Fe-4S]-containing and cluster-free forms of Streptomyces WhiD

PubMed Central

Crack, Jason C.; den Hengst, Chris D.; Jakimowicz, Piotr; Subramanian, Sowmya; Johnson, Michael K.; Buttner, Mark J.; Thomson, Andrew J.; Le Brun, Nick E.

2009-01-01

WhiD, a member of the WhiB-like (Wbl) family of iron-sulfur proteins found exclusively within the actinomycetes, is required for the late stages of sporulation in Streptomyces coelicolor. Like all other Wbl proteins, WhiD has not so far been purified in a soluble form that contains a significant amount of cluster and characterization has relied on cluster-reconstituted protein. Thus, a major goal in Wbl research is to obtain and characterize native protein containing iron-sulfur clusters. Here we report the analysis of S. coelicolor WhiD purified anaerobically from E. coli as a soluble protein containing a single [4Fe-4S]2+ cluster ligated by four cysteines. Upon exposure to oxygen, spectral features associated with the [4Fe-4S] cluster were lost in a slow reaction that unusually yielded apo-WhiD directly without significant concentrations of cluster intermediates. This process was found to be highly pH dependent with an optimal stability observed between pH 7.0 and 8.0. Low molecular weight thiols, including a mycothiol analogue and thioredoxin, exerted a small but significant protective effect against WhiD cluster loss, an activity that could be of physiological importance. [4Fe-4S]2+ WhiD was found to react much more rapidly with superoxide than with either oxygen or hydrogen peroxide, which may also be of physiological significance. Loss of the [4Fe-4S] cluster to form apo-protein destabilized the protein fold significantly, but did not lead to complete unfolding. Finally, apo-WhiD exhibited negligible activity in an insulin-based disulfide reductase assay demonstrating that it does not function as a general protein disulfide reductase. PMID:19954209

Modulation of nucleotide sensitivity of ATP-sensitive potassium channels by phosphatidylinositol-4-phosphate 5-kinase.

PubMed

Shyng, S L; Barbieri, A; Gumusboga, A; Cukras, C; Pike, L; Davis, J N; Stahl, P D; Nichols, C G

2000-01-18

ATP-sensitive potassium channels (K(ATP) channels) regulate cell excitability in response to metabolic changes. K(ATP) channels are formed as a complex of a sulfonylurea receptor (SURx), a member of the ATP-binding cassette protein family, and an inward rectifier K(+) channel subunit (Kir6.x). Membrane phospholipids, in particular phosphatidylinositol (PI) 4,5-bisphosphate (PIP(2)), activate K(ATP) channels and antagonize ATP inhibition of K(ATP) channels when applied to inside-out membrane patches. To examine the physiological relevance of this regulatory mechanism, we manipulated membrane PIP(2) levels by expressing either the wild-type or an inactive form of PI-4-phosphate 5-kinase (PIP5K) in COSm6 cells and examined the ATP sensitivity of coexpressed K(ATP) channels. Channels from cells expressing the wild-type PIP5K have a 6-fold lower ATP sensitivity (K(1/2), the half maximal inhibitory concentration, approximately 60 microM) than the sensitivities from control cells (K(1/2) approximately 10 microM). An inactive form of the PIP5K had little effect on the K(1/2) of wild-type channels but increased the ATP-sensitivity of a mutant K(ATP) channel that has an intrinsically lower ATP sensitivity (from K(1/2) approximately 450 microM to K(1/2) approximately 100 microM), suggesting a decrease in membrane PIP(2) levels as a consequence of a dominant-negative effect of the inactive PIP5K. These results show that PIP5K activity, which regulates PIP(2) and PI-3,4,5-P(3) levels, is a significant determinant of the physiological nucleotide sensitivity of K(ATP) channels.

Modulation of nucleotide sensitivity of ATP-sensitive potassium channels by phosphatidylinositol-4-phosphate 5-kinase

PubMed Central

Shyng, S.-L.; Barbieri, A.; Gumusboga, A.; Cukras, C.; Pike, L.; Davis, J. N.; Stahl, P. D.; Nichols, C. G.

2000-01-01

ATP-sensitive potassium channels (KATP channels) regulate cell excitability in response to metabolic changes. KATP channels are formed as a complex of a sulfonylurea receptor (SURx), a member of the ATP-binding cassette protein family, and an inward rectifier K+ channel subunit (Kir6.x). Membrane phospholipids, in particular phosphatidylinositol (PI) 4,5-bisphosphate (PIP2), activate KATP channels and antagonize ATP inhibition of KATP channels when applied to inside-out membrane patches. To examine the physiological relevance of this regulatory mechanism, we manipulated membrane PIP2 levels by expressing either the wild-type or an inactive form of PI-4-phosphate 5-kinase (PIP5K) in COSm6 cells and examined the ATP sensitivity of coexpressed KATP channels. Channels from cells expressing the wild-type PIP5K have a 6-fold lower ATP sensitivity (K1/2, the half maximal inhibitory concentration, ≈ 60 μM) than the sensitivities from control cells (K1/2 ≈ 10 μM). An inactive form of the PIP5K had little effect on the K1/2 of wild-type channels but increased the ATP-sensitivity of a mutant KATP channel that has an intrinsically lower ATP sensitivity (from K1/2 ≈ 450 μM to K1/2 ≈ 100 μM), suggesting a decrease in membrane PIP2 levels as a consequence of a dominant-negative effect of the inactive PIP5K. These results show that PIP5K activity, which regulates PIP2 and PI-3,4,5-P3 levels, is a significant determinant of the physiological nucleotide sensitivity of KATP channels. PMID:10639183

A direct method to visualise the aryl acylamidase activity on cholinesterases in polyacrylamide gels

PubMed Central

Jaganathan, Lakshmanan; Boopathy, Rathanam

2000-01-01

Background In vertebrates, two types of cholinesterases exist, acetylcholinesterase and butyrylcholinesterase. The function of acetylcholinesterase is to hydrolyse acetylcholine, thereby terminating the neurotransmission at cholinergic synapse, while the precise physiological function of butyrylcholinesterase has not been identified. The presence of cholinesterases in tissues that are not cholinergically innervated indicate that cholinesterases may have functions unrelated to neurotransmission. Furthermore, cholinesterases display a genuine aryl acylamidase activity apart from their predominant acylcholine hydrolase activity. The physiological significance of this aryl acylamidase activity is also not known. The study on the aryl acylamidase has been, in part hampered by the lack of a specific method to visualise this activity. We have developed a method to visualise the aryl acylamidase activity on cholinesterase in polyacrylamide gels. Results The o-nitroaniline liberated from o-nitroacetanilide by the action of aryl acylamidase activity on cholinesterases, in the presence of nitrous acid formed a diazonium compound. This compound gave an azo dye complex with N-(1-napthyl)-ethylenediamine, which appeared as purple bands in polyacrylamide gels. Treating the stained gels with trichloroacetic acid followed by Tris-HCl buffer helped in fixation of the stain in the gels. By using specific inhibitors for acetylcholinesterase and butyrylcholinesterase, respectively, differential staining for the aryl acylamidase activities on butyrylcholinesterase and acetylcholinesterase in a sample containing both these enzymes has been demonstrated. A linear relationship between the intensity of colour developed and activity of the enzyme was obtained. Conclusions A novel method to visualise the aryl acylamidase activity on cholinesterases in polyacrylamide gels has been developed. PMID:11231883

A direct method to visualise the aryl acylamidase activity on cholinesterases in polyacrylamide gels.

PubMed

Jaganathan, L; Boopathy, R

2000-01-01

In vertebrates, two types of cholinesterases exist, acetylcholinesterase and butyrylcholinesterase. The function of acetylcholinesterase is to hydrolyse acetylcholine, thereby terminating the neurotransmission at cholinergic synapse, while the precise physiological function of butyrylcholinesterase has not been identified. The presence of cholinesterases in tissues that are not cholinergically innervated indicate that cholinesterases may have functions unrelated to neurotransmission. Furthermore, cholinesterases display a genuine aryl acylamidase activity apart from their predominant acylcholine hydrolase activity. The physiological significance of this aryl acylamidase activity is also not known. The study on the aryl acylamidase has been, in part hampered by the lack of a specific method to visualise this activity. We have developed a method to visualise the aryl acylamidase activity on cholinesterase in polyacrylamide gels. The o-nitroaniline liberated from o-nitroacetanilide by the action of aryl acylamidase activity on cholinesterases, in the presence of nitrous acid formed a diazonium compound. This compound gave an azo dye complex with N-(1-napthyl)-ethylenediamine, which appeared as purple bands in polyacrylamide gels. Treating the stained gels with trichloroacetic acid followed by Tris-HCl buffer helped in fixation of the stain in the gels. By using specific inhibitors for acetylcholinesterase and butyrylcholinesterase, respectively, differential staining for the aryl acylamidase activities on butyrylcholinesterase and acetylcholinesterase in a sample containing both these enzymes has been demonstrated. A linear relationship between the intensity of colour developed and activity of the enzyme was obtained. A novel method to visualise the aryl acylamidase activity on cholinesterases in polyacrylamide gels has been developed.

Effects of salinity on the growth, physiology and relevant gene expression of an annual halophyte grown from heteromorphic seeds

PubMed Central

Cao, Jing; Lv, Xiu Yun; Chen, Ling; Xing, Jia Jia; Lan, Hai Yan

2015-01-01

Seed heteromorphism provides plants with alternative strategies for survival in unfavourable environments. However, the response of descendants from heteromorphic seeds to stress has not been well documented. Suaeda aralocaspica is a typical annual halophyte, which produces heteromorphic seeds with disparate forms and different germination characteristics. To gain an understanding of the salt tolerance of descendants and the impact of seed heteromorphism on progeny of this species, we performed a series of experiments to investigate the plant growth and physiological parameters (e.g. osmolytes, oxidative/antioxidative agents and enzymes), as well as expression patterns of corresponding genes. Results showed that osmolytes (proline and glycinebetaine) were significantly increased and that excess reactive oxygen species (O2−, H2O2) produced under high salinity were scavenged by increased levels of antioxidant enzymes (superoxide dismutase, ascorbate peroxidase and glutathione reductase) and corresponding antioxidants (ascorbic acid and glutathione). Moreover, enhancement of phosphoenolpyruvate carboxylase activity at high salt intensity had a positive effect on photosynthesis. The descendants from heteromorphic seeds presented no significant difference in performance with or without salinity. In conclusion, we found that high salinity induced the same active physiological responses in plants from heteromorphic seeds of S. aralocaspica, there was no carry-over of seed heteromorphism to plants: all the descendants required salinity for optimal growth and adaptation to their natural habitat. PMID:26386128

Corticosterone predicts foraging behavior and parental care in macaroni penguins.

PubMed

Crossin, Glenn T; Trathan, Phil N; Phillips, Richard A; Gorman, Kristen B; Dawson, Alistair; Sakamoto, Kentaro Q; Williams, Tony D

2012-07-01

Corticosterone has received considerable attention as the principal hormonal mediator of allostasis or physiological stress in wild animals. More recently, it has also been implicated in the regulation of parental care in breeding birds, particularly with respect to individual variation in foraging behavior and provisioning effort. There is also evidence that prolactin can work either inversely or additively with corticosterone to achieve this. Here we test the hypothesis that endogenous corticosterone plays a key physiological role in the control of foraging behavior and parental care, using a combination of exogenous corticosterone treatment, time-depth telemetry, and physiological sampling of female macaroni penguins (Eudyptes chrysolophus) during the brood-guard period of chick rearing, while simultaneously monitoring patterns of prolactin secretion. Plasma corticosterone levels were significantly higher in females given exogenous implants relative to those receiving sham implants. Increased corticosterone levels were associated with significantly higher levels of foraging and diving activity and greater mass gain in implanted females. Elevated plasma corticosterone was also associated with an apparent fitness benefit in the form of increased chick mass. Plasma prolactin levels did not correlate with corticosterone levels at any time, nor was prolactin correlated with any measure of foraging behavior or parental care. Our results provide support for the corticosterone-adaptation hypothesis, which predicts that higher corticosterone levels support increased foraging activity and parental effort.

Acid-Sensing Ion Channel Pharmacology, Past, Present, and Future ….

PubMed

Rash, Lachlan D

2017-01-01

pH is one of the most strictly controlled parameters in mammalian physiology. An extracellular pH of ~7.4 is crucial for normal physiological processes, and perturbations to this have profound effects on cell function. Acidic microenvironments occur in many physiological and pathological conditions, including inflammation, bone remodeling, ischemia, trauma, and intense synaptic activity. Cells exposed to these conditions respond in different ways, from tumor cells that thrive to neurons that are either suppressed or hyperactivated, often fatally. Acid-sensing ion channels (ASICs) are primary pH sensors in mammals and are expressed widely in neuronal and nonneuronal cells. There are six main subtypes of ASICs in rodents that can form homo- or heteromeric channels resulting in many potential combinations. ASICs are present and activated under all of the conditions mentioned earlier, suggesting that they play an important role in how cells respond to acidosis. Compared to many other ion channel families, ASICs were relatively recently discovered-1997-and there is a substantial lack of potent, subtype-selective ligands that can be used to elucidate their structural and functional properties. In this chapter I cover the history of ASIC channel pharmacology, which began before the proteins were even identified, and describe the current arsenal of tools available, their limitations, and take a glance into the future to predict from where new tools are likely to emerge. © 2017 Elsevier Inc. All rights reserved.

Increased Interest in Physiology and Science among Adolescents after Presentations and Activities Administered by Undergraduate Physiology Students

ERIC Educational Resources Information Center

da Silva de Vargas, Liane; Rosa de Menezes, Jefferson; Billig Mello-Carpes, Pâmela

2016-01-01

In this article, the authors describe a set of activities performed in south Brazil that are aligned with the objectives of PhUn Week and promote the integration between universities and public schools and the dissemination of knowledge of physiology. To achieve this goal, the authors adopted a program in which undergraduate physiology students…

The magnitude of growth hormone elevation is related with the proportion of monomeric form in acromegaly.

PubMed

Ochoa, R; Fonseca, E; Mercado, M; Galván, R E; Hernández, M; Zárate, A

1995-01-01

In acromegalic patients monomeric GH form constitutes the larger proportion of circulating GH; however, no data are available concerning the relation between total GH elevation and the predominance of GH forms. Therefore, we studied the relationship between the degree of GH elevation and the proportion of GH isoforms. Sera from 11 patients with active acromegaly were subjected to gel chromatography on Sephadex G-100 column and fractions were collected for RIA to measure GH. The monomeric form of GH was predominant and exhibited a lineal correlation (r = 0.76, p < 0.01) with the circulating GH, thus the higher elevation of GH, the major proportion of monomeric GH. IGF-1 changes correlate with changes in monomeric GH but no better than for total GH. There was a correlation observed (r = 0.65) between the proportion of low GH forms and the presence of hyperglycemia, although the physiological role of the lower molecular GH forms is still unknown. In conclusion, it was demonstrated that the relative proportion of GH molecular forms changes according to the magnitude of the elevation of total GH.

Biowaiver Monographs for Immediate-Release Solid Oral Dosage Forms: Folic Acid.

PubMed

Hofsäss, Martin A; Souza, Jacqueline de; Silva-Barcellos, Neila M; Bellavinha, Karime R; Abrahamsson, Bertil; Cristofoletti, Rodrigo; Groot, D W; Parr, Alan; Langguth, Peter; Polli, James E; Shah, Vinod P; Tajiri, Tomokazu; Mehta, Mehul U; Dressman, Jennifer B

2017-12-01

This work presents a review of literature and experimental data relevant to the possibility of waiving pharmacokinetic bioequivalence studies in human volunteers for approval of immediate-release solid oral pharmaceutical forms containing folic acid as the single active pharmaceutical ingredient. For dosage forms containing 5 mg folic acid, the highest dose strength on the World Health Organization Essential Medicines List, the dose/solubility ratio calculated from solubility studies was higher than 250 mL, corresponding to a classification as "not highly soluble." Small, physiological doses of folic acid (≤320 μg) seem to be absorbed completely via active transport, but permeability data for higher doses of 1-5 mg are inconclusive. Following a conservative approach, folic acid is classified as a Biopharmaceutics Classification System class IV compound until more reliable data become available. Commensurate with its solubility characteristics, the results of dissolution studies indicated that none of the folic acid products evaluated showed rapid dissolution in media at pH 1.2 or 4.5. Therefore, according to the current criteria of the Biopharmaceutics Classification System, the biowaiver approval procedure cannot be recommended for immediate-release solid oral dosage forms containing folic acid. Copyright © 2017 American Pharmacists Association®. All rights reserved.

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

PubMed

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

2011-09-01

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

Constrained synaptic connectivity in functional mammalian neuronal networks grown on patterned surfaces.

PubMed

Wyart, Claire; Ybert, Christophe; Bourdieu, Laurent; Herr, Catherine; Prinz, Christelle; Chatenay, Didier

2002-06-30

The use of ordered neuronal networks in vitro is a promising approach to study the development and the activity of small neuronal assemblies. However, in previous attempts, sufficient growth control and physiological maturation of neurons could not be achieved. Here we describe an original protocol in which polylysine patterns confine the adhesion of cellular bodies to prescribed spots and the neuritic growth to thin lines. Hippocampal neurons in these networks are maintained healthy in serum free medium up to 5 weeks in vitro. Electrophysiology and immunochemistry show that neurons exhibit mature excitatory and inhibitory synapses and calcium imaging reveals spontaneous activity of neurons in isolated networks. We demonstrate that neurons in these geometrical networks form functional synapses preferentially to their first neighbors. We have, therefore, established a simple and robust protocol to constrain both the location of neuronal cell bodies and their pattern of connectivity. Moreover, the long term maintenance of the geometry and the physiology of the networks raises the possibility of new applications for systematic screening of pharmacological agents and for electronic to neuron devices.

Conserved structures formed by heterogeneous RNA sequences drive silencing of an inflammation responsive post-transcriptional operon

PubMed Central

Basu, Abhijit; Jain, Niyati; Tolbert, Blanton S.; Komar, Anton A.

2017-01-01

Abstract RNA–protein interactions with physiological outcomes usually rely on conserved sequences within the RNA element. By contrast, activity of the diverse gamma-interferon-activated inhibitor of translation (GAIT)-elements relies on the conserved RNA folding motifs rather than the conserved sequence motifs. These elements drive the translational silencing of a group of chemokine (CC/CXC) and chemokine receptor (CCR) mRNAs, thereby helping to resolve physiological inflammation. Despite sequence dissimilarity, these RNA elements adopt common secondary structures (as revealed by 2D-1H NMR spectroscopy), providing a basis for their interaction with the RNA-binding GAIT complex. However, many of these elements (e.g. those derived from CCL22, CXCL13, CCR4 and ceruloplasmin (Cp) mRNAs) have substantially different affinities for GAIT complex binding. Toeprinting analysis shows that different positions within the overall conserved GAIT element structure contribute to differential affinities of the GAIT protein complex towards the elements. Thus, heterogeneity of GAIT elements may provide hierarchical fine-tuning of the resolution of inflammation. PMID:29069516

Histolocalization and physico-chemical characterization of dihydrochalcones: Insight into the role of apple major flavonoids.

PubMed

Gaucher, Matthieu; Dugé de Bernonville, Thomas; Lohou, David; Guyot, Sylvain; Guillemette, Thomas; Brisset, Marie-Noëlle; Dat, James F

2013-06-01

Flavonoids, like other metabolites synthesized via the phenylpropanoid pathway, possess a wide range of biological activities including functions in plant development and its interaction with the environment. Dihydrochalcones (mainly phloridzin, sieboldin, trilobatin, phloretin) represent the major flavonoid subgroup in apple green tissues. Although this class of phenolic compounds is found in very large amounts in some tissues (≈200mg/g of leaf DW), their physiological significance remains unclear. In the present study, we highlight their tissue-specific localization in young growing shoots suggesting a specific role in important physiological processes, most notably in response to biotic stress. Indeed, dihydrochalcones could constitute a basal defense, in particular phloretin which exhibits a strong broad-range bactericidal and fungicidal activity. Our results also indicate that sieboldin forms complexes with iron with strong affinity, reinforcing its antioxidant properties and conferring to this dihydrochalcone a potential for iron seclusion and/or storage. The importance of localization and biochemical properties of dihydrochalcones are discussed in view of the apple tree defense strategy against both biotic and abiotic stresses. Copyright © 2013 Elsevier Ltd. All rights reserved.

Dysfunction of pulmonary surfactant mediated by phospholipid oxidation is cholesterol-dependent.

PubMed

Al-Saiedy, Mustafa; Pratt, Ryan; Lai, Patrick; Kerek, Evan; Joyce, Heidi; Prenner, Elmar; Green, Francis; Ling, Chang-Chun; Veldhuizen, Ruud; Ghandorah, Salim; Amrein, Matthias

2018-04-01

Pulmonary surfactant forms a cohesive film at the alveolar air-lung interface, lowering surface tension, and thus reducing the work of breathing and preventing atelectasis. Surfactant function becomes impaired during inflammation due to degradation of the surfactant lipids and proteins by free radicals. In this study, we examine the role of reactive nitrogen (RNS) and oxygen (ROS) species on surfactant function with and without physiological cholesterol levels (5-10%). Surface activity was assessed in vitro in a captive bubble surfactometer (CBS). Surfactant chemistry, monolayer fluidity and thermodynamic behavior were also recorded before and after oxidation. We report that physiologic amounts of cholesterol combined with oxidation results in severe impairment of surfactant function. We also show that surfactant polyunsaturated phospholipids are the most susceptible to oxidative alteration. Membrane thermodynamic experiments showed significant surfactant film stiffening after free radical exposure in the presence of cholesterol. These results point to a previously unappreciated role for cholesterol in amplifying defects in surface activity caused by oxidation of pulmonary surfactant, a finding that may have implications for treating several lung diseases. Copyright © 2018 Elsevier B.V. All rights reserved.

Characterization of Electrocardiogram Changes Throughout a Marathon

PubMed Central

Callaway, Clifton; Salcido, David; McEntire, Serina; Roth, Ronald; Hostler, David

2014-01-01

Purpose There are few data examining cardiovascular physiology throughout a marathon. This study was devised to characterize electrocardiographic activity continuously throughout a marathon. Methods Cardiac activity was recorded from 19 subjects wearing a Holter monitor during a marathon. The 19 subjects (14 men and 5 women) were aged 39 ± 16 years (mean ± SD) and completed a marathon in 4:32:16 ± 1:23:35. Heart rate (HR), heart rate variability (HRV), T-wave amplitude, T-wave amplitude variability, and T-wave alternans (TWA) were evaluated continuously throughout the marathon. Results Averaged across all subjects, HRV, T-wave amplitude variability, and TWA increased throughout the marathon. Increased variability in T-wave amplitude occurred in 86% of subjects, characterized by complex oscillatory patterns and TWA. Three minutes after the marathon, HR was elevated and HRV was suppressed relative to the pre-marathon state. Conclusion HRV and T-wave amplitude variability, especially in the form of TWA, increase throughout a marathon. Increasing TWA as a marathon progresses likely represents a physiologic process as no arrhythmias or cardiac events were observed. PMID:24832192

¹H, ¹³C and ¹⁵N resonance assignment for the human K-Ras at physiological pH.

PubMed

Vo, Uybach; Embrey, Kevin J; Breeze, Alexander L; Golovanov, Alexander P

2013-10-01

K-Ras, a member of the Ras family of small GTPases, is involved in cell growth, proliferation, differentiation and apoptosis and is frequently mutated in cancer. The activity of Ras is mediated by the inter-conversion between GTP- and GDP- bound states. This conversion is regulated by binding of effector proteins such as guanine nucleotide exchange factors and GTPase activating proteins. Previously, NMR signals from these effector-binding regions of Ras often remained unassigned and largely unobservable due to conformational exchange and polysterism inherent to this protein. In this paper, we report the complete backbone and C(β), as well as partial H(α), H(β) and C(γ), NMR assignment for human K-Ras (residues 1-166) in the GDP-bound form at a physiological pH of 7.4. These data thereby make possible detailed monitoring of the functional cycle of Ras and its interactions with nucleotides and effector proteins through the observation of fingerprint signals from all the functionally important regions of the protein.

Lipid Raft Redox Signaling: Molecular Mechanisms in Health and Disease

PubMed Central

Zhou, Fan; Katirai, Foad

2011-01-01

Abstract Lipid rafts, the sphingolipid and cholesterol-enriched membrane microdomains, are able to form different membrane macrodomains or platforms upon stimulations, including redox signaling platforms, which serve as a critical signaling mechanism to mediate or regulate cellular activities or functions. In particular, this raft platform formation provides an important driving force for the assembling of NADPH oxidase subunits and the recruitment of other related receptors, effectors, and regulatory components, resulting, in turn, in the activation of NADPH oxidase and downstream redox regulation of cell functions. This comprehensive review attempts to summarize all basic and advanced information about the formation, regulation, and functions of lipid raft redox signaling platforms as well as their physiological and pathophysiological relevance. Several molecular mechanisms involving the formation of lipid raft redox signaling platforms and the related therapeutic strategies targeting them are discussed. It is hoped that all information and thoughts included in this review could provide more comprehensive insights into the understanding of lipid raft redox signaling, in particular, of their molecular mechanisms, spatial-temporal regulations, and physiological, pathophysiological relevances to human health and diseases. Antioxid. Redox Signal. 15, 1043–1083. PMID:21294649

NADPH OXIDASE: STRUCTURE AND ACTIVATION MECHANISMS (REVIEW). NOTE I.

PubMed

Filip-Ciubotaru, Florina; Manciuc, Carmen; Stoleriu, Gabriela; Foia, Liliana

2016-01-01

NADPH oxidase (nicotinamide adenine dinucleotide phosphate-oxidase), with its generically termed NOX isoforms, is the major source of ROS (reactive oxigen species) in biological systems. ROS are small oxygen-derived molecules with an important role in various biological processes (physiological or pathological). If under physiological conditions some processes are beneficial and necessary for life, under pathophysiological conditions they are noxious, harmful. NADPH oxidases are present in phagocytes and in a wide variety of nonphagocytic cells. The enzyme generates superoxide by transferring electrons from NADPH inside the cell across the membrane and coupling them to molecular oxygen to produce superoxide anion, a reactive free-radical. Structurally, NADPH oxidase is a multicomponent enzyme which includes two integral membrane proteins, glycoprotein gp9 1 Phox and adaptor protein p22(phox), which together form the heterodimeric flavocytochrome b558 that constitutes the core of the enzyme. During the resting state, the multidomain regulatory subunits p40P(phox), p47(phox), p67(Phox) are located in the cytosol organized as a complex. The activation of phagocytic NADPH oxidase occurs through a complex series of protein interactions.

Effects of pelleted or powdered diets containing soy protein or sodium caseinate on lipid concentrations and bile acid excretion in golden Syrian hamsters.

PubMed

Butteiger, Dustie N; Krul, Elaine S

2015-08-01

Custom diets are a convenient vector for oral administration of test articles, but the processing and physical form of a diet can affect its nutritional properties and how it is consumed. Here, the authors evaluated the feeding behavior and physiology of golden Syrian hamsters fed diets of either soy or caseinate protein in pelleted or powdered forms for 28 d to determine whether dietary processing and form mediates the physiological effects of dietary proteins. The authors compared body weight, food consumption, serum cholesterol concentration, serum triglyceride concentration, fecal weight and fecal excretion of bile acids between treatment groups. Hamsters fed powdered diets showed higher food consumption than hamsters fed pelleted diets, regardless of protein source. Hamsters fed soy pelleted diets showed lower serum cholesterol concentration and higher fecal excretion of bile acid than hamsters fed caseinate pelleted diets, and serum cholesterol concentration correlated strongly with fecal excretion of bile acid. This correlation suggests that the physiological effects of soy protein on cholesterol and excretion of bile acid might be related or similarly mediated through diet. The differences observed between hamsters on different diets indicate that dietary form can influence both feeding behavior and the physiological effects of a diet in hamsters.

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.

PubMed

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.

Antibiofilm Activities of a Novel Chimeolysin against Streptococcus mutans under Physiological and Cariogenic Conditions.

PubMed

Yang, Hang; Bi, Yongli; Shang, Xiaoran; Wang, Mengyue; Linden, Sara B; Li, Yunpeng; Li, Yuhong; Nelson, Daniel C; Wei, Hongping

2016-12-01

Streptococcus mutans often survives as a biofilm on the tooth surface and contributes to the development of dental caries. We investigated the efficacy of ClyR, an engineered chimeolysin, against S. mutans biofilms under physiological and cariogenic conditions. Susceptibility tests showed that ClyR was active against all clinical S. mutans isolates tested as well as S. mutans biofilms that displayed resistance to penicillin. The S. mutans biofilms that formed on hydroxyapatite discs under physiological sugar conditions and cariogenic conditions were reduced ∼2 logs and 3 logs after treatment with 100 μg/ml ClyR, respectively. In comparison, only a 1-log reduction was observed in the chlorhexidine gluconate (ChX)-treated group, and no killing effect was observed in the NaF-treated group. A mouse dental colonization model showed that repeated use of ClyR for 3 weeks (5 μg/day) reduced the number of colonized S. mutans cells in the dental plaques significantly (P < 0.05) and had no harmful effects on the mice. Furthermore, toxicity was not noted at concentrations exceeding those used for the in vitro and in vivo studies, and ClyR-specific antibodies could not be detected in mouse saliva after repeated use of ClyR in the oral cavity. Our data collectively demonstrate that ClyR is active against S. mutans biofilms both in vitro and in vivo, thus representing a preventative or therapeutic agent for use against dental caries. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Who perceives they are smarter? Exploring the influence of student characteristics on student academic self-concept in physiology.

PubMed

Cooper, Katelyn M; Krieg, Anna; Brownell, Sara E

2018-06-01

Academic self-concept is one's perception of his or her ability in an academic domain and is formed by comparing oneself to other students. As college biology classrooms transition from lecturing to active learning, students interact more with each other and are likely comparing themselves more to other students in the class. Student characteristics can impact students' academic self-concept; however, this has been unexplored in the context of undergraduate biology. In this study, we explored whether student characteristics can affect academic self-concept in the context of an active learning college physiology course. Using a survey, students self-reported how smart they perceived themselves to be in the context of physiology relative to the whole class and relative to their groupmate, the student with whom they worked most closely in class. Using linear regression, we found that men and native English speakers had significantly higher academic self-concept relative to the whole class compared with women and nonnative English speakers. Using logistic regression, we found that men had significantly higher academic self-concept relative to their groupmate compared with women. Using constant comparison methods, we identified nine factors that students reported influenced how they determined whether they were more or less smart than their groupmate. Finally, we found that students were more likely to report participating more than their groupmate if they had a higher academic self-concept. These findings suggest that student characteristics can influence students' academic self-concept, which in turn may influence their participation in small-group discussion and their academic achievement in active learning classes.

The Effect of Different Levels of Cu, Zn and Mn Nanoparticles in Hen Turkey Diet on the Activity of Aminopeptidases.

PubMed

Jóźwik, Artur; Marchewka, Joanna; Strzałkowska, Nina; Horbańczuk, Jarosław Olav; Szumacher-Strabel, Małgorzata; Cieślak, Adam; Lipińska-Palka, Paulina; Józefiak, Damian; Kamińska, Agnieszka; Atanasov, Atanas G

2018-05-11

The aim of the study was to estimate the influence of the different levels of Cu, Zn, and Mn nanoparticles on the activity of aminopeptidases in turkey. An experiment was carried out on 144 turkey hen Hybrid Converter. The birds were divided into groups given standard- and nanoparticle-supplementation of different level of copper (Cu 20, 10, 2 mg/kg), zinc (Zn 100, 50, 10 ppm), and manganese (Mn 100, 50, 10 ppm), covering respectively 100%, 50%, and 10% of the physiological demands for those minerals in the diet. The activity of aminopeptidases (alanyl: AlaAP, leucyl: LeuAP and arginyl: ArgAP) after supplementation of minerals was determined in the breast and thigh turkey muscle. The strongest effect of interaction among minerals supplementation form and dose on the activity levels of the aminopeptidases in thigh muscle was observed for nano-Cu already at the lowest dose of 2 mg/kg. In this dose (covering 10% of the birds’ demand) nano form of supplementation significantly increased the activity of Ala-, Leu-, and ArgAP (877, 201, and 719, respectively), compared to standard form of supplementation (461, 90.5, and 576, respectively). In turn, in breast muscle, after supplementation covering 10% of the demand with the nano-Cu, nano-Zn, and nano-Mn compared to the standard form, we did not observe any significant difference in the activity levels of any of the investigated aminopeptidases, except for AlaAP under Zn supplementation. Supplementation with the 20 mg/kg of Nano-Cu (100% of demand) and with 10 mg/kg of Nano-Cu (50% of demand) inhibited the activity of all of the three aminopeptidases in thigh muscle. Supplementation of the minerals in nano form into the diet, especially of Cu and Zn in the dose covering 10% of the demand is relevant to maintain homeostasis in turkey muscles, as indicated by the activity of the aminopeptidases.

Pharmacologic Calcitriol Inhibits Osteoclast Lineage Commitment via the BMP-Smad1 and IκB-NF-κB Pathways.

PubMed

Li, Anna; Cong, Qian; Xia, Xuechun; Leong, Wai Fook; Yeh, James; Miao, Dengshun; Mishina, Yuji; Liu, Huijuan; Li, Baojie

2017-07-01

Vitamin D is involved in a range of physiological processes and its active form and analogs have been used to treat diseases such as osteoporosis. Yet how vitamin D executes its function remains unsolved. Here we show that the active form of vitamin D calcitriol increases the peak bone mass in mice by inhibiting osteoclastogenesis and bone resorption. Although calcitriol modestly promoted osteoclast maturation, it strongly inhibited osteoclast lineage commitment from its progenitor monocyte by increasing Smad1 transcription via the vitamin D receptor and enhancing BMP-Smad1 activation, which in turn led to increased IκBα expression and decreased NF-κB activation and NFATc1 expression, with IκBα being a Smad1 target gene. Inhibition of BMP type I receptor or ablation of Bmpr1a in monocytes alleviated the inhibitory effects of calcitriol on osteoclast commitment, bone resorption, and bone mass augmentation. These findings uncover crosstalk between the BMP-Smad1 and RANKL-NF-κB pathways during osteoclastogenesis that underlies the action of active vitamin D on bone health. © 2017 American Society for Bone and Mineral Research. © 2017 American Society for Bone and Mineral Research.

Tauroursodeoxycholic acid binds to the G-protein site on light activated rhodopsin.

PubMed

Lobysheva, E; Taylor, C M; Marshall, G R; Kisselev, O G

2018-05-01

The heterotrimeric G-protein binding site on G-protein coupled receptors remains relatively unexplored regarding its potential as a new target of therapeutic intervention or as a secondary site of action by the existing drugs. Tauroursodeoxycholic acid bears structural resemblance to several compounds that were previously identified to specifically bind to the light-activated form of the visual receptor rhodopsin and to inhibit its activation of transducin. We show that TUDCA stabilizes the active form of rhodopsin, metarhodopsin II, and does not display the detergent-like effects of common amphiphilic compounds that share the cholesterol scaffold structure, such as deoxycholic acid. Computer docking of TUDCA to the model of light-activated rhodopsin revealed that it interacts using similar mode of binding to the C-terminal domain of transducin alpha subunit. The ring regions of TUDCA made hydrophobic contacts with loop 3 region of rhodopsin, while the tail of TUDCA is exposed to solvent. The results show that TUDCA interacts specifically with rhodopsin, which may contribute to its wide-ranging effects on retina physiology and as a potential therapeutic compound for retina degenerative diseases. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

Detection of Intracellular Reduced (Catalytically Active) SHP-1 and Analyses of Catalytically Inactive SHP-1 after Oxidation by Pervanadate or H2O2.

PubMed

Choi, Seeyoung; Love, Paul E

2018-01-05

Oxidative inactivation of cysteine-dependent Protein Tyrosine Phosphatases (PTPs) by cellular reactive oxygen species (ROS) plays a critical role in regulating signal transduction in multiple cell types. The phosphatase activity of most PTPs depends upon a 'signature' cysteine residue within the catalytic domain that is maintained in the de-protonated state at physiological pH rendering it susceptible to ROS-mediated oxidation. Direct and indirect techniques for detection of PTP oxidation have been developed (Karisch and Neel, 2013). To detect catalytically active PTPs, cell lysates are treated with iodoacetyl-polyethylene glycol-biotin (IAP-biotin), which irreversibly binds to reduced (S - ) cysteine thiols. Irreversible oxidation of SHP-1 after treatment of cells with pervanadate or H 2 O 2 is detected with antibodies specific for the sulfonic acid (SO 3 H) form of the conserved active site cysteine of PTPs. In this protocol, we describe a method for the detection of the reduced (S - ; active) or irreversibly oxidized (SO 3 H; inactive) form of the hematopoietic PTP SHP-1 in thymocytes, although this method is applicable to any cysteine-dependent PTP in any cell type.

Hotspot Mutations in KIT Receptor Differentially Modulate Its Allosterically Coupled Conformational Dynamics: Impact on Activation and Drug Sensitivity

PubMed Central

Chauvot de Beauchêne, Isaure; Allain, Ariane; Panel, Nicolas; Laine, Elodie; Trouvé, Alain; Dubreuil, Patrice; Tchertanov, Luba

2014-01-01

Receptor tyrosine kinase KIT controls many signal transduction pathways and represents a typical allosterically regulated protein. The mutation-induced deregulation of KIT activity impairs cellular physiological functions and causes serious human diseases. The impact of hotspots mutations (D816H/Y/N/V and V560G/D) localized in crucial regulatory segments, the juxtamembrane region (JMR) and the activation (A-) loop, on KIT internal dynamics was systematically studied by molecular dynamics simulations. The mutational outcomes predicted in silico were correlated with in vitro and in vivo activation rates and drug sensitivities of KIT mutants. The allosteric regulation of KIT in the native and mutated forms is described in terms of communication between the two remote segments, JMR and A-loop. A strong correlation between the communication profile and the structural and dynamical features of KIT in the native and mutated forms was established. Our results provide new insight on the determinants of receptor KIT constitutive activation by mutations and resistance of KIT mutants to inhibitors. Depiction of an intra-molecular component of the communication network constitutes a first step towards an integrated description of vast communication pathways established by KIT in physiopathological contexts. PMID:25079768

Cryo-EM structures of the human endolysosomal TRPML3 channel in three distinct states.

PubMed

Zhou, Xiaoyuan; Li, Minghui; Su, Deyuan; Jia, Qi; Li, Huan; Li, Xueming; Yang, Jian

2017-12-01

TRPML3 channels are mainly localized to endolysosomes and play a critical role in the endocytic pathway. Their dysfunction causes deafness and pigmentation defects in mice. TRPML3 activity is inhibited by low endolysosomal pH. Here we present cryo-electron microscopy (cryo-EM) structures of human TRPML3 in the closed, agonist-activated, and low-pH-inhibited states, with resolutions of 4.06, 3.62, and 4.65 Å, respectively. The agonist ML-SA1 lodges between S5 and S6 and opens an S6 gate. A polycystin-mucolipin domain (PMD) forms a luminal cap. S1 extends into this cap, forming a 'gating rod' that connects directly to a luminal pore loop, which undergoes dramatic conformational changes in response to low pH. S2 extends intracellularly and interacts with several intracellular regions to form a 'gating knob'. These unique structural features, combined with the results of electrophysiological studies, indicate a new mechanism by which luminal pH and other physiological modulators such as PIP 2 regulate TRPML3 by changing S1 and S2 conformations.

Dance as an eccentric form of exercise: practical implications.

PubMed

Paschalis, Vassilis; Nikolaidis, Michalis G; Jamurtas, Athanasios Z; Owolabi, Emmanuel O; Kitas, George D; Wyon, Matthew A; Koutedakis, Yiannis

2012-06-01

The eccentric action is an integral part of the stretch-shortening (or eccentric-concentric) cycle of muscle movement, especially when repositioning of the centre of gravity is required. Jumps and landing tasks are examples of this cycle and are incorporated in most dance activities. However, unaccustomed eccentric muscle action can cause muscle damage, which is characterised by the development of delayed-onset muscle soreness and swelling, decline of pain-free range of motion, as well as sustained loss of muscle force and range of motion. Furthermore, unaccustomed eccentric muscle action can induce disturbances in movement economy and energy expenditure, so dancers spend more energy during a routine than usual. Such negative effects are gradually reduced and eventually disappear due to physiological adaptations to this form of muscular activity. Given that eccentric exercises also appear to induce greater muscle performance improvements than other forms of muscle conditioning, it is advised that they should be integrated into dancers' weekly schedules. The purpose of the present review is to examine the possible effects of the eccentric component of dance on the performance and health status of dancers.

Application of activity-based protein profiling to study enzyme function in adipocytes.

PubMed

Galmozzi, Andrea; Dominguez, Eduardo; Cravatt, Benjamin F; Saez, Enrique

2014-01-01

Activity-based protein profiling (ABPP) is a chemical proteomics approach that utilizes small-molecule probes to determine the functional state of enzymes directly in native systems. ABPP probes selectively label active enzymes, but not their inactive forms, facilitating the characterization of changes in enzyme activity that occur without alterations in protein levels. ABPP can be a tool superior to conventional gene expression and proteomic profiling methods to discover new enzymes active in adipocytes and to detect differences in the activity of characterized enzymes that may be associated with disorders of adipose tissue function. ABPP probes have been developed that react selectively with most members of specific enzyme classes. Here, using as an example the serine hydrolase family that includes many enzymes with critical roles in adipocyte physiology, we describe methods to apply ABPP analysis to the study of adipocyte enzymatic pathways. © 2014 Elsevier Inc. All rights reserved.

Kinetics and thermodynamics of the interchange of the morpheein forms of human porphobilinogen synthase.

PubMed

Selwood, Trevor; Tang, Lei; Lawrence, Sarah H; Anokhina, Yana; Jaffe, Eileen K

2008-03-11

A morpheein is a homo-oligomeric protein that can adopt different nonadditive quaternary assemblies (morpheein forms) with different functionalities. The human porphobilinogen synthase (PBGS) morpheein forms are a high activity octamer, a low activity hexamer, and two structurally distinct dimer conformations. Conversion between hexamer and octamer involves dissociation to dimers, conformational change at the dimer level, followed by association to the alternate assembly. The current work promotes an alternative and novel view of the physiologically relevant dimeric structures, which are derived from the crystal structures, but are distinct from the asymmetric units of their crystal forms. Using a well characterized heteromeric system (WT+F12L; Tang, L. et al. (2005) J. Biol. Chem. 280, 15786-15793), extensive study of the human PBGS morpheein reequilibration process now reveals that the intervening dimers do not dissociate to monomers. The morpheein equilibria of wild type (WT) human PBGS are found to respond to changes in pH, PBGS concentration, and substrate turnover. Notably, the WT enzyme is predominantly an octamer at neutral pH, but increasing pH results in substantial conversion to lower order oligomers. Most significantly, the free energy of activation for the conversion of WT+F12L human PBGS heterohexamers to hetero-octamers is determined to be the same as that for the catalytic conversion of substrate to product by the octamer, remarkably suggesting a common rate-limiting step for both processes, which is postulated to be the opening/closing of the active site lid.

Role of sph2 Gene Regulation in Hemolytic and Sphingomyelinase Activities Produced by Leptospira interrogans.

PubMed

Narayanavari, Suneel A; Lourdault, Kristel; Sritharan, Manjula; Haake, David A; Matsunaga, James

2015-01-01

Pathogenic members of the genus Leptospira are the causative agents of leptospirosis, a neglected disease of public and veterinary health concern. Leptospirosis is a systemic disease that in its severest forms leads to renal insufficiency, hepatic dysfunction, and pulmonary failure. Many strains of Leptospira produce hemolytic and sphingomyelinase activities, and a number of candidate leptospiral hemolysins have been identified based on sequence similarity to well-characterized bacterial hemolysins. Five of the putative hemolysins are sphingomyelinase paralogs. Although recombinant forms of the sphingomyelinase Sph2 and other hemolysins lyse erythrocytes, none have been demonstrated to contribute to the hemolytic activity secreted by leptospiral cells. In this study, we examined the regulation of sph2 and its relationship to hemolytic and sphingomyelinase activities produced by several L. interrogans strains cultivated under the osmotic conditions found in the mammalian host. The sph2 gene was poorly expressed when the Fiocruz L1-130 (serovar Copenhageni), 56601 (sv. Lai), and L495 (sv. Manilae) strains were cultivated in the standard culture medium EMJH. Raising EMJH osmolarity to physiological levels with sodium chloride enhanced Sph2 production in all three strains. In addition, the Pomona subtype kennewicki strain LC82-25 produced substantially greater amounts of Sph2 during standard EMJH growth than the other strains, and sph2 expression increased further by addition of salt. When 10% rat serum was present in EMJH along with the sodium chloride supplement, Sph2 production increased further in all strains. Osmotic regulation and differences in basal Sph2 production in the Manilae L495 and Pomona strains correlated with the levels of secreted hemolysin and sphingomyelinase activities. Finally, a transposon insertion in sph2 dramatically reduced hemolytic and sphingomyelinase activities during incubation of L. interrogans at physiologic osmolarity. Complementation of the mutation with the sph2 gene partially restored production of hemolytic and sphingomyelinase activities. These results indicate that the sph2 gene product contributes to the hemolytic and sphingomyelinase activities secreted by L. interrogans and most likely dominates those functions under the culture condition tested.

In Vivo Studies in Rhodospirillum rubrum Indicate That Ribulose-1,5-bisphosphate Carboxylase/Oxygenase (Rubisco) Catalyzes Two Obligatorily Required and Physiologically Significant Reactions for Distinct Carbon and Sulfur Metabolic Pathways*♦

PubMed Central

Dey, Swati; North, Justin A.; Sriram, Jaya; Evans, Bradley S.; Tabita, F. Robert

2015-01-01

All organisms possess fundamental metabolic pathways to ensure that needed carbon and sulfur compounds are provided to the cell in the proper chemical form and oxidation state. For most organisms capable of using CO2 as sole source of carbon, ribulose-1,5-bisphosphate (RuBP) carboxylase/oxygenase (Rubisco) catalyzes primary carbon dioxide assimilation. In addition, sulfur salvage pathways are necessary to ensure that key sulfur-containing compounds are both available and, where necessary, detoxified in the cell. Using knock-out mutations and metabolomics in the bacterium Rhodospirillum rubrum, we show here that Rubisco concurrently catalyzes key and essential reactions for seemingly unrelated but physiologically essential central carbon and sulfur salvage metabolic pathways of the cell. In this study, complementation and mutagenesis studies indicated that representatives of all known extant functional Rubisco forms found in nature are capable of simultaneously catalyzing reactions required for both CO2-dependent growth as well as growth using 5-methylthioadenosine as sole sulfur source under anaerobic photosynthetic conditions. Moreover, specific inactivation of the CO2 fixation reaction did not affect the ability of Rubisco to support anaerobic 5-methylthioadenosine metabolism, suggesting that the active site of Rubisco has evolved to ensure that this enzyme maintains both key functions. Thus, despite the coevolution of both functions, the active site of this protein may be differentially modified to affect only one of its key functions. PMID:26511314

Multimodal integration of anatomy and physiology classes: How instructors utilize multimodal teaching in their classrooms

NASA Astrophysics Data System (ADS)

McGraw, Gerald M., Jr.

Multimodality is the theory of communication as it applies to social and educational semiotics (making meaning through the use of multiple signs and symbols). The term multimodality describes a communication methodology that includes multiple textual, aural, and visual applications (modes) that are woven together to create what is referred to as an artifact. Multimodal teaching methodology attempts to create a deeper meaning to course content by activating the higher cognitive areas of the student's brain, creating a more sustained retention of the information (Murray, 2009). The introduction of multimodality educational methodologies as a means to more optimally engage students has been documented within educational literature. However, studies analyzing the distribution and penetration into basic sciences, more specifically anatomy and physiology, have not been forthcoming. This study used a quantitative survey design to determine the degree to which instructors integrated multimodality teaching practices into their course curricula. The instrument used for the study was designed by the researcher based on evidence found in the literature and sent to members of three associations/societies for anatomy and physiology instructors: the Human Anatomy and Physiology Society; the iTeach Anatomy & Physiology Collaborate; and the American Physiology Society. Respondents totaled 182 instructor members of two- and four-year, private and public higher learning colleges collected from the three organizations collectively with over 13,500 members in over 925 higher learning institutions nationwide. The study concluded that the expansion of multimodal methodologies into anatomy and physiology classrooms is at the beginning of the process and that there is ample opportunity for expansion. Instructors continue to use lecture as their primary means of interaction with students. Email is still the major form of out-of-class communication for full-time instructors. Instructors with greater than 16 years of teaching anatomy and physiology are less likely to use video or animation in their classroom than instructors with fewer years.

Haptoglobin, hemopexin, and related defense pathways-basic science, clinical perspectives, and drug development.

PubMed

Schaer, Dominik J; Vinchi, Francesca; Ingoglia, Giada; Tolosano, Emanuela; Buehler, Paul W

2014-01-01

Hemolysis, which occurs in many disease states, can trigger a diverse pathophysiologic cascade that is related to the specific biochemical activities of free Hb and its porphyrin component heme. Normal erythropoiesis and concomitant removal of senescent red blood cells (RBC) from the circulation occurs at rates of approximately 2 × 10(6) RBCs/second. Within this physiologic range of RBC turnover, a small fraction of hemoglobin (Hb) is released into plasma as free extracellular Hb. In humans, there is an efficient multicomponent system of Hb sequestration, oxidative neutralization and clearance. Haptoglobin (Hp) is the primary Hb-binding protein in human plasma, which attenuates the adverse biochemical and physiologic effects of extracellular Hb. The cellular receptor target of Hp is the monocyte/macrophage scavenger receptor, CD163. Following Hb-Hp binding to CD163, cellular internalization of the complex leads to globin and heme metabolism, which is followed by adaptive changes in antioxidant and iron metabolism pathways and macrophage phenotype polarization. When Hb is released from RBCs within the physiologic range of Hp, the potential deleterious effects of Hb are prevented. However, during hyper-hemolytic conditions or with chronic hemolysis, Hp is depleted and Hb readily distributes to tissues where it might be exposed to oxidative conditions. In such conditions, heme can be released from ferric Hb. The free heme can then accelerate tissue damage by promoting peroxidative reactions and activation of inflammatory cascades. Hemopexin (Hx) is another plasma glycoprotein able to bind heme with high affinity. Hx sequesters heme in an inert, non-toxic form and transports it to the liver for catabolism and excretion. In the present review we discuss the components of physiologic Hb/heme detoxification and their potential therapeutic application in a wide range of hemolytic conditions.

When pain and hunger collide; psychological influences on differences in brain activity during physiological and non-physiological gastric distension.

PubMed

Coen, S J

2011-06-01

Functional neuroimaging has been used extensively in conjunction with gastric balloon distension in an attempt to unravel the relationship between the brain, regulation of hunger, satiety, and food intake tolerance. A number of researchers have also adopted a more physiological approach using intra-gastric administration of a liquid meal which has revealed different brain responses to gastric balloon distension. These differences are important as they question the utility and relevance of non-physiological models such as gastric balloon distension, especially when investigating mechanisms of feeding behavior such as satiety. However, an assessment of the relevance of physiological versus non-physiological gastric distension has been problematic due to differences in distension volumes between studies. In this issue of Neurogastroenterology and Motility, Geeraerts et al. compare brain activity during volume matched nutrient gastric distension and balloon distension in healthy volunteers. Gastric balloon distension activated the 'visceral pain neuromatrix'. This network of brain regions was deactivated during nutrient infusion, supporting the notion that brain activity during physiological versus non-physiological distension is indeed different. The authors suggest deactivation of the pain neuromatrix during nutrient infusion serves as a prerequisite for tolerance of normal meal volumes in health. © 2011 Blackwell Publishing Ltd.

Protection from oxidative inactivation of the 20S proteasome by heat-shock protein 90.

PubMed Central

Conconi, M; Petropoulos, I; Emod, I; Turlin, E; Biville, F; Friguet, B

1998-01-01

Heat-shock protein 90 (Hsp 90) has been implicated in both protection against oxidative inactivation and inhibition of the multicatalytic proteinase (MCP, also known as 20 S proteasome). We report here that the protective and inhibitory effects of Hsp 90 depend on the activation state of the proteasome. Hsp 90 (and also alpha-crystallin) inhibits the N-Cbz-Leu-Leu-Leu-MCA-hydrolysing activity (Cbz=benzyloxycarbonyl; MCA=7-amido-4-methylcoumarin) when the rat liver MCP is in its latent form, but no inhibitory effects are observed when the MCP is in its active form. Metal-catalysed oxidation of the active MCP inactivates the Ala-Ala-Phe-MCA-hydrolysing (chymotrypsin-like), N-Boc-Leu-Ser-Thr-Arg-MCA-hydrolysing (trypsin-like; Boc=t-butyloxycarbonyl), N-Cbz-Leu-Leu-Glu-beta-naphthylamine-hydrolysing (peptidylglutamyl-peptide hydrolase) and N-Cbz-Leu-Leu-Leu-MCA-hydrolysing activities, whereas these activities are actually increased when the MCP is in its latent form. Hsp 90 protects against oxidative inactivation of the trypsin-like and N-Cbz-Leu-Leu-Leu-MCA-hydrolysing activities of the MCP active form, and alpha-crystallin protects the trypsin-like activity. The specificity of the Hsp 90-mediated protection was assessed by a quantitative analysis of the two-dimensional electrophoretic pattern of MCP subunits before and after oxidation of the MCP, in the presence or absence of Hsp 90. Treatment of the FAO hepatoma cell line with iron and ascorbate was found to inactivate the MCP. Hsp 90 overexpression obtained by challenging the cells with iron was associated with a decreased susceptibility to oxidative inactivation of the MCP trypsin-like activity. Depletion of Hsp 90 by using antisense oligonucleotides resulted in an increased susceptibility to oxidative inactivation of the MCP trypsin-like activity, providing evidence for the physiological relevance of Hsp 90-mediated protection of the MCP. PMID:9657982

Protection from oxidative inactivation of the 20S proteasome by heat-shock protein 90.

PubMed

Conconi, M; Petropoulos, I; Emod, I; Turlin, E; Biville, F; Friguet, B

1998-07-15

Heat-shock protein 90 (Hsp 90) has been implicated in both protection against oxidative inactivation and inhibition of the multicatalytic proteinase (MCP, also known as 20 S proteasome). We report here that the protective and inhibitory effects of Hsp 90 depend on the activation state of the proteasome. Hsp 90 (and also alpha-crystallin) inhibits the N-Cbz-Leu-Leu-Leu-MCA-hydrolysing activity (Cbz=benzyloxycarbonyl; MCA=7-amido-4-methylcoumarin) when the rat liver MCP is in its latent form, but no inhibitory effects are observed when the MCP is in its active form. Metal-catalysed oxidation of the active MCP inactivates the Ala-Ala-Phe-MCA-hydrolysing (chymotrypsin-like), N-Boc-Leu-Ser-Thr-Arg-MCA-hydrolysing (trypsin-like; Boc=t-butyloxycarbonyl), N-Cbz-Leu-Leu-Glu-beta-naphthylamine-hydrolysing (peptidylglutamyl-peptide hydrolase) and N-Cbz-Leu-Leu-Leu-MCA-hydrolysing activities, whereas these activities are actually increased when the MCP is in its latent form. Hsp 90 protects against oxidative inactivation of the trypsin-like and N-Cbz-Leu-Leu-Leu-MCA-hydrolysing activities of the MCP active form, and alpha-crystallin protects the trypsin-like activity. The specificity of the Hsp 90-mediated protection was assessed by a quantitative analysis of the two-dimensional electrophoretic pattern of MCP subunits before and after oxidation of the MCP, in the presence or absence of Hsp 90. Treatment of the FAO hepatoma cell line with iron and ascorbate was found to inactivate the MCP. Hsp 90 overexpression obtained by challenging the cells with iron was associated with a decreased susceptibility to oxidative inactivation of the MCP trypsin-like activity. Depletion of Hsp 90 by using antisense oligonucleotides resulted in an increased susceptibility to oxidative inactivation of the MCP trypsin-like activity, providing evidence for the physiological relevance of Hsp 90-mediated protection of the MCP.

Extracellular enzymatic activities and physiological profiles of yeasts colonizing fruit trees.

PubMed

Molnárová, Jana; Vadkertiová, Renáta; Stratilová, Eva

2014-07-01

Yeasts form a significant and diverse part of the phyllosphere microbiota. Some yeasts that inhabit plants have been found to exhibit extracellular enzymatic activities. The aim of the present study was to investigate the ability of yeasts isolated from leaves, fruits, and blossoms of fruit trees cultivated in Southwest Slovakia to produce extracellular enzymes, and to discover whether the yeasts originating from these plant organs differ from each other in their physiological properties. In total, 92 strains belonging to 29 different species were tested for: extracellular protease, β-glucosidase, lipase, and polygalacturonase activities; fermentation abilities; the assimilation of xylose, saccharose and alcohols (methanol, ethanol, glycerol); and for growth in a medium with 33% glucose. The black yeast Aureobasidium pullulans showed the largest spectrum of activities of all the species tested. Almost 70% of the strains tested demonstrated some enzymatic activity, and more than 90% utilized one of the carbon compounds tested. Intraspecies variations were found for the species of the genera Cryptococcus and Pseudozyma. Interspecies differences of strains exhibiting some enzymatic activities and utilizing alcohols were also noted. The largest proportion of the yeasts exhibited β-glucosidase activity and assimilated alcohols independently of their origin. The highest number of strains positive for all activities tested was found among the yeasts associated with leaves. Yeasts isolated from blossoms assimilated saccharose and D-xylose the most frequently of all the yeasts tested. The majority of the fruit-inhabiting yeasts grew in the medium with higher osmotic pressure. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Initial blood storage experiment

NASA Technical Reports Server (NTRS)

Surgenor, Douglas MACN.

1988-01-01

The possibility of conducting experiments with the formed elements of the blood under conditions of microgravity opens up important opportunities to improve the understanding of basic formed element physiology, as well as, contribution to improved preservation of the formed elements for use in transfusion. The physiological, biochemical, and physical changes of the membrane of the erythrocyte, platelet, and leukocyte was studied during storage under two specific conditions: standard blood bank conditions and microgravity, utilizing three FDA approved plastic bags. Storage lesions; red cell storage on Earth; platelet storage on Earth; and leukocyte storage Earth were examined. The interaction of biomaterials and blood cells was studied during storage.

Rapid and automated enumeration of viable bacteria in compost using a micro-colony auto counting system.

PubMed

Wang, Xiaodan; Yamaguchi, Nobuyasu; Someya, Takashi; Nasu, Masao

2007-10-01

The micro-colony method was used to enumerate viable bacteria in composts. Cells were vacuum-filtered onto polycarbonate filters and incubated for 18 h on LB medium at 37 degrees C. Bacteria on the filters were stained with SYBR Green II, and enumerated using a newly developed micro-colony auto counting system which can automatically count micro-colonies on half the area of the filter within 90 s. A large number of bacteria in samples retained physiological activity and formed micro-colonies within 18 h, whereas most could not form large colonies on conventional media within 1 week. The results showed that this convenient technique can enumerate viable bacteria in compost rapidly for its efficient quality control.

Synaptic communication between neurons and NG2+ cells.

PubMed

Paukert, Martin; Bergles, Dwight E

2006-10-01

Chemical synaptic transmission provides the basis for much of the rapid signaling that occurs within neuronal networks. However, recent studies have provided compelling evidence that synapses are not used exclusively for communication between neurons. Physiological and anatomical studies indicate that a distinct class of glia known as NG2(+) cells also forms direct synaptic junctions with both glutamatergic and GABAergic neurons. Glutamatergic signaling can influence intracellular Ca(2+) levels in NG2(+) cells by activating Ca(2+) permeable AMPA receptors, and these inputs can be potentiated through high frequency stimulation. Although the significance of this highly differentiated form of communication remains to be established, these neuro-glia synapses might enable neurons to influence rapidly the behavior of this ubiquitous class of glial progenitors.

Deleterious effects of neuronal accumulation of glycogen in flies and mice.

PubMed

Duran, Jordi; Tevy, María Florencia; Garcia-Rocha, Mar; Calbó, Joaquim; Milán, Marco; Guinovart, Joan J

2012-08-01

Under physiological conditions, most neurons keep glycogen synthase (GS) in an inactive form and do not show detectable levels of glycogen. Nevertheless, aberrant glycogen accumulation in neurons is a hallmark of patients suffering from Lafora disease or other polyglucosan disorders. Although these diseases are associated with mutations in genes involved in glycogen metabolism, the role of glycogen accumulation remains elusive. Here, we generated mouse and fly models expressing an active form of GS to force neuronal accumulation of glycogen. We present evidence that the progressive accumulation of glycogen in mouse and Drosophila neurons leads to neuronal loss, locomotion defects and reduced lifespan. Our results highlight glycogen accumulation in neurons as a direct cause of neurodegeneration. Copyright © 2012 EMBO Molecular Medicine.

Deleterious effects of neuronal accumulation of glycogen in flies and mice

PubMed Central

Duran, Jordi; Tevy, María Florencia; Garcia-Rocha, Mar; Calbó, Joaquim; Milán, Marco; Guinovart, Joan J

2012-01-01

Under physiological conditions, most neurons keep glycogen synthase (GS) in an inactive form and do not show detectable levels of glycogen. Nevertheless, aberrant glycogen accumulation in neurons is a hallmark of patients suffering from Lafora disease or other polyglucosan disorders. Although these diseases are associated with mutations in genes involved in glycogen metabolism, the role of glycogen accumulation remains elusive. Here, we generated mouse and fly models expressing an active form of GS to force neuronal accumulation of glycogen. We present evidence that the progressive accumulation of glycogen in mouse and Drosophila neurons leads to neuronal loss, locomotion defects and reduced lifespan. Our results highlight glycogen accumulation in neurons as a direct cause of neurodegeneration. PMID:22549942

Segregation of Form, Color, Movement, and Depth: Anatomy, Physiology, and Perception.

ERIC Educational Resources Information Center

Livingstone, Margaret; Hubel, David

1988-01-01

Summarizes the anatomical, physiological, and psychological evidence related to the primate visual system. States that comparison of perceptual abilities with the electrophysiological properties of neurons may help deduce functions of visual areas. (RT)

Prebiotics, Fermentable Dietary Fiber, and Health Claims.

PubMed

Delcour, Jan A; Aman, Per; Courtin, Christophe M; Hamaker, Bruce R; Verbeke, Kristin

2016-01-01

Since the 1970s, the positive effects of dietary fiber on health have increasingly been recognized. The collective term "dietary fiber" groups structures that have different physiologic effects. Since 1995, some dietary fibers have been denoted as prebiotics, implying a beneficial physiologic effect related to increasing numbers or activity of the gastrointestinal microbiota. Given the complex composition of the microbiota, the demonstration of such beneficial effects is difficult. In contrast, an exploration of the metabolites of dietary fiber formed as a result of its fermentation in the colon offers better perspectives for providing mechanistic links between fiber intake and health benefits. Positive outcomes of such studies hold the promise that claims describing specific health benefits can be granted. This would help bridge the "fiber gap"-that is, the considerable difference between recommended and actual fiber intakes by the average consumer. © 2016 American Society for Nutrition.

Prebiotics, Fermentable Dietary Fiber, and Health Claims12

PubMed Central

Aman, Per; Courtin, Christophe M; Hamaker, Bruce R; Verbeke, Kristin

2016-01-01

Since the 1970s, the positive effects of dietary fiber on health have increasingly been recognized. The collective term “dietary fiber” groups structures that have different physiologic effects. Since 1995, some dietary fibers have been denoted as prebiotics, implying a beneficial physiologic effect related to increasing numbers or activity of the gastrointestinal microbiota. Given the complex composition of the microbiota, the demonstration of such beneficial effects is difficult. In contrast, an exploration of the metabolites of dietary fiber formed as a result of its fermentation in the colon offers better perspectives for providing mechanistic links between fiber intake and health benefits. Positive outcomes of such studies hold the promise that claims describing specific health benefits can be granted. This would help bridge the “fiber gap”—that is, the considerable difference between recommended and actual fiber intakes by the average consumer. PMID:26773010

Iminoboronate Formation Leads to Fast and Reversible Conjugation Chemistry of α-Nucleophiles at Neutral pH.

PubMed

Bandyopadhyay, Anupam; Gao, Jianmin

2015-10-12

Bioorthogonal reactions that are fast and reversible under physiological conditions are in high demand for biological applications. Herein, it is shown that an ortho boronic acid substituent makes aryl ketones rapidly conjugate with α-nucleophiles at neutral pH. Specifically, 2-acetylphenylboronic acid and derivatives were found to conjugate with phenylhydrazine with rate constants of 10(2) to 10(3) M(-1) s(-1) , comparable to the fastest bioorthogonal conjugations known to date. (11) B NMR analysis revealed the varied extent of iminoboronate formation of the conjugates, in which the imine nitrogen forms a dative bond with boron. The iminoboronate formation activates the imines for hydrolysis and exchange, rendering these oxime/hydrazone conjugations reversible and dynamic under physiological conditions. The fast and dynamic nature of the iminoboronate chemistry should find wide applications in biology. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Effects of Hypogravity on Osteoblast Differentiation

NASA Technical Reports Server (NTRS)

Globus, Ruth; Doty, Steven

1997-01-01

Weightbearing is essential for normal skeletal function. Without weightbearing, the rate of bone formation by osteoblasts decreases in the growing rat. Defective formation may account for the decrease in the maturation, strength and mass of bone that is caused by spaceflight. These skeletal defects may be mediated by a combination of physiologic changes triggered by spaceflight, including skeletal unloading, fluid shifts, and stress-induced endocrine factors. The fundamental question of whether the defects in osteoblast function due to weightlessness are mediated by localized skeletal unloading or by systemic physiologic adaptations such as fluid shifts has not been answered. Furthermore, bone-forming activity of osteoblasts during unloading may be affected by paracrine signals from vascular, monocytic, and neural cells that also reside in skeletal tissue. Therefore we proposed to examine whether exposure of cultured rat osteoblasts to spaceflight inhibits cellular differentiation and impairs mineralization when isolated from the influence of both systemic factors and other skeletal cells.

Contribution of Glucose Transport to the Control of the Glycolytic Flux in Trypanosoma brucei

NASA Astrophysics Data System (ADS)

Bakker, Barbara M.; Walsh, Michael C.; Ter Kuile, Benno H.; Mensonides, Femke I. C.; Michels, Paul A. M.; Opperdoes, Fred R.; Westerhoff, Hans V.

1999-08-01

The rate of glucose transport across the plasma membrane of the bloodstream form of Trypanosoma brucei was modulated by titration of the hexose transporter with the inhibitor phloretin, and the effect on the glycolytic flux was measured. A rapid glucose uptake assay was developed to measure the transport activity independently of the glycolytic flux. Phloretin proved a competitive inhibitor. When the effect of the intracellular glucose concentration on the inhibition was taken into account, the flux control coefficient of the glucose transporter was between 0.3 and 0.5 at 5 mM glucose. Because the flux control coefficients of all steps in a metabolic pathway sum to 1, this result proves that glucose transport is not the rate-limiting step of trypanosome glycolysis. Under physiological conditions, transport shares the control with other steps. At glucose concentrations much lower than physiological, the glucose carrier assumed all control, in close agreement with model predictions.

The endothelial glycocalyx

PubMed Central

Yang, Yimu; Schmidt, Eric P.

2013-01-01

Once thought to be a structure of small size and uncertain significance, the endothelial glycocalyx is now known to be an important regulator of endothelial function. Studies of the systemic vasculature have demonstrated that the glycocalyx forms a substantial in vivo endothelial surface layer (ESL) critical to inflammation, barrier function and mechanotransduction. The pulmonary ESL is significantly thicker than the systemic ESL, suggesting unique physiologic function. We have recently demonstrated that the pulmonary ESL regulates exposure of endothelial surface adhesion molecules, thereby serving as a barrier to neutrophil adhesion and extravasation. While the pulmonary ESL is not a critical structural component of the endothelial barrier to fluid and protein, it serves a major role in the mechanotransduction of vascular pressure, with impact on the active regulation of endothelial permeability. It is likely that the ESL serves numerous additional functions in vascular physiology, representing a fertile area for future investigation. PMID:24073386

The cannabinoid receptor CB1 modulates the signaling properties of the lysophosphatidylinositol receptor GPR55.

PubMed

Kargl, Julia; Balenga, Nariman; Parzmair, Gerald P; Brown, Andrew J; Heinemann, Akos; Waldhoer, Maria

2012-12-28

The G protein-coupled receptor (GPCR) 55 (GPR55) and the cannabinoid receptor 1 (CB1R) are co-expressed in many tissues, predominantly in the central nervous system. Seven transmembrane spanning (7TM) receptors/GPCRs can form homo- and heteromers and initiate distinct signaling pathways. Recently, several synthetic CB1 receptor inverse agonists/antagonists, such as SR141716A, AM251, and AM281, were reported to activate GPR55. Of these, SR141716A was marketed as a promising anti-obesity drug, but was withdrawn from the market because of severe side effects. Here, we tested whether GPR55 and CB1 receptors are capable of (i) forming heteromers and (ii) whether such heteromers could exhibit novel signaling patterns. We show that GPR55 and CB1 receptors alter each others signaling properties in human embryonic kidney (HEK293) cells. We demonstrate that the co-expression of FLAG-CB1 receptors in cells stably expressing HA-GPR55 specifically inhibits GPR55-mediated transcription factor activation, such as nuclear factor of activated T-cells and serum response element, as well as extracellular signal-regulated kinases (ERK1/2) activation. GPR55 and CB1 receptors can form heteromers, but the internalization of both receptors is not affected. In addition, we observe that the presence of GPR55 enhances CB1R-mediated ERK1/2 and nuclear factor of activated T-cell activation. Our data provide the first evidence that GPR55 can form heteromers with another 7TM/GPCR and that this interaction with the CB1 receptor has functional consequences in vitro. The GPR55-CB1R heteromer may play an important physiological and/or pathophysiological role in tissues endogenously co-expressing both receptors.

The Cannabinoid Receptor CB1 Modulates the Signaling Properties of the Lysophosphatidylinositol Receptor GPR55*

PubMed Central

Kargl, Julia; Balenga, Nariman; Parzmair, Gerald P.; Brown, Andrew J.; Heinemann, Akos; Waldhoer, Maria

2012-01-01

The G protein-coupled receptor (GPCR) 55 (GPR55) and the cannabinoid receptor 1 (CB1R) are co-expressed in many tissues, predominantly in the central nervous system. Seven transmembrane spanning (7TM) receptors/GPCRs can form homo- and heteromers and initiate distinct signaling pathways. Recently, several synthetic CB1 receptor inverse agonists/antagonists, such as SR141716A, AM251, and AM281, were reported to activate GPR55. Of these, SR141716A was marketed as a promising anti-obesity drug, but was withdrawn from the market because of severe side effects. Here, we tested whether GPR55 and CB1 receptors are capable of (i) forming heteromers and (ii) whether such heteromers could exhibit novel signaling patterns. We show that GPR55 and CB1 receptors alter each others signaling properties in human embryonic kidney (HEK293) cells. We demonstrate that the co-expression of FLAG-CB1 receptors in cells stably expressing HA-GPR55 specifically inhibits GPR55-mediated transcription factor activation, such as nuclear factor of activated T-cells and serum response element, as well as extracellular signal-regulated kinases (ERK1/2) activation. GPR55 and CB1 receptors can form heteromers, but the internalization of both receptors is not affected. In addition, we observe that the presence of GPR55 enhances CB1R-mediated ERK1/2 and nuclear factor of activated T-cell activation. Our data provide the first evidence that GPR55 can form heteromers with another 7TM/GPCR and that this interaction with the CB1 receptor has functional consequences in vitro. The GPR55-CB1R heteromer may play an important physiological and/or pathophysiological role in tissues endogenously co-expressing both receptors. PMID:23161546

Active Learning Improves Student Performance in a Respiratory Physiology Lab

ERIC Educational Resources Information Center

Wolf, Alex M.; Liachovitzky, Carlos; Abdullahi, Abass S.

2015-01-01

This study assessed the effectiveness of the introduction of active learning exercises into the anatomy and physiology curriculum in a community college setting. Specifically, the incorporation of a spirometry-based respiratory physiology lab resulted in improved student performance in two concepts (respiratory volumes and the hallmarks of…

Control of Promatrilysin (MMP7) Activation and Substrate-specific Activity by Sulfated Glycosaminoglycans*

PubMed Central

Ra, Hyun-Jeong; Harju-Baker, Susanna; Zhang, Fuming; Linhardt, Robert J.; Wilson, Carole L.; Parks, William C.

2009-01-01

Matrix metalloproteinases are maintained in an inactive state by a bond between the thiol of a conserved cysteine in the prodomain and a zinc atom in the catalytic domain. Once this bond is disrupted, MMPs become active proteinases and can act on a variety of extracellular protein substrates. In vivo, matrilysin (MMP7) activates pro-α-defensins (procryptdins), but in vitro, processing of these peptides is slow, with about 50% conversion in 8–12 h. Similarly, autolytic activation of promatrilysin in vitro can take up to 12–24 h for 50% conversion. These inefficient reactions suggest that natural cofactors enhance the activation and activity of matrilysin. We determined that highly sulfated glycosaminoglycans (GAG), such as heparin, chondroitin-4,6-sulfate (CS-E), and dermatan sulfate, markedly enhanced (>50-fold) the intermolecular autolytic activation of promatrilysin and the activity of fully active matrilysin to cleave specific physiologic substrates. In contrast, heparan sulfate and less sulfated forms of chondroitin sulfate did not augment matrilysin activation or activity. Chondroitin-2,6-sulfate (CS-D) also did not enhance matrilysin activity, suggesting that the presentation of sulfates is more important than the overall degree of sulfation. Surface plasmon resonance demonstrated that promatrilysin bound heparin (KD, 400 nm) and CS-E (KD, 630 nm). Active matrilysin bound heparin (KD, 150 nm) but less so to CS-E (KD, 60 μm). Neither form bound heparan sulfate. These observations demonstrate that sulfated GAGs regulate matrilysin activation and its activity against specific substrates. PMID:19654318

Sleep, consciousness and the spontaneous and evoked electrical activity of the brain. Is there a cortical integrating mechanism?

PubMed

Evans, B M

2003-02-01

The physiological mechanisms that underlie consciousness and unconsciousness are the sleep/wake mechanisms. Deep sleep is a state of physiological reversible unconsciousness. The change from that state to wakefulness is mediated by the reticular activating mechanism. The reverse change from wakefulness to sleep is also an active process effected by an arousal inhibitory mechanism based on a partial blockade of the thalamus and upper brain stem, associated with thalamic sleep spindles and also with cortical sub-delta activity (<1 Hz). The deactivation of the thalamus has been demonstrated both electrically and by positron emission tomography during deep sleep. Normally, wakefulness is associated with instant awareness (defined as the ability to integrate all sensory information from the external environment and the internal environment of the body). Awareness may be a function of the thalamo-cortical network in the cerebral hemispheres, which forms the final path of the sleep/wake mechanism. Anatomical and physiological studies suggest that there may be a double thalamo-cortical network; one relating to cortical and thalamic areas with specific functions and the other global, involving all cortical areas and so-called 'non-specific' thalamic nuclei. The global system might function as a cortical integrating mechanism permitting the spread of information between the specific cortical areas and thus underlying awareness. The global system may also be responsible for much of the spontaneous and evoked electrical activity of the brain. The cognitive change between sleep and wakefulness is accompanied by changes in the autonomic system, the cerebral blood flow and cerebral metabolism. Awareness is an essential component of total consciousness (defined as continuous awareness of the external and internal environment, both past and present, together with the emotions arising from it). In addition to awareness, full consciousness requires short-term and explicit memory and intact emotional responses.

[The hypothalamic syndrome in childhood (its epidemiological and clinico-electrophysiological aspects)].

PubMed

Solov'eva, A D; Vorob'eva, O V; Loseva, M M; Khaspekova, N B; Fedorova, V I; Musaeva, Z A; Filatova, E G

1994-01-01

The epidemiological survey covered 2000 city schoolchildren. They ranged in age from 7 to 15 years. Hypothalamic deficiency (HD) was detected in 5% of the examinees. Clinical and physiological findings on HD children are provided. They were found to have the history of hereditary or natal damage evidencing the acquired nature of the disease. Special emphasis is placed on HD manifestations in prepubertal and pubertal age. The authors show defective regulation of nonspecific brain systems in the form of predominant activation of the septohippocampal system and relative insufficiency of the brain stem mesencephalic reticular formation. Activation of cerebral ergotropic vegetative mechanisms combines with peripheral vegetative failure (sympathetic and parasympathetic), probably, of congenital origin.

The β1 Subunit Enhances Oxidative Regulation of Large-Conductance Calcium-activated K+ Channels

PubMed Central

Santarelli, Lindsey Ciali; Chen, Jianguo; Heinemann, Stefan H.; Hoshi, Toshinori

2004-01-01

Oxidative stress may alter the functions of many proteins including the Slo1 large conductance calcium-activated potassium channel (BKCa). Previous results demonstrated that in the virtual absence of Ca2+, the oxidant chloramine-T (Ch-T), without the involvement of cysteine oxidation, increases the open probability and slows the deactivation of BKCa channels formed by human Slo1 (hSlo1) α subunits alone. Because native BKCa channel complexes may include the auxiliary subunit β1, we investigated whether β1 influences the oxidative regulation of hSlo1. Oxidation by Ch-T with β1 present shifted the half-activation voltage much further in the hyperpolarizing direction (−75 mV) as compared with that with α alone (−30 mV). This shift was eliminated in the presence of high [Ca2+]i, but the increase in open probability in the virtual absence of Ca2+ remained significant at physiologically relevant voltages. Furthermore, the slowing of channel deactivation after oxidation was even more dramatic in the presence of β1. Oxidation of cysteine and methionine residues within β1 was not involved in these potentiated effects because expression of mutant β1 subunits lacking cysteine or methionine residues produced results similar to those with wild-type β1. Unlike the results with α alone, oxidation by Ch-T caused a significant acceleration of channel activation only when β1 was present. The β1 M177 mutation disrupted normal channel activation and prevented the Ch-T–induced acceleration of activation. Overall, the functional effects of oxidation of the hSlo1 pore-forming α subunit are greatly amplified by the presence of β1, which leads to the additional increase in channel open probability and the slowing of deactivation. Furthermore, M177 within β1 is a critical structural determinant of channel activation and oxidative sensitivity. Together, the oxidized BKCa channel complex with β1 has a considerable chance of being open within the physiological voltage range even at low [Ca2+]i. PMID:15452197

Physician Education: Apoptosis.

PubMed

Kataoka; Tsuruo

1996-01-01

We have come to understand apoptosis as not merely a single form of cell death, but as a fundamental theme in cell biology that has far-reaching implications in the fields of physiology and pathology. At the present time, however, the mechanism of apoptosis is not clearly understood, as research into apoptosis is still at the initial stages. Nevertheless, the links between apoptosis and a variety of pathological conditions are gradually becoming clearer. In this article, we will provide a simple explanation of apoptosis and its mechanism as a novel concept of cell death and discuss the way in which apoptosis has been linked to a variety of pathological conditions. WHAT IS APOPTOSIS?: In normal tissue, cells that are no longer needed are rapidly eliminated without affecting the overall function of the tissue. In this process cells undergo an active and spontaneous suicide called programmed cell death. In fact, the majority of physiological cell deaths take the form of apoptosis. The word apoptosis is used, in contrast to necrosis, to describe the situation in which a cell actively pursues a course toward death upon receiving certain stimuli [1]. The morphological changes of apoptosis found in most cell types first involve contraction in cell volume and condensation of the nucleus. When this happens the intracellular organelles such as the mitochondria retain their normal morphology. As apoptosis proceeds, blebbing of the plasma membrane occurs, and the nucleus becomes fragmented. Finally, the cell itself fragments to form apoptotic bodies that are engulfed by nearby phagocytes. With respect to biochemical changes, it is known that the chromosomes become fragmented into nucleosome units, and DNA forms characteristic ladder patterns when subjected to agarose gel electrophoresis. MECHANISM OF APOPTOSIS: It has been reported that apoptosis is induced in various cells by many kinds of irritations, but the precise mechanism is still unclear. Cell injuries that induce apoptosis include those that cause DNA damage such as radiation and anticancer drugs, those that are mediated by the TNF receptor and Fas receptor (the so-called "death signal receptors"), and the deprivation of cytokines that supply survival signals such as IL-3 and erythropoietin. The tumor suppressor gene p53 plays a very important role in apoptosis induced by damage to DNA. This has been demonstrated by studying resistance to apoptosis of cells derived from p53 knockout mice [2]. Other than the irritations that induce apoptosis, molecules that have been strongly implicated as major players in the drama of apoptosis include the Bcl-2 family proteins and the IL-1 converting enzyme (ICE) and its homolog proteases (caspase family). Both groups of proteins show homology with proteins that affect cell death in nematodes. It is believed that molecules that contribute to cell death have been well conserved in multicellular organisms all the way from the relatively primitive nematodes to mammals including humans. It was discovered that Bcl-2 suppressed apoptosis induced in IL-3 dependent cells by deprivation of IL-3 [3]. It has since become the gene around which apoptosis research revolves. Recently, it has become clear that cell death involving the Bcl-2 protein is under the control of similar proteins from the same family [4]. It is interesting that the phenomenon of cell death may be regulated by the balance of the molecules involved in it. APOPTOSIS ABNORMALITIES AND DISEASE: Physiological cell death plays a major role in the growth and permanent maintenance of the human body [5]. In the process of forming the nervous system, neurons that do not form proper connections die. Physiological cell death also accompanies the removal of virus-infected cells by cytotoxic T cells, the elimination of autoreactive immune cells, the formation of the gut, the reconstitution of cartilage and bone, etc. When physiological cell death that normally should occur is inhibited, inappropriate physiological cell death may occur that is harmful to the body and forms the basis of disease. For example, in patients with neural degenerative disorders such as Alzheimer's disease and Parkinson's disease, we can find premature cell death in a particular subset of neurons. The death of T cells in AIDS patients is also a form of physiological cell death. Inhibition of cell death in the immune system enables the survival of autoreactive B cells and T cells, and is therefore a cause of autoimmune disorders. Apoptosis has been particularly linked to cancer. Normal cells are programmed for death if they are subjected to many types of non-physiological stress such as anticancer drugs or radiation, if they become isolated from surrounding cells and are unable to receive their tissue-specific survival signals [6], or if oncogenes are expressed haphazardly [7]. On the other hand, it is believed that the ability to survive is enhanced in transformed cancer cells because they are more resistant to apoptosis, they exhibit resistance to anticancer drugs, they are no longer dependent on survival signals, and they can metastasize. Therefore, the cancer progresses as the cancer cells maintain the proliferative superiority they acquire from their oncogenes. In other words, when cancer cells become resistant to apoptosis, they become resistant to treatment, metastasize, and proliferate destructively. The concept that the malignancy of cancer is due to its resistance to apoptosis is a relatively new one and is worthy of further study.

Biopharmaceutical considerations and characterizations in development of colon targeted dosage forms for inflammatory bowel disease.

PubMed

Malayandi, Rajkumar; Kondamudi, Phani Krishna; Ruby, P K; Aggarwal, Deepika

2014-04-01

Colon targeted dosage forms have been extensively studied for the localized treatment of inflammatory bowel disease. These dosage forms not only improve the therapeutic efficacy but also reduce the incidence of adverse drug reactions and hence improve the patient compliance. However, complex and highly variable gastro intestinal physiology limits the clinical success of these dosage forms. Biopharmaceutical characteristics of these dosage forms play a key role in rapid formulation development and ensure the clinical success. The complexity in product development and clinical success of colon targeted dosage forms are based on the biopharmaceutical characteristics such as physicochemical properties of drug substances, pharmaceutical characteristics of dosage form, physiological conditions and pharmacokinetic properties of drug substances as well as drug products. Various in vitro and in vivo techniques have been employed in past to characterize the biopharmaceutical properties of colon targeted dosage forms. This review focuses on the factors influencing the biopharmaceutical performances of the dosage forms, in vitro characterization techniques and in vivo studies.

The Protective Antigen Component of Anthrax Toxin Forms Functional Octameric Complexes

PubMed Central

Kintzer, Alexander F.; Thoren, Katie L.; Sterling, Harry J.; Dong, Ken C.; Feld, Geoffrey K.; Tang, Iok I.; Zhang, Teri T.; Williams, Evan R.; Berger, James M.; Krantz, Bryan A.

2009-01-01

The assembly of bacterial toxins and virulence factors is critical to their function, but the regulation of assembly during infection has not been studied. We begin to address this question using anthrax toxin as a model. The protective antigen (PA) component of the toxin assembles into ring-shaped homooligomers that bind the two other enzyme components of the toxin, lethal factor (LF) and edema factor (EF), to form toxic complexes. To disrupt the host, these toxic complexes are endocytosed, such that the PA oligomer forms a membrane-spanning channel that LF and EF translocate through to enter the cytosol. We show using single-channel electrophysiology that PA channels contain two populations of conductance states, which correspond with two different PA pre-channel oligomers observed by electron microscopy—the well-described heptamer and a novel octamer. Mass spectrometry demonstrates that the PA octamer binds four LFs, and assembly routes leading to the octamer are populated with even-numbered, dimeric and tetrameric, PA intermediates. Both heptameric and octameric PA complexes can translocate LF and EF with similar rates and efficiencies. Here we also report a 3.2-Å crystal structure of the PA octamer. The octamer comprises ∼20−30% of the oligomers on cells, but outside of the cell, the octamer is more stable than the heptamer under physiological pH. Thus the PA octamer is a physiological, stable, and active assembly state capable of forming lethal toxins that may withstand the hostile conditions encountered in the bloodstream. This assembly mechanism may provide a novel means to control cytotoxicity. PMID:19627991

The Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels: from Biophysics to Pharmacology of a Unique Family of Ion Channels.

PubMed

Sartiani, Laura; Mannaioni, Guido; Masi, Alessio; Novella Romanelli, Maria; Cerbai, Elisabetta

2017-10-01

Hyperpolarization-activated, cyclic nucleotide-gated (HCN) channels are important members of the voltage-gated pore loop channels family. They show unique features: they open at hyperpolarizing potential, carry a mixed Na/K current, and are regulated by cyclic nucleotides. Four different isoforms have been cloned (HCN1-4) that can assemble to form homo- or heterotetramers, characterized by different biophysical properties. These proteins are widely distributed throughout the body and involved in different physiologic processes, the most important being the generation of spontaneous electrical activity in the heart and the regulation of synaptic transmission in the brain. Their role in heart rate, neuronal pacemaking, dendritic integration, learning and memory, and visual and pain perceptions has been extensively studied; these channels have been found also in some peripheral tissues, where their functions still need to be fully elucidated. Genetic defects and altered expression of HCN channels are linked to several pathologies, which makes these proteins attractive targets for translational research; at the moment only one drug (ivabradine), which specifically blocks the hyperpolarization-activated current, is clinically available. This review discusses current knowledge about HCN channels, starting from their biophysical properties, origin, and developmental features, to (patho)physiologic role in different tissues and pharmacological modulation, ending with their present and future relevance as drug targets. Copyright © 2017 by The American Society for Pharmacology and Experimental Therapeutics.

Acoustic sensor array extracts physiology during movement

NASA Astrophysics Data System (ADS)

Scanlon, Michael V.

2001-08-01

An acoustic sensor attached to a person's neck can extract heart and breath sounds, as well as voice and other physiology related to their health and performance. Soldiers, firefighters, law enforcement, and rescue personnel, as well as people at home or in health care facilities, can benefit form being remotely monitored. ARLs acoustic sensor, when worn around a person's neck, picks up the carotid artery and breath sounds very well by matching the sensor's acoustic impedance to that of the body via a gel pad, while airborne noise is minimized by an impedance mismatch. Although the physiological sounds have high SNR, the acoustic sensor also responds to motion-induced artifacts that obscure the meaningful physiology. To exacerbate signal extraction, these interfering signals are usually covariant with the heart sounds, in that as a person walks faster the heart tends to beat faster, and motion noises tend to contain low frequency component similar to the heart sounds. A noise-canceling configuration developed by ARL uses two acoustic sensor on the front sides of the neck as physiology sensors, and two additional acoustic sensor on the back sides of the neck as noise references. Breath and heart sounds, which occur with near symmetry and simultaneously at the two front sensor, will correlate well. The motion noise present on all four sensor will be used to cancel the noise on the two physiology sensors. This report will compare heart rate variability derived from both the acoustic array and from ECG data taken simultaneously on a treadmill test. Acoustically derived breath rate and volume approximations will be introduced as well. A miniature 3- axis accelerometer on the same neckband provides additional noise references to validate footfall and motion activity.

Short-Chain Fatty Acid Acetate Stimulates Adipogenesis and Mitochondrial Biogenesis via GPR43 in Brown Adipocytes.

PubMed

Hu, Jiamiao; Kyrou, Ioannis; Tan, Bee K; Dimitriadis, Georgios K; Ramanjaneya, Manjunath; Tripathi, Gyanendra; Patel, Vanlata; James, Sean; Kawan, Mohamed; Chen, Jing; Randeva, Harpal S

2016-05-01

Short-chain fatty acids play crucial roles in a range of physiological functions. However, the effects of short-chain fatty acids on brown adipose tissue have not been fully investigated. We examined the role of acetate, a short-chain fatty acid formed by fermentation in the gut, in the regulation of brown adipocyte metabolism. Our results show that acetate up-regulates adipocyte protein 2, peroxisomal proliferator-activated receptor-γ coactivator-1α, and uncoupling protein-1 expression and affects the morphological changes of brown adipocytes during adipogenesis. Moreover, an increase in mitochondrial biogenesis was observed after acetate treatment. Acetate also elicited the activation of ERK and cAMP response element-binding protein, and these responses were sensitive to G(i/o)-type G protein inactivator, Gβγ-subunit inhibitor, phospholipase C inhibitor, and MAPK kinase inhibitor, indicating a role for the G(i/o)βγ/phospholipase C/protein kinase C/MAPK kinase signaling pathway in these responses. These effects of acetate were mimicked by treatment with 4-chloro-α-(1-methylethyl)-N-2-thiazolylbenzeneacetamide, a synthetic G protein-coupled receptor 43 (GPR43) agonist and were impaired in GPR43 knockdown cells. Taken together, our results indicate that acetate may have important physiological roles in brown adipocytes through the activation of GPR43.

Zingiber officinale: Its antibacterial activity on Pseudomonas aeruginosa and mode of action evaluated by flow cytometry.

PubMed

Chakotiya, Ankita Singh; Tanwar, Ankit; Narula, Alka; Sharma, Rakesh Kumar

2017-06-01

Biofilm formation, low membrane permeability and efflux activity developed by Pseudomonas aeruginosa, play an important role in the mechanism of infection and antimicrobial resistance. In the present study we evaluate the antibacterial effect of Zingiber officinale against multi-drug resistant strain of P. aeruginosa. The study explores antibacterial efficacy and time-kill study concomitantly the effect of herbal extract on bacterial cell physiology with the use of flow cytometry and inhibition of biofilm formation. Z. officinale was found to inhibit the growth of P. aeruginosa, significantly. A major decline in the Colony Forming Units was observed with 3 log 10  at 12 h of treatment. Also it is found to affect the membrane integrity of the pathogen, as 70.06 ± 2.009% cells were found to stain with Propidium iodide. In case of efflux activity 86.9 ± 2.08% cells were found in Ethidium bromide positive region. Biofilm formation inhibition ability was found in the range of 68.13 ± 4.11% to 84.86 ± 2.02%. Z.officinale is effective for killing Multi-Drug Resistant P. aeruginosa clinical isolate by affecting the cellular physiology and inhibiting the biofilm formation. Copyright © 2017 Elsevier Ltd. All rights reserved.

Differential and Conditional Activation of PKC-Isoforms Dictates Cardiac Adaptation during Physiological to Pathological Hypertrophy

PubMed Central

Naskar, Shaon; Datta, Kaberi; Mitra, Arkadeep; Pathak, Kanchan; Datta, Ritwik; Bansal, Trisha; Sarkar, Sagartirtha

2014-01-01

A cardiac hypertrophy is defined as an increase in heart mass which may either be beneficial (physiological hypertrophy) or detrimental (pathological hypertrophy). This study was undertaken to establish the role of different protein kinase-C (PKC) isoforms in the regulation of cardiac adaptation during two types of cardiac hypertrophy. Phosphorylation of specific PKC-isoforms and expression of their downstream proteins were studied during physiological and pathological hypertrophy in 24 week male Balb/c mice (Mus musculus) models, by reverse transcriptase-PCR, western blot analysis and M-mode echocardiography for cardiac function analysis. PKC-δ was significantly induced during pathological hypertrophy while PKC-α was exclusively activated during physiological hypertrophy in our study. PKC-δ activation during pathological hypertrophy resulted in cardiomyocyte apoptosis leading to compromised cardiac function and on the other hand, activation of PKC-α during physiological hypertrophy promoted cardiomyocyte growth but down regulated cellular apoptotic load resulting in improved cardiac function. Reversal in PKC-isoform with induced activation of PKC-δ and simultaneous inhibition of phospho-PKC-α resulted in an efficient myocardium to deteriorate considerably resulting in compromised cardiac function during physiological hypertrophy via augmentation of apoptotic and fibrotic load. This is the first report where PKC-α and -δ have been shown to play crucial role in cardiac adaptation during physiological and pathological hypertrophy respectively thereby rendering compromised cardiac function to an otherwise efficient heart by conditional reversal of their activation. PMID:25116170

GDF3 is a BMP inhibitor that can activate Nodal signaling only at very high doses

PubMed Central

Levine, Ariel J.; Levine, Zachary J.; Brivanlou, Ali H.

2013-01-01

Within the TGF-β superfamily, there are approximately forty ligands divided into two major branches: the TGF-β/Activin/Nodal ligands and the BMP/GDF ligands. We studied the ligand GDF3 and found that it inhibits signaling by its co-family members, the BMPs; however, GDF3 has been described by others to have Nodal-like activity. Here, we show that GDF3 can activate Nodal signaling, but only at very high doses and only upon mRNA over-expression. In contrast, GDF3 inhibits BMP signaling upon over-expression of GDF3 mRNA, as recombinant protein, and regardless of its dose. We therefore further characterized the mechanism through which GDF3 protein acts as a specific BMP inhibitor and found that the BMP inhibitory activity of GDF3 resides redundantly in the unprocessed, predominant form and in the mature form of the protein. These results confirm and extend the activity that we described for GDF3 and illuminate the experimental basis for the different observations of others. We suggest that GDF3 is either a bi-functional TGF-β ligand, or, more likely, that it is a BMP inhibitor that can artificially activate Nodal signaling under non-physiological conditions. PMID:18823971

Turn-Directed α-β Conformational Transition of α-syn12 Peptide at Different pH Revealed by Unbiased Molecular Dynamics Simulations

PubMed Central

Liu, Lei; Cao, Zanxia

2013-01-01

The transition from α-helical to β-hairpin conformations of α-syn12 peptide is characterized here using long timescale, unbiased molecular dynamics (MD) simulations in explicit solvent models at physiological and acidic pH values. Four independent normal MD trajectories, each 2500 ns, are performed at 300 K using the GROMOS 43A1 force field and SPC water model. The most clustered structures at both pH values are β-hairpin but with different turns and hydrogen bonds. Turn9-6 and four hydrogen bonds (HB9-6, HB6-9, HB11-4 and HB4-11) are formed at physiological pH; turn8-5 and five hydrogen bonds (HB8-5, HB5-8, HB10-3, HB3-10 and HB12-1) are formed at acidic pH. A common folding mechanism is observed: the formation of the turn is always before the formation of the hydrogen bonds, which means the turn is always found to be the major determinant in initiating the transition process. Furthermore, two transition paths are observed at physiological pH. One of the transition paths tends to form the most-clustered turn and improper hydrogen bonds at the beginning, and then form the most-clustered hydrogen bonds. Another transition path tends to form the most-clustered turn, and turn5-2 firstly, followed by the formation of part hydrogen bonds, then turn5-2 is extended and more hydrogen bonds are formed. The transition path at acidic pH is as the same as the first path described at physiological pH. PMID:23708094

A Highly Toxic Cellular Prion Protein Induces a Novel, Nonapoptotic Form of Neuronal Death

PubMed Central

Christensen, Heather M.; Dikranian, Krikor; Li, Aimin; Baysac, Kathleen C.; Walls, Ken C.; Olney, John W.; Roth, Kevin A.; Harris, David A.

2010-01-01

Several different deletions within the N-terminal tail of the prion protein (PrP) induce massive neuronal death when expressed in transgenic mice. This toxicity is dose-dependently suppressed by coexpression of full-length PrP, suggesting that it results from subversion of a normal physiological activity of cellular PrP. We performed a combined biochemical and morphological analysis of Tg(ΔCR) mice, which express PrP carrying a 21-aa deletion (residues 105-125) within a highly conserved region of the protein. Death of cerebellar granule neurons in Tg(ΔCR) mice is not accompanied by activation of either caspase-3 or caspase-8 or by increased levels of the autophagy marker, LC3-II. In electron micrographs, degenerating granule neurons displayed a unique morphology characterized by heterogeneous condensation of the nuclear matrix without formation of discrete chromatin masses typical of neuronal apoptosis. Our data demonstrate that perturbations in PrP functional activity induce a novel, nonapoptotic, nonautophagic form of neuronal death whose morphological features are reminiscent of those associated with excitotoxic stress. PMID:20472884

WAVE2 Forms a Complex with PKA and Is Involved in PKA Enhancement of Membrane Protrusions*

PubMed Central

Yamashita, Hiroshi; Ueda, Kazumitsu; Kioka, Noriyuki

2011-01-01

PKA contributes to many physiological processes, including glucose homeostasis and cell migration. The substrate specificity of PKA is low compared with other kinases; thus, complex formation with A-kinase-anchoring proteins is important for the localization of PKA in specific subcellular regions and the phosphorylation of specific substrates. Here, we show that PKA forms a complex with WAVE2 (Wiskott-Aldrich syndrome protein family verprolin-homologous protein 2) in MDA-MB-231 breast cancer cells and mouse brain extracts. Two separate regions of WAVE2 are involved in WAVE2-PKA complex formation. This complex localizes to the leading edge of MDA-MB-231 cells. PKA activation results in enlargement of the membrane protrusion. WAVE2 depletion impairs PKA localization at membrane protrusions and the enlargement of membrane protrusion induced by PKA activation. Together, these results suggest that WAVE2 works as an A-kinase-anchoring protein that recruits PKA at membrane protrusions and plays a role in the enlargement of membrane protrusions induced by PKA activation. PMID:21119216

Production and Physiological Effects of Hydrogen Sulfide

PubMed Central

2014-01-01

Abstract Significance: Hydrogen sulfide (H2S) has been recognized as a physiological mediator with a variety of functions. It regulates synaptic transmission, vascular tone, inflammation, transcription, and angiogenesis; protects cells from oxidative stress and ischemia-reperfusion injury; and promotes healing of ulcers. Recent Advances: In addition to cystathionine β-synthase and cystathionine γ-lyase, 3-mercaptopyruvate sulfurtransferase along with cysteine aminotransferase was recently demonstrated to produce H2S. Even in bacteria, H2S produced by these enzymes functions as a defense against antibiotics, suggesting that the cytoprotective effect of H2S is a universal defense mechanism in organisms from bacteria to mammals. Critical Issues: The functional form of H2S—undissociated H2S gas, dissociated HS ion, or some other form of sulfur—has not been identified. Future Directions: The regulation of H2S production by three enzymes may lead to the identification of the physiological signals that are required to release H2S. The identification of the physiological functions of other forms of sulfur may also help understand the biological significance of H2S. Antioxid. Redox Signal. 20, 783–793. PMID:23581969

[Cellular and intracellular transport of vitamin C. The physiologic aspects].

PubMed

Szarka, András; Lőrincz, Tamás

2013-10-20

Vitamin C requirement is satisfied by natural sources and vitamin C supplements in the ordinary human diet. The two major forms of vitamin C in the diet are L-ascorbic acid and L-dehydroascorbic acid. Both ascorbate and dehydroascorbate are absorbed along the entire length of the human intestine. The reduced form, L-ascorbic acid is imported by an active mechanism, requiring two sodium-dependent vitamin C transporters (SVCT1 and SVCT2). The transport of the oxidized form, dehydroascorbate is mediated by glucose transporters GLUT1, GLUT3 and possibly GLUT4. Initial rate of uptake of both ascorbate and dehydroascorbate is saturable with increasing external substrate concentration. Vitamin C plasma concentrations are tightly controlled when the vitamin is taken orally. It has two simple reasons, on the one hand, the capacity of the transporters is limited, on the other hand the two Na+-dependent transporters can be down-regulated by an elevated level of ascorbate.

[Role of nitric oxide as a regulator of cell processes in the formation of multiple organ failure].

PubMed

Riabov, G A; Azisov, Iu M

2001-01-01

Main aspects of functional activity of nitric oxide (NO) are discussed. Physicochemical properties of NO, routes of its formation in man, and mechanism of its effects on physiological processes are described. In human body NO is formed as a result of activity of a specific enzyme, nitric oxide synthase. Three isoforms of the enzyme are known: neuronal, inducible, and endothelial. NO regulates vascular tone, cell adhesion, neurotransmission, bronchodilatation, and platelet aggregation. NO can protect and damage cells under different conditions. The effect of NO can be direct and mediated. Mechanisms of vasodilating effect of NO and of its effect on apoptosis are discussed. The role of NO in regulation of the functional activity of hepatocytes is described. Regulation of NO level in human organism is discussed.

An N-terminally truncated form of cyclic GMP-dependent protein kinase Iα (PKG Iα) is monomeric and autoinhibited and provides a model for activation.

PubMed

Moon, Thomas M; Sheehe, Jessica L; Nukareddy, Praveena; Nausch, Lydia W; Wohlfahrt, Jessica; Matthews, Dwight E; Blumenthal, Donald K; Dostmann, Wolfgang R

2018-05-25

The type I cGMP-dependent protein kinases (PKG I) serve essential physiological functions, including smooth muscle relaxation, cardiac remodeling, and platelet aggregation. These enzymes form homodimers through their N-terminal dimerization domains, a feature implicated in regulating their cooperative activation. Previous investigations into the activation mechanisms of PKG I isoforms have been largely influenced by structures of the cAMP-dependent protein kinase (PKA). Here, we examined PKG Iα activation by cGMP and cAMP by engineering a monomeric form that lacks N-terminal residues 1-53 (Δ53). We found that the construct exists as a monomer as assessed by whole-protein MS, size-exclusion chromatography, and small-angle X-ray scattering (SAXS). Reconstruction of the SAXS 3D envelope indicates that Δ53 has a similar shape to the heterodimeric RIα-C complex of PKA. Moreover, we found that the Δ53 construct is autoinhibited in its cGMP-free state and can bind to and be activated by cGMP in a manner similar to full-length PKG Iα as assessed by surface plasmon resonance (SPR) spectroscopy. However, we found that the Δ53 variant does not exhibit cooperative activation, and its cyclic nucleotide selectivity is diminished. These findings support a model in which, despite structural similarities, PKG Iα activation is distinct from that of PKA, and its cooperativity is driven by in trans interactions between protomers. © 2018 by The American Society for Biochemistry and Molecular Biology, Inc.

New scientific challenges - the possibilities of using selenium in poultry nutrition and impact on meat quality

NASA Astrophysics Data System (ADS)

Marković, R.; Glišić, M.; Bošković, M.; Baltić, M. Ž.

2017-09-01

Physiological stress is one of many concerns facing modern broiler production. In conditions when birds are exposed to stress, supplementation of selenium, which is a crucial glutathione peroxidase enzymatic cofactor, increases the antioxidant capacity of the animals and decreases the harmful effects of free radicals. Dietary selenium improves production performance and health of animals, and positively affects the immune system, the quality, selenium content and fatty acid composition of meat and eggs. There are several different forms of selenium, the most common dietary supplements being an inorganic form (sodium selenite) and anorganic form (selenomethionine). However, in recent years, new forms of selenium, such as a 2-hydroxy-4-methylselenobutanoic acid (HMSeBA) and nanoselenium, which have more bioavailability, bioefficacy, and low toxicity have been designed. In this short comparative overview discusses the effects of inorganic, organic and nanoforms of selenium on production results, glutathione peroxidase activity, meat quality and level of toxicity in poultry.

Cannabis: old medicine with new promise for neurological disorders.

PubMed

Carter, Gregory T; Weydt, Patrick

2002-03-01

Marijuana is a complex substance containing over 60 different forms of cannabinoids, the active ingredients. Cannabinoids are now known to have the capacity for neuromodulation, via direct, receptor-based mechanisms at numerous levels within the nervous system. These have therapeutic properties that may be applicable to the treatment of neurological disorders; including anti-oxidative, neuroprotective, analgesic and anti-inflammatory actions; immunomodulation, modulation of glial cells and tumor growth regulation. This article reviews the emerging research on the physiological mechanisms of endogenous and exogenous cannabinoids in the context of neurological disease.

Endocannabinoid signaling in reward and addiction

PubMed Central

Parsons, Loren H.; Hurd, Yasmin L.

2015-01-01

Brain endocannabinoid signaling influences the motivation for natural rewards (such as palatable food, sexual activity and social interaction) and modulates the rewarding effects of addictive drugs. Pathological forms of natural and drug-induced reward are associated with dysregulated endocannabinoid signaling that may derive from pre-existing genetic factors or from prolonged drug exposure. Impaired endocannabinoid signaling contributes to dysregulated synaptic plasticity, increased stress responsivity, negative emotional states, and craving that propel addiction. Understanding the contributions of endocannabinoid disruptions to behavioral and physiological traits provides insight into the endocannabinoid influence on addiction vulnerability. PMID:26373473

Motor stereotypies.

PubMed

Singer, Harvey S

2009-06-01

Stereotypic movements are ubiquitous, occur in a variety of forms, and exist in different populations, ranging from individuals with autism to typically developing children. Although such movements are required to be restricted, repetitive, and purposeless, their definition and included activities remain broad and imprecise. Movements are typically classified into 2 groups, primary (physiological) and secondary (pathological), depending upon the presence of additional signs or symptoms. Although some view these movements as behaviors produced to alter a state of arousal, there is increasing evidence to support a neurobiological mechanism. Behavioral and pharmacological therapies have been used with varying effect.

Sequence and functional characterization of hypoxia-inducible factors, HIF1α, HIF2αa, and HIF3α, from the estuarine fish, Fundulus heteroclitus.

PubMed

Townley, Ian K; Karchner, Sibel I; Skripnikova, Elena; Wiese, Thomas E; Hahn, Mark E; Rees, Bernard B

2017-03-01

The hypoxia-inducible factor (HIF) family of transcription factors plays central roles in the development, physiology, pathology, and environmental adaptation of animals. Because many aquatic habitats are characterized by episodes of low dissolved oxygen, fish represent ideal models to study the roles of HIF in the response to aquatic hypoxia. The estuarine fish Fundulus heteroclitus is found in habitats prone to hypoxia. It responds to low oxygen via behavioral, physiological, and molecular changes, and one member of the HIF family, HIF2α, has been previously described. Herein, cDNA sequencing, phylogenetic analyses, and genomic approaches were used to determine other members of the HIFα family from F. heteroclitus and their relationships to HIFα subunits from other vertebrates. In vitro and cellular approaches demonstrated that full-length forms of HIF1α, HIF2α, and HIF3α independently formed complexes with the β-subunit, aryl hydrocarbon receptor nuclear translocator, to bind to hypoxia response elements and activate reporter gene expression. Quantitative PCR showed that HIFα mRNA abundance varied among organs of normoxic fish in an isoform-specific fashion. Analysis of the F. heteroclitus genome revealed a locus encoding a second HIF2α-HIF2αb-a predicted protein lacking oxygen sensing and transactivation domains. Finally, sequence analyses demonstrated polymorphism in the coding sequence of each F. heteroclitus HIFα subunit, suggesting that genetic variation in these transcription factors may play a role in the variation in hypoxia responses among individuals or populations. Copyright © 2017 the American Physiological Society.

Potato (Solanum tuberosum L.) tuber ageing induces changes in the proteome and antioxidants associated with the sprouting pattern.

PubMed

Delaplace, Pierre; Fauconnier, Marie-Laure; Sergeant, Kjell; Dierick, Jean-François; Oufir, Mouhssin; van der Wal, Froukje; America, Antoine H P; Renaut, Jenny; Hausman, Jean-François; du Jardin, Patrick

2009-01-01

During post-harvest storage, potato tubers age as they undergo an evolution of their physiological state influencing their sprouting pattern. In the present study, physiological and biochemical approaches were combined to provide new insights on potato (Solanum tuberosum L. cv. Désirée) tuber ageing. An increase in the physiological age index (PAI) value from 0.14 to 0.83 occurred during storage at 4 degrees C over 270 d. Using this reference frame, a proteomic approach was followed based on two-dimensional electrophoresis. In the experimental conditions of this study, a marked proteolysis of patatin occurred after the PAI reached a value of 0.6. In parallel, several glycolytic enzymes were up-regulated and cellular components influencing protein conformation and the response to stress were altered. The equilibrium between the 20S and 26S forms of the proteasome was modified, the 20S form that recycles oxidized proteins being up-regulated. Two proteins belonging to the cytoskeleton were also differentially expressed during ageing. As most of these changes are also observed in an oxidative stress context, an approach focused on antioxidant compounds and enzymes as well as oxidative damage on polyunsaturated fatty acids and proteins was conducted. All the changes observed during ageing seemed to allow the potato tubers to maintain their radical scavenging activity until the end of the storage period as no accumulation of oxidative damage was observed. These data are interpreted considering the impact of reactive oxygen species on the development and the behaviour of other plant systems undergoing ageing or senescence processes.

ADP-ribosylation by cholera toxin: functional analysis of a cellular system that stimulates the enzymic activity of cholera toxin fragment A/sub 1/

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

Gill, D.M.; Coburn, J.

1987-10-06

The authors have clarified relationships between cholera toxin, cholera toxin substrates, a membrane protein S that is required for toxin activity, and a soluble protein CF that is needed for the function of S. The toxin has little intrinsic ability to catalyze ADP-ribosylations unless it encounters the active form of the S protein, which is S liganded to GTP or to a GTP analogue. In the presence of CF, S x GTP forms readily, though reversibly, but a more permanent active species, S-guanosine 5'-O-(3-thiotriphosphate) (S x GTP..gamma..S), forms over a period of 10-15 min at 37/sup 0/C. Both guanosine 5'-O-(2-thiodiphosphate)more » and GTP block this quasi-permanent activation. Some S x GTP..gamma..S forms in membranes that are exposed to CF alone and then to GTP..gamma..S, with a wash in between, and it is possible that CF facilitates a G nucleotide exchange. S x GTP..gamma..S dissolved by nonionic detergents persists in solution and can be used to support the ADP-ribosylation of nucleotide-free substrates. In this circumstance, added guanyl nucleotides have no further effect. This active form of S is unstable, especially when heated, but the thermal inactivation above 45/sup 0/C is decreased by GTP..gamma..S. Active S is required equally for the ADP-ribosylation of all of cholera toxin's protein substrates, regardless of whether they bind GTP or not. They suggest that active S interacts directly with the enzymic A/sub 1/ fragments of cholera toxin and not with any toxin substrate. The activation and activity of S are independent of the state, or even the presence, of adenylate cyclase and seem to be involved with the cyclase system only via cholera toxin. S is apparently not related by function to certain other GTP binding proteins, including p21/sup ras/, and appears to be a new GTP binding protein whose physiologic role remains to be identified.« less

Complement activation by ligand-driven juxtaposition of discrete pattern recognition complexes

PubMed Central

Degn, Søren E.; Kjaer, Troels R.; Kidmose, Rune T.; Jensen, Lisbeth; Hansen, Annette G.; Tekin, Mustafa; Jensenius, Jens C.; Andersen, Gregers R.; Thiel, Steffen

2014-01-01

Defining mechanisms governing translation of molecular binding events into immune activation is central to understanding immune function. In the lectin pathway of complement, the pattern recognition molecules (PRMs) mannan-binding lectin (MBL) and ficolins complexed with the MBL-associated serine proteases (MASP)-1 and MASP-2 cleave C4 and C2 to generate C3 convertase. MASP-1 was recently found to be the exclusive activator of MASP-2 under physiological conditions, yet the predominant oligomeric forms of MBL carry only a single MASP homodimer. This prompted us to investigate whether activation of MASP-2 by MASP-1 occurs through PRM-driven juxtaposition on ligand surfaces. We demonstrate that intercomplex activation occurs between discrete PRM/MASP complexes. PRM ligand binding does not directly escort the transition of MASP from zymogen to active enzyme in the PRM/MASP complex; rather, clustering of PRM/MASP complexes directly causes activation. Our results support a clustering-based mechanism of activation, fundamentally different from the conformational model suggested for the classical pathway of complement. PMID:25197071

Digital Health: Tracking Physiomes and Activity Using Wearable Biosensors Reveals Useful Health-Related Information

PubMed Central

Zhou, Gao; Zhou, Wenyu; Schüssler-Fiorenza Rose, Sophia Miryam; Perelman, Dalia; Colbert, Elizabeth; Runge, Ryan; Rego, Shannon; Sonecha, Ria; Datta, Somalee; McLaughlin, Tracey; Snyder, Michael P.

2017-01-01

A new wave of portable biosensors allows frequent measurement of health-related physiology. We investigated the use of these devices to monitor human physiological changes during various activities and their role in managing health and diagnosing and analyzing disease. By recording over 250,000 daily measurements for up to 43 individuals, we found personalized circadian differences in physiological parameters, replicating previous physiological findings. Interestingly, we found striking changes in particular environments, such as airline flights (decreased peripheral capillary oxygen saturation [SpO2] and increased radiation exposure). These events are associated with physiological macro-phenotypes such as fatigue, providing a strong association between reduced pressure/oxygen and fatigue on high-altitude flights. Importantly, we combined biosensor information with frequent medical measurements and made two important observations: First, wearable devices were useful in identification of early signs of Lyme disease and inflammatory responses; we used this information to develop a personalized, activity-based normalization framework to identify abnormal physiological signals from longitudinal data for facile disease detection. Second, wearables distinguish physiological differences between insulin-sensitive and -resistant individuals. Overall, these results indicate that portable biosensors provide useful information for monitoring personal activities and physiology and are likely to play an important role in managing health and enabling affordable health care access to groups traditionally limited by socioeconomic class or remote geography. PMID:28081144

"Physiology in the News": Using Press Releases to Enhance Lay Communication and Introduce Current Physiology Research to Undergraduates

ERIC Educational Resources Information Center

Kelly, Kevin L.; Poteracki, James M.; Steury, Michael D.; Wehrwein, Erica A.

2015-01-01

Michigan State University's senior-level undergraduate physiology capstone laboratory uses a simple exercise termed "Physiology in the News," to help students explore the current research within the field of physiology while also learning to communicate science in lay terms. "Physiology in the News" is an activity that charges…

The Structural Basis of IKs Ion-Channel Activation: Mechanistic Insights from Molecular Simulations.

PubMed

Ramasubramanian, Smiruthi; Rudy, Yoram

2018-06-05

Relating ion channel (iCh) structural dynamics to physiological function remains a challenge. Current experimental and computational techniques have limited ability to explore this relationship in atomistic detail over physiological timescales. A framework associating iCh structure to function is necessary for elucidating normal and disease mechanisms. We formulated a modeling schema that overcomes the limitations of current methods through applications of artificial intelligence machine learning. Using this approach, we studied molecular processes that underlie human IKs voltage-mediated gating. IKs malfunction underlies many debilitating and life-threatening diseases. Molecular components of IKs that underlie its electrophysiological function include KCNQ1 (a pore-forming tetramer) and KCNE1 (an auxiliary subunit). Simulations, using the IKs structure-function model, reproduced experimentally recorded saturation of gating-charge displacement at positive membrane voltages, two-step voltage sensor (VS) movement shown by fluorescence, iCh gating statistics, and current-voltage relationship. Mechanistic insights include the following: 1) pore energy profile determines iCh subconductance; 2) the entire protein structure, not limited to the pore, contributes to pore energy and channel subconductance; 3) interactions with KCNE1 result in two distinct VS movements, causing gating-charge saturation at positive membrane voltages and current activation delay; and 4) flexible coupling between VS and pore permits pore opening at lower VS positions, resulting in sequential gating. The new modeling approach is applicable to atomistic scale studies of other proteins on timescales of physiological function. Copyright © 2018 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Dynamical analysis of uterine cell electrical activity model.

PubMed

Rihana, S; Santos, J; Mondie, S; Marque, C

2006-01-01

The uterus is a physiological system consisting of a large number of interacting smooth muscle cells. The uterine excitability changes remarkably with time, generally quiescent during pregnancy, the uterus exhibits forceful synchronized contractions at term leading to fetus expulsion. These changes characterize thus a dynamical system susceptible of being studied through formal mathematical tools. Multiple physiological factors are involved in the regulation process of this complex system. Our aim is to relate the physiological factors to the uterine cell dynamic behaviors. Taking into account a previous work presented, in which the electrical activity of a uterine cell is described by a set of ordinary differential equations, we analyze the impact of physiological parameters on the response of the model, and identify the main subsystems generating the complex uterine electrical activity, with respect to physiological data.

PSYCHOSOCIAL INTERVENTION EFFECTS ON ADAPTATION, DISEASE COURSE AND BIOBEHAVIORAL PROCESSES IN CANCER

PubMed Central

Antoni, Michael H.

2012-01-01

A diagnosis of cancer and subsequent treatments place demands on psychological adaptation. Behavioral research suggests the importance of cognitive, behavioral, and social factors in facilitating adaptation during active treatment and throughout cancer survivorship, which forms the rationale for the use of many psychosocial interventions in cancer patients. This cancer experience may also affect physiological adaptation systems (e.g., neuroendocrine) in parallel with psychological adaptation changes (negative affect). Changes in adaptation may alter tumor growth-promoting processes (increased angiogenesis, migration and invasion, and inflammation) and tumor defense processes (decreased cellular immunity) relevant for cancer progression and the quality of life of cancer patients. Some evidence suggests that psychosocial intervention can improve psychological and physiological adaptation indicators in cancer patients. However, less is known about whether these interventions can influence tumor activity and tumor growth-promoting processes and whether changes in these processes could explain the psychosocial intervention effects on recurrence and survival documented to date. Documenting that psychosocial interventions can modulate molecular activities (e.g., transcriptional indicators of cell signaling) that govern tumor promoting and tumor defense processes on the one hand, and clinical disease course on the other is a key challenge for biobehavioral oncology research. This mini-review will summarize current knowledge on psychological and physiological adaptation processes affected throughout the stress of the cancer experience, and the effects of psychosocial interventions on psychological adaptation, cancer disease progression, and changes in stress-related biobehavioral processes that may mediate intervention effects on clinical cancer outcomes. Very recent intervention work in breast cancer will be used to illuminate emerging trends in molecular probes of interest in the hope of highlighting future paths that could move the field of biobehavioral oncology intervention research forward. PMID:22627072

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

PubMed Central

Mori, Tomohisa; Hayashi, Teruo

2012-01-01

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

Psychosocial intervention effects on adaptation, disease course and biobehavioral processes in cancer.

PubMed

Antoni, Michael H

2013-03-01

A diagnosis of cancer and subsequent treatments place demands on psychological adaptation. Behavioral research suggests the importance of cognitive, behavioral, and social factors in facilitating adaptation during active treatment and throughout cancer survivorship, which forms the rationale for the use of many psychosocial interventions in cancer patients. This cancer experience may also affect physiological adaptation systems (e.g., neuroendocrine) in parallel with psychological adaptation changes (negative affect). Changes in adaptation may alter tumor growth-promoting processes (increased angiogenesis, migration and invasion, and inflammation) and tumor defense processes (decreased cellular immunity) relevant for cancer progression and the quality of life of cancer patients. Some evidence suggests that psychosocial intervention can improve psychological and physiological adaptation indicators in cancer patients. However, less is known about whether these interventions can influence tumor activity and tumor growth-promoting processes and whether changes in these processes could explain the psychosocial intervention effects on recurrence and survival documented to date. Documenting that psychosocial interventions can modulate molecular activities (e.g., transcriptional indicators of cell signaling) that govern tumor promoting and tumor defense processes on the one hand, and clinical disease course on the other is a key challenge for biobehavioral oncology research. This mini-review will summarize current knowledge on psychological and physiological adaptation processes affected throughout the stress of the cancer experience, and the effects of psychosocial interventions on psychological adaptation, cancer disease progression, and changes in stress-related biobehavioral processes that may mediate intervention effects on clinical cancer outcomes. Very recent intervention work in breast cancer will be used to illuminate emerging trends in molecular probes of interest in the hope of highlighting future paths that could move the field of biobehavioral oncology intervention research forward. Copyright © 2012 Elsevier Inc. All rights reserved.

Aldo-keto reductase family 1 B10 protein detoxifies dietary and lipid-derived alpha, beta-unsaturated carbonyls at physiological levels.

PubMed

Zhong, Linlin; Liu, Ziwen; Yan, Ruilan; Johnson, Stephen; Zhao, Yupei; Fang, Xiubin; Cao, Deliang

2009-09-18

Alpha, beta-unsaturated carbonyls are highly reactive mutagens and carcinogens to which humans are exposed on a daily basis. This study demonstrates that aldo-keto reductase family 1 member B10 (AKR1B10) is a critical protein in detoxifying dietary and lipid-derived unsaturated carbonyls. Purified AKR1B10 recombinant protein efficiently catalyzed the reduction to less toxic alcohol forms of crotonaldehyde at 0.90 microM, 4-hydroxynonenal (HNE) at 0.10 microM, trans-2-hexanal at 0.10 microM, and trans-2,4-hexadienal at 0.05 microM, the concentrations at or lower than physiological exposures. Ectopically expressed AKR1B10 in 293T cells eliminated immediately HNE at 1 (subtoxic) or 5 microM (toxic) by converting to 1,4-dihydroxynonene, protecting the cells from HNE toxicity. AKR1B10 protein also showed strong enzymatic activity toward glutathione-conjugated carbonyls. Taken together, our study results suggest that AKR1B10 specifically expressed in the intestine is physiologically important in protecting the host cell against dietary and lipid-derived cytotoxic carbonyls.

Aldo-keto reductase family 1 B10 protein detoxifies dietary and lipid-derived alpha, beta-unsaturated carbonyls at physiological levels

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

Zhong, Linlin; Department of Neurobiology and Anatomy, China Medical University, Shenyang 110001; Liu, Ziwen

2009-09-18

Alpha, beta-unsaturated carbonyls are highly reactive mutagens and carcinogens to which humans are exposed on a daily basis. This study demonstrates that aldo-keto reductase family 1 member B10 (AKR1B10) is a critical protein in detoxifying dietary and lipid-derived unsaturated carbonyls. Purified AKR1B10 recombinant protein efficiently catalyzed the reduction to less toxic alcohol forms of crotonaldehyde at 0.90 {mu}M, 4-hydroxynonenal (HNE) at 0.10 {mu}M, trans-2-hexanal at 0.10 {mu}M, and trans-2,4-hexadienal at 0.05 {mu}M, the concentrations at or lower than physiological exposures. Ectopically expressed AKR1B10 in 293T cells eliminated immediately HNE at 1 (subtoxic) or 5 {mu}M (toxic) by converting to 1,4-dihydroxynonene,more » protecting the cells from HNE toxicity. AKR1B10 protein also showed strong enzymatic activity toward glutathione-conjugated carbonyls. Taken together, our study results suggest that AKR1B10 specifically expressed in the intestine is physiologically important in protecting the host cell against dietary and lipid-derived cytotoxic carbonyls.« less

Compact continuum brain model for human electroencephalogram

NASA Astrophysics Data System (ADS)

Kim, J. W.; Shin, H.-B.; Robinson, P. A.

2007-12-01

A low-dimensional, compact brain model has recently been developed based on physiologically based mean-field continuum formulation of electric activity of the brain. The essential feature of the new compact model is a second order time-delayed differential equation that has physiologically plausible terms, such as rapid corticocortical feedback and delayed feedback via extracortical pathways. Due to its compact form, the model facilitates insight into complex brain dynamics via standard linear and nonlinear techniques. The model successfully reproduces many features of previous models and experiments. For example, experimentally observed typical rhythms of electroencephalogram (EEG) signals are reproduced in a physiologically plausible parameter region. In the nonlinear regime, onsets of seizures, which often develop into limit cycles, are illustrated by modulating model parameters. It is also shown that a hysteresis can occur when the system has multiple attractors. As a further illustration of this approach, power spectra of the model are fitted to those of sleep EEGs of two subjects (one with apnea, the other with narcolepsy). The model parameters obtained from the fittings show good matches with previous literature. Our results suggest that the compact model can provide a theoretical basis for analyzing complex EEG signals.

[THE STATUS OF CERTAIN PHYSIOLOGICAL ADRENERGIC RESPONSES IN ALBINO RATS DURING DEVELOPMENT OF EXPERIMENTAL HYPERTHYROIDISM].

PubMed

Osman, Nizar Salim; Ismail, Mohsen

2015-01-01

In this paper we investigated the effects of thyroid hormones on the expression of physiological reactions during adrenergic stimulation (20 min at a dose of 2.0 mg x kg(-1) x min(-1)) during the development of experimental hyperthyroidism. Rats were divided into two groups. The animals in Group 1 were injected woth triiodothyronine. The duration of injection ranged from 1 to 12 days. Consequently, 12 subgroups were formed. The second group was the control group. It is shown that in the process of development of experimental hyperthyroidism all physiological responses vary in accordance with the law, which can be described by a parabola of general form with the value of the degree in the equation equal to three.

Physiological differentiation within a single-species biofilm fueled by serpentinization.

PubMed

Brazelton, William J; Mehta, Mausmi P; Kelley, Deborah S; Baross, John A

2011-01-01

Carbonate chimneys at the Lost City hydrothermal field are coated in biofilms dominated by a single phylotype of archaea known as Lost City Methanosarcinales. In this study, we have detected surprising physiological complexity in single-species biofilms, which is typically indicative of multispecies biofilm communities. Multiple cell morphologies were visible within the biofilms by transmission electron microscopy, and some cells contained intracellular membranes that may facilitate methane oxidation. Both methane production and oxidation were detected at 70 to 80°C and pH 9 to 10 in samples containing the single-species biofilms. Both processes were stimulated by the presence of hydrogen (H(2)), indicating that methane production and oxidation are part of a syntrophic interaction. Metagenomic data included a sequence encoding AMP-forming acetyl coenzyme A synthetase, indicating that acetate may play a role in the methane-cycling syntrophy. A wide range of nitrogen fixation genes were also identified, many of which were likely acquired via lateral gene transfer (LGT). Our results indicate that cells within these single-species biofilms may have differentiated into multiple physiological roles to form multicellular communities linked by metabolic interactions and LGT. Communities similar to these Lost City biofilms are likely to have existed early in the evolution of life, and we discuss how the multicellular characteristics of ancient hydrogen-fueled biofilm communities could have stimulated ecological diversification, as well as unity of biochemistry, during the earliest stages of cellular evolution. Our previous work at the Lost City hydrothermal field has shown that its carbonate chimneys host microbial biofilms dominated by a single uncultivated "species" of archaea. In this paper, we integrate evidence from these previous studies with new data on the metabolic activity and cellular morphology of these archaeal biofilms. We conclude that the archaeal biofilm must contain cells that are physiologically and possibly genetically differentiated with respect to each other. These results are especially interesting considering the possibility that the first cells originated and evolved in hydrothermal systems similar to Lost City.

Social variables exert selective pressures in the evolution and form of primate mimetic musculature.

PubMed

Burrows, Anne M; Li, Ly; Waller, Bridget M; Micheletta, Jerome

2016-04-01

Mammals use their faces in social interactions more so than any other vertebrates. Primates are an extreme among most mammals in their complex, direct, lifelong social interactions and their frequent use of facial displays is a means of proximate visual communication with conspecifics. The available repertoire of facial displays is primarily controlled by mimetic musculature, the muscles that move the face. The form of these muscles is, in turn, limited by and influenced by phylogenetic inertia but here we use examples, both morphological and physiological, to illustrate the influence that social variables may exert on the evolution and form of mimetic musculature among primates. Ecomorphology is concerned with the adaptive responses of morphology to various ecological variables such as diet, foliage density, predation pressures, and time of day activity. We present evidence that social variables also exert selective pressures on morphology, specifically using mimetic muscles among primates as an example. Social variables include group size, dominance 'style', and mating systems. We present two case studies to illustrate the potential influence of social behavior on adaptive morphology of mimetic musculature in primates: (1) gross morphology of the mimetic muscles around the external ear in closely related species of macaque (Macaca mulatta and Macaca nigra) characterized by varying dominance styles and (2) comparative physiology of the orbicularis oris muscle among select ape species. This muscle is used in both facial displays/expressions and in vocalizations/human speech. We present qualitative observations of myosin fiber-type distribution in this muscle of siamang (Symphalangus syndactylus), chimpanzee (Pan troglodytes), and human to demonstrate the potential influence of visual and auditory communication on muscle physiology. In sum, ecomorphologists should be aware of social selective pressures as well as ecological ones, and that observed morphology might reflect a compromise between the demands of the physical and the social environments. © 2016 Anatomical Society.

From the Cover: Disease-Induced Disparities in Formation of the Nanoparticle-Biocorona and the Toxicological Consequences

PubMed Central

Shannahan, Jonathan H.; Fritz, Kristofer S.; Raghavendra, Achyut J.; Podila, Ramakrishna; Persaud, Indushekar; Brown, Jared M.

2016-01-01

Nanoparticle (NP) association with macromolecules in a physiological environment forms a biocorona (BC), which alters NP distribution, activity, and toxicity. While BC formation is dependent on NP physicochemical properties, little information exists on the influence of the physiological environment. Obese individuals and those with cardiovascular disease exist with altered serum chemistry, which is expected to influence BC formation and NP toxicity. We hypothesize that a BC formed on NPs following incubation in hyperlipidemic serum will result in altered NP–BC protein content, cellular association, and toxicity compared to normal serum conditions. We utilized Fe3O4 NPs, which are being developed as MRI contrast and tumor targeting agents to test our hypothesis. We used rat aortic endothelial cells (RAECs) within a dynamic flow in vitro exposure system to more accurately depict the in vivo environment. A BC was formed on 20nm PVP-suspended Fe3O4 NPs following incubation in water, 10% normal or hyperlipidemic rat serum. Addition of BCs resulted in increased hydrodynamic size and decreased surface charge. More cholesterol associated with Fe3O4 NPs after incubation in hyperlipidemic as compared with normal serum. Using quantitative proteomics, we identified unique differences in BC protein components between the 2 serum types. Under flow conditions, formation of a BC from both serum types reduced RAECs association of Fe3O4 NPs. Addition of BCs was found to exacerbate RAECs inflammatory gene responses to Fe3O4 NPs (Fe3O4-hyperlipidemic > Fe3O4-normal > Fe3O4) including increased expression of IL-6, TNF-α, Cxcl-2, VCAM-1, and ICAM-1. Overall, these findings demonstrate that disease-induced variations in physiological environments have a significant impact NP-BC formation, cellular association, and cell response. PMID:27255384

Dihydrotestosterone activates the MAPK pathway and modulates maximum isometric force through the EGF receptor in isolated intact mouse skeletal muscle fibres.

PubMed

Hamdi, M M; Mutungi, G

2010-02-01

It is generally believed that steroid hormones have both genomic and non-genomic (rapid) actions. Although the latter form an important component of the physiological response of these hormones, little is known about the cellular signalling pathway(s) mediating these effects and their physiological functions in adult mammalian skeletal muscle fibres. Therefore, the primary aim of this study was to investigate the non-genomic actions of dihydrotestosterone (DHT) and their physiological role in isolated intact mammalian skeletal muscle fibre bundles. Our results show that treating the fibre bundles with physiological concentrations of DHT increases both twitch and tetanic contractions in fast twitch fibres. However, it decreases them in slow twitch fibres. These changes in force are accompanied by an increase in the phosphorylation of MAPK/ERK1/2 in both fibre types and that of regulatory myosin light chains in fast twitch fibres. Both effects were insensitive to inhibitors of Src kinase, androgen receptor, insulin-like growth factor 1 receptor and platelet-derived growth factor receptor. However, they were abolished by the MAPK/ERK1/2 kinase inhibitor PD98059 and the epidermal growth factor (EGF) receptor inhibitor tyrphostin AG 1478. In contrast, testosterone had no effect on force and increased the phosphorylation of ERK1/2 in slow twitch fibres only. From these results we conclude that sex steroids have non-genomic actions in isolated intact mammalian skeletal muscle fibres. These are mediated through the EGF receptor and one of their main physiological functions is the enhancement of force production in fast twitch skeletal muscle fibres.

Nanosized self-emulsifying lipid vesicles of diacylglycerol-PEG lipid conjugates: Biophysical characterization and inclusion of lipophilic dietary supplements

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

Koynova, Rumiana; Tihova, Mariana; Biopharma)

Hydrated diacylglycerol-PEG lipid conjugates, glyceryl dioleate-PEG12 (GDO-PEG12) and glyceryl dipalmitate-PEG23 (GDP-PEG23), spontaneously form uni- or oligolamellar liposomes in their liquid crystalline phase, in distinct difference from the PEGylated phospholipids which form micelles. GDP-PEG23 exhibits peculiar hysteretic phase behavior and can arrange into a long-living hexagonal phase at ambient and physiological temperatures. Liposomes of GDO-PEG12 and its mixture with soy lecithin exchange lipids with the membranes much more actively than common lecithin liposomes; such an active lipid exchange might facilitate the discharging of the liposome cargo upon uptake and internalization, and can thus be important in drug delivery applications. Diacylglycerol-PEG lipidmore » liposome formulations can encapsulate up to 20-30 wt.% lipophilic dietary supplements such as fish oil, coenzyme Q10, and vitamins D and E. The encapsulation is feasible by way of dry mixing, avoiding the use of organic solvent.« less

Mechanical injury and repair of cells

NASA Technical Reports Server (NTRS)

Miyake, Katsuya; McNeil, Paul L.

2003-01-01

OBJECTIVE: To concisely review the field of cell plasma membrane disruption (torn cell surface) and repair. MAIN POINTS: Plasma membrane disruption is a common form of cell injury under physiologic conditions, after trauma, in certain muscular dystrophies, and during certain forms of clinical intervention. Rapid repair of a disruption is essential to cell survival and involves a complex and active cell response that includes membrane fusion and cytoskeletal activation. Tissues, such as cardiac and skeletal muscle, adapt to a disruption injury by hypertrophying. Cells adapt by increasing the efficiency of their resealing response. CONCLUSION: Plasma membrane disruption is an important cellular event in both health and disease. The disruption repair mechanism is now well understood at the cellular level, but much remains to be learned at the molecular level. Cell and tissue level adaptational responses to the disruption either prevent its further occurrence or facilitate future repairs. Therapeutically useful drugs might result if, using this accumulating knowledge, chemical agents can be developed that can enhance repair or adaptive responses.

Hepatic transcriptome profiles differ among maturing beef heifers supplemented with inorganic, organic, or mixed (50% inorganic:50% organic) forms of dietary selenium.

PubMed

Matthews, James C; Zhang, Zhi; Patterson, Jennifer D; Bridges, Phillip J; Stromberg, Arnold J; Boling, J A

2014-09-01

Selenium (Se) is an important trace mineral that, due to deficiencies in the soil in many parts of the USA, must be supplemented directly to the diet of foraging cattle. Both organic and inorganic forms of dietary Se supplements are available and commonly used, and it is known that Se form affects tissue assimilation, bioavailability, and physiological responses. However, little is known about the effects of form of dietary Se supplements on gene expression profiles, which ostensibly account for Se form-dependent physiological processes. To determine if hepatic transcriptomes of growing beef (Angus-cross) heifers (0.5 kg gain/day) was altered by form of dietary supplemental Se, none (Control), or 3 mg Se/day as inorganic Se (ISe, sodium selenite), organic (OSe, Sel-Plex®), or a blend of ISe and OSe (1.5 mg:1.5 mg, Mix) Se was fed for 168 days, and the RNA expression profiles from biopsied liver tissues was compared by microarray analysis. The relative abundance of 139 RNA transcripts was affected by Se treatment, with 86 of these with complete gene annotations. Statistical and bioinformatic analysis of the annotated RNA transcripts revealed clear differences among the four Se treatment groups in their hepatic expression profiles, including (1) solely and commonly affected transcripts; (2) Control and OSe profiles being more similar than Mix and ISe treatments; (3) distinct OSe-, Mix-, and ISe-Se treatment-induced "phenotypes" that possessed both common and unique predicted physiological capacities; and (4) expression of three microRNAs were uniquely sensitive to OSe, ISe, or Mix treatments, including increased capacity for redox potential induced by OSe and Mix Se treatments resulting from decreased expression of MiR2300b messenger RNA. These findings indicate that the form of supplemental dietary Se consumed by cattle will affect the composition of liver transcriptomes resulting, presumably, in different physiological capacities.

Epilithic Chamaesiphon (Synechococcales, Cyanobacteria) species in mountain streams of the Alps-interspecific differences in photo-physiological traits.

PubMed

Aigner, Siegfried; Herburger, Klaus; Holzinger, Andreas; Karsten, Ulf

2018-01-01

Many alpine streams inhabit conspicuous epilithic biofilms on pebbles and rocks that are formed by members of the cyanobacterial genus Chamaesiphon (Synechococcales). In the Austrian Alps, some Chamaesiphon species can even overgrow up to 70% of the surface of river rocks, and hence they must play an important but still unstudied ecological role in the organic matter flux. Since photo-biological traits have not been investigated so far, photosynthetic features, pigments, and UV-sunscreen compounds were studied in three Chamaesiphon morphospecies ( C. geitleri , C. polonicus , C. starmachii ). These species form conspicuously differently colored spots on cobbles and boulders in the alpine streams. While C. polonicus typically forms red crusts on flat pebble conglomerate, C. geitleri and C. starmachii are characterized by dark brown and black biofilms in the field, respectively. Photosynthesis-irradiance (PE) curves indicate that all three Chamaesiphon species have different light requirements for photosynthesis, with C. starmachii and C. polonicus preferring high and low photon fluence rates, respectively, while C. geitleri takes a position in between. This low-light requirement of C. polonicus is also reflected in ca. ten-times lower chlorophyll a , zeaxanthin, and ß-carotene concentrations, as well as in a lack of the UV-sunscreen scytonemin. All Chamaesiphon morphospecies exhibit the mycosporine-like amino acid porphyra-334. The physiological and biochemical data indicate strong intraspecific differences in photosynthetic activity and pigment patterns, which explain well the distinct preferences of the three studied Chamaesiphon morphospecies for sun-exposed or shaded habitats.

P-selectin ligation induces platelet activation and enhances microaggregate and thrombus formation.

PubMed

Théorêt, Jean-François; Yacoub, Daniel; Hachem, Ahmed; Gillis, Marc-Antoine; Merhi, Yahye

2011-09-01

Platelet P-selectin is a thrombo-inflammatory molecule involved in platelet activation and aggregation. This may occur via the adhesive function of P-selectin and its potential capacity to trigger intracellular signaling. However, its impact on platelet function remains elusive. This study was therefore designed to investigate the relationship between the signaling potential of platelet P-selectin and its function in platelet physiology. Human and mouse platelets were freshly isolated from whole blood. Platelet activation was assessed using flow cytometry and western blot analysis, while platelet physiological responses were evaluated through aggregation, microaggregate formation and in a thrombosis model in wild-type and P-selectin-deficient (CD62P(-/-)) mice. Interaction of P-selectin with its high-affinity ligand, a recombinant soluble form of P-Selectin Glycoprotein Ligand-1 (rPSGL-1), enhances platelet activation, adhesion and microaggregate formation. This augmented platelet microaggregates requires an intact cytoskeleton, but occurs independently of platelet α(IIb)β(3). Thrombus formation and microaggregate were both enhanced by rPSGL-1 in wild-type, but not in CD62P(-/-) mice. In addition, CD62P(-/-) mice exhibited thrombosis abnormalities without an α(IIb)β(3) activation defect. This study demonstrates that the role of platelet P-selectin is not solely adhesive; its binding to PSGL-1 induces platelet activation that enhances platelet aggregation and thrombus formation. Therefore, targeting platelet P-selectin or its ligand PSGL-1 could provide a potential therapeutic approach in the management of thrombotic disorders. Copyright © 2011 Elsevier Ltd. All rights reserved.

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

NASA Astrophysics Data System (ADS)

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

2017-05-01

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

Phase-Locked Loop for Precisely Timed Acoustic Stimulation during Sleep

PubMed Central

Santostasi, Giovanni; Malkani, Roneil; Riedner, Brady; Bellesi, Michele; Tononi, Giulio; Paller, Ken A.; Zee, Phyllis C.

2016-01-01

Background A Brain-Computer Interface could potentially enhance the various benefits of sleep. New Method We describe a strategy for enhancing slow-wave sleep (SWS) by stimulating the sleeping brain with periodic acoustic stimuli that produce resonance in the form of enhanced slow-wave activity in the electroencephalogram (EEG). The system delivers each acoustic stimulus at a particular phase of an electrophysiological rhythm using a Phase-Locked Loop (PLL). Results The PLL is computationally economical and well suited to follow and predict the temporal behavior of the EEG during slow-wave sleep. Comparison with Existing Methods Acoustic stimulation methods may be able to enhance SWS without the risks inherent in electrical stimulation or pharmacological methods. The PLL method differs from other acoustic stimulation methods that are based on detecting a single slow wave rather than modeling slow-wave activity over an extended period of time. Conclusions By providing real-time estimates of the phase of ongoing EEG oscillations, the PLL can rapidly adjust to physiological changes, thus opening up new possibilities to study brain dynamics during sleep. Future application of these methods hold promise for enhancing sleep quality and associated daytime behavior and improving physiologic function. PMID:26617321

Modular extracellular sensor architecture for engineering mammalian cell-based devices.

PubMed

Daringer, Nichole M; Dudek, Rachel M; Schwarz, Kelly A; Leonard, Joshua N

2014-12-19

Engineering mammalian cell-based devices that monitor and therapeutically modulate human physiology is a promising and emerging frontier in clinical synthetic biology. However, realizing this vision will require new technologies enabling engineered circuitry to sense and respond to physiologically relevant cues. No existing technology enables an engineered cell to sense exclusively extracellular ligands, including proteins and pathogens, without relying upon native cellular receptors or signal transduction pathways that may be subject to crosstalk with native cellular components. To address this need, we here report a technology we term a Modular Extracellular Sensor Architecture (MESA). This self-contained receptor and signal transduction platform is maximally orthogonal to native cellular processes and comprises independent, tunable protein modules that enable performance optimization and straightforward engineering of novel MESA that recognize novel ligands. We demonstrate ligand-inducible activation of MESA signaling, optimization of receptor performance using design-based approaches, and generation of MESA biosensors that produce outputs in the form of either transcriptional regulation or transcription-independent reconstitution of enzymatic activity. This systematic, quantitative platform characterization provides a framework for engineering MESA to recognize novel ligands and for integrating these sensors into diverse mammalian synthetic biology applications.

Phenolic metabolites in carnivorous plants: Inter-specific comparison and physiological studies.

PubMed

Kováčik, Jozef; Klejdus, Bořivoj; Repčáková, Klára

2012-03-01

Despite intensive phytochemical research, data related to the accumulation of phenols in carnivorous plants include mainly qualitative reports. We have quantified phenolic metabolites in three species: Drosera capensis, Dionaea muscipula and Nepenthes anamensis in the "leaf" (assimilatory part) and the "trap" (digestive part). For comparison, commercial green tea was analysed. Phenylalanine ammonia-lyase (PAL) activities in Dionaea and Nepenthes were higher in the trap than in the leaf while the opposite was found in Drosera. Soluble phenols and majority of phenolic acids were mainly accumulated in the trap among species. Flavonoids were abundant in Drosera and Dionaea traps but not in Nepenthes. Phenolic acids were preferentially accumulated in a glycosidically-bound form and gallic acid was the main metabolite. Green tea contained more soluble phenols and phenolic acids but less quercetin. In vitro experiments with Drosera spathulata revealed that nitrogen deficiency enhances PAL activity, accumulation of phenols and sugars while PAL inhibitor (2-aminoindane-2-phosphonic acid) depleted phenols and some amino acids (but free phenylalanine and sugars were elevated). Possible explanations in physiological, biochemical and ecological context are discussed. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

Update on the slow delayed rectifier potassium current (I(Ks)): role in modulating cardiac function.

PubMed

Liu, Zhenzhen; Du, Lupei; Li, Minyong

2012-01-01

The slow delayed rectifier current (I(Ks)) is the slow component of cardiac delayed rectifier current and is critical for the late phase repolarization of cardiac action potential. This current is also an important target for Sympathetic Nervous System (SNS) to regulate the cardiac electivity to accommodate to heart rate alterations in response to exercise or emotional stress and can be up-regulated by β- adrenergic or other signal molecules. I(Ks) channel is originated by the co-assembly of pore-forming KCNQ1 α-subunit and accessory KCNE1 β-subunit. Mutations in any subunit can bring about severe long QT syndrome (LQT-1, LQT-5) as characterized by deliquium, seizures and sudden death. This review summarizes the normal physiological functions and molecular basis of I(Ks) channels, as well as illustrates up-to-date development on its blockers and activators. Therefore, the current extensive survey should generate fundamental understanding of the role of I(Ks) channel in modulating cardiac function and donate some instructions to the progression of I(Ks) blockers and activators as potential antiarrhythmic agents or pharmacological tools to determine the physiological and pathological function of I(Ks).

Bioactive Components in Fish Venoms

PubMed Central

Ziegman, Rebekah; Alewood, Paul

2015-01-01

Animal venoms are widely recognized excellent resources for the discovery of novel drug leads and physiological tools. Most are comprised of a large number of components, of which the enzymes, small peptides, and proteins are studied for their important bioactivities. However, in spite of there being over 2000 venomous fish species, piscine venoms have been relatively underrepresented in the literature thus far. Most studies have explored whole or partially fractioned venom, revealing broad pharmacology, which includes cardiovascular, neuromuscular, cytotoxic, inflammatory, and nociceptive activities. Several large proteinaceous toxins, such as stonustoxin, verrucotoxin, and Sp-CTx, have been isolated from scorpaenoid fish. These form pores in cell membranes, resulting in cell death and creating a cascade of reactions that result in many, but not all, of the physiological symptoms observed from envenomation. Additionally, Natterins, a novel family of toxins possessing kininogenase activity have been found in toadfish venom. A variety of smaller protein toxins, as well as a small number of peptides, enzymes, and non-proteinaceous molecules have also been isolated from a range of fish venoms, but most remain poorly characterized. Many other bioactive fish venom components remain to be discovered and investigated. These represent an untapped treasure of potentially useful molecules. PMID:25941767

Metabolomic, enzymatic, and histochemical analyzes of cassava roots during postharvest physiological deterioration.

PubMed

Uarrota, Virgílio Gavicho; Maraschin, Marcelo

2015-11-05

Under postharvest physiological deterioration cassava root tubers alter the expression of biosynthetic pathways of certain primary and secondary metabolites, as well as the activity of some scavenging enzymes. Therefore, in this study we hypothesized that cassava cultivars differ as to their physiological responses to deterioration and their biochemical profiles can be an indicative of the tolerance or susceptibility to deterioration. The results corroborate the working hypothesis, revealing that high Levels of phenolic acids, scopoletin, carotenoids, proteins, and augmented activities of guaiacol peroxidase and hydrogen peroxide in non-stored cassava roots can be used as potential biomarkers of cassava deterioration. Cassava physiological deterioration depends on cultivar and many compounds are up and downregulated during storage time. Secondary metabolites, enzymes, scopoletin, scavenging reactive oxygen species, and acidic polysaccharides are activated as responses to the physiological stress induced in root tubers.

The ins and outs of breath holding: simple demonstrations of complex respiratory physiology.

PubMed

Skow, Rachel J; Day, Trevor A; Fuller, Jonathan E; Bruce, Christina D; Steinback, Craig D

2015-09-01

The physiology of breath holding is complex, and voluntary breath-hold duration is affected by many factors, including practice, psychology, respiratory chemoreflexes, and lung stretch. In this activity, we outline a number of simple laboratory activities or classroom demonstrations that illustrate the complexity of the integrative physiology behind breath-hold duration. These activities require minimal equipment and are easily adapted to small-group demonstrations or a larger-group inquiry format where students can design a protocol and collect and analyze data from their classmates. Specifically, breath-hold duration is measured during a number of maneuvers, including after end expiration, end inspiration, voluntary prior hyperventilation, and inspired hyperoxia. Further activities illustrate the potential contribution of chemoreflexes through rebreathing and repeated rebreathing after a maximum breath hold. The outcome measures resulting from each intervention are easily visualized and plotted and can comprise a comprehensive data set to illustrate and discuss complex and integrated cardiorespiratory physiology. Copyright © 2015 The American Physiological Society.

The Effects Of An Exercise Physiology Program on Physical Fitness Variables, Body Satisfaction, and Physiology Knowledge.

ERIC Educational Resources Information Center

Perry, Arlette C.; Rosenblatt, Evelyn S.; Kempner, Lani; Feldman, Brandon B.; Paolercio, Maria A.; Van Bemden, Angie L.

2002-01-01

Examined the effects of an exercise physiology program on high school students' physical fitness, body satisfaction, and physiology knowledge. Intervention students received exercise physiology theory and active aerobic and resistance exercise within their biology course. Data from student surveys and measurements indicated that the integrated…

Enhancement of dynamin polymerization and GTPase activity by Arc/Arg3.1

PubMed Central

Byers, Christopher E.; Barylko, Barbara; Ross, Justin A.; Southworth, Daniel R.; James, Nicholas G.; Taylor, Clinton A.; Wang, Lei; Collins, Katie A.; Estrada, Armando; Waung, Maggie; Tassin, Tara C.; Huber, Kimberly M.; Jameson, David.M.; Albanesi, Joseph P.

2015-01-01

BACKGROUND The Activity-regulated cytoskeleton-associated protein, Arc, is an immediate-early gene product implicated in various forms of synaptic plasticity. Arc promotes endocytosis of AMPA type glutamate receptors and regulates cytoskeletal assembly in neuronal dendrites. Its role in endocytosis may be mediated by its reported interaction with dynamin 2 (Dyn2), a 100 kDa GTPase that polymerizes around the necks of budding vesicles and catalyzes membrane scission. METHODS Enzymatic and turbidity assays are used in this study to monitor effects of Arc on dynamin activity and polymerization. Arc oligomerization is measured using a combination of approaches, including size exclusion chromatography, sedimentation analysis, dynamic light scattering, fluorescence correlation spectroscopy, and electron microscopy. RESULTS We present evidence that bacterially-expressed His6-Arc facilitates the polymerization of Dyn2 and stimulates its GTPase activity under physiologic conditions (37°C and 100 mM NaCl). At lower ionic strength Arc also stabilizes pre-formed Dyn2 polymers against GTP-dependent disassembly, thereby prolonging assembly-dependent GTP hydrolysis catalyzed by Dyn2. Arc also increases the GTPase activity of Dyn3, an isoform of implicated in dendrite remodeling, but does not affect the activity of Dyn1, a neuron-specific isoform involved in synaptic vesicle recycling. We further show in this study that Arc (either His6-tagged or untagged) has a tendency to form large soluble oligomers, which may function as a scaffold for dynamin assembly and activation. CONCLUSIONS and GENERAL SIGNIFICANCE The ability of Arc to enhance dynamin polymerization and GTPase activation may provide a mechanism to explain Arc-mediated endocytosis of AMPA receptors and the accompanying effects on synaptic plasticity. This study represents the first detailed characterization of the physical properties of Arc. PMID:25783003

Enhancement of dynamin polymerization and GTPase activity by Arc/Arg3.1.

PubMed

Byers, Christopher E; Barylko, Barbara; Ross, Justin A; Southworth, Daniel R; James, Nicholas G; Taylor, Clinton A; Wang, Lei; Collins, Katie A; Estrada, Armando; Waung, Maggie; Tassin, Tara C; Huber, Kimberly M; Jameson, David M; Albanesi, Joseph P

2015-06-01

The Activity-regulated cytoskeleton-associated protein, Arc, is an immediate-early gene product implicated in various forms of synaptic plasticity. Arc promotes endocytosis of AMPA type glutamate receptors and regulates cytoskeletal assembly in neuronal dendrites. Its role in endocytosis may be mediated by its reported interaction with dynamin 2, a 100 kDa GTPase that polymerizes around the necks of budding vesicles and catalyzes membrane scission. Enzymatic and turbidity assays are used in this study to monitor effects of Arc on dynamin activity and polymerization. Arc oligomerization is measured using a combination of approaches, including size exclusion chromatography, sedimentation analysis, dynamic light scattering, fluorescence correlation spectroscopy, and electron microscopy. We present evidence that bacterially-expressed His6-Arc facilitates the polymerization of dynamin 2 and stimulates its GTPase activity under physiologic conditions (37°C and 100mM NaCl). At lower ionic strength Arc also stabilizes pre-formed dynamin 2 polymers against GTP-dependent disassembly, thereby prolonging assembly-dependent GTP hydrolysis catalyzed by dynamin 2. Arc also increases the GTPase activity of dynamin 3, an isoform of implicated in dendrite remodeling, but does not affect the activity of dynamin 1, a neuron-specific isoform involved in synaptic vesicle recycling. We further show in this study that Arc (either His6-tagged or untagged) has a tendency to form large soluble oligomers, which may function as a scaffold for dynamin assembly and activation. The ability of Arc to enhance dynamin polymerization and GTPase activation may provide a mechanism to explain Arc-mediated endocytosis of AMPA receptors and the accompanying effects on synaptic plasticity. Copyright © 2015 Elsevier B.V. All rights reserved.

Formative assessment in physiology teaching using a wireless classroom communication system.

PubMed

Paschal, Cynthia B

2002-12-01

Systems physiology, studied by biomedical engineers, is an analytical way to approach the homeostatic foundations of basic physiology. In many systems physiology courses, students attend lectures and are given homework and reading assignments to complete outside of class. The effectiveness of this traditional approach was compared with an approach in which a wireless classroom communication system was used to provide instant feedback on in-class learning activities and reading assignment quizzes. Homework was eliminated in this approach. The feedback system used stimulated 100% participation in class and facilitated rapid formative assessment. The results of this study indicate that learning of systems physiology concepts including physiology is at least, as if not more, effective when in-class quizzes and activities with instant feedback are used in place of traditional learning activities including homework. When results of this study are interpreted in light of possible effects of the September 11, 2001 terrorist attacks on student learning in the test group, it appears that the modified instruction may be more effective than the traditional instruction.

Degradome Products of the Matricellular Protein CCN1 as Modulators of Pathological Angiogenesis in the Retina*

PubMed Central

Choi, Jinok; Lin, Ann; Shrier, Eric; Lau, Lester F.; Grant, Maria B.; Chaqour, Brahim

2013-01-01

CCN1 is a matricellular protein involved in normal vascular development and tissue repair. CCN1 exhibits cell- and context-dependent activities that are reflective of its tetramodular structure phylogenetically linked to four domains found in various matrix proteins. Here, we show that vitreal fluids from patients with proliferative diabetic retinopathy (PDR) were enriched with a two-module form of CCN1 comprising completely or partially the insulin-like growth factor-binding protein (IGFBP) and von Willebrand factor type C (vWC) domains. The two- and three-module forms comprising, in addition to IGFBP and vWC, the thrombospondin type 1 (TSP1) repeats are CCN1 degradome products by matrix metalloproteinase-2 and -14. The functional significance of CCN1 and its truncated variants was determined in the mouse model of oxygen-induced retinopathy, which simulates neovascular growth associated with PDR and assesses treatment outcomes. In this model, lentivirus-mediated expression of either CCN1 or the IGFBP-vWC-TSP1 form reduced ischemia-induced neovascularization, whereas ectopic expression of the IGFBP-vWC variant exacerbated pathological angiogenesis. The IGFBP-vWC form has potent proangiogenic properties promoting retinal endothelial cell growth, migration, and three-dimensional tubular structure formation, whereas the IGFBP-vWC-TSP1 variant suppressed cell growth and angiogenic gene expression. Both IGFBP-vWC and IGFBP-vWC-TSP1 forms exhibited predictable variations of their domain folding that enhanced their functional potential. These data provide new insights into the formation and activities of CCN1-truncated variants and raise the predictive value of the form containing completely or partially the IGFBP and vWC domains as a surrogate marker of CCN1 activity in PDR distinguishing pathological from physiological angiogenesis. PMID:23798676

3-hydroxy-2(1H)-pyridinone chelating agents

DOEpatents

Raymond, K.; Xu, J.

1999-04-06

Disclosed is a series of improved chelating agents and the chelates formed from these agents, which are highly effective upon both injection and oral administration. Several of the most effective are of low toxicity. These chelating agents incorporate within their structure 3-hydroxy-2-pyridinone (3,2-HOPO) moieties with a substituted carbamoyl group ortho to the hydroxy group of the hydroxypyridinone ring. The electron-withdrawing carbamoyl group increases the acidity, as well as the chemical stability towards oxidation and reduction, of the hydroxypyridinones. In the metal complexes of the chelating agents, the amide protons form very strong hydrogen bonds with the adjacent HOPO oxygen donor, making these complexes very stable at physiological conditions. The terminal N-substituents provide a certain degree of lipophilicity to the 3,2-HOPO, increasing oral activity. 2 figs.

3-hydroxy-2(1H)-pyridinone chelating agents

DOEpatents

Raymond, Kenneth; Xu, Jide

1999-01-01

Disclosed is a series of improved chelating agents and the chelates formed from these agents, which are highly effective upon both injection and oral administration. Several of the most effective are of low toxicity. These chelating agents incorporate within their structure 3-hydroxy-2-pyridinone (3,2-HOPO) moieties with a substituted carbamoyl group ortho to the hydroxy group of the hydroxypyridinone ring. The electron-withdrawing carbamoyl group increases the acidity, as well as the chemical stability towards oxidation and reduction, of the hydroxypyridinones. In the metal complexes of the chelating agents, the amide protons form very strong hydrogen bonds with the adjacent HOPO oxygen donor, making these complexes very stable at physiological conditions. The terminal N-substituents provide a certain degree of lipophilicity to the 3,2-HOPO, increasing oral activity.

The influences of metabotropic receptor activation on cellular signaling and synaptic function in amacrine cells.

PubMed

Gleason, Evanna

2012-01-01

Amacrine cells receive glutamatergic input from bipolar cells and GABAergic, glycinergic, cholinergic, and dopaminergic input from other amacrine cells. Glutamate, GABA, glycine, and acetylcholine (ACh) interact with ionotropic receptors and it is these interactions that form much of the functional circuitry in the inner retina. However, glutamate, GABA, ACh, and dopamine also activate metabotropic receptors linked to second messenger pathways that have the potential to modify the function of individual cells as well as retinal circuitry. Here, the physiological effects of activating dopamine receptors, metabotropic glutamate receptors, GABAB receptors, and muscarinic ACh receptors on amacrine cells will be discussed. The retina also expresses metabotropic receptors and the biochemical machinery associated with the synthesis and degradation of endocannabinoids and sphingosine-1-phosphate (S1P). The effects of activating cannabinoid receptors and S1P receptors on amacrine cell function will also be addressed. Copyright © Cambridge University Press, 2012

Na, K-ATPase activity regulates AMPA receptor turnover through proteasome-mediated proteolysis

PubMed Central

Zhang, Dawei; Hou, Qingming; Wang, Min; Lin, Amy; Jarzylo, Larissa; Navis, Allison; Raissi, Aram; Liu, Fang; Man, Heng-Ye

2009-01-01

Neuronal activity largely depends on two key components on the membrane: the Na, K-ATPase (NKA) that maintains the ion gradients and sets the foundation of excitability, and the ionotropic glutamatergic AMPA receptors (AMPARs) through which sodium influx forms the driving force for excitation. Because the frequent sodium transients from glutamate receptor activity need to be efficiently extruded, a functional coupling between NKA and AMPARs should be a necessary cellular device for synapse physiology. We show that NKA is enriched at synapses and associates with AMPARs. NKA dysfunction induces a rapid reduction in AMPAR cell-surface expression as well as total protein abundance, leading to a long-lasting depression in synaptic transmission. AMPAR proteolysis requires sodium influx, proteasomal activity and receptor internalization. These data elucidate a novel mechanism by which NKA regulates AMPAR turnover and thereby synaptic strength and brain function. PMID:19357275

Human Decision Making Based on Variations in Internal Noise: An EEG Study

PubMed Central

Amitay, Sygal; Guiraud, Jeanne; Sohoglu, Ediz; Zobay, Oliver; Edmonds, Barrie A.; Zhang, Yu-Xuan; Moore, David R.

2013-01-01

Perceptual decision making is prone to errors, especially near threshold. Physiological, behavioural and modeling studies suggest this is due to the intrinsic or ‘internal’ noise in neural systems, which derives from a mixture of bottom-up and top-down sources. We show here that internal noise can form the basis of perceptual decision making when the external signal lacks the required information for the decision. We recorded electroencephalographic (EEG) activity in listeners attempting to discriminate between identical tones. Since the acoustic signal was constant, bottom-up and top-down influences were under experimental control. We found that early cortical responses to the identical stimuli varied in global field power and topography according to the perceptual decision made, and activity preceding stimulus presentation could predict both later activity and behavioural decision. Our results suggest that activity variations induced by internal noise of both sensory and cognitive origin are sufficient to drive discrimination judgments. PMID:23840904

Estrogen modulation properties of mangiferin and quercetin and the mangiferin metabolite norathyriol.

PubMed

Wilkinson, Ashley S; Taing, Meng-Wong; Pierson, Jean Thomas; Lin, Chun-Nam; Dietzgen, Ralf G; Shaw, P Nicholas; Gidley, Michael J; Monteith, Gregory R; Roberts-Thomson, Sarah J

2015-06-01

Mango fruit contain many bioactive compounds, some of which are transcription factor regulators. Estrogen receptor alpha (ERα) and beta (ERβ) are two regulators of gene transcription that are important in a variety of physiological processes and also in diseases including breast cancer. We examined the ability of the mango constituents quercetin, mangiferin, and the aglycone form of mangiferin, norathyriol, to activate both isoforms of the estrogen receptor. Quercetin and norathyriol decreased the viability of MCF-7 breast cancer cells whereas mangiferin had no effect on MCF-7 cells. We also determined that quercetin and mangiferin selectively activated ERα whereas norathyriol activated both ERα and ERβ. Despite quercetin, mangiferin and norathyriol having similar polyphenolic structural motifs, only norathyriol activated ERβ, showing that bioactive agents in mangoes have very specific biological effects. Such specificity may be important given the often-opposing roles of ERα and ERβ in breast cancer proliferation and other cellular processes.

Intragroup Emotions: Physiological Linkage and Social Presence.

PubMed

Järvelä, Simo; Kätsyri, Jari; Ravaja, Niklas; Chanel, Guillaume; Henttonen, Pentti

2016-01-01

We investigated how technologically mediating two different components of emotion-communicative expression and physiological state-to group members affects physiological linkage and self-reported feelings in a small group during video viewing. In different conditions the availability of second screen text chat (communicative expression) and visualization of group level physiological heart rates and their dyadic linkage (physiology) was varied. Within this four person group two participants formed a physically co-located dyad and the other two were individually situated in two separate rooms. We found that text chat always increased heart rate synchrony but HR visualization only with non-co-located dyads. We also found that physiological linkage was strongly connected to self-reported social presence. The results encourage further exploration of the possibilities of sharing group member's physiological components of emotion by technological means to enhance mediated communication and strengthen social presence.

In Vivo Studies in Rhodospirillum rubrum Indicate That Ribulose-1,5-bisphosphate Carboxylase/Oxygenase (Rubisco) Catalyzes Two Obligatorily Required and Physiologically Significant Reactions for Distinct Carbon and Sulfur Metabolic Pathways.

PubMed

Dey, Swati; North, Justin A; Sriram, Jaya; Evans, Bradley S; Tabita, F Robert

2015-12-25

All organisms possess fundamental metabolic pathways to ensure that needed carbon and sulfur compounds are provided to the cell in the proper chemical form and oxidation state. For most organisms capable of using CO2 as sole source of carbon, ribulose-1,5-bisphosphate (RuBP) carboxylase/oxygenase (Rubisco) catalyzes primary carbon dioxide assimilation. In addition, sulfur salvage pathways are necessary to ensure that key sulfur-containing compounds are both available and, where necessary, detoxified in the cell. Using knock-out mutations and metabolomics in the bacterium Rhodospirillum rubrum, we show here that Rubisco concurrently catalyzes key and essential reactions for seemingly unrelated but physiologically essential central carbon and sulfur salvage metabolic pathways of the cell. In this study, complementation and mutagenesis studies indicated that representatives of all known extant functional Rubisco forms found in nature are capable of simultaneously catalyzing reactions required for both CO2-dependent growth as well as growth using 5-methylthioadenosine as sole sulfur source under anaerobic photosynthetic conditions. Moreover, specific inactivation of the CO2 fixation reaction did not affect the ability of Rubisco to support anaerobic 5-methylthioadenosine metabolism, suggesting that the active site of Rubisco has evolved to ensure that this enzyme maintains both key functions. Thus, despite the coevolution of both functions, the active site of this protein may be differentially modified to affect only one of its key functions. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Structural alterations by five disease-causing mutations in the low-pH conformation of human dihydrolipoamide dehydrogenase (hLADH) analyzed by molecular dynamics - Implications in functional loss and modulation of reactive oxygen species generation by pathogenic hLADH forms.

PubMed

Ambrus, Attila; Mizsei, Reka; Adam-Vizi, Vera

2015-07-01

Human dihydrolipoamide dehydrogenase (hLADH) is a flavoenzyme component (E3) of the human alpha-ketoglutarate dehydrogenase complex (α-KGDHc) and few other dehydrogenase complexes. Pathogenic mutations of hLADH cause severe metabolic diseases (atypical forms of E3 deficiency) that often escalate to cardiological or neurological presentations and even premature death; the pathologies are generally accompanied by lactic acidosis. hLADH presents a distinct conformation under acidosis (pH 5.5-6.8) with lower physiological activity and the capacity of generating reactive oxygen species (ROS). It has been shown by our laboratory that selected pathogenic mutations, besides lowering the physiological activity of hLADH, significantly stimulate ROS generation by hLADH, especially at lower pH, which might play a role in the pathogenesis of E3-deficiency in respective cases. Previously, we generated by molecular dynamics (MD) simulation the low-pH hLADH structure and analyzed the structural changes induced in this structure by eight of the pathogenic mutations of hLADH. In the absence of high resolution mutant structures these pieces of information are crucial for the mechanistic investigation of the molecular pathogeneses of the hLADH protein. In the present work we analyzed by molecular dynamics simulation the structural changes induced in the low-pH conformation of hLADH by five pathogenic mutations of hLADH; the structures of these disease-causing mutants of hLADH have never been examined before.

A Psychophysiological Interpretation of Voodoo Illness and Voodoo Death.

ERIC Educational Resources Information Center

Lachman, Sheldon J.

1982-01-01

Discusses voodoo illness, a form of psychosomatic illness which can result in death when sufficiently intense and prolonged. The extreme physiological arousal pattern to stimulation that comprises emotional behavior produces pathological changes in physiological functioning. Persons who are socially prepared or physically predisposed are…

Development of a chicken enterocyte culture to study its functional physiology

USDA-ARS?s Scientific Manuscript database

We developed a method to culture chicken intestinal enterocytes, the cells that absorb and form protective barriers against enteric bacteria, to study their functional physiologies. Using intestinal villi, harvested from day old broiler chicks, the enterocytes were isolated by sequential digestion ...

Life in the sea of plenty: Seasonal and regional comparison of physiological performance of Euphausia hanseni in the northern Benguela upwelling system

NASA Astrophysics Data System (ADS)

Werner, Thorsten; Buchholz, Cornelia; Buchholz, Friedrich

2015-09-01

Variability in upwelling events may lead to periods of constrained food availability in the northern Benguela upwelling system (NBUS), thereby affecting the physiological state and metabolic activity of euphausiids. Most attention has so far been paid to seasonal effects but little is known about regional variability. Metabolic activity (expressed by respiration and excretion rates) and physiological state (expressed by reproductive effort and moult activity) in Euphausia hanseni were examined at different stations during austral summer (minimum upwelling) and austral winter (maximum upwelling). Overall, regional differences in physiological state, influencing metabolic activity, were greater than seasonal ones, indicating favourable conditions for growth and reproduction year-round. Higher respiration rates were found for females in more advanced stages of sexual development. Moult stage did not affect oxygen consumption rates, however. The physiological state of E. hanseni at the time of capture may serve as a meaningful indicator of the associated hydrographic conditions in the NBUS, to be further used in eco-system analysis on seasonal or long-term time scales. A latitudinal comparison of species highlights the extraordinary physiological plasticity of euphausiids.

Thermodynamics of transport through the ammonium transporter Amt-1 investigated with free energy calculations.

PubMed

Ullmann, R Thomas; Andrade, Susana L A; Ullmann, G Matthias

2012-08-16

Amt-1 from Archaeoglobus fulgidus (AfAmt-1) belongs to the Amt/Rh family of ammonium/ammonia transporting membrane proteins. The transport mode and the precise microscopic permeation mechanism utilized by these proteins are intensely debated. Open questions concern the identity of the transported substrate (ammonia and/or ammonium) and whether the transport is passive or active. To address these questions, we studied the overall thermodynamics of the different transport modes as a function of the environmental conditions. Then, we investigated the thermodynamics of the underlying microscopic transport mechanisms with free energy calculations within a continuum electrostatics model. The formalism developed for this purpose is of general utility in the calculation of binding free energies for ligands with multiple protonation forms or other binding forms. The results of our calculations are compared to the available experimental and theoretical data on Amt/Rh proteins and discussed in light of the current knowledge on the physiological conditions experienced by microorganisms and plants. We found that microscopic models of electroneutral and electrogenic transport modes are in principle thermodynamically viable. However, only the electrogenic variants have a net thermodynamic driving force under the physiological conditions experienced by microorganisms and plants. Thus, the transport mechanism of AfAmt-1 is most likely electrogenic.

A review of major factors influencing plant responses to recreation impacts

NASA Astrophysics Data System (ADS)

Kuss, Fred R.

1986-09-01

This article reviews some of the more important factors found to influence the susceptibility of plants to trampling impacts associated with recreational use of natural areas. A three-way interaction mediates plant responses to impacts: plant x environment x stress level(s). Plant responses vary in part according to the genetic constitution of the plant, life and growth form, the adaptive flexibility of the plant, and anatomical differences inherent to growth habit and morphology. Other factors that influence plant sensitivities to impacts are the habitat environments in which plants grow, since a number of conditions such as moisture excesses or deficiencies, nitrogen or oxygen starvation, late frosts, etc., cause physiological injury and may increase plant sensitivity to impacts. Among the environmental factors that may increase or lessen plant sensitivities to impacts are soil moisture levels, canopy density, elevation, aspect, microclimate, soil drainage, texture, fertility and productivity. Seasonal influences also bear consideration since environmental changes and phonological and physiological events are mediated by time of year. Stresses are caused by both direct and indirect forms of impact and vary according to season of use, frequency and amount of use, and the type of activity. These interactions are further complicated by evidence that inter- and intraspecific competition, antagonism, and commensalism may influence differences in the sensitivity of plant communities to impacts.

A sequential assignment procedure for proteins that have intermediate line widths in MAS NMR spectra: amyloid fibrils of human CA150.WW2.

PubMed

Becker, Johanna; Ferguson, Neil; Flinders, Jeremy; van Rossum, Barth-Jan; Fersht, Alan R; Oschkinat, Hartmut

2008-08-11

The second WW domain (WW2) of CA150, a human transcriptional activator, forms amyloid fibrils in vitro under physiological conditions. Based on experimental constraints from MAS NMR spectroscopy experiments, alanine scanning and electron microscopy, a structural model of CA150.WW2 amyloid fibrils was calculated earlier. Here, the assignment strategy is presented and suggested as a general approach for proteins that show intermediate line width. The (13)C,(13)C correlation experiments were recorded on fully or partially (13)C-labelled fibrils. The earlier (13)C assignment (26 residues) was extended to 34 of the 40 residues by direct (13)C-excitation experiments by using a deuterated sample that showed strongly improved line width. A 3D HNC-TEDOR (transferred-echo double-resonance) experiment with deuterated CA150.WW2 fibrils yielded 14 amide nitrogen and proton resonance assignments. The obtained chemical shifts were compared with the chemical shifts determined with the natively folded WW domain. TALOS (Torsion angle likelihood obtained from shift and sequence similarity) predictions confirmed that, under physiological conditions, the fibrillar form of CA150.WW2 adopts a significantly different beta structure than the native WW-domain fold.

Calcium sensitive ring-like oligomers formed by synaptotagmin

PubMed Central

Wang, Jing; Bello, Oscar; Auclair, Sarah M.; Wang, Jing; Coleman, Jeff; Pincet, Frederic; Krishnakumar, Shyam S.; Sindelar, Charles V.; Rothman, James E.

2014-01-01

The synaptic vesicle protein synaptotagmin-1 (SYT) is required to couple calcium influx to the membrane fusion machinery. However, the structural mechanism underlying this process is unclear. Here we report an unexpected circular arrangement (ring) of SYT’s cytosolic domain (C2AB) formed on lipid monolayers in the absence of free calcium ions as revealed by electron microscopy. Rings vary in diameter from 18–43 nm, corresponding to 11–26 molecules of SYT. Continuous stacking of the SYT rings occasionally converts both lipid monolayers and bilayers into protein-coated tubes. Helical reconstruction of the SYT tubes shows that one of the C2 domains (most likely C2B, based on its biochemical properties) interacts with the membrane and is involved in ring formation, and the other C2 domain points radially outward. SYT rings are disrupted rapidly by physiological concentrations of free calcium but not by magnesium. Assuming that calcium-free SYT rings are physiologically relevant, these results suggest a simple and novel mechanism by which SYT regulates neurotransmitter release: The ring acts as a spacer to prevent the completion of the soluble N-ethylmaleimide–sensitive factor activating protein receptor (SNARE) complex assembly, thereby clamping fusion in the absence of calcium. When the ring disassembles in the presence of calcium, fusion proceeds unimpeded. PMID:25201968

Competitive fitness of a predominant pelagic calcifier impaired by ocean acidification

NASA Astrophysics Data System (ADS)

Riebesell, Ulf; Bach, Lennart T.; Bellerby, Richard G. J.; Monsalve, J. Rafael Bermúdez; Boxhammer, Tim; Czerny, Jan; Larsen, Aud; Ludwig, Andrea; Schulz, Kai G.

2017-01-01

Coccolithophores--single-celled calcifying phytoplankton--are an important group of marine primary producers and the dominant builders of calcium carbonate globally. Coccolithophores form extensive blooms and increase the density and sinking speed of organic matter via calcium carbonate ballasting. Thereby, they play a key role in the marine carbon cycle. Coccolithophore physiological responses to experimental ocean acidification have ranged from moderate stimulation to substantial decline in growth and calcification rates, combined with enhanced malformation of their calcite platelets. Here we report on a mesocosm experiment conducted in a Norwegian fjord in which we exposed a natural plankton community to a wide range of CO2-induced ocean acidification, to test whether these physiological responses affect the ecological success of coccolithophore populations. Under high-CO2 treatments, Emiliania huxleyi, the most abundant and productive coccolithophore species, declined in population size during the pre-bloom period and lost the ability to form blooms. As a result, particle sinking velocities declined by up to 30% and sedimented organic matter was reduced by up to 25% relative to controls. There were also strong reductions in seawater concentrations of the climate-active compound dimethylsulfide in CO2-enriched mesocosms. We conclude that ocean acidification can lower calcifying phytoplankton productivity, potentially creating a positive feedback to the climate system.

Physiological and neural correlates of worry and rumination: Support for the contrast avoidance model of worry.

PubMed

Steinfurth, Elisa C K; Alius, Manuela G; Wendt, Julia; Hamm, Alfons O

2017-02-01

The current experiments tested neural and physiological correlates of worry and rumination in comparison to thinking about neutral events. According to the avoidance model-stating that worry is a strategy to reduce intense emotions-physiological and neurobiological activity during worried thinking should not differ from activation during neutral thinking. According to the contrast avoidance model-stating that worry is a strategy to reduce abrupt shifts of emotions-activity should be increased. To test these competing models, we induced worry and neutral thinking in healthy participants using personal topics. A rumination condition was added to investigate the specificity of changes induced by the mental process. Two experiments were conducted assessing the effects on different response levels: (1) neural activation using fMRI, and (2) physiological response mobilization using startle and autonomic measures. During worry, participants showed a potentiated startle response and BOLD activity indicative of emotional network activation. These data partly support the contrast avoidance model of worry. Both mental processes showed elevated activity in a common network referred to as default network indicating self-referential activity. © 2016 Society for Psychophysiological Research.

The model of active participation of the father in childbirth, based on the preferences of the parturient women.

PubMed

Sioma-Markowska, Urszula; Poręba, Ryszard; Skrzypulec-Plinta, Violetta

2015-01-01

The model of family-assisted birth is an element of obstetric care that met with large interest, with the development of perinatology in numerous countries. The modern father is expected to more actively participate both during pregnancy and birth, and also in the childcare. The comparative analysis of the parturient Polish women and the forms of activity of the fathers participating in family-assisted births in order to know which forms of father's activity correlate with the expectations of women in labor and define the range of tasks for the father (model of action for family-assisted birth) that would correspond to the preferences of parturient women. 250 parturient women and 250 fathers who participated in the delivery were included in the survey. Couples after physiological delivery with the participation of father in all stages of childbirth were qualified. The surveys were conducted in the first day after the childbirth. The survey tool was an author-developed survey questionnaire in two versions: (A) for the mother and (B) for the child's father who participated in the birth. The statistical calculations were performed with use of the Statistical PL software. The frequency of occurrence of respective quality (non-measurable) features was evaluated with χ² (chi-square) nonparametric test. The level of statistical significance adopted for tests was p<0.05. The largest coherence between the form of father's activity and the expectations of the parturient woman was found in case of psychical support in every stage of the delivery. Another form of activity of fathers, that in 85% of cases was concurrent with the expectations of women in labor was the act of cutting the umbilical cord and the participation of father in the child measurements and tests (78.5% coherence) and the need of stay of father with the woman and the newborn in the post-delivery period (70% coherence). Obstetric care should take the preferences, connected with family-assisted birth, of both parents into account. The model of active participation of father in family-assisted birth forms a practical guideline for fathers willing to actively participate in the childbirth.

Metabolism of. cap alpha. -C/sup 14/-histidine in the intact rat. II. Radioactive excretion products in urine

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

Wolf, G.; Wu, P.H.L.; Heck, W.W.

1956-09-01

The normal metabolic pathways in the intact rat was investigated via the radioactive urinary excretion products following administration of a physiological dose of a radioactive compound such as ..cap alpha..-C/sup 14/-DL-histidine. The major metabolites, except one, excreted in the urine 5 hours after administration of ..cap alpha..-C/sup 14/-DL-histidine were isolated and identified. Glutamic acid and urocanic acids had simlar and low activities, whereas carboxyl-labeled imidazoacetic acid was found to be the principal metabolite with a high level of activity. It was concluded that the main end-product of the catabolism of DL-histidine is imidazoleacetic acid probably formed through imidazolepyruvic acid.

[Bioavailability and factors influencing its rate].

PubMed

Vraníková, Barbora; Gajdziok, Jan

Bioavailability can be defined as the rate and range of active ingredient absorption, when it becomes available in the systemic circulation or at the desired site of drug action, respectively. Drug bioavailability after oral administration is affected by anumber of different factors, including physicochemical properties of the drug, physiological aspects, the type of dosage form, food intake, biorhythms, and intra- and interindividual variability of the human population. This article is the first from the series dealing with the bioavailability and methods leading to its improvement. The aim of the present paper is to provide an overview of aspects influencing the rate of bioavailability after oral administration of the active ingredient. Subsequentarticles will provide detailed descriptions of methods used for dug bioavailability improvement, which are here only summarized.

[Effect of warm and cold honey solutions on acid-forming function of the stomach].

PubMed

Kas'ianenko, V I; Selezneva, E Ia; Markarova, N V

2002-01-01

Apitherapy is treatment of diseases with biologically active products of bee-keeping (BAPB), which is developing in an intensive way all over the world. The interest in apitherapy is explained, on the one hand, by a great number of natural compounds produced by bees as a result of their vital functions and having high physiological activity, and on the other hand, by the universal nature of bees occurrence and comparative simplicity of getting the bee-keeping products. In apitherapy literature many authors point to the fact that honey has an impact on gastric secretion: a cold honey solution stimulates, and a warm one inhibits acid excretion. Yet there are no results of studies confirming this action in all publications.

RAR/RXR and PPAR/RXR Signaling in Spinal Cord Injury

PubMed Central

van Neerven, Sabien; Mey, Jörg

2007-01-01

The retinoid acid receptors (RAR) and peroxisome proliferator-activated receptors (PPAR) have been implicated in the regulation of inflammatory reactions. Both receptor families contain ligand-activated transcription factors which form heterodimers with retinoid X receptors (RXR). We review data that imply RAR/RXR and PPAR/RXR pathways in physiological reactions after spinal cord injury. Experiments show how RAR signaling may improve axonal regeneration and modulate reactions of glia cells. While anti-inflammatory properties of PPAR are well documented in the periphery, their possible roles in the central nervous system have only recently become evident. Due to its anti-inflammatory function this transcription factor family promises to be a useful target after spinal cord or brain lesions. PMID:18060014

1,2-Diacylglycerols, but not phorbol esters, activate a potential inhibitory pathway for protein kinase C in GH3 pituitary cells. Evidence for involvement of a sphingomyelinase.

PubMed

Kolesnick, R N; Clegg, S

1988-05-15

It has been suggested that sphingoid bases may serve as physiologic inhibitors of protein kinase C. Because 1,2-diacylglycerols, but not phorbol esters, enhance sphingomyelin degradation via a sphingomyelinase in GH3 pituitary cells (Kolesnick, R. N. (1987) J. Biol. Chem. 262, 16759-16762), the effects of phorbol esters, 1,2-diacylglycerols, and sphingomyelinase on protein kinase C activation were assessed. Under basal conditions, the inactive cytosolic form of protein kinase C predominated. 1,2-Diacylglycerols stimulated transient protein kinase C redistribution to the membrane. 1,2-Dioctanoylglycerol (200 micrograms/ml) reduced cytosolic protein kinase C activity to 67% of control from 72 to 48 pmol.min-1.10(6) cells-1 and enhanced membrane-bound activity to 430% of control from 6 to 25 pmol.min-1.10(6) cells-1 after 4 min of stimulation. Thereafter, protein kinase C activity returned to the cytosol. In contrast, the phorbol ester, 12-O-tetradecanoylphorbol-13-acetate (TPA), stimulated redistribution to the membrane without return to the cytosol. Exogenous sphingomyelinase reduced membrane-bound protein kinase C activity to 30% of control, yet did not alter cytosolic activity. Sphingomyelinase, added after phorbol ester-induced redistribution was completed, restored activity to the cytosol. In these studies, TPA (10(-8) M) reduced cytosolic activity to 62% of control and elevated membrane-bound protein kinase C activity to 650% of control. Sphingomyelinase restored cytosolic activity to 84% of control and reduced membrane-bound activity to 297% of control. Similarly, the free sphingoid bases, sphingosine, sphinganine, and phytosphingosine, reversed phorbol ester-induced protein kinase C redistribution. Since 1,2-diacylglycerols activate a sphingomyelinase and sphingomyelinase action can reverse protein kinase C activation, these studies suggest that a pathway involving a sphingomyelinase might comprise a physiologic negative effector system for protein kinase C. Further, the failure of phorbol esters to activate this system might account for some differences between these agents.

Functional Groups Based on Leaf Physiology: Are they Spatially and Temporally Robust?

NASA Technical Reports Server (NTRS)

Foster, Tammy E.; Brooks, J. Renee; Quincy, Charles (Technical Monitor)

2002-01-01

The functional grouping hypothesis, which suggests that complexity in function can be simplified by grouping species with similar responses, was tested in the Florida scrub habitat. Functional groups were identified based on how species in fire maintained FL scrub function in terms of carbon, water and nitrogen dynamics. The suite of physiologic parameters measured to determine function included both instantaneous gas exchange measurements obtained from photosynthetic light response curves and integrated measures of function. Using cluster analysis, five distinct physiologically-based functional groups were identified. Using non-parametric multivariate analyses, it was determined that these five groupings were not altered by plot differences or by the three different management regimes; prescribed burn, mechanically treated and burn, and fire-suppressed. The physiological groupings also remained robust between the two years 1999 and 2000. In order for these groupings to be of use for scaling ecosystem processes, there needs to be an easy-to-measure morphological indicator of function. Life form classifications were able to depict the physiological groupings more adequately than either specific leaf area or leaf thickness. THe ability of life forms to depict the groupings was improved by separating the parasitic Ximenia americana from the shrub category.

Failure of physiologic transformation of spiral arteries, endothelial and trophoblast cell activation, and acute atherosis in the basal plate of the placenta

PubMed Central

Labarrere, Carlos A.; DiCarlo, Hector L.; Bammerlin, Elaine; Hardin, James W.; Kim, Yeon Mee; Chaemsaithong, Piya; Haas, David M.; Kassab, Ghassan S.; Romero, Roberto

2018-01-01

Background Failure of physiologic transformation of spiral arteries has been reported in preeclampsia, fetal growth restriction, fetal death, and spontaneous preterm labor with intact or ruptured membranes. Spiral arteries with failure of physiologic transformation are prone to develop atherosclerotic-like lesions of atherosis. There are striking parallels between preeclampsia and atherosclerotic disease, and between lesions of atherosis and atherosclerosis. Endothelial activation, identified by intercellular adhesion molecule-1 expression, is present in atherosclerotic-like lesions of heart transplantation and considered a manifestation of rejection. Similarly, endothelial activation/dysfunction has been implicated in the pathophysiology of atherosclerosis and preeclampsia. Intercellular adhesion molecule-1-overexpressing-activated endothelial cells are more resistant to trophoblast displacement than nonactivated endothelium and may contribute to shallow spiral artery trophoblastic invasion in obstetrical syndromes having failure of physiologic transformation. Objective To determine whether failure of spiral artery physiologic transformation was associated with activation of interstitial extravillous trophoblasts and/or spiral artery endothelium and presence of acute atherosis in the placental basal plate. Study Design A cross-sectional study of 123 placentas (19-42 weeks’ gestation) obtained from normal pregnancies (n = 22), preterm prelabor rupture of membranes (n = 26), preterm labor (n = 23), preeclampsia (n = 27), intrauterine fetal death (n = 15), and small for gestational age (n = 10) was performed. Failure of spiral artery physiologic transformation and presence of cell activation was determined using immunohistochemistry of placental basal plates containing a median of 4 (minimum: 1; maximum: 9) vessels per placenta. Endothelial/trophoblast cell activation was defined by the expression of intercellular adhesion molecule-1 (ICAM-1). Investigators examining microscopic sections were blinded to clinical diagnosis. Pairwise comparisons among placenta groups were performed with the Fisher’s exact and Wilcoxon rank sum tests using a Bonferroni-adjusted level of significance (.025). Results 87% (94/108) of placentas having spiral arteries with failure of physiologic transformation (actin-positive and cytokeratin-negative) in the basal plate, and 0% (0/15) of placentas having only spiral arteries with complete physiologic transformation (cytokeratin-positive and actin-negative), had arterial endothelial and/or interstitial extravillous trophoblasts reactive with the ICAM-1 activation marker (P < .001). A significant correlation (R2 = 0.84) was found between expression of spiral artery endothelial and interstitial extravillous trophoblast ICAM-1 (P < .001) in activated placentas. Lesions of atherosis were found in 31.9% (30/94) of placentas with complete and/or partial failure of physiologic transformation of spiral arteries that were ICAM-1-positive, in none of the 14 placentas with failure of physiologic transformation that were ICAM-1-negative, and in none of the 15 placentas with complete spiral artery physiologic transformation without failure (P = .001). All placentas (30/30, 100%) with atherosis were identified in placentas having concomitant spiral artery endothelial and interstitial extravillous trophoblast activation. Conclusion Failure of spiral artery physiologic transformation in the placental basal plate is associated with interstitial extravillous trophoblast and arterial endothelial activation along with increased frequency of spiral artery atherosis. These findings may be used to improve the characterization of different disorders of the placental bed such as in refining the existing tools for the early prediction of risk for preterm, preeclamptic, and other abnormal pregnancies. PMID:28034657

Failure of physiologic transformation of spiral arteries, endothelial and trophoblast cell activation, and acute atherosis in the basal plate of the placenta.

PubMed

Labarrere, Carlos A; DiCarlo, Hector L; Bammerlin, Elaine; Hardin, James W; Kim, Yeon M; Chaemsaithong, Piya; Haas, David M; Kassab, Ghassan S; Romero, Roberto

2017-03-01

Failure of physiologic transformation of spiral arteries has been reported in preeclampsia, fetal growth restriction, fetal death, and spontaneous preterm labor with intact or ruptured membranes. Spiral arteries with failure of physiologic transformation are prone to develop atherosclerotic-like lesions of atherosis. There are striking parallels between preeclampsia and atherosclerotic disease, and between lesions of atherosis and atherosclerosis. Endothelial activation, identified by intercellular adhesion molecule-1 expression, is present in atherosclerotic-like lesions of heart transplantation, and is considered a manifestation of rejection. Similarly, endothelial activation/dysfunction has been implicated in the pathophysiology of atherosclerosis and preeclampsia. Intercellular adhesion molecule-1-overexpressing-activated endothelial cells are more resistant to trophoblast displacement than nonactivated endothelium, and may contribute to shallow spiral artery trophoblastic invasion in obstetrical syndromes having failure of physiologic transformation. We sought to determine whether failure of spiral artery physiologic transformation was associated with activation of interstitial extravillous trophoblasts and/or spiral artery endothelium and presence of acute atherosis in the placental basal plate. A cross-sectional study of 123 placentas (19-42 weeks' gestation) obtained from normal pregnancies (n = 22), preterm prelabor rupture of membranes (n = 26), preterm labor (n = 23), preeclampsia (n = 27), intrauterine fetal death (n = 15), and small for gestational age (n = 10) was performed. Failure of spiral artery physiologic transformation and presence of cell activation was determined using immunohistochemistry of placental basal plates containing a median of 4 (minimum: 1; maximum: 9) vessels per placenta. Endothelial/trophoblast cell activation was defined by the expression of intercellular adhesion molecule-1. Investigators examining microscopic sections were blinded to clinical diagnosis. Pairwise comparisons among placenta groups were performed with Fisher exact test and Wilcoxon rank sum test using a Bonferroni-adjusted level of significance (.025). We found that 87% (94/108) of placentas having spiral arteries with failure of physiologic transformation (actin-positive and cytokeratin-negative) in the basal plate, and 0% (0/15) of placentas having only spiral arteries with complete physiologic transformation (cytokeratin-positive and actin-negative), had arterial endothelial and/or interstitial extravillous trophoblasts reactive with the intercellular adhesion molecule-1 activation marker (P < .001). A significant correlation (R 2  = 0.84) was found between expression of spiral artery endothelial and interstitial extravillous trophoblast intercellular adhesion molecule-1 (P < .001) in activated placentas. Lesions of atherosis were found in 31.9% (30/94) of placentas with complete and/or partial failure of physiologic transformation of spiral arteries that were intercellular adhesion molecule-1-positive, in none of the 14 placentas with failure of physiologic transformation that were intercellular adhesion molecule-1-negative, and in none of the 15 placentas with complete spiral artery physiologic transformation without failure (P = .001). All placentas (30/30, 100%) with atherosis were identified in placentas having concomitant spiral artery endothelial and interstitial extravillous trophoblast activation. Failure of spiral artery physiologic transformation in the placental basal plate is associated with interstitial extravillous trophoblast and arterial endothelial activation along with increased frequency of spiral artery atherosis. These findings may be used to improve the characterization of different disorders of the placental bed such as in refining the existing tools for the early prediction of risk for preterm, preeclamptic, and other abnormal pregnancies. Copyright © 2016 Elsevier Inc. All rights reserved.

Sleep-Active Neurons: Conserved Motors of Sleep

PubMed Central

Bringmann, Henrik

2018-01-01

Sleep is crucial for survival and well-being. This behavioral and physiological state has been studied in all major genetically accessible model animals, including rodents, fish, flies, and worms. Genetic and optogenetic studies have identified several neurons that control sleep, making it now possible to compare circuit mechanisms across species. The “motor” of sleep across animal species is formed by neurons that depolarize at the onset of sleep to actively induce this state by directly inhibiting wakefulness. These sleep-inducing neurons are themselves controlled by inhibitory or activating upstream pathways, which act as the “drivers” of the sleep motor: arousal inhibits “sleep-active” neurons whereas various sleep-promoting “tiredness” pathways converge onto sleep-active neurons to depolarize them. This review provides the first overview of sleep-active neurons across the major model animals. The occurrence of sleep-active neurons and their regulation by upstream pathways in both vertebrate and invertebrate species suggests that these neurons are general and ancient components that evolved early in the history of nervous systems. PMID:29618588

It's Difficult to Change the Way We Teach: Lessons from the Integrative Themes in Physiology Curriculum Module Project

ERIC Educational Resources Information Center

Silverthorn, Dee U.; Thorn, Patti M.; Svinicki, Marilla D.

2006-01-01

The Integrative Themes in Physiology (ITIP) project was a National Science Foundation-funded collaboration between the American Physiological Society (APS) and the Human Anatomy and Physiology Society (HAPS). The project goal was to create instructional resources that emphasized active learning in undergraduate anatomy and physiology classrooms.…

CCK-58 Elicits Both Satiety and Satiation in Rats while CCK-8 Elicits Only Satiation

PubMed Central

Overduin, Joost; Gibbs, James; Cummings, David E.; Reeve, Joseph R.

2014-01-01

Reduction of food intake by exogenous cholecystokinin (CCK) has been demonstrated primarily for its short molecular form, CCK-8. Mounting evidence, however, implicates CCK-58 as a major physiologically active CCK form, with different neural and exocrine response profiles than CCK-8. In three studies, we compared meal-pattern effects of intraperitoneal injections CCK-8 vs. CCK-58 in undeprived male Sprague-Dawley rats consuming sweetened condensed milk. In study one, rats (N=10) received CCK-8, CCK-58 (0.45, 0.9, 1.8 and 3.6 nmole/kg) or vehicle before a 4-hour test-food presentation. At most doses, both CCK-8 and CCK-58 reduced meal size relative to vehicle. Meal-size reduction prompted a compensatory shortening of the intermeal interval (IMI) after CCK-8, but not after CCK-58, which uniquely increased the satiety ratio (IMI/size of the preceding meal). In the second study, lick patterns were monitored after administration of 0.9nmole/kg CCK-58, CCK-8 or vehicle. Lick cluster size, lick efficiency and interlick-interval distribution remained unaltered compared to vehicle, implying natural satiation, rather than illness, following both CCK forms. In study 3, threshold satiating doses of the two CCK forms were given at 5 and 30 minutes after meal termination, respectively. CCK 58, but not CCK-8 increased the intermeal interval and satiety ratio compared to vehicle. In conclusion, while CCK 58 and CCK-8 both stimulate satiation, thereby reducing meal size, CCK-58 consistently exerts a satiety effect, prolonging IMI. Given the physiological prominence of CCK-58, these results suggest that CCK’s role in food intake regulation may require reexamination. PMID:24468546

Regulatory physiology discipline science plan

NASA Technical Reports Server (NTRS)

1991-01-01

The focus of the Regulatory Physiology discipline of the Space Physiology and Countermeasures Program is twofold. First, to determine and study how microgravity and associated factors of space flight affect the regulatory mechanisms by which humans adapt and achieve homeostasis and thereby regulate their ability to respond to internal and external signals; and, second, to study selected physiological systems that have been demonstrated to be influenced by gravity. The Regulatory Physiology discipline, as defined here, is composed of seven subdisciplines: (1) Circadian Rhythms, (2) Endocrinology, (3) Fluid and Electrolyte Regulation, (4) Hematology, (5) Immunology, (6) Metabolism and Nutrition, and (7) Temperature Regulation. The purpose of this Discipline Science Plan is to provide a conceptual strategy for NASA's Life Sciences Division research and development activities in the area of regulatory physiology. It covers the research areas critical to NASA's programmatic requirements for the Extended-Duration Orbiter, Space Station Freedom, and exploration mission science activities. These science activities include ground-based and flight; basic, applied, and operational; and animal and human research and development. This document summarizes the current status of the program, outlines available knowledge, establishes goals and objectives, identifies science priorities, and defines critical questions in regulatory physiology. It contains a general plan that will be used by both NASA Headquarters Program Offices and the field centers to review and plan basic, applied, and operational intramural and extramural research and development activities in this area.

3D printing of hybrid biomaterials for bone tissue engineering: Calcium-polyphosphate microparticles encapsulated by polycaprolactone.

PubMed

Neufurth, Meik; Wang, Xiaohong; Wang, Shunfeng; Steffen, Renate; Ackermann, Maximilian; Haep, Natalie D; Schröder, Heinz C; Müller, Werner E G

2017-12-01

Here we describe the formulation of a morphogenetically active bio-ink consisting of amorphous microparticles (MP) prepared from Ca 2+ and the physiological inorganic polymer, polyphosphate (polyP). Those MP had been fortified by mixing with poly-ε-caprolactone (PCL) to allow 3D-bioprinting. The resulting granular PCL/Ca-polyP-MP hybrid material, liquefied by short-time heating to 100 °C, was used for the 3D-printing of tissue-like scaffolds formed by strands with a thickness of 400 µm and a stacked architecture leaving ≈0.5 mm 2 -sized open holes enabling cell migration. The printed composite scaffold turned out to combine suitable biomechanical properties (Young's modulus of 1.60 ± 0.1 GPa; Martens hardness of 153 ± 28 MPa), matching those of cortical and trabecular bone, with morphogenetic activity. This scaffold was capable of attracting and promoting the growth of human bone-related SaOS-2 cells as demonstrated by staining for cell viability (Calcein AM), cell density (DRAQ5) and SEM studies. Furthermore, the hybrid material was demonstrated to upregulate the steady-state-expression of the cell migration-inducing chemokine SDF-1α. EDX analysis and FTIR measurements revealed the presence of hydroxyapatite in the mineral deposits formed on the scaffold surface. Based on the results we conclude that granular PCL/Ca-polyP-MP hybrid material is suitable for the fabrication of bioprintable scaffold which comprises not only biomechanical stability but also morphogenetic potential. In present-day regenerative engineering efforts, biomaterial- and cell-based strategies are proposed that meet the required functional and spatial characteristics and variations, especially in the transition regions between soft (cartilage, tendon or ligament) and hard (bone) tissues. In a biomimetic approach we succeeded to fabricate amorphous Ca-polyP nanoparticles/microparticles which are highly biocompatible. Together with polycaprolactone (PCL), polyP can be bio-printed. This hybrid material attracts the cells, as documented optically as well as by a gene-expression studies. Since PCL is already a FDA-approved organic and inert polymer and polyP a physiological biologically active component this new bio-hybrid material has the potential to restore physiological functions, including bone remodelling and regeneration if used as implant. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Contact activation: a revision.

PubMed

Schmaier, A H

1997-07-01

In conclusion, a revised view of the contact system has been presented. This system has little to do with the initiation of hemostasis. Like lupus anticoagulants, deficiencies of contact proteins give prolonged APTTs but may be risk factors for thrombosis. BK from kininogens is a potent modulator of vascular biology inducing vasodilation, tissue plasminogen activator release, and prostacyclin liberation. Kininogens, themselves, are selective inhibitors of alpha-thrombin-induced platelet activation preventing alpha-thrombin from cleaving the cloned thrombin receptor after arginine41. Kininogens' alpha-thrombin inhibitory activity exists in intact kininogens, BK, and all of BK's breakdown products. HK also is the pivotal protein for contact protein assembly on endothelium. It is the receptor for prekallikrein which when bound to HK becomes activated to kallikrein by an endothelial cell enzyme system independent of activated forms of plasma factor XII. Prekallikrein activation on endothelial cells results in kinetically favorable single chain urokinase and plasminogen activation. Thus the "physiologic, negatively charged surface" for contact system activation is really the assembly of these proteins on cell membranes and activation by membrane-associated enzymes.

Use of Case-Based or Hands-On Laboratory Exercises with Physiology Lectures Improves Knowledge Retention, but Veterinary Medicine Students Prefer Case-Based Activities

ERIC Educational Resources Information Center

McFee, Renee M.; Cupp, Andrea S.; Wood, Jennifer R.

2018-01-01

Didactic lectures are prevalent in physiology courses within veterinary medicine programs, but more active learning methods have also been utilized. Our goal was to identify the most appropriate learning method to augment the lecture component of our physiology course. We hypothesized that case-based learning would be well received by students and…

REVEALING THE ACTIVATION PATHWAY FOR TMEM16A CHLORIDE CHANNELS FROM MACROSCOPIC CURRENTS AND KINETIC MODELS

PubMed Central

Contreras-Vite, Juan A.; Cruz-Rangel, Silvia; De Jesús-Pérez, José J.; Aréchiga Figueroa, Iván A.; Rodríguez-Menchaca, Aldo A.; Pérez-Cornejo, Patricia; Hartzell, H. Criss; Arreola, Jorge

2017-01-01

TMEM16A (ANO1), the pore-forming subunit of calcium-activated chloride channels, regulates several physiological and pathophysiological processes such as smooth muscle contraction, cardiac and neuronal excitability, salivary secretion, tumour growth, and cancer progression. Gating of TMEM16A is complex because it involves the interplay between increases in intracellular calcium concentration ([Ca2+]i), membrane depolarization, extracellular Cl− or permeant anions, and intracellular protons. Our goal here was to understand how these variables regulate TMEM16A gating and to explain four observations. a) TMEM16A is activated by voltage in the absence of intracellular Ca2+. b) The Cl− conductance is decreased after reducing extracellular Cl− concentration ([Cl−]o). c) ICl is regulated by physiological concentrations of [Cl−]o. d) In cells dialyzed with 0.2 µM [Ca2+]i, Cl− has a bimodal effect: at [Cl−]o < 30 mM TMEM16A current activates with a monoexponential time course, but above 30 mM [Cl−]o ICl activation displays fast and slow kinetics. To explain the contribution of Vm, Ca2+ and Cl− to gating, we developed a 12-state Markov chain model. This model explains TMEM16A activation as a sequential, direct, and Vm-dependent binding of two Ca2+ ions coupled to a Vm-dependent binding of an external Cl− ion, with Vm-dependent transitions between states. Our model predicts that extracellular Cl− does not alter the apparent Ca2+ affinity of TMEM16A, which we corroborated experimentally. Rather, extracellular Cl− acts by stabilizing the open configuration induced by Ca2+ and by contributing to the Vm dependence of activation. PMID:27138167

Bacillopeptidase F: two forms of a glycoprotein serine protease from Bacillus subtilis 168.

PubMed Central

Roitsch, C A; Hageman, J H

1983-01-01

Bacillopeptidase F is a serine endopeptidase excreted by Bacillus subtilis 168 after the end of exponential growth. As a step toward discovering a physiological function for this protease, an enzymological and immunological study was undertaken. When bacillopeptidase F was purified at pH 10, a number of enzymically active, rapidly moving electrophoretic forms were observed, as had been previously reported. Rabbit antiserum was prepared against one form. When the enzyme was purified at pH 6.0 in the presence of the covalent inhibitor phenylmethylsulfonyl fluoride, using the rabbit antiserum to detect the bacillopeptidase F protein, no fast-moving electrophoretic forms were observed. Instead, only two forms of the enzyme were isolated. One form had a molecular weight of 33,000, and the other had a molecular weight of 50,000, as determined by equilibrium sedimentation methods. Both forms appeared to be glycoproteins, both contained compounds, released on acid hydrolysis, which cochromatographed with phosphoserine and galactosamine, and the two gave identical immunoprecipitin lines in Ouchterlony double-diffusion tests. The smaller form had a pI of 4.4, whereas the larger had a pI of 5.4. The data suggest that bacillopeptidase F is distinct from all other proteases of B. subtilis. Images PMID:6408058

Intragroup Emotions: Physiological Linkage and Social Presence

PubMed Central

Järvelä, Simo; Kätsyri, Jari; Ravaja, Niklas; Chanel, Guillaume; Henttonen, Pentti

2016-01-01

We investigated how technologically mediating two different components of emotion—communicative expression and physiological state—to group members affects physiological linkage and self-reported feelings in a small group during video viewing. In different conditions the availability of second screen text chat (communicative expression) and visualization of group level physiological heart rates and their dyadic linkage (physiology) was varied. Within this four person group two participants formed a physically co-located dyad and the other two were individually situated in two separate rooms. We found that text chat always increased heart rate synchrony but HR visualization only with non-co-located dyads. We also found that physiological linkage was strongly connected to self-reported social presence. The results encourage further exploration of the possibilities of sharing group member's physiological components of emotion by technological means to enhance mediated communication and strengthen social presence. PMID:26903913

Functional Mapping of the Lectin Activity Site on the β-Prism Domain of Vibrio cholerae Cytolysin

PubMed Central

Rai, Anand Kumar; Paul, Karan; Chattopadhyay, Kausik

2013-01-01

Vibrio cholerae cytolysin (VCC) is a prominent member in the family of β-barrel pore-forming toxins. It induces lysis of target eukaryotic cells by forming transmembrane oligomeric β-barrel channels. VCC also exhibits prominent lectin-like activity in interacting with β1-galactosyl-terminated glycoconjugates. Apart from the cytolysin domain, VCC harbors two lectin-like domains: the β-Trefoil and the β-Prism domains; however, precise contribution of these domains in the lectin property of VCC is not known. Also, role(s) of these lectin-like domains in the mode of action of VCC remain obscure. In the present study, we show that the β-Prism domain of VCC acts as the structural scaffold to determine the lectin activity of the protein toward β1-galactosyl-terminated glycoconjugates. Toward exploring the physiological implication of the β-Prism domain, we demonstrate that the presence of the β-Prism domain-mediated lectin activity is crucial for an efficient interaction of the toxin toward the target cells. Our results also suggest that such lectin activity may act to regulate the oligomerization ability of the membrane-bound VCC toxin. Based on the data presented here, and also consistent with the existing structural information, we propose a novel mechanism of regulation imposed by the β-Prism domain's lectin activity, implicated in the process of membrane pore formation by VCC. PMID:23209283

Generation of thromboxane A2 and aorta-contracting activity from platelets stimulated with modified C-reactive protein.

PubMed Central

Simpson, R M; Prancan, A; Izzi, J M; Fiedel, B A

1982-01-01

The classical acute phase reactant, C-reactive protein (CRP), appears in markedly elevated concentration in the sera of individuals undergoing reactions of acute inflammation and tissue degradation. We previously demonstrated that like IgG, appropriately purified CRP could be thermally modified (H-CRP) such that it enhanced platelet activation in plasma and initiated platelet responses in isolated systems. We now report that this direct platelet activation by modified CRP results in the secretion of both platelet dense body and alpha-granule constituents, and is sensitive to non-steroidal anti-inflammatory drugs as well as the adenosine diphosphate (ADP)-removing enzyme system creatine phosphate/creatine phosphokinase. Thin-layer chromatographic (TLC) analysis of prostanoate endproducts following platelet activation with H-CRP revealed the formation of thromboxane B2 (the hydrated endproduct of thromboxane A2), an important endogenous platelet activator and contractor of vascular tissue; bioassay on rabbit aorta strips of supernatants obtained from platelets undergoing challenge with H-CRP supported the TLC analysis. Complexes formed between CRP and one major ligand, the polycation, were found to share certain platelet activating properties with H-CRP, as does latex-aggregated CRP. These data imply a potential agonist role for this acute phase reactant in platelet physiology and suggest that the interaction of modified forms of CRP with the platelet at sites of vascular damage could have pathological significance. PMID:7118160

Novel Glucagon-Like Peptide-1 Analog Delivered Orally Reduces Postprandial Glucose Excursions in Porcine and Canine Models

PubMed Central

Eldor, Roy; Kidron, Miriam; Greenberg-Shushlav, Yael; Arbit, Ehud

2010-01-01

Background Glucagon-like peptide-1 (GLP-1) and its analogs are associated with a gamut of physiological processes, including induction of insulin release, support of normoglycemia, β-cell function preservation, improved lipid profiles, and increased insulin sensitivity. Thus, GLP-1 harbors significant therapeutic potential for regulating type 2 diabetes mellitus, where its physiological impact is markedly impaired. To date, GLP-1 analogs are only available as injectable dosage forms, and its oral delivery is expected to provide physiological portal/peripheral concentration ratios while fostering patient compliance and adherence. Methods Healthy, fasting, enterically cannulated pigs and beagle canines were administered a single dose of the exenatide-based ORMD-0901 formulation 30 min before oral glucose challenges. Blood samples were collected every 15 min for evaluation of ORMD-0901 safety and efficacy in regulating postchallenge glucose excursions. Results Enterically delivered ORMD-0901 was well tolerated by all animals. ORMD-0901 formulations RG3 and AG2 led to reduced glucose excursions in pigs when delivered prior to a 5 g/kg glucose challenge, where area under the curve (AUC)0–120 values were up to 43% lower than in control sessions. All canines challenged with a glucose load with no prior exposure to exenatide, demonstrated higher AUC0–150 values than in their exenatide-treated sessions. Subcutaneous exenatide delivery amounted to a 51% reduction in mean glucose AUC0–150, while formulations AG4 and AG3 prompted 43% and 29% reductions, respectively. Conclusions When delivered enterically, GLP-1 (ORMD-0901) is absorbed from the canine and porcine gastrointestinal tracts and retains its biological activity. Further development of this drug class in an oral dosage form is expected to enhance diabetes control and patient compliance. PMID:21129350

Periodontal Ligament Entheses and their Adaptive Role in the Context of Dentoalveolar Joint Function

PubMed Central

Lin, Jeremy D.; Jang, Andrew T.; Kurylo, Michael P.; Hurng, Jonathan; Yang, Feifei; Yang, Lynn; Pal, Arvin; Chen, Ling; Ho, Sunita P.

2017-01-01

Objectives The dynamic bone-periodontal ligament (PDL)-tooth fibrous joint consists of two adaptive functionally graded interfaces (FGI), the PDL-bone and PDL-cementum that respond to mechanical strain transmitted during mastication. In general, from a materials and mechanics perspective, FGI prevent catastrophic failure during prolonged cyclic loading. This review is a discourse of results gathered from literature to illustrate the dynamic adaptive nature of the fibrous joint in response to physiologic and pathologic simulated functions, and experimental tooth movement. Methods Historically, studies have investigated soft to hard tissue transitions through analytical techniques that provided insights into structural, biochemical, and mechanical characterization methods. Experimental approaches included two dimensional to three dimensional advanced in situ imaging and analytical techniques. These techniques allowed mapping and correlation of deformations to physicochemical and mechanobiological changes within volumes of the complex subjected to concentric and eccentric loading regimes respectively. Results Tooth movement is facilitated by mechanobiological activity at the interfaces of the fibrous joint and generates elastic discontinuities at these interfaces in response to eccentric loading. Both concentric and eccentric loads mediated cellular responses to strains, and prompted self-regulating mineral forming and resorbing zones that in turn altered the functional space of the joint. Significance A multiscale biomechanics and mechanobiology approach is important for correlating joint function to tissue-level strain-adaptive properties with overall effects on joint form as related to physiologic and pathologic functions. Elucidating the shift in localization of biomolecules specifically at interfaces during development, function, and therapeutic loading of the joint is critical for developing “functional regeneration and adaptation” strategies with an emphasis on restoring physiologic joint function. PMID:28476202

Endoplasmic reticulum-plasma membrane junctions: structure, function and dynamics.

PubMed

Okeke, Emmanuel; Dingsdale, Hayley; Parker, Tony; Voronina, Svetlana; Tepikin, Alexei V

2016-06-01

Endoplasmic reticulum (ER)-plasma membrane (PM) junctions are contact sites between the ER and the PM; the distance between the two organelles in the junctions is below 40 nm and the membranes are connected by protein tethers. A number of molecular tools and technical approaches have been recently developed to visualise, modify and characterise properties of ER-PM junctions. The junctions serve as the platforms for lipid exchange between the organelles and for cell signalling, notably Ca(2+) and cAMP signalling. Vice versa, signalling events regulate the development and properties of the junctions. Two Ca(2+) -dependent mechanisms of de novo formation of ER-PM junctions have been recently described and characterised. The junction-forming proteins and lipids are currently the focus of vigorous investigation. Junctions can be relatively short-lived and simple structures, forming and dissolving on the time scale of a few minutes. However, complex, sophisticated and multifunctional ER-PM junctions, capable of attracting numerous protein residents and other cellular organelles, have been described in some cell types. The road from simplicity to complexity, i.e. the transformation from simple 'nascent' ER-PM junctions to advanced stable multiorganellar complexes, is likely to become an attractive research avenue for current and future junctologists. Another area of considerable research interest is the downstream cellular processes that can be activated by specific local signalling events in the ER-PM junctions. Studies of the cell physiology and indeed pathophysiology of ER-PM junctions have already produced some surprising discoveries, likely to expand with advances in our understanding of these remarkable organellar contact sites. © 2016 The Authors. The Journal of Physiology © 2016 The Physiological Society.

Potato (Solanum tuberosum L.) tuber ageing induces changes in the proteome and antioxidants associated with the sprouting pattern

PubMed Central

Delaplace, Pierre; Fauconnier, Marie-Laure; Sergeant, Kjell; Dierick, Jean-François; Oufir, Mouhssin; van der Wal, Froukje; America, Antoine H. P.; Renaut, Jenny; Hausman, Jean-François; du Jardin, Patrick

2009-01-01

During post-harvest storage, potato tubers age as they undergo an evolution of their physiological state influencing their sprouting pattern. In the present study, physiological and biochemical approaches were combined to provide new insights on potato (Solanum tuberosum L. cv. Désirée) tuber ageing. An increase in the physiological age index (PAI) value from 0.14 to 0.83 occurred during storage at 4 °C over 270 d. Using this reference frame, a proteomic approach was followed based on two-dimensional electrophoresis. In the experimental conditions of this study, a marked proteolysis of patatin occurred after the PAI reached a value of 0.6. In parallel, several glycolytic enzymes were up-regulated and cellular components influencing protein conformation and the response to stress were altered. The equilibrium between the 20S and 26S forms of the proteasome was modified, the 20S form that recycles oxidized proteins being up-regulated. Two proteins belonging to the cytoskeleton were also differentially expressed during ageing. As most of these changes are also observed in an oxidative stress context, an approach focused on antioxidant compounds and enzymes as well as oxidative damage on polyunsaturated fatty acids and proteins was conducted. All the changes observed during ageing seemed to allow the potato tubers to maintain their radical scavenging activity until the end of the storage period as no accumulation of oxidative damage was observed. These data are interpreted considering the impact of reactive oxygen species on the development and the behaviour of other plant systems undergoing ageing or senescence processes. PMID:19204031

Immunomodulatory activities of alpha lipoic acid with a special focus on its efficacy in preventing miscarriage.

PubMed

Monastra, Giovanni; De Grazia, Sara; Cilaker Micili, Serap; Goker, Asli; Unfer, Vittorio

2016-12-01

Alpha lipoic acid (ALA) is an essential mitochondrial co-factor and, as a free molecule, it can exert multi-level immunomodulatory functions. Both ALA and its reduced form, dihydrolipoic acid (DHLA), are believed to be able to chelate heavy metals, to regenerate essential antioxidants and to repair important molecules damaged by oxidation. The largest part of the effects of ALA/DHLA couple can be explained by a specific stimulatory activity on Nrf2-dependent gene transcription and by the inhibition of NF-kB activity. These features have prompted its use as a drug for several diseases. Areas covered: This article surveys the main features of ALA/DHLA and its therapeutic effects. Its complex and differentiated function cannot simply be reduced to anti-inflammatory, antioxidant and detoxifying action. We highlight its capability to finely modulate several physiological pathways when unbalanced. In particular, we focus our attention on pregnancy, in relation to ALA administration by oral route and by a new formulation for vaginal delivery, in patients with threatened miscarriage. Expert opinion: Future efforts should be devoted to explaining carefully ALA/DHLA mechanism of action to reactivate the physiological balance when modified during pregnancy. On the other hand, ALA safety in pregnant women and its pharmacokinetics by vaginal route, have to be studied in depth. Moreover, ALA efficacy has to be confirmed in a much larger sample of patients.

Physiological responses of biomass allocation, root architecture, and invertase activity to copper stress in young seedlings from two populations of Kummerowia stipulacea (maxim.) Makino.

PubMed

Zhang, Luan; Pan, Yuxue; Lv, Wei; Xiong, Zhi-ting

2014-06-01

In the current study, we hypothesize that mine (metallicolous) populations of metallophytes form a trade-off between the roots and shoots when under copper (Cu) stress to adapt themselves to heavy metal contaminated habitats, and thus, differ from normal (non-metallicolous) populations in biomass allocation. To test the hypothesis, two populations of the metallophyte Kummerowia stipulacea, one from an ancient Cu mine (MP) and the other from a non-contaminated site (NMP), were treated with Cu(2+) in hydroponic conditions. The results showed that MP plants had higher root/shoot biomass allocation and more complicated root system architecture compared to those of the NMP plants when under Cu stress. The net photosynthetic capacity was more inhibited in the NMP plants than in the MP plants when under Cu stress. The sugar (sucrose and hexose) contents and acid invertase activities of MP plants were elevated while those in NMP plants were inhibited after Cu treatment. The neutral/alkaline invertase activities and sucrose synthase level showed no significant differences between the two populations when under Cu stress. The results showed that acid invertase played an important role in biomass allocation and that the physiological responses were beneficial for the high root/shoot biomass allocation, which were advantageous during adaptive evolution to Cu-enriched mine soils. Copyright © 2014 Elsevier Inc. All rights reserved.

[Isolation and characterization of a lytic bacteriophage from Mingyong glacier melt water].

PubMed

Li, Mingyuan; Ji, Xiuling; Wang, Baoqiang; Zhang, Qi; Lin, Lianbing; Zhang, Bing; Wei, Yunlin

2012-02-04

Glacier is a unique ecological system. This study focused on the isolation and characterization of a cold-active bateriophage from Mingyong glacier area in northwest Yunnan. Bacterial strains isolated from glacial melt water were used as host cells to isolate and purify bacteriophages by double-layer plate method. The morphology of the isolated phages and their host strains were observed by electron microscope. Restriction fragment length polymorphism (RFLP) analysis of genomic DNA, constituent proteins and physiological analysis of the bacteriophages were further carried out to characterize the phages. A lytic cold-active bacteriophage, designated as MYSP03, was isolated from Mingyong glacier. Its host strain MYB03 was identified as a member of genus Flavobacterium, based on the 16S rRNA sequence analysis. The bacteriophage MYSP03 has a isometric head (about 72 nm in diameter) and a long tail (about 240 nm in length and 10 nm in width), but no envelope was detected. Physiological analysis results showed that MYSP03 had infection activity at 4 degrees C, and clear and transparent plaques were formed on double-layer plates between 4 and 20 degrees C. Its optimum infection temperature was 10 degrees C and optimal pH 9.4, respectively. It is insensitive to chloroform. Furthermore, the genome of MYSP03 consists of double-stranded DNA and is approximately 66 kb.

GROWTH RATES, PHYSIOLOGICAL INDICATORS AND ELEMENTAL COMPOSITION OF THE RED-TIDE DINOFLAGELLATE, ALEXANDRIUM MONILATUM

EPA Science Inventory

Alexandrium monilatum is a thecate, autotrophic, bioluminescent and chain-forming dinoflagellate. Although it has been known to be associated with red tides and fish kills along the US Gulf of Mexico coast for almost 50 years, little basic physiological information is available f...

Combinations of Physiologic Estrogens with Xenoestrogens Alter ERK Phosphorylation Profiles in Rat Pituitary Cells

PubMed Central

Jeng, Yow-Jiun; Watson, Cheryl S.

2011-01-01

Background Estrogens are potent nongenomic phospho-activators of extracellular-signal–regulated kinases (ERKs). A major concern about the toxicity of xenoestrogens (XEs) is potential alteration of responses to physiologic estrogens when XEs are present simultaneously. Objectives We examined estrogen-induced ERK activation, comparing the abilities of structurally related XEs (alkylphenols and bisphenol A) to alter ERK responses induced by physiologic concentrations (1 nM) of estradiol (E2), estrone (E1), and estriol (E3). Methods We quantified hormone/mimetic-induced ERK phosphorylations in the GH3/B6/F10 rat pituitary cell line using a plate immunoassay, comparing effects with those on cell proliferation and by estrogen receptor subtype-selective ligands. Results Alone, these structurally related XEs activate ERKs in an oscillating temporal pattern similar (but not identical) to that with physiologic estrogens. The potency of all estrogens was similar (active between femtomolar and nanomolar concentrations). XEs potently disrupted physiologic estrogen signaling at low, environmentally relevant concentrations. Generally, XEs potentiated (at the lowest, subpicomolar concentrations) and attenuated (at the highest, picomolar to 100 nM concentrations) the actions of the physiologic estrogens. Some XEs showed pronounced nonmonotonic responses/inhibitions. The phosphorylated ERK and proliferative responses to receptor-selective ligands were only partially correlated. Conclusions XEs are both imperfect potent estrogens and endocrine disruptors; the more efficacious an XE, the more it disrupts actions of physiologic estrogens. This ability to disrupt physiologic estrogen signaling suggests that XEs may disturb normal functioning at life stages where actions of particular estrogens are important (e.g., development, reproductive cycling, pregnancy, menopause). PMID:20870566

The Impact of Protein Phosphorylation on Chlamydial Physiology

PubMed Central

Claywell, Ja E.; Matschke, Lea M.; Fisher, Derek J.

2016-01-01

Chlamydia are Gram negative bacterial pathogens responsible for disease in humans and economically important domesticated animals. As obligate intracellular bacteria, they must gain entry into a host cell where they propagate within a parasitophorous organelle that serves as an interactive interface between the bacterium and the host. Nutrient acquisition, growth, and evasion of host defense mechanisms occur from this location. In addition to these cellular and bacterial dynamics, Chlamydia differentiate between two morphologically distinct forms, the elementary body and reticulate body, that are optimized for either extracellular or intracellular survival, respectively. The mechanisms regulating and mediating these diverse physiological events remain largely unknown. Reversible phosphorylation, including classical two-component signaling systems, partner switching mechanisms, and the more recently appreciated bacterial Ser/Thr/Tyr kinases and phosphatases, has gained increasing attention for its role in regulating important physiological processes in bacteria including metabolism, development, and virulence. Phosphorylation modulates these events via rapid and reversible modification of protein substrates leading to changes in enzyme activity, protein oligomerization, cell signaling, and protein localization. The characterization of several conserved chlamydial protein kinases and phosphatases along with phosphoproteome analysis suggest that Chlamydia are capable of global and growth stage-specific protein phosphorylation. This mini review will highlight the current knowledge of protein phosphorylation in Chlamydia and its potential role in chlamydial physiology and, consequently, virulence. Comparisons with other minimal genome intracellular bacterial pathogens also will be addressed with the aim of illustrating the importance of this understudied regulatory mechanism on pathogenesis and the principle questions that remain unanswered. PMID:28066729

DIAGNOSIS OF ENDOCRINE DISEASE: Differentiation of pathologic/neoplastic hypercortisolism (Cushing's syndrome) from physiologic/non-neoplastic hypercortisolism (formerly known as pseudo-Cushing's syndrome).

PubMed

Findling, James W; Raff, Hershel

2017-05-01

Endogenous hypercortisolism (Cushing's syndrome) usually implies the presence of a pathologic condition caused by either an ACTH-secreting neoplasm or autonomous cortisol secretion from a benign or malignant adrenal neoplasm. However, sustained or intermittent hypercortisolism may also accompany many medical disorders that stimulate physiologic/non-neoplastic activation of the HPA axis (formerly known as pseudo-Cushing's syndrome); these two entities may share indistinguishable clinical and biochemical features. A thorough history and physical examination is often the best (and sometimes only) way to exclude pathologic/neoplastic hypercortisolism. The presence of alcoholism, renal failure, poorly controlled diabetes and severe neuropsychiatric disorders should always raise suspicion that the presence of hypercortisolism may be related to physiologic/non-neoplastic Cushing's syndrome. As late-night salivary cortisol and low-dose dexamethasone suppression have good sensitivity and negative predictive value, normal studies exclude Cushing's syndrome of any form. However, these tests have imperfect specificity and additional testing over time with clinical follow-up is often needed. When there is persistent diagnostic uncertainty, secondary tests such as the DDAVP stimulation test and the dexamethasone-CRH test may provide evidence for the presence or absence of an ACTH-secreting tumor. This review will define and characterize the numerous causes of physiologic/non-neoplastic hypercortisolism and provide a rational clinical and biochemical approach to distinguish it from pathologic/neoplastic hypercortisolism (true Cushing's syndrome). © 2017 European Society of Endocrinology.

Use of phytochrome-dependent reaction in evaluating the effect of space flight factors on the plant organism

NASA Technical Reports Server (NTRS)

Shteyne, B. A.; Nevzgodina, L. V.; Miller, A. T.

1982-01-01

The effects of space flight factors on lettuce seeds aboard the Kosmos-936 and Kosmos-1129 satellites for 20 days were studied. The phytochrome dependent (PD) reaction of light sensitive seeds was a sensitive criterion for evaluating the biological effects of space flight factors. The PD reaction of air dry lettuce seeds was suppressed after space flight, especially if the seeds were exposed to open space during the flight. Space flight affects the physiological activity of both phytochrome forms, and both the phi sub 730 dependent reactions of lettuce seeds were suppressed.

A-Kinase Anchoring Proteins: From protein complexes to physiology and disease

PubMed Central

Carnegie, Graeme K.; Means, Christopher K.; Scott, John D.

2009-01-01

Protein scaffold complexes are a key mechanism by which a common signaling pathway can serve many different functions. Sequestering a signaling enzyme to a specific subcellular environment not only ensures that the enzyme is near its relevant targets, but also segregates this activity to prevent indiscriminate phosphorylation of other substrates. One family of diverse, well-studied scaffolding proteins are the A-kinase anchoring proteins (AKAPs). These anchoring proteins form multi-protein complexes that integrate cAMP signaling with other pathways and signaling events. In this review we focus on recent advances in the elucidation of AKAP function. PMID:19319965

A-kinase anchoring proteins: from protein complexes to physiology and disease.

PubMed

Carnegie, Graeme K; Means, Christopher K; Scott, John D

2009-04-01

Protein scaffold complexes are a key mechanism by which a common signaling pathway can serve many different functions. Sequestering a signaling enzyme to a specific subcellular environment not only ensures that the enzyme is near its relevant targets, but also segregates this activity to prevent indiscriminate phosphorylation of other substrates. One family of diverse, well-studied scaffolding proteins are the A-kinase anchoring proteins (AKAPs). These anchoring proteins form multi-protein complexes that integrate cAMP signaling with other pathways and signaling events. In this review, we focus on recent advances in the elucidation of AKAP function.

Role of Pannexin-1 hemichannels and purinergic receptors in the pathogenesis of human diseases

PubMed Central

Velasquez, Stephani; Eugenin, Eliseo A.

2014-01-01

In the last decade several groups have determined the key role of hemichannels formed by pannexins or connexins, extracellular ATP and purinergic receptors in physiological and pathological conditions. Our work and the work of others, indicate that the opening of Pannexin-1 hemichannels and activation of purinergic receptors by extracellular ATP is essential for HIV infection, cellular migration, inflammation, atherosclerosis, stroke, and apoptosis. Thus, this review discusses the importance of purinergic receptors, Panx-1 hemichannels and extracellular ATP in the pathogenesis of several human diseases and their potential use to design novel therapeutic approaches. PMID:24672487

Positron Emission Tomography (PET)

DOE R&D Accomplishments Database

Welch, M. J.

1990-01-01

Positron emission tomography (PET) assesses biochemical processes in the living subject, producing images of function rather than form. Using PET, physicians are able to obtain not the anatomical information provided by other medical imaging techniques, but pictures of physiological activity. In metaphoric terms, traditional imaging methods supply a map of the body's roadways, its, anatomy; PET shows the traffic along those paths, its biochemistry. This document discusses the principles of PET, the radiopharmaceuticals in PET, PET research, clinical applications of PET, the cost of PET, training of individuals for PET, the role of the United States Department of Energy in PET, and the futures of PET.

Study of the cell activity in three-dimensional cell culture by using Raman spectroscopy

NASA Astrophysics Data System (ADS)

Arunngam, Pakajiraporn; Mahardika, Anggara; Hiroko, Matsuyoshi; Andriana, Bibin Bintang; Tabata, Yasuhiko; Sato, Hidetoshi

2018-02-01

The purpose of this study is to develop a estimation technique of local cell activity in cultured 3D cell aggregate with gelatin hydrogel microspheres by using Raman spectroscopy. It is an invaluable technique allowing real-time, nondestructive, and invasive measurement. Cells in body generally exist in 3D structure, which physiological cell-cell interaction enhances cell survival and biological functions. Although a 3D cell aggregate is a good model of the cells in living tissues, it was difficult to estimate their physiological conditions because there is no effective technique to make observation of intact cells in the 3D structure. In this study, cell aggregates were formed by MC3T-E1 (pre-osteoblast) cells and gelatin hydrogel microspheres. In appropriate condition MC3T-E1 cells can differentiate into osteoblast. We assume that the activity of the cell would be different according to the location in the aggregate because the cells near the surface of the aggregate have more access to oxygen and nutrient. Raman imaging technique was applied to measure 3D image of the aggregate. The concentration of the hydroxyapatite (HA) is generated by osteoblast was estimated with a strong band at 950-970 cm-1 which assigned to PO43- in HA. It reflects an activity of the specific site in the cell aggregate. The cell density in this specific site was analyzed by multivariate analysis of the 3D Raman image. Hence, the ratio between intensity and cell density in the site represents the cell activity.

Brain, body, and cognition: Neural, physiological and self-report correlates of phobic and normative fear

PubMed Central

Schaefer, Hillary S.; Larson, Christine L.; Davidson, Richard J.; Coan, James A.

2014-01-01

The phobic fear response appears to resemble an intense form of normal threat responding that can be induced in a nonthreatening situation. However, normative and phobic fear are rarely contrasted directly, thus the degree to which these two types of fear elicit similar neural and bodily responses is not well understood. To examine biological correlates of normal and phobic fear, 21 snake phobic and 21 nonphobic controls saw videos of slithering snakes, attacking snakes and fish in an event-related fMRI design. Simultaneous eletrodermal, pupillary, and self-reported affective responses were collected. Nonphobic fear activated a network of threat-responsive brain regions and involved pupillary dilation, electrodermal response and self-reported affect selective to the attacking snakes. Phobic fear recruited a large array of brain regions including those active in normal fear plus additional structures and also engendered increased pupil dilation, electrodermal and self-reported responses that were greater to any snake versus fish. Importantly, phobics showed greater between- and within-subject concordance among neural, electrodermal, pupillary, and subjective report measures. These results suggest phobic responses recruit overlapping but more strongly activated and more extensive networks of brain activity as compared to normative fear, and are characterized by greater concordance among neural activation, peripheral physiology and self-report. It is yet unclear whether concordance is unique to psychopathology, or rather simply an indicator of the intense fear seen in the phobic response, but these results underscore the importance of synchrony between brain, body, and cognition during the phobic reaction. PMID:24561099

The GATOR1 Complex Regulates Metabolic Homeostasis and the Response to Nutrient Stress in Drosophila melanogaster.

PubMed

Wei, Youheng; Reveal, Brad; Cai, Weili; Lilly, Mary A

2016-12-07

TORC1 regulates metabolism and growth in response to a large array of upstream inputs. The evolutionarily conserved trimeric GATOR1 complex inhibits TORC1 activity in response to amino acid limitation. In humans, the GATOR1 complex has been implicated in a wide array of pathologies including cancer and hereditary forms of epilepsy. However, the precise role of GATOR1 in animal physiology remains largely undefined. Here, we characterize null mutants of the GATOR1 components nprl2, nprl3, and iml1 in Drosophila melanogaster We demonstrate that all three mutants have inappropriately high baseline levels of TORC1 activity and decreased adult viability. Consistent with increased TORC1 activity, GATOR1 mutants exhibit a cell autonomous increase in cell growth. Notably, escaper nprl2 and nprl3 mutant adults have a profound locomotion defect. In line with a nonautonomous role in the regulation of systemic metabolism, expressing the Nprl3 protein in the fat body, a nutrient storage organ, and hemocytes but not muscles and neurons rescues the motility of nprl3 mutants. Finally, we show that nprl2 and nprl3 mutants fail to activate autophagy in response to amino acid limitation and are extremely sensitive to both amino acid and complete starvation. Thus, in Drosophila, in addition to maintaining baseline levels of TORC1 activity, the GATOR1 complex has retained a critical role in the response to nutrient stress. In summary, the TORC1 inhibitor GATOR1 contributes to multiple aspects of the development and physiology of Drosophila. Copyright © 2016 Wei et al.

Brain, body, and cognition: neural, physiological and self-report correlates of phobic and normative fear.

PubMed

Schaefer, Hillary S; Larson, Christine L; Davidson, Richard J; Coan, James A

2014-04-01

The phobic fear response appears to resemble an intense form of normal threat responding that can be induced in a nonthreatening situation. However, normative and phobic fear are rarely contrasted directly, thus the degree to which these two types of fear elicit similar neural and bodily responses is not well understood. To examine biological correlates of normal and phobic fear, 21 snake phobic and 21 nonphobic controls saw videos of slithering snakes, attacking snakes and fish in an event-related fMRI design. Simultaneous eletrodermal, pupillary, and self-reported affective responses were collected. Nonphobic fear activated a network of threat-responsive brain regions and involved pupillary dilation, electrodermal response and self-reported affect selective to the attacking snakes. Phobic fear recruited a large array of brain regions including those active in normal fear plus additional structures and also engendered increased pupil dilation, electrodermal and self-reported responses that were greater to any snake versus fish. Importantly, phobics showed greater between- and within-subject concordance among neural, electrodermal, pupillary, and subjective report measures. These results suggest phobic responses recruit overlapping but more strongly activated and more extensive networks of brain activity as compared to normative fear, and are characterized by greater concordance among neural activation, peripheral physiology and self-report. It is yet unclear whether concordance is unique to psychopathology, or rather simply an indicator of the intense fear seen in the phobic response, but these results underscore the importance of synchrony between brain, body, and cognition during the phobic reaction. Copyright © 2014. Published by Elsevier B.V.

Evidence for a curvilinear relationship between sympathetic nervous system activation and women's physiological sexual arousal.

PubMed

Lorenz, Tierney Ahrold; Harte, Christopher B; Hamilton, Lisa Dawn; Meston, Cindy M

2012-01-01

There is increasing evidence that women's physiological sexual arousal is facilitated by moderate sympathetic nervous system (SNS) activation. Literature also suggests that the level of SNS activation may play a role in the degree to which SNS activity affects sexual arousal. We provide the first empirical examination of a possible curvilinear relationship between SNS activity and women's genital arousal using a direct measure of SNS activation in 52 sexually functional women. The relationship between heart rate variability (HRV), a specific and sensitive marker of SNS activation, and vaginal pulse amplitude (VPA), a measure of genital arousal, was analyzed. Moderate increases in SNS activity were associated with higher genital arousal, while very low or very high SNS activation was associated with lower genital arousal. These findings imply that there is an optimal level of SNS activation for women's physiological sexual arousal. Copyright © 2011 Society for Psychophysiological Research.

Subcellular localization and logistics of integral membrane protein biogenesis in Escherichia coli.

PubMed

Bogdanov, Mikhail; Aboulwafa, Mohammad; Saier, Milton H

2013-01-01

Transporters catalyze entry and exit of molecules into and out of cells and organelles, and protein-lipid interactions influence their activities. The bacterial phosphoenolpyruvate: sugar phosphotransferase system (PTS) catalyzes transport-coupled sugar phosphorylation as well as nonvectorial sugar phosphorylation in the cytoplasm. The vectorial process is much more sensitive to the lipid environment than the nonvectorial process. Moreover, cytoplasmic micellar forms of these enzyme-porters have been identified, and non-PTS permeases have similarly been shown to exist in 'soluble' forms. The latter porters exhibit lipid-dependent activities and can adopt altered topologies by simply changing the lipid composition. Finally, intracellular membranes and vesicles exist in Escherichia coli leading to the following unanswered questions: (1) what determines whether a PTS permease catalyzes vectorial or nonvectorial sugar phosphorylation? (2) How do phospholipids influence relative amounts of the plasma membrane, intracellular membrane, inner membrane-derived vesicles and cytoplasmic micelles? (3) What regulates the route(s) of permease insertion and transfer into and between the different subcellular sites? (4) Do these various membranous forms have distinct physiological functions? (5) What methods should be utilized to study the biogenesis and interconversion of these membranous structures? While research concerning these questions is still in its infancy, answers will greatly enhance our understanding of protein-lipid interactions and how they control the activities, conformations, cellular locations and biogenesis of integral membrane proteins. Copyright © 2013 S. Karger AG, Basel.

Active and inactive β1 integrins segregate into distinct nanoclusters in focal adhesions.

PubMed

Spiess, Matthias; Hernandez-Varas, Pablo; Oddone, Anna; Olofsson, Helene; Blom, Hans; Waithe, Dominic; Lock, John G; Lakadamyali, Melike; Strömblad, Staffan

2018-06-04

Integrins are the core constituents of cell-matrix adhesion complexes such as focal adhesions (FAs) and play key roles in physiology and disease. Integrins fluctuate between active and inactive conformations, yet whether the activity state influences the spatial organization of integrins within FAs has remained unclear. In this study, we address this question and also ask whether integrin activity may be regulated either independently for each integrin molecule or through locally coordinated mechanisms. We used two distinct superresolution microscopy techniques, stochastic optical reconstruction microscopy (STORM) and stimulated emission depletion microscopy (STED), to visualize active versus inactive β1 integrins. We first reveal a spatial hierarchy of integrin organization with integrin molecules arranged in nanoclusters, which align to form linear substructures that in turn build FAs. Remarkably, within FAs, active and inactive β1 integrins segregate into distinct nanoclusters, with active integrin nanoclusters being more organized. This unexpected segregation indicates synchronization of integrin activities within nanoclusters, implying the existence of a coordinate mechanism of integrin activity regulation. © 2018 Spiess et al.

Expanding the agenda for research on the physically active aging body.

PubMed

Phoenix, Cassandra; Grant, Bevan

2009-07-01

In this article, the authors consider the different approaches that can be used to examine the relationship between physical activity and aging. They propose that much is to be gained in our awareness of this dynamic relationship by drawing on multiple forms of knowledge that can generate diverse understandings regarding the impact of physical activity on physiological, psychological, and social aspects of aging. Accordingly, 3 different approaches to understanding the older physically (in)active body are presented. These are categorized as (a) the objective truth about the aging, physically active body; (b) the subjective truth about the aging, physically active body; and (c) "tales" about the aging, physically active body. The key underpinnings, strengths, and weaknesses of each approach are outlined. A number of examples from the literature are also offered to demonstrate where and how each approach has been used to contribute to our understanding about older people and physical activity. The more thorough, multidisciplinary, and wide spanning our knowledge of the aging, active body is, the more informed we might become in every dimension of its existence.

Personality, emotion, and individual differences in physiological responses.

PubMed

Stemmler, Gerhard; Wacker, Jan

2010-07-01

A dominant paradigm in biopsychological personality research seeks to establish links between emotional and motivational traits and habitual, transsituationally consistent individual differences in measures of physiological activity. An alternative approach conceptualizes traits as dispositions that are only operative in certain situational contexts and consequently predicts associations between emotional and motivational traits and physiological activity only for trait-relevant situational contexts in which the physiological systems underlying the traits in question are engaged. In the present paper we first examine and contrast these personistic and interactionistic conceptualizations of personality and personality-physiology associations and then present data from several large studies (N>100) in which electrocortical (e.g., frontal alpha asymmetry) and somatovisceral parameters were measured in various situational contexts (e.g., after the induction of either anger, or fear, or anxiety). As predicted by the interactionistic conceptualization of traits as dispositions the situational context and its subjective representation by the participants moderated the personality-physiology relationships for measures of both central and peripheral nervous system activity. We conclude by outlining the implications of the interactionistic approach for biopsychological personality research. Copyright © 2009 Elsevier B.V. All rights reserved.

The anatomy and physiology of normal and abnormal swallowing in oropharyngeal dysphagia.

PubMed

Sasegbon, A; Hamdy, S

2017-11-01

Eating and drinking are enjoyable activities that positively impact on an individual's quality of life. The ability to swallow food and fluid is integral to the process of eating. Swallowing occupies a dual role being both part of the enjoyment of eating and being a critically important utilitarian activity to enable adequate nutrition and hydration. Any impairment to the process of swallowing can negatively affect a person's perception of their quality of life. The process of swallowing is highly complex and involves muscles in the mouth, pharynx, larynx, and esophagus. The oropharynx is the anatomical region encompassing the oral cavity and the pharynx. Food must be masticated, formed into a bolus and transported to the pharynx by the tongue whereas fluids are usually held within the mouth before being transported ab-orally. The bolus must then be transported through the pharynx to the esophagus without any matter entering the larynx. The muscles needed for all these steps are coordinated by swallowing centers within the brainstem which are supplied with sensory information by afferent nerve fibers from several cranial nerves. The swallowing centers also receive modulatory input from higher centers within the brain. Hence, a swallow has both voluntary and involuntary physiologic components and the term dysphagia is given to difficult swallowing while oropharyngeal dysphagia is difficult swallowing due to pathology within the oropharynx. Problems affecting any point along the complex swallowing pathway can result in dysphagia. This review focuses on the anatomy and physiology behind normal and abnormal oropharyngeal swallowing. It also details the common diseases and pathology causing oropharyngeal dysphagia. © 2017 John Wiley & Sons Ltd.

Physiological impacts of acute Cu exposure on deep-sea vent mussel Bathymodiolus azoricus under a deep-sea mining activity scenario.

PubMed

Martins, Inês; Goulart, Joana; Martins, Eva; Morales-Román, Rosa; Marín, Sergio; Riou, Virginie; Colaço, Ana; Bettencourt, Raul

2017-12-01

Over the past years, several studies have been dedicated to understanding the physiological ability of the vent mussel Bathymodiolus azoricus to overcome the high metal concentrations present in their surrounding hydrothermal environment. Potential deep-sea mining activities at Azores Triple junction hydrothermal vent deposits would inevitably lead to the emergence of new fluid sources close to mussel beds, with consequent emission of high metal concentrations and potential resolubilization of Cu from minerals formed during the active phase of the vent field. Copper is an essential metal playing a key role in the activation of metalloenzymes and metalloproteins responsible for important cellular metabolic processes and tissue homeostasis. However, excessive intracellular amounts of reactive Cu ions may cause irreversible damages triggering possible cell apoptosis. In the present study, B. azoricus was exposed to increasing concentrations of Cu for 96h in conditions of temperature and hydrostatic pressure similar to those experienced at the Lucky Strike hydrothermal vent field. Specimens were kept in 1L flasks, exposed to four Cu concentrations: 0μg/L (control), 300, 800 and 1600μg/L and pressurized to 1750bar. We addressed the question of how increased Cu concentration would affect the function of antioxidant defense proteins and expression of antioxidant and immune-related genes in B. azoricus. Both antioxidant enzymatic activities and gene expression were examined in gills, mantle and digestive gland tissues of exposed vent mussels. Our study reveals that stressful short-term Cu exposure has a strong effect on molecular metabolism of the hydrothermal vent mussel, especially in gill tissue. Initially, both the stress caused by unpressurization or by Cu exposure was associated with high antioxidant enzyme activities and tissue-specific transcriptional up-regulation. However, mussels exposed to increased Cu concentrations showed both antioxidant and immune-related gene suppression. Under a mining activity scenario, the release of an excess of dissolved Cu to the vent environment may cause serious changes in cellular defense mechanisms of B. azoricus. This outcome, while adding to our knowledge of Cu toxicity, highlights the potentially deleterious impacts of mining activities on the physiology of deep-sea organisms. Copyright © 2017 Elsevier B.V. All rights reserved.

Modulation of BK channels by ethanol

PubMed Central

Dopico, Alex M.; Bukiya, Anna N.; Kuntamallappanavar, Guruprasad; Liu, Jianxi

2017-01-01

In alcohol-naïve systems, ethanol (<100 mM) exposure of calcium-gated BK channels perturbs physiology and behavior. Brief (several minutes) ethanol exposure usually leads to increased BK current, which results from ethanol interaction with a pocket mapped to the BK channel-forming slo1 protein cytosolic tail domain. The importance of this region in alcohol-induced intoxication has been addressed in Caenorhabditis elegans slo1 mutants. However, ethanol-induced BK activation is not universal as refractoriness and inhibition have been reported. The final effect depends on many factors, including intracellular calcium levels, slo1 isoform, BK beta subunit composition, post-translational modification of BK proteins, channel lipid microenvironment and type of ethanol administration. Studies in Drosophila melanogaster, Caenorhabditis elegans and rodents show that protracted/repeated ethanol administration leads to tolerance to alcohol-induced modification of BK-driven physiology and behavior. Unveiling the mechanisms underlying tolerance is of major importance, as tolerance to alcohol has been proposed as predictor of risk for alcoholism. PMID:27238266

Application of muscadine grape (Vitis rotundifolia Michx.) pomace extract to reduce carcinogenic acrylamide.

PubMed

Xu, Changmou; Yagiz, Yavuz; Marshall, Sara; Li, Zheng; Simonne, Amarat; Lu, Jiang; Marshall, Maurice R

2015-09-01

Acrylamide is a byproduct of the Maillard reaction and is formed in a variety of heat-treated commercial starchy foods. It is known to be toxic and potentially carcinogenic to humans. Muscadine grape polyphenols and standard phenolic compounds were examined on the reduction of acrylamide in an equimolar asparagine/glucose chemical model, a potato chip model, and a simulated physiological system. Polyphenols were found to significantly reduce acrylamide in the chemical model, with reduced rates higher than 90% at 100 μg/ml. In the potato chip model, grape polyphenols reduced the acrylamide level by 60.3% as concentration was increased to 0.1%. However, polyphenols exhibited no acrylamide reduction in the simulated physiological system. Results also indicated no significant correlation between the antioxidant activities of polyphenols and their acrylamide inhibition. This study demonstrated muscadine grape extract can mitigate acrylamide formation in the Maillard reaction, which provides a new value-added application for winery pomace waste. Copyright © 2015 Elsevier Ltd. All rights reserved.

Sensing human physiological response using wearable carbon nanotube-based fabrics

NASA Astrophysics Data System (ADS)

Wang, Long; Loh, Kenneth J.; Koo, Helen S.

2016-04-01

Flexible and wearable sensors for human monitoring have received increased attention. Besides detecting motion and physical activity, measuring human vital signals (e.g., respiration rate and body temperature) provide rich data for assessing subjects' physiological or psychological condition. Instead of using conventional, bulky, sensing transducers, the objective of this study was to design and test a wearable, fabric-like sensing system. In particular, multi-walled carbon nanotube (MWCNT)-latex thin films of different MWCNT concentrations were first fabricated using spray coating. Freestanding MWCNT-latex films were then sandwiched between two layers of flexible fabric using iron-on adhesive to form the wearable sensor. Second, to characterize its strain sensing properties, the fabric sensors were subjected to uniaxial and cyclic tensile load tests, and they exhibited relatively stable electromechanical responses. Finally, the wearable sensors were placed on a human subject for monitoring simple motions and for validating their practical strain sensing performance. Overall, the wearable fabric sensor design exhibited advances such as flexibility, ease of fabrication, light weight, low cost, noninvasiveness, and user comfort.

Chaperonin polymers in archaea: The cytoskeleton of prokaryotes?

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

Trent, J.D.; Kagawa, H.K.; Zaluzec, N.J.

Chaperonins are protein complexes that play a critical role in folding nascent polypeptides under normal conditions and refolding damaged proteins under stress conditions. In all organisms these complexes are composed of evolutionarily conserved 60-kDa proteins arranged in double-ring structures with between 7 and 9 protein subunits per ring. These double ring structures are assumed to be the functional units in vivo, although they have never been observed inside cells. Here the authors show that the purified chaperonin from the hyperthermophilic archaeon Sulfolobus shibatae, which is closely related to chaperonins in eukaryotes, has a double ring structure at low concentrations (0.1more » mg/ml), but at more physiological concentrations, the rings stack end to end to form polymers. The polymers are stable at physiological temperatures (75 C) and closely resemble structures observed inside unfixed S. shibatae cells. The authors suggest that in vivo chaperonin activity may be regulated by polymerization and that chaperonin polymers may act as a cytoskeleton-like structure in archaea and bacteria.« less

Biomolecular filters for improved separation of output signals in enzyme logic systems applied to biomedical analysis.

PubMed

Halámek, Jan; Zhou, Jian; Halámková, Lenka; Bocharova, Vera; Privman, Vladimir; Wang, Joseph; Katz, Evgeny

2011-11-15

Biomolecular logic systems processing biochemical input signals and producing "digital" outputs in the form of YES/NO were developed for analysis of physiological conditions characteristic of liver injury, soft tissue injury, and abdominal trauma. Injury biomarkers were used as input signals for activating the logic systems. Their normal physiological concentrations were defined as logic-0 level, while their pathologically elevated concentrations were defined as logic-1 values. Since the input concentrations applied as logic 0 and 1 values were not sufficiently different, the output signals being at low and high values (0, 1 outputs) were separated with a short gap making their discrimination difficult. Coupled enzymatic reactions functioning as a biomolecular signal processing system with a built-in filter property were developed. The filter process involves a partial back-conversion of the optical-output-signal-yielding product, but only at its low concentrations, thus allowing the proper discrimination between 0 and 1 output values.

Let's Walk Outdoors! Self-Paced Walking Outdoors Improves Future Intention to Exercise in Women With Obesity.

PubMed

Krinski, Kleverton; Machado, Daniel G S; Lirani, Luciana S; DaSilva, Sergio G; Costa, Eduardo C; Hardcastle, Sarah J; Elsangedy, Hassan M

2017-04-01

In order to examine whether environmental settings influence psychological and physiological responses of women with obesity during self-paced walking, 38 women performed two exercise sessions (treadmill and outdoors) for 30 min, where oxygen uptake, heart rate, ratings of perceived exertion, affect, attentional focus, enjoyment, and future intentions to walk were analyzed. Physiological responses were similar during both sessions. However, during outdoor exercise, participants displayed higher externally focused attention, positive affect, and lower ratings of perceived exertion, followed by greater enjoyment and future intention to participate in outdoor walking. The more externally focused attention predicted greater future intentions to participate in walking. Therefore, women with obesity self-selected an appropriate exercise intensity to improve fitness and health in both environmental settings. Also, self-paced outdoor walking presented improved psychological responses. Health care professionals should consider promoting outdoor forms of exercise to maximize psychological benefits and promote long-term adherence to a physically active lifestyle.

Targeting multidrug resistance protein 1 (MRP1, ABCC1): past, present, and future.

PubMed

Cole, Susan P C

2014-01-01

The human ATP-binding cassette transporter multidrug resistance protein 1 (MRP1), encoded by ABCC1, was initially identified because of its ability to confer multidrug resistance in lung cancer cells. It is now established that MRP1 plays a role in protecting certain tissues from xenobiotic insults and that it mediates the cellular efflux of the proinflammatory cysteinyl leukotriene C4 as well as a vast array of other endo- and xenobiotic organic anions. Many of these are glutathione (GSH) or glucuronide conjugates, the products of Phase II drug metabolism. MRP1 also plays a role in the cellular efflux of the reduced and oxidized forms of GSH and thus contributes to the many physiological and pathophysiological processes influenced by these small peptides, including oxidative stress. In this review, the pharmacological and physiological aspects of MRP1 are considered in the context of the current status and future prospects of pharmacological and genetic modulation of MRP1 activity.

Reconstruction and Simulation of Neocortical Microcircuitry.

PubMed

Markram, Henry; Muller, Eilif; Ramaswamy, Srikanth; Reimann, Michael W; Abdellah, Marwan; Sanchez, Carlos Aguado; Ailamaki, Anastasia; Alonso-Nanclares, Lidia; Antille, Nicolas; Arsever, Selim; Kahou, Guy Antoine Atenekeng; Berger, Thomas K; Bilgili, Ahmet; Buncic, Nenad; Chalimourda, Athanassia; Chindemi, Giuseppe; Courcol, Jean-Denis; Delalondre, Fabien; Delattre, Vincent; Druckmann, Shaul; Dumusc, Raphael; Dynes, James; Eilemann, Stefan; Gal, Eyal; Gevaert, Michael Emiel; Ghobril, Jean-Pierre; Gidon, Albert; Graham, Joe W; Gupta, Anirudh; Haenel, Valentin; Hay, Etay; Heinis, Thomas; Hernando, Juan B; Hines, Michael; Kanari, Lida; Keller, Daniel; Kenyon, John; Khazen, Georges; Kim, Yihwa; King, James G; Kisvarday, Zoltan; Kumbhar, Pramod; Lasserre, Sébastien; Le Bé, Jean-Vincent; Magalhães, Bruno R C; Merchán-Pérez, Angel; Meystre, Julie; Morrice, Benjamin Roy; Muller, Jeffrey; Muñoz-Céspedes, Alberto; Muralidhar, Shruti; Muthurasa, Keerthan; Nachbaur, Daniel; Newton, Taylor H; Nolte, Max; Ovcharenko, Aleksandr; Palacios, Juan; Pastor, Luis; Perin, Rodrigo; Ranjan, Rajnish; Riachi, Imad; Rodríguez, José-Rodrigo; Riquelme, Juan Luis; Rössert, Christian; Sfyrakis, Konstantinos; Shi, Ying; Shillcock, Julian C; Silberberg, Gilad; Silva, Ricardo; Tauheed, Farhan; Telefont, Martin; Toledo-Rodriguez, Maria; Tränkler, Thomas; Van Geit, Werner; Díaz, Jafet Villafranca; Walker, Richard; Wang, Yun; Zaninetta, Stefano M; DeFelipe, Javier; Hill, Sean L; Segev, Idan; Schürmann, Felix

2015-10-08

We present a first-draft digital reconstruction of the microcircuitry of somatosensory cortex of juvenile rat. The reconstruction uses cellular and synaptic organizing principles to algorithmically reconstruct detailed anatomy and physiology from sparse experimental data. An objective anatomical method defines a neocortical volume of 0.29 ± 0.01 mm(3) containing ~31,000 neurons, and patch-clamp studies identify 55 layer-specific morphological and 207 morpho-electrical neuron subtypes. When digitally reconstructed neurons are positioned in the volume and synapse formation is restricted to biological bouton densities and numbers of synapses per connection, their overlapping arbors form ~8 million connections with ~37 million synapses. Simulations reproduce an array of in vitro and in vivo experiments without parameter tuning. Additionally, we find a spectrum of network states with a sharp transition from synchronous to asynchronous activity, modulated by physiological mechanisms. The spectrum of network states, dynamically reconfigured around this transition, supports diverse information processing strategies. VIDEO ABSTRACT. Copyright © 2015 Elsevier Inc. All rights reserved.

Chaperonin Polymers in Archaea: The Cytoskeleton of Prokaryotes?

DOE R&D Accomplishments Database

Trent, J. D.; Kagawa, H. K.; Zaluzec, N. J.

1997-07-01

Chaperonins are protein complexes that play a critical role in folding nascent polypeptides under normal conditions and refolding damaged proteins under stress conditions. In all organisms these complexes are composed of evolutionarily conserved 60-kDa proteins arranged in double-ring structures with between 7 and 9 protein subunits per ring. These double ring structures are assumed to be the functional units in vivo, although they have never been observed inside cells. Here the authors show that the purified chaperonin from the hyperthermophilic archaeon Sulfolobus shibatae, which is closely related to chaperonins in eukaryotes, has a double ring structure at low concentrations (0.1 mg/ml), but at more physiological concentrations, the rings stack end to end to form polymers. The polymers are stable at physiological temperatures (75 C) and closely resemble structures observed inside unfixed S. shibatae cells. The authors suggest that in vivo chaperonin activity may be regulated by polymerization and that chaperonin polymers may act as a cytoskeleton-like structure in archaea and bacteria.

Once and for all, LXRα and LXRβ are gatekeepers of the endocrine system.

PubMed

Maqdasy, Salwan; Trousson, Amalia; Tauveron, Igor; Volle, David H; Baron, Silvère; Lobaccaro, Jean-Marc A

2016-06-01

Liver X receptors (LXRs) α and β are nuclear receptors whose transcriptional activity is regulated by oxysterols, the oxidized forms of cholesterol. Described in the late 1990s as lipid sensors, both LXRs regulate cholesterol and fatty acid homeostasis. Over the years, deep phenotypic analyses of mouse models deficient for LXRα and/or LXRβ have pointed out various other physiological functions including glucose homeostasis, immunology, and neuroprotection. This review enlightens the "endocrine" functions of LXRs; they deeply impact plasma glucose directly and by modulating insulin signaling, renin-angiotensin-aldosterone axis, thyroid and pituitary hormone levels, and bone homeostasis. Besides, LXR signaling is also involved in adrenal physiology, steroid synthesis, and male and female reproduction. Hence, LXRs are definitely involved in the endocrine system and could thus be considered as endocrine receptors, even though oxysterols do not fully correspond to the definition of hormones. Finally, because they are ligand-regulated transcription factors, LXRs are potential pharmacological targets with promising beneficial metabolic effects. Copyright © 2016 Elsevier Ltd. All rights reserved.

Physiological and health implications of a sedentary lifestyle.

PubMed

Tremblay, Mark Stephen; Colley, Rachel Christine; Saunders, Travis John; Healy, Genevieve Nissa; Owen, Neville

2010-12-01

Sedentary behaviour is associated with deleterious health outcomes, which differ from those that can be attributed to a lack of moderate to vigorous physical activity. This has led to the field of "sedentary physiology", which may be considered as separate and distinct from exercise physiology. This paper gives an overview of this emerging area of research and highlights the ways that it differs from traditional exercise physiology. Definitions of key terms associated with the field of sedentary physiology and a review of the self-report and objective methods for assessing sedentary behaviour are provided. Proposed mechanisms of sedentary physiology are examined, and how they differ from those linking physical activity and health are highlighted. Evidence relating to associations of sedentary behaviours with major health outcomes and the population prevalence and correlates of sedentary behaviours are reviewed. Recommendations for future research are proposed.

In vitro immune functions in thiamine-replete and -depleted lake trout (Salvelinus namaycush).

PubMed

Ottinger, Christopher A; Honeyfield, Dale C; Densmore, Christine L; Iwanowicz, Luke R

2014-05-01

In this study we examined the impacts of in vivo thiamine deficiency on lake trout leukocyte function measured in vitro. When compared outside the context of individual-specific thiamine concentrations no significant differences were observed in leukocyte bactericidal activity or in concanavalin A (Con A), and phytohemagglutinin-P (PHA-P) stimulated leukocyte proliferation. Placing immune functions into context with the ratio of in vivo liver thiamine monophosphate (TMP--biologically inactive form) to thiamine pyrophosphate (TPP--biologically active form) proved to be the best indicator of thiamine depletion impacts as determined using regression modeling. These observed relationships indicated differential effects on the immune measures with bactericidal activity exhibiting an inverse relationship with TMP to TPP ratios, Con A stimulated mitogenesis exhibiting a positive relationship with TMP to TPP ratios and PHA-P stimulated mitogenesis exhibiting no significant relationships. In addition, these relationships showed considerable complexity which included the consistent observation of a thiamine-replete subgroup with characteristics similar to those seen in the leukocytes from thiamine-depleted fish. When considered together, our observations indicate that lake trout leukocytes experience cell-type specific impacts as well as an altered physiologic environment when confronted with a thiamine-limited state. Published by Elsevier Ltd.

In vitro immune functions in thiamine-replete and -depleted lake trout (Salvelinus namaycush)

USGS Publications Warehouse

Ottinger, Christopher A.; Honeyfield, Dale C.; Densmore, Christine L.; Iwanowicz, Luke R.

2014-01-01

In this study we examined the impacts of in vivo thiamine deficiency on lake trout leukocyte function measured in vitro. When compared outside the context of individual-specific thiamine concentrations no significant differences were observed in leukocyte bactericidal activity or in concanavalin A (Con A), and phytohemagglutinin-P (PHA-P) stimulated leukocyte proliferation. Placing immune functions into context with the ratio of in vivo liver thiamine monophosphate (TMP – biologically inactive form) to thiamine pyrophosphate (TPP – biologically active form) proved to be the best indicator of thiamine depletion impacts as determined using regression modeling. These observed relationships indicated differential effects on the immune measures with bactericidal activity exhibiting an inverse relationship with TMP to TPP ratios, Con A stimulated mitogenesis exhibiting a positive relationship with TMP to TPP ratios and PHA-P stimulated mitogenesis exhibiting no significant relationships. In addition, these relationships showed considerable complexity which included the consistent observation of a thiamine-replete subgroup with characteristics similar to those seen in the leukocytes from thiamine-depleted fish. When considered together, our observations indicate that lake trout leukocytes experience cell-type specific impacts as well as an altered physiologic environment when confronted with a thiamine-limited state.

Do physical activity levels influence the cardiovascular-related physiological characteristics of postmenopausal women?

PubMed

Barnett, Fiona

2009-12-01

This study aimed to determine whether cardiovascular-related physiological differences existed among postmenopausal women in relation to their physical activity levels. Participants were postmenopausal women (n= 101) resident in North Queensland. A self-report questionnaire determined recent exercise history. Anthropometric and physiological measures were obtained. Participants also performed a six-minute graded exercise test to determine cardiorespiratory fitness. Compared with the women who exercised, those women who did not exercise had a lower level of cardiorespiratory fitness (P= 0.00) and higher resting diastolic blood pressure (P= 0.01), BMI (P= 0.00) and WHR (P= 0.02). Discriminant function analysis found that a combination of BMI and cardiorespiratory fitness discriminated between the two groups. Postmenopausal women who performed moderate-intensity physical activity had more favourable cardiovascular-related physiological characteristics. Health professionals should encourage more postmenopausal women to participate in moderate-intensity activity to reduce the risk of cardiovascular disease.

Use and physiological responses of portable dynamic office workstations in an occupational setting - A field study.

PubMed

Schellewald, Vera; Kleinert, Jens; Ellegast, Rolf

2018-09-01

The aim of this study was to investigate the use of two types of dynamic workstations (Deskbike, activeLife Trainer) and their effects on physiological activation in an occupational setting. 30 employees were given access to the devices for 28 days. Frequency and duration of borrowing and use was recorded by a Chipcard-system. Physiological activation (energy expenditure, heart rate) while working in a seated position and using the workstations was measured with the activity tracker Fitbit Charge HR. Participants used dynamic workstations on 40% of their working days for an average of 54.3 ± 23.9 min per day. Energy expenditure and heart rate increased significantly while using the workstations compared to working seated. The Deskbike was used more frequently and resulted in greater heart rate elevation. Both types of dynamic workstations were used by the employees and had positive effects on physiological activation. The implementation of either type can be recommended. Copyright © 2018 Elsevier Ltd. All rights reserved.

Designing a dynamic dissolution method: a review of instrumental options and corresponding physiology of stomach and small intestine.

PubMed

Culen, Martin; Rezacova, Anna; Jampilek, Josef; Dohnal, Jiri

2013-09-01

Development of new pharmaceutical compounds and dosage forms often requires in vitro dissolution testing with the closest similarity to the human gastrointestinal (GI) tract. To create such conditions, one needs a suitable dissolution apparatus and the appropriate data on the human GI physiology. This review discusses technological approaches applicable in biorelevant dissolutions as well as the physiology of stomach and small intestine in both fasted and fed state, that is, volumes of contents, transit times for water/food and various solid oral dosage forms, pH, osmolality, surface tension, buffer capacity, and concentrations of bile salts, phospholipids, enzymes, and Ca(2+) ions. The information is aimed to provide clear suggestions on how these conditions should be set in a dynamic biorelevant dissolution test. Copyright © 2013 Wiley Periodicals, Inc.

Catalytic Asymmetric Synthesis of Butenolides and Butyrolactones

PubMed Central

2017-01-01

γ-Butenolides, γ-butyrolactones, and derivatives, especially in enantiomerically pure form, constitute the structural core of numerous natural products which display an impressive range of biological activities which are important for the development of novel physiological and therapeutic agents. Furthermore, optically active γ-butenolides and γ-butyrolactones serve also as a prominent class of chiral building blocks for the synthesis of diverse biological active compounds and complex molecules. Taking into account the varying biological activity profiles and wide-ranging structural diversity of the optically active γ-butenolide or γ-butyrolactone structure, the development of asymmetric synthetic strategies for assembling such challenging scaffolds has attracted major attention from synthetic chemists in the past decade. This review offers an overview of the different enantioselective synthesis of γ-butenolides and γ-butyrolactones which employ catalytic amounts of metal complexes or organocatalysts, with emphasis focused on the mechanistic issues that account for the observed stereocontrol of the representative reactions, as well as practical applications and synthetic potentials. PMID:28640622

Peroxiredoxin 6 in the repair of peroxidized cell membranes and cell signaling.

PubMed

Fisher, Aron B

2017-03-01

Peroxiredoxin 6 represents a widely distributed group of peroxiredoxins that contain a single conserved cysteine in the protein monomer (1-cys Prdx). The cys when oxidized to the sulfenic form is reduced with glutathione (GSH) catalyzed by the π isoform of GSH-S-transferase. Three enzymatic activities of the protein have been described:1) peroxidase with H 2 O 2 , short chain hydroperoxides, and phospholipid hydroperoxides as substrates; 2) phospholipase A 2 (PLA 2 ); and 3) lysophosphatidylcholine acyl transferase (LPCAT). These activities have important physiological roles in antioxidant defense, turnover of cellular phospholipids, and the generation of superoxide anion via initiation of the signaling cascade for activation of NADPH oxidase (type 2). The ability of Prdx6 to reduce peroxidized cell membrane phospholipids (peroxidase activity) and also to replace the oxidized sn-2 fatty acyl group through hydrolysis/reacylation (PLA 2 and LPCAT activities) provides a complete system for the repair of peroxidized cell membranes. Copyright © 2016 Elsevier Inc. All rights reserved.

Identification of structural determinants controlling human and mouse stromelysin-3 proteolytic activities.

PubMed

Noël, A; Santavicca, M; Stoll, I; L'Hoir, C; Staub, A; Murphy, G; Rio, M C; Basset, P

1995-09-29

Matrix metalloproteinases (matrixins) constitute a group of extracellular proteinases belonging to the metzincin superfamily. They are involved in both physiological and pathological tissue remodeling processes, including those associated with cancer progression. Stromelysin-3, which is expressed in most invasive human carcinomas, is a matrix metalloproteinase with unusual functional properties. In particular, its mature form does not cleave any of the major extracellular matrix components. To define critical structural determinants involved in controlling stromelysin-3 proteolytic activity, we have used site-directed mutagenesis. We show that the deletion of at least 175 C-terminal amino-acids is sufficient to endow mouse stromelysin-3 with activities against casein, laminin, and type IV collagen. In the case of the human enzyme, however, a further and single Ala-235-->Pro substitution is necessary to observe similar activities. Ala-235, which characterizes human stromelysin-3 among matrixins, is located immediately after the C terminus of the "Met-turn," which forms a hydrophobic basis for the catalytic zinc atom in the metzincin family. We conclude that human stromelysin-3 has gained specific functional properties during evolution by amino acid substitution in the catalytic zinc environment, and that it represents an attractive target for specific inhibitors that may be used to prevent cancer progression.

GLIS1-3 transcription factors: critical roles in the regulation of multiple physiological processes and diseases.

PubMed

Jetten, Anton M

2018-05-19

Krüppel-like zinc finger proteins form one of the largest families of transcription factors. They function as key regulators of embryonic development and a wide range of other physiological processes, and are implicated in a variety of pathologies. GLI-similar 1-3 (GLIS1-3) constitute a subfamily of Krüppel-like zinc finger proteins that act either as activators or repressors of gene transcription. GLIS3 plays a critical role in the regulation of multiple biological processes and is a key regulator of pancreatic β cell generation and maturation, insulin gene expression, thyroid hormone biosynthesis, spermatogenesis, and the maintenance of normal kidney functions. Loss of GLIS3 function in humans and mice leads to the development of several pathologies, including neonatal diabetes and congenital hypothyroidism, polycystic kidney disease, and infertility. Single nucleotide polymorphisms in GLIS3 genes have been associated with increased risk of several diseases, including type 1 and type 2 diabetes, glaucoma, and neurological disorders. GLIS2 plays a critical role in the kidney and GLIS2 dysfunction leads to nephronophthisis, an end-stage, cystic renal disease. In addition, GLIS1-3 have regulatory functions in several stem/progenitor cell populations. GLIS1 and GLIS3 greatly enhance reprogramming efficiency of somatic cells into induced embryonic stem cells, while GLIS2 inhibits reprogramming. Recent studies have obtained substantial mechanistic insights into several physiological processes regulated by GLIS2 and GLIS3, while a little is still known about the physiological functions of GLIS1. The localization of some GLIS proteins to the primary cilium suggests that their activity may be regulated by a downstream primary cilium-associated signaling pathway. Insights into the upstream GLIS signaling pathway may provide opportunities for the development of new therapeutic strategies for diabetes, hypothyroidism, and other diseases.

pH-Dependent Solution Structure and Activity of a Reduced Form of the Host-Defense Peptide Myticin C (Myt C) from the Mussel Mytilus galloprovincialis

PubMed Central

Martinez-Lopez, Alicia; Encinar, Jose Antonio; Medina-Gali, Regla Maria; Balseiro, Pablo; Garcia-Valtanen, Pablo; Figueras, Antonio; Novoa, Beatriz; Estepa, Amparo

2013-01-01

Myticin C (Myt C) is a highly variable host-defense peptide (HDP) associated to the immune response in the mediterranean mussel (Mytilus galloprovincialis), which has shown to be active across species due to its strong antiviral activity against a fish rhabdovirus found in fish cells overexpressing this HDP. However, the potential antimicrobial properties of any synthetic analogue of Myt C has not yet been analysed. Thus, in this work we have synthesised the sequence of the mature peptide of Myt C variant c and analysed the structure activity relationships of its reduced (non-oxidized) form (red-MytCc). In contrast to results previously reported for oxidized isoforms of mussel myticins, red-MytCc was not active against bacteria at physiological pH and showed a moderate antiviral activity against the viral haemorrhagic septicaemia (VHS) rhabdovirus. However, its chemotactic properties remained active. Structure/function studies in neutral and acid environments by means of infrared spectroscopy indicated that the structure of red-MytCc is pH dependent, with acid media increasing its alpha-helical content. Furthermore, red-MytCc was able to efficiently aggregate artificial phospholipid membranes at low pH, as well as to inhibit the Escherichia coli growth, suggesting that this activity is attributable to its more structured form in an acidic environment. All together, these results highlight the dynamic and environmentally sensitive behavior of red-Myt C in solution, and provide important insights into Myt C structure/activity relationships and the requirements to exert its antimicrobial/immunomodulatory activities. On the other hand, the pH-dependent direct antimicrobial activity of Myt C suggests that this HDP may be a suitable template for the development of antimicrobial agents that would function selectively in specific pH environments, which are sorely needed in this “antibiotic-resistance era”. PMID:23880927

Outside of the laboratory: Associations of working-memory performance with psychological and physiological arousal vary with age.

PubMed

Riediger, Michaela; Wrzus, Cornelia; Klipker, Kathrin; Müller, Viktor; Schmiedek, Florian; Wagner, Gert G

2014-03-01

We investigated age differences in associations among self-reported experiences of tense and energetic arousal, physiological activation indicated by heart rate, and working-memory performance in everyday life. The sample comprised 92 participants aged 14-83 years. Data were collected for 24 hr while participants pursued their normal daily routines. Participants wore an ambulatory biomonitoring system that recorded their cardiac and physical activity. Using mobile phones as assessment devices, they also provided an average of 7 assessments of their momentary experiences of tense arousal (feeling nervous) and energetic arousal (feeling wide-awake) and completed 2 trials of a well-practiced working-memory task. Experiences of higher energetic arousal were associated with higher heart rate in participants younger than 50 years of age but not in participants older than that, and energetic arousal was unrelated to within-person fluctuations in working-memory performance. Experiences of tense arousal were associated with higher heart rate independent of participants' age. Tense arousal and physiological activation were accompanied by momentary impairments in working-memory performance in middle-aged and older adults but not in younger individuals. Results suggest that psychological arousal experiences are associated with lower working-memory performance in middle-aged and older adults when they are accompanied by increased physiological activation and that the same is true for physiological activation deriving from other influences. Hence, age differences in cognitive performance may be exaggerated when the assessment situation itself elicits tense arousal or occurs in situations with higher physiological arousal arising from affective experiences, physical activity, or circadian rhythms. (c) 2014 APA, all rights reserved.

Determining environmental causes of biological effects: the need for a mechanistic physiological dimension in conservation biology.

PubMed

Seebacher, Frank; Franklin, Craig E

2012-06-19

The emerging field of Conservation Physiology links environmental change and ecological success by the application of physiological theory, approaches and tools to elucidate and address conservation problems. Human activity has changed the natural environment to a point where the viability of many ecosystems is now under threat. There are already many descriptions of how changes in biological patterns are correlated with environmental changes. The next important step is to determine the causative relationship between environmental variability and biological systems. Physiology provides the mechanistic link between environmental change and ecological patterns. Physiological research, therefore, should be integrated into conservation to predict the biological consequences of human activity, and to identify those species or populations that are most vulnerable.

Predicting preschoolers' social-cognitive play behavior: attachment, peers, temperament, and physiological regulation.

PubMed

Porter, Christin L

2009-04-01

Research on children's social-cognitive play typologies (i.e., active and passive forms of solitary and social play) suggests links of early play behaviors and later social development and risk status. To date, few studies have examined simultaneously suspected links between children's social-cognitive play types and factors believed to shape these early social-play behaviors. This study examined a simultaneous model of individual (temperament, physiology) and relational variables (attachment, peer networks) believed to influence children's social-cognitive play types, including individual characteristics drawn from the Child Behavior Questionnaire which measures dimensions of shyness and impulsivity, a lab-based assessment of social withdrawal, and physiological markers linked to social regulation (cardiac vagal tone and vagal regulation). Children's attachment status to parents was gathered using Q-Sort methodology, and a measure of previous peer network size was obtained from parents' reports to examine potential links between relational history and social-cognitive play types. Predictive discriminant function analysis showed that children's (N = 54, age range 35 to 58 months) social-cognitive play was better predicted on the basis of multiple independent variables than individual, zero-order relations. When predicting children's social-cognitive play typologies, a multidimensional view which encompasses both individual characteristics and social-relational variables may best predict social -cognitive play types and help understanding of children's social trajectories.

Using a Combined Approach of Guided Inquiry & Direct Instruction to Explore How Physiology Affects Behavior

ERIC Educational Resources Information Center

Machtinger, Erika T.

2014-01-01

Hands-on activities with live organisms allow students to actively explore scientific investigation. Here, I present activities that combine guided inquiry with direct instruction and relate how nutrition affects the physiology and behavior of the common housefly. These experiments encourage student involvement in the formulation of experimental…

Physiological investigation of automobile driver's activation index using simulated monotonous driving.

PubMed

Yamakoshi, T; Yamakoshi, K; Tanaka, S; Nogawa, M; Kusakabe, M; Kusumi, M; Tanida, K

2004-01-01

Monotonous automobile operation in our daily life may cause the lowering of what might be termed an activation state of the human body, resulting in an increased risk of an accident. We therefore propose to create a more suitable environment in-car so as to allow active operation of the vehicle, hopefully thus avoiding potentially dangerous situations during driving. In order to develop such an activation method as a final goal, we have firstly focused on the acquisition of physiological variables, including cardiovascular parameters, during presentation to the driver of a monotonous screen image, simulating autonomous travel of constant-speed on a motorway. Subsequently, we investigated the derivation of a driver's activation index. During the screen image presentation, a momentary electrical stimulation of about 1 second duration was involuntarily applied to a subject's shoulder to obtain a physiological response. We have successfully monitored various physiological variables during the image presentation, and results suggest that a peculiar pattern in the beat-by-beat change of blood pressure in response to the involuntary stimulus may be an appropriate, and feasible, index relevant to activation state.

Stereocomplexes Formed From Select Oligomers of Polymer d-lactic Acid (PDLA) and l-lactate May Inhibit Growth of Cancer Cells and Help Diagnose Aggressive Cancers-Applications of the Warburg Effect.

PubMed

Goldberg, Joel S

2011-02-15

It is proposed that select oligomers of polymer d-lactic acid (PDLA) will form a stereocomplex with l-lactate in vivo, producing lactate deficiency in tumor cells. Those cancer cells that utilize transport of lactate to maintain electrical neutrality may cease to multiply or die because of lactate trapping, and those cancer cells that benefit from utilization of extracellular lactate may be impaired. Intracellular trapping of lactate produces a different physiology than inhibition of LDH because the cell loses the option of shuttling pyruvate to an alternative pathway to produce an anion. Conjugated with stains or fluorescent probes, PDLA oligomers may be an agent for the diagnosis of tissue lactate and possibly cell differentiation in biopsy specimens. Preliminary experimental evidence is presented confirming that PDLA in high concentrations is cytotoxic and that l-lactate forms a presumed stereocomplex with PDLA. Future work should be directed at isolation of biologically active oligomers of PDLA.

Carboxylic Acids Plasma Membrane Transporters in Saccharomyces cerevisiae.

PubMed

Casal, Margarida; Queirós, Odília; Talaia, Gabriel; Ribas, David; Paiva, Sandra

2016-01-01

This chapter covers the functionally characterized plasma membrane carboxylic acids transporters Jen1, Ady2, Fps1 and Pdr12 in the yeast Saccharomyces cerevisiae, addressing also their homologues in other microorganisms, as filamentous fungi and bacteria. Carboxylic acids can either be transported into the cells, to be used as nutrients, or extruded in response to acid stress conditions. The secondary active transporters Jen1 and Ady2 can mediate the uptake of the anionic form of these substrates by a H(+)-symport mechanism. The undissociated form of carboxylic acids is lipid-soluble, crossing the plasma membrane by simple diffusion. Furthermore, acetic acid can also be transported by facilitated diffusion via Fps1 channel. At the cytoplasmic physiological pH, the anionic form of the acid prevails and it can be exported by the Pdr12 pump. This review will highlight the mechanisms involving carboxylic acids transporters, and the way they operate according to the yeast cell response to environmental changes, as carbon source availability, extracellular pH and acid stress conditions.

Source-based neurofeedback methods using EEG recordings: training altered brain activity in a functional brain source derived from blind source separation

PubMed Central

White, David J.; Congedo, Marco; Ciorciari, Joseph

2014-01-01

A developing literature explores the use of neurofeedback in the treatment of a range of clinical conditions, particularly ADHD and epilepsy, whilst neurofeedback also provides an experimental tool for studying the functional significance of endogenous brain activity. A critical component of any neurofeedback method is the underlying physiological signal which forms the basis for the feedback. While the past decade has seen the emergence of fMRI-based protocols training spatially confined BOLD activity, traditional neurofeedback has utilized a small number of electrode sites on the scalp. As scalp EEG at a given electrode site reflects a linear mixture of activity from multiple brain sources and artifacts, efforts to successfully acquire some level of control over the signal may be confounded by these extraneous sources. Further, in the event of successful training, these traditional neurofeedback methods are likely influencing multiple brain regions and processes. The present work describes the use of source-based signal processing methods in EEG neurofeedback. The feasibility and potential utility of such methods were explored in an experiment training increased theta oscillatory activity in a source derived from Blind Source Separation (BSS) of EEG data obtained during completion of a complex cognitive task (spatial navigation). Learned increases in theta activity were observed in two of the four participants to complete 20 sessions of neurofeedback targeting this individually defined functional brain source. Source-based EEG neurofeedback methods using BSS may offer important advantages over traditional neurofeedback, by targeting the desired physiological signal in a more functionally and spatially specific manner. Having provided preliminary evidence of the feasibility of these methods, future work may study a range of clinically and experimentally relevant brain processes where individual brain sources may be targeted by source-based EEG neurofeedback. PMID:25374520

Involvement of distinct arrestin-1 elements in binding to different functional forms of rhodopsin

PubMed Central

Zhuang, Tiandi; Chen, Qiuyan; Cho, Min-Kyu; Vishnivetskiy, Sergey A.; Iverson, Tina M.; Gurevich, Vsevolod V.; Sanders, Charles R.

2013-01-01

Solution NMR spectroscopy of labeled arrestin-1 was used to explore its interactions with dark-state phosphorylated rhodopsin (P-Rh), phosphorylated opsin (P-opsin), unphosphorylated light-activated rhodopsin (Rh*), and phosphorylated light-activated rhodopsin (P-Rh*). Distinct sets of arrestin-1 elements were seen to be engaged by Rh* and inactive P-Rh, which induced conformational changes that differed from those triggered by binding of P-Rh*. Although arrestin-1 affinity for Rh* was seen to be low (KD > 150 μM), its affinity for P-Rh (KD ∼80 μM) was comparable to the concentration of active monomeric arrestin-1 in the outer segment, suggesting that P-Rh generated by high-gain phosphorylation is occupied by arrestin-1 under physiological conditions and will not signal upon photo-activation. Arrestin-1 was seen to bind P-Rh* and P-opsin with fairly high affinity (KD of ∼50 and 800 nM, respectively), implying that arrestin-1 dissociation is triggered only upon P-opsin regeneration with 11-cis-retinal, precluding noise generated by opsin activity. Based on their observed affinity for arrestin-1, P-opsin and inactive P-Rh very likely affect the physiological monomer-dimer-tetramer equilibrium of arrestin-1, and should therefore be taken into account when modeling photoreceptor function. The data also suggested that complex formation with either P-Rh* or P-opsin results in a global transition in the conformation of arrestin-1, possibly to a dynamic molten globule-like structure. We hypothesize that this transition contributes to the mechanism that triggers preferential interactions of several signaling proteins with receptor-activated arrestins. PMID:23277586

Involvement of distinct arrestin-1 elements in binding to different functional forms of rhodopsin.

PubMed

Zhuang, Tiandi; Chen, Qiuyan; Cho, Min-Kyu; Vishnivetskiy, Sergey A; Iverson, Tina M; Gurevich, Vsevolod V; Sanders, Charles R

2013-01-15

Solution NMR spectroscopy of labeled arrestin-1 was used to explore its interactions with dark-state phosphorylated rhodopsin (P-Rh), phosphorylated opsin (P-opsin), unphosphorylated light-activated rhodopsin (Rh*), and phosphorylated light-activated rhodopsin (P-Rh*). Distinct sets of arrestin-1 elements were seen to be engaged by Rh* and inactive P-Rh, which induced conformational changes that differed from those triggered by binding of P-Rh*. Although arrestin-1 affinity for Rh* was seen to be low (K(D) > 150 μM), its affinity for P-Rh (K(D) ~80 μM) was comparable to the concentration of active monomeric arrestin-1 in the outer segment, suggesting that P-Rh generated by high-gain phosphorylation is occupied by arrestin-1 under physiological conditions and will not signal upon photo-activation. Arrestin-1 was seen to bind P-Rh* and P-opsin with fairly high affinity (K(D) of~50 and 800 nM, respectively), implying that arrestin-1 dissociation is triggered only upon P-opsin regeneration with 11-cis-retinal, precluding noise generated by opsin activity. Based on their observed affinity for arrestin-1, P-opsin and inactive P-Rh very likely affect the physiological monomer-dimer-tetramer equilibrium of arrestin-1, and should therefore be taken into account when modeling photoreceptor function. The data also suggested that complex formation with either P-Rh* or P-opsin results in a global transition in the conformation of arrestin-1, possibly to a dynamic molten globule-like structure. We hypothesize that this transition contributes to the mechanism that triggers preferential interactions of several signaling proteins with receptor-activated arrestins.

Tumor regression achieved by encapsulating a moderately soluble drug into a polymeric thermogel

PubMed Central

Ci, Tianyuan; Chen, Liang; Yu, Lin; Ding, Jiandong

2014-01-01

For cancer chemotherapy, a tumor regression without any surgical resection and severe side effects is greatly preferred to merely slowing down the growth of tumors. Here, we report a formulation composed of irinotecan (IRN) and poly(D,L-lactide-co-glycolide)-b-poly(ethylene glycol)-b-poly(D,L-lactide-co-glycolide) (PLGA-PEG-PLGA). IRN is a clinically used antitumor drug with active and inactive chemical forms in equilibrium, and the major form at physiological conditions is inactive but still has side effects. The aqueous solution of the PLGA-PEG-PLGA is a sol at room temperature and physically gels at body temperature, forming a thermogel. We successfully mixed this moderately soluble drug into the amphiphilic copolymer aqueous solution for the first time. The mixture was subcutaneously injected into nude mice with xenografted SW620 human colon tumors. Excellent in vivo antitumor efficacy was observed in the group that received the IRN-loaded thermogel. The tumor was significantly regressed after being treated with the IRN/thermogel, and the side effects (blood toxicity and body weight decrease) were very mild. These results might be attributed to the ideal sustained release profile and period of release of the drug from the thermogel and to the significant enhancement of the fraction of the active form of the drug by the thermogel. PMID:24980734

Tumor regression achieved by encapsulating a moderately soluble drug into a polymeric thermogel

NASA Astrophysics Data System (ADS)

Ci, Tianyuan; Chen, Liang; Yu, Lin; Ding, Jiandong

2014-07-01

For cancer chemotherapy, a tumor regression without any surgical resection and severe side effects is greatly preferred to merely slowing down the growth of tumors. Here, we report a formulation composed of irinotecan (IRN) and poly(D,L-lactide-co-glycolide)-b-poly(ethylene glycol)-b-poly(D,L-lactide-co-glycolide) (PLGA-PEG-PLGA). IRN is a clinically used antitumor drug with active and inactive chemical forms in equilibrium, and the major form at physiological conditions is inactive but still has side effects. The aqueous solution of the PLGA-PEG-PLGA is a sol at room temperature and physically gels at body temperature, forming a thermogel. We successfully mixed this moderately soluble drug into the amphiphilic copolymer aqueous solution for the first time. The mixture was subcutaneously injected into nude mice with xenografted SW620 human colon tumors. Excellent in vivo antitumor efficacy was observed in the group that received the IRN-loaded thermogel. The tumor was significantly regressed after being treated with the IRN/thermogel, and the side effects (blood toxicity and body weight decrease) were very mild. These results might be attributed to the ideal sustained release profile and period of release of the drug from the thermogel and to the significant enhancement of the fraction of the active form of the drug by the thermogel.

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

PubMed

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

2007-06-01

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

The Comparative Research on Sex Education for Adolescents of China and the US

ERIC Educational Resources Information Center

Yu-feng, Zhou

2012-01-01

Sex education refers to people's comprehension about sex, which involves not only sexual structure (anatomy, physiology, birth control, pregnancy, etc.), but also sexual relationships concerning human and moral problems. It includes at least sexual physiology, sexual psychology, sexual ethic, sexual law, etc., which aims to help people form the…

Effects of different forms of physiology instruction on the development of students' conceptions of and approaches to science learning.

PubMed

Lin, Yi-Hui; Liang, Jyh-Chong; Tsai, Chin-Chung

2012-03-01

The purpose of this study was to investigate students' conceptions of and approaches to learning science in two different forms: internet-assisted instruction and traditional (face-to-face only) instruction. The participants who took part in the study were 79 college students enrolled in a physiology class in north Taiwan. In all, 46 of the participants were from one class and 33 were from another class. Using a quasi-experimental research approach, the class of 46 students was assigned to be the "internet-assisted instruction group," whereas the class of 33 students was assigned to be the "traditional instruction group." The treatment consisted of a series of online inquiry activities. To explore the effects of different forms of instruction on students' conceptions of and approaches to learning science, two questionnaires were administered before and after the instruction: the Conceptions of Learning Science Questionnaire and the Approaches to Learning Science Questionnaire. Analysis of covariance results revealed that the students in the internet-assisted instruction group showed less agreement than the traditional instruction group in the less advanced conceptions of learning science (such as learning as memorizing and testing). In addition, the internet-assisted instruction group displayed significantly more agreement than the traditional instruction group in more sophisticated conceptions (such as learning as seeing in a new way). Moreover, the internet-assisted instruction group expressed more orientation toward the approaches of deep motive and deep strategy than the traditional instruction group. However, the students in the internet-assisted instruction group also showed more surface motive than the traditional instruction group did.

Pseudomonas putida KT2440 Strain Metabolizes Glucose through a Cycle Formed by Enzymes of the Entner-Doudoroff, Embden-Meyerhof-Parnas, and Pentose Phosphate Pathways.

PubMed

Nikel, Pablo I; Chavarría, Max; Fuhrer, Tobias; Sauer, Uwe; de Lorenzo, Víctor

2015-10-23

The soil bacterium Pseudomonas putida KT2440 lacks a functional Embden-Meyerhof-Parnas (EMP) pathway, and glycolysis is known to proceed almost exclusively through the Entner-Doudoroff (ED) route. To investigate the raison d'être of this metabolic arrangement, the distribution of periplasmic and cytoplasmic carbon fluxes was studied in glucose cultures of this bacterium by using (13)C-labeled substrates, combined with quantitative physiology experiments, metabolite quantification, and in vitro enzymatic assays under both saturating and non-saturating, quasi in vivo conditions. Metabolic flux analysis demonstrated that 90% of the consumed sugar was converted into gluconate, entering central carbon metabolism as 6-phosphogluconate and further channeled into the ED pathway. Remarkably, about 10% of the triose phosphates were found to be recycled back to form hexose phosphates. This set of reactions merges activities belonging to the ED, the EMP (operating in a gluconeogenic fashion), and the pentose phosphate pathways to form an unforeseen metabolic architecture (EDEMP cycle). Determination of the NADPH balance revealed that the default metabolic state of P. putida KT2440 is characterized by a slight catabolic overproduction of reducing power. Cells growing on glucose thus run a biochemical cycle that favors NADPH formation. Because NADPH is required not only for anabolic functions but also for counteracting different types of environmental stress, such a cyclic operation may contribute to the physiological heftiness of this bacterium in its natural habitats. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Differential Activation of Pontomedullary Nuclei by Acid Perfusion of Different Regions of the Esophagus

PubMed Central

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

2010-01-01

The objective of this study was to determine the brain stem nuclei and physiological responses activated by esophageal acidification. The effects of perfusion of the cervical (ESOc), or thoracic (ESOt) esophagus with PBS or HCl on c-fos immunoreactivity of the brain stem or on physiological variables, and the effects of vagotomy were examined in anesthetized cats. We found that acidification of the ESOc increased the number of c-fos positive neurons in the area postrema (AP), vestibular nucleus (VN), parabrachial nucleus (PBN), nucleus ambiguus (NA), dorsal motor nucleus (DMN), and all subnuclei of the nucleus tractus solitarius (NTS), but one. Acidification of the ESOt activated neurons in the central (CE), caudal (CD), dorsomedial (DM), dorsolateral (DL), ventromedial (VM) subnuclei of NTS, and the DMN. Vagotomy blocked all c-fos responses to acid perfusion of the whole esophagus (ESOw). Perfusion of the ESOc or ESOt with PBS activated secondary peristalsis (2P), but had no effect on blood pressure, heart rate, or respiratory rate. Perfusion of the ESOc, but not ESOt, with HCL activated pharyngeal swallowing (PS), profuse salivation, or physiological correlates of emesis. Vagotomy blocked all physiological effects of ESOw perfusion. We conclude that acidification of the ESOc and ESOt activate different sets of pontomedullary nuclei and different physiological responses. The NTSce, NTScom, NTSdm, and DMN are associated with activation of 2P, the NTSim and NTSis, are associated with activation of PS, and the AP, VN, and PBN are associated with activation of emesis and perhaps nausea. All responses to esophageal fluid perfusion or acidification are mediated by the vagus nerves. PMID:20655885

Controversial constitutive TSHR activity: patients, physiology, and in vitro characterization.

PubMed

Huth, S; Jaeschke, H; Schaarschmidt, J; Paschke, R

2014-06-01

G protein-coupled receptors constitute a large family of transmembrane receptors, which activate cellular responses by signal transmission and regulation of second messenger metabolism after ligand binding. For several of these receptors it is known that they also signal ligand-independently. The G protein-coupled thyroid stimulating hormone receptor (TSHR) is characterized by a high level of constitutive activity in the wild type state. However, little is known yet concerning the physiological relevance of the constitutive wild type TSHR activity. Certainly, knowledge of the physiological relevance of constitutive wild type receptor activity is necessary to better understand thyroid physiology and it is a prerequisite for the development of better therapies for nonautoimmune hyperthyroidism and thyroid cancer. Based on a literature search regarding all published TSHR mutations, this review covers several mutations which are clearly associated with a hyperthyroidism-phenotype, but interestingly show a lack of constitutive activity determined by in vitro characterization. Possible reasons for the observed discrepancies between clinical phenotypes and in vitro characterization results for constitutive TSHR activity are reviewed. All current in vitro characterization methods for constitutive TSHR mutations are "preliminary attempts" and may well be revised by more comprehensive and even better approaches. However, a standardized approach for the determination of constitutive activity can help to identify TSHR mutations for which the investigation of additional signaling mechanisms would be most interesting to find explanations for the current clinical phenotype/in vitro discrepancies and thereby also define suitable methods to explore the physiological relevance of constitutive wild type TSHR activity. © Georg Thieme Verlag KG Stuttgart · New York.

Mechanisms of physiological and pathological cardiac hypertrophy.

PubMed

Nakamura, Michinari; Sadoshima, Junichi

2018-04-19

Cardiomyocytes exit the cell cycle and become terminally differentiated soon after birth. Therefore, in the adult heart, instead of an increase in cardiomyocyte number, individual cardiomyocytes increase in size, and the heart develops hypertrophy to reduce ventricular wall stress and maintain function and efficiency in response to an increased workload. There are two types of hypertrophy: physiological and pathological. Hypertrophy initially develops as an adaptive response to physiological and pathological stimuli, but pathological hypertrophy generally progresses to heart failure. Each form of hypertrophy is regulated by distinct cellular signalling pathways. In the past decade, a growing number of studies have suggested that previously unrecognized mechanisms, including cellular metabolism, proliferation, non-coding RNAs, immune responses, translational regulation, and epigenetic modifications, positively or negatively regulate cardiac hypertrophy. In this Review, we summarize the underlying molecular mechanisms of physiological and pathological hypertrophy, with a particular emphasis on the role of metabolic remodelling in both forms of cardiac hypertrophy, and we discuss how the current knowledge on cardiac hypertrophy can be applied to develop novel therapeutic strategies to prevent or reverse pathological hypertrophy.

Mitochondrial adaptations to physiological vs. pathological cardiac hypertrophy

PubMed Central

Abel, E. Dale; Doenst, Torsten

2011-01-01

Cardiac hypertrophy is a stereotypic response of the heart to increased workload. The nature of the workload increase may vary depending on the stimulus (repetitive, chronic, pressure, or volume overload). If the heart fully adapts to the new loading condition, the hypertrophic response is considered physiological. If the hypertrophic response is associated with the ultimate development of contractile dysfunction and heart failure, the response is considered pathological. Although divergent signalling mechanisms may lead to these distinct patterns of hypertrophy, there is some overlap. Given the close relationship between workload and energy demand, any form of cardiac hypertrophy will impact the energy generation by mitochondria, which are the key organelles for cellular ATP production. Significant changes in the expression of nuclear and mitochondrially encoded transcripts that impact mitochondrial function as well as altered mitochondrial proteome composition and mitochondrial energetics have been described in various forms of cardiac hypertrophy. Here, we review mitochondrial alterations in pathological and physiological hypertrophy. We suggest that mitochondrial adaptations to pathological and physiological hypertrophy are distinct, and we shall review potential mechanisms that might account for these differences. PMID:21257612

Adenosine receptors regulate gap junction coupling of the human cerebral microvascular endothelial cells hCMEC/D3 by Ca2+ influx through cyclic nucleotide-gated channels.

PubMed

Bader, Almke; Bintig, Willem; Begandt, Daniela; Klett, Anne; Siller, Ina G; Gregor, Carola; Schaarschmidt, Frank; Weksler, Babette; Romero, Ignacio; Couraud, Pierre-Olivier; Hell, Stefan W; Ngezahayo, Anaclet

2017-04-15

Gap junction channels are essential for the formation and regulation of physiological units in tissues by allowing the lateral cell-to-cell diffusion of ions, metabolites and second messengers. Stimulation of the adenosine receptor subtype A 2B increases the gap junction coupling in the human blood-brain barrier endothelial cell line hCMEC/D3. Although the increased gap junction coupling is cAMP-dependent, neither the protein kinase A nor the exchange protein directly activated by cAMP were involved in this increase. We found that cAMP activates cyclic nucleotide-gated (CNG) channels and thereby induces a Ca 2+ influx, which leads to the increase in gap junction coupling. The report identifies CNG channels as a possible physiological link between adenosine receptors and the regulation of gap junction channels in endothelial cells of the blood-brain barrier. The human cerebral microvascular endothelial cell line hCMEC/D3 was used to characterize the physiological link between adenosine receptors and the gap junction coupling in endothelial cells of the blood-brain barrier. Expressed adenosine receptor subtypes and connexin (Cx) isoforms were identified by RT-PCR. Scrape loading/dye transfer was used to evaluate the impact of the A 2A and A 2B adenosine receptor subtype agonist 2-phenylaminoadenosine (2-PAA) on the gap junction coupling. We found that 2-PAA stimulated cAMP synthesis and enhanced gap junction coupling in a concentration-dependent manner. This enhancement was accompanied by an increase in gap junction plaques formed by Cx43. Inhibition of protein kinase A did not affect the 2-PAA-related enhancement of gap junction coupling. In contrast, the cyclic nucleotide-gated (CNG) channel inhibitor l-cis-diltiazem, as well as the chelation of intracellular Ca 2+ with BAPTA, or the absence of external Ca 2+ , suppressed the 2-PAA-related enhancement of gap junction coupling. Moreover, we observed a 2-PAA-dependent activation of CNG channels by a combination of electrophysiology and pharmacology. In conclusion, the stimulation of adenosine receptors in hCMEC/D3 cells induces a Ca 2+ influx by opening CNG channels in a cAMP-dependent manner. Ca 2+ in turn induces the formation of new gap junction plaques and a consecutive sustained enhancement of gap junction coupling. The report identifies CNG channels as a physiological link that integrates gap junction coupling into the adenosine receptor-dependent signalling of endothelial cells of the blood-brain barrier. © 2017 The Authors. The Journal of Physiology © 2017 The Physiological Society.

Impact of hand forces and start/stop frequency on physiological responses to three forms of pushing and pulling: a South African perspective.

PubMed

Ai, Todd

2012-01-01

There has been limited attention given to the physiological demands of pushing and pulling, especially in industrially developing countries such as South Africa. Two key factors affecting the physiological demands of these tasks are the hand forces exerted and the start/stop frequency. The purpose of the current study was therefore to investigate the physiological responses to pushing and pulling at various loads and start/stop frequencies. 36 male subjects participated in the study and were required to complete a total of 18 conditions (three techniques: pushing, two- and one-handed pulling; three loads: 200, 350 and 500 kg; and two frequencies: 2 and 4 stops per minute). During each condition the heart rate, oxygen uptake and energy expenditure were measured. Pushing was found to elicit significantly lower responses for all three dependent variables than either form of pulling. The start/stop frequency was also found to have a significant impact on subject responses. The findings of this study indicate that the technique adopted to maneuver loads is critical in determining the physical demands placed on the human operator. Furthermore increasing the frequency of start/stops plays an important role, thus the forces exerted during these two phases are important from a physiological perspective.

A double-blind atropine trial for active learning of autonomic function.

PubMed

Fry, Jeffrey R; Burr, Steven A

2011-12-01

Here, we describe a human physiology laboratory class measuring changes in autonomic function over time in response to atropine. Students use themselves as subjects, generating ownership and self-interest in the learning as well as directly experiencing the active link between physiology and pharmacology in people. The class is designed to concomitantly convey the importance of bias in experimentation by adopting a double-blind placebo-controlled approach. We have used this class effectively in various forms with ∼600 students receiving atropine over the last 16 yr. This class has received favorable feedback from staff and students of medicine, pharmacy, and neuroscience, and we recommend it for such undergraduates. The learning objectives that students are expected to achieve are to be able to 1) know the ethical, safety, and hygiene requirements for using human volunteers as subjects; 2) implement and explain a double-blind placebo-controlled trial; 3) design, agree, and execute a protocol for making (and accurately recording) precise reproducible measurements of pulse rate, pupil diameter, and salivary flow; 4) evaluate the importance of predose periods and measurement consistency to detect effects (including any reversibility) after an intervention; 5) experience direct cause-and-effect relationships integrating physiology with pharmacology in people; 6) calculate appropriate summary statistics to describe the data and determine the data's statistical significance; 7) recognize normal variability both within and between subjects in baseline physiological parameters and also recognize normal variability in response to pharmacological treatment; 8) infer the distribution and role of muscarinic receptors in the autonomic nervous system with respect to the heart, eye, and mouth; 9) identify and explain the clinical significance of differences in effect due to the route and formulation of atropine; 10) produce and deliver a concise oral presentation of experimental findings; and 11) produce a written report in the form of a short scientific research article. The results of a typical study are presented, which demonstrate that the administration of atropine by a subcutaneous injection elicited a significant increase in pulse rate and pupil diameter and a significant decrease in salivary flow, whereas administration of atropine in an oral liquid elicited significant effects on pulse rate and salivary flow, and an oral solid format elicited a significant alteration in salivary flow alone. More detailed analysis of the salivary flow data demonstrated clear differences between the routes of administration and formulation in the onset and magnitude of action of atropine.

Stimulation of endogenous cardioblasts by exogenous cell therapy after myocardial infarction

PubMed Central

Malliaras, Konstantinos; Ibrahim, Ahmed; Tseliou, Eleni; Liu, Weixin; Sun, Baiming; Middleton, Ryan C; Seinfeld, Jeffrey; Wang, Lai; Sharifi, Behrooz G; Marbán, Eduardo

2014-01-01

Controversy surrounds the identity, origin, and physiologic role of endogenous cardiomyocyte progenitors in adult mammals. Using an inducible genetic labeling approach to identify small non-myocyte cells expressing cardiac markers, we find that activated endogenous cardioblasts are rarely evident in the normal adult mouse heart. However, myocardial infarction results in significant cardioblast activation at the site of injury. Genetically labeled isolated cardioblasts express cardiac transcription factors and sarcomeric proteins, exhibit spontaneous contractions, and form mature cardiomyocytes in vivo after injection into unlabeled recipient hearts. The activated cardioblasts do not arise from hematogenous seeding, cardiomyocyte dedifferentiation, or mere expansion of a preformed progenitor pool. Cell therapy with cardiosphere-derived cells amplifies innate cardioblast-mediated tissue regeneration, in part through the secretion of stromal cell-derived factor 1 by transplanted cells. Thus, stimulation of endogenous cardioblasts by exogenous cells mediates therapeutic regeneration of injured myocardium. PMID:24797668

Neural Pathways of Embarrassment and their Modulation by Social Anxiety

PubMed Central

Müller-Pinzler, L; Gazzola, V; Keysers, C; Sommer, J; Jansen, A; Frässle, S; Einhäuser, W

2016-01-01

While being in the center of attention and exposed to other’s evaluations humans are prone to experience embarrassment. To characterize the neural underpinnings of such aversive moments, we induced genuine experiences of embarrassment during person-group interactions in a functional neuroimaging study. Using a mock-up scenario with three confederates, we examined how the presence of an audience affected physiological and neural responses and the reported emotional experiences of failures and achievements. The results indicated that publicity induced activations in mentalizing areas and failures led to activations in arousal processing systems. Mentalizing activity as well as attention towards the audience were increased in socially anxious participants. The converging integration of information from mentalizing areas and arousal processing systems within the ventral anterior insula and amygdala form the neural pathways of embarrassment. Targeting these neural markers of embarrassment in the (para-)limbic system provides new perspectives for developing treatment strategies for social anxiety disorders. PMID:26093329

ATP sulfurylase from higher plants: kinetic and structural characterization of the chloroplast and cytosol enzymes from spinach leaf.

PubMed

Renosto, F; Patel, H C; Martin, R L; Thomassian, C; Zimmerman, G; Segel, I H

1993-12-01

Two forms of ATP sulfurylase were purified from spinach leaf. The major (chloroplast) form accounts for 85 to 90% of the total leaf activity (0.03 +/- 0.01 adenosine-5'-phosphosulfate (APS) synthesis units x gram fresh weight-1). Both enzyme forms appear to be tetramers composed of 49- to 50-kDa subunits with the minor (cytosolic) form being slightly larger than the chloroplast form. The specific activities (units x milligram protein-1) of the chloroplast form at pH 8.0, 30 degrees C, were as follows: APS synthesis, 16; molybdolysis, 229; ATP synthesis, 267; selenolysis, 4.1; fluorophosphate activation, 11. Kinetic constants for the physiological reaction were as follows: KmA = 0.046 mM, K(ia) = 0.85 mM, KmB = 0.25 mM, KmQ = 0.37 microM, K(iq) = 64-85 nM, and KmP = 10 microM, where A = MgATP, B = SO4(2-), P = total PPi at 5 mM Mg2+, and Q = APS. The kinetic constants for molybdolysis were similar to those of the APS synthesis reaction. The kinetic constants of the minor (cytosol) form were similar to those of the major form with two exceptions: (a) The molybdolysis activity was 120 units x milligram protein-1, yielding a Vmax (ATP synthesis)/Vmax (molybdolysis) ratio close to 2 (compared to about unity for the chloroplast form) and (b) KmA was greater (0.24 and 0.15 mM for APS synthesis and molybdolysis, respectively). Initial velocity measurements (made over an extended range of MgATP and SO4(2-) concentrations), product inhibition studies (by initial velocity methods and by reaction progress curve analyses), dead end inhibition studies (with monovalent and divalent oxyanions), and kcat/Km comparisons (for SO4(2-) and MoO4(2-) support a random AB-ordered PQ kinetic mechanism in which MgATP and SO4(2-) bind in a highly synergistic manner. Equilibrium binding studies indicated the presence of one APS site per subunit. HPLC elution profiles of chymotryptic and tryptic peptides were essentially the same for both enzyme forms. The N-terminal sequence of residues 5-20 of the cytosol enzyme was identical to residues 1-16 of the chloroplast enzyme.

Effect of 11-Cis 13-Demethylretinal on Phototransduction in Bleach-Adapted Rod and Cone Photoreceptors

PubMed Central

Corson, D.Wesley; Kefalov, Vladimir J.; Cornwall, M. Carter; Crouch, Rosalie K.

2000-01-01

We used 11-cis 13-demethylretinal to examine the physiological consequences of retinal's noncovalent interaction with opsin in intact rod and cone photoreceptors during visual pigment regeneration. 11-Cis 13-demethylretinal is an analog of 11-cis retinal in which the 13 position methyl group has been removed. Biochemical experiments have shown that it is capable of binding in the chromophore pocket of opsin, forming a Schiff-base linkage with the protein to produce a pigment, but at a much slower rate than the native 11-cis retinal (Nelson, R., J. Kim deReil, and A. Kropf. 1970. Proc. Nat. Acad. Sci. USA. 66:531–538). Experimentally, this slow rate of pigment formation should allow separate physiological examination of the effects of the initial binding of retinal in the pocket and the subsequent formation of the protonated Schiff-base linkage. Currents from solitary rods and cones from the tiger salamander were recorded in darkness before and after bleaching and then after exposure to 11-cis 13-demethylretinal. In bleach-adapted rods, 11-cis 13-demethylretinal caused transient activation of phototransduction, as evidenced by a decrease of the dark current and sensitivity, acceleration of the dim flash responses, and activation of cGMP phosphodiesterase and guanylyl cyclase. The steady state of phototransduction activity was still higher than that of the bleach-adapted rod. In contrast, exposure of bleach-adapted cones to 11-cis 13-demethylretinal resulted in an immediate deactivation of transduction as measured by the same parameters. These results extend the validity of a model for the effects of the noncovalent binding of a retinoid in the chromophore pockets of rod and cone opsins to analogs capable of forming a Schiff-base and imply that the noncovalent binding by itself may play a role for the dark adaptation of photoreceptors. PMID:10919871

Biologically Active and Antimicrobial Peptides from Plants

PubMed Central

Salas, Carlos E.; Badillo-Corona, Jesus A.; Ramírez-Sotelo, Guadalupe; Oliver-Salvador, Carmen

2015-01-01

Bioactive peptides are part of an innate response elicited by most living forms. In plants, they are produced ubiquitously in roots, seeds, flowers, stems, and leaves, highlighting their physiological importance. While most of the bioactive peptides produced in plants possess microbicide properties, there is evidence that they are also involved in cellular signaling. Structurally, there is an overall similarity when comparing them with those derived from animal or insect sources. The biological action of bioactive peptides initiates with the binding to the target membrane followed in most cases by membrane permeabilization and rupture. Here we present an overview of what is currently known about bioactive peptides from plants, focusing on their antimicrobial activity and their role in the plant signaling network and offering perspectives on their potential application. PMID:25815307

An in vivo strategy to counteract post-administration anticoagulant activity of azido-Warfarin

NASA Astrophysics Data System (ADS)

Ursuegui, Sylvain; Recher, Marion; Krężel, Wojciech; Wagner, Alain

2017-05-01

Drugs, usually long acting and metabolically stable molecules, might be the source of adverse effects triggered by complex drug interactions, anaphylaxis and drug-induced coagulopathy. To circumvent this growing drug safety issue, we herein investigate the opportunity offered by bio-orthogonal chemistry for in vivo drug neutralization. We design a small-molecule anticoagulant drug (Warfarin) containing an azide group that acts as a safety pin. It allows drug deactivation and restoration of physiological coagulation via in vivo click reaction with a suitable cyclooctyne-based neutralizing agent. In this strategy, the new molecule formed by reaction of the drug and the antidote is deprived of biological activity and prone to fast renal clearance. This `Click & Clear' approach lays ground for new strategies in designing drugs with switchable biophysical properties.

Efficient production of infectious viruses requires enzymatic activity of Epstein-Barr virus protein kinase.

PubMed

Murata, Takayuki; Isomura, Hiroki; Yamashita, Yoriko; Toyama, Shigenori; Sato, Yoshitaka; Nakayama, Sanae; Kudoh, Ayumi; Iwahori, Satoko; Kanda, Teru; Tsurumi, Tatsuya

2009-06-20

The Epstein-Barr virus (EBV) BGLF4 gene product is the only protein kinase encoded by the virus genome. In order to elucidate its physiological roles in viral productive replication, we here established a BGLF4-knockout mutant and a revertant virus. While the levels of viral DNA replication of the deficient mutant were equivalent to those of the wild-type and the revertant, virus production was significantly impaired. Expression of the BGLF4 protein in trans fully complemented the low yield of the mutant virus, while expression of a kinase-dead (K102I) form of the protein failed to restore the virus titer. These results demonstrate that BGLF4 plays a significant role in production of infectious viruses and that the kinase activity is crucial.

Neural control of renal function in health and disease.

PubMed

DiBona, G F

1994-04-01

The renal sympathetic innervation of the kidney exerts significant effects on multiple aspects of renal function, including renal haemodynamics, tubular sodium and water reabsorption and renin secretion. These effects constitute an important control system which is important in the physiological regulation of arterial pressure and total body fluid and sodium homeostasis. Abnormalities in this regulatory mechanism have pathophysiological consequences and are manifest in clinically relevant human disease states. Decreased renal sympathetic nerve activity results in impaired renin secretion, the inability to conserve sodium normally and an attenuated ability to dispose of both acute and chronic sodium loads. Increased renal sympathetic nerve activity contributes significantly to the excess renal sodium retention and related renal abnormalities observed in both hypertension and oedema forming conditions, such as cardiac failure, cirrhosis and nephrotic syndrome.

Soluble Proteins Form Film by the Treatment of Low Temperature Plasma

NASA Astrophysics Data System (ADS)

Ikehara, Sanae; Sakakita, Hajime; Ishikawa, Kenji; Akimoto, Yoshihiro; Nakanishi, Hayao; Shimizu, Nobuyuki; Hori, Masaru; Ikehara, Yuzuru

2015-09-01

It has been pointed out that low temperature plasma in atmosphere was feasible to use for hemostasis without heat injury. Indeed, earlier studies demonstrated that low temperature plasma played an important role to stimulate platelets to aggregate and turned on the proteolytic activities of coagulation factors, resulting in the acceleration of the natural blood coagulation process. On the other hands, our developed equips could immediately form clots upon the contact with plasma flair, while the histological appearance was different from natural coagulation. Based on these findings in formed clots, we sought to determine if plasma flair supplied by our devices was capable of forming film using a series of soluble proteins Following plasma treatment, films were formed from bovine serum albumin, and the other plasma proteins at physiological concentration. Analysis of trans-electron microscope demonstrated that plasma treatment generated small protein particles and made them fuse to be larger aggregations The combined results demonstrated that plasma are capable of aggregating soluble proteins and that platelets and coagulation factors are not necessary for plasma induced blood coagulation. Supported in part by Grants-in-Aid for Scientific Research on Priority Area (21590454, 24590498, and 24108006 to Y. I.).

Polysaccharopeptides of Coriolus versicolor: physiological activity, uses, and production.

PubMed

Cui, Jian; Chisti, Yusuf

2003-04-01

The protein-bound polysaccharides or polysaccharopeptides produced by Coriolus versicolor are effective immunopotentiators, which are used to supplement the chemotherapy and radiotherapy of cancers and various infectious diseases. Antitumor activity of polysaccharopeptides has been documented. Several kinds of protein-bound polysaccharides have been shown to be produced by the white rot fungus, C. versicolor. Although some of these polymers are structurally distinct, they are not distinguishable in terms of their physiological activity. This review focuses on the physiologically active polysaccharopeptides of C. versicolor. In nature, C. versicolor occurs as a mushroom body, but the fungus can be grown as mycelial biomass in submerged culture in bioreactors. Mushrooms gathered in the wild, cultivated mushrooms, and the mycelial biomass of submerged culture are used to produce the polysaccharopeptides. Submerged cultures are typically carried out in batches lasting 5-7 days and at 25-27 degrees C. Hot water extraction of the biomass is used to recover the thermostable polysaccharopeptides that are concentrated, purified, and dried into a powder for medicinal use. In view of the documented physiological benefits of these compounds, extensive research is underway on the structure, composition, production methods, and use of new C. versicolor strains for producing the therapeutic biopolymers. Properties, physiological activity, recovery, and purification of the bioactive polysaccharopeptides are discussed.

The not-so-bitter pill: Effects of combined oral contraceptives on peripheral physiological indicators of emotional reactivity.

PubMed

Armbruster, Diana; Kirschbaum, Clemens; Strobel, Alexander

2017-08-01

Combined oral contraceptives (COC) are used by millions of women worldwide. Although findings are not entirely consistent, COC have been found to impact on brain function and, thus, to modulate affective processes. Here, we investigated electro-physiological responses to emotional stimuli in free cycling women in both the early follicular and late luteal phase as well as in COC users. Skin conductance response (SCR), startle reflex, corrugator and zygomaticus activity were assessed. COC users showed reduced overall startle magnitude and SCR amplitude, but heightened overall zygomaticus activity, although effect sizes were small. Thus, COC users displayed reduced physiological reactions indicating negative affect and enhanced physiological responses signifying positive affect. In free cycling women, endogenous 17β-estradiol levels were associated with fear potentiated startle in both cycle phases as well as with SCR and zygomaticus activity during the follicular phase. Testosterone was associated with corrugator and zygomaticus activity during the luteal phase, while progesterone levels correlated with corrugator activity in the follicular phase. To the contrary, in COC users, endogenous hormones were not associated with electro-physiological measures. The results further underscore the importance of considering COC use in psychophysiological studies on emotional processing. Copyright © 2017 Elsevier Inc. All rights reserved.

Tailoring Enzyme-Like Activities of Gold Nanoclusters by Polymeric Tertiary Amines for Protecting Neurons Against Oxidative Stress.

PubMed

Liu, Ching-Ping; Wu, Te-Haw; Lin, Yu-Lung; Liu, Chia-Yeh; Wang, Sabrina; Lin, Shu-Yi

2016-08-01

The cytotoxicity of nanozymes has drawn much attention recently because their peroxidase-like activity can decompose hydrogen peroxide (H2 O2 ) to produce highly toxic hydroxyl radicals (•OH) under acidic conditions. Although catalytic activities of nanozymes are highly associated with their surface properties, little is known about the mechanism underlying the surface coating-mediated enzyme-like activities. Herein, it is reported for the first time that amine-terminated PAMAM dendrimer-entrapped gold nanoclusters (AuNCs-NH2 ) unexpectedly lose their peroxidase-like activity while still retaining their catalase-like activity in physiological conditions. Surprisingly, the methylated form of AuNCs-NH2 (i.e., MAuNCs-N(+) R3 , where R = H or CH3 ) results in a dramatic recovery of the intrinsic peroxidase-like activity while blocking most primary and tertiary amines (1°- and 3°-amines) of dendrimers to form quaternary ammonium ions (4°-amines). However, the hidden peroxidase-like activity is also found in hydroxyl-terminated dendrimer-encapsulated AuNCs (AuNCs-OH, inside backbone with 3°-amines), indicating that 3°-amines are dominant in mediating the peroxidase-like activity. The possible mechanism is further confirmed that the enrichment of polymeric 3°-amines on the surface of dendrimer-encapsulated AuNCs provides sufficient suppression of the critical mediator •OH for the peroxidase-like activity. Finally, it is demonstrated that AuNCs-NH2 with diminished cytotoxicity have great potential for use in primary neuronal protection against oxidative damage. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Aluminum ammonium sulfate dodecahydrate purified from traditional Chinese medicinal herb Korean monkshood root is a potent matrix metalloproteinase inhibitor.

PubMed

Shen, Yehua; Liu, Sen; Jin, Fenghai; Mu, Tianyang; Li, Cong; Jiang, Kun; Tian, Weihua; Yu, Dahai; Zhang, Yingqi; Fang, Xuexun

2012-06-01

Matrix metalloproteinases (MMPs) are zinc-dependent endopeptidases and key regulators for many physiological and pathological functions. The MMP inhibitors have been shown to modulate diseases such as cancer, inflammation, and cardiovascular diseases. In this paper we tracked the MMP inhibitory activities of the traditional Chinese medicinal herb Korean Monkshood Root. The purified active ingredient was identified by the elemental analysis, infrared spectrum (IR) and X-ray diffraction as aluminum ammonium sulfate dodecahydrate. This inorganic compound showed inhibitory activities toward a number of MMP family members. In particular, it has a strong inhibitory effect toward MMP-2 and MMP-9, with IC50 values of 0.54 and 0.50 μM, respectively. Further analysis suggested that the MMP inhibitory activity is mainly due to Al(3+). Cell viability assays using human fibrosarcoma HT1080 cells showed aluminum ammonium sulfate had minimal cyto-toxicity with a concentration up to 500 μM. However, within 50 μM, it exhibited significant inhibition of cell invasion. To our knowledge, there has been no previous report of inorganic form of the MMP inhibitor with strong inhibitory activity. Our results for the first time showed that aluminum ammonium sulfate is an inorganic form of MMP inhibitor with high potency, and can be used to interfere with MMP related cellular processes.

An experimental comparison of the relative benefits of work and torque assistance in ankle exoskeletons.

PubMed

Jackson, Rachel W; Collins, Steven H

2015-09-01

Techniques proposed for assisting locomotion with exoskeletons have often included a combination of active work input and passive torque support, but the physiological effects of different assistance techniques remain unclear. We performed an experiment to study the independent effects of net exoskeleton work and average exoskeleton torque on human locomotion. Subjects wore a unilateral ankle exoskeleton and walked on a treadmill at 1.25 m·s(-1) while net exoskeleton work rate was systematically varied from -0.054 to 0.25 J·kg(-1)·s(-1), with constant (0.12 N·m·kg(-1)) average exoskeleton torque, and while average exoskeleton torque was systematically varied from approximately zero to 0.18 N·m·kg(-1), with approximately zero net exoskeleton work. We measured metabolic rate, center-of-mass mechanics, joint mechanics, and muscle activity. Both techniques reduced effort-related measures at the assisted ankle, but this form of work input reduced metabolic cost (-17% with maximum net work input) while this form of torque support increased metabolic cost (+13% with maximum average torque). Disparate effects on metabolic rate seem to be due to cascading effects on whole body coordination, particularly related to assisted ankle muscle dynamics and the effects of trailing ankle behavior on leading leg mechanics during double support. It would be difficult to predict these results using simple walking models without muscles or musculoskeletal models that assume fixed kinematics or kinetics. Data from this experiment can be used to improve predictive models of human neuromuscular adaptation and guide the design of assistive devices. Copyright © 2015 the American Physiological Society.

Time courses of changes of para-, meta-, and ortho-tyrosine in septic patients: A pilot study.

PubMed

Szélig, Lívia; Kun, Szilárd; Woth, Gábor; Molnár, Gergő A; Zrínyi, Zita; Kátai, Emese; Lantos, János; Wittmann, István; Bogár, Lajos; Miseta, Attila; Csontos, Csaba

2016-07-01

Sepsis is associated with oxidative stress. Due to oxidative stress, three tyrosine isoforms, para-, meta-, and ortho-tyrosine (p-, m-, and o-Tyr), can be formed non-enzymatically in smaller amounts. p-Tyr is mainly formed physiologically in the kidneys through the activity of the phenylalanine hydroxylase enzyme. The three tyrosine isoforms may undergo different renal handling. Twenty septic patients were involved in the study and 25 healthy individuals served as controls. Blood and urine levels of p-, m-, and o-Tyr were measured on admission and four consecutive days. Serum m-Tyr levels were higher in septic patients than in controls on days 2 (P = 0.031) and 3 (P = 0.035). Serum p-Tyr levels were lower in the cases than in controls on days 1 (P = 0.005) and 2 (P = 0.040), and subsequently normalized due to a day-by-day elevation (P = 0.002). The tendency of urinary m-Tyr concentration was decreasing (P = 0.041), while that of urinary p-Tyr concentration was increasing (P = 0.001). Fractional excretion of m-Tyr (FEm-Tyr) showed a decreasing tendency (P = 0.009), and was, on all days, higher than FEp-Tyr, which remained near-normal, less than 4%. Procalcitonin showed significant correlation with FEm-Tyr (r = 0.454; P < 0.001). Our data suggest that the oxidative stress marker m-Tyr and physiologic p-Tyr may be handled differently in septic patients. The excretion of m-Tyr correlates with inflammation. m-Tyr may be actively secreted or produced in the kidney in some patients, whereas the decreased serum level of p-Tyr is a consequence of diminished renal production and not of renal loss.

[Readjustment of the efferent activity of the scratching generator in response to stimulation of muscle afferents of the hindlimb of the decerebrate immobilized cat].

PubMed

Shimanskiĭ, Iu P; Baev, K V

1987-01-01

Rebuildings of the scratching generator activity caused by phasic electrical stimulation of ipsilateral hindlimb muscle nerves during different hindlimb positions were studied in decerebrated immobilized cats. Strong dependence of these rebuildings on the stimulation phase was observed. The character of the "scratch" cycle duration rebuilding was formed by the scratching generator tendency to bring efferent activity into such correlation with the stimulus that the stimulation moment coincided with the moment of efferent activity phase triggering. Phasic altering of the efferent activity intensity rebuilding was observed against a background of "aiming" and "scratching" activity correlation shift in the direction of strengthening activation of muscles innervated by the stimulated nerve. This rebuilding was intensified when the hindlimb deflects from the aimed position in the direction of corresponding muscles stretching. Physiological sense of "rebuilding absence phases" is discussed. It is postulated that absence of the duration and intensity changes can be achieved simultaneously only with definite correlation between phase and intensity of the afferent impulsation burst.

Model of personal consumption under conditions of modern economy

NASA Astrophysics Data System (ADS)

Rakhmatullina, D. K.; Akhmetshina, E. R.; Ignatjeva, O. A.

2017-12-01

In the conditions of the modern economy, in connection with the development of production, the expansion of the market for goods and services, its differentiation, active use of marketing tools in the sphere of sales, changes occur in the system of values and consumer needs. Motives that drive the consumer are transformed, stimulating it to activity. The article presents a model of personal consumption that takes into account modern trends in consumer behavior. The consumer, making a choice, seeks to maximize the overall utility from consumption, physiological and socio-psychological satisfaction, in accordance with his expectations, preferences and conditions of consumption. The system of his preferences is formed under the influence of factors of a different nature. It is also shown that the structure of consumer spending allows us to characterize and predict its further behavior in the market. Based on the proposed model and analysis of current trends in consumer behavior, conclusions and recommendations have been made that can be used by legislative and executive government bodies, business organizations, research centres and other structures to form a methodological and analytical tool for preparing a forecast model of consumption.

A contemporary view of atrioventricular nodal physiology.

PubMed

Markowitz, Steven M; Lerman, Bruce B

2018-06-16

In delaying transmission of the cardiac impulse from the atria to the ventricles, the atrioventricular (AV) node serves a critical function in augmenting ventricular filling during diastole and limiting the ventricular response during atrial tachyarrhythmias. The complex structure of the nodal region, however, also provides the substrate for reentrant rhythms. Recent discoveries have elucidated the cellular basis and anatomical determinants of slow conduction in the node. Based on analysis of gap junction proteins, distinct structural components of the AV node have been defined, including the compact node, right and left inferior nodal extensions, the lower nodal bundle, and transitional tissue. Emerging evidence supports the role of the inferior nodal extensions in mediating slow pathway conduction. The most common form of reentry involving the node, slow-fast AV nodal reentrant tachycardia (AVNRT), utilizes the inferior nodal extensions for anterograde slow pathway conduction; the structures responsible for retrograde fast pathway activation in the superior septum are less well defined and likely heterogeneous. Atypical forms of AVNRT arise from circuits that activate at least one of the inferior extensions in the retrograde direction.

What amyloidoses may tell us about normal protein folding: The Alzheimer's disease story

NASA Astrophysics Data System (ADS)

Teplow, David B.

2002-03-01

Alzheimer's disease (AD) is a progressive, neurodegenerative disorder characterized by severe neuronal injury and death. A prominent histopathologic feature of AD is disseminated parenchymal and vascular amyloid deposition. The fibrils in these deposits are composed of the amyloid β-protein (Aβ), a peptide of 4 kDa mass. In vitro and in vivo studies of Aβ fibril formation have shown that both oligomeric and polymeric Aβ assemblies have neurotoxic activity. Understanding how these assemblies form thus could be of direct therapeutic relevance. However, the aggregation and fibril-forming propensities of Aβ have complicated structure determination. Nevertheless, careful morphologic, spectroscopic, protein chemical, and physiologic analyses of the time-dependent changes in Aβ conformation, assembly state, and biological activity which occur during fibrillogenesis have significantly advanced our understanding of this clinically important process. Here, I will discuss recent findings about the pathway(s) of Aβ folding and assembly and about key structural features of Aβ which control the associated kinetics. Interestingly, the amyloidogenic folding pathway of Aβ is in some respects the mirror image of that through which natively folded amyloidogenic proteins proceed.

A Blended Approach to Active Learning in a Physiology Laboratory-Based Subject Facilitated by an e-Learning Component

ERIC Educational Resources Information Center

Dantas, Arianne M.; Kemm, Robert E.

2008-01-01

Learning via online activities (e-learning) was introduced to facilitate existing face-to-face teaching to encourage more effective student preparation and then informed participation in an undergraduate physiology laboratory-based course. Active learning was encouraged by hypothesis formation and predictions prior to classes, with opportunities…

Knowledge of the physiology of spore-forming bacteria can explain the origin of spores in the food environment.

PubMed

Gauvry, Emilie; Mathot, Anne-Gabrielle; Leguérinel, Ivan; Couvert, Olivier; Postollec, Florence; Broussolle, Véronique; Coroller, Louis

2017-05-01

Spore-forming bacteria are able to grow under a wide range of environmental conditions, to form biofilms and to differentiate into resistant forms: spores. This resistant form allows their dissemination in the environment; consequently, they may contaminate raw materials. Sporulation can occur all along the food chain, in raw materials, but also in food processes, leading to an increase in food contamination. However, the problem of sporulation during food processing is poorly addressed and sporulation niches are difficult to identify from the farm to the fork. Sporulation is a survival strategy. Some environmental factors are required to trigger this differentiation process and others act by modulating it. The efficiency of sporulation is the result of the combined effects of these two types of factors on vegetative cell metabolism. This paper aims to explain and help identify sporulation niches in the food chain, based on features of spore-former physiology. Copyright © 2016 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

Iron, oxidative stress, and redox signaling in the cardiovascular system.

PubMed

Gudjoncik, Aurélie; Guenancia, Charles; Zeller, Marianne; Cottin, Yves; Vergely, Catherine; Rochette, Luc

2014-08-01

The redox state of the cell is predominantly dependent on an iron redox couple and is maintained within strict physiological limits. Iron is an essential metal for hemoglobin synthesis in erythrocytes, for oxidation-reduction reactions, and for cellular proliferation. The maintenance of stable iron concentrations requires the coordinated regulation of iron transport into plasma from dietary sources in the duodenum, from recycled senescent red cells in macrophages, and from storage in hepatocytes. The absorption of dietary iron, which is present in heme or nonheme form, is carried out by mature villus enterocytes of the duodenum and proximal jejunum. Multiple physiological processes are involved in maintaining iron homeostasis. These include its storage at the intracellular and extracellular level. Control of iron balance in the whole organism requires communication between sites of uptake, utilization, and storage. Key protein transporters and the molecules that regulate their activities have been identified. In this field, ferritins and hepcidin are the major regulator proteins. A variety of transcription factors may be activated depending on the level of oxidative stress, leading to the expression of different genes. Major preclinical and clinical trials have shown advances in iron-chelation therapy for the treatment of iron-overload disease as well as cardiovascular and chronic inflammatory diseases. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Lacosamide protects striatal and hippocampal neurons from in vitro ischemia without altering physiological synaptic plasticity.

PubMed

Mazzocchetti, Petra; Tantucci, Michela; Bastioli, Guendalina; Calabrese, Valeria; Di Filippo, Massimiliano; Tozzi, Alessandro; Calabresi, Paolo; Costa, Cinzia

2018-06-01

Lacosamide ([(R)-2-acetamido-N-benzyl-3-methoxypropanamide], LCM), is an antiepileptic that exerts anticonvulsant activity by selectively enhancing slow sodium channel inactivation. By inhibiting seizures and neuronal excitability it might therefore be a good candidate to stabilize neurons and protect them from energetic insults. Using electrophysiological analyses, we have investigated in mice the possible neuroprotective effect of LCM against in vitro ischemia obtained by oxygen and glucose deprivation (ODG), in striatal and hippocampal tissues, two brain structures particularly susceptible to ischemic injury and of pivotal importance for different form of learning and memory. We also explored in these regions the influence of LCM on firing discharge and on long-term synaptic plasticity. We found that in both areas LCM reduced the neuronal firing activity in a use-dependent manner without influencing the physiological synaptic transmission, confirming its anticonvulsant effects. Moreover, we found that this AED is able to protect, in a dose dependent manner, striatal and hippocampal neurons from energy metabolism failure produced by OGD. This neuroprotective effect does not imply impairment of long-term potentiation of striatal and hippocampal synapses and suggests that LCM might exert additional beneficial therapeutic effects beyond its use as antiepileptic. Copyright © 2018 Elsevier Ltd. All rights reserved.

Mechanisms of Human Erythrocytic Bioactivation of Nitrite*

PubMed Central

Liu, Chen; Wajih, Nadeem; Liu, Xiaohua; Basu, Swati; Janes, John; Marvel, Madison; Keggi, Christian; Helms, Christine C.; Lee, Amber N.; Belanger, Andrea M.; Diz, Debra I.; Laurienti, Paul J.; Caudell, David L.; Wang, Jun; Gladwin, Mark T.; Kim-Shapiro, Daniel B.

2015-01-01

Nitrite signaling likely occurs through its reduction to nitric oxide (NO). Several reports support a role of erythrocytes and hemoglobin in nitrite reduction, but this remains controversial, and alternative reductive pathways have been proposed. In this work we determined whether the primary human erythrocytic nitrite reductase is hemoglobin as opposed to other erythrocytic proteins that have been suggested to be the major source of nitrite reduction. We employed several different assays to determine NO production from nitrite in erythrocytes including electron paramagnetic resonance detection of nitrosyl hemoglobin, chemiluminescent detection of NO, and inhibition of platelet activation and aggregation. Our studies show that NO is formed by red blood cells and inhibits platelet activation. Nitric oxide formation and signaling can be recapitulated with isolated deoxyhemoglobin. Importantly, there is limited NO production from erythrocytic xanthine oxidoreductase and nitric-oxide synthase. Under certain conditions we find dorzolamide (an inhibitor of carbonic anhydrase) results in diminished nitrite bioactivation, but the role of carbonic anhydrase is abrogated when physiological concentrations of CO2 are present. Importantly, carbon monoxide, which inhibits hemoglobin function as a nitrite reductase, abolishes nitrite bioactivation. Overall our data suggest that deoxyhemoglobin is the primary erythrocytic nitrite reductase operating under physiological conditions and accounts for nitrite-mediated NO signaling in blood. PMID:25471374

Subarachnoid Hemorrhage Severely Impairs Brain Parenchymal Cerebrospinal Fluid Circulation in Nonhuman Primate.

PubMed

Goulay, Romain; Flament, Julien; Gauberti, Maxime; Naveau, Michael; Pasquet, Nolwenn; Gakuba, Clement; Emery, Evelyne; Hantraye, Philippe; Vivien, Denis; Aron-Badin, Romina; Gaberel, Thomas

2017-08-01

Subarachnoid hemorrhage (SAH) is a devastating form of stroke with neurological outcomes dependent on the occurrence of delayed cerebral ischemia. It has been shown in rodents that some of the mechanisms leading to delayed cerebral ischemia are related to a decreased circulation of the cerebrospinal fluid (CSF) within the brain parenchyma. Here, we evaluated the cerebral circulation of the CSF in a nonhuman primate in physiological condition and after SAH. We first evaluated in physiological condition the circulation of the brain CSF in Macaca facicularis , using magnetic resonance imaging of the temporal DOTA-Gd distribution after its injection into the CSF. Then, animals were subjected to a minimally invasive SAH before an MRI evaluation of the impact of SAH on the brain parenchymal CSF circulation. We first demonstrate that the CSF actively penetrates the brain parenchyma. Two hours after injection, almost the entire brain is labeled by DOTA-Gd. We also show that our model of SAH in nonhuman primate displays the characteristics of SAH in humans and leads to a dramatic impairment of the brain parenchymal circulation of the CSF. The CSF actively penetrates within the brain parenchyma in the gyrencephalic brain, as described for the glymphatic system in rodent. This parenchymal CSF circulation is severely impaired by SAH. © 2017 American Heart Association, Inc.

Outcomes of physiological and active third stage labour care amongst women in New Zealand.

PubMed

Dixon, Lesley; Tracy, Sally K; Guilliland, Karen; Fletcher, Lynn; Hendry, Chris; Pairman, Sally

2013-01-01

during the third stage of labour there are two approaches for care provision - active management or physiological (expectant) care. The aim of this research was to describe, analyse and compare the midwifery care pathway and outcomes provided to a selected cohort of New Zealand women during the third stage of labour between the years 2004 and 2008. These women received continuity of care from a midwife Lead Maternity Carer and gave birth in a variety of birth settings (home, primary, secondary and tertiary maternity units). retrospective aggregated clinical information was extracted from the New Zealand College of Midwives research database. Factors such as type of third stage labour care provided; estimated blood loss; rate of treatment (separate to prophylaxis) with a uterotonic; and placental condition were compared amongst women who had a spontaneous onset of labour and no further assistance during the labour and birth. The results were adjusted for age, ethnicity, parity, place of birth, length of labour and weight of the baby. the rates of physiological third stage care (expectant) and active management within the cohort were similar (48.1% vs. 51.9%). Women who had active management had a higher risk of a blood loss of more than 500mL, the risk was 2.761 when a woman was actively managed (95% CI: 2.441-3.122) when compared to physiological management. Women giving birth at home and in a primary unit were more likely to have physiological management. A longer labour and higher parity increased the odds of having active management. Manual removal of the placenta was more likely with active management (0.7% active management - 0.2% physiological p<0.0001). For women who were given a uterotonic drug as a treatment rather than prophylaxis a postpartum haemorrhage of more than 500mL was twice as likely in the actively managed group compared to the physiological managed group (6.9% vs. 3.7%, RR 0.54, CI: 0.5, 0.6). the use of physiological care during the third stage of labour should be considered and supported for women who are healthy and have had a spontaneous labour and birth regardless of birth place setting. Further research should determine whether the use of a uterotonic as a treatment in the first instance may be more effective than as a treatment following initial exposure prophylactically. Copyright © 2011 Elsevier Ltd. All rights reserved.

A day of immersive physiology experiments increases knowledge and excitement towards physiology and scientific careers in Native American students.

PubMed

Becker, Bryan K; Schiller, Alicia M; Zucker, Irving H; Eager, Eric A; Bronner, Liliana P; Godfrey, Maurice

2017-03-01

Underserved minority groups are disproportionately absent from the pursuit of careers in science, technology, engineering, and mathematics (STEM) fields. One such underserved population, Native Americans, are particularly underrepresented in STEM fields. Although recent advocacy and outreach designed toward increasing minority involvement in health care-related occupations have been mostly successful, little is known about the efficacy of outreach programs in increasing minority enthusiasm toward careers in traditional scientific professions. Furthermore, very little is known about outreach among Native American schools toward increasing involvement in STEM. We collaborated with tribal middle and high schools in South Dakota and Nebraska through a National Institutes of Health Science Education Partnership Award to hold a day-long physiology, activity-based event to increase both understanding of physiology and enthusiasm to scientific careers. We recruited volunteer biomedical scientists and trainees from the University of Nebraska Medical Center, Nebraska Wesleyan University, and University of South Dakota. To evaluate the effectiveness of the day of activities, 224 of the ~275-300 participating students completed both a pre- and postevent evaluation assessment. We observed increases in both students self-perceived knowledge of physiology and enthusiasm toward scientific career opportunities after the day of outreach activities. We conclude that activity-based learning opportunities in underserved populations are effective in increasing both knowledge of science and interest in scientific careers. Copyright © 2017 the American Physiological Society.

Physiological Effects of Nature Therapy: A Review of the Research in Japan.

PubMed

Song, Chorong; Ikei, Harumi; Miyazaki, Yoshifumi

2016-08-03

Humans have evolved into what they are today after the passage of 6-7 million years. If we define the beginning of urbanization as the rise of the industrial revolution, less than 0.01% of our species' history has been spent in modern surroundings. Humans have spent over 99.99% of their time living in the natural environment. The gap between the natural setting, for which our physiological functions are adapted, and the highly urbanized and artificial setting that we inhabit is a contributing cause of the "stress state" in modern people. In recent years, scientific evidence supporting the physiological effects of relaxation caused by natural stimuli has accumulated. This review aimed to objectively demonstrate the physiological effects of nature therapy. We have reviewed research in Japan related to the following: (1) the physiological effects of nature therapy, including those of forests, urban green space, plants, and wooden material and (2) the analyses of individual differences that arise therein. The search was conducted in the PubMed database using various keywords. We applied our inclusion/exclusion criteria and reviewed 52 articles. Scientific data assessing physiological indicators, such as brain activity, autonomic nervous activity, endocrine activity, and immune activity, are accumulating from field and laboratory experiments. We believe that nature therapy will play an increasingly important role in preventive medicine in the future.

Investigating the physiology of brain activation with MRI

NASA Astrophysics Data System (ADS)

Buxton, Richard B.; Uludag, Kamil; Dubowitz, David J.

2004-04-01

Functional magnetic resonance imaging (fMRI) has become a powerful tool for investigating the working human brain based on the blood oxygenation level dependent (BOLD) effect on the MR signal. However, despite the widespread use of fMRI techniques for mapping brain activation, the basic physiological mechanisms underlying the observed signal changes are still poorly understood. Arterial spin labeling (ASL) techniques, which measure cerebral blood flow (CBF) and the BOLD effect simultaneously, provide a useful tool for investigating these physiological questions. In this paper, recent results of studies manipulating the baseline CBF both pharmacologically and physiologically will be discussed. These data are consistent with a feed-forward mechanism of neurovascular coupling, and suggest that the CBF change itself may be a more robust reflection of neural activity changes than the BOLD effect. Consistent with these data, a new thermodynamic hypothesis is proposed for the physiological function of CBF regulation: maintenance of the [O2]/[CO2] concentration ratio at the mitochondria in order to preserve the free energy available from oxidative metabolism. A kinetic model based on this hypothesis provides a reasonable quantitative description of the CBF changes associated with neural activity and altered blood gases (CO2 and O2).

Hypertension: physiology and pathophysiology.

PubMed

Hall, John E; Granger, Joey P; do Carmo, Jussara M; da Silva, Alexandre A; Dubinion, John; George, Eric; Hamza, Shereen; Speed, Joshua; Hall, Michael E

2012-10-01

Despite major advances in understanding the pathophysiology of hypertension and availability of effective and safe antihypertensive drugs, suboptimal blood pressure (BP) control is still the most important risk factor for cardiovascular mortality and is globally responsible for more than 7 million deaths annually. Short-term and long-term BP regulation involve the integrated actions of multiple cardiovascular, renal, neural, endocrine, and local tissue control systems. Clinical and experimental observations strongly support a central role for the kidneys in the long-term regulation of BP, and abnormal renal-pressure natriuresis is present in all forms of chronic hypertension. Impaired renal-pressure natriuresis and chronic hypertension can be caused by intrarenal or extrarenal factors that reduce glomerular filtration rate or increase renal tubular reabsorption of salt and water; these factors include excessive activation of the renin-angiotensin-aldosterone and sympathetic nervous systems, increased formation of reactive oxygen species, endothelin, and inflammatory cytokines, or decreased synthesis of nitric oxide and various natriuretic factors. In human primary (essential) hypertension, the precise causes of impaired renal function are not completely understood, although excessive weight gain and dietary factors appear to play a major role since hypertension is rare in nonobese hunter-gathers living in nonindustrialized societies. Recent advances in genetics offer opportunities to discover gene-environment interactions that may also contribute to hypertension, although success thus far has been limited mainly to identification of rare monogenic forms of hypertension. © 2012 American Physiological Society

Vortex formation and instability in the left ventricle

NASA Astrophysics Data System (ADS)

Le, Trung Bao; Sotiropoulos, Fotis; Coffey, Dane; Keefe, Daniel

2012-09-01

We study the formation of the mitral vortex ring during early diastolic filling in a patient-specific left ventricle (LV) using direct numerical simulation. The geometry of the left ventricle is reconstructed from Magnetic Resonance Imaging (MRI) data of a healthy human subject. The left ventricular kinematics is modeled via a cell-based activation methodology, which is inspired by cardiac electro-physiology and yields physiologic LV wall motion. In the fluid dynamics videos, we describe in detail the three-dimensional structure of the mitral vortex ring, which is formed during early diastolic filling. The ring starts to deform as it propagates toward the apex of the heart and becomes inclined. The trailing secondary vortex tubes are formed as the result of interaction between the vortex ring and the LV wall. These vortex tubes wrap around the circumference and begin to interact with and destabilize the mitral vortex ring. At the end of diastole, the vortex ring impinges on the LV wall and the large-scale intraventricular flow rotates in clockwise direction. We show for the first time that the mitral vortex ring evolution is dominated by a number of vortex-vortex and vortex-wall interactions, including lateral straining and deformation of vortex ring, the interaction of two vortex tubes with unequal strengths, helicity polarization of vortex tubes and twisting instabilities of the vortex cores.

Physiological tolerance to uncompensated heat stress in soldiers: effects of various types of body cooling systems.

PubMed

Jovanović, Dalibor; Karkalić, Radovan; Zeba, Snjezana; Pavlović, Miroslav; Radaković, Sonja S

2014-03-01

In military services, emergency situations when soldiers are exposed to a combination of nuclear, biological and chemical (NBC) contamination combined with heat stress, are frequent and complex. In these specific conditions, usage of personal body cooling systems may be effective in reducing heat stress. The present study was conducted in order to evaluate the efficiency of four various types of contemporary personal body cooling systems based on the "Phase Change Material" (PCM), and its effects on soldiers' subjective comfort and physiological performance during exertional heat stress in hot environments. Ten male soldiers were voluntarily subjected to exertional heat stress tests (EHSTs) consisted of walking on a treadmill (5.5 km/h) in hot conditions (40 degreesC) in climatic chamber, wearing NBC isolating impermeable protective suits. One of the tests was performed without any additional cooling solution (NOCOOL), and four tests were performed while using different types of cooling systems: three in a form of vests and one as underwear. Physiological strain was determined by the mean skin temperature (Tsk), tympanic temperature (Tty), and heart rate values (HR), while sweat rates (SwR) indicated changes in hydration status. In all the cases EHST induced physiological response manifested through increasing Tty, HR and SwR. Compared to NOCOOL tests, when using cooling vests, Tty and Tsk were significantly lower (on 35th min, for 0.44 +/- 0.03 and 0.49 +/- 0.05 degrees C, respectively; p < 0.05), as well as the average SwR (0.17 +/- 0.03 L/m2/h). When using underwear, the values of given parameters were not significantly different compared to NOCOOL tests. Using a body cooling system based on PCM in the form of vest under NBC protective clothes during physical activity in hot conditions, reduces sweating and alleviates heat stress manifested by increased core and skin temperatures and heart rate values. These effects directly improve heat tolerance, hydration state, decrease in the risk of heat illness, and extends the duration of soldiers' exposure to extreme conditions.

Body Composition and Physiological Responses of Masters Female Swimmers 20 to 70 Years of Age.

ERIC Educational Resources Information Center

Vaccaro, Paul; And Others

1984-01-01

Female masters swimmers ranging in age from 20 to 69 were chosen for a study of their body composition and physiological responses at rest and during exercise. Two training groups were formed that differed on the basis of frequency, duration, and intensity of swimming workouts. Results are discussed. (Author/DF)

"I Was Told That My First Duty Was to Forget Physiology, Which Had No Relation to Medicine"

ERIC Educational Resources Information Center

Walsh, Kieran

2016-01-01

There has been much recent commentary on integration in health care professional education. This commentary is of importance to physiology education as integration often touches on integration between preclinical and clinical sciences. There are different forms of integration, from horizontal to vertical to spiral, and different theories underpin…

Pros and Cons of a Group Webpage Design Project in a Freshman Anatomy and Physiology Course

ERIC Educational Resources Information Center

Crisp, Kevin M.; Jensen, Murray; Moore, Randy

2007-01-01

To generate motivation and promote the development of written communication skills, students in a freshman-level anatomy and physiology course for nonmajors created group webpages describing historically important diseases. After the groups had been formed, each individual was assigned specific components of the disease (e.g., causes or…

Pilot Workload Measurement and Experience on Supersonic Cruise Aircraft

NASA Technical Reports Server (NTRS)

Rezek, T. W.

1978-01-01

Aircraft parameters and physiological parameters most indicative of crew workload were investigated. Recommendations were used to form the basis for a continuing study in which variations of the interval between heart beats are used as a measure of nonphysical workload. Preliminary results are presented and current efforts in further defining this physiological measure are outlined.

Myths and Truths from Exercise Physiology

ERIC Educational Resources Information Center

Kieffer, H. Scott

2008-01-01

This article addresses some of the common myths in the field of exercise physiology. Some of the myths are misconstrued facts that have developed over time, such as the myth of localized fat reduction. Other myths are unproved or collective beliefs used to justify a social institution; we see this occur in the form of "fitness fads." Society is…

Physiological responses to prolonged bed rest in humans: A compendium of research, 1981-1988

NASA Technical Reports Server (NTRS)

Luu, Phuong B.; Ortiz, Vanessa; Barnes, Paul R.; Greenleaf, John E.

1990-01-01

Clinical observations and results form more basic studies that help to elucidate the physiological mechanisms of the adaptation of humans to prolonged bed rest. If the authors' abstract or summary was appropriate, it was included. In some cases a more detailed synopsis was provided under the subheadings of purpose, methods, results, and conclusions.

Conserved Loop Cysteines of Vitamin K Epoxide Reductase Complex Subunit 1-like 1 (VKORC1L1) Are Involved in Its Active Site Regeneration*

PubMed Central

Tie, Jian-Ke; Jin, Da-Yun; Stafford, Darrel W.

2014-01-01

Vitamin K epoxide reductase complex subunit 1 (VKORC1) reduces vitamin K epoxide in the vitamin K cycle for post-translational modification of proteins that are involved in a variety of biological functions. However, the physiological function of VKORC1-like 1 (VKORC1L1), a paralogous enzyme sharing about 50% protein identity with VKORC1, is unknown. Here we determined the structural and functional differences of these two enzymes using fluorescence protease protection (FPP) assay and an in vivo cell-based activity assay. We show that in vivo VKORC1L1 reduces vitamin K epoxide to support vitamin K-dependent carboxylation as efficiently as does VKORC1. However, FPP assays show that unlike VKORC1, VKORC1L1 is a four-transmembrane domain protein with both its termini located in the cytoplasm. Moreover, the conserved loop cysteines, which are not required for VKORC1 activity, are essential for VKORC1L1's active site regeneration. Results from domain exchanges between VKORC1L1 and VKORC1 suggest that it is VKORC1L1's overall structure that uniquely allows for active site regeneration by the conserved loop cysteines. Intermediate disulfide trapping results confirmed an intra-molecular electron transfer pathway for VKORC1L1's active site reduction. Our results allow us to propose a concerted action of the four conserved cysteines of VKORC1L1 for active site regeneration; the second loop cysteine, Cys-58, attacks the active site disulfide, forming an intermediate disulfide with Cys-139; the first loop cysteine, Cys-50, attacks the intermediate disulfide resulting in active site reduction. The different membrane topologies and reaction mechanisms between VKORC1L1 and VKORC1 suggest that these two proteins might have different physiological functions. PMID:24532791

Conserved loop cysteines of vitamin K epoxide reductase complex subunit 1-like 1 (VKORC1L1) are involved in its active site regeneration.

PubMed

Tie, Jian-Ke; Jin, Da-Yun; Stafford, Darrel W

2014-03-28

Vitamin K epoxide reductase complex subunit 1 (VKORC1) reduces vitamin K epoxide in the vitamin K cycle for post-translational modification of proteins that are involved in a variety of biological functions. However, the physiological function of VKORC1-like 1 (VKORC1L1), a paralogous enzyme sharing about 50% protein identity with VKORC1, is unknown. Here we determined the structural and functional differences of these two enzymes using fluorescence protease protection (FPP) assay and an in vivo cell-based activity assay. We show that in vivo VKORC1L1 reduces vitamin K epoxide to support vitamin K-dependent carboxylation as efficiently as does VKORC1. However, FPP assays show that unlike VKORC1, VKORC1L1 is a four-transmembrane domain protein with both its termini located in the cytoplasm. Moreover, the conserved loop cysteines, which are not required for VKORC1 activity, are essential for VKORC1L1's active site regeneration. Results from domain exchanges between VKORC1L1 and VKORC1 suggest that it is VKORC1L1's overall structure that uniquely allows for active site regeneration by the conserved loop cysteines. Intermediate disulfide trapping results confirmed an intra-molecular electron transfer pathway for VKORC1L1's active site reduction. Our results allow us to propose a concerted action of the four conserved cysteines of VKORC1L1 for active site regeneration; the second loop cysteine, Cys-58, attacks the active site disulfide, forming an intermediate disulfide with Cys-139; the first loop cysteine, Cys-50, attacks the intermediate disulfide resulting in active site reduction. The different membrane topologies and reaction mechanisms between VKORC1L1 and VKORC1 suggest that these two proteins might have different physiological functions.