Physiology and pathophysiology of potassium homeostasis.

PubMed

Palmer, Biff F; Clegg, Deborah J

2016-12-01

Total body potassium content and proper distribution of potassium across the cell membrane is of critical importance for normal cellular function. Potassium homeostasis is maintained by several different methods. In the kidney, total body potassium content is achieved by alterations in renal excretion of potassium in response to variations in intake. Insulin and beta-adrenergic tone play critical roles in maintaining the internal distribution of potassium under normal conditions. Despite homeostatic pathways designed to maintain potassium levels within the normal range, disorders of altered potassium homeostasis are common. The clinical approach to designing effective treatments relies on understanding the pathophysiology and regulatory influences which govern the internal distribution and external balance of potassium. Here we provide an overview of the key regulatory aspects of normal potassium physiology. This review is designed to provide an overview of potassium homeostasis as well as provide references of seminal papers to guide the reader into a more in depth discussion of the importance of potassium balance. This review is designed to be a resource for educators and well-informed clinicians who are teaching trainees about the importance of potassium balance. Copyright © 2016 the American Physiological Society.

Seasonal differences in the physiology of Carcinus maenas (Crustacea: Decapoda) from estuaries with varying levels of anthropogenic contamination

NASA Astrophysics Data System (ADS)

Dissanayake, Awantha; Galloway, Tamara S.; Jones, Malcolm B.

2011-07-01

This study reports the seasonal variability in aspects of the physiology of the shore crab Carcinus maenas from three estuaries in South-west England, each with varying anthropogenic inputs: Avon Estuary ('relatively low' impact), Yealm Estuary ('intermediate' impact) and Plym Estuary ('relatively high' impact). Crabs collected over 12 months from the Avon had a significantly 'lower' physiological condition in winter and spring compared to summer and autumn; in particular, haemocyte phagocytic capability (a general indicator of immune function) was significantly higher in winter and spring compared to summer and autumn, and total haemolymph antioxidant status (an indicator of oxidative stress) was significantly lower in winter compared to the remainder of the year. Potentially, shore crabs may be more susceptible to the effects of contaminant exposure, such as increased immunotoxicity (thus, reduction of immune function) and/or oxyradicals (or reactive oxygen species) exposure) especially in seasons of increased susceptibility i.e. summer/autumn (lower phagocytic capability) and winter (lowest antioxidant function). As the Avon was taken to represent the 'reference' site, this pattern is considered to reflect the 'normal' seasonal variability in shore crab physiology. Shore crab physiological condition from the 'relatively high' impact estuary (Plym) revealed increased cellular viability and antioxidant status in autumn and winter compared with that of the 'standard' pattern (Avon) However, crabs from the intermediate impact estuary (Yealm) only demonstrated significant physiological differences in summer as shown by a lower cellular viability. All crabs had been exposed to PAHs (confirmed by the presence of PAH metabolites in their urine) which may account for the observed differences in shore crab physiology. In conclusion, to aid understanding of the potential contaminant impacts on biota it is imperative that the 'normal' seasonal variability of physiological condition be established. Biological effects-based monitoring studies should therefore be employed seasonally to potentially highlight 'windows of sensitivity' to contaminant impact.

Physiological work performance in chronic low back disability: effects of a progressive activity program.

PubMed

Thomas, L K; Hislop, H J; Waters, R L

1980-04-01

Fifteen patients were tested before and after treatment in a multifaceted inpatient program for chronic low back pain to determine if a gradually progressive activity program affected gait performance and physiological capacity. Before treatment, all patients demonstrated decreased physiological conditioning by higher-than-expected values for oxygen consumption and heart rate and by lower-than-normal gait velocity, stride length, and cadence. After treatment, an increase in mean walking velocity of 19 meters/minute reflected parallel gains in cadence and stride length. Improved mechanical performance resulted in improved "energetics." Energy spent per unit of distance walked decreased by 18 percent after treatment, providing a useful measure of increased physiological efficiency. Results indicated that patients with chronic low back disability can derive significant conditioning effects from an exercise program based on general function.

Aging and physiological changes of the kidneys including changes in glomerular filtration rate.

PubMed

Musso, Carlos G; Oreopoulos, Dimitrios G

2011-01-01

In addition to the structural changes in the kidney associated with aging, physiological changes in renal function are also found in older adults, such as decreased glomerular filtration rate, vascular dysautonomia, altered tubular handling of creatinine, reduction in sodium reabsorption and potassium secretion, and diminished renal reserve. These alterations make aged individuals susceptible to the development of clinical conditions in response to usual stimuli that would otherwise be compensated for in younger individuals, including acute kidney injury, volume depletion and overload, disorders of serum sodium and potassium concentration, and toxic reactions to water-soluble drugs excreted by the kidneys. Additionally, the preservation with aging of a normal urinalysis, normal serum urea and creatinine values, erythropoietin synthesis, and normal phosphorus, calcium and magnesium tubular handling distinguishes decreased GFR due to normal aging from that due to chronic kidney disease. Copyright © 2011 S. Karger AG, Basel.

Effect of noisy stimulation on neurobiological sensitization systems and its role for normal and pathological physiology

NASA Astrophysics Data System (ADS)

Huber, Martin; Braun, Hans; Krieg, J.\\:Urgen-Christian

2004-03-01

Sensitization is discussed as an important phenomenon playing a role in normal physiology but also with respect to the initiation and progression of a variety of neuropsychiatric disorders such as epilepsia, substance-related disorders or recurrent affective disorders. The relevance to understand the dynamics of sensitization phenomena is emphasized by recent findings that even single stimulations can induce longlasting changes in biological systems. To address specific questions associated with the sensitization dynamics, we use a computational approach and develop simple but physiologically-plausible models. In the present study we examine the effect of noisy stimulation on sensitization development in the model. We consider sub- and suprathresold stimulations with varying noise intensities and determine as response measures the (i) absolute number of stimulus-induced sensitzations and (ii) the temporal relsation of stimulus-sensitization coupling. The findings indicate that stochastic effects including stochastic resonance might well contribute to the physiology of sensitization mechanisms under both nomal and pathological conditions.

Effects of abnormal light-rearing conditions on retinal physiology in larvae zebrafish.

PubMed

Saszik, S; Bilotta, J

1999-11-01

Anatomic studies have found that zebrafish retinal neurons develop in a sequential fashion. In addition, exposure to abnormal light-rearing conditions produces deficits in visual behavior of larvae zebrafish, even though there appears to be little effect of the light-rearing conditions on the gross morphology of the retina. The purpose of this study was to assess the effects of abnormal light-rearing conditions on larvae zebrafish retinal physiology. Larvae zebrafish (Danio rerio) were exposed to constant light (LL), constant dark (DD), or normal cyclic light (LD) from fertilization to 6 days postfertilization (dpf). After 6 days, the animals were placed into normal cyclic light and tested at 6 to 8, 13 to 15, and 21 to 24 dpf. Electroretinogram (ERG) responses to visual stimuli, consisting of various wavelengths and irradiances, were recorded. Comparisons were made across the three age groups and the three light-rearing conditions. Deficits from the light-rearing conditions were seen immediately after exposure (6 8 dpf). The LL-condition subjects showed the greatest deficit in the UV and short-wavelength areas and the DD-condition subjects showed a slight deficit across the entire spectrum. At 13 to 15 dpf, the LL and DD groups showed an increase in sensitivity and by 21 to 24 dpf, the groups no longer differed from controls. Abnormal lighting environments can adversely influence the physiological development of the larvae zebrafish retina. The pattern of damage that was seen in zebrafish is similar to that found in other vertebrates, including higher vertebrates. However, unlike higher vertebrates, the zebrafish appears to be capable of regeneration. This suggests that the zebrafish would be a viable model for light environment effects and neural regeneration.

Cardiac damage in athlete's heart: When the "supernormal" heart fails!

PubMed

Carbone, Andreina; D'Andrea, Antonello; Riegler, Lucia; Scarafile, Raffaella; Pezzullo, Enrica; Martone, Francesca; America, Raffaella; Liccardo, Biagio; Galderisi, Maurizio; Bossone, Eduardo; Calabrò, Raffaele

2017-06-26

Intense exercise may cause heart remodeling to compensate increases in blood pressure or volume by increasing muscle mass. Cardiac changes do not involve only the left ventricle, but all heart chambers. Physiological cardiac modeling in athletes is associated with normal or enhanced cardiac function, but recent studies have documented decrements in left ventricular function during intense exercise and the release of cardiac markers of necrosis in athlete's blood of uncertain significance. Furthermore, cardiac remodeling may predispose athletes to heart disease and result in electrical remodeling, responsible for arrhythmias. Athlete's heart is a physiological condition and does not require a specific treatment. In some conditions, it is important to differentiate the physiological adaptations from pathological conditions, such as hypertrophic cardiomyopathy, arrhythmogenic dysplasia of the right ventricle, and non-compaction myocardium, for the greater risk of sudden cardiac death of these conditions. Moreover, some drugs and performance-enhancing drugs can cause structural alterations and arrhythmias, therefore, their use should be excluded.

Cardiac damage in athlete’s heart: When the “supernormal” heart fails!

PubMed Central

Carbone, Andreina; D’Andrea, Antonello; Riegler, Lucia; Scarafile, Raffaella; Pezzullo, Enrica; Martone, Francesca; America, Raffaella; Liccardo, Biagio; Galderisi, Maurizio; Bossone, Eduardo; Calabrò, Raffaele

2017-01-01

Intense exercise may cause heart remodeling to compensate increases in blood pressure or volume by increasing muscle mass. Cardiac changes do not involve only the left ventricle, but all heart chambers. Physiological cardiac modeling in athletes is associated with normal or enhanced cardiac function, but recent studies have documented decrements in left ventricular function during intense exercise and the release of cardiac markers of necrosis in athlete’s blood of uncertain significance. Furthermore, cardiac remodeling may predispose athletes to heart disease and result in electrical remodeling, responsible for arrhythmias. Athlete’s heart is a physiological condition and does not require a specific treatment. In some conditions, it is important to differentiate the physiological adaptations from pathological conditions, such as hypertrophic cardiomyopathy, arrhythmogenic dysplasia of the right ventricle, and non-compaction myocardium, for the greater risk of sudden cardiac death of these conditions. Moreover, some drugs and performance-enhancing drugs can cause structural alterations and arrhythmias, therefore, their use should be excluded. PMID:28706583

TRPM7 Is Required for Normal Synapse Density, Learning, and Memory at Different Developmental Stages.

PubMed

Liu, Yuqiang; Chen, Cui; Liu, Yunlong; Li, Wei; Wang, Zhihong; Sun, Qifeng; Zhou, Hang; Chen, Xiangjun; Yu, Yongchun; Wang, Yun; Abumaria, Nashat

2018-06-19

The TRPM7 chanzyme contributes to several biological and pathological processes in different tissues. However, its role in the CNS under physiological conditions remains unclear. Here, we show that TRPM7 knockdown in hippocampal neurons reduces structural synapse density. The synapse density is rescued by the α-kinase domain in the C terminus but not by the ion channel region of TRPM7 or by increasing extracellular concentrations of Mg 2+ or Zn 2+ . Early postnatal conditional knockout of TRPM7 in mice impairs learning and memory and reduces synapse density and plasticity. TRPM7 knockdown in the hippocampus of adult rats also impairs learning and memory and reduces synapse density and synaptic plasticity. In knockout mice, restoring expression of the α-kinase domain in the brain rescues synapse density/plasticity and memory, probably by interacting with and phosphorylating cofilin. These results suggest that brain TRPM7 is important for having normal synaptic and cognitive functions under physiological, non-pathological conditions. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

CO2-induced pH reduction increases physiological toxicity of nano-TiO2 in the mussel Mytilus coruscus

PubMed Central

Hu, Menghong; Lin, Daohui; Shang, Yueyong; Hu, Yi; Lu, Weiqun; Huang, Xizhi; Ning, Ke; Chen, Yimin; Wang, Youji

2017-01-01

The increasing usage of nanoparticles has caused their considerable release into the aquatic environment. Meanwhile, anthropogenic CO2 emissions have caused a reduction of seawater pH. However, their combined effects on marine species have not been experimentally evaluated. This study estimated the physiological toxicity of nano-TiO2 in the mussel Mytilus coruscus under high pCO2 (2500–2600 μatm). We found that respiration rate (RR), food absorption efficiency (AE), clearance rate (CR), scope for growth (SFG) and O:N ratio were significantly reduced by nano-TiO2, whereas faecal organic weight rate and ammonia excretion rate (ER) were increased under nano-TiO2 conditions. High pCO2 exerted lower effects on CR, RR, ER and O:N ratio than nano-TiO2. Despite this, significant interactions of CO2-induced pH change and nano-TiO2 were found in RR, ER and O:N ratio. PCA showed close relationships among most test parameters, i.e., RR, CR, AE, SFG and O:N ratio. The normal physiological responses were strongly correlated to a positive SFG with normal pH and no/low nano-TiO2 conditions. Our results indicate that physiological functions of M. coruscus are more severely impaired by the combination of nano-TiO2 and high pCO2. PMID:28054631

The reduction potential of nitric oxide (NO) and its importance to NO biochemistry

PubMed Central

Bartberger, Michael D.; Liu, Wei; Ford, Eleonora; Miranda, Katrina M.; Switzer, Christopher; Fukuto, Jon M.; Farmer, Patrick J.; Wink, David A.; Houk, Kendall N.

2002-01-01

A potential of about −0.8 (±0.2) V (at 1 M versus normal hydrogen electrode) for the reduction of nitric oxide (NO) to its one-electron reduced species, nitroxyl anion (3NO−) has been determined by a combination of quantum mechanical calculations, cyclic voltammetry measurements, and chemical reduction experiments. This value is in accord with some, but not the most commonly accepted, previous electrochemical measurements involving NO. Reduction of NO to 1NO− is highly unfavorable, with a predicted reduction potential of about −1.7 (±0.2) V at 1 M versus normal hydrogen electrode. These results represent a substantial revision of the derived and widely cited values of +0.39 V and −0.35 V for the NO/3NO− and NO/1NO− couples, respectively, and provide support for previous measurements obtained by electrochemical and photoelectrochemical means. With such highly negative reduction potentials, NO is inert to reduction compared with physiological events that reduce molecular oxygen to superoxide. From these reduction potentials, the pKa of 3NO− has been reevaluated as 11.6 (±3.4). Thus, nitroxyl exists almost exclusively in its protonated form, HNO, under physiological conditions. The singlet state of nitroxyl anion, 1NO−, is physiologically inaccessible. The significance of these potentials to physiological and pathophysiological processes involving NO and O2 under reductive conditions is discussed. PMID:12177417

CO2-induced pH reduction increases physiological toxicity of nano-TiO2 in the mussel Mytilus coruscus

NASA Astrophysics Data System (ADS)

Hu, Menghong; Lin, Daohui; Shang, Yueyong; Hu, Yi; Lu, Weiqun; Huang, Xizhi; Ning, Ke; Chen, Yimin; Wang, Youji

2017-01-01

The increasing usage of nanoparticles has caused their considerable release into the aquatic environment. Meanwhile, anthropogenic CO2 emissions have caused a reduction of seawater pH. However, their combined effects on marine species have not been experimentally evaluated. This study estimated the physiological toxicity of nano-TiO2 in the mussel Mytilus coruscus under high pCO2 (2500-2600 μatm). We found that respiration rate (RR), food absorption efficiency (AE), clearance rate (CR), scope for growth (SFG) and O:N ratio were significantly reduced by nano-TiO2, whereas faecal organic weight rate and ammonia excretion rate (ER) were increased under nano-TiO2 conditions. High pCO2 exerted lower effects on CR, RR, ER and O:N ratio than nano-TiO2. Despite this, significant interactions of CO2-induced pH change and nano-TiO2 were found in RR, ER and O:N ratio. PCA showed close relationships among most test parameters, i.e., RR, CR, AE, SFG and O:N ratio. The normal physiological responses were strongly correlated to a positive SFG with normal pH and no/low nano-TiO2 conditions. Our results indicate that physiological functions of M. coruscus are more severely impaired by the combination of nano-TiO2 and high pCO2.

Functional spasm of accommodation: Changes on scheimpflug imaging

PubMed Central

Sukhija, Jaspreet; Dogra, Mangat R.; Zadeng, Thara; Ram, Jagat

2014-01-01

Spasm of accommodation is a rare condition characterized by a sudden increase in myopia. It can occur in emmetropes, hypermetropes and myopes. All the physiological changes that occur in normal accommodation are exaggerated. Mostly the cause is functional disorder and the condition gradually improves. We hereby present the changes occurring in spasm of accommodation as seen on Scheimpflug imaging. PMID:25378883

Physiological functions of MTA family of proteins.

PubMed

Sen, Nirmalya; Gui, Bin; Kumar, Rakesh

2014-12-01

Although the functional significance of the metastasic tumor antigen (MTA) family of chromatin remodeling proteins in the pathobiology of cancer is fairly well recognized, the physiological role of MTA proteins continues to be an understudied research area and is just beginning to be recognized. Similar to cancer cells, MTA1 also modulates the expression of target genes in normal cells either by acting as a corepressor or coactivator. In addition, physiological functions of MTA proteins are likely to be influenced by its differential expression, subcellular localization, and regulation by upstream modulators and extracellular signals. This review summarizes our current understanding of the physiological functions of the MTA proteins in model systems. In particular, we highlight recent advances of the role MTA proteins play in the brain, eye, circadian rhythm, mammary gland biology, spermatogenesis, liver, immunomodulation and inflammation, cellular radio-sensitivity, and hematopoiesis and differentiation. Based on the growth of knowledge regarding the exciting new facets of the MTA family of proteins in biology and medicine, we speculate that the next burst of findings in this field may reveal further molecular regulatory insights of non-redundant functions of MTA coregulators in the normal physiology as well as in pathological conditions outside cancer.

Measurement of physiological traits of paddy rice in temperature gradient chamber using Normalized Difference Vegetation Index and Photochemical Reflectance Index

NASA Astrophysics Data System (ADS)

Ryu, J. H.; Oh, D.; Cho, J.

2017-12-01

Global warming has been affecting the phenological and physiological conditions of crop plants due to heat stress. Thus, the scientific understanding of not only crop-yield change, but also growth progress during high temperature condition is necessary. In this study, growth response and yield of paddy rice depending on air temperature (Ta) has been studied in a Temperature Gradient Chamber (TGC) that is composed of higher Ta than actual Ta (ambient temperature). The results on imitating experiment of global warming provided the reduced production of crop by heat stress. Therefore, it is important to quickly detect the condition of a plant in order to minimize damage to heat stress on global warming. Phenological and physiological changes depending on Ta was detected using optical spectroscopy sensors because remote sensing is useful and efficient technology to monitor quickly and continually. Two vegetation indices, Normalized Difference Vegetation Index (NDVI) and Photochemical Reflectance Index (PRI), were applied to monitor paddy rice growth using hyperspectral and multispectral radiometer. Ta in TGC was gradually set from actual Ta + 0 ° to actual Ta + 3 °. The variations of NDVI and PRI were different during rice growth period, and also these patterns were changed depending on Ta condition. NDVI and PRI under +3 ° condition increase faster than ambient temperature. After heading stage, the values of NDVI and PRI were dropped. However, the NDVI and PRI of rice under heat stress were relatively slowly decreased. In addition, we found that the yield of rice decreased in the case of delayed drop patterns of NDVI and PRI after heading stage. Our results will be useful to understand crop plant conditions using vegetation index under global warming situations.

Insomnia, metabolic rate and sleep restoration.

PubMed

Bonnet, M H; Arand, D L

2003-07-01

Studies have shown occasional evidence of increased physiological activity in patients with primary insomnia. We hypothesized that metabolic rate, as measured by overall oxygen use (VO2), might be a more general index of increased physiological activity. An initial experiment found elevated VO2 both at night and during the day in patients with primary insomnia as compared with matched normal sleepers. A second experiment found significant but more modest increases in VO2 in patients with Sleep State Misperception Insomnia [who complain of poor sleep but who had normal sleep by electroencephalographic (EEG) criteria]. In a third experiment, normal young adults were given caffeine 400 mg three times per day (TID) for 1 week as a means of increasing VO2 and possibly producing other symptoms of insomnia. Participants developed many symptoms consistent with those seen in patients with primary insomnia (poor sleep, increased latency on the Multiple Sleep Latency Test, increasing fatigue despite physiological activation, and increased anxiety on the Minnesota Multiphasic Personality Inventory (MMPI)). In a final experiment, physiological arousal was again produced by caffeine to determine if sleep with elevated arousal would be less restorative. All subjects (Ss) slept for 3.5 h after being given 400 mg of caffeine. During 41 h of sleep deprivation that followed, there was no significant condition difference for the Multiple Sleep Latency Test or mood measures. The results provided only weak support for the idea that sleep is less restorative after physiological arousal.

Murine Electrophysiological Models of Cardiac Arrhythmogenesis

PubMed Central

2016-01-01

Cardiac arrhythmias can follow disruption of the normal cellular electrophysiological processes underlying excitable activity and their tissue propagation as coherent wavefronts from the primary sinoatrial node pacemaker, through the atria, conducting structures and ventricular myocardium. These physiological events are driven by interacting, voltage-dependent, processes of activation, inactivation, and recovery in the ion channels present in cardiomyocyte membranes. Generation and conduction of these events are further modulated by intracellular Ca2+ homeostasis, and metabolic and structural change. This review describes experimental studies on murine models for known clinical arrhythmic conditions in which these mechanisms were modified by genetic, physiological, or pharmacological manipulation. These exemplars yielded molecular, physiological, and structural phenotypes often directly translatable to their corresponding clinical conditions, which could be investigated at the molecular, cellular, tissue, organ, and whole animal levels. Arrhythmogenesis could be explored during normal pacing activity, regular stimulation, following imposed extra-stimuli, or during progressively incremented steady pacing frequencies. Arrhythmic substrate was identified with temporal and spatial functional heterogeneities predisposing to reentrant excitation phenomena. These could arise from abnormalities in cardiac pacing function, tissue electrical connectivity, and cellular excitation and recovery. Triggering events during or following recovery from action potential excitation could thereby lead to sustained arrhythmia. These surface membrane processes were modified by alterations in cellular Ca2+ homeostasis and energetics, as well as cellular and tissue structural change. Study of murine systems thus offers major insights into both our understanding of normal cardiac activity and its propagation, and their relationship to mechanisms generating clinical arrhythmias. PMID:27974512

Acid-Base Homeostasis

PubMed Central

Nakhoul, Nazih; Hering-Smith, Kathleen S.

2015-01-01

Acid-base homeostasis and pH regulation are critical for both normal physiology and cell metabolism and function. The importance of this regulation is evidenced by a variety of physiologic derangements that occur when plasma pH is either high or low. The kidneys have the predominant role in regulating the systemic bicarbonate concentration and hence, the metabolic component of acid-base balance. This function of the kidneys has two components: reabsorption of virtually all of the filtered HCO3− and production of new bicarbonate to replace that consumed by normal or pathologic acids. This production or generation of new HCO3− is done by net acid excretion. Under normal conditions, approximately one-third to one-half of net acid excretion by the kidneys is in the form of titratable acid. The other one-half to two-thirds is the excretion of ammonium. The capacity to excrete ammonium under conditions of acid loads is quantitatively much greater than the capacity to increase titratable acid. Multiple, often redundant pathways and processes exist to regulate these renal functions. Derangements in acid-base homeostasis, however, are common in clinical medicine and can often be related to the systems involved in acid-base transport in the kidneys. PMID:26597304

Global Deletion of TSPO Does Not Affect the Viability and Gene Expression Profile

PubMed Central

Wang, Huaishan; Yang, Jia; Yang, Qi; Fu, Yi; Hu, Yu; Liu, Fang; Wang, Weiqing; Cui, Lianxian; Chen, Hui; Zhang, Jianmin; He, Wei

2016-01-01

Translocator Protein (18kDa, TSPO) is a mitochondrial outer membrane transmembrane protein. Its expression is elevated during inflammation and injury. However, the function of TSPO in vivo is still controversial. Here, we constructed a TSPO global knockout (KO) mouse with a Cre-LoxP system that abolished TSPO protein expression in all tissues and showed normal phenotypes in the physiological condition. The birth rates of TSPO heterozygote (Het) x Het or KO x KO breeding were consistent with Mendel’s Law, suggesting a normal viability of TSPO KO mice at birth. RNA-seq analysis showed no significant difference in the gene expression profile of lung tissues from TSPO KO mice compared with wild type mice, including the genes associated with bronchial alveoli immune homeostasis. The alveolar macrophage population was not affected by TSPO deletion in the physiological condition. Our findings contradict the results of Papadopoulos, but confirmed Selvaraj’s findings. This study confirms TSPO deficiency does not affect viability and bronchial alveolar immune homeostasis. PMID:27907096

Effect of simulated microgravity on growth and production of exopolymeric substances of Micrococcus luteus space and earth isolates.

PubMed

Mauclaire, Laurie; Egli, Marcel

2010-08-01

Microorganisms tend to form biofilms on surfaces, thereby causing deterioration of the underlaying material. In addition, biofilm is a potential health risk to humans. Therefore, microorganism growth is not only an issue on Earth but also in manned space habitats like the International Space Station (ISS). The aim of the study was to identify physiological processes relevant for Micrococcus luteus attachment under microgravity conditions. The results demonstrate that simulated microgravity influences physiological processes which trigger bacterial attachment and biofilm formation. The ISS strains produced larger amounts of exopolymeric substances (EPS) compared with a reference strain from Earth. In contrast, M. luteus strains were growing faster, and Earth as well as ISS isolates produced a higher yield of biomass under microgravity conditions than under normal gravity. Furthermore, microgravity caused a reduction of the colloidal EPS production of ISS isolates in comparison with normal gravity, which probably influences biofilm thickness and stability as well.

What goes on behind closed doors: physiological vs. pharmacological steroid hormone actions

PubMed Central

Simons, S. Stoney

2009-01-01

Summary Steroid hormone-activated receptor proteins are among the best understood class of factors for altering gene transcription in cells. Steroid receptors are of major importance in maintaining normal human physiology by responding to circulating concentrations of steroid in the nM range. Nonetheless, most studies of steroid receptor action have been conducted using the supra-physiological conditions of saturating concentrations (≥100 nM) of potent synthetic steroid agonists. Here we summarize the recent developments arising from experiments using two clinically relevant conditions: subsaturating concentrations of agonist (to mimic the circulating concentrations in mammals) and saturating concentrations of antagonists (which are employed in endocrine therapies to block the actions of endogenous steroids). These studies have revealed new facets of steroid hormone action that could not be uncovered by conventional experiments with saturating concentrations of agonist steroids, such as a plethora of factors/conditions for the differential control of gene expression by physiological levels of steroid, a rational approach for examining the gene-specific variations in partial agonist activity of antisteroids, and a dissociation of steroid potency and efficacy that implies the existence of separate, and possibly novel, mechanistic steps and cofactors. PMID:18623071

Irregular or absent periods--what can an ultrasound scan tell you?

PubMed

Khalid, Asma

2004-02-01

Transvaginal ultrasonography has increased our appreciation of the physiological changes in the ovary and endometrium that occur during the normal menstrual cycle. It has become a primary investigative tool in women with irregular or absent periods. Its usefulness in cases of primary amenorrhoea to assess anatomy is also undisputed although it may have limitations in terms of its specificity. However, the interpretation of ultrasound images in women with irregular menses or secondary amenorrhoea is not entirely straightforward. This is particularly true in the diagnosis of polycystic ovary syndrome, a condition of uncertain aetiology, which may present with oligoamenorrhoea. This chapter aims to discuss the benefits and limitations of ultrasound while taking into account the broad overlap between normal and abnormal physiology, some of which has still to be elucidated.

Microfluidic cardiac cell culture model (μCCCM).

PubMed

Giridharan, Guruprasad A; Nguyen, Mai-Dung; Estrada, Rosendo; Parichehreh, Vahidreza; Hamid, Tariq; Ismahil, Mohamed Ameen; Prabhu, Sumanth D; Sethu, Palaniappan

2010-09-15

Physiological heart development and cardiac function rely on the response of cardiac cells to mechanical stress during hemodynamic loading and unloading. These stresses, especially if sustained, can induce changes in cell structure, contractile function, and gene expression. Current cell culture techniques commonly fail to adequately replicate physical loading observed in the native heart. Therefore, there is a need for physiologically relevant in vitro models that recreate mechanical loading conditions seen in both normal and pathological conditions. To fulfill this need, we have developed a microfluidic cardiac cell culture model (μCCCM) that for the first time allows in vitro hemodynamic stimulation of cardiomyocytes by directly coupling cell structure and function with fluid induced loading. Cells are cultured in a small (1 cm diameter) cell culture chamber on a thin flexible silicone membrane. Integrating the cell culture chamber with a pump, collapsible pulsatile valve and an adjustable resistance element (hemostatic valve) in series allow replication of various loading conditions experienced in the heart. This paper details the design, modeling, fabrication and characterization of fluid flow, pressure and stretch generated at various frequencies to mimic hemodynamic conditions associated with the normal and failing heart. Proof-of-concept studies demonstrate successful culture of an embryonic cardiomyoblast line (H9c2 cells) and establishment of an in vivo like phenotype within this system.

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

PubMed

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

2012-04-01

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

Effect of incorporating low intensity exercise into the recovery period after a rugby match.

PubMed

Suzuki, M; Umeda, T; Nakaji, S; Shimoyama, T; Mashiko, T; Sugawara, K

2004-08-01

The psychological and physiological condition of athletes affect both their performance in competitions and their health. Rugby is an intense sport which appears to impose psychological and physiological stress on players. However, there have been few studies of the most appropriate resting techniques to deliver effective recovery from a match. To compare the difference in recovery after a match using resting techniques with or without exercise. Fifteen Japanese college rugby football players were studied. Seven performed only normal daily activities and eight performed additional low intensity exercise during the post-match rest period. Players were examined just before and immediately after the match and one and two days after the match. Blood biochemistry and two neutrophil functions, phagocytic activity and oxidative burst, were measured to assess physiological condition, and the profile of mood states (POMS) scores were examined to evaluate psychological condition. Immediately after the match, muscle damage, decreases in neutrophil functions, and mental fatigue were observed in both groups. Muscle damage and neutrophil functions recovered with time almost equally in the two groups, but the POMS scores were significantly decreased only in subjects in the low intensity exercise group. Rugby matches impose both physiological and psychological stress on players. The addition of low intensity exercise to the rest period did not adversely affect physiological recovery and had a significantly beneficial effect on psychological recovery by enhancing relaxation.

Dysphagia in Infants with Single Ventricle Anatomy Following Stage 1 Palliation: Physiologic Correlates and Response to Treatment

PubMed Central

McGrattan, Katlyn Elizabeth; McGhee, Heather; DeToma, Allan; Hill, Elizabeth G.; Zyblewski, Sinai C.; Lefton-Greif, Maureen; Halstead, Lucinda; Bradley, Scott M.; Martin-Harris, Bonnie

2017-01-01

Background Deficits in swallowing physiology are a leading morbidity for infants with functional single ventricles and systemic outflow tract obstruction following stage 1 palliation. Despite the high prevalence of this condition, the underlying deficits that cause this post-operative impairment remain poorly understood. Objective Identify the physiologic correlates of dysphagia in infants with functional single ventricles and systemic outflow tract obstruction following stage 1 palliative surgery. Methods Postoperative fiberoptic laryngoscopies and videofluoroscopic swallow studies (VFSS) were conducted sequentially on infants with functional single ventricles following stage 1 palliative surgery. Infants were dichotomized as having normal or impaired laryngeal function based on laryngoscopy findings. VFSS were evaluated frame-by-frame using a scale that quantifies performance within 11 components of swallowing physiology. Physiologic attributes within each component were categorized as high functioning or low functioning based on their ability to support milk ingestion without bolus airway entry. Results Thirty-six infants (25 male) were included in the investigation. Twenty-four underwent the Norwood procedure and twelve underwent the Hybrid procedure. Low function physiologic patterns were observed within multiple swallowing components during the ingestion of thin barium as characterized by ≥ 4 sucks per swallow (36%), initiation of pharyngeal swallow below the level of the valleculae (83%), and incomplete late laryngeal vestibular closure (56%) at the height of the swallow. Swallowing deficits contributed to aspiration in 50% of infants. Although nectar thick liquids reduced the rate of aspiration (p=0.006), aspiration rates remained high (27%). No differences in rates of penetration or aspiration were observed between infants with normal and impaired laryngeal function. Conclusions Deficits in swallowing physiology contribute to penetration and aspiration following stage 1 palliation among infants with normal and impaired laryngeal function. Although thickened liquids may improve airway protection for select infants, they may inhibit their ability to extract the bolus and meet nutritional needs. PMID:28244680

Dysphagia in infants with single ventricle anatomy following stage 1 palliation: Physiologic correlates and response to treatment.

PubMed

McGrattan, Katlyn Elizabeth; McGhee, Heather; DeToma, Allan; Hill, Elizabeth G; Zyblewski, Sinai C; Lefton-Greif, Maureen; Halstead, Lucinda; Bradley, Scott M; Martin-Harris, Bonnie

2017-05-01

Deficits in swallowing physiology are a leading morbidity for infants with functional single ventricles and systemic outflow tract obstruction following stage 1 palliation. Despite the high prevalence of this condition, the underlying deficits that cause this post-operative impairment remain poorly understood. Identify the physiologic correlates of dysphagia in infants with functional single ventricles and systemic outflow tract obstruction following stage 1 palliative surgery. Postoperative fiberoptic laryngoscopies and videofluoroscopic swallow studies (VFSS) were conducted sequentially on infants with functional single ventricles following stage 1 palliative surgery. Infants were dichotomized as having normal or impaired laryngeal function based on laryngoscopy findings. VFSS were evaluated frame-by-frame using a scale that quantifies performance within 11 components of swallowing physiology. Physiologic attributes within each component were categorized as high functioning or low functioning based on their ability to support milk ingestion without bolus airway entry. Thirty-six infants (25 male) were included in the investigation. Twenty-four underwent the Norwood procedure and twelve underwent the Hybrid procedure. Low function physiologic patterns were observed within multiple swallowing components during the ingestion of thin barium as characterized by ≥4 sucks per swallow (36%), initiation of pharyngeal swallow below the level of the valleculae (83%), and incomplete late laryngeal vestibular closure (56%) at the height of the swallow. Swallowing deficits contributed to aspiration in 50% of infants. Although nectar thick liquids reduced the rate of aspiration (P = .006), aspiration rates remained high (27%). No differences in rates of penetration or aspiration were observed between infants with normal and impaired laryngeal function. Deficits in swallowing physiology contribute to penetration and aspiration following stage 1 palliation among infants with normal and impaired laryngeal function. Although thickened liquids may improve airway protection for select infants, they may inhibit their ability to extract the bolus and meet nutritional needs. © 2017 Wiley Periodicals, Inc.

Lysosomal membrane permeabilization in cell death: new evidence and implications for health and disease.

PubMed

Serrano-Puebla, Ana; Boya, Patricia

2016-05-01

Recent studies have demonstrated that, in addition to their central role in cellular catabolic reactions, lysosomes are implicated in many cellular processes, including metabolism, membrane repair, and cell death. Lysosomal membrane permeabilization (LMP) has emerged as a pathway by which cell demise is regulated under physiological conditions and contributes to cell death in many pathological situations. Here, we review the latest evidence on LMP-mediated cell death, the upstream and downstream signals involved, and the role of LMP in the normal physiology of organisms. We also discuss the contributions of lysosomal damage and LMP to the pathogenic features of several disease states, such as lysosomal storage disorders and other neurodegenerative conditions. © 2015 New York Academy of Sciences.

The Unexpected and Exceptionally Facile Chemical Modification of the Phenolic Hydroxyl Group of Tyrosine by Polyhalogenated Quinones under Physiological Conditions.

PubMed

Qu, Na; Li, Feng; Shao, Bo; Shao, Jie; Zhai, Guijin; Wang, Fuyi; Zhu, Ben-Zhan

2016-10-17

The phenolic hydroxyl group of tyrosine residue plays a crucial role in the structure and function of many proteins. However, little study has been reported about its modification by chemical agents under physiological conditions. In this study, we found, unexpectedly, that the phenolic hydroxyl group of tyrosine can be rapidly and efficiently modified by tetrafluoro-1,4-benzoquinone and other polyhalogenated quinones, which are the major genotoxic and carcinogenic quinoid metabolites of polyhalogenated aromatic compounds. The modification was found to be mainly due to the formation of a variety of fluoroquinone-O-tyrosine conjugates and their hydroxylated derivatives via nucleophilic substitution pathway. Analogous modifications were observed for tyrosine-containing peptides. Further studies showed that the blockade of the reactive phenolic hydroxyl group of tyrosine in the substrate peptide, even by very low concentration of tetrafluoro-1,4-benzoquinone, can prevent the kinase catalyzed tyrosine phosphorylation. This is the first report showing the exceptionally facile chemical modification of the phenolic hydroxyl group of tyrosine by polyhalogenated quinones under normal physiological conditions, which may have potential biological and toxicological implications.

Thermal Stress

DTIC Science & Technology

2011-01-01

can have a significant impact on normal physiological functioning if precipitous increases in core temperature are not adequately controlled with...anterior hypothalamusIntroduction Thermal stress can have a significant impact on normal physiological functioning if precipitous increases in core...fat and skin). The regulation of a relatively constant internal temperature is critical for normal physiological functioning of tissues and cells, as

The Tentative Nature of Scientific Knowledge: Why Should We Teach More about Diabetes Mellitus?

ERIC Educational Resources Information Center

Biermann, Carol A.

1993-01-01

Almost 70 years of scientific research leaves many unanswered questions concerning diabetes mellitus. This disease can be viewed as an illustration of the complexity of biological systems. Textbooks stress normal rather than abnormal physiology and rarely share the difficulties encountered in understanding those abnormal conditions (PR)

Impaired angiogenesis in aminopeptidase N-null mice

PubMed Central

Rangel, Roberto; Sun, Yan; Guzman-Rojas, Liliana; Ozawa, Michael G.; Sun, Jessica; Giordano, Ricardo J.; Van Pelt, Carolyn S.; Tinkey, Peggy T.; Behringer, Richard R.; Sidman, Richard L.; Arap, Wadih; Pasqualini, Renata

2007-01-01

Aminopeptidase N (APN, CD13; EC 3.4.11.2) is a transmembrane metalloprotease with several functions, depending on the cell type and tissue environment. In tumor vasculature, APN is overexpressed in the endothelium and promotes angiogenesis. However, there have been no reports of in vivo inactivation of the APN gene to validate these findings. Here we evaluated, by targeted disruption of the APN gene, whether APN participates in blood vessel formation and function under normal conditions. Surprisingly, APN-null mice developed with no gross or histological abnormalities. Standard neurological, cardiovascular, metabolic, locomotor, and hematological studies revealed no alterations. Nonetheless, in oxygen-induced retinopathy experiments, APN-deficient mice had a marked and dose-dependent deficiency of the expected retinal neovascularization. Moreover, gelfoams embedded with growth factors failed to induce functional blood vessel formation in APN-null mice. These findings establish that APN-null mice develop normally without physiological alterations and can undergo physiological angiogenesis but show a severely impaired angiogenic response under pathological conditions. Finally, in addition to vascular biology research, APN-null mice may be useful reagents in other medical fields such as malignant, cardiovascular, immunological, or infectious diseases. PMID:17360568

Selecting boundary conditions in physiological strain analysis of the femur: Balanced loads, inertia relief method and follower load.

PubMed

Heyland, Mark; Trepczynski, Adam; Duda, Georg N; Zehn, Manfred; Schaser, Klaus-Dieter; Märdian, Sven

2015-12-01

Selection of boundary constraints may influence amount and distribution of loads. The purpose of this study is to analyze the potential of inertia relief and follower load to maintain the effects of musculoskeletal loads even under large deflections in patient specific finite element models of intact or fractured bone compared to empiric boundary constraints which have been shown to lead to physiological displacements and surface strains. The goal is to elucidate the use of boundary conditions in strain analyses of bones. Finite element models of the intact femur and a model of clinically relevant fracture stabilization by locking plate fixation were analyzed with normal walking loading conditions for different boundary conditions, specifically re-balanced loading, inertia relief and follower load. Peak principal cortex surface strains for different boundary conditions are consistent (maximum deviation 13.7%) except for inertia relief without force balancing (maximum deviation 108.4%). Influence of follower load on displacements increases with higher deflection in fracture model (from 3% to 7% for force balanced model). For load balanced models, follower load had only minor influence, though the effect increases strongly with higher deflection. Conventional constraints of fixed nodes in space should be carefully reconsidered because their type and position are challenging to justify and for their potential to introduce relevant non-physiological reaction forces. Inertia relief provides an alternative method which yields physiological strain results. Copyright © 2015 IPEM. Published by Elsevier Ltd. All rights reserved.

Separation of metabolic supply and demand: aerobic glycolysis as a normal physiological response to fluctuating energetic demands in the membrane.

PubMed

Epstein, Tamir; Xu, Liping; Gillies, Robert J; Gatenby, Robert A

2014-01-01

Cancer cells, and a variety of normal cells, exhibit aerobic glycolysis, high rates of glucose fermentation in the presence of normal oxygen concentrations, also known as the Warburg effect. This metabolism is considered abnormal because it violates the standard model of cellular energy production that assumes glucose metabolism is predominantly governed by oxygen concentrations and, therefore, fermentative glycolysis is an emergency back-up for periods of hypoxia. Though several hypotheses have been proposed for the origin of aerobic glycolysis, its biological basis in cancer and normal cells is still not well understood. We examined changes in glucose metabolism following perturbations in membrane activity in different normal and tumor cell lines and found that inhibition or activation of pumps on the cell membrane led to reduction or increase in glycolysis, respectively, while oxidative phosphorylation remained unchanged. Computational simulations demonstrated that these findings are consistent with a new model of normal physiological cellular metabolism in which efficient mitochondrial oxidative phosphorylation supplies chronic energy demand primarily for macromolecule synthesis and glycolysis is necessary to supply rapid energy demands primarily to support membrane pumps. A specific model prediction was that the spatial distribution of ATP-producing enzymes in the glycolytic pathway must be primarily localized adjacent to the cell membrane, while mitochondria should be predominantly peri-nuclear. The predictions were confirmed experimentally. Our results show that glycolytic metabolism serves a critical physiological function under normoxic conditions by responding to rapid energetic demand, mainly from membrane transport activities, even in the presence of oxygen. This supports a new model for glucose metabolism in which glycolysis and oxidative phosphorylation supply different types of energy demand. Cells use efficient but slow-responding aerobic metabolism to meet baseline, steady energy demand and glycolytic metabolism, which is inefficient but can rapidly increase adenosine triphosphate (ATP) production, to meet short-timescale energy demands, mainly from membrane transport activities. In this model, the origin of the Warburg effect in cancer cells and aerobic glycolysis in general represents a normal physiological function due to enhanced energy demand for membrane transporters activity required for cell division, growth, and migration.

Definition of normality of pressure-flow parameters based on observations in asymptomatic men.

PubMed

Rosario, Derek J; Woo, Henry H; Chapple, Christopher R

2008-01-01

Clinical nomograms for differentiating obstructed from unobstructed voiding and poor detrusor contractility from normal contractility have traditionally been drawn on the basis of symptomatic response to outflow tract surgery or on urodynamic changes in men with LUTS before and after surgery. The aim of this study was to examine pressure-flow parameters in asymptomatic male volunteers before age-related changes in the lower urinary tract had taken place and to assess detrusor contractility and outflow conditions during physiological bladder filling against clinically used pressure-flow nomograms. Thirty-seven healthy male subjects between the ages of 18 and 40 years volunteered to undergo AUM. A total of 66 fill-void cycles in 25 individuals were evaluable. Mean p(det.Qmax) for the group was 53 +/- 3 cmH(2)O with a mean Q(max) of 24 +/- 2 ml sec(-1). URA of 21 cmH(2)O defined the upper border of normality for the outflow condition. Schäfer's OCO showed the most consistent relationship between estimated urethral pressure at minimal flow and true measured urethral closure pressure. From a clinical perspective, the linear nomograms (ICS and Schäfer) are more easily accessible with the ICS BOOI and obstruction index being the simplest to calculate manually. Minimal differences found between these urodynamic nomograms confirm the clinical value of recommending a single method to facilitate future comparisons between studies. An upper limit of normality for the male outflow condition can be defined by an URA of 21 cmH(2)O, AGN of 40 cmH(2)O or OCO of 1. Results above these reference values should be considered abnormal in this age group and where identified in a different age-group should be explained by physiological or pathophysiological events.

Things Don’t Just Go Back to Normal: The Implications of Antenatal and Postpartum Physiology and Morphology for the Resumption of Fitness Testing

DTIC Science & Technology

2015-04-08

September 2014 - April 2015 Things Don’t Just Go Back to Normal: The Implications of Antenatal and Postpartum Physiology and Morphology for the...physiology; morphology Unclassified Unclassified Unclassified UU 56 Marine Corps University/Command a (703) 784-3330 (Admin Office) United States Marine...MASTER OF MILITARY STUDIES Things Don’t Just Go Back to Normal: The Implications of Antenatal and Postpartum Physiology and Morphology for the

Functionality of empirical model-based predictive analytics for the early detection of hemodynamic instabilty.

PubMed

Summers, Richard L; Pipke, Matt; Wegerich, Stephan; Conkright, Gary; Isom, Kristen C

2014-01-01

Background. Monitoring cardiovascular hemodynamics in the modern clinical setting is a major challenge. Increasing amounts of physiologic data must be analyzed and interpreted in the context of the individual patient’s pathology and inherent biologic variability. Certain data-driven analytical methods are currently being explored for smart monitoring of data streams from patients as a first tier automated detection system for clinical deterioration. As a prelude to human clinical trials, an empirical multivariate machine learning method called Similarity-Based Modeling (“SBM”), was tested in an In Silico experiment using data generated with the aid of a detailed computer simulator of human physiology (Quantitative Circulatory Physiology or “QCP”) which contains complex control systems with realistic integrated feedback loops. Methods. SBM is a kernel-based, multivariate machine learning method that that uses monitored clinical information to generate an empirical model of a patient’s physiologic state. This platform allows for the use of predictive analytic techniques to identify early changes in a patient’s condition that are indicative of a state of deterioration or instability. The integrity of the technique was tested through an In Silico experiment using QCP in which the output of computer simulations of a slowly evolving cardiac tamponade resulted in progressive state of cardiovascular decompensation. Simulator outputs for the variables under consideration were generated at a 2-min data rate (0.083Hz) with the tamponade introduced at a point 420 minutes into the simulation sequence. The functionality of the SBM predictive analytics methodology to identify clinical deterioration was compared to the thresholds used by conventional monitoring methods. Results. The SBM modeling method was found to closely track the normal physiologic variation as simulated by QCP. With the slow development of the tamponade, the SBM model are seen to disagree while the simulated biosignals in the early stages of physiologic deterioration and while the variables are still within normal ranges. Thus, the SBM system was found to identify pathophysiologic conditions in a timeframe that would not have been detected in a usual clinical monitoring scenario. Conclusion. In this study the functionality of a multivariate machine learning predictive methodology that that incorporates commonly monitored clinical information was tested using a computer model of human physiology. SBM and predictive analytics were able to differentiate a state of decompensation while the monitored variables were still within normal clinical ranges. This finding suggests that the SBM could provide for early identification of a clinical deterioration using predictive analytic techniques. predictive analytics, hemodynamic, monitoring.

Effects of scopolamine on autonomic profiles underlying motion sickness susceptibility

NASA Technical Reports Server (NTRS)

Uijtdehaage, Sebastian H. J.; Stern, Robert M.; Koch, Kenneth L.

1993-01-01

The purpose of this study was to examine the effects of scopolamine on the physiological patterns occurring prior to and during motion sickness stimulation. In addition, the use of physiological profiles in the prediction of motion sickness was evaluated. Sixty subjects ingested either 0.6 mg scopolamine, 2.5 mg methoscopolamine, or a placebo. Heart rate (HR), respiratory sinus arrhythmia (an index of vagal tone), and electrogastrograms were measured prior to and during the exposure to a rotating optokinetic drum. Compared to the other groups, the scopolamine group reported fewer motion sickness symptoms, and displayed lower HR, higher vagal tone, enhanced normal gastric myoelectric activity, and depressed gastric dysrhythmias before and during motion sickness induction. Distinct physiological profiles prior to drum rotation could reliably differentiate individuals who would develop gastric discomfort from those who would not. Symptom-free subjects were characterized by high levels of vagal tone and low HR across conditions, and by maintaining normal (3 cpm) electrogastrographic activity during drum rotation. It was concluded that scopolamine offered motion sickness protection by initiating a pattern of increased vagal tone and gastric myoelectric stability.

Effect of high wavelengths low intensity light during dark period on physical exercise performance, biochemical and haematological parameters of swimming rats.

PubMed

Beck, W; Gobatto, C

2016-03-01

Nocturnal rodents should be assessed at an appropriate time of day, which leads to a challenge in identifying an adequate environmental light which allows animal visualisation without perturbing physiological homeostasis. Thus, we analysed the influence of high wavelength and low intensity light during dark period on physical exercise and biochemical and haematological parameters of nocturnal rats. We submitted 80 animals to an exhaustive exercise at individualised intensity under two different illuminations during dark period. Red light (> 600 nm; < 15lux) was applied constantly during dark period (EI; for experimental illumination groups) or only for handling and assessments (SI; for standard illumination groups). EI led to worse haematological and biochemical conditions, demonstrating that EI alone can influence physiological parameters and jeopardise result interpretation. SI promotes normal physiological conditions and greater aerobic tolerance than EI, showing the importance of a correct illumination pattern for all researchers that employ nocturnal rats for health/disease or sports performance experiments.

Altered LARK Expression Perturbs Development and Physiology of the Drosophila PDF Clock Neurons

PubMed Central

Huang, Yanmei; Howlett, Eric; Stern, Michael; Jackson, F. Rob

2009-01-01

The LARK RNA-binding protein (RBP) has well documented roles in the circadian systems of Drosophila and mammals. Recent studies have demonstrated that the Drosophila LARK RBP is associated with many mRNA targets, in vivo, including those that regulate either neurophysiology or development of the nervous system. In the present study, we have employed conditional expression techniques to distinguish developmental and physiological functions of LARK for a defined class of neurons: the Pigment Dispersing Factor (PDF)-containing LNv clock neurons. We found that increased LARK expression during development dramatically alters the small LNv class of neurons with no obvious effects on the large LNv cells. Conversely, conditional expression of LARK at the adult stage results in altered clock protein rhythms and circadian locomotor activity, even though neural morphology is normal in such animals. Electrophysiological analyses at the larval neuromuscular junction indicate a role for LARK in regulating neuronal excitability. Altogether, our results demonstrate that LARK activity is critical for neuronal development and physiology. PMID:19303442

Luminal glucose concentrations in the gut under normal conditions.

PubMed

Ferraris, R P; Yasharpour, S; Lloyd, K C; Mirzayan, R; Diamond, J M

1990-11-01

Luminal glucose (Glc) concentrations in the small intestine (SI) are widely assumed to be 50-500 mM. These values have posed problems for interpreting SI luminal osmolality and absorptive capacity, Glc transporter Michaelis-Menten constants (Km), and the physiological role of active Glc transport and its regulation. Hence we measured luminal contents, osmolality, and Glc, Na+, and K+ concentrations in normally feeding rats, rabbits, and dogs. Measured Glc concentrations were compatible with the portion of measured osmolality not accounted for by Na+ and K+ salts, amino acids, and peptides. Mean SI luminal osmolalities were less than or equal to 100 mosmol/kg hypertonic. For animals on the most nearly physiological diets, SI Glc concentrations averaged 0.4-24 mM and ranged with time and SI region from 0.2 to a maximum of 48 mM. The older published very high values are artifacts of direct infusion of concentrated Glc solutions into the gut, nonspecific Glc assays, and failure to test for quantitative recovery or to centrifuge samples in the cold. By storing food after meals and releasing it between meals, rat stomach greatly damps diurnal fluctuations in quantity and osmolality of food reaching the SI and hence also damps fluctuations in absorption rates. These new values for luminal Glc have five important physiological implications: the problem of accounting for apparently very hypertonic SI contents in the face of high osmotic water permeability disappears; the effective Km of the SI Glc transporter is now comparable to prevailing Glc concentrations; the SI no longer appears to have enormous excess absorptive capacity for Glc; regulation of Glc transport by dietary intake now makes functional sense; and the claim that high luminal Glc concentrations permit solvent drag to become the major mode of Glc absorption under normal conditions is undermined.

Catch-up Growth: Cellular and Molecular Mechanisms

PubMed Central

Finkielstain, GP; Lui, JC; Baron, J

2012-01-01

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

Long-term memory deficits in Pavlovian fear conditioning in Ca2+/calmodulin kinase kinase alpha-deficient mice.

PubMed

Blaeser, Frank; Sanders, Matthew J; Truong, Nga; Ko, Shanelle; Wu, Long Jun; Wozniak, David F; Fanselow, Michael S; Zhuo, Min; Chatila, Talal A

2006-12-01

Signaling by the Ca(2+)/calmodulin kinase (CaMK) cascade has been implicated in neuronal gene transcription, synaptic plasticity, and long-term memory consolidation. The CaM kinase kinase alpha (CaMKKalpha) isoform is an upstream component of the CaMK cascade whose function in different behavioral and learning and memory paradigms was analyzed by targeted gene disruption in mice. CaMKKalpha mutants exhibited normal long-term spatial memory formation and cued fear conditioning but showed deficits in context fear during both conditioning and long-term follow-up testing. They also exhibited impaired activation of the downstream kinase CaMKIV/Gr and its substrate, the transcription factor cyclic AMP-responsive element binding protein (CREB) upon fear conditioning. Unlike CaMKIV/Gr-deficient mice, the CaMKKalpha mutants exhibited normal long-term potentiation and normal levels of anxiety-like behavior. These results demonstrate a selective role for CaMKKalpha in contextual fear memory and suggest that different combinations of upstream and downstream components of the CaMK cascade may serve distinct physiological functions.

Sleep Physiology, Abnormal States, and Therapeutic Interventions

PubMed Central

Wickboldt, Alvah T.; Bowen, Alex F.; Kaye, Aaron J.; Kaye, Adam M.; Rivera Bueno, Franklin; Kaye, Alan D.

2012-01-01

Sleep is essential. Unfortunately, a significant portion of the population experiences altered sleep states that often result in a multitude of health-related issues. The regulation of sleep and sleep-wake cycles is an area of intense research, and many options for treatment are available. The following review summarizes the current understanding of normal and abnormal sleep-related conditions and the available treatment options. All clinicians managing patients must recommend appropriate therapeutic interventions for abnormal sleep states. Clinicians' solid understanding of sleep physiology, abnormal sleep states, and treatments will greatly benefit patients regardless of their disease process. PMID:22778676

International differences in the links between obesity and physiological dysregulation: the United States, England, and Taiwan.

PubMed

Vasunilashorn, Sarinnapha; Kim, Jung Ki; Crimmins, Eileen M

2013-01-01

Excess weight has generally been associated with adverse health outcomes; however, the link between overweight and health outcomes may vary with socioeconomic, cultural, and epidemiological conditions. We examine associations of weight with indicators of biological risk in three nationally representative populations: the US National Health and Nutrition Examination Survey, the English Longitudinal Study of Ageing, and the Social Environment and Biomarkers of Aging Study in Taiwan. Indicators of biological risk were compared for obese (defined using body mass index (BMI) and waist circumference) and normal weight individuals aged 54+. Generally, obesity in England was associated with elevated risk for more markers examined; obese Americans also had elevated risks except that they did not have elevated blood pressure (BP). Including waist circumference in our consideration of BMI indicated different links between obesity and waist size across countries; we found higher physiological dysregulation among those with high waist but normal BMI compared to those with normal waist and normal BMI. Americans had the highest levels of biological risk in all weight/waist groups. Cross-country variation in biological risk associated with obesity may reflect differences in health behaviors, lifestyle, medication use, and culture.

International Differences in the Links between Obesity and Physiological Dysregulation: The United States, England, and Taiwan

PubMed Central

Vasunilashorn, Sarinnapha; Kim, Jung Ki; Crimmins, Eileen M.

2013-01-01

Excess weight has generally been associated with adverse health outcomes; however, the link between overweight and health outcomes may vary with socioeconomic, cultural, and epidemiological conditions. We examine associations of weight with indicators of biological risk in three nationally representative populations: the US National Health and Nutrition Examination Survey, the English Longitudinal Study of Ageing, and the Social Environment and Biomarkers of Aging Study in Taiwan. Indicators of biological risk were compared for obese (defined using body mass index (BMI) and waist circumference) and normal weight individuals aged 54+. Generally, obesity in England was associated with elevated risk for more markers examined; obese Americans also had elevated risks except that they did not have elevated blood pressure (BP). Including waist circumference in our consideration of BMI indicated different links between obesity and waist size across countries; we found higher physiological dysregulation among those with high waist but normal BMI compared to those with normal waist and normal BMI. Americans had the highest levels of biological risk in all weight/waist groups. Cross-country variation in biological risk associated with obesity may reflect differences in health behaviors, lifestyle, medication use, and culture. PMID:23781331

Stability of Reference Genes for Real-Time PCR Analyses in Channel Catfish (Ictalurus punctatus) Tissues Under Varying Physiological Conditions

USDA-ARS?s Scientific Manuscript database

Real-time PCR is a highly sensitive, relatively easy to perform assay for quantifying mRNA abundance. However, there are several complexities built into the assay that can affect data interpretation. Most notably, the selection of an appropriate internal control for normalization is essential for ...

Cotton Physiological Responses to Application of Urea with NBPT and DCD Under Normal and High Temperature Conditions

USDA-ARS?s Scientific Manuscript database

Nitrogen fertilization is one the most expensive agricultural practices and crops are known to recover only about a third of the N fertilizer applied. A practice commonly recommended to improve N use efficiency is the incorporation of urease and/or nitrification inhibitor into N fertilizers. The ob...

Auditory steady state response in sound field.

PubMed

Hernández-Pérez, H; Torres-Fortuny, A

2013-02-01

Physiological and behavioral responses were compared in normal-hearing subjects via analyses of the auditory steady-state response (ASSR) and conventional audiometry under sound field conditions. The auditory stimuli, presented through a loudspeaker, consisted of four carrier tones (500, 1000, 2000, and 4000 Hz), presented singly for behavioral testing but combined (multiple frequency technique), to estimate thresholds using the ASSR. Twenty normal-hearing adults were examined. The average differences between the physiological and behavioral thresholds were between 17 and 22 dB HL. The Spearman rank correlation between ASSR and behavioral thresholds was significant for all frequencies (p < 0.05). Significant differences were found in the ASSR amplitude among frequencies, and strong correlations between the ASSR amplitude and the stimulus level (p < 0.05). The ASSR in sound field testing was found to yield hearing threshold estimates deemed to be reasonably well correlated with behaviorally assessed thresholds.

Bioengineering a vaginal replacement using a small biopsy of autologous tissue.

PubMed

Dorin, Ryan P; Atala, Anthony; Defilippo, Roger E

2011-01-01

Many congenital and acquired diseases result in the absence of a normal vagina. Patients with these conditions often require reconstructive surgery to achieve satisfactory cosmesis and physiological function, and a variety of materials have been used as tissue sources. Currently employed graft materials such as collagen scaffolds and small intestine are not ideal in that they fail to mimic the physiology of normal vaginal tissue. Engineering of true vaginal tissue from a small biopsy of autologous vagina should produce a superior graft material for vaginal reconstruction. This review describes our current experience with the engineering of such tissue and its use for vaginal reconstruction in animal models. Our successful construction and implantation of neovaginas through tissue engineering techniques demonstrates the feasibility of similar endeavors in human patients. Additionally, the use of pluripotent stem cells instead of autologous tissue could provide an "off-the-shelf" tissue source for vaginal reconstruction.

Corticotropin-releasing factor: effect on cerebral blood flow in physiologic and ischaemic conditions.

PubMed

De Michele, Manuela; Touzani, Omar; Foster, Alan C; Fieschi, Cesare; Sette, Giuliano; McCulloch, James

2005-09-01

The expression of corticotrophin-releasing factor (CRF) receptors in cerebral arteries and arterioles suggests that CRF may modulate cerebral blood flow (CBF). In the present study, the effects of CRF, CRF-like peptides and the CRF broad spectrum antagonist DPhe-CRF on CBF have been investigated under normal physiologic conditions and in the margins of focal ischaemic insult. The experiments were carried out in anaesthetised and ventilated rats. Changes in CBF after subarachnoid microapplication of CRF and related peptides were assessed with a laser-Doppler flowmetry (LDF) probe. In the ischaemic animals, agents were injected approximately 60 minutes after permanent middle cerebral artery occlusion (MCAo). Microapplication of CRF and related peptides in normal rats into the subarachnoid space produced sustained concentration-dependent increases in CBF. This effect was attenuated by co-application with DPhe-CRF, which did not alter CBF itself. A second microapplication of CRF 30 min after the first failed to produce increases in CBF in normal animals. Microapplication of CRF in the subarachnoid space overlying the ischaemic cortex effected minor increases in CBF whereas D-Phe-CRF had no significant effect on CBF. Activation of the CRF peptidergic system increases CBF in the rat. Repeated activation of CRF receptors results in tachyphylaxis of the vasodilator response. CRF vasodilator response is still present after MCAo in the ischaemic penumbra, suggesting that the CRF peptidergic system may modulate CBF in ischaemic stroke.

No overt structural or functional changes associated with PEG-coated gold nanoparticles accumulation with acute exposure in the mouse heart.

PubMed

Yang, Chengzhi; Yang, Hui; Wu, Jimin; Meng, Zenghui; Xing, Rui; Tian, Aiju; Tian, Xin; Guo, Lijun; Zhang, Youyi; Nie, Guangjun; Li, Zijian

2013-10-24

In this study, we investigated the cardiac biodistribution of polyethylene glycol (PEG)-coated AuNPs and their effects on cardiac function, structure and inflammation in both normal and cardiac remodeling mice. The model of cardiac remodeling was induced by subcutaneously injection of isoproterenol (ISO), a non-selective beta-adrenergic agonist, for 7 days. After AuNPs were injected intravenously in mice for 7 consecutive days, Au content in different organs was determined quantitatively by inductively coupled plasma mass spectrometry (ICP-MS), cardiac function and structure were measured by echocardiography, cardiac fibrosis was examined with picrosirius red staining, the morphology of cardiomyocytes was observed with hematoxylin and eosin (H & E) staining. The accumulation of AuNPs in hearts did not affect cardiac function or induce cardiac hypertrophy, cardiac fibrosis and cardiac inflammation under normal physiological condition. Cardiac AuNPs content was 6-fold higher in the cardiac remodeling mouse than normal mice. However, the increased accumulation of AuNPs in the heart did not aggravate ISO-induced cardiac hypertrophy, cardiac fibrosis or cardiac inflammation. These observations suggest that PEG-coated AuNPs possess excellent biocompatibility under both physiological and pathological conditions. Thus, AuNPs may be safe for cardiac patients and hold great promise for further development for various biomedical applications. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

The Frank-Starling mechanism involves deceleration of cross-bridge kinetics and is preserved in failing human right ventricular myocardium.

PubMed

Milani-Nejad, Nima; Canan, Benjamin D; Elnakish, Mohammad T; Davis, Jonathan P; Chung, Jae-Hoon; Fedorov, Vadim V; Binkley, Philip F; Higgins, Robert S D; Kilic, Ahmet; Mohler, Peter J; Janssen, Paul M L

2015-12-15

Cross-bridge cycling rate is an important determinant of cardiac output, and its alteration can potentially contribute to reduced output in heart failure patients. Additionally, animal studies suggest that this rate can be regulated by muscle length. The purpose of this study was to investigate cross-bridge cycling rate and its regulation by muscle length under near-physiological conditions in intact right ventricular muscles of nonfailing and failing human hearts. We acquired freshly explanted nonfailing (n = 9) and failing (n = 10) human hearts. All experiments were performed on intact right ventricular cardiac trabeculae (n = 40) at physiological temperature and near the normal heart rate range. The failing myocardium showed the typical heart failure phenotype: a negative force-frequency relationship and β-adrenergic desensitization (P < 0.05), indicating the expected pathological myocardium in the right ventricles. We found that there exists a length-dependent regulation of cross-bridge cycling kinetics in human myocardium. Decreasing muscle length accelerated the rate of cross-bridge reattachment (ktr) in both nonfailing and failing myocardium (P < 0.05) equally; there were no major differences between nonfailing and failing myocardium at each respective length (P > 0.05), indicating that this regulatory mechanism is preserved in heart failure. Length-dependent assessment of twitch kinetics mirrored these findings; normalized dF/dt slowed down with increasing length of the muscle and was virtually identical in diseased tissue. This study shows for the first time that muscle length regulates cross-bridge kinetics in human myocardium under near-physiological conditions and that those kinetics are preserved in the right ventricular tissues of heart failure patients. Copyright © 2015 the American Physiological Society.

The Roles of Glutamine in the Intestine and Its Implication in Intestinal Diseases

PubMed Central

Kim, Min-Hyun; Kim, Hyeyoung

2017-01-01

Glutamine, the most abundant free amino acid in the human body, is a major substrate utilized by intestinal cells. The roles of glutamine in intestinal physiology and management of multiple intestinal diseases have been reported. In gut physiology, glutamine promotes enterocyte proliferation, regulates tight junction proteins, suppresses pro-inflammatory signaling pathways, and protects cells against apoptosis and cellular stresses during normal and pathologic conditions. As glutamine stores are depleted during severe metabolic stress including trauma, sepsis, and inflammatory bowel diseases, glutamine supplementation has been examined in patients to improve their clinical outcomes. In this review, we discuss the physiological roles of glutamine for intestinal health and its underlying mechanisms. In addition, we discuss the current evidence for the efficacy of glutamine supplementation in intestinal diseases. PMID:28498331

Effects of larval growth condition and water availability on desiccation resistance and its physiological basis in adult Anopheles gambiae sensu stricto

PubMed Central

2010-01-01

Background Natural populations of the malaria mosquito Anopheles gambiae s.s. are exposed to large seasonal and daily fluctuations in relative humidity and temperature, which makes coping with drought a crucial aspect of their ecology. Methods To better understand natural variation in desiccation resistance in this species, the effects of variation in larval food availability and access to water as an adult on subsequent phenotypic quality and desiccation resistance of adult females of the Mopti chromosomal form were tested experimentally. Results It was found that, under normal conditions, larval food availability and adult access to water had only small direct effects on female wet mass, dry mass, and water, glycogen and body lipid contents corrected for body size. In contrast, when females subsequently faced a strong desiccation challenge, larval food availability and adult access to water had strong carry-over effects on most measured physiological and metabolic parameters, and affected female survival. Glycogen and water content were the most used physiological reserves in relative terms, but their usage significantly depended on female phenotypic quality. Adult access to water significantly influenced the use of water and body lipid reserves, which subsequently affected desiccation resistance. Conclusions These results demonstrate the importance of growth conditions and water availability on adult physiological status and subsequent resistance to desiccation. PMID:20691104

Effect of the spider toxin Tx3-3 on spinal processing of sensory information in naive and neuropathic rats: an in vivo electrophysiological study.

PubMed

Dalmolin, Gerusa D; Bannister, Kirsty; Gonçalves, Leonor; Sikandar, Shafaq; Patel, Ryan; Cordeiro, Marta do Nascimento; Gomez, Marcus Vinícius; Ferreira, Juliano; Dickenson, Anthony H

2017-07-01

Drugs that counteract nociceptive transmission in the spinal dorsal horn preferentially after nerve injury are being pursued as possible neuropathic pain treatments. In a previous behavioural study, the peptide toxin Tx3-3, which blocks P/Q- and R-type voltage-gated calcium channels, was effective in neuropathic pain models. In the present study, we aimed to investigate the effect of Tx3-3 on dorsal horn neuronal responses in rats under physiological conditions and neuropathic pain condition induced by spinal nerve ligation (SNL). In vivo electrophysiological recordings of dorsal horn neuronal response to electrical and natural (mechanical and thermal) stimuli were made in rats under normal physiological state (naive rats) or after the SNL model of neuropathic pain. Tx3-3 (0.3-100 pmol/site) exhibited greater inhibitory effect on electrical-evoked neuronal response of SNL rats than naive rats, inhibiting nociceptive C-fibre and Aδ-fibre responses only in SNL rats. The wind-up of neurones, a measurement of spinal cord hyperexcitability, was also more susceptible to a dose-related inhibition by Tx3-3 after nerve injury. Moreover, Tx3-3 exhibited higher potency to inhibit mechanical- and thermal-evoked neuronal response in conditions of neuropathy. Tx3-3 mediated differential inhibitory effect under physiological and neuropathic conditions, exhibiting greater potency in conditions of neuropathic pain.

Normal Variants and Pitfalls Encountered in PET Assessment of Gynecologic Malignancies.

PubMed

Yu, Jian Q; Doss, Mohan; Alpaugh, R Katherine

2018-04-01

Combined PET/computed tomography is used for oncological indications. PET/computed tomography benefits from the metabolic information of PET and the anatomic localization of computed tomography. The integrated scanner provides data with accurate registration of anatomy and molecular information. Many physiologic conditions, normal variants, and benign lesions within the pelvis and the body can cause confusion and uncertainty. False-negative results owing to low 18 F-fluorodeoxyglucose uptake from the tumor can produce diagnostic challenges and inaccurate conclusions. This article reviews normal variants and potential pitfalls encountered in PET assessment of gynecologic malignancies to provide useful information for the referring and reporting physicians. Copyright © 2017 Elsevier Inc. All rights reserved.

Big-conductance Ca2+-activated K+ channels in physiological and pathophysiological urinary bladder smooth muscle cells

PubMed Central

Parajuli, Shankar P.; Zheng, Yun-Min; Levin, Robert; Wang, Yong-Xiao

2016-01-01

ABSTRACT Contraction and relaxation of urinary bladder smooth muscle cells (UBSMCs) represent the important physiological functions of the bladder. Contractile responses in UBSMCs are regulated by a number of ion channels including big-conductance Ca2+- activated K+ (BK) channels. Great progress has been made in studies of BK channels in UBSMCs. The intent of this review is to summarize recent exciting findings with respect to the functional interactions of BK channels with muscarinic receptors, ryanodine receptors (RyRs) and inositol triphosphate receptors (IP3Rs) as well as their functional importance under normal and pathophysiological conditions. BK channels are highly expressed in UBSMCs. Activation of muscarinic M3 receptors inhibits the BK channel activity, facilitates opening of voltage-dependent Ca2+ (CaV) channels, and thereby enhances excitability and contractility of UBSMCs. Signaling molecules and regulatory mechanisms involving RyRs and IP3Rs have a significant effect on functions of BK channels and thereby regulate cellular responses in UBSMCs under normal and pathophysiological conditions including overactive bladders. Moreover, BK channels may represent a novel target for the treatment of bladder dysfunctions. PMID:27101440

Co-delivery of cisplatin and CJM-126 via photothermal conversion nanoparticles for enhanced synergistic antitumor efficacy

NASA Astrophysics Data System (ADS)

You, Chaoqun; Wu, Hongshuai; Wang, Mingxin; Gao, Zhiguo; Zhang, Xiangyang; Sun, Baiwang

2018-01-01

Polymeric biomaterials that can be smartly disassembled through the cleavage of the covalent bonds in a controllable way upon an environmental stimulus such as pH change, redox, special enzymes, temperature, or ultrasound, as well as light irradiation, but are otherwise stable under normal physiological conditions have attracted great attention in recent decades. The 2-(4-aminophenyl) benzothiazole molecule (CJM-126), as one of the benzothiazole derivatives, has exhibited a synergistic effect with cisplatin (CDDP) and restrains the bioactivities of a series of human breast cancer cell lines. In our study, novel NIR-responsive targeted binary-drug-loaded nanoparticles encapsulating indocyanine green (ICG) dye were prepared as a new co-delivery and combined therapeutic vehicle. The prepared drug-loaded polymeric nanoparticles (TNPs/CDDP-ICG) are stable under normal physiological conditions, while burst drugs release upon NIR laser irradiation in a mild acidic environment. The results further confirmed that the designed co-delivery platform showed higher cytotoxicity than the single free CDDP due to the synergistic treatment of CJM-126 and CDDP in vitro. Taken together, the work might provide a promising approach for effective site-specific antitumor therapy.

Status of research on MMPs in India.

PubMed

Saravanan, Chinnadurai; Singh, Sushil Kumar

2011-06-01

MMPs are metal-dependant endopeptidases capable of degrading any one of the components of the extracellular matrix. In normal physiological conditions it is regulated by tissue inhibitors of metalloproteinases, and any alteration in this regulatory process leads to pathological conditions. This review discusses the status of MMP research in India. The first research paper was published in 1998; the subsequent developments in this field led to an increase in the number of publications. This review highlights the growth of MMP research in India based on the research papers published from 1998 to 2010. We identify four major subject areas: cancer, arthritis, ulcer and quantitative structure-activity relationship. The diseases involved are discussed along with the required steps for improving treatments. Indian researchers need to work on new molecules with specific MMP inhibitory activity for cancer and communicable and geriatric diseases. Although several publications on natural products have appeared from India, they are very few considering the number of medicinal plants available in the country. Inhibiting MMPs could be both beneficial and detrimental to cells, owing to the inter-relationship between normal physiology and pathology; thus, targeting MMPs with broad MMP inhibitors can have mixed blessings.

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

PubMed Central

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

2014-01-01

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

Sensitivity of housekeeping genes in the suprachiasmatic nucleus of the mouse brain to diet and the daily light-dark cycle.

PubMed

Cleal, Jane K; Shepherd, James N; Shearer, Jasmine L; Bruce, Kimberley D; Cagampang, Felino R

2014-08-05

The endogenous timing system within the suprachiasmatic nuclei (SCN) of the hypothalamus drives the cyclic expression of the clock molecules across the 24h day-night cycle controlling downstream molecular pathways and physiological processes. The developing fetal clock system is sensitive to the environment and physiology of the pregnant mother and as such disruption of this system could lead to altered physiology in the offspring. Characterizing the gene profiles of the endogenous molecular clock system by quantitative reverse transcription polymerase chain reaction is dependent on normalization by appropriate housekeeping genes (HKGs). However, many HKGs commonly used as internal controls, although stably expressed under control conditions, can vary significantly in their expression under certain experimental conditions. Here we analyzed the expression of 10 classic HKG across the 24h light-dark cycle in the SCN of mouse offspring exposed to normal chow or a high fat diet during early development and in postnatal life. We found that the HKGs glyceraldehyde-3-phosphate dehydrogenase, beta actin and adenosine triphosphate synthase subunit to be the most stably expressed genes in the SCN regardless of diet or time within the 24h light-dark cycle, and are therefore suitable to be used as internal controls. However SCN samples collected during the light and dark periods did show differences in expression and as such the timing of collection should be considered when carrying out gene expression studies. Copyright © 2014 Elsevier B.V. All rights reserved.

Independence of nutrient limitation and carbon dioxide impacts on the Southern Ocean coccolithophore Emiliania huxleyi.

PubMed

Müller, Marius N; Trull, Thomas W; Hallegraeff, Gustaaf M

2017-08-01

Future oceanic conditions induced by anthropogenic greenhouse gas emissions include warming, acidification and reduced nutrient supply due to increased stratification. Some parts of the Southern Ocean are expected to show rapid changes, especially for carbonate mineral saturation. Here we compare the physiological response of the model coccolithophore Emiliania huxleyi (strain EHSO 5.14, originating from 50 o S, 149 o E) with pH/CO 2 gradients (mimicking ocean acidification ranging from 1 to 4 × current pCO 2 levels) under nutrient-limited (nitrogen and phosphorus) and -replete conditions. Both nutrient limitations decreased per cell photosynthesis (particulate organic carbon (POC) production) and calcification (particulate inorganic carbon (PIC) production) rates for all pCO 2 levels, with more than 50% reductions under nitrogen limitation. These impacts, however, became indistinguishable from nutrient-replete conditions when normalized to cell volume. Calcification decreased three-fold and linearly with increasing pCO 2 under all nutrient conditions, and was accompanied by a smaller ~30% nonlinear reduction in POC production, manifested mainly above 3 × current pCO 2 . Our results suggest that normalization to cell volume allows the major impacts of nutrient limitation (changed cell sizes and reduced PIC and POC production rates) to be treated independently of the major impacts of increasing pCO 2 and, additionally, stresses the importance of including cell volume measurements to the toolbox of standard physiological analysis of coccolithophores in field and laboratory studies.

Independence of nutrient limitation and carbon dioxide impacts on the Southern Ocean coccolithophore Emiliania huxleyi

PubMed Central

Müller, Marius N; Trull, Thomas W; Hallegraeff, Gustaaf M

2017-01-01

Future oceanic conditions induced by anthropogenic greenhouse gas emissions include warming, acidification and reduced nutrient supply due to increased stratification. Some parts of the Southern Ocean are expected to show rapid changes, especially for carbonate mineral saturation. Here we compare the physiological response of the model coccolithophore Emiliania huxleyi (strain EHSO 5.14, originating from 50oS, 149oE) with pH/CO2 gradients (mimicking ocean acidification ranging from 1 to 4 × current pCO2 levels) under nutrient-limited (nitrogen and phosphorus) and -replete conditions. Both nutrient limitations decreased per cell photosynthesis (particulate organic carbon (POC) production) and calcification (particulate inorganic carbon (PIC) production) rates for all pCO2 levels, with more than 50% reductions under nitrogen limitation. These impacts, however, became indistinguishable from nutrient-replete conditions when normalized to cell volume. Calcification decreased three-fold and linearly with increasing pCO2 under all nutrient conditions, and was accompanied by a smaller ~30% nonlinear reduction in POC production, manifested mainly above 3 × current pCO2. Our results suggest that normalization to cell volume allows the major impacts of nutrient limitation (changed cell sizes and reduced PIC and POC production rates) to be treated independently of the major impacts of increasing pCO2 and, additionally, stresses the importance of including cell volume measurements to the toolbox of standard physiological analysis of coccolithophores in field and laboratory studies. PMID:28430186

Sleep and the Cardiovascular System in Children.

PubMed

Paul, Grace R; Pinto, Swaroop

2017-06-01

Subspecialty pediatric practice provides comprehensive medical care for a range of ages, from premature infants to children, and often includes adults with complex medical and surgical issues that warrant multidisciplinary care. Normal physiologic variations involving different body systems occur during sleep and these vary with age, stage of sleep, and underlying health conditions. This article is a concise review of the cardiovascular (CV) physiology and pathophysiology in children, sleep-disordered breathing (SDB) contributing to CV morbidity, congenital and acquired CV pathology resulting in SDB, and the relationship between SDB and CV morbidity in different clinical syndromes and systemic diseases in the expanded pediatric population. Copyright © 2017 Elsevier Inc. All rights reserved.

Fractal mechanisms in the electrophysiology of the heart

NASA Technical Reports Server (NTRS)

Goldberger, A. L.

1992-01-01

The mathematical concept of fractals provides insights into complex anatomic branching structures that lack a characteristic (single) length scale, and certain complex physiologic processes, such as heart rate regulation, that lack a single time scale. Heart rate control is perturbed by alterations in neuro-autonomic function in a number of important clinical syndromes, including sudden cardiac death, congestive failure, cocaine intoxication, fetal distress, space sickness and physiologic aging. These conditions are associated with a loss of the normal fractal complexity of interbeat interval dynamics. Such changes, which may not be detectable using conventional statistics, can be quantified using new methods derived from "chaos theory.".

Update in TSH Receptor Agonists and Antagonists

PubMed Central

Neumann, Susanne

2012-01-01

The physiological role of the TSH receptor (TSHR) as a major regulator of thyroid function is well understood, but TSHRs are also expressed in multiple normal extrathyroidal tissues, and the physiological roles of TSHRs in these tissues are unclear. Moreover, TSHRs play a major role in several pathological conditions including hyperthyroidism, hypothyroidism, and thyroid tumors. Small molecule, “drug-like” TSHR agonists, neutral antagonists, and inverse agonists may be useful as probes of TSHR function in extrathyroidal tissues and as leads to develop drugs for several diseases of the thyroid. In this Update, we review the most recent findings regarding the development and use of these small molecule TSHR ligands. PMID:23019348

Cardiac anatomy and physiology: a review.

PubMed

Gavaghan, M

1998-04-01

This article reviews the normal anatomy and physiology of the heart. Understanding the normal anatomic and physiologic relationships described in this article will help perioperative nurses care for patients who are undergoing cardiac procedures. Such knowledge also assists nurses in educating patients about cardiac procedures and about activities that can prevent, reverse, or improve cardiac illness.

Misophonia: physiological investigations and case descriptions.

PubMed

Edelstein, Miren; Brang, David; Rouw, Romke; Ramachandran, Vilayanur S

2013-01-01

Misophonia is a relatively unexplored chronic condition in which a person experiences autonomic arousal (analogous to an involuntary "fight-or-flight" response) to certain innocuous or repetitive sounds such as chewing, pen clicking, and lip smacking. Misophonics report anxiety, panic, and rage when exposed to trigger sounds, compromising their ability to complete everyday tasks and engage in healthy and normal social interactions. Across two experiments, we measured behavioral and physiological characteristics of the condition. Interviews (Experiment 1) with misophonics showed that the most problematic sounds are generally related to other people's behavior (pen clicking, chewing sounds). Misophonics are however not bothered when they produce these "trigger" sounds themselves, and some report mimicry as a coping strategy. Next, (Experiment 2) we tested the hypothesis that misophonics' subjective experiences evoke an anomalous physiological response to certain auditory stimuli. Misophonic individuals showed heightened ratings and skin conductance responses (SCRs) to auditory, but not visual stimuli, relative to a group of typically developed controls, supporting this general viewpoint and indicating that misophonia is a disorder that produces distinct autonomic effects not seen in typically developed individuals.

Misophonia: physiological investigations and case descriptions

PubMed Central

Edelstein, Miren; Brang, David; Rouw, Romke; Ramachandran, Vilayanur S.

2013-01-01

Misophonia is a relatively unexplored chronic condition in which a person experiences autonomic arousal (analogous to an involuntary “fight-or-flight” response) to certain innocuous or repetitive sounds such as chewing, pen clicking, and lip smacking. Misophonics report anxiety, panic, and rage when exposed to trigger sounds, compromising their ability to complete everyday tasks and engage in healthy and normal social interactions. Across two experiments, we measured behavioral and physiological characteristics of the condition. Interviews (Experiment 1) with misophonics showed that the most problematic sounds are generally related to other people's behavior (pen clicking, chewing sounds). Misophonics are however not bothered when they produce these “trigger” sounds themselves, and some report mimicry as a coping strategy. Next, (Experiment 2) we tested the hypothesis that misophonics' subjective experiences evoke an anomalous physiological response to certain auditory stimuli. Misophonic individuals showed heightened ratings and skin conductance responses (SCRs) to auditory, but not visual stimuli, relative to a group of typically developed controls, supporting this general viewpoint and indicating that misophonia is a disorder that produces distinct autonomic effects not seen in typically developed individuals. PMID:23805089

Disentangling Emotion Processes in Borderline Personality Disorder: Physiological and Self-reported Assessment of Biological Vulnerability, Baseline Intensity, and Reactivity to Emotionally-Evocative Stimuli

PubMed Central

Kuo, Janice R.; Linehan, Marsha M.

2014-01-01

This study investigated Linehan’s (1993) theory that individuals meeting criteria for borderline personality disorder (BPD) have high biological vulnerability to emotion dysregulation, including high baseline emotional intensity and high reactivity to emotionally-evocative stimuli. Twenty individuals with BPD, 20 age-matched individuals with generalized social anxiety disorder (SAD), and 20 age-matched normal controls (NC) participated in two separate emotion induction conditions, a standardized condition and a personally-relevant condition. Respiratory sinus arrhythmia (RSA), skin conductance response (SCR), and self-report measures were collected throughout the experiment. BPD participants displayed heightened biological vulnerability compared with NC as indicated by reduced basal RSA. BPD participants also exhibited high baseline emotional intensity, characterized by heightened SCR and heightened self-reported negative emotions at baseline. However, the BPD group did not display heightened reactivity as their physiological and self-reported changes from baseline to the emotion inductions tasks were not greater than the other two groups. PMID:19685950

Contractile properties of single permeabilized muscle fibers from congenital cleft palates and normal palates of Spanish goats.

PubMed

Hanes, Michael C; Weinzweig, Jeffrey; Kuzon, William M; Panter, Kip E; Buchman, Steven R; Faulkner, John A; Yu, Deborah; Cederna, Paul S; Larkin, Lisa M

2007-05-01

Analysis of the composition of muscle fibers constituent to a cleft palate could provide significant insight into the cause of velopharyngeal inadequacy. The authors hypothesized that levator veli palatini muscle dysfunction inherent to cleft palates could affect the timing and outcome of cleft palate repair. Single, permeabilized muscle fibers from levator veli palatini muscles of three normal (n = 19 fibers) and three chemically induced congenital cleft palates (n = 21 fibers) of 14-month-old goats were isolated, and contractile properties were evaluated. The maximum isometric force and rate constants of tension redevelopment (ktr) were measured, and the specific force and normalized power were calculated for each fiber. The ktr measures indicate that cleft fibers are predominantly fast-fatigable; normal fibers are slow fatigue-resistant: after a 10-minute isometric contraction, fibers from cleft palates had a loss of force 16 percent greater than that from normal palates (p = 0.0001). The cross-sectional areas of the fibers from cleft palates (2750 +/- 209 microm2) were greater (p = 0.05) than those from normal palates (2226 +/- 143 microm2). Specific forces did not differ between the two groups. Maximum normalized power of fibers from cleft palates (11.05 +/- 1.82 W/l) was greater (p = 0.0001) than fibers from normal palates (1.60 +/- 0.12 W/l). There are clear physiologic differences in single muscle fibers from cleft palates and normal palates: cleft palate fibers are physiologically fast, have greater fatigability, and have greater power production. Detection of functional and/or fiber type differences in muscles of cleft palates may provide preoperative identification of a patient's susceptibility to velopharyngeal inadequacy and permit early surgical intervention to correct this clinical condition.

Oscillographic and Physiological Measurements of Delayed Auditory Feedback and Anxiety Factors in Stutterers and Non-Stutterers.

ERIC Educational Resources Information Center

Timmons, Beverly A.; Boudreau, James P.

Reported are five studies on the use of delayed auditory feedback (DAF) with stutterers. The first study indicates that sex differences and age differences in temporal reaction were found when subjects (5-, 7-, 9-, 11-, and 13-years-old) recited a nursery rhyme under DAF and NAF (normal auditory feedback) conditions. The second study is reported…

Timely Degradation of Wip1 Phosphatase by APC/C Activator Protein Cdh1 is Necessary for Normal Mitotic Progression.

PubMed

Jeong, Ho-Chang; Gil, Na-Yeon; Lee, Ho-Soo; Cho, Seung-Ju; Kim, Kyungtae; Chun, Kwang-Hoon; Cho, Hyeseong; Cha, Hyuk-Jin

2015-08-01

Wip1 belongs to the protein phosphatase C (PP2C) family, of which expression is up-regulated by a number of external stresses, and serves as a stress modulator in normal physiological conditions. When overexpressed, premature dephosphorylation of stress-mediators by Wip1 results in abrogation of tumor surveillance, thus Wip1 acts as an oncogene. Previously, the functional regulation of Wip1 in cell-cycle progression by counteracting cellular G1 and G2/M checkpoint activity in response to DNA damage was reported. However, other than in stress conditions, the function and regulatory mechanism of Wip1 has not been fully determined. Herein, we demonstrated that protein regulation of Wip1 occurs in a cell cycle-dependent manner, which is directly governed by APC/C(Cdh1) at the end of mitosis. In particular, we also showed evidence that Wip1 phosphatase activity is closely associated with its own protein stability, suggesting that reduced phosphatase activity of Wip1 during mitosis could trigger its degradation. Furthermore, to verify the physiological role of its phosphatase activity during mitosis, we established doxycycline-inducible cell models, including a Wip1 wild type (WT) and phosphatase dead mutant (Wip1 DA). When ectopically expressing Wip1 WT, we observed a delay in the transition from metaphase to anaphase. In conclusion, these studies show that mitotic degradation of Wip1 by APC/C(Cdh1) is important for normal mitotic progression. © 2015 Wiley Periodicals, Inc.

Increase of Chamazulene and α-Bisabolol Contents of the Essential Oil of German Chamomile (Matricaria chamomilla L.) Using Salicylic Acid Treatments under Normal and Heat Stress Conditions.

PubMed

Ghasemi, Mojtaba; Babaeian Jelodar, Nadali; Modarresi, Mohammad; Bagheri, Nadali; Jamali, Abbas

2016-08-27

The chamazulene and α-(-)-bisabolol contents and quality of the chamomile oil are affected by genetic background and environmental conditions. Salicylic acid (SA), as a signaling molecule, plays a significant role in the plant physiological processes. The aim of this study was to evaluate the chemical profile, quantity, and improve the essential oil quality as a consequence of the increase of chamazulene and α-(-)-bisabol using salicylic acid under normal and heat stress conditions by the gas chromatography-mass spectrometry (GC-MS) technique. The factorial experiments were carried out during the 2011-2012 hot season using a randomized complete block design with three replications. The factors include four salicylic acid concentrations (0 (control), 10, 25 and 100 mg·L -1 ), and three chamomile cultivars (Bushehr, Bona, Bodegold) were sown on two different planting dates under field conditions. Fourteen compounds were identified from the extracted oil of the samples treated with salicylic acid under normal and heat stress conditions. The major identified oil compositions from chamomile cultivars treated with salicylic acid were chamazulene, α-(-)-bisabolol, bisabolone oxide, β-farnesene, en-yn-dicycloether, and bisabolol oxide A and B. Analysis of variance showed that the simple effects (environmental conditions, cultivar and salicylic acid) and their interaction were significant on all identified compounds, but the environmental conditions had no significant effect on bisabolol oxide A. The greatest amount of chamazulene obtained was 6.66% at the concentration of 10 mg·L -1 SA for the Bona cultivar under heat stress conditions, whereas the highest α-(-)-bisabolol amount attained was 3.41% at the concentration of 100 mg·L -1 SA for the Bona cultivar under normal conditions. The results demonstrated that the application of exogenous salicylic acid increases the quantity and essential oil quality as a consequence of the increase of chamazulene and α-(-)-bisabolol under normal and heat stress conditions.

A prospective randomized trial of two solutions for intrapartum amnioinfusion: effects on fetal electrolytes, osmolality, and acid-base status.

PubMed

Pressman, E K; Blakemore, K J

1996-10-01

Our purpose was to compare the effects of intrapartum amnioinfusion with normal saline solution versus lactated Ringer's solution plus physiologic glucose on neonatal electrolytes and acid-base balance. Patients undergoing amnioinfusion for obstetric indications were randomized to receive normal saline solution or lactated Ringer's solution plus physiologic glucose at standardized amnioinfusion rates. Data were collected prospectively on maternal demographics, course of labor, and maternal and neonatal outcome. Arterial cord blood was obtained for analysis of electrolytes, glucose, osmolality, lactic acid, and blood gases. Control subjects with normal fetal heart rate patterns, and clear amniotic fluid not receiving amnioinfusion were studied concurrently. Data were collected on 59 patients (21 normal saline solution, 18 lactated Ringer's solution plus physiologic glucose, and 20 controls). Maternal demographics, course of labor, and neonatal outcome were similar in all three groups. Cesarean sections were performed more often in the amnioinfusion groups (33.3% for normal saline solution, 38.9% for lactated Ringer's solution plus physiologic glucose) than in the control group (5.0%), p < 0.05. Cord arterial electrolytes, glucose, osmolality, lactic acid, and blood gases were not altered by amnioinfusion with either solution. Intrapartum amnioinfusion with normal saline solution or lactated Ringer's solution plus physiologic glucose has no effect on neonatal electrolytes or acid-base balance.

Near-Infrared Fluorescent Nanoprobes for Revealing the Role of Dopamine in Drug Addiction.

PubMed

Feng, Peijian; Chen, Yulei; Zhang, Lei; Qian, Cheng-Gen; Xiao, Xuanzhong; Han, Xu; Shen, Qun-Dong

2018-02-07

Brain imaging techniques enable visualizing the activity of central nervous system without invasive neurosurgery. Dopamine is an important neurotransmitter. Its fluctuation in brain leads to a wide range of diseases and disorders, like drug addiction, depression, and Parkinson's disease. We designed near-infrared fluorescence dopamine-responsive nanoprobes (DRNs) for brain activity imaging during drug abuse and addiction process. On the basis of light-induced electron transfer between DRNs and dopamine and molecular wire effect of the DRNs, we can track the dynamical change of the neurotransmitter level in the physiological environment and the releasing of the neurotransmitter in living dopaminergic neurons in response to nicotine stimulation. The functional near-infrared fluorescence imaging can dynamically track the dopamine level in the mice midbrain under normal or drug-activated condition and evaluate the long-term effect of addictive substances to the brain. This strategy has the potential for studying neural activity under physiological condition.

Does the hair influence heat extraction from the head during head cooling under heat stress?

PubMed Central

SHIN, Sora; PARK, Joonhee; LEE, Joo-Young

2015-01-01

The purpose of this study was to investigate the effects of head hair on thermoregulatory responses when cooling the head under heat stress. Eight young males participated in six experimental conditions: normal hair (100–130 mm length) and cropped hair (5 mm length) with three water inlet temperatures of 10, 15, and 20°C. The head and neck of subjects were cooled by a liquid perfused hood while immersing legs at 42°C water for 60 min in a sitting position at the air temperature of 28°C with 30% RH. The results showed that heat removal from the normal hair condition was not significantly different from the cropped hair condition. Rectal and mean skin temperatures, and sweat rate showed no significant differences between the normal and cropped hair conditions. Heat extraction from the head was significantly greater in 10°C than in 15 or 20°C cooling (p<0.05) for both normal and cropped hair, whereas subjects preferred the 15°C more than the 10 or 20°C cooling regimen. These results indicate that the selection of effective cooling temperature is more crucial than the length of workers’ hair during head cooling under heat stress, and such selection should be under the consideration of subjective perceptions with physiological responses. PMID:26165361

Long-term high-soybean oil feeding alters regulation of body temperature in rats.

PubMed

Tsushima, Hiromi; Yamada, Kazuyo; Miyazawa, Daisuke; Mori, Mayumi; Hashimoto, Yoko; Ohkubo, Takeshi; Hibino, Hidehiko; Okuyama, Harumi

2014-01-01

We investigated whether body temperature (BT) regulatory mechanisms are influenced by dietary fatty acids (FA). Male Wistar rats were fed a high-fat diet containing fish oil (HFD), soybean oil (HSD) or lard (HLD). At the 20-week intervention, the BT of the HSD and HLD groups were lower than that of the normal diet (ND) group in the light and dark periods. The intracerebroventricular injections of interleukin-1β and bombesin in the HSD group induced greater hyperthermia and weaker hypothermia, respectively, than in the ND group. The HSD differentially affected BT under both physiological and pharmacological conditions. In the hypothalamus, the ratio of n-6/n-3 FAs was higher in the HSD group compared with the ND group. DNA microarrays revealed increased expression of thyroid-stimulating hormone β-subunit, and decreased expression of several genes in the hypothalamus of the HSD group compared with the ND group. The HSD feeding increased several adipokine concentrations in the plasma. However, there were no adipokines or gene expressions that changed in only the HSD and HLD groups showing significant hypothermia under the physiological condition. These findings suggested that long-term HSD intake produces abnormal BT regulation. It is less likely that adipokines or proteins/peptides are involved in abnormal BT regulation under the physiological conditions after HSD feeding.

The normal and pathologic renal medulla: a comprehensive overview.

PubMed

López, José I; Larrinaga, Gorka; Kuroda, Naoto; Angulo, Javier C

2015-04-01

The renal medulla comprises an intricate system of tubules, blood vessels and interstitium that is not well understood by most general pathologists. We conducted an extensive review of the literature on the renal medulla, in both normal and pathologic conditions. We set out in detail the points of key interest to pathologists: normal and pathological development, physiology, microscopic anatomy, histology and immunohistochemistry; and the specific and most common other types of disease associated with this part of the kidney: developmental abnormalities, (multicystic dysplastic kidney, autosomal dominant and recessive polycystic kidney diseases, medullary cystic kidney disease), inflammatory conditions (xanthogranulomatous pyelonephritis, malakoplakia), hyperplasia and dysplasia, and neoplastic processes (oncocytoma, atypical oncocytic tumors, chromophobe cell carcinoma, collecting duct carcinoma, urothelial carcinoma, other carcinomas, renal medullary fibroma and metastatic tumors). This condensed overview of the origin, function and pathology of the renal medulla, both in terms of development, inflammation and neoplastic processes, should help focus the interest of clinical pathologists on this widely overlooked part of the kidney. Copyright © 2014 Elsevier GmbH. All rights reserved.

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

Cytoplasmic RNA Granules in Somatic Maintenance.

PubMed

Moujaber, Ossama; Stochaj, Ursula

2018-05-30

Cytoplasmic RNA granules represent subcellular compartments that are enriched in protein-bound RNA species. RNA granules are produced by evolutionary divergent eukaryotes, including yeast, mammals, and plants. The functions of cytoplasmic RNA granules differ widely. They are dictated by the cell type and physiological state, which in turn is determined by intrinsic cell properties and environmental factors. RNA granules provide diverse cellular functions. However, all of the granules contribute to aspects of RNA metabolism. This is exemplified by transcription, RNA storage, silencing, and degradation, as well as mRNP remodeling and regulated translation. Several forms of cytoplasmic mRNA granules are linked to normal physiological processes. For instance, they may coordinate protein synthesis and thereby serve as posttranscriptional "operons". RNA granules also participate in cytoplasmic mRNA trafficking, a process particularly well understood for neurons. Many forms of RNA granules support the preservation of somatic cell performance under normal and stress conditions. On the other hand, severe insults or disease can cause the formation and persistence of RNA granules that contribute to cellular dysfunction, especially in the nervous system. Neurodegeneration and many other diseases linked to RNA granules are associated with aging. Nevertheless, information related to the impact of aging on the various types of RNA granules is presently very limited. This review concentrates on cytoplasmic RNA granules and their role in somatic cell maintenance. We summarize the current knowledge on different types of RNA granules in the cytoplasm, their assembly and function under normal, stress, or disease conditions. Specifically, we discuss processing bodies, neuronal granules, stress granules, and other less characterized cytoplasmic RNA granules. Our focus is primarily on mammalian and yeast models, because they have been critical to unravel the physiological role of various RNA granules. RNA granules in plants and pathogens are briefly described. We conclude our viewpoint by summarizing the emerging concepts for RNA granule biology and the open questions that need to be addressed in future studies. © 2018 S. Karger AG, Basel.

Operant conditioning of the soleus H-reflex does not induce long-term changes in the gastrocnemius H-reflexes and does not disturb normal locomotion in humans.

PubMed

Makihara, Yukiko; Segal, Richard L; Wolpaw, Jonathan R; Thompson, Aiko K

2014-09-15

In normal animals, operant conditioning of the spinal stretch reflex or the H-reflex has lesser effects on synergist muscle reflexes. In rats and people with incomplete spinal cord injury (SCI), soleus H-reflex operant conditioning can improve locomotion. We studied in normal humans the impact of soleus H-reflex down-conditioning on medial (MG) and lateral gastrocnemius (LG) H-reflexes and on locomotion. Subjects completed 6 baseline and 30 conditioning sessions. During conditioning trials, the subject was encouraged to decrease soleus H-reflex size with the aid of visual feedback. Every sixth session, MG and LG H-reflexes were measured. Locomotion was assessed before and after conditioning. In successfully conditioned subjects, the soleus H-reflex decreased 27.2%. This was the sum of within-session (task dependent) adaptation (13.2%) and across-session (long term) change (14%). The MG H-reflex decreased 14.5%, due mainly to task-dependent adaptation (13.4%). The LG H-reflex showed no task-dependent adaptation or long-term change. No consistent changes were detected across subjects in locomotor H-reflexes, EMG activity, joint angles, or step symmetry. Thus, in normal humans, soleus H-reflex down-conditioning does not induce long-term changes in MG/LG H-reflexes and does not change locomotion. In these subjects, task-dependent adaptation of the soleus H-reflex is greater than it is in people with SCI, whereas long-term change is less. This difference from results in people with SCI is consistent with the fact that long-term change is beneficial in people with SCI, since it improves locomotion. In contrast, in normal subjects, long-term change is not beneficial and may necessitate compensatory plasticity to preserve satisfactory locomotion. Copyright © 2014 the American Physiological Society.

Exercise Hypertension.

PubMed

Schultz, Martin G; Sharman, James E

2014-05-01

Irrespective of apparent 'normal' resting blood pressure (BP), some individuals may experience an excessive elevation in BP with exercise (i.e. systolic BP ≥210 mm Hg in men or ≥190 mm Hg in women or diastolic BP ≥110 mm Hg in men or women), a condition termed exercise hypertension or a 'hypertensive response to exercise' (HRE). An HRE is a relatively common condition that is identified during standard exercise stress testing; however, due to a lack of information with respect to the clinical ramifications of an HRE, little value is usually placed on such a finding. In this review, we discuss both the clinical importance and underlying physiological contributors of exercise hypertension. Indeed, an HRE is associated with an increased propensity for target organ damage and also predicts the future development of hypertension, cardiovascular events and mortality, independent of resting BP. Moreover, recent work has highlighted that some of the elevated cardiovascular risks associated with an HRE may be related to high-normal resting BP (pre-hypertension) or ambulatory 'masked' hypertension and that an HRE may be an early warning signal of abnormal BP control that is otherwise undetected with clinic BP. Whilst an HRE may be amenable to treatment via pharmacological and lifestyle interventions, the exact physiological mechanism of an HRE remains elusive, but it is likely a manifestation of multiple factors including large artery stiffness, increased peripheral resistance, neural circulatory control and metabolic irregularity. Future research focus may be directed towards determining threshold values to denote the increased risk associated with an HRE and further resolution of the underlying physiological factors involved in the pathogenesis of an HRE.

Nonlinear dynamics applied to the study of cardiovascular effects of stress

NASA Astrophysics Data System (ADS)

Anishchenko, T. G.; Igosheva, N. B.

1998-03-01

We study cardiovascular responses to emotional stresses in humans and rats using traditional physiological parameters and methods of nonlinear dynamics. We found that emotional stress results in significant changes of chaos degree of ECG and blood pressure signals, estimated using a normalized entropy. We demonstrate that the normalized entropy is a more sensitive indicator of the stress-induced changes in cardiovascular systems compared with traditional physiological parameters Using the normalized entropy we discovered the significant individual differences in cardiovascular stress-reactivity that was impossible to obtain by traditional physiological methods.

Exercise and Human Immunodeficiency Virus (HIV-1) Infection

NASA Technical Reports Server (NTRS)

Lawless, DeSales; Jackson, Catherine G. R.; Greenleaf, John E.

1995-01-01

The human immune system is highly efficient and remarkably protective when functioning properly. Similar to other physiological systems, it functions best when the body is maintained with a balanced diet, sufficient rest and a moderately stress-free lifestyle. It can be disrupted by inappropriate drug use and extreme emotion or exertion. The functioning of normal or compromised immune systems can be enhanced by properly prescribed moderate exercise conditioning regimens in healthy people, and in some human immunodeficiency virus (HIV-1)-infected patients but not in others who unable to complete an interval training program. Regular exercise conditioning in healthy people reduces cardiovascular risk factors, increases stamina, facilitates bodyweight control, and reduces stress by engendering positive feelings of well-being. Certain types of cancer may also be suppressed by appropriate exercise conditioning. Various exercise regimens are being evaluated as adjunct treatments for medicated patients with the HIV-1 syndrome. Limited anecdotal evidence from patients suggests that moderate exercise conditioning is per se responsible for their survival well beyond expectancy. HIV-1-infected patients respond positively, both physiologically and psychologically, to moderate exercise conditioning. However, the effectiveness of any exercise treatment programme depends on its mode, frequency, intensity and duration when prescribed o complement the pathological condition of the patient. The effectiveness of exercise conditioning regimens in patients with HIV-1 infection is reviewed in this article. In addition, we discuss mechanisms and pathways, involving the interplay of psychological and physiological factors, through which the suppressed immune system can be enhanced. The immune modulators discussed are endogenous opioids, cytokines, neurotransmitters and other hormones. Exercise conditioning treatment appears to be more effective when combined with other stress management procedures.

Taurine flux in chicken erythrocytes.

PubMed

Porter, D W; Martin, W G

1992-05-01

1. The intracellular taurine concentration in chick erythrocytes increased with age. 2. Erythrocyte taurine influx and efflux rates increased with age. 3. Erythrocyte taurine influx decreased when the extracellular sodium concentration was below normal physiological concentrations. 4. Under hypo-osmotic conditions, taurine efflux from erythrocytes increased. 5. The data suggest that chick erythrocyte taurine metabolism changes during early post-hatch development and that one taurine function may be as an osmoregulator.

[Biotoxic effects of aqueous humour-a unifying pathogenetic theory, based on certain hypothetic biotoxic factors in aqueus (author's transl)].

PubMed

Worst, J G

1975-09-01

A hypothesis is proposed attributing a number of biotoxic effects to aqueous humor (ABC equals Aqueous Biotoxic Complex). Under normal anatomical and physiological conditions aqueous humour is contained in the anterior and posterior chamber reservoir and the ABC effects remain silent because the boundaries of the aqueous humour reservoir are resistant to these biotoxic factors. These factors are biochemically undefined but fall in the category of collagenolysins and anti-vascular enzymes (Prostaglandins?). Outside the normal reservoir these biotoxic effects result in a specific pathology such as corneal edema, subconjunctival edema, lens fiber edema, macular edema, papilledema and chorioidal edema.

Role of the medulla oblongata in normal and high arterial blood pressure regulation: the contribution of Escola Paulista de Medicina - UNIFESP.

PubMed

Cravo, Sergio L; Campos, Ruy R; Colombari, Eduardo; Sato, Mônica A; Bergamaschi, Cássia M; Pedrino, Gustavo R; Ferreira-Neto, Marcos L; Lopes, Oswaldo U

2009-09-01

Several forms of experimental evidence gathered in the last 37 years have unequivocally established that the medulla oblongata harbors the main neural circuits responsible for generating the vasomotor tone and regulating arterial blood pressure. Our current understanding of this circuitry derives mainly from the studies of Pedro Guertzenstein, a former student who became Professor of Physiology at UNIFESP later, and his colleagues. In this review, we have summarized the main findings as well as our collaboration to a further understanding of the ventrolateral medulla and the control of arterial blood pressure under normal and pathological conditions.

Thyroid Hormones and Growth in Health and Disease

PubMed Central

Tarım, Ömer

2011-01-01

Thyroid hormones regulate growth by several mechanisms. In addition to their negative feedback effect on the stimulatory hormones thyrotropin-releasing hormone (TRH) and thyrotropin (TSH), thyroid hormones also regulate their receptors in various physiological and pathological conditions. Up-regulation and down-regulation of the thyroid receptors fine-tune the biological effects exerted by the thyroid hormones. Interestingly, the deiodinase enzyme system is another intrinsic regulator of thyroid physiology that adjusts the availability of thyroid hormones to the tissues, which is essential for normal growth and development. Almost all chronic diseases of childhood impair growth and development. Every disease may have a unique mechanism to halt linear growth, but reduced serum concentration or diminished local availability of thyroid hormones seems to be a common pathway. Therefore, the effects of systemic diseases on thyroid physiology must be taken into consideration in the evaluation of growth retardation in affected children. Conflict of interest:None declared. PMID:21750631

EMG normalization to study muscle activation in cycling.

PubMed

Rouffet, David M; Hautier, Christophe A

2008-10-01

The value of electromyography (EMG) is sensitive to many physiological and non-physiological factors. The purpose of the present study was to determine if the torque-velocity test (T-V) can be used to normalize EMG signals into a framework of biological significance. Peak EMG amplitude of gluteus maximus (GMAX), vastus lateralis (VL), rectus femoris (RF), biceps femoris long head (BF), gastrocnemius medialis (GAS) and soleus (SOL) was calculated for nine subjects during isometric maximal voluntary contractions (IMVC) and torque-velocity bicycling tests (T-V). Then, the reference EMG signals obtained from IMVC and T-V bicycling tests were used to normalize the amplitude of the EMG signals collected for 15 different submaximal pedaling conditions. The results of this study showed that the repeatability of the measurements between IMVC (from 10% to 23%) and T-V (from 8% to 20%) was comparable. The amplitude of the peak EMG of VL was 99+/-43% higher (p<0.001) when measured during T-V. Moreover, the inter-individual variability of the EMG patterns calculated for submaximal cycling exercises differed significantly when using T-V bicycling normalization method (GMAX: 0.33+/-0.16 vs. 1.09+/-0.04, VL: 0.07+/-0.02 vs. 0.64+/-0.14, SOL: 0.07+/-0.03 vs. 1.00+/-0.07, RF: 1.21+/-0.20 vs. 0.92+/-0.13, BF: 1.47+/-0.47 vs. 0.84+/-0.11). It was concluded that T-V bicycling test offers the advantage to be less time and energy-consuming and to be as repeatable as IMVC tests to measure peak EMG amplitude. Furthermore, this normalization method avoids the impact of non-physiological factors on the amplitude of the EMG signals so that it allows quantifying better the activation level of lower limb muscles and the variability of the EMG patterns during submaximal bicycling exercises.

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.

Description of intraoral pressures on sub-palatal space in young adult patients with normal occlusion.

PubMed

Fuentes, Ramón; Engelke, Wilfried; Flores, Tania; Navarro, Pablo; Borie, Eduardo; Curiqueo, Aldo; Salamanca, Carlos

2015-01-01

Under normal conditions, the oral cavity presents a perfect system of equilibrium between teeth, soft tissues and tongue. The equilibrium of soft tissues forms a closed capsular matrix, generating differences with the atmospheric environment. This difference is known as intraoral pressure. Negative intraoral pressure is fundamental to the stabilization of the soft palate and tongue, reducing neuromuscular activity for the permeability of the respiratory tract. Thus, the aim of this study was to describe the variations of intraoral pressure of the sub-palatal space (SPS) under different physiological conditions and biofunctional phases. A case series was conducted with 20 individuals aged between 18 and 25. The intraoral pressures were measured through a system of cannulae connected to a digital pressure meter in the SPS during seven biofunctional phases. Descriptive statistics were used based on the mean and standard deviation. The data recorded pressure variations under physiological conditions, reaching 65 mbar as the intraoral peak in forced inspiration. In the swallowing phase, peaks reached -91.9 mbar. No pressure variations were recorded in terms of atmospheric changes with the mouth open and semi-open. The data obtained during the swallowing and forced inspiration phases indicated forced lingual activity. In the swallowing phase, the adequate position of the tongue creates negative intraoral pressure, which represents a fundamental mechanism for the physical stabilization of the soft palate. This information could contribute to subsequent research into the treatment of primary roncopathies.

Homeostasis 5: nurses as external agents of control in breast cancer.

PubMed

Clancy, John; McVicar, Andrew

Breast cancer is caused by a homeostatic imbalance of cell division. Healthcare practitioners need to understand cellular activities to appreciate the physiological basis of health (homeostasis), the pathophysiological basis of illness and the physiological rationale of healthcare. Cells are the 'basic unit of life' (Clancy and McVicar, 2011a). This article describes normal cell division and the anatomy and physiology of the breast and, using a case study, will show how breast cancer is a homeostatic imbalance of cell division. There are analogies between the components of homeostasis and the components of the nursing (healthcare) process (Clancy and McVicar, 2011b) in the condition of breast cancer. After reading this article, nurses should be able to: understand that breast cancer is a cellular hence chemical imbalance that causes uncontrollable mitotic division of breast cells; understand how the cell cycle of cancer cells differs from that of normal cells; identify nature-nurture interactions involved in the aetiology of breast cancer; understand that when caring for people with breast cancer, health professionals including oncology nurses are acting as external agents of homeostatic control as the patient 'recovers' from breast cancer, and also to some extent when reducing signs and symptoms, hence quality of life, by providing palliative care.

Humanized medium (h7H) allows long-term primary follicular thyroid cultures from human normal thyroid, benign neoplasm, and cancer.

PubMed

Bravo, Susana B; Garcia-Rendueles, Maria E R; Garcia-Rendueles, Angela R; Rodrigues, Joana S; Perez-Romero, Sihara; Garcia-Lavandeira, Montserrat; Suarez-Fariña, Maria; Barreiro, Francisco; Czarnocka, Barbara; Senra, Ana; Lareu, Maria V; Rodriguez-Garcia, Javier; Cameselle-Teijeiro, Jose; Alvarez, Clara V

2013-06-01

Mechanisms of thyroid physiology and cancer are principally studied in follicular cell lines. However, human thyroid cancer lines were found to be heavily contaminated by other sources, and only one supposedly normal-thyroid cell line, immortalized with SV40 antigen, is available. In primary culture, human follicular cultures lose their phenotype after passage. We hypothesized that the loss of the thyroid phenotype could be related to culture conditions in which human cells are grown in medium optimized for rodent culture, including hormones with marked differences in its affinity for the relevant rodent/human receptor. The objective of the study was to define conditions that allow the proliferation of primary human follicular thyrocytes for many passages without losing phenotype. Concentrations of hormones, transferrin, iodine, oligoelements, antioxidants, metabolites, and ethanol were adjusted within normal homeostatic human serum ranges. Single cultures were identified by short tandem repeats. Human-rodent interspecies contamination was assessed. We defined an humanized 7 homeostatic additives medium enabling growth of human thyroid cultures for more than 20 passages maintaining thyrocyte phenotype. Thyrocytes proliferated and were grouped as follicle-like structures; expressed Na+/I- symporter, pendrin, cytokeratins, thyroglobulin, and thyroperoxidase showed iodine-uptake and secreted thyroglobulin and free T3. Using these conditions, we generated a bank of thyroid tumors in culture from normal thyroids, Grave's hyperplasias, benign neoplasms (goiter, adenomas), and carcinomas. Using appropriate culture conditions is essential for phenotype maintenance in human thyrocytes. The bank of thyroid tumors in culture generated under humanized humanized 7 homeostatic additives culture conditions will provide a much-needed tool to compare similarly growing cells from normal vs pathological origins and thus to elucidate the molecular basis of thyroid disease.

Tunable cytotoxicity of rhodamine 6G via anion variations.

PubMed

Magut, Paul K S; Das, Susmita; Fernand, Vivian E; Losso, Jack; McDonough, Karen; Naylor, Brittni M; Aggarwal, Sita; Warner, Isiah M

2013-10-23

Chemotherapeutic agents with low toxicity to normal tissues are a major goal in cancer research. In this regard, the therapeutic activities of cationic dyes, such as rhodamine 6G, toward cancer cells have been studied for decades with observed toxicities toward normal and cancer cells. Herein, we report rhodamine 6G-based organic salts with varying counteranions that are stable under physiological conditions, display excellent fluorescence photostability, and more importantly have tunable chemotherapeutic properties. Our in vitro studies indicate that the hydrophobic compounds of this series allow production of nanoparticles which are nontoxic to normal cells and toxic to cancer cells. Furthermore, the anions, in combination with cations such as sodium, were observed to be nontoxic to both normal and cancer cells. To the best of our knowledge, this is the first demonstration that both the cation and anion play an extremely important and cooperative role in the antitumor properties of these compounds.

Metabolic Adaptation to Muscle Ischemia

NASA Technical Reports Server (NTRS)

Cabrera, Marco E.; Coon, Jennifer E.; Kalhan, Satish C.; Radhakrishnan, Krishnan; Saidel, Gerald M.; Stanley, William C.

2000-01-01

Although all tissues in the body can adapt to varying physiological/pathological conditions, muscle is the most adaptable. To understand the significance of cellular events and their role in controlling metabolic adaptations in complex physiological systems, it is necessary to link cellular and system levels by means of mechanistic computational models. The main objective of this work is to improve understanding of the regulation of energy metabolism during skeletal/cardiac muscle ischemia by combining in vivo experiments and quantitative models of metabolism. Our main focus is to investigate factors affecting lactate metabolism (e.g., NADH/NAD) and the inter-regulation between carbohydrate and fatty acid metabolism during a reduction in regional blood flow. A mechanistic mathematical model of energy metabolism has been developed to link cellular metabolic processes and their control mechanisms to tissue (skeletal muscle) and organ (heart) physiological responses. We applied this model to simulate the relationship between tissue oxygenation, redox state, and lactate metabolism in skeletal muscle. The model was validated using human data from published occlusion studies. Currently, we are investigating the difference in the responses to sudden vs. gradual onset ischemia in swine by combining in vivo experimental studies with computational models of myocardial energy metabolism during normal and ischemic conditions.

Relating normalization to neuronal populations across cortical areas.

PubMed

Ruff, Douglas A; Alberts, Joshua J; Cohen, Marlene R

2016-09-01

Normalization, which divisively scales neuronal responses to multiple stimuli, is thought to underlie many sensory, motor, and cognitive processes. In every study where it has been investigated, neurons measured in the same brain area under identical conditions exhibit a range of normalization, ranging from suppression by nonpreferred stimuli (strong normalization) to additive responses to combinations of stimuli (no normalization). Normalization has been hypothesized to arise from interactions between neuronal populations, either in the same or different brain areas, but current models of normalization are not mechanistic and focus on trial-averaged responses. To gain insight into the mechanisms underlying normalization, we examined interactions between neurons that exhibit different degrees of normalization. We recorded from multiple neurons in three cortical areas while rhesus monkeys viewed superimposed drifting gratings. We found that neurons showing strong normalization shared less trial-to-trial variability with other neurons in the same cortical area and more variability with neurons in other cortical areas than did units with weak normalization. Furthermore, the cortical organization of normalization was not random: neurons recorded on nearby electrodes tended to exhibit similar amounts of normalization. Together, our results suggest that normalization reflects a neuron's role in its local network and that modulatory factors like normalization share the topographic organization typical of sensory tuning properties. Copyright © 2016 the American Physiological Society.

Critical dynamics of Hopf bifurcations in the corticothalamic system: Transitions from normal arousal states to epileptic seizures.

PubMed

Yang, Dong-Ping; Robinson, P A

2017-04-01

A physiologically based corticothalamic model of large-scale brain activity is used to analyze critical dynamics of transitions from normal arousal states to epileptic seizures, which correspond to Hopf bifurcations. This relates an abstract normal form quantitatively to underlying physiology that includes neural dynamics, axonal propagation, and time delays. Thus, a bridge is constructed that enables normal forms to be used to interpret quantitative data. The normal form of the Hopf bifurcations with delays is derived using Hale's theory, the center manifold theorem, and normal form analysis, and it is found to be explicitly expressed in terms of transfer functions and the sensitivity matrix of a reduced open-loop system. It can be applied to understand the effect of each physiological parameter on the critical dynamics and determine whether the Hopf bifurcation is supercritical or subcritical in instabilities that lead to absence and tonic-clonic seizures. Furthermore, the effects of thalamic and cortical nonlinearities on the bifurcation type are investigated, with implications for the roles of underlying physiology. The theoretical predictions about the bifurcation type and the onset dynamics are confirmed by numerical simulations and provide physiologically based criteria for determining bifurcation types from first principles. The results are consistent with experimental data from previous studies, imply that new regimes of seizure transitions may exist in clinical settings, and provide a simplified basis for control-systems interventions. Using the normal form, and the full equations from which it is derived, more complex dynamics, such as quasiperiodic cycles and saddle cycles, are discovered near the critical points of the subcritical Hopf bifurcations.

Critical dynamics of Hopf bifurcations in the corticothalamic system: Transitions from normal arousal states to epileptic seizures

NASA Astrophysics Data System (ADS)

Yang, Dong-Ping; Robinson, P. A.

2017-04-01

A physiologically based corticothalamic model of large-scale brain activity is used to analyze critical dynamics of transitions from normal arousal states to epileptic seizures, which correspond to Hopf bifurcations. This relates an abstract normal form quantitatively to underlying physiology that includes neural dynamics, axonal propagation, and time delays. Thus, a bridge is constructed that enables normal forms to be used to interpret quantitative data. The normal form of the Hopf bifurcations with delays is derived using Hale's theory, the center manifold theorem, and normal form analysis, and it is found to be explicitly expressed in terms of transfer functions and the sensitivity matrix of a reduced open-loop system. It can be applied to understand the effect of each physiological parameter on the critical dynamics and determine whether the Hopf bifurcation is supercritical or subcritical in instabilities that lead to absence and tonic-clonic seizures. Furthermore, the effects of thalamic and cortical nonlinearities on the bifurcation type are investigated, with implications for the roles of underlying physiology. The theoretical predictions about the bifurcation type and the onset dynamics are confirmed by numerical simulations and provide physiologically based criteria for determining bifurcation types from first principles. The results are consistent with experimental data from previous studies, imply that new regimes of seizure transitions may exist in clinical settings, and provide a simplified basis for control-systems interventions. Using the normal form, and the full equations from which it is derived, more complex dynamics, such as quasiperiodic cycles and saddle cycles, are discovered near the critical points of the subcritical Hopf bifurcations.

Development of a rate model to investigate contributions of anatomic and physiologic determinants of in vivo skin permeation

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

Fleischer, N.M.

The skin is a heterogeneous, bi-directional impediment to chemical flux, in which the stratum corneum is a major, though not the sole, rate-limiting barrier layer to permeation. Systemic toxicity following dermal exposure to environmental chemicals and use of skin as a portal for systemic administration of drugs have led to extensive investigations of the inward flux of xenobiotics applied to the outer surface of skin. Those investigations mainly utilized in vitro experimental systems that were limited by the absence of normal physiologic functions. The objective of the present research was to investigate an in vivo skin permeation model system thatmore » was sensitive to perturbations of skin capillary physiology and stratum corneum. A [open quotes]fuzzy[close quotes] rat model system was devised that employed outward cutaneous migration of a systemically administered permeation probe, isoflurane. Specially devised, transdermal vapor collection devices were used to capture the outward flux of isoflurane through the skin. Isoflurane flux measurements, coupled with blood isoflurane concentrations, were used to calculate cutaneous permeability coefficients (K[sub p]) of isolflurane, as an index of permeation, under various conditions of normal or perturbed cutaneous physiologic states. Physiologic perturbations were performed to test the sensitivity of the model system to detect effects of minoxidil-mediated vasodilation, phenylephrine-mediated vasoconstriction, and leukotriene D[sub 4]-mediated increased capillary permeability on the outward flux of isoflurane. Tape stripping and topical ether-ethanol application produced either physical removal or chemical disruption of the stratum corneum, respectively. Minoxidil, leukotriene D[sub 4], tape stripping of stratum corneum, and topical ether-ethanol experiments produced statistically significant increases (52 to 193%) in the K[sub p's], while phenylephrine had no significant effect on isoflurane permeation.« less

Acute vascular effects of carbonated warm water lower leg immersion in healthy young adults.

PubMed

Ogoh, Shigehiko; Nagaoka, Ryohei; Mizuno, Takamasa; Kimura, Shohei; Shidahara, Yasuhiro; Ishii, Tomomi; Kudoh, Michinari; Iwamoto, Erika

2016-12-01

Endothelial dysfunction is associated with increased cardiovascular mortality and morbidity; however, this dysfunction may be ameliorated by several therapies. For example, it has been reported that heat-induced increases in blood flow and shear stress enhance endothelium-mediated vasodilator function. Under these backgrounds, we expect that carbon dioxide (CO 2 )-rich water-induced increase in skin blood flow improves endothelium-mediated vasodilation with less heat stress. To test our hypothesis, we measured flow-mediated dilation (FMD) before and after acute immersion of the lower legs and feet in mild warm (38°C) normal or CO 2 -rich tap water (1000 ppm) for 20 min in 12 subjects. Acute immersion of the lower legs and feet in mild warm CO 2 -rich water increased FMD (P < 0.01) despite the lack of change in this parameter upon mild warm normal water immersion. In addition, FMD was positively correlated with change in skin blood flow regardless of conditions (P < 0.01), indicating that an increase in skin blood flow improves endothelial-mediated vasodilator function. Importantly, the temperature of normal tap water must reach approximately 43°C to achieve the same skin blood flow level as that obtained during mild warm CO 2 -rich water immersion (38°C). These findings suggest that CO 2 -rich water-induced large increases in skin blood flow may improve endothelial-mediated vasodilator function while causing less heat stress. © 2016 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

Human conditions of insulin-like growth factor-I (IGF-I) deficiency

PubMed Central

2012-01-01

Insulin-like growth factor I (IGF-I) is a polypeptide hormone produced mainly by the liver in response to the endocrine GH stimulus, but it is also secreted by multiple tissues for autocrine/paracrine purposes. IGF-I is partly responsible for systemic GH activities although it possesses a wide number of own properties (anabolic, antioxidant, anti-inflammatory and cytoprotective actions). IGF-I is a closely regulated hormone. Consequently, its logical therapeutical applications seems to be limited to restore physiological circulating levels in order to recover the clinical consequences of IGF-I deficiency, conditions where, despite continuous discrepancies, IGF-I treatment has never been related to oncogenesis. Currently the best characterized conditions of IGF-I deficiency are Laron Syndrome, in children; liver cirrhosis, in adults; aging including age-related-cardiovascular and neurological diseases; and more recently, intrauterine growth restriction. The aim of this review is to summarize the increasing list of roles of IGF-I, both in physiological and pathological conditions, underlying that its potential therapeutical options seem to be limited to those proven states of local or systemic IGF-I deficiency as a replacement treatment, rather than increasing its level upper the normal range. PMID:23148873

Campomanesia adamantium (Cambess.) O. Berg seed desiccation: influence on vigor and nucleic acids.

PubMed

Dresch, Daiane M; Masetto, Tathiana E; Scalon, Silvana P Q

2015-01-01

The aim of this study was to evaluate the sensitivity of Campomanesia adamantium seeds to desiccation by drying in activated silica gel (fast) and under laboratory conditions (slow). To assess the sensitivity of the seeds to desiccation, we used drying with silica gel and drying under laboratory conditions (25 °C), in order to obtain seeds with moisture content of 45, 35, 30, 25, 20, 15, 10 and 5%. The physiological potential of the seeds after desiccation was evaluated by measuring primary root protrusion, percentage of normal seedlings, germination seed index, seedling length, total seedling dry mass, electrical conductivity and DNA and RNA integrities. The C. adamantium seeds were sensitive to desiccation and to a reduction in moisture content to 21.1% or less by desiccation using silica gel, and to 17.2% or less by desiccation under laboratory conditions; impairment of the physiological potential of the seeds was observed at these low moisture content levels. The integrity of the seed genomic DNA was not affected after drying seeds in the two methods. However, drying in silica gel to 4.5% moisture content and drying under laboratory conditions to 5.4% moisture content resulted in the loss of seed RNA integrity.

A computational study of the respiratory airflow characteristics in normal and obstructed human airways.

PubMed

Sul, Bora; Wallqvist, Anders; Morris, Michael J; Reifman, Jaques; Rakesh, Vineet

2014-09-01

Obstructive lung diseases in the lower airways are a leading health concern worldwide. To improve our understanding of the pathophysiology of lower airways, we studied airflow characteristics in the lung between the 8th and the 14th generations using a three-dimensional computational fluid dynamics model, where we compared normal and obstructed airways for a range of breathing conditions. We employed a novel technique based on computing the Pearson׳s correlation coefficient to quantitatively characterize the differences in airflow patterns between the normal and obstructed airways. We found that the airflow patterns demonstrated clear differences between normal and diseased conditions for high expiratory flow rates (>2300ml/s), but not for inspiratory flow rates. Moreover, airflow patterns subjected to filtering demonstrated higher sensitivity than airway resistance for differentiating normal and diseased conditions. Further, we showed that wall shear stresses were not only dependent on breathing rates, but also on the distribution of the obstructed sites in the lung: for the same degree of obstruction and breathing rate, we observed as much as two-fold differences in shear stresses. In contrast to previous studies that suggest increased wall shear stress due to obstructions as a possible damage mechanism for small airways, our model demonstrated that for flow rates corresponding to heavy activities, the wall shear stress in both normal and obstructed airways was <0.3Pa, which is within the physiological limit needed to promote respiratory defense mechanisms. In summary, our model enables the study of airflow characteristics that may be impractical to assess experimentally. Published by Elsevier Ltd.

Microgravity Analogues of Herpes Virus Pathogenicity: Human Cytomegalovirus (hCMV) and Varicella Zoster (VZV) Infectivity in Human Tissue Like Assemblies (TLAs)

NASA Technical Reports Server (NTRS)

Goodwin, T. J.; McCarthy, M.; Albrecht, T.; Cohrs, R.

2009-01-01

The old adage we are our own worst enemies may perhaps be the most profound statement ever made when applied to man s desire for extraterrestrial exploration and habitation of Space. Consider the immune system protects the integrity of the entire human physiology and is comprised of two basic elements the adaptive or circulating and the innate immune system. Failure of the components of the adaptive system leads to venerability of the innate system from opportunistic microbes; viral, bacteria, and fungal, which surround us, are transported on our skin, and commonly inhabit the human physiology as normal and imunosuppressed parasites. The fine balance which is maintained for the preponderance of our normal lives, save immune disorders and disease, is deregulated in microgravity. Thus analogue systems to study these potential Risks are essential for our progress in conquering Space exploration and habitation. In this study we employed two known physiological target tissues in which the reactivation of hCMV and VZV occurs, human neural and lung systems created for the study and interaction of these herpes viruses independently and simultaneously on the innate immune system. Normal human neural and lung tissue analogues called tissue like assemblies (TLAs) were infected with low MOIs of approximately 2 x 10(exp -5) pfu hCMV or VZV and established active but prolonged low grade infections which spanned .7-1.5 months in length. These infections were characterized by the ability to continuously produce each of the viruses without expiration of the host cultures. Verification and quantification of viral replication was confirmed via RT_PCR, IHC, and confocal spectral analyses of the respective essential viral genomes. All host TLAs maintained the ability to actively proliferate throughout the entire duration of the experiments as is analogous to normal in vivo physiological conditions. These data represent a significant advance in the ability to study the triggering mechanisms which surround Herpes vial reactivation and proliferation. Additionally, prolonged replication of these viruses will allow the tracking of viral genomic shift.

Effect of eggshell temperature and oxygen concentration during incubation on the developmental and physiological status of broiler hatchlings in the perinatal period.

PubMed

Molenaar, R; van den Anker, I; Meijerhof, R; Kemp, B; van den Brand, H

2011-06-01

This study evaluated the influence of incubation conditions on the developmental and physiological status of birds in the perinatal period, which spans the end of incubation until the early posthatch period. Embryos were incubated at a normal (37.8°C) or high (38.9°C) eggshell temperature (EST) and a low (17%), normal (21%), or high (25%) O(2) concentration from d 7 until 19 of incubation. After d 19 of incubation, EST was maintained, but O(2) concentrations were 21% for all embryos. Body and organ weights, and hepatic glycogen levels were measured at d 18 of incubation and at 12 and 48 h after emergence from the eggshell. In addition, blood metabolites were measured at 12 and 48 h after emergence from the eggshell. Embryos incubated at a high EST and low O(2) concentration had the highest mortality in the last week of incubation, which may be related to their low yolk-free body mass (YFBM) or a reduced nutrient availability for hatching (i.e., hepatic glycogen). High EST, compared with normal EST, decreased YFBM. This may be due to the shorter incubation duration of 8 h, the lower weight of supply organs (i.e., heart and lung), or a lack of glucose precursors. Because of this lack of glucose precursors, embryos incubated at high EST may have used proteins for energy production instead of for body development at the end of incubation. The YFBM at d 18 of incubation increased with an increase in O(2) concentration. However, differences between the normal and high O(2) concentration disappeared at 12 and 48 h after emergence, possibly because the high O(2) concentration had difficulties adapting to lower O(2) concentrations in the perinatal period. Blood metabolites and hepatic glycogen were comparable among O(2) concentrations, indicating that the physiological status at hatch may be related to the environment that the embryo experienced during the hatching process. In conclusion, EST and O(2) concentration differentially influence the developmental and physiological status of broilers during the perinatal period.

Fractal dynamics in physiology: Alterations with disease and aging

PubMed Central

Goldberger, Ary L.; Amaral, Luis A. N.; Hausdorff, Jeffrey M.; Ivanov, Plamen Ch.; Peng, C.-K.; Stanley, H. Eugene

2002-01-01

According to classical concepts of physiologic control, healthy systems are self-regulated to reduce variability and maintain physiologic constancy. Contrary to the predictions of homeostasis, however, the output of a wide variety of systems, such as the normal human heartbeat, fluctuates in a complex manner, even under resting conditions. Scaling techniques adapted from statistical physics reveal the presence of long-range, power-law correlations, as part of multifractal cascades operating over a wide range of time scales. These scaling properties suggest that the nonlinear regulatory systems are operating far from equilibrium, and that maintaining constancy is not the goal of physiologic control. In contrast, for subjects at high risk of sudden death (including those with heart failure), fractal organization, along with certain nonlinear interactions, breaks down. Application of fractal analysis may provide new approaches to assessing cardiac risk and forecasting sudden cardiac death, as well as to monitoring the aging process. Similar approaches show promise in assessing other regulatory systems, such as human gait control in health and disease. Elucidating the fractal and nonlinear mechanisms involved in physiologic control and complex signaling networks is emerging as a major challenge in the postgenomic era. PMID:11875196

Endogenous Retrovirus 3 – History, Physiology, and Pathology

PubMed Central

Bustamante Rivera, Yomara Y.; Brütting, Christine; Schmidt, Caroline; Volkmer, Ines; Staege, Martin S.

2018-01-01

Endogenous viral elements (EVE) seem to be present in all eukaryotic genomes. The composition of EVE varies between different species. The endogenous retrovirus 3 (ERV3) is one of these elements that is present only in humans and other Catarrhini. Conservation of ERV3 in most of the investigated Catarrhini and the expression pattern in normal tissues suggest a putative physiological role of ERV3. On the other hand, ERV3 has been implicated in the pathogenesis of auto-immunity and cancer. In the present review we summarize knowledge about this interesting EVE. We propose the model that expression of ERV3 (and probably other EVE loci) under pathological conditions might be part of a metazoan SOS response. PMID:29379485

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.

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.

Orchestrating brain-cell renewal: the role of immune cells in adult neurogenesis in health and disease.

PubMed

Ziv, Yaniv; Schwartz, Michal

2008-11-01

Immune cells and immune molecules have recently been shown to support neurogenesis from neural stem and progenitor cells in the adult brain. This non-classical immune activity takes place constantly under normal physiological conditions and is extended under acute pathological conditions to include the attraction of progenitor cells and induction of neurogenesis in regions of the adult central nervous system (CNS) in which formation of new neurons does not normally occur. We suggest that the immune system should be viewed as a novel player in the adult neural stem cell niche and a coordinator of cell renewal processes after injury. We discuss these notions in light of the well-known facts that both immune-cell activity and cell renewal are inherently limited in the adult CNS and that immune and stem cells provide the body's mechanisms of repair.

Is Snow a sufficient Source of Water for Horses kept Outdoors in Winter? A Case Report

PubMed Central

Mejdell, CM; Simensen, E; Bøe, KE

2005-01-01

Due to extreme weather conditions, a flock of outwintered Icelandic horses had to manage for several days on snow as the source of free water. They were fed grass silage ad lib, and any change in feed consumption was not observed. After nine days, blood samples were taken and analysed for plasma osmolality, they were subjected to a simple clinical examination, and offered drinking water. Osmolality levels were within normal limits and mean value did not differ significantly from samples which previously were taken of the same individuals. The general condition of the horses was normal, with no signs of clinical dehydration or disease. The horses showed very little interest for the offered drinking water. This suggests that in cold winter weather, horses being fed grass silage and adjusted to eat snow, can manage for several days with snow substituting liquid water without their physiology and welfare being challenged. PMID:16108209

Exercise Hypertension

PubMed Central

Schultz, Martin G.; Sharman, James E.

2014-01-01

Irrespective of apparent ‘normal' resting blood pressure (BP), some individuals may experience an excessive elevation in BP with exercise (i.e. systolic BP ≥210 mm Hg in men or ≥190 mm Hg in women or diastolic BP ≥110 mm Hg in men or women), a condition termed exercise hypertension or a ‘hypertensive response to exercise' (HRE). An HRE is a relatively common condition that is identified during standard exercise stress testing; however, due to a lack of information with respect to the clinical ramifications of an HRE, little value is usually placed on such a finding. In this review, we discuss both the clinical importance and underlying physiological contributors of exercise hypertension. Indeed, an HRE is associated with an increased propensity for target organ damage and also predicts the future development of hypertension, cardiovascular events and mortality, independent of resting BP. Moreover, recent work has highlighted that some of the elevated cardiovascular risks associated with an HRE may be related to high-normal resting BP (pre-hypertension) or ambulatory ‘masked' hypertension and that an HRE may be an early warning signal of abnormal BP control that is otherwise undetected with clinic BP. Whilst an HRE may be amenable to treatment via pharmacological and lifestyle interventions, the exact physiological mechanism of an HRE remains elusive, but it is likely a manifestation of multiple factors including large artery stiffness, increased peripheral resistance, neural circulatory control and metabolic irregularity. Future research focus may be directed towards determining threshold values to denote the increased risk associated with an HRE and further resolution of the underlying physiological factors involved in the pathogenesis of an HRE. PMID:26587435

Effect of vision, touch and stance on cerebellar vermian-related sway and tremor: a quantitative physiological and MRI study.

PubMed

Sullivan, Edith V; Rose, Jessica; Pfefferbaum, Adolf

2006-08-01

Postural balance is impaired in individuals with pathology of the anterior superior vermis of the cerebellum. Chronic alcoholism, with its known vermian pathology, provides a viable model for studying the relationship between cerebellar pathology and postural stability. Decades of separate study of recovering alcoholics and post-mortem neuroanatomical analysis have demonstrated vermian pathology but few studies have used quantitative posturography, acquired concurrently with quantitative neuroimaging, to establish whether this brain structure-function relationship is selective in vivo. Here, 30 healthy men and 39 chronic alcoholic men, abstinent from alcohol for several months, underwent MRI for volumetric quantitation of the cerebellar vermis and three comparison brain regions, the cerebellar hemispheres, supratentorial cortex and corpus callosum. All subjects also participated in an experiment involving a force platform that measured sway path length and tremor during static standing balance under four sensory conditions and two stance conditions. Three novel findings emerged: (i) sway path length, a physiological index of postural control, was selectively related to volume of the cerebellar vermis and not to any comparison brain region in the alcoholics; (ii) spectral analysis revealed sway prominence in the 2-5 Hz band, another physiological sign of vermian lesions and also selectively related to vermian volume in the alcoholics; and (iii) despite substantial postural sway in the patients, they successfully used vision, touch and stance to normalize sway and reduce tremor. The selective relationship of sway path to vermian but not lateral cerebellar volume provides correlational evidence for functional differentiation of these cerebellar regions. Improvement to virtual normal levels in balance and reduction in sway and tremor with changes in vision, touch and stance provide evidence that adaptive mechanisms recruiting sensorimotor integration can be invoked to compensate for underlying cerebellar vermian-related dysfunction.

Spine micromorphology of normal and hyperhydric Mammillaria gracilis Pfeiff. (Cactaceae) shoots.

PubMed

Peharec, P; Posilović, H; Balen, B; Krsnik-Rasol, M

2010-07-01

Artificial conditions of tissue culture affect growth and physiology of crassulacean acid metabolism plants which often results in formation of hyperhydric shoots. In in vitro conditions Mammillaria gracilis Pfeiff. (Cactaceae) growth switches from organized to unorganized way, producing a habituated organogenic callus which simultaneously regenerates morphologically normal as well as altered hyperhydric shoots. In this study, influence of tissue culture conditions on morphology of cactus spines of normal and hyperhydric shoots was investigated. Spines of pot-grown Mammillaria plants and of in vitro regenerated shoots were examined with stereo microscope and scanning electron microscope. The pot-grown plants had 16-17 spines per areole. In vitro grown normal shoots, even though they kept typical shoot morphology, had lower number of spines (11-12) and altered spine morphology. This difference was even more pronounced in spine number (six to seven) and morphology of the hyperhydric shoots. Scanning electron microscopy analysis revealed remarkable differences in micromorphology of spine surface between pot-grown and in vitro grown shoots. Spines of in vitro grown normal shoots showed numerous long trichomes, which were more elongated on spines of the hyperhydric shoots; the corresponding structures on spine surface of pot-grown plants were noticed only as small protrusions. Scanning electron microscopy morphometric studies showed that the spines of pot-grown plants were significantly longer compared to the spines of shoots grown in tissue culture. Moreover, transverse section shape varies from elliptical in pot-grown plants to circular in normal and hyperhydric shoots grown in vitro. Cluster and correspondence analyses performed on the scanning electron microscope obtained results suggest great variability among spines of pot-grown plants. Spines of in vitro grown normal and hyperhydric shoots showed low level of morphological variation among themselves despite the significant difference in shoot morphology.

Friction and lubrication of pleural tissues.

PubMed

D'Angelo, Edgardo; Loring, Stephen H; Gioia, Magda E; Pecchiari, Matteo; Moscheni, Claudia

2004-08-20

The frictional behaviour of rabbit's visceral pleura sliding against parietal pleura was assessed in vitro while oscillating at physiological velocities and amplitudes under physiological normal forces. For sliding velocities up to 3 cm s(-1) and normal compressive loads up to 12 cm H2O, the average value of the coefficient of kinetic friction (mu) was constant at 0.019 +/- 0.002 (S.E.) with pleural liquid as lubricant. With Ringer-bicarbonate solution, mu was still constant, but significantly increased (Deltamu = 0.008 +/- 0.001; P < 0.001). Under these conditions, no damage of the sliding pleural surfaces was found on light and electron microscopy. Additional measurements, performed also on peritoneum, showed that changes in nominal contact area or strain of the mesothelia, temperature in the range 19-39 degrees C, and prolonged sliding did not affect mu. Gentle application of filter paper increased mu approximately 10-fold and irreversibly, suggesting alteration of the mesothelia. With packed the red blood cells (RBC) between the sliding mesothelia, mu increased appreciably but reversibly on removal of RBC suspension, whilst no ruptures of RBC occurred. In conclusion, the results indicate a low value of sliding friction in pleural tissues, partly related to the characteristics of the pleural liquid, and show that friction is independent of velocity, normal load, and nominal contact area, consistent with boundary lubrication.

Increase of Chamazulene and α-Bisabolol Contents of the Essential Oil of German Chamomile (Matricaria chamomila L.) Using Salicylic Acid Treatments under Normal and Heat Stress Conditions

PubMed Central

Ghasemi, Mojtaba; Babaeian Jelodar, Nadali; Modarresi, Mohammad; Bagheri, Nadali; Jamali, Abbas

2016-01-01

The chamazulene and α-(−)-bisabolol contents and quality of the chamomile oil are affected by genetic background and environmental conditions. Salicylic acid (SA), as a signaling molecule, plays a significant role in the plant physiological processes. The aim of this study was to evaluate the chemical profile, quantity, and improve the essential oil quality as a consequence of the increase of chamazulene and α-(−)-bisabol using salicylic acid under normal and heat stress conditions by the gas chromatography-mass spectrometry (GC-MS) technique. The factorial experiments were carried out during the 2011–2012 hot season using a randomized complete block design with three replications. The factors include four salicylic acid concentrations (0 (control), 10, 25 and 100 mg·L−1), and three chamomile cultivars (Bushehr, Bona, Bodegold) were sown on two different planting dates under field conditions. Fourteen compounds were identified from the extracted oil of the samples treated with salicylic acid under normal and heat stress conditions. The major identified oil compositions from chamomile cultivars treated with salicylic acid were chamazulene, α-(−)-bisabolol, bisabolone oxide, β-farnesene, en-yn-dicycloether, and bisabolol oxide A and B. Analysis of variance showed that the simple effects (environmental conditions, cultivar and salicylic acid) and their interaction were significant on all identified compounds, but the environmental conditions had no significant effect on bisabolol oxide A. The greatest amount of chamazulene obtained was 6.66% at the concentration of 10 mg·L−1 SA for the Bona cultivar under heat stress conditions, whereas the highest α-(−)-bisabolol amount attained was 3.41% at the concentration of 100 mg·L−1 SA for the Bona cultivar under normal conditions. The results demonstrated that the application of exogenous salicylic acid increases the quantity and essential oil quality as a consequence of the increase of chamazulene and α-(−)-bisabolol under normal and heat stress conditions. PMID:28231151

Power spectral density analysis of physiological, rest and action tremor in Parkinson’s disease patients treated with deep brain stimulation

PubMed Central

2013-01-01

Background Observation of the signals recorded from the extremities of Parkinson’s disease patients showing rest and/or action tremor reveal a distinct high power resonance peak in the frequency band corresponding to tremor. The aim of the study was to investigate, using quantitative measures, how clinically effective and less effective deep brain stimulation protocols redistribute movement power over the frequency bands associated with movement, pathological and physiological tremor, and whether normal physiological tremor may reappear during those periods that tremor is absent. Methods The power spectral density patterns of rest and action tremor were studied in 7 Parkinson’s disease patients treated with (bilateral) deep brain stimulation of the subthalamic nucleus. Two tests were carried out: 1) the patient was sitting at rest; 2) the patient performed a hand or foot tapping movement. Each test was repeated four times for each extremity with different stimulation settings applied during each repetition. Tremor intermittency was taken into account by classifying each 3-second window of the recorded angular velocity signals as a tremor or non-tremor window. Results The distribution of power over the low frequency band (<3.5 Hz – voluntary movement), tremor band (3.5-7.5 Hz) and high frequency band (>7.5 Hz – normal physiological tremor) revealed that rest and action tremor show a similar power-frequency shift related to tremor absence and presence: when tremor is present most power is contained in the tremor frequency band; when tremor is absent lower frequencies dominate. Even under resting conditions a relatively large low frequency component became prominent, which seemed to compensate for tremor. Tremor absence did not result in the reappearance of normal physiological tremor. Conclusion Parkinson’s disease patients continuously balance between tremor and tremor suppression or compensation expressed by power shifts between the low frequency band and the tremor frequency band during rest and voluntary motor actions. This balance shows that the pathological tremor is either on or off, with the latter state not resembling that of a healthy subject. Deep brain stimulation can reverse the balance thereby either switching tremor on or off. PMID:23834737

Quantitative analysis of the Ca2+ -dependent regulation of delayed rectifier K+ current IKs in rabbit ventricular myocytes.

PubMed

Bartos, Daniel C; Morotti, Stefano; Ginsburg, Kenneth S; Grandi, Eleonora; Bers, Donald M

2017-04-01

[Ca 2+ ] i enhanced rabbit ventricular slowly activating delayed rectifier K + current (I Ks ) by negatively shifting the voltage dependence of activation and slowing deactivation, similar to perfusion of isoproterenol. Rabbit ventricular rapidly activating delayed rectifier K + current (I Kr ) amplitude and voltage dependence were unaffected by high [Ca 2+ ] i . When measuring or simulating I Ks during an action potential, I Ks was not different during a physiological Ca 2+ transient or when [Ca 2+ ] i was buffered to 500 nm. The slowly activating delayed rectifier K + current (I Ks ) contributes to repolarization of the cardiac action potential (AP). Intracellular Ca 2+ ([Ca 2+ ] i ) and β-adrenergic receptor (β-AR) stimulation modulate I Ks amplitude and kinetics, but details of these important I Ks regulators and their interaction are limited. We assessed the [Ca 2+ ] i dependence of I Ks in steady-state conditions and with dynamically changing membrane potential and [Ca 2+ ] i during an AP. I Ks was recorded from freshly isolated rabbit ventricular myocytes using whole-cell patch clamp. With intracellular pipette solutions that controlled free [Ca 2+ ] i , we found that raising [Ca 2+ ] i from 100 to 600 nm produced similar increases in I Ks as did β-AR activation, and the effects appeared additive. Both β-AR activation and high [Ca 2+ ] i increased maximally activated tail I Ks , negatively shifted the voltage dependence of activation, and slowed deactivation kinetics. These data informed changes in our well-established mathematical model of the rabbit myocyte. In both AP-clamp experiments and simulations, I Ks recorded during a normal physiological Ca 2+ transient was similar to I Ks measured with [Ca 2+ ] i clamped at 500-600 nm. Thus, our study provides novel quantitative data as to how physiological [Ca 2+ ] i regulates I Ks amplitude and kinetics during the normal rabbit AP. Our results suggest that micromolar [Ca 2+ ] i , in the submembrane or junctional cleft space, is not required to maximize [Ca 2+ ] i -dependent I Ks activation during normal Ca 2+ transients. © 2016 The Authors. The Journal of Physiology © 2016 The Physiological Society.

Effect of speed endurance training and reduced training volume on running economy and single muscle fiber adaptations in trained runners.

PubMed

Skovgaard, Casper; Christiansen, Danny; Christensen, Peter M; Almquist, Nicki W; Thomassen, Martin; Bangsbo, Jens

2018-02-01

The aim of the present study was to examine whether improved running economy with a period of speed endurance training and reduced training volume could be related to adaptations in specific muscle fibers. Twenty trained male (n = 14) and female (n = 6) runners (maximum oxygen consumption (VO 2 -max): 56.4 ± 4.6 mL/min/kg) completed a 40-day intervention with 10 sessions of speed endurance training (5-10 × 30-sec maximal running) and a reduced (36%) volume of training. Before and after the intervention, a muscle biopsy was obtained at rest, and an incremental running test to exhaustion was performed. In addition, running at 60% vVO 2 -max, and a 10-km run was performed in a normal and a muscle slow twitch (ST) glycogen-depleted condition. After compared to before the intervention, expression of mitochondrial uncoupling protein 3 (UCP3) was lower (P < 0.05) and dystrophin was higher (P < 0.05) in ST muscle fibers, and sarcoplasmic reticulum calcium ATPase 1 (SERCA1) was lower (P < 0.05) in fast twitch muscle fibers. Running economy at 60% vVO 2 -max (11.6 ± 0.2 km/h) and at v10-km (13.7 ± 0.3 km/h) was ~2% better (P < 0.05) after the intervention in the normal condition, but unchanged in the ST glycogen-depleted condition. Ten kilometer performance was improved (P < 0.01) by 3.2% (43.7 ± 1.0 vs. 45.2 ± 1.2 min) and 3.9% (45.8 ± 1.2 vs. 47.7 ± 1.3 min) in the normal and the ST glycogen-depleted condition, respectively. VO 2 -max was the same, but vVO 2 -max was 2.0% higher (P < 0.05; 19.3 ± 0.3 vs. 18.9 ± 0.3 km/h) after than before the intervention. Thus, improved running economy with intense training may be related to changes in expression of proteins linked to energy consuming processes in primarily ST muscle fibers. © 2018 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

Ecological comparison of cellular stress responses among populations - normalizing RT-qPCR values to investigate differential environmental adaptations.

PubMed

Koenigstein, Stefan; Pöhlmann, Kevin; Held, Christoph; Abele, Doris

2013-05-16

Rising temperatures and other environmental factors influenced by global climate change can cause increased physiological stress for many species and lead to range shifts or regional population extinctions. To advance the understanding of species' response to change and establish links between individual and ecosystem adaptations, physiological reactions have to be compared between populations living in different environments. Although changes in expression of stress genes are relatively easy to quantify, methods for reliable comparison of the data remain a contentious issue. Using normalization algorithms and further methodological considerations, we compare cellular stress response gene expression levels measured by RT-qPCR after air exposure experiments among different subpopulations of three species of the intertidal limpet Nacella. Reference gene assessment algorithms reveal that stable reference genes can differ among investigated populations and / or treatment groups. Normalized expression values point to differential defense strategies to air exposure in the investigated populations, which either employ a pronounced cellular stress response in the inducible Hsp70 forms, or exhibit a comparatively high constitutive expression of Hsps (heat shock proteins) while showing only little response in terms of Hsp induction. This study serves as a case study to explore the methodological prerequisites of physiological stress response comparisons among ecologically and phylogenetically different organisms. To improve the reliability of gene expression data and compare the stress responses of subpopulations under potential genetic divergence, reference gene stability algorithms are valuable and necessary tools. As the Hsp70 isoforms have been shown to play different roles in the acute stress responses and increased constitutive defenses of populations in their different habitats, these comparative studies can yield insight into physiological strategies of adaptation to environmental stress and provide hints for the prudent use of the cellular stress response as a biomarker to study environmental stress and stress adaptation of populations under changing environmental conditions.

Effect of halo-vest components on stabilizing the injured cervical spine.

PubMed

Ivancic, Paul C; Beauchman, Naseem N; Tweardy, Lisa

2009-01-15

An in vitro biomechanical study. The objectives were to develop a new biofidelic skull-neck-thorax model capable of quantifying motion patterns of the cervical spine in the presence of a halo-vest; to investigate the effects of vest loosening, superstructure loosening, and removal of the posterior uprights; and to evaluate the ability of the halo-vest to stabilize the neck within physiological motion limits. Previous clinical and biomechanical studies have investigated neck motion with the halo-vest only in the sagittal plane or only at the injured spinal level. No previous studies have quantified three-dimensional intervertebral motion patterns throughout the injured cervical spine stabilized with the halo-vest or studied the effect of halo-vest components on these motions. The halo-vest was applied to the skull-neck-thorax model. Six osteoligamentous whole cervical spine specimens (occiput through T1 vertebra) were used that had sustained multiplanar ligamentous injuries at C3/4 through C7-T1 during a previous protocol. Flexibility tests were performed with normal halo-vest application, loose vest, loose superstructure, and following removal of the posterior uprights. Average total range of motion for each experimental condition was statistically compared (P < 0.05) with the physiologic rotation limit for each spinal level. Cervical spine snaking was observed in both the sagittal and frontal planes. The halo-vest, applied normally, generally limited average spinal motions to within average physiological limits. No significant increases in average spinal motions above physiologic were observed due to loose vest, loose superstructure, or removal of the posterior uprights. However, a trend toward increased motion at C6/7 in lateral bending was observed due to loose superstructure. The halo-vest, applied normally, effectively immobilized the cervical spine. Sagittal or frontal plane snaking of the cervical spine due to the halo-vest may reduce its immobilization capability at the upper cervical spine and cervicothoracic junction.

Ecological comparison of cellular stress responses among populations – normalizing RT-qPCR values to investigate differential environmental adaptations

PubMed Central

2013-01-01

Background Rising temperatures and other environmental factors influenced by global climate change can cause increased physiological stress for many species and lead to range shifts or regional population extinctions. To advance the understanding of species’ response to change and establish links between individual and ecosystem adaptations, physiological reactions have to be compared between populations living in different environments. Although changes in expression of stress genes are relatively easy to quantify, methods for reliable comparison of the data remain a contentious issue. Using normalization algorithms and further methodological considerations, we compare cellular stress response gene expression levels measured by RT-qPCR after air exposure experiments among different subpopulations of three species of the intertidal limpet Nacella. Results Reference gene assessment algorithms reveal that stable reference genes can differ among investigated populations and / or treatment groups. Normalized expression values point to differential defense strategies to air exposure in the investigated populations, which either employ a pronounced cellular stress response in the inducible Hsp70 forms, or exhibit a comparatively high constitutive expression of Hsps (heat shock proteins) while showing only little response in terms of Hsp induction. Conclusions This study serves as a case study to explore the methodological prerequisites of physiological stress response comparisons among ecologically and phylogenetically different organisms. To improve the reliability of gene expression data and compare the stress responses of subpopulations under potential genetic divergence, reference gene stability algorithms are valuable and necessary tools. As the Hsp70 isoforms have been shown to play different roles in the acute stress responses and increased constitutive defenses of populations in their different habitats, these comparative studies can yield insight into physiological strategies of adaptation to environmental stress and provide hints for the prudent use of the cellular stress response as a biomarker to study environmental stress and stress adaptation of populations under changing environmental conditions. PMID:23680017

A Matter of Life or Death: Untangling the Coupled Roles of Behavior, Microclimate and Physiological Polymorphism in Governing Vulnerability of Intertidal Snails to Heat Stress

NASA Astrophysics Data System (ADS)

Dong, Y.; Li, X.; Choi, F.; Willams, G.; Somero, G. N.; Helmuth, B.

2016-12-01

Changing patterns of species' biogeographic distributions are driven by cumulative effects of much smaller scale processes. Specifically, vulnerability of animals to thermal stress is the result of physiological sensitivities to body temperature (Tb), local microclimatic conditions, and abilities to anticipate extreme conditions and move to cooler refugia. These variables have rarely been quantified simultaneously over large geographic scales. We analyzed the thermal tolerances of three species of rocky intertidal snails from eight sites spanning 11.5 degrees of latitude along the Chinese coast. Using a biophysical model, we estimated potential Tb in sun-exposed and shaded microhabitats for all species at these sites for 30 years. We then compared maximum predicted Tb against the temperatures at which cardiac function was impaired (Arrhenius Break Temperatures, ABT) and lethal limits were reached (cardiac Flat Line Temperatures, FLT) to calculate thermal Safety Margins (TSM) for normal physiological function (TSMABT) and heat death (TSMFLT). Regular exceedance of FLT in sun-exposed microhabitats was predicted for only one site in the middle of the geographic gradient. However, ABT was exceeded at sun-exposed microhabitats in most sites, suggesting significant physiological impairment for snails that fail to move into the shade. An autocorrelation analysis of snail Tb showed that predictability of extreme temperatures was lowest at the hottest sites, an indication that reliance on behavioral thermoregulation may be a risky strategy. Observed large differences in ABT and FLT among conspecifics emphasize the critical role of physiological polymorphisms in governing the vulnerability of populations to heat stress.

Sex-comparative study of mouse cerebellum physiology under adult-onset hypothyroidism: The significance of GC-MS metabolomic data normalization in meta-analysis.

PubMed

Maga-Nteve, Christoniki; Vasilopoulou, Catherine G; Constantinou, Caterina; Margarity, Marigoula; Klapa, Maria I

2017-01-15

A systematic data quality validation and normalization strategy is an important component of the omic profile meta-analysis, ensuring comparability of the profiles and exclusion of experimental biases from the derived biological conclusions. In this study, we present the normalization methodology applied on the sets of cerebellum gas chromatography-mass spectrometry metabolic profiles of 124days old male and female animals in an adult-onset-hypothyroidism (AOH) mouse model before combining them into a sex-comparative analysis. The employed AOH model concerns the monitoring of the brain physiology of Balb/cJ mice after eight-week administration of 1%w/v KClO 4 in the drinking water, initiated on the 60th day of their life. While originating from the same animal study, the tissues of the two sexes were processed and their profiles acquired and analyzed at different time periods. Hence, the previously published profile set of male mice was first re-annotated based on the presently available resources. Then, after being validated as acquired under the same analytical conditions, both profiles sets were corrected for derivatization biases and filtered for low-confidence measurements based on the same criteria. The final normalized 73-metabolite profiles contribute to the currently few available omic datasets of the AOH effect on brain molecular physiology, especially with respect to sex differentiation. Multivariate statistical analysis indicated one (unknown) and three (succinate, benzoate, myristate) metabolites with significantly higher and lower, respectively, cerebellum concentration in the hypothyroid compared to the euthyroid female mice. The respective numbers for the males were two and 24. Comparison of the euthyroid cerebellum metabolic profiles between the two sexes indicated 36 metabolites, including glucose, myo- and scyllo-inositol, with significantly lower concentration in the females versus the males. This implies that the female mouse cerebellum has been conditioned to smaller changes in its metabolic activity with respect to the pathways involving these metabolites compared to the male animals. In conclusion, our study indicated a much subtler AOH effect on the cerebellum metabolic activity of the female compared to the male mice. The leaner metabolic profile of the female mouse cerebellum was suggested as a potential factor contributing to this phenomenon. Copyright © 2016 Elsevier B.V. All rights reserved.

The sleepy teenager - diagnostic challenges.

PubMed

Landtblom, Anne-Marie; Engström, Maria

2014-01-01

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

The Sleepy Teenager – Diagnostic Challenges

PubMed Central

Landtblom, Anne-Marie; Engström, Maria

2014-01-01

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

In vivo Magnetic Resonance Spectroscopy of cerebral glycogen metabolism in animals and humans.

PubMed

Khowaja, Ameer; Choi, In-Young; Seaquist, Elizabeth R; Öz, Gülin

2015-02-01

Glycogen serves as an important energy reservoir in the human body. Despite the abundance of glycogen in the liver and skeletal muscles, its concentration in the brain is relatively low, hence its significance has been questioned. A major challenge in studying brain glycogen metabolism has been the lack of availability of non-invasive techniques for quantification of brain glycogen in vivo. Invasive methods for brain glycogen quantification such as post mortem extraction following high energy microwave irradiation are not applicable in the human brain. With the advent of (13)C Magnetic Resonance Spectroscopy (MRS), it has been possible to measure brain glycogen concentrations and turnover in physiological conditions, as well as under the influence of stressors such as hypoglycemia and visual stimulation. This review presents an overview of the principles of the (13)C MRS methodology and its applications in both animals and humans to further our understanding of glycogen metabolism under normal physiological and pathophysiological conditions such as hypoglycemia unawareness.

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

An integrated mathematical model of the human cardiopulmonary system: model development.

PubMed

Albanese, Antonio; Cheng, Limei; Ursino, Mauro; Chbat, Nicolas W

2016-04-01

Several cardiovascular and pulmonary models have been proposed in the last few decades. However, very few have addressed the interactions between these two systems. Our group has developed an integrated cardiopulmonary model (CP Model) that mathematically describes the interactions between the cardiovascular and respiratory systems, along with their main short-term control mechanisms. The model has been compared with human and animal data taken from published literature. Due to the volume of the work, the paper is divided in two parts. The present paper is on model development and normophysiology, whereas the second is on the model's validation on hypoxic and hypercapnic conditions. The CP Model incorporates cardiovascular circulation, respiratory mechanics, tissue and alveolar gas exchange, as well as short-term neural control mechanisms acting on both the cardiovascular and the respiratory functions. The model is able to simulate physiological variables typically observed in adult humans under normal and pathological conditions and to explain the underlying mechanisms and dynamics. Copyright © 2016 the American Physiological Society.

In vivo Magnetic Resonance Spectroscopy of cerebral glycogen metabolism in animals and humans

PubMed Central

Khowaja, Ameer; Choi, In-Young; Seaquist, Elizabeth R.; Öz, Gülin

2015-01-01

Glycogen serves as an important energy reservoir in the human body. Despite the abundance of glycogen in the liver and skeletal muscles, its concentration in the brain is relatively low, hence its significance has been questioned. A major challenge in studying brain glycogen metabolism has been the lack of availability of non-invasive techniques for quantification of brain glycogen in vivo. Invasive methods for brain glycogen quantification such as post mortem extraction following high energy microwave irradiation are not applicable in the human brain. With the advent of 13C Magnetic Resonance Spectroscopy (MRS), it has been possible to measure brain glycogen concentrations and turnover in physiological conditions, as well as under the influence of stressors such as hypoglycemia and visual stimulation. This review presents an overview of the principles of the 13C MRS methodology and its applications in both animals and humans to further our understanding of glycogen metabolism under normal physiological and pathophysiological conditions such as hypoglycemia unawareness. PMID:24676563

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.

Seeding materials: Health and safety considerations

NASA Technical Reports Server (NTRS)

Brown, R. D.

1985-01-01

The choice of a proper seeding material for laser velocimeters must include health and safety considerations. Failure to do so can lead to catastrophic results. All materials are toxic, and laser velocimeter seeding materials are no exception. Toxicity may be considered an inherent property of a given material. The manifestation of that property or the physiological response to the material is dependent on dose and exposure conditions. An approximate physiological classification of toxicity is given in tablular form. Toxicity in some situations is not necessarily the most restrictive factor in selection of materials. It is also very important to consider how the material is used so that actual exposure to the material in a damaging form can result. For example, nickel and cadmium are both extremely toxic as systemic poisons and in the case of nickel as a carcinogen. Seeding materials are dispersed in air under conditions that favor personnel exposure. Dispersal equipment is frequently if not normally manned, and personnel are often required to make frequent adjustments to assure proper operations.

Multiscale entropy analysis of human gait dynamics

NASA Astrophysics Data System (ADS)

Costa, M.; Peng, C.-K.; L. Goldberger, Ary; Hausdorff, Jeffrey M.

2003-12-01

We compare the complexity of human gait time series from healthy subjects under different conditions. Using the recently developed multiscale entropy algorithm, which provides a way to measure complexity over a range of scales, we observe that normal spontaneous walking has the highest complexity when compared to slow and fast walking and also to walking paced by a metronome. These findings have implications for modeling locomotor control and for quantifying gait dynamics in physiologic and pathologic states.

Design-Optimization and Material Selection for a Proximal Radius Fracture-Fixation Implant

NASA Astrophysics Data System (ADS)

Grujicic, M.; Xie, X.; Arakere, G.; Grujicic, A.; Wagner, D. W.; Vallejo, A.

2010-11-01

The problem of optimal size, shape, and placement of a proximal radius-fracture fixation-plate is addressed computationally using a combined finite-element/design-optimization procedure. To expand the set of physiological loading conditions experienced by the implant during normal everyday activities of the patient, beyond those typically covered by the pre-clinical implant-evaluation testing procedures, the case of a wheel-chair push exertion is considered. Toward that end, a musculoskeletal multi-body inverse-dynamics analysis is carried out of a human propelling a wheelchair. The results obtained are used as input to a finite-element structural analysis for evaluation of the maximum stress and fatigue life of the parametrically defined implant design. While optimizing the design of the radius-fracture fixation-plate, realistic functional requirements pertaining to the attainment of the required level of the devise safety factor and longevity/lifecycle were considered. It is argued that the type of analyses employed in the present work should be: (a) used to complement the standard experimental pre-clinical implant-evaluation tests (the tests which normally include a limited number of daily-living physiological loading conditions and which rely on single pass/fail outcomes/decisions with respect to a set of lower-bound implant-performance criteria) and (b) integrated early in the implant design and material/manufacturing-route selection process.

Endurance Exercise: Normal Physiology and Limitations Imposed by Pathological Processes (Part 1).

ERIC Educational Resources Information Center

Frontera, Walter R.; Adams, Richard P.

1986-01-01

The physiologic and metabolic adjustments of the body to a single endurance exercise session are analyzed in terms of the respiratory system, the cardiovascular system, and oxygen delivery to the muscles. Patients with cardiorespiratory and neuromuscular diseases are compared to normal individuals. (Author/MT)

Normalization of Reverse Transcription Quantitative PCR Data During Ageing in Distinct Cerebral Structures.

PubMed

Bruckert, G; Vivien, D; Docagne, F; Roussel, B D

2016-04-01

Reverse transcription quantitative-polymerase chain reaction (RT-qPCR) has become a routine method in many laboratories. Normalization of data from experimental conditions is critical for data processing and is usually achieved by the use of a single reference gene. Nevertheless, as pointed by the Minimum Information for Publication of Quantitative Real-Time PCR Experiments (MIQE) guidelines, several reference genes should be used for reliable normalization. Ageing is a physiological process that results in a decline of many expressed genes. Reliable normalization of RT-qPCR data becomes crucial when studying ageing. Here, we propose a RT-qPCR study from four mouse brain regions (cortex, hippocampus, striatum and cerebellum) at different ages (from 8 weeks to 22 months) in which we studied the expression of nine commonly used reference genes. With the use of two different algorithms, we found that all brain structures need at least two genes for a good normalization step. We propose specific pairs of gene for efficient data normalization in the four brain regions studied. These results underline the importance of reliable reference genes for specific brain regions in ageing.

Evaluation of reference genes for insect olfaction studies.

PubMed

Omondi, Bonaventure Aman; Latorre-Estivalis, Jose Manuel; Rocha Oliveira, Ivana Helena; Ignell, Rickard; Lorenzo, Marcelo Gustavo

2015-04-22

Quantitative reverse transcription PCR (qRT-PCR) is a robust and accessible method to assay gene expression and to infer gene regulation. Being a chain of procedures, this technique is subject to systematic error due to biological and technical limitations mainly set by the starting material and downstream procedures. Thus, rigorous data normalization is critical to grant reliability and repeatability of gene expression quantification by qRT-PCR. A number of 'housekeeping genes', involved in basic cellular functions, have been commonly used as internal controls for this normalization process. However, these genes could themselves be regulated and must therefore be tested a priori. We evaluated eight potential reference genes for their stability as internal controls for RT-qPCR studies of olfactory gene expression in the antennae of Rhodnius prolixus, a Chagas disease vector. The set of genes included were: α-tubulin; β-actin; Glyceraldehyde-3-phosphate dehydrogenase; Eukaryotic initiation factor 1A; Glutathione-S-transferase; Serine protease; Succinate dehydrogenase; and Glucose-6-phosphate dehydrogenase. Five experimental conditions, including changes in age,developmental stage and feeding status were tested in both sexes. We show that the evaluation of candidate reference genes is necessary for each combination of sex, tissue and physiological condition analyzed in order to avoid inconsistent results and conclusions. Although, Normfinder and geNorm software yielded different results between males and females, five genes (SDH, Tub, GAPDH, Act and G6PDH) appeared in the first positions in all rankings obtained. By using gene expression data of a single olfactory coreceptor gene as an example, we demonstrated the extent of changes expected using different internal standards. This work underlines the need for a rigorous selection of internal standards to grant the reliability of normalization processes in qRT-PCR studies. Furthermore, we show that particular physiological or developmental conditions require independent evaluation of a diverse set of potential reference genes.

Effects of TiO2 nanoparticles on wheat (Triticum aestivum L.) seedlings cultivated under super-elevated and normal CO2 conditions.

PubMed

Jiang, Fuping; Shen, Yunze; Ma, Chuanxin; Zhang, Xiaowen; Cao, Weidong; Rui, Yukui

2017-01-01

Concerns over the potential risks of nanomaterials to ecosystem have been raised, as it is highly possible that nanomaterials could be released to the environment and result in adverse effects on living organisms. Carbon dioxide (CO2) is one of the main greenhouse gases. The level of CO2 keeps increasing and subsequently causes a series of environmental problems, especially for agricultural crops. In the present study, we investigated the effects of TiO2 NPs on wheat seedlings cultivated under super-elevated CO2 conditions (5000 mg/L CO2) and under normal CO2 conditions (400 mg/L CO2). Compared to the normal CO2 condition, wheat grown under the elevated CO2 condition showed increases of root biomass and large numbers of lateral roots. Under both CO2 cultivation conditions, the abscisic acid (ABA) content in wheat seedlings increased with increasing concentrations of TiO2 NPs. The indolepropioponic acid (IPA) and jasmonic acid (JA) content notably decreased in plants grown under super-elevated CO2 conditions, while the JA content increased with increasing concentrations of TiO2 NPs. Ti accumulation showed a dose-response manner in both wheat shoots and roots as TiO2 NPs concentrations increased. Additionally, the presence of elevated CO2 significantly promoted Ti accumulation and translocation in wheat treated with certain concentrations of TiO2 NPs. This study will be of benefit to the understanding of the joint effects and physiological mechanism of high-CO2 and nanoparticle to terrestrial plants.

Impaired leptin expression and abnormal response to fasting in corticotropin-releasing hormone-deficient mice.

PubMed

Jeong, Kyeong-Hoon; Sakihara, Satoru; Widmaier, Eric P; Majzoub, Joseph A

2004-07-01

Leptin has been postulated to comprise part of an adipostat, whereby during states of excessive energy storage, elevated levels of the hormone prevent further weight gain by inhibiting appetite. A physiological role for leptin in this regard remains unclear because the presence of excessive food, and therefore the need to restrain overeating under natural conditions, is doubtful. We have previously shown that CRH-deficient (Crh(-/-)) mice have glucocorticoid insufficiency and lack the fasting-induced increase in glucocorticoid, a hormone important in stimulating leptin synthesis and secretion. We hypothesized that these mice might have low circulating leptin. Indeed, Crh(-/-) mice exhibited no diurnal variation of leptin, whereas normal littermates showed a clear rhythm, and their leptin levels were lower than their counterparts. A continuous peripheral CRH infusion to Crh(-/-) mice not only restored corticosterone levels, but it also increased leptin expression to normal. Surprisingly, 36 h of fasting elevated leptin levels in Crh(-/-) mice, rather than falling as in normal mice. This abnormal leptin change during fasting in Crh(-/-) mice was corrected by corticosterone replacement. Furthermore, Crh(-/-) mice lost less body weight during 24 h of fasting and ate less food during refeeding than normal littermates. Taken together, we conclude that glucocorticoid insufficiency in Crh(-/-) mice results in impaired leptin production as well as an abnormal increase in leptin during fasting, and propose that the fast-induced physiological reduction in leptin may play an important role to stimulate food intake during the recovery from fasting.

GSNOR Deficiency Enhances In Situ Skeletal Muscle Strength, Fatigue Resistance, and RyR1 S-Nitrosylation Without Impacting Mitochondrial Content and Activity

PubMed Central

Moon, Younghye; Cao, Yenong; Zhu, Jingjing; Xu, Yuanyuan; Balkan, Wayne; Buys, Emmanuel S.; Diaz, Francisca; Kerrick, W. Glenn; Hare, Joshua M.

2017-01-01

Abstract Aim: Nitric oxide (NO) plays important, but incompletely defined roles in skeletal muscle. NO exerts its regulatory effects partly though S-nitrosylation, which is balanced by denitrosylation by enzymes such as S-nitrosoglutathione reductase (GSNOR), whose functions in skeletal muscle remain to be fully deciphered. Results: GSNOR null (GSNOR−/−) tibialis anterior (TA) muscles showed normal growth and were stronger and more fatigue resistant than controls in situ. However, GSNOR−/− lumbrical muscles showed normal contractility and Ca2+ handling in vitro, suggesting important differences in GSNOR function between muscles or between in vitro and in situ environments. GSNOR−/− TA muscles exhibited normal mitochondrial content, and capillary densities, but reduced type IIA fiber content. GSNOR inhibition did not impact mitochondrial respiratory complex I, III, or IV activities. These findings argue that enhanced GSNOR−/− TA contractility is not driven by changes in mitochondrial content or activity, fiber type, or blood vessel density. However, loss of GSNOR led to RyR1 hypernitrosylation, which is believed to increase muscle force output under physiological conditions. cGMP synthesis by soluble guanylate cyclase (sGC) was decreased in resting GSNOR−/− muscle and was more responsive to agonist (DETANO, BAY 41, and BAY 58) stimulation, suggesting that GSNOR modulates cGMP production in skeletal muscle. Innovation: GSNOR may act as a “brake” on skeletal muscle contractile performance under physiological conditions by modulating nitrosylation/denitrosylation balance. Conclusions: GSNOR may play important roles in skeletal muscle contractility, RyR1 S-nitrosylation, fiber type specification, and sGC activity. Antioxid. Redox Signal. 26, 165–181. PMID:27412893

Chronic administration of parecoxib exerts anxiolytic-like and memory enhancing effects and modulates synaptophysin expression in mice.

PubMed

Wang, Bo; Jin, Xin; Kuang, Xin; Tian, Shaowen

2017-11-13

Previous studies have shown that cyclooxygenase-2, a key enzyme that converts arachidonic acid to prostaglandins, is involved in anxiety and cognitive processes, but few studies have investigated the effects of chronic administration of cyclooxygenase-2 inhibitors on anxiety, learning and memory under normal physiological conditions. The aim of the study was to investigate the effects of chronic administration of parecoxib, a cyclooxygenase-2 inhibitor, on anxiety behavior and memory performance under normal physiological conditions and to explore the possible neural mechanism underlying parecoxib-mediated effects. Adult male ICR mice were randomly divided into four groups: the control group and three parecoxib groups. Mice received normal saline or parecoxib (2.5, 5.0 or 10 mg/kg) intraperitoneal injection once a day for 21 days, respectively. Elevated plus-maze, novel object recognition and Y maze tests were conducted on day 23, 24 and 26, respectively. Four additional groups that received same drug treatment were used to measure synaptophysin protein levels by western blot and prostaglandin E2 (PGE2) levels by ELISA in the amygdala and hippocampus on day 26. Chronic parecoxib exerted an anxiolytic-like effect in the plus-maze test test, and enhanced memory performance in the novel object recognition and Y maze tests. Western blot analysis showed that chronic parecoxib down-regulated synaptophysin levels in the amygdala and up-regulated synaptophysin levels in the hippocampus. ELISA assay showed that chronic parecoxib inhibited PGE2 in the hippocampus but not amygdala. Chronic parecoxib exerts anxiolytic-like and memory enhancing effects, which might be mediated through differential modulation of synaptophysin and PGE2 in the amygdala and hippocampus.

Respiration, and growth-efficiency of coastal prokaryote communities in continuous cultures under different growth rates and temperatures.

NASA Astrophysics Data System (ADS)

Maske, H.; Cajal-Medrano, R.; Villegas-Mendoza, J.

2016-02-01

Organotrophic prokaryotes in aquatic environments account for about half of community respiration in surface oceans and are key trophic links in the plankton food web connecting dissolved organics and higher trophic levels. The transfer efficiency is partially characterized by the ratio of prokaryote respiration rates (r, day-1) to growth rates (m, day-1) and the resulting growth efficiency (Y). Much literature has been published about the response of these parameters to temperature in monospecific cultures, but little is known about the response of a community of pelagic prokaryotes were the sum of the genotypes and phenotype define the physiological potential. We inoculated 10 turbidostats and 39 chemostats with coastal bacteria and measured CO2 production, carbon biomass and cell abundance, with m ranging from 0.05 to 62 day-1 between 10 and 26oC. Under substrate limited conditions, common in the ocean, r showed no significant trend with temperature and was proportional to m implying constant Y. Under temperature-limited, nutrient replete growth the m of coastal prokaryote communities increased with temperature but r decreased (Q10: 0.4), resulting in an increase of Y with temperature (Q10: 2.5). The carbon demand rate (b, fmol C (cell day)-1) of turbidostat cultures showed a very high Q10 of 8.4. Casting the data in the framework of the metabolic theory of ecology (MTE), the physiological rates normalized to cell carbon showed no significant changes with temperature using either respiration or carbon demand as a proxy for physiological rate. Our results suggest that physiological patterns related to temperature are very different under nutrient limited or replete conditions and under neither condition it followed the pattern expected by MTE.

Understanding fetal physiology and second line monitoring during labor.

PubMed

Garabedian, C; De Jonckheere, J; Butruille, L; Deruelle, P; Storme, L; Houfflin-Debarge, V

2017-02-01

Cardiotocography (CTG) is a technique used to monitor intrapartum fetal condition and is one of the most common obstetric procedures. Second line methods of fetal monitoring have been developed in an attempt to reduce unnecessary interventions due to continuous cardiotocography and to better identify fetuses at risk of intrapartum asphyxia. The acid-base balance of the fetus is evaluated by fetal blood scalp samples, the modification of the myocardial oxygenation by the fetal ECG ST-segment analysis (STAN) and the autonomic nervous system by the power spectral analysis of the fetal heart variability. To correctly interpret the features observed on CTG traces or second line methods, it seems important to understand normal physiology during labor and the compensatory mechanisms of the fetus in case of hypoxemia. Therefore, the aim of this review is first to describe fetal physiology during labor and then to explain the modification of the second line monitoring during labor. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Vortex Formation Time is Not an Index of Ventricular Function

PubMed Central

Vlachos, Pavlos P.; Little, William C.

2015-01-01

The diastolic intraventricular ring vortex formation and pinch-off process may provide clinically useful insights into diastolic function in health and disease. The vortex ring formation time (FT) concept, based on hydrodynamic experiments dealing with unconfined (large tank) flow, has attracted considerable attention and popularity. Dynamic conditions evolving within the very confined space of a filling, expansible ventricular chamber with relaxing and rebounding viscoelastic muscular boundaries, diverge from unconfined (large tank) flow and encompass rebounding walls’ suction and myocardial relaxation. Indeed, clinical/physiological findings seeking validation in vivo failed to support the notion that FT is an index of normal/abnormal diastolic ventricular function. Therefore, FT as originally proposed cannot and should not be utilized as such an index. Evidently, physiologically accurate models accounting for coupled hydrodynamic and (patho)physiological myocardial wall interactions with the intraventricular flow are still needed to enhance our understanding and yield diastolic function indices useful and reliable in the clinical setting. PMID:25609509

Homoeolog-specific activation of genes for heat acclimation in the allopolyploid grass Brachypodium hybridum.

PubMed

Takahagi, Kotaro; Inoue, Komaki; Shimizu, Minami; Uehara-Yamaguchi, Yukiko; Onda, Yoshihiko; Mochida, Keiichi

2018-04-01

Allopolyploid plants often show wider environmental tolerances than their ancestors; this is expected to be due to the merger of multiple distinct genomes with a fixed heterozygosity. The complex homoeologous gene expression could have been evolutionarily advantageous for the adaptation of allopolyploid plants. Despite multiple previous studies reporting homoeolog-specific gene expression in allopolyploid species, there are no clear examples of homoeolog-specific function in acclimation to a long-term stress condition. We found that the allopolyploid grass Brachypodium hybridum and its ancestor Brachypodium stacei show long-term heat stress tolerance, unlike its other ancestor, Brachypodium distachyon. To understand the physiological traits of B. hybridum, we compared the transcriptome of the 3 Brachypodium species grown under normal and heat stress conditions. We found that the expression patterns of approximately 26% and approximately 38% of the homoeolog groups in B. hybridum changed toward nonadditive expression and nonancestral expression, respectively, under normal condition. Moreover, we found that B. distachyon showed similar expression patterns between normal and heat stress conditions, whereas B. hybridum and B. stacei significantly altered their transcriptome in response to heat after 3 days of stress exposure, and homoeologs that were inherited from B. stacei may have contributed to the transcriptional stress response to heat in B. hybridum. After 15 days of heat exposure, B. hybridum and B. stacei maintained transcriptional states similar to those under normal conditions. These results suggest that an earlier response to heat that was specific to homoeologs originating from B. stacei contributed to cellular homeostasis under long-term heat stress in B. hybridum. Our results provide insights into different regulatory events of the homoeo-transcriptome that are associated with stress acclimation in allopolyploid plants.

Cooling induces phase separation in membranes derived from isolated CNS myelin

PubMed Central

Pusterla, Julio M.; Schneck, Emanuel; Funari, Sérgio S.; Démé, Bruno; Tanaka, Motomu

2017-01-01

Purified myelin membranes (PMMs) are the starting material for biochemical analyses such as the isolation of detergent-insoluble glycosphingolipid-rich domains (DIGs), which are believed to be representatives of functional lipid rafts. The normal DIGs isolation protocol involves the extraction of lipids under moderate cooling. Here, we thus address the influence of cooling on the structure of PMMs and its sub-fractions. Thermodynamic and structural aspects of periodic, multilamellar PMMs are examined between 4°C and 45°C and in various biologically relevant aqueous solutions. The phase behavior is investigated by small-angle X-ray scattering (SAXS) and differential scanning calorimetry (DSC). Complementary neutron diffraction (ND) experiments with solid-supported myelin multilayers confirm that the phase behavior is unaffected by planar confinement. SAXS and ND consistently show that multilamellar PMMs in pure water become heterogeneous when cooled by more than 10–15°C below physiological temperature, as during the DIGs isolation procedure. The heterogeneous state of PMMs is stabilized in physiological solution, where phase coexistence persists up to near the physiological temperature. This result supports the general view that membranes under physiological conditions are close to critical points for phase separation. In presence of elevated Ca2+ concentrations (> 10 mM), phase coexistence is found even far above physiological temperatures. The relative fractions of the two phases, and thus presumably also their compositions, are found to vary with temperature. Depending on the conditions, an “expanded” phase with larger lamellar period or a “compacted” phase with smaller lamellar period coexists with the native phase. Both expanded and compacted periods are also observed in DIGs under the respective conditions. The observed subtle temperature-dependence of the phase behavior of PMMs suggests that the composition of DIGs is sensitive to the details of the isolation protocol. PMID:28915267

The development of a whole-body algorithm

NASA Technical Reports Server (NTRS)

Kay, F. J.

1973-01-01

The whole-body algorithm is envisioned as a mathematical model that utilizes human physiology to simulate the behavior of vital body systems. The objective of this model is to determine the response of selected body parameters within these systems to various input perturbations, or stresses. Perturbations of interest are exercise, chemical unbalances, gravitational changes and other abnormal environmental conditions. This model provides for a study of man's physiological response in various space applications, underwater applications, normal and abnormal workloads and environments, and the functioning of the system with physical impairments or decay of functioning components. Many methods or approaches to the development of a whole-body algorithm are considered. Of foremost concern is the determination of the subsystems to be included, the detail of the subsystems and the interaction between the subsystems.

Near-infrared spectroscopy and skeletal muscle oxidative function in vivo in health and disease: a review from an exercise physiology perspective

NASA Astrophysics Data System (ADS)

Grassi, Bruno; Quaresima, Valentina

2016-09-01

In most daily activities related to work or leisure, the energy for muscle work substantially comes from oxidative metabolism. Functional limitations or impairments of this metabolism can significantly affect exercise tolerance and performance. As a method for the functional evaluation of skeletal muscle oxidative metabolism, near-infrared spectroscopy (NIRS) has important strengths but also several limitations, some of which have been overcome by recent technological developments. Skeletal muscle fractional O2 extraction, the main variable which can be noninvasively evaluated by NIRS, is the result of the dynamic balance between O2 utilization and O2 delivery; it can yield relevant information on key physiological and pathophysiological mechanisms, relevant in the evaluation of exercise performance and exercise tolerance in healthy subjects (in normal and in altered environmental conditions) and in patients. In the right hands, NIRS can offer insights into the physiological and pathophysiological adaptations to conditions of increased O2 needs that involve, in an integrated manner, different organs and systems of the body. In terms of patient evaluation, NIRS allows determination of the evolution of the functional impairments, to identify their correlations with clinical symptoms, to evaluate the effects of therapeutic or rehabilitative interventions, and to gain pathophysiological and diagnostic insights.

Near-infrared spectroscopy and skeletal muscle oxidative function in vivo in health and disease: a review from an exercise physiology perspective.

PubMed

Grassi, Bruno; Quaresima, Valentina

2016-09-01

In most daily activities related to work or leisure, the energy for muscle work substantially comes from oxidative metabolism. Functional limitations or impairments of this metabolism can significantly affect exercise tolerance and performance. As a method for the functional evaluation of skeletal muscle oxidative metabolism, near-infrared spectroscopy (NIRS) has important strengths but also several limitations, some of which have been overcome by recent technological developments. Skeletal muscle fractional O2 extraction, the main variable which can be noninvasively evaluated by NIRS, is the result of the dynamic balance between O2 utilization and O2 delivery; it can yield relevant information on key physiological and pathophysiological mechanisms, relevant in the evaluation of exercise performance and exercise tolerance in healthy subjects (in normal and in altered environmental conditions) and in patients. In the right hands, NIRS can offer insights into the physiological and pathophysiological adaptations to conditions of increased O2 needs that involve, in an integrated manner, different organs and systems of the body. In terms of patient evaluation, NIRS allows determination of the evolution of the functional impairments, to identify their correlations with clinical symptoms, to evaluate the effects of therapeutic or rehabilitative interventions, and to gain pathophysiological and diagnostic insights.

Normal and system lupus erythematosus red blood cell interactions studied by double trap optical tweezers: direct measurements of aggregation forces

NASA Astrophysics Data System (ADS)

Khokhlova, Maria D.; Lyubin, Eugeny V.; Zhdanov, Alexander G.; Rykova, Sophia Yu.; Sokolova, Irina A.; Fedyanin, Andrey A.

2012-02-01

Direct measurements of aggregation forces in piconewton range between two red blood cells in pair rouleau are performed under physiological conditions using double trap optical tweezers. Aggregation and disaggregation properties of healthy and pathologic (system lupus erythematosis) blood samples are analyzed. Strong difference in aggregation speed and behavior is revealed using the offered method which is proposed to be a promising tool for SLE monitoring at single cell level.

Electrophoretic cell separation by means of microspheres

NASA Technical Reports Server (NTRS)

Smolka, A. J. K.; Nerren, B. H.; Margel, S.; Rembaum, A.

1979-01-01

The electrophoretic mobility of fixed human erythrocytes immunologically labeled with poly(vinylpyridine) or poly(glutaraldehyde) microspheres was reduced by approximately 40%. This observation was utilized in preparative scale electrophoretic separations of fixed human and turkey erythrocytes, the mobilities of which under normal physiological conditions do not differ sufficiently to allow their separation by continuous flow electrophoresis. We suggest that resolution in the electrophoretic separation of cell subpopulations, currently limited by finite and often overlapping mobility distributions, may be significantly enhanced by immunospecific labeling of target populations using microspheres.

An Uncommon Complication With Use of Topical Local Anesthetic Agents: Methemoglobinemia.

PubMed

Panikkath, Ragesh; Panikkath, Deepa; Wischmeyer, Jason

Although the use of topical local anesthetics is generally safe, several potentially fatal complications have been reported. Methemoglobinemia is a rare but potentially fatal complication. Methemoglobin is a naturally occurring oxidized metabolite of hemoglobin, and physiologic levels (<1%) are normal. Methemoglobinemia can be congenital or acquired. Several drugs including topical anesthetic agents like benzocaine can induce this condition. Sudden appearance of cyanosis, with a disproportionately better oxygen saturation of 85% after use of local anesthetics can be a helpful for diagnosis.

Regulating billions of blood platelets: glycans and beyond

PubMed Central

Grozovsky, Renata; Giannini, Silvia; Falet, Hervé

2015-01-01

The human body produces and removes 1011 platelets daily to maintain a normal steady state platelet count. Platelet production must be regulated to avoid spontaneous bleeding or arterial occlusion and organ damage. Multifaceted and complex mechanisms control platelet production and removal in physiological and pathological conditions. This review will focus on different mechanisms of platelet senescence and clearance with specific emphasis on the role of posttranslational modifications. It will also briefly address platelet transfusion and the role of glycans in the clearance of stored platelets. PMID:26330242

[Novel concepts in biology of diffuse endocrine system: results and future investigations].

PubMed

Iaglov, V V; Iaglova, N V

2012-01-01

Diffuse endocrine system is a largest part of endocrine system of vertebrates. Recend findings showed that DES-cells are not neuroectodermal but have ectodermal, mesodermal, and entodermal ontogeny. The article reviews novel concept of diffuse endocrine system anatomy and physiology, functional role of DES hormones and poorly investigated aspects like DES-cell morphology, hormones secretion in normal and pathologic conditions. Further research of diffuse endocrine system has a great significance for biochemistry, morphology, and clinical medicine.

Evaluating acoustic speaker normalization algorithms: evidence from longitudinal child data.

PubMed

Kohn, Mary Elizabeth; Farrington, Charlie

2012-03-01

Speaker vowel formant normalization, a technique that controls for variation introduced by physical differences between speakers, is necessary in variationist studies to compare speakers of different ages, genders, and physiological makeup in order to understand non-physiological variation patterns within populations. Many algorithms have been established to reduce variation introduced into vocalic data from physiological sources. The lack of real-time studies tracking the effectiveness of these normalization algorithms from childhood through adolescence inhibits exploration of child participation in vowel shifts. This analysis compares normalization techniques applied to data collected from ten African American children across five time points. Linear regressions compare the reduction in variation attributable to age and gender for each speaker for the vowels BEET, BAT, BOT, BUT, and BOAR. A normalization technique is successful if it maintains variation attributable to a reference sociolinguistic variable, while reducing variation attributable to age. Results indicate that normalization techniques which rely on both a measure of central tendency and range of the vowel space perform best at reducing variation attributable to age, although some variation attributable to age persists after normalization for some sections of the vowel space. © 2012 Acoustical Society of America

Pivotal advance: CTLA-4+ T cells exhibit normal antiviral functions during acute viral infection.

PubMed

Raué, Hans-Peter; Slifka, Mark K

2007-05-01

Previous studies have shown that T cells, which are genetically deficient in CTLA-4/CD152 expression, will proliferate uncontrollably, resulting in lethal autoimmune disease. This and other evidence indicate that CTLA-4 plays a critical role in the negative regulation of effector T cell function. In contrast to expectations, BrdU incorporation experiments demonstrated that CTLA-4 expression was associated with normal or even enhanced in vivo proliferation of virus-specific CD4+ and CD8+ T cells following acute lymphocytic choriomeningitis virus or vaccinia virus infection. When compared with CTLA-4- T cells directly ex vivo, CTLA-4+ T cells also exhibited normal antiviral effector functions following stimulation with peptide-coated cells, virus-infected cells, plate-bound anti-CD3/anti-CTLA-4, or the cytokines IL-12 and IL-18. Together, this indicates that CTLA-4 does not directly inhibit antiviral T cell expansion or T cell effector functions, at least not under the normal physiological conditions associated with either of these two acute viral infections.

First-Year Medical Students' Naïve Beliefs about Respiratory Physiology

ERIC Educational Resources Information Center

Badenhorst, Elmi; Mamede, Silvia; Abrahams, Amaal; Bugarith, Kishor; Friedling, Jacqui; Gunston, Geney; Kelly-Laubscher, Roisin; Schmidt, Henk G.

2016-01-01

The present study explored the nature and frequency of physiology naïve beliefs by investigating novices' understanding of the respiratory system. Previous studies have shown considerable misconceptions related to physiology but focused mostly on specific physiological processes of normal respiration. Little is known about novices' broader…

Reduced G tolerance associated with supplement use.

PubMed

Barker, Patrick D

2011-02-01

High G forces encountered in tactical military aviation and aerobatic flight produce a host of physiologic responses aimed at preserving cerebral perfusion. The military has instituted measures to augment the physiologic response in order to avoid G-induced loss of consciousness (G-LOC) because of its potential to cause a catastrophic mishap. The case presented here details a Naval Aviator who experienced reduced G tolerance over two successive flights with a temporal relationship of starting a new supplement. Two components of the supplement, coenzyme Q10 and niacin, are highlighted here for their hemodynamic effects. After stopping the supplement the aviator regained his normal G tolerance and had no further issues in flight. There are several factors that can reduce G tolerance and supplement use has to be considered here because of the potential for altering the normal physiological response to increased G force. Our discussion reviews the physiological effects of increased G force, the spectrum of signs of decompensation under the stress of G force, and the potential effects this supplement had on the normal physiological response to increased G force, thus reducing the aviator's G tolerance.

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

PubMed Central

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

2016-01-01

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

Differential distribution of blood and lymphatic vessels in the murine cornea.

PubMed

Ecoiffier, Tatiana; Yuen, Don; Chen, Lu

2010-05-01

Because of its unique characteristics, the cornea has been widely used for blood and lymphatic vessel research. However, whether limbal or corneal vessels are evenly distributed under normal or inflamed conditions has never been studied. The purpose of this study was to investigate this question and to examine whether and how the distribution patterns change during corneal inflammatory lymphangiogenesis (LG) and hemangiogenesis (HG). Corneal inflammatory LG and HG were induced in two most commonly used mouse strains, BALB/c and C57BL/6 (6-8 weeks of age), by a standardized two-suture placement model. Oriented flat-mount corneas together with the limbal tissues were used for immunofluorescence microscope studies. Blood and lymphatic vessels under normal and inflamed conditions were analyzed and quantified to compare their distributions. The data demonstrate, for the first time, greater distribution of both blood and lymphatic vessels in the nasal side in normal murine limbal areas. This nasal-dominant pattern was maintained during corneal inflammatory LG, whereas it was lost for HG. Blood and lymphatic vessels are not evenly distributed in normal limbal areas. Furthermore, corneal LG and HG respond differently to inflammatory stimuli. These new findings will shed some light on corneal physiology and pathogenesis and on the development of experimental models and therapeutic strategies for corneal diseases.

Experimental investigation of the effects of aromatic hydrocarbons on a sediment food web. University research initiative. Final draft report

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

Carman, K.R.; Fleeger, J.W.; Pomarico, S.M.

1994-07-01

The influence of polynuclear aromatic hydrocarbons (PAH) on a sedimentary salt-marsh food web was examined using microcosm and laboratory experiments that simulated natural conditions. Microcosms were dosed with concentrations of PAH-contaminated sediment collected from a produced water site at Pass Fourchon, LA. Bacterial activity and abundance were not influenced by PAH, but microalgal activity and physiological condition were. Grazing by copepods on benthic microalgae was not significantly influenced by PAH concentration, nor was the physiological condition of copepods. Meiofaunal community composition was influenced by PAH, as nematodes became disproportionally abundant, and the nauplius/copepod ratio increased in high-PAH treatments. Overall, sublethalmore » effects of PAH were not pronounced at the concentrations (0.3 to 3.0 ppm) we examined. Fish-predation studies indicated that Leiostomus xanthurus could not detect PAH-contaminated sediments, and continued to feed normally when exposed to them. PAH contamination did not decrease the number of feeding strikes or sediment processing time. This lack of ability to discriminate between contaminated and uncontaminated sediments could have serious implications in terms of bioaccumulation of PAH (or other contaminants) by these bottom-feeding fish.« less

Hypercholesterolemia induces adipose dysfunction in conditions of obesity and nonobesity.

PubMed

Aguilar, David; Fernandez, Maria Luz

2014-09-01

It is well known that hypercholesterolemia can lead to atherosclerosis and coronary heart disease. Adipose tissue represents an active endocrine and metabolic site, which might be involved in the development of chronic disease. Because adipose tissue is a key site for cholesterol metabolism and the presence of hypercholesterolemia has been shown to induce adipocyte cholesterol overload, it is critical to investigate the role of hypercholesterolemia on normal adipose function. Studies in preadipocytes revealed that cholesterol accumulation can impair adipocyte differentiation and maturation by affecting multiple transcription factors. Hypercholesterolemia has been observed to cause adipocyte hypertrophy, adipose tissue inflammation, and disruption of endocrine function in animal studies. Moreover, these effects can also be observed in obesity-independent conditions as confirmed by clinical trials. In humans, hypercholesterolemia disrupts adipose hormone secretion of visfatin, leptin, and adiponectin, adipokines that play a central role in numerous metabolic pathways and regulate basic physiologic responses such as appetite and satiety. Remarkably, treatment with cholesterol-lowering drugs has been shown to restore adipose tissue endocrine function. In this review the role of hypercholesterolemia on adipose tissue differentiation and maturation, as well as on hormone secretion and physiologic outcomes, in obesity and non–obesity conditions is presented.

Neural Correlates of the Binaural Masking Level Difference in Human Frequency-Following Responses.

PubMed

Clinard, Christopher G; Hodgson, Sarah L; Scherer, Mary Ellen

2017-04-01

The binaural masking level difference (BMLD) is an auditory phenomenon where binaural tone-in-noise detection is improved when the phase of either signal or noise is inverted in one of the ears (S π N o or S o N π , respectively), relative to detection when signal and noise are in identical phase at each ear (S o N o ). Processing related to BMLDs and interaural time differences has been confirmed in the auditory brainstem of non-human mammals; in the human auditory brainstem, phase-locked neural responses elicited by BMLD stimuli have not been systematically examined across signal-to-noise ratio. Behavioral and physiological testing was performed in three binaural stimulus conditions: S o N o , S π N o , and S o N π . BMLDs at 500 Hz were obtained from 14 young, normal-hearing adults (ages 21-26). Physiological BMLDs used the frequency-following response (FFR), a scalp-recorded auditory evoked potential dependent on sustained phase-locked neural activity; FFR tone-in-noise detection thresholds were used to calculate physiological BMLDs. FFR BMLDs were significantly smaller (poorer) than behavioral BMLDs, and FFR BMLDs did not reflect a physiological release from masking, on average. Raw FFR amplitude showed substantial reductions in the S π N o condition relative to S o N o and S o N π conditions, consistent with negative effects of phase summation from left and right ear FFRs. FFR amplitude differences between stimulus conditions (e.g., S o N o amplitude-S π N o amplitude) were significantly predictive of behavioral S π N o BMLDs; individuals with larger amplitude differences had larger (better) behavioral B MLDs and individuals with smaller amplitude differences had smaller (poorer) behavioral B MLDs. These data indicate a role for sustained phase-locked neural activity in BMLDs of humans and are the first to show predictive relationships between behavioral BMLDs and human brainstem responses.

[The disease of beta 2-amyloid deposition in the differential diagnosis of juxta-articular subchondral geode lesions].

PubMed

Marri, C; Romagnoli, C; Solano, G; Caldeo, A; Emiliani, G

1993-01-01

Beta-2 amyloidosis deposition is a new type of amyloidosis recently observed in long-term hemodialysis patients. One of the major osteoarticular complications of this disease is the appearance of subchondral bone cysts. In this paper the radiologic features of such radiolucencies are described and the criteria are outlined of the differential diagnosis from the geodes found in other arthropathies or para-physiologic conditions. The importance of the status of the joint space is stressed: on the basis of its patterns, arthropathies may be grouped as follows: inhomogeneous space narrowing in degenerative arthritis; homogeneous space narrowing in inflammatory arthritis; normal or nearly normal joint space if there is no/not-prevalent involvement of articular cartilage.

Research of pulse signal processing based on sleep-monitoring alarm system

NASA Astrophysics Data System (ADS)

Zhang, Kaisheng; Zeng, Yuan

2009-07-01

From pulse diagnosis of Chinese herbalist doctor to the research of cardiovascular system by modem iatrology,they all have showed and proved that human pulse has a good affinity with diseases,especially cardiovascular diseases. Human pulse contains much physical information, and it will be propitious to know the human healthy state early so as to get therapy and recovery early when pulse signal is often detected and analyzed. study how to use the embedded microcontroller to transmit physiological signal from human to personal computer by infrared communication, and the normal sphygmic parameter in one's sleeping is compared with the one measured in order to judge whether one's sleeping condition is normal, finally ascertain the best control plan.

The effect of normalization of Partial Directed Coherence on the statistical assessment of connectivity patterns: a simulation study.

PubMed

Toppi, J; Petti, M; Vecchiato, G; Cincotti, F; Salinari, S; Mattia, D; Babiloni, F; Astolfi, L

2013-01-01

Partial Directed Coherence (PDC) is a spectral multivariate estimator for effective connectivity, relying on the concept of Granger causality. Even if its original definition derived directly from information theory, two modifies were introduced in order to provide better physiological interpretations of the estimated networks: i) normalization of the estimator according to rows, ii) squared transformation. In the present paper we investigated the effect of PDC normalization on the performances achieved by applying the statistical validation process on investigated connectivity patterns under different conditions of Signal to Noise ratio (SNR) and amount of data available for the analysis. Results of the statistical analysis revealed an effect of PDC normalization only on the percentages of type I and type II errors occurred by using Shuffling procedure for the assessment of connectivity patterns. No effects of the PDC formulation resulted on the performances achieved during the validation process executed instead by means of Asymptotic Statistic approach. Moreover, the percentages of both false positives and false negatives committed by Asymptotic Statistic are always lower than those achieved by Shuffling procedure for each type of normalization.

Cardiac considerations in the triathlete.

PubMed

Douglas, P S

1989-10-01

The cardiac adaptation to exercise training produces a variety of adaptations in cardiac size, shape, and function. To further define these changes and to investigate the effects of maximal conditioning, we studied ultraendurance triathletes training for the Hawaii Ironman Triathlon using echocardiography, Doppler ultrasound, and electrocardiography. In this population, the left ventricle (LV) was of normal size but had increased wall thickness and mass. Systolic function was normal and diastolic function was normal or supernormal (increased ratio of rapid to atrial LV filling velocities). The finding of a pattern of concentric hypertrophy was reinforced by a close relationship between submaximal exercise systolic blood pressure and LV mass (r = 0.88). Examination of valvular function by Doppler ultrasound revealed significantly increased prevalences of mitral and tricuspid regurgitation in athletes, with 91% of athletes (vs 38% of controls) having regurgitation detected in at least one cardiac valve. Analysis of athletes using standard electrocardiographic criteria for the detection of left ventricular hypertrophy showed that these criteria did not reliably detect increased mass. However, changes such as marked QRS prolongation and nonvoltage criteria for LV hypertrophy and RV hypertrophy may be useful in separating physiologic from pathologic hypertrophy. Our studies provide additional descriptions of cardiac changes produced by ultraendurance exercise training and suggest that the hemodynamic load imposed by exercise may be a contributing cause to physiologic hypertrophy. Much yet remains to be learned about the cardiac adaptation to exercise training.

Physiological Parameter Response to Variation of Mental Workload.

PubMed

Marinescu, Adrian Cornelius; Sharples, Sarah; Ritchie, Alastair Campbell; Sánchez López, Tomas; McDowell, Michael; Morvan, Hervé P

2018-02-01

To examine the relationship between experienced mental workload and physiological response by noninvasive monitoring of physiological parameters. Previous studies have examined how individual physiological measures respond to changes in mental demand and subjective reports of workload. This study explores the response of multiple physiological parameters and quantifies their added value when estimating the level of demand. The study presented was conducted in laboratory conditions and required participants to perform a visual-motor task that imposed varying levels of demand. The data collected consisted of physiological measurements (heart interbeat intervals, breathing rate, pupil diameter, facial thermography), subjective ratings of workload (Instantaneous Self-Assessment Workload Scale [ISA] and NASA-Task Load Index), and the performance. Facial thermography and pupil diameter were demonstrated to be good candidates for noninvasive workload measurements: For seven out of 10 participants, pupil diameter showed a strong correlation ( R values between .61 and .79 at a significance value of .01) with mean ISA normalized values. Facial thermography measures added on average 47.7% to the amount of variability in task performance explained by a regression model. As with the ISA ratings, the relationship between the physiological measures and performance showed strong interparticipant differences, with some individuals demonstrating a much stronger relationship between workload and performance measures than others. The results presented in this paper demonstrate that physiological and pupil diameter can be used for noninvasive real-time measurement of workload. The methods presented in this article, with current technological capabilities, are better suited for workplaces where the person is seated, offering the possibility of being applied to pilots and air traffic controllers.

Can preeclampsia be considered a renal compartment syndrome? A hypothesis and analysis of the literature.

PubMed

Reuter, David G; Law, Yuk; Levy, Wayne C; Seslar, Stephen P; Zierler, R Eugene; Ferguson, Mark; Chattra, James; McQuinn, Tim; Liu, Lenna L; Terry, Mark; Coffey, Patricia S; Dimer, Jane A; Hanevold, Coral; Flynn, Joseph T; Stapleton, F Bruder

2016-11-01

The morbidity and mortality associated with preeclampsia is staggering. The physiology of the Page kidney, a condition in which increased intrarenal pressure causes hypertension, appears to provide a unifying framework to explain the complex pathophysiology. Page kidney hypertension is renin-mediated acutely and ischemia-mediated chronically. Renal venous outflow obstruction also causes a Page kidney phenomenon, providing a hypothesis for the increased vulnerability of a subset of women who have what we are hypothesizing is a "renal compartment syndrome" due to inadequate ipsilateral collateral renal venous circulation consistent with well-known variation in normal venous anatomy. Dynamic changes in renal venous anatomy and physiology in pregnancy appear to correlate with disease onset, severity, and recurrence. Since maternal recumbent position is well known to affect renal perfusion and since chronic outflow obstruction makes women vulnerable to the ischemic/inflammatory sequelae, heightened awareness of renal compartment syndrome physiology is critical. The anatomic and physiologic insights provide immediate strategies to predict and prevent preeclampsia with straightforward, low-cost interventions that make renewed global advocacy for pregnant women a realistic goal. Copyright © 2016 American Society of Hypertension. Published by Elsevier Inc. All rights reserved.

Sex-Based Differences in Physiology: What Should We Teach in the Medical Curriculum?

ERIC Educational Resources Information Center

Blair, Martha L.

2007-01-01

An abundance of recent research indicates that there are multiple differences between males and females both in normal physiology and in the pathophysiology of disease. The Refresher Course on Gender Differences in Physiology, sponsored by the American Physiological Society Education Committee at the 2006 Experimental Biology Meeting in San…

Three-Dimensional Normal Human Neutral Progenitor Tissue-Like Assemblies: A Model for Persistent Varicella-Zoster Virus Infection and Platform to Study Oxidate Stress and Damage in Multiple Hit Scenarios

NASA Technical Reports Server (NTRS)

Goodwin, Thomas J.; McCarthy, M.; Osterrieder, N.; Cohrs, R. J.; Kaufer, B. B.

2014-01-01

The environment of space results in a multitude of challenges to the human physiology that present barriers to extended habitation and exploration. Over 40 years of investigation to define countermeasures to address space flight adaptation has left gaps in our knowledge regarding mitigation strategies partly due to the lack of investigative tools, monitoring strategies, and real time diagnostics to understand the central causative agent(s) responsible for physiologic adaptation and maintaining homeostasis. Spaceflight-adaptation syndrome is the combination of space environmental conditions and the synergistic reaction of the human physiology. Our work addresses the role of oxidative stress and damage (OSaD) as a negative and contributing Risk Factor (RF) in the following areas of combined spaceflight related dysregulation: i) radiation induced cellular damage [1], [2] ii) immune impacts and the inflammatory response [3], [4] and iii) varicella zoster virus (VZV) reactivation [5]. Varicella-zoster (VZV)/Chicken Pox virus is a neurotropic human alphaherpes virus resulting in varicella upon primary infection, suppressed by the immune system becomes latent in ganglionic neurons, and reactivates under stress events to re-express in zoster and possibly shingles. Our laboratory has developed a complex three-dimensional (3D) normal human neural tissue model that emulates several characteristics of the human trigeminal ganglia (TG) and allows the study of combinatorial experimentation which addresses, simultaneously, OSaD associated with Spaceflight adaptation and habitation [6]. By combining the RFs of microgravity, radiation, and viral infection we will demonstrate that living in the space environment leads to significant physiological consequences for the peripheral and subsequently the central nervous system (PNS, CNS) associated with OSaD generation and consequentially endangers long-duration and exploration-class missions.

Electroencephalogram spindle activity during dexmedetomidine sedation and physiological sleep.

PubMed

Huupponen, E; Maksimow, A; Lapinlampi, P; Särkelä, M; Saastamoinen, A; Snapir, A; Scheinin, H; Scheinin, M; Meriläinen, P; Himanen, S-L; Jääskeläinen, S

2008-02-01

Dexmedetomidine, a selective alpha(2)-adrenoceptor agonist, induces a unique, sleep-like state of sedation. The objective of the present work was to study human electroencephalogram (EEG) sleep spindles during dexmedetomidine sedation and compare them with spindles during normal physiological sleep, to test the hypothesis that dexmedetomidine exerts its effects via normal sleep-promoting pathways. EEG was continuously recorded from a bipolar frontopolar-laterofrontal derivation with Entropy Module (GE Healthcare) during light and deep dexmedetomidine sedation (target-controlled infusions set at 0.5 and 3.2 ng/ml) in 11 healthy subjects, and during physiological sleep in 10 healthy control subjects. Sleep spindles were visually scored and quantitatively analyzed for density, duration, amplitude (band-pass filtering) and frequency content (matching pursuit approach), and compared between the two groups. In visual analysis, EEG activity during dexmedetomidine sedation was similar to physiological stage 2 (S2) sleep with slight to moderate amount of slow-wave activity and abundant sleep spindle activity. In quantitative EEG analyses, sleep spindles were similar during dexmedetomidine sedation and normal sleep. No statistically significant differences were found in spindle density, amplitude or frequency content, but the spindles during dexmedetomidine sedation had longer duration (mean 1.11 s, SD 0.14 s) than spindles in normal sleep (mean 0.88 s, SD 0.14 s; P=0.0014). Analysis of sleep spindles shows that dexmedetomidine produces a state closely resembling physiological S2 sleep in humans, which gives further support to earlier experimental evidence for activation of normal non-rapid eye movement sleep-promoting pathways by this sedative agent.

Pro-apoptotic BIM is an essential initiator of physiological endothelial cell death independent of regulation by FOXO3.

PubMed

Koenig, M N; Naik, E; Rohrbeck, L; Herold, M J; Trounson, E; Bouillet, P; Thomas, T; Voss, A K; Strasser, A; Coultas, L

2014-11-01

The growth of new blood vessels by angiogenesis is essential for normal development, but can also cause or contribute to the pathology of numerous diseases. Recent studies have shown that BIM, a pro-apoptotic BCL2-family protein, is required for endothelial cell apoptosis in vivo, and can contribute to the anti-angiogenic effect of VEGF-A inhibitors in certain tumor models. Despite its importance, the extent to which BIM is autonomously required for physiological endothelial apoptosis remains unknown and its regulation under such conditions is poorly defined. While the transcription factor FOXO3 has been proposed to induce Bim in response to growth factor withdrawal, evidence for this function is circumstantial. We report that apoptosis was reduced in Bim(-/-) primary endothelial cells, demonstrating a cell-autonomous role for BIM in endothelial death following serum and growth factor withdrawal. In conflict with in vitro studies, BIM-dependent endothelial death in vivo did not require FOXO3. Moreover, endothelial apoptosis proceeded normally in mice lacking FOXO-binding sites in the Bim promoter. Bim mRNA was upregulated in endothelial cells starved of serum and growth factors and this was accompanied by the downregulation of miRNAs of the miR-17∼92 cluster. Bim mRNA levels were also elevated in miR-17∼92(+/-) endothelial cells cultured under steady-state conditions, suggesting that miR-17∼92 cluster miRNAs may contribute to regulating overall Bim mRNA levels in endothelial cells.

Tear dynamics in healthy and dry eyes.

PubMed

Cerretani, Colin F; Radke, C J

2014-06-01

Dry-eye disease, an increasingly prevalent ocular-surface disorder, significantly alters tear physiology. Understanding the basic physics of tear dynamics in healthy and dry eyes benefits both diagnosis and treatment of dry eye. We present a physiological-based model to describe tear dynamics during blinking. Tears are compartmentalized over the ocular surface; the blink cycle is divided into three repeating phases. Conservation laws quantify the tear volume and tear osmolarity of each compartment during each blink phase. Lacrimal-supply and tear-evaporation rates are varied to reveal the dependence of tear dynamics on dry-eye conditions, specifically tear osmolarity, tear volume, tear-turnover rate (TTR), and osmotic water flow. Predicted periodic-steady tear-meniscus osmolarity is 309 and 321 mOsM in normal and dry eyes, respectively. Tear osmolarity, volume, and TTR all match available clinical measurements. Osmotic water flow through the cornea and conjunctiva contribute 10 and 50% to the total tear supply in healthy and dry-eye conditions, respectively. TTR in aqueous-deficient dry eye (ADDE) is only half that in evaporative dry eye (EDE). The compartmental periodic-steady tear-dynamics model accurately predicts tear behavior in normal and dry eyes. Inclusion of osmotic water flow is crucial to match measured tear osmolarity. Tear-dynamics predictions corroborate the use of TTR as a clinical discriminator between ADDE and EDE. The proposed model is readily extended to predict the dynamics of aqueous solutes such as drugs or fluorescent tags.

Thin and open vessel windows for intra-vital fluorescence imaging of murine cochlear blood flow

PubMed Central

Shi, Xiaorui; Zhang, Fei; Urdang, Zachary; Dai, Min; Neng, Lingling; Zhang, Jinhui; Chen, Songlin; Ramamoorthy, Sripriya; Nuttall, Alfred L.

2014-01-01

Normal microvessel structure and function in the cochlea is essential for maintaining the ionic and metabolic homeostasis required for hearing function. Abnormal cochlear microcirculation has long been considered an etiologic factor in hearing disorders. A better understanding of cochlear blood flow (CoBF) will enable more effective amelioration of hearing disorders that result from aberrant blood flow. However, establishing the direct relationship between CoBF and other cellular events in the lateral wall and response to physio-pathological stress remains a challenge due to the lack of feasible interrogation methods and difficulty in accessing the inner ear. Here we report on new methods for studying the CoBF in a mouse model using a thin or open vessel-window in combination with fluorescence intra-vital microscopy (IVM). An open vessel-window enables investigation of vascular cell biology and blood flow permeability, including pericyte (PC) contractility, bone marrow cell migration, and endothelial barrier leakage, in wild type and fluorescent protein-labeled transgenic mouse models with high spatial and temporal resolution. Alternatively, the thin vessel-window method minimizes disruption of the homeostatic balance in the lateral wall and enables study CoBF under relatively intact physiological conditions. A thin vessel-window method can also be used for time-based studies of physiological and pathological processes. Although the small size of the mouse cochlea makes surgery difficult, the methods are sufficiently developed for studying the structural and functional changes in CoBF under normal and pathological conditions. PMID:24780131

Probiotics normalize the gut-brain-microbiota axis in immunodeficient mice.

PubMed

Smith, Carli J; Emge, Jacob R; Berzins, Katrina; Lung, Lydia; Khamishon, Rebecca; Shah, Paarth; Rodrigues, David M; Sousa, Andrew J; Reardon, Colin; Sherman, Philip M; Barrett, Kim E; Gareau, Mélanie G

2014-10-15

The gut-brain-microbiota axis is increasingly recognized as an important regulator of intestinal physiology. Exposure to psychological stress causes activation of the hypothalamic-pituitary-adrenal (HPA) axis and causes altered intestinal barrier function, intestinal dysbiosis, and behavioral changes. The primary aim of this study was to determine whether the effects of psychological stress on intestinal physiology and behavior, including anxiety and memory, are mediated by the adaptive immune system. Furthermore, we wanted to determine whether treatment with probiotics would normalize these effects. Here we demonstrate that B and T cell-deficient Rag1(-/-) mice displayed altered baseline behaviors, including memory and anxiety, accompanied by an overactive HPA axis, increased intestinal secretory state, dysbiosis, and decreased hippocampal c-Fos expression. Both local (intestinal physiology and microbiota) and central (behavioral and hippocampal c-Fos) changes were normalized by pretreatment with probiotics, indicating an overall benefit on health conferred by changes in the microbiota, independent of lymphocytes. Taken together, these findings indicate a role for adaptive immune cells in maintaining normal intestinal and brain health in mice and show that probiotics can overcome this immune-mediated deficit in the gut-brain-microbiota axis. Copyright © 2014 the American Physiological Society.

pH regulators in invadosomal functioning: proton delivery for matrix tasting.

PubMed

Brisson, Lucie; Reshkin, Stephan J; Goré, Jacques; Roger, Sébastien

2012-01-01

Invadosomes are actin-rich finger-like cellular structures sensing and interacting with the surrounding extracellular matrix (ECM) and involved in its proteolytic remodeling. Invadosomes are structures distinct from other adhesion complexes, and have been identified in normal cells that have to cross tissue barriers to fulfill their function such as leukocytes, osteoclasts and endothelial cells. They also represent features of highly aggressive cancer cells, allowing them to escape from the primary tumor, to invade surrounding tissues and to reach systemic circulation. They are localized to the ventral membrane of cells grown under 2-dimensional conditions and are supposed to be present all around cells grown in 3-dimensional matrices. Indeed invadosomes are key structures in physiological processes such as inflammation and the immune response, bone remodeling, tissue repair, but also in pathological conditions such as osteopetrosis and the development of metastases. Invadosomes are subdivided into podosomes, found in normal cells, and into invadopodia specific for cancer cells. While these two structures exhibit differences in organization, size, number and half-life, they share similarities in molecular composition, participation in cell-matrix adhesion and promoting matrix degradation. A key determinant in invadosomal function is the recruitment and release of proteases, such as matrix metalloproteinases (MMPs), serine proteases and cysteine cathepsins, together with their activation in a tightly controlled and highly acidic microenvironment. Therefore numerous pH regulators such as V-ATPases and Na(+)/H(+) exchangers, are found in invadosomes and are directly involved in their constitution as well as their functioning. This review focuses on the participation of pH regulators in invadosome function in physiological and pathological conditions, with a particular emphasis on ECM remodeling by osteoclasts during bone resorption and by cancer cells. Copyright © 2012 Elsevier GmbH. All rights reserved.

Engineering mechanical gradients in next generation biomaterials - Lessons learned from medical textile design.

PubMed

Ng, Joanna L; Collins, Ciara E; Knothe Tate, Melissa L

2017-07-01

Nonwoven and textile membranes have been applied both externally and internally to prescribe boundary conditions for medical conditions as diverse as oedema and tissue defects. Incorporation of mechanical gradients in next generation medical membrane design offers great potential to enhance function in a dynamic, physiological context. Yet the gradient properties and resulting mechanical performance of current membranes are not well described. To bridge this knowledge gap, we tested and compared the mechanical properties of bounding membranes used in both external (compression sleeves for oedema, exercise bands) and internal (surgical membranes) physiological contexts. We showed that anisotropic compression garment textiles, isotropic exercise bands and surgical membranes exhibit similar ranges of resistance to tension under physiologic strains. However, their mechanical gradients and resulting stress-strain relationships show differences in work capacity and energy expenditure. Exercise bands' moduli of elasticity and respective thicknesses allow for controlled, incremental increases in loading to facilitate healing as injured tissues return to normal structure and function. In contrast, the gradients intrinsic to compression sleeve design exhibit gaps in the middle range (1-5N) of physiological strains and also inconsistencies along the length of the sleeve, resulting in less than optimal performance of these devices. These current shortcomings in compression textile and garment design may be addressed in the future through implementation of novel approaches. For example, patterns, fibre compositions, and fibre anisotropy can be incorporated into biomaterial design to achieve seamless mechanical gradients in structure and resulting dynamic function, which would be particularly useful in physiological contexts. These concepts can be applied further to biomaterial design to deliver pressure gradients during movement of oedematous limbs (compression garments) and facilitate transport of molecules and cells during tissue genesis within tissue defects (surgical membranes). External and internal biomaterial membranes prescribe boundary conditions for treatment of medical disorders, from oedema to tissue defects. Studies are needed to guide the design of next generation biomaterials and devices that incorporate gradient engineering approaches, which offer great potential to enhance function in a dynamic and physiological context. Mechanical gradients intrinsic to currently implemented biomaterials such as medical textiles and surgical interface membranes are poorly understood. Here we characterise quantitatively the mechanics of textile and nonwoven biomaterial membranes for external and internal use. The lack of seamless gradients in compression medical textiles contrasts with the graded mechanical effects achieved by elastomeric exercise bands, which are designed to deliver controlled, incremental increases in loading to facilitate healing as injured tissues return to normal structure and function. Engineering textiles with a prescient choice of fibre composition/size, type of knit/weave and inlay fibres, and weave density/anisotropy will enable creation of fabrics that can deliver spatially and temporally controlled mechanical gradients to maintain force balances at tissue boundaries, e.g. to treat oedema or tissue defects. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Potassium up-regulates antioxidant metabolism and alleviates growth inhibition under water and osmotic stress in wheat (Triticum aestivum L).

PubMed

Ahanger, Mohammad Abass; Agarwal, R M

2017-07-01

Pot experiments were conducted to find out the effectivity of K on Triticum aestivum L cultivars. Polyethylene glycol 6000 (PEG 6000) was used as an osmoticum to induce osmotic stress under sand culture setting up the water potential of external solution at -3 and -5 bars. In pots, plants were raised under restricted and normal irrigation and K was applied in varying doses (0, 20, 40, 60 kg ha -1 ) and estimation of different physiological and biochemical parameters was done at two developmental stages, i.e., preflowering and flowering. Supplementation of K resulted in obvious increase in growth and activity of antioxidant enzymes in both normal and stressed plants. Added potassium increased total phenols and tannins thereby strengthening the components of both the enzymatic as well as non-enzymatic antioxidant system. Under both normal and stressed conditions, K-fed plants experienced significant increase in the synthesis of osmolytes like free proline, amino acids, and sugars which assumes special significance in growth under water stress conditions. Wheat plants accumulating greater K were able to counteract the water stress-induced changes by maintaining lower Na/K ratio.

Gold nanoparticles as physiological markers of urine internalization into urothelial cells in vivo

PubMed Central

Hudoklin, Samo; Zupančič, Daša; Makovec, Darko; Kreft, Mateja Erdani; Romih, Rok

2013-01-01

Background Urothelial bladder is the reservoir of urine and the urothelium minimizes the exchange of urine constituents with this tissue. Our aim was to test 1.9 nm biocompatible gold nanoparticles as a novel marker of internalization into the urothelial cells under physiological conditions in vivo. Methods We compared normal and neoplastic mice urothelium. Neoplastic lesions were induced by 0.05% N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) in drinking water for 10 weeks. Nanoparticles, intravenously injected into normal and BBN-treated mice, were filtered through the kidneys and became constituents of the urine within 90 minutes after injection. Results Gold nanoparticles were densely accumulated in the urine, while their internalization into urothelial cells depended on the cell differentiation stage. In the terminally differentiated superficial urothelial cells of normal animals, nanoparticles were occasionally found in the endosomes, but not in the fusiform vesicles. Regions of exfoliated cells were occasionally found in the normal urothelium. Superficial urothelial cells located next to exfoliated regions contained gold nanoparticles in the endosomes and in the cytosol beneath the apical plasma membrane. The urothelium of BBN-treated animals developed fat hyperplasia with moderate dysplasia. The superficial cells of BBN-treated animals were partially differentiated as demonstrated by the lack of fusiform vesicles. These cells contained the gold nanoparticles distributed in the endosomes and throughout their cytosol. Conclusion Gold nanoparticles are a valuable marker to study urine internalization into urothelial cells in vivo. Moreover, they can be used as a sensitive marker of differentiation and functionality of urothelial cells. PMID:24143099

Stirring images: fear, not happiness or arousal, makes art more sublime.

PubMed

Eskine, Kendall J; Kacinik, Natalie A; Prinz, Jesse J

2012-10-01

Which emotions underlie our positive experiences of art? Although recent evidence from neuroscience suggests that emotions play a critical role in art perception, no research to date has explored the extent to which specific emotional states affect aesthetic experiences or whether general physiological arousal is sufficient. Participants were assigned to one of five conditions-sitting normally, engaging in 15 or 30 jumping jacks, or viewing a happy or scary video-prior to rating abstract works of art. Only the fear condition resulted in significantly more positive judgments about the art. These striking findings provide the first evidence that fear uniquely inspires positively valenced aesthetic judgments. The results are discussed in the context of embodied cognition.

Sodium chloride stress induced morphological and ultrastructural changes in Aspergillus repens.

PubMed

Kelavkar, U; Rao, K S; Ghhatpar, H S

1993-06-01

Halotolerant fungus, A. repens, showed a considerable difference in its growth rate, morphology, ultrastructural and molecular composition under NaCl stress as compared to control i.e. non-stressed condition. Light microscopic observations revealed significant differences in their mycelial thickness, their branching and septa. Transmission electron microscopic observations of both the conditions depicted significant differences in the qualitative and quantitative changes in mitochondria. Frequent pinocytotic vesiculation (vacuoles) of plasma membrane was observed in fungus under stress but no such vesiculation in control. The multivesiculate structures observed under stress with their origin from the cell membranes and subsequent release into vacuoles have not been reported in fungi under normal physiological conditions. The observations on pinocytosis are discussed in relation to ion compartmentation and salt tolerance in A. repens.

Group management influences reproductive function of the male cheetah (Acinonyx jubatus).

PubMed

Koester, Diana C; Freeman, Elizabeth W; Wildt, David E; Terrell, Kimberly A; Franklin, Ashley D; Meeks, Karen; Crosier, Adrienne E

2017-03-01

Although the free-ranging cheetah is generally socially solitary, as many as 60% of males live in same-sex (usually sibling) coalitions. Under ex situ conditions, the cheetah experiences low reproductive success with only ~18% of males having ever produced young. Most male cheetahs (85%) are managed in captivity in coalitions, but with no data on the influence of social grouping on reproductive parameters. We examined the influence of singleton versus coalition management on various male cheetah physiological traits, including ejaculate quality and gonadal and adrenal hormone metabolite concentrations. We also assessed behaviour within coalitions for evidence of social hierarchy through initiation of interactions with group mates and relatedness to physiological traits. Ejaculate quality (including total motile and structurally normal spermatozoa per ejaculate) and androgen concentration profiles were higher (P<0.05) in coalition compared with singleton males. These results support the conclusion that testis function in the cheetah, specifically related to the development of normal, motile spermatozoa and androgen production, is influenced by management with same-sex conspecifics. The findings have implications for ex situ conservation breeding programs by suggesting that reproductive quality can be enhanced through group maintenance of cheetah males.

Broad AOX expression in a genetically tractable mouse model does not disturb normal physiology

PubMed Central

Szibor, Marten; Dhandapani, Praveen K.; Dufour, Eric; Holmström, Kira M.; Zhuang, Yuan; Salwig, Isabelle; Wittig, Ilka; Heidler, Juliana; Gizatullina, Zemfira; Fuchs, Helmut; Gailus-Durner, Valérie; de Angelis, Martin Hrabě; Nandania, Jatin; Velagapudi, Vidya; Wietelmann, Astrid; Rustin, Pierre; Gellerich, Frank N.; Braun, Thomas

2017-01-01

ABSTRACT Plants and many lower organisms, but not mammals, express alternative oxidases (AOXs) that branch the mitochondrial respiratory chain, transferring electrons directly from ubiquinol to oxygen without proton pumping. Thus, they maintain electron flow under conditions when the classical respiratory chain is impaired, limiting excess production of oxygen radicals and supporting redox and metabolic homeostasis. AOX from Ciona intestinalis has been used to study and mitigate mitochondrial impairments in mammalian cell lines, Drosophila disease models and, most recently, in the mouse, where multiple lentivector-AOX transgenes conferred substantial expression in specific tissues. Here, we describe a genetically tractable mouse model in which Ciona AOX has been targeted to the Rosa26 locus for ubiquitous expression. The AOXRosa26 mouse exhibited only subtle phenotypic effects on respiratory complex formation, oxygen consumption or the global metabolome, and showed an essentially normal physiology. AOX conferred robust resistance to inhibitors of the respiratory chain in organello; moreover, animals exposed to a systemically applied LD50 dose of cyanide did not succumb. The AOXRosa26 mouse is a useful tool to investigate respiratory control mechanisms and to decipher mitochondrial disease aetiology in vivo. PMID:28067626

Ultradian rhythmicity of plasma cortisol is necessary for normal emotional and cognitive responses in man.

PubMed

Kalafatakis, K; Russell, G M; Harmer, C J; Munafo, M R; Marchant, N; Wilson, A; Brooks, J C; Durant, C; Thakrar, J; Murphy, P; Thai, N J; Lightman, S L

2018-04-24

Glucocorticoids (GCs) are secreted in an ultradian, pulsatile pattern that emerges from delays in the feedforward-feedback interaction between the anterior pituitary and adrenal glands. Dynamic oscillations of GCs are critical for normal cognitive and metabolic function in the rat and have been shown to modulate the pattern of GC-sensitive gene expression, modify synaptic activity, and maintain stress responsiveness. In man, current cortisol replacement therapy does not reproduce physiological hormone pulses and is associated with psychopathological symptoms, especially apathy and attenuated motivation in engaging with daily activities. In this work, we tested the hypothesis that the pattern of GC dynamics in the brain is of crucial importance for regulating cognitive and behavioral processes. We provide evidence that exactly the same dose of cortisol administered in different patterns alters the neural processing underlying the response to emotional stimulation, the accuracy in recognition and attentional bias toward/away from emotional faces, the quality of sleep, and the working memory performance of healthy male volunteers. These data indicate that the pattern of the GC rhythm differentially impacts human cognition and behavior under physiological, nonstressful conditions and has major implications for the improvement of cortisol replacement therapy.

A systematic survey of lipids across mouse tissues

PubMed Central

Jain, Mohit; Ngoy, Soeun; Sheth, Sunil A.; Swanson, Raymond A.; Rhee, Eugene P.; Liao, Ronglih; Clish, Clary B.; Mootha, Vamsi K.

2014-01-01

Lipids are a diverse collection of macromolecules essential for normal physiology, but the tissue distribution and function for many individual lipid species remain unclear. Here, we report a mass spectrometry survey of lipid abundance across 18 mouse tissues, detecting ∼1,000 mass spectrometry features, of which we identify 179 lipids from the glycerolipids, glycerophospholipids, lysophospholipids, acylcarnitines, sphingolipids, and cholesteryl ester classes. Our data reveal tissue-specific organization of lipids and can be used to generate testable hypotheses. For example, our data indicate that circulating triglycerides positively and negatively associated with future diabetes in humans are enriched in mouse adipose tissue and liver, respectively, raising hypotheses regarding the tissue origins of these diabetes-associated lipids. We also integrate our tissue lipid data with gene expression profiles to predict a number of substrates of lipid-metabolizing enzymes, highlighting choline phosphotransferases and sterol O-acyltransferases. Finally, we identify several tissue-specific lipids not present in plasma under normal conditions that may be of interest as biomarkers of tissue injury, and we show that two of these lipids are released into blood following ischemic brain injury in mice. This resource complements existing compendia of tissue gene expression and may be useful for integrative physiology and lipid biology. PMID:24518676

[Results of a dynamic study on the status of health and nutrition of a Siberian vegan settlement].

PubMed

Medkova, I L; Mosiakina, L I; Biriukova, L S

2001-01-01

In 1996 for the first time a study of state of health, living conditions and nutrition status of 84 persons from the Siberian settlement of the rigorous vegetarians--vegans and 26 aboriginal inhabitants who feed on a traditional mixed diet was carried out. The clinical and laboratory investigations are kept. The positive influencing vegan ration on a serum lipids, body weight, state of cardiovascular system was showed. The contents of vitamin B12 and serum iron in vegans was in normal physiological range. The level of blood calcium was reduced in comparison with control. Increased contents of copper and zinc in blood was marked both in vegans and in control group. The repeated examination of 77 vegans of the same settlement in 1999 has revealed positive alterations in serum lipids: augmentation of cholesterol of high density lipoproteins on the average on 54.3%, that result in a reliable decrease of atherogenicity coefficient. The decrease to normal amounts of blood copper and zinc, and also increase of blood calcium on the average on 16% was marked. However level of calcium remained below than physiological values.

Translational neurocardiology: preclinical models and cardioneural integrative aspects.

PubMed

Ardell, J L; Andresen, M C; Armour, J A; Billman, G E; Chen, P-S; Foreman, R D; Herring, N; O'Leary, D S; Sabbah, H N; Schultz, H D; Sunagawa, K; Zucker, I H

2016-07-15

Neuronal elements distributed throughout the cardiac nervous system, from the level of the insular cortex to the intrinsic cardiac nervous system, are in constant communication with one another to ensure that cardiac output matches the dynamic process of regional blood flow demand. Neural elements in their various 'levels' become differentially recruited in the transduction of sensory inputs arising from the heart, major vessels, other visceral organs and somatic structures to optimize neuronal coordination of regional cardiac function. This White Paper will review the relevant aspects of the structural and functional organization for autonomic control of the heart in normal conditions, how these systems remodel/adapt during cardiac disease, and finally how such knowledge can be leveraged in the evolving realm of autonomic regulation therapy for cardiac therapeutics. © 2016 The Authors. The Journal of Physiology © 2016 The Physiological Society.

Physiological effects of bioceramic material: harvard step, resting metabolic rate and treadmill running assessments.

PubMed

Leung, Ting-Kai; Kuo, Chia-Hua; Lee, Chi-Ming; Kan, Nai-Wen; Hou, Chien-Wen

2013-12-31

Previous biomolecular and animal studies have shown that a room-temperature far-infrared-rayemitting ceramic material (bioceramic) demonstrates physical-biological effects, including the normalization of psychologically induced stress-conditioned elevated heart rate in animals. In this clinical study, the Harvard step test, the resting metabolic rate (RMR) assessment and the treadmill running test were conducted to evaluate possible physiological effects of the bioceramic material in human patients. The analysis of heart rate variability (HRV) during the Harvard step test indicated that the bioceramic material significantly increased the high-frequency (HF) power spectrum. In addition, the results of RMR analysis suggest that the bioceramic material reduced oxygen consumption (VO2). Our results demonstrate that the bioceramic material has the tendency to stimulate parasympathetic responses, which may reduce resting energy expenditure and improve cardiorespiratory recovery following exercise.

Three-Dimensional Normal Human Neural Progenitor Tissue-Like Assemblies: A Model for Persistent Varicell-Zoster Virus Infection and Platform to Study Viral Infectivity and Oxidative Stress and Damage

NASA Technical Reports Server (NTRS)

Goodwin, T. J.; McCarthy, M.; Osterrieder, N.; Cohrs, R. J.; Kaufer, B. B.

2014-01-01

The environment of space results in a multitude of challenges to the human physiology that present barriers to extended habitation and exploration. Over 40 years of investigation to define countermeasures to address space flight adaptation has left gaps in our knowledge regarding mitigation strategies partly due to the lack of investigative tools, monitoring strategies, and real time diagnostics to understand the central causative agent(s) responsible for physiologic adaptation and maintaining homeostasis. Spaceflight-adaptation syndrome is the combination of space environmental conditions and the synergistic reaction of the human physiology. Our work addresses the role of oxidative stress and damage (OSaD) as a negative and contributing Risk Factor (RF) in the following areas of combined spaceflight related dysregulation: i) radiation induced cellular damage [1], [2] ii) immune impacts and the inflammatory response [3], [4] and iii) varicella zoster virus (VZV) reactivation [5]. Varicella-zoster (VZV)/Chicken Pox virus is a neurotropic human alphaherpesvirus resulting in varicella upon primary infection, suppressed by the immune system becomes latent in ganglionic neurons, and reactivates under stress events to re-express in zoster and possibly shingles. Our laboratory has developed a complex threedimensional (3D) normal human neural tissue model that emulates several characteristics of the human trigeminal ganglia (TG) and allows the study of combinatorial experimentation which addresses, simultaneously, OSaD associated with Spaceflight adaptation and habitation [6].

Extracellular calcium controls the expression of two different forms of ripple-like hippocampal oscillations.

PubMed

Aivar, Paloma; Valero, Manuel; Bellistri, Elisa; Menendez de la Prida, Liset

2014-02-19

Hippocampal high-frequency oscillations (HFOs) are prominent in physiological and pathological conditions. During physiological ripples (100-200 Hz), few pyramidal cells fire together coordinated by rhythmic inhibitory potentials. In the epileptic hippocampus, fast ripples (>200 Hz) reflect population spikes (PSs) from clusters of bursting cells, but HFOs in the ripple and the fast ripple range are vastly intermixed. What is the meaning of this frequency range? What determines the expression of different HFOs? Here, we used different concentrations of Ca(2+) in a physiological range (1-3 mM) to record local field potentials and single cells in hippocampal slices from normal rats. Surprisingly, we found that this sole manipulation results in the emergence of two forms of HFOs reminiscent of ripples and fast ripples recorded in vivo from normal and epileptic rats, respectively. We scrutinized the cellular correlates and mechanisms underlying the emergence of these two forms of HFOs by combining multisite, single-cell and paired-cell recordings in slices prepared from a rat reporter line that facilitates identification of GABAergic cells. We found a major effect of extracellular Ca(2+) in modulating intrinsic excitability and disynaptic inhibition, two critical factors shaping network dynamics. Moreover, locally modulating the extracellular Ca(2+) concentration in an in vivo environment had a similar effect on disynaptic inhibition, pyramidal cell excitability, and ripple dynamics. Therefore, the HFO frequency band reflects a range of firing dynamics of hippocampal networks.

Monitoring environmental state of Alaskan forests with AIRSAR

NASA Technical Reports Server (NTRS)

Mcdonald, Kyle C.; Way, Jobea; Rignot, Eric; Williams, Cindy; Viereck, Les; Adams, Phylis

1992-01-01

During March 1988 and May 1991, the JPL airborne synthetic aperture radar, AIRSAR, collected sets of multi-temporal imagery of the Bonanza Creek Experimental Forest near Fairbanks, Alaska. These data sets consist of series of multi-polarized images collected at P-, L-, and C-bands each over a period of a few days. The AIRSAR campaigns were complemented with extensive ground measurements that included observations of both static canopy characteristics such as forest architecture as well as properties that vary on short term time scales such as canopy dielectric conditions. Observations exist for several stands of deciduous and coniferous species including white spruce (Picea glauca), black spruce (Picea mariana), and balsam poplar (Populus balsamifera). Although the duration of each campaign was fairly short, significant changes in environmental conditions caused notable variations in the physiological state of the canopies. During the 1988 campaign, environmental conditions ranged from unseasonably warm to more normal subfreezing temperatures. This permitted AIRSAR observations of frozen and thawed canopy states. During May 1991, ice jams that occurred along the river caused many stands to flood while the subsequent clearing of the river then allowed the waters to recede, leaving a snow covered ground surface. This allowed observations of several stands during both flooded and nonflooded conditions. Furthermore, the local weather varied from clear sunny days to heavy overcast days with some occurrence of rain. Measurements of leaf water potential indicated that this caused significant variations in canopy water status, allowing SAR observations of water stressed and unstressed trees. Mean backscatter from several stands is examined for the various canopy physiological states. The changes in canopy backscatter that occur as a function of environmental and physiological state are analyzed. Preliminary results of a backscatter signature modeling analysis are presented. The implications of using SAR to monitor canopy phenological state are addressed.

Implantable biosensors: analysis of fluorescent light propagation through skin

NASA Astrophysics Data System (ADS)

O'Neal, D. P.; McShane, Michael J.; Pishko, Michael V.; Cote, Gerard L.

2001-06-01

Progress towards a painless and hygienic glucose monitoring procedure for diabetics continues as the growth of diabetes mellitus reaches epidemic proportions in the American population. Utilizing an implantable fluorescence based glucose assay, the minimally invasive approach presented here has previously shown promise towards this goal in terms of glucose specificity and quantification for in vitro environments. However, in realistic physiological circumstances the depth of the implant can vary and optical properties of skin can change due to normal physiological conditions. Additionally, naturally occurring auto-fluorescence can obscure the sensor signal. An important concern under these conditions is that variations of fluorescent intensity due to these or other causes might be mistaken for glucose concentration fluctuations. New data shows that fluorescence-based glucose assays can be probed and interpreted in terms of glucose concentrations through pig skin at depths of up to 700 mm when immobilized in a bio-compatible polymer. When a combination of two fluorophores are employed as demonstrated here, reasonable changes in skin thickness and the confounding effects of the variations inherent in skin can be overcome for this glucose sensing application.

Measuring listening-related effort and fatigue in school-aged children using pupillometry.

PubMed

McGarrigle, Ronan; Dawes, Piers; Stewart, Andrew J; Kuchinsky, Stefanie E; Munro, Kevin J

2017-09-01

Stress and fatigue from effortful listening may compromise well-being, learning, and academic achievement in school-aged children. The aim of this study was to investigate the effect of a signal-to-noise ratio (SNR) typical of those in school classrooms on listening effort (behavioral and pupillometric) and listening-related fatigue (self-report and pupillometric) in a group of school-aged children. A sample of 41 normal-hearing children aged 8-11years performed a narrative speech-picture verification task in a condition with recommended levels of background noise ("ideal": +15dB SNR) and a condition with typical classroom background noise levels ("typical": -2dB SNR). Participants showed increased task-evoked pupil dilation in the typical listening condition compared with the ideal listening condition, consistent with an increase in listening effort. No differences were found between listening conditions in terms of performance accuracy and response time on the behavioral task. Similarly, no differences were found between listening conditions in self-report and pupillometric markers of listening-related fatigue. This is the first study to (a) examine listening-related fatigue in children using pupillometry and (b) demonstrate physiological evidence consistent with increased listening effort while listening to spoken narratives despite ceiling-level task performance accuracy. Understanding the physiological mechanisms that underpin listening-related effort and fatigue could inform intervention strategies and ultimately mitigate listening difficulties in children. Copyright © 2017 Elsevier Inc. All rights reserved.

Fibroblast-matrix interplay: Nintedanib and pirfenidone modulate the effect of IPF fibroblast-conditioned matrix on normal fibroblast phenotype.

PubMed

Epstein Shochet, Gali; Wollin, Lutz; Shitrit, David

2018-03-12

Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease with poor prognosis. Activated fibroblasts are the key effector cells in fibrosis, producing excessive amounts of collagen and extracellular matrix (ECM) proteins. Whether the ECM conditioned by IPF fibroblasts determines the phenotype of naïve fibroblasts is difficult to explore. IPF-derived primary fibroblasts were cultured on Matrigel and then cleared using ammonium hydroxide, creating an IPF-conditioned matrix (CM). Normal fibroblast CM served as control. Normal fibroblasts were cultured on both types of CM, and cell count, cell distribution and markers of myofibroblast differentiation; transforming growth factor beta (TGFβ) signalling; and ECM expression were assessed. The effects of the anti-fibrotic drugs nintedanib and pirfenidone at physiologically relevant concentrations were also explored. Normal fibroblasts cultured on IPF-CM arranged in large aggregates as a result of increased proliferation and migration. Moreover, increased levels of pSmad3, pSTAT3 (phospho signal transducer and activator of transcription 3), alpha smooth muscle actin (αSMA) and Collagen1a were found, suggesting a differentiation towards a myofibroblast-like phenotype. SB505124 (10 μmol/L) partially reversed these alterations, suggesting a TGFβ contribution. Furthermore, nintedanib at 100 nmol/L and, to a lesser extent, pirfenidone at 100 μmol/L prevented the IPF-CM-induced fibroblast phenotype alterations, suggesting an attenuation of the ECM-fibroblast interplay. IPF fibroblasts alter the ECM, thus creating a CM that further propagates an IPF-like phenotype in normal fibroblasts. This assay demonstrated differences in drug activities for approved IPF drugs at clinically relevant concentrations. Thus, the matrix-fibroblast phenotype interplay might be a relevant assay to explore drug candidates for IPF treatment. © 2018 Asian Pacific Society of Respirology.

The Effect of Simulated Microgravity Environment of RWV Bioreactors on Surface Reactions and Adsorption of Serum Proteins on Bone-bioactive Microcarriers

NASA Technical Reports Server (NTRS)

Radin, Shula; Ducheyne, P.; Ayyaswamy, P. S.

2003-01-01

Biomimetically modified bioactive materials with bone-like surface properties are attractive candidates for use as microcarriers for 3-D bone-like tissue engineering under simulated microgravity conditions of NASA designed rotating wall vessel (RWV) bioreactors. The simulated microgravity environment is attainable under suitable parametric conditions of the RWV bioreactors. Ca-P containing bioactive glass (BG), whose stimulatory effect on bone cell function had been previously demonstrated, was used in the present study. BG surface modification via reactions in solution, resulting formation of bone-like minerals at the surface and adsorption of serum proteins is critical for obtaining the stimulatory effect. In this paper, we report on the major effects of simulated microgravity conditions of the RWV on the BG reactions surface reactions and protein adsorption in physiological solutions. Control tests at normal gravity were conducted at static and dynamic conditions. The study revealed that simulated microgravity remarkably enhanced reactions involved in the BG surface modification, including BG dissolution, formation of bone-like minerals at the surface and adsorption of serum proteins. Simultaneously, numerical models were developed to simulate the mass transport of chemical species to and from the BG surface under normal gravity and simulated microgravity conditions. The numerical results showed an excellent agreement with the experimental data at both testing conditions.

Insulin-producing cells could not mimic the physiological regulation of insulin secretion performed by pancreatic beta cells

PubMed Central

2013-01-01

Objective The aim of this study was to compare the difference between insulin-producing cells (IPCs) and normal human pancreatic beta cells both in physiological function and morphological features in cellular level. Methods The levels of insulin secretion were measured by enzyme-linked immunosorbent assay. The insulin gene expression was determined by real-time quantitative polymerase chain reaction. The morphological features were detected by atomic force microscopy (AFM) and laser confocal scanning microscopy. Results IPCs and normal human pancreatic beta cells were similar to each other under the observation in AFM with the porous structure features in the cytoplasm. Both number of membrane particle size and average roughness of normal human beta cells were higher than those of IPCs. Conclusions Our results firstly revealed that the cellular ultrastructure of IPCs was closer to that of normal human pancreatic beta cells, but they still could not mimic the physiological regulation of insulin secretion performed by pancreatic beta cells. PMID:23421382

Protein S-nitrosylation as a therapeutic target for neurodegenerative diseases

PubMed Central

Nakamura, Tomohiro; Lipton, Stuart A.

2015-01-01

At physiological levels, nitric oxide (NO) contributes to the maintenance of normal neuronal activity and survival, thus serving as an important regulatory mechanism in the central nervous system. In contrast, accumulating evidence suggests that exposure to environmental toxins or the normal aging process can trigger excessive production of reactive oxygen/nitrogen species (such as NO), contributing to the etiology of several neurodegenerative diseases. Here we highlight protein S-nitrosylation, resulting from covalent attachment of an NO group to a cysteine thiol of the target protein, as a ubiquitous effector of NO signaling in both health and disease. We review our current understanding of this redox-dependent posttranslational modification under neurodegenerative conditions, and evaluate how targeting dysregulated protein S-nitrosylation can lead to novel therapeutics. PMID:26707925

Normal Values of Tissue-Muscle Perfusion Indexes of Lower Limbs Obtained with a Scintigraphic Method.

PubMed

Manevska, Nevena; Stojanoski, Sinisa; Pop Gjorceva, Daniela; Todorovska, Lidija; Miladinova, Daniela; Zafirova, Beti

2017-09-01

Introduction Muscle perfusion is a physiologic process that can undergo quantitative assessment and thus define the range of normal values of perfusion indexes and perfusion reserve. The investigation of the microcirculation has a crucial role in determining the muscle perfusion. Materials and method The study included 30 examinees, 24-74 years of age, without a history of confirmed peripheral artery disease and all had normal findings on Doppler ultrasonography and pedo-brachial index of lower extremity (PBI). 99mTc-MIBI tissue muscle perfusion scintigraphy of lower limbs evaluates tissue perfusion in resting condition "rest study" and after workload "stress study", through quantitative parameters: Inter-extremity index (for both studies), left thigh/right thigh (LT/RT) left calf/right calf (LC/RC) and perfusion reserve (PR) for both thighs and calves. Results In our investigated group we assessed the normal values of quantitative parameters of perfusion indexes. Indexes ranged for LT/RT in rest study 0.91-1.05, in stress study 0.92-1.04. LC/RC in rest 0.93-1.07 and in stress study 0.93-1.09. The examinees older than 50 years had insignificantly lower perfusion reserve of these parameters compared with those younger than 50, LC (p=0.98), and RC (p=0.6). Conclusion This non-invasive scintigraphic method allows in individuals without peripheral artery disease to determine the range of normal values of muscle perfusion at rest and stress condition and to clinically implement them in evaluation of patients with peripheral artery disease for differentiating patients with normal from those with impaired lower limbs circulation.

Electrophoretic cell separation by means of immunomicrospheres

NASA Technical Reports Server (NTRS)

Rembaum, A.; Smolka, A. J. K.

1980-01-01

The electrophoretic mobility of fixed human red blood cells immunologically labeled with polymeric (4-vinyl)pyridine or polyglutaraldehyde microspheres was altered to a considerable extent. This observation was utilized in the preparative scale electrophoretic separation of human and turkey fixed red blood cells, whose mobilities under normal physiological conditions do not differ sufficiently to allow their separation by continuous flow electrophoresis. It is suggested that resolution in the electrophoretic separation of cell subpopulations, currently limited by finite and often overlapping mobility distributions, may be significantly enhanced by immuno-specific labeling of target populations using microspheres.

[Adaptive optics for ophthalmology].

PubMed

Saleh, M

2016-04-01

Adaptive optics is a technology enhancing the visual performance of an optical system by correcting its optical aberrations. Adaptive optics have already enabled several breakthroughs in the field of visual sciences, such as improvement of visual acuity in normal and diseased eyes beyond physiologic limits, and the correction of presbyopia. Adaptive optics technology also provides high-resolution, in vivo imaging of the retina that may eventually help to detect the onset of retinal conditions at an early stage and provide better assessment of treatment efficacy. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Exogenous antioxidants—Double-edged swords in cellular redox state

PubMed Central

Bohn, Torsten

2010-01-01

The balance between oxidation and antioxidation is believed to be critical in maintaining healthy biological systems. Under physiological conditions, the human antioxidative defense system including e.g., superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione (GSH) and others, allows the elimination of excess reactive oxygen species (ROS) including, among others superoxide anions (O2.-), hydroxyl radicals (OH.), alkoxyl radicals (RO.) and peroxyradicals (ROO.). However, our endogenous antioxidant defense systems are incomplete without exogenous originating reducing compounds such as vitamin C, vitamin E, carotenoids and polyphenols, playing an essential role in many antioxidant mechanisms in living organisms. Therefore, there is continuous demand for exogenous antioxidants in order to prevent oxidative stress, representing a disequilibrium redox state in favor of oxidation. However, high doses of isolated compounds may be toxic, owing to prooxidative effects at high concentrations or their potential to react with beneficial concentrations of ROS normally present at physiological conditions that are required for optimal cellular functioning. This review aims to examine the double-edged effects of dietary originating antioxidants with a focus on the most abundant compounds, especially polyphenols, vitamin C, vitamin E and carotenoids. Different approaches to enrich our body with exogenous antioxidants such as via synthetic antioxidants, diets rich in fruits and vegetables and taking supplements will be reviewed and experimental and epidemiological evidences discussed, highlighting that antioxidants at physiological doses are generally safe, exhibiting interesting health beneficial effects. PMID:20972369

Neuronal Responses to Physiological Stress

PubMed Central

Kagias, Konstantinos; Nehammer, Camilla; Pocock, Roger

2012-01-01

Physiological stress can be defined as any external or internal condition that challenges the homeostasis of a cell or an organism. It can be divided into three different aspects: environmental stress, intrinsic developmental stress, and aging. Throughout life all living organisms are challenged by changes in the environment. Fluctuations in oxygen levels, temperature, and redox state for example, trigger molecular events that enable an organism to adapt, survive, and reproduce. In addition to external stressors, organisms experience stress associated with morphogenesis and changes in inner chemistry during normal development. For example, conditions such as intrinsic hypoxia and oxidative stress, due to an increase in tissue mass, have to be confronted by developing embryos in order to complete their development. Finally, organisms face the challenge of stochastic accumulation of molecular damage during aging that results in decline and eventual death. Studies have shown that the nervous system plays a pivotal role in responding to stress. Neurons not only receive and process information from the environment but also actively respond to various stresses to promote survival. These responses include changes in the expression of molecules such as transcription factors and microRNAs that regulate stress resistance and adaptation. Moreover, both intrinsic and extrinsic stresses have a tremendous impact on neuronal development and maintenance with implications in many diseases. Here, we review the responses of neurons to various physiological stressors at the molecular and cellular level. PMID:23112806

Sitting-Meditation Interventions Among Youth: A Review of Treatment Efficacy

PubMed Central

Black, David S.; Milam, Joel; Sussman, Steve

2011-01-01

OBJECTIVE Although the efficacy of meditation interventions has been examined among adult samples, meditation treatment effects among youth are relatively unknown. We systematically reviewed empirical studies for the health-related effects of sitting-meditative practices implemented among youth aged 6 to 18 years in school, clinic, and community settings. METHODS A systematic review of electronic databases (PubMed, Ovid, Web of Science, Cochrane Reviews Database, Google Scholar) was conducted from 1982 to 2008, obtaining a sample of 16 empirical studies related to sitting-meditation interventions among youth. RESULTS Meditation modalities included mindfulness meditation, transcendental meditation, mindfulness-based stress reduction, and mindfulness-based cognitive therapy. Study samples primarily consisted of youth with preexisting conditions such as high-normal blood pressure, attention-deficit/hyperactivity disorder, and learning disabilities. Studies that examined physiologic outcomes were composed almost entirely of African American/black participants. Median effect sizes were slightly smaller than those obtained from adult samples and ranged from 0.16 to 0.29 for physiologic outcomes and 0.27 to 0.70 for psychosocial/behavioral outcomes. CONCLUSIONS Sitting meditation seems to be an effective intervention in the treatment of physiologic, psychosocial, and behavioral conditions among youth. Because of current limitations, carefully constructed research is needed to advance our understanding of sitting meditation and its future use as an effective treatment modality among younger populations. PMID:19706568

Polarization-resolved SHG microscopy in cardiac hypertrophy study (Conference Presentation)

NASA Astrophysics Data System (ADS)

Wang, Zhonghai; Yuan, Cai; Shao, Yonghong; Bradshaw, Amy D.; Borg, Thomas K.; Gao, Bruce Z.

2017-02-01

Cardiac hypertrophy, a process initiated by mechanical alterations, is hypothesized to cause long-term molecular-level alteration in the sarcomere lattice, which is the main force-generating component in the heart muscle. This molecular-level alteration is beyond the resolving capacity of common light microscopy. Second harmonic generation (SHG) microscopy has unique capability for visualizing ordered molecular structures in biological tissues without labeling. Combined with polarization imaging technique, SHG microscopy is able to extract structural details of myosin at the molecular level so as to reveal molecular-level alterations that occur during hypertrophy. The myosin filaments are believed to possess C6 symmetry; thus, the nonlinear polarization response relationship between generated second harmonic light I^2ωand incident fundamental light I^ω is determined by nonlinear coefficients, χ_15, χ_31 and χ_33. χ_31/χ_15 is believed to be an indicator of the molecular symmetry of myosin filament, whileχ_33/χ_15represents the intramyosin orientation angle of the double helix. By changing the polarization of the incident light and evaluating the corresponding SHG signals, the molecular structure of the myosin, reflected by the χ coefficients, can be revealed. With this method, we studied the structural properties of heart tissues in different conditions, including those in normal, physiologically hypertrophic (heart tissue from postpartum female rats), and pathologically hypertrophic (heart tissue from transverse-aorta constricted rats) conditions. We found that ratios of χ_31/χ_15 showed no significant difference between heart tissues from different conditions; their values were all close to 1, which demonstrated that Kleinman symmetry held for all conditions. Ratios of χ_33/χ_15 from physiologically or pathologically hypertrophic heart tissues were raised and showed significant difference from those from normal heart tissues, which indicated that the intramyosin orientation angle of the double helix was altered when heart tissues hypertrophied. Polarization-resolved SHG microscopy permitted us to study heart tissues at the molecular level and may serve as a diagnostic tool for cardiac hypertrophy.

New insight into the role of the β3 subunit of the GABAA-R in development, behavior, body weight regulation, and anesthesia revealed by conditional gene knockout

PubMed Central

Ferguson, Carolyn; Hardy, Steven L; Werner, David F; Hileman, Stanley M; DeLorey, Timothy M; Homanics, Gregg E

2007-01-01

Background The β3 subunit of the γ-aminobutyric acid type A receptor (GABAA-R) has been reported to be important for palate formation, anesthetic action, and normal nervous system function. This subunit has also been implicated in the pathogenesis of Angelman syndrome and autism spectrum disorder. To further investigate involvement of this subunit, we previously produced mice with a global knockout of β3. However, developmental abnormalities, compensation, reduced viability, and numerous behavioral abnormalities limited the usefulness of that murine model. To overcome many of these limitations, a mouse line with a conditionally inactivated β3 gene was engineered. Results Gene targeting and embryonic stem cell technologies were used to create mice in which exon 3 of the β3 subunit was flanked by loxP sites (i.e., floxed). Crossing the floxed β3 mice to a cre general deleter mouse line reproduced the phenotype of the previously described global knockout. Pan-neuronal knockout of β3 was achieved by crossing floxed β3 mice to Synapsin I-cre transgenic mice. Palate development was normal in pan-neuronal β3 knockouts but ~61% died as neonates. Survivors were overtly normal, fertile, and were less sensitive to etomidate. Forebrain selective knockout of β3 was achieved using α CamKII-cre transgenic mice. Palate development was normal in forebrain selective β3 knockout mice. These knockouts survived the neonatal period, but ~30% died between 15–25 days of age. Survivors had reduced reproductive fitness, reduced sensitivity to etomidate, were hyperactive, and some became obese. Conclusion Conditional inactivation of the β3 gene revealed novel insight into the function of this GABAA-R subunit. The floxed β3 knockout mice described here will be very useful for conditional knockout studies to further investigate the role of the β3 subunit in development, ethanol and anesthetic action, normal physiology, and pathophysiologic processes. PMID:17927825

Physiological Parameter Response to Variation of Mental Workload

PubMed Central

Marinescu, Adrian Cornelius; Sharples, Sarah; Ritchie, Alastair Campbell; Sánchez López, Tomas; McDowell, Michael; Morvan, Hervé P.

2017-01-01

Objective: To examine the relationship between experienced mental workload and physiological response by noninvasive monitoring of physiological parameters. Background: Previous studies have examined how individual physiological measures respond to changes in mental demand and subjective reports of workload. This study explores the response of multiple physiological parameters and quantifies their added value when estimating the level of demand. Method: The study presented was conducted in laboratory conditions and required participants to perform a visual-motor task that imposed varying levels of demand. The data collected consisted of physiological measurements (heart interbeat intervals, breathing rate, pupil diameter, facial thermography), subjective ratings of workload (Instantaneous Self-Assessment Workload Scale [ISA] and NASA-Task Load Index), and the performance. Results: Facial thermography and pupil diameter were demonstrated to be good candidates for noninvasive workload measurements: For seven out of 10 participants, pupil diameter showed a strong correlation (R values between .61 and .79 at a significance value of .01) with mean ISA normalized values. Facial thermography measures added on average 47.7% to the amount of variability in task performance explained by a regression model. As with the ISA ratings, the relationship between the physiological measures and performance showed strong interparticipant differences, with some individuals demonstrating a much stronger relationship between workload and performance measures than others. Conclusion: The results presented in this paper demonstrate that physiological and pupil diameter can be used for noninvasive real-time measurement of workload. Application: The methods presented in this article, with current technological capabilities, are better suited for workplaces where the person is seated, offering the possibility of being applied to pilots and air traffic controllers. PMID:28965433

Abnormal pulmonary function in adults with sickle cell anemia.

PubMed

Klings, Elizabeth S; Wyszynski, Diego F; Nolan, Vikki G; Steinberg, Martin H

2006-06-01

Pulmonary complications of sickle cell anemia (Hb-SS) commonly cause morbidity, yet few large studies of pulmonary function tests (PFTs) in this population have been reported. PFTs (spirometry, lung volumes, and diffusion capacity for carbon monoxide [DLCO]) from 310 adults with Hb-SS were analyzed to determine the pattern of pulmonary dysfunction and their association with other systemic complications of sickle cell disease. Raw PFT data were compared with predicted values. Each subject was subclassified into one of five groups: obstructive physiology, restrictive physiology, mixed obstructive/restrictive physiology, isolated low DLCO, or normal. The association between laboratory data of patients with decreased DLCO or restrictive physiology and those of normal subjects was assessed by multivariate linear regression. Normal PFTs were present in only 31 of 310 (10%) patients. Overall, adults with Hb-SS were characterized by decreased total lung capacities (70.2 +/- 14.7% predicted) and DLCO (64.5 +/- 19.9%). The most common PFT patterns were restrictive physiology (74%) and isolated low DLCO (13%). Decreased DLCO was associated with thrombocytosis (p = 0.05), with hepatic dysfunction (elevated alanine aminotransferase; p = 0.07), and a trend toward renal dysfunction (elevated blood urea nitrogen and creatinine; p = 0.05 and 0.07, respectively). Pulmonary function is abnormal in 90% of adult patients with Hb-SS. Common abnormalities include restrictive physiology and decreased DLCO. Decreased DLCO may indicate more severe sickle vasculopathy characterized by impaired hepatic and renal function.

Sensory memory during physiological aging indexed by mismatch negativity (MMN).

PubMed

Ruzzoli, Manuela; Pirulli, Cornelia; Brignani, Debora; Maioli, Claudio; Miniussi, Carlo

2012-03-01

Physiological aging affects early sensory-perceptual processes. The aim of this experiment was to evaluate changes in auditory sensory memory in physiological aging using the Mismatch Negativity (MMN) paradigm as index. The MMN is a marker recorded through the electroencephalogram and is used to evaluate the integrity of the memory system. We adopted a new, faster paradigm to look for differences between 3 groups of subjects of different ages (young, middle age and older adults) as a function of short or long intervals between stimuli. We found that older adults did not show MMN at long interval condition and that the duration of MMN varied according to the participants' age. The current study provides electrophysiological evidence supporting the theory that the encoding of stimuli is preserved during normal aging, whereas the maintenance of sensory memory is impaired. Considering the advantage offered by the MMN paradigm used here, these data might be a useful reference point for the assessment of auditory sensory memory in pathological aging (e.g., in neurodegenerative diseases). Copyright © 2012 Elsevier Inc. All rights reserved.

Unperturbed vs. post-transplantation hematopoiesis: both in vivo but different.

PubMed

Busch, Katrin; Rodewald, Hans-Reimer

2016-07-01

Hematopoietic stem cell (HSC) transplantation has yielded tremendous information on experimental properties of HSCs. Yet, it remains unclear whether transplantation reflects the physiology of hematopoiesis. A limitation is the difficulty in accessing HSC functions without isolation, in-vitro manipulation and readout for potential. New genetic fate mapping and clonal marking techniques now shed light on hematopoiesis under physiological conditions. Transposon-based genetic marks were introduced across the entire hematopoietic system to follow the clonal dynamics of these tags over time. A polyclonal source downstream from stem cells was found responsible for the production of at least granulocytes. In independent experiments, HSCs were genetically marked in adult mice, and the kinetics of label emergence throughout the system was followed over time. These experiments uncovered that during physiological steady-state hematopoiesis large numbers of HSCs yield differentiated progeny. Individual HSCs were active only rarely, indicating their very slow periodicity of differentiation rather than quiescence. Noninvasive genetic experiments in mice have identified a major role of stem and progenitor cells downstream from HSCs as drivers of adult hematopoiesis, and revealed that post-transplantation hematopoiesis differs quantitatively from normal steady-state hematopoiesis.

[Clinical interest of fMRI and functional exploration methods of brain activity and interactivity: physical and neurophysiological considerations].

PubMed

de Marco, G; Menuel, C; Guillevin, R; Vallée, J-N; Lehmann, P; Fall, S; Quaglino, V; Bourdin, B; Devauchelle, B; Chiras, J

2008-07-01

After having provided a brief reminder of the principle of the blood oxygen level-dependent (BOLD) contrast effect, the physiological bases of brain activity and the concepts of functional integration and effective connectivity, we describe the most recent approaches, which permit to explore brain activity and putative networks of interconnected active areas in order to examine the normal brain physiology and its dysfunctions. We present various methods and studies of brain activity analysis clinically applicable, and we detail the concepts of functional and effective connectivity, which allow to study the cerebral plasticity which occurs at the child's during the maturation (e.g., dyslexia), at the adult during the ageing (e.g., Alzheimer disease), or still in schizophrenia or Parkinson disease. The study of specific circuits in networks has to allow defining in a more realistic way the dynamic of the central nervous system, which underlies various cerebral functions, both in physiological and pathological conditions. This connectivity approach should improve the diagnostic and facilitate the development of new therapeutic strategies.

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

PubMed

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

2011-02-25

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

Physiological advantages of dwarfing in surviving extinctions in high-CO2 oceans

NASA Astrophysics Data System (ADS)

Garilli, Vittorio; Rodolfo-Metalpa, Riccardo; Scuderi, Danilo; Brusca, Lorenzo; Parrinello, Daniela; Rastrick, Samuel P. S.; Foggo, Andy; Twitchett, Richard J.; Hall-Spencer, Jason M.; Milazzo, Marco

2015-07-01

Excessive CO2 in the present-day ocean-atmosphere system is causing ocean acidification, and is likely to cause a severe biodiversity decline in the future, mirroring effects in many past mass extinctions. Fossil records demonstrate that organisms surviving such events were often smaller than those before, a phenomenon called the Lilliput effect. Here, we show that two gastropod species adapted to acidified seawater at shallow-water CO2 seeps were smaller than those found in normal pH conditions and had higher mass-specific energy consumption but significantly lower whole-animal metabolic energy demand. These physiological changes allowed the animals to maintain calcification and to partially repair shell dissolution. These observations of the long-term chronic effects of increased CO2 levels forewarn of changes we can expect in marine ecosystems as CO2 emissions continue to rise unchecked, and support the hypothesis that ocean acidification contributed to past extinction events. The ability to adapt through dwarfing can confer physiological advantages as the rate of CO2 emissions continues to increase.

The control of calcium metabolism by parathyroid hormone, calcitonin and vitamin D

NASA Technical Reports Server (NTRS)

Potts, J. T., Jr.

1976-01-01

Advances in analysis of chemistry and physiology of parathyroid hormone, calcitonin, and Vitamin D are described along with development of techniques in radioassay methods. Emphasis is placed on assessment of normal and abnormal patterns of secretion of these hormones in specific relation to the physiological adaptations of weightlessness and space flight. Related diseases that involve perturbations in normal skeletal and calcium homeostasis are also considered.

Disadvantages of interfragmentary shear on fracture healing--mechanical insights through numerical simulation.

PubMed

Steiner, Malte; Claes, Lutz; Ignatius, Anita; Simon, Ulrich; Wehner, Tim

2014-07-01

The outcome of secondary fracture healing processes is strongly influenced by interfragmentary motion. Shear movement is assumed to be more disadvantageous than axial movement, however, experimental results are contradictory. Numerical fracture healing models allow simulation of the fracture healing process with variation of single input parameters and under comparable, normalized mechanical conditions. Thus, a comparison of the influence of different loading directions on the healing process is possible. In this study we simulated fracture healing under several axial compressive, and translational and torsional shear movement scenarios, and compared their respective healing times. Therefore, we used a calibrated numerical model for fracture healing in sheep. Numerous variations of movement amplitudes and musculoskeletal loads were simulated for the three loading directions. Our results show that isolated axial compression was more beneficial for the fracture healing success than both isolated shearing conditions for load and displacement magnitudes which were identical as well as physiological different, and even for strain-based normalized comparable conditions. Additionally, torsional shear movements had less impeding effects than translational shear movements. Therefore, our findings suggest that osteosynthesis implants can be optimized, in particular, to limit translational interfragmentary shear under musculoskeletal loading. © 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

[Ryanodine receptor, calcium leak and arrhythmias].

PubMed

Rueda, Angélica; de Alba-Aguayo, David R; Valdivia, Héctor H

2014-01-01

The participation of the ionic Ca(2+) release channel/ryanodine receptor in cardiac excitation-contraction coupling is well known since the late '80s, when various seminal papers communicated its purification for the first time and its identity with the "foot" structures located at the terminal cisternae of the sarcoplasmic reticulum. In addition to its main role as the Ca(2+) channel responsible for the transient Ca(2+) increase that activates the contractile machinery of the cardiomyocytes, the ryanodine receptor releases Ca(2+) during the relaxation phase of the cardiac cycle, giving rise to a diastolic Ca(2+) leak. In normal physiological conditions, diastolic Ca(2+) leak regulates the proper level of luminal Ca(2+), but in pathological conditions it participates in the generation of both, acquired and hereditary arrhythmias. Very recently, several groups have focused their efforts into the development of pharmacological tools to control the altered diastolic Ca(2+) leak via ryanodine receptors. In this review, we focus our interest on describing the participation of cardiac ryanodine receptor in the diastolic Ca(2+) leak under physiological or pathological conditions and also on the therapeutic approaches to control its undesired exacerbated activity during diastole. Copyright © 2013 Instituto Nacional de Cardiología Ignacio Chávez. Published by Masson Doyma México S.A. All rights reserved.

Chain Collapse of an Amyloidogenic Intrinsically Disordered Protein

PubMed Central

Jain, Neha; Bhattacharya, Mily; Mukhopadhyay, Samrat

2011-01-01

Natively unfolded or intrinsically disordered proteins (IDPs) are under intense scrutiny due to their involvement in both normal biological functions and abnormal protein misfolding disorders. Polypeptide chain collapse of amyloidogenic IDPs is believed to play a key role in protein misfolding, oligomerization, and aggregation leading to amyloid fibril formation, which is implicated in a number of human diseases. In this work, we used bovine κ-casein, which serves as an archetypal model protein for amyloidogenic IDPs. Using a variety of biophysical tools involving both prediction and spectroscopic techniques, we first established that monomeric κ-casein adopts a collapsed premolten-globule-like conformational ensemble under physiological conditions. Our time-resolved fluorescence and light-scattering data indicate a change in the mean hydrodynamic radius from ∼4.6 nm to ∼1.9 nm upon chain collapse. We then took the advantage of two cysteines separated by 77 amino-acid residues and covalently labeled them using thiol-reactive pyrene maleimide. This dual-labeled protein demonstrated a strong excimer formation upon renaturation from urea- and acid-denatured states under both equilibrium and kinetic conditions, providing compelling evidence of polypeptide chain collapse under physiological conditions. The implication of the IDP chain collapse in protein aggregation and amyloid formation is also discussed. PMID:21961598

Backdoor pathway for dihydrotestosterone biosynthesis: implications for normal and abnormal human sex development.

PubMed

Fukami, Maki; Homma, Keiko; Hasegawa, Tomonobu; Ogata, Tsutomu

2013-04-01

We review the current knowledge about the "backdoor" pathway for the biosynthesis of dihydrotestosterone (DHT). While DHT is produced from cholesterol through the conventional "frontdoor" pathway via testosterone, recent studies have provided compelling evidence for the presence of an alternative "backdoor" pathway to DHT without testosterone intermediacy. This backdoor pathway is known to exist in the tammar wallaby pouch young testis and the immature mouse testis, and has been suggested to be present in the human as well. Indeed, molecular analysis has identified pathologic mutations of genes involved in the backdoor pathway in genetic male patients with undermasculinized external genitalia, and urine steroid profile analysis has argued for the relevance of the activated backdoor pathway to abnormal virilization in genetic females with cytochrome P450 oxidoreductase deficiency and 21-hydroxylase deficiency. It is likely that the backdoor pathway is primarily operating in the fetal testis in a physiological condition to produce a sufficient amount of DHT for male sex development, and that the backdoor pathway is driven with a possible interaction between fetal and permanent adrenals in pathologic conditions with increased 17-hydroxyprogesterone levels. These findings provide novel insights into androgen biosynthesis in both physiological and pathological conditions. Copyright © 2012 Wiley Periodicals, Inc., a Wiley company.

Conditional expression of Pomc in the Lepr-positive subpopulation of POMC neurons is sufficient for normal energy homeostasis and metabolism.

PubMed

Lam, Daniel D; Attard, Courtney A; Mercer, Aaron J; Myers, Martin G; Rubinstein, Marcelo; Low, Malcolm J

2015-04-01

Peptides derived from the proopiomelanocortin (POMC) precursor are critical for the normal regulation of many physiological parameters, and POMC deficiency results in severe obesity and metabolic dysfunction. Conversely, augmentation of central nervous system melanocortin function is a promising therapeutic avenue for obesity and diabetes but is confounded by detrimental cardiovascular effects including hypertension. Because the hypothalamic population of POMC-expressing neurons is neurochemically and neuroanatomically heterogeneous, there is interest in the possible dissociation of functionally distinct POMC neuron subpopulations. We used a Cre recombinase-dependent and hypothalamus-specific reactivatable PomcNEO allele to restrict Pomc expression to hypothalamic neurons expressing leptin receptor (Lepr) in mice. In contrast to mice with total hypothalamic Pomc deficiency, which are severely obese, mice with Lepr-restricted Pomc expression displayed fully normal body weight, food consumption, glucose homeostasis, and locomotor activity. Thus, Lepr+ POMC neurons, which constitute approximately two-thirds of the total POMC neuron population, are sufficient for normal regulation of these parameters. This functional dissociation approach represents a promising avenue for isolating therapeutically relevant POMC neuron subpopulations.

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

Vasuri, Francesco; Capizzi, Elisa; Bellavista, Elena

Despite the central role of proteasomes in relevant physiological pathways and pathological processes, this topic is unexpectedly largely unexplored in human liver. Here we present data on the presence of proteasome and immunoproteasome in human livers from normal adults, fetuses and patients affected by major hepatic diseases such as cirrhosis and chronic active hepatitis. Immunohistochemistry for constitutive ({alpha}4 and {beta}1) and inducible (LMP2 and LMP7) proteasome subunits, and for the PA28{alpha}{beta} regulator, was performed in liver samples from 38 normal subjects, 6 fetuses, 2 pediatric cases, and 19 pathological cases (10 chronic active hepatitis and 9 cirrhosis). The immunohistochemical datamore » have been validated and quantified by Western blotting analysis. The most striking result we found was the concomitant presence in hepatocyte cytoplasm of all healthy subjects, including the pediatric cases, of constitutive proteasome and immunoproteasome subunits, as well as PA28{alpha}{beta}. At variance, immunoproteasome was not present in hepatocytes from fetuses, while a strong cytoplasmic and nuclear positivity for LMP2 and LMP7 was found in pathological samples, directly correlated to the histopathological grade of inflammation. At variance from other organs such as the brain, immunoproteasome is present in livers from normal adult and pediatric cases, in apparent absence of pathological processes, suggesting the presence of a peculiar regulation of the proteasome/immunoproteasome system, likely related to the physiological stimuli derived from the gut microbiota after birth. Other inflammatory stimuli contribute in inducing high levels of immunoproteasome in pathological conditions, where its role deserve further attention.« less

Neutropenia - infants

MedlinePlus

... Bliss JM, Mariscalco MM. Normal and abnormal neutrophil physiology in the newborn. In: Polin RA, Abman SH, ... Benitz WE, Fox WW, eds. Fetal and Neonatal Physiology . 5th ed. Philadelphia, PA: Elsevier; 2017:chap 126. ...

A physiological frequency-position map of the chinchilla cochlea.

PubMed

Müller, Marcus; Hoidis, Silvi; Smolders, Jean W T

2010-09-01

Accumulating evidence indicates that mammalian cochlear frequency-position maps (location of maximum vibration of the basilar membrane as a function of frequency) depend on the physiological condition of the inner ear. Cochlear damage desensitizes the ear, after the damage the original location of maximum vibration is tuned to a lower sound frequency. This suggests that frequency-position maps, derived from such desensitized ears, are shifted to lower frequencies, corresponding to a shift of the basilar membrane vibration pattern towards the base for a given stimulus frequency. To test this hypothesis, we re-mapped the cochlear frequency-position map in the chinchilla. We collected frequency-position data from chinchillas in normal physiological condition ("physiological map") and compared these to data previously established from sound overexposed ears ("anatomical map"). The characteristic frequency (CF) of neurons in the cochlear nucleus was determined. Horse-radish peroxidase (HRP) or biocytin (BCT) were injected iontophoretically to trace auditory nerve fibers towards their innervation site in the organ of Corti. The relationship between distance from the base (d, percent) and frequency (f, kHz) was described best by a simple exponential function: d = 61.2 - 42.2 x log(f). The slope of the function was 2.55 mm/octave. Compared to the "anatomical map", the "physiological map" was shifted by about 0.3 octaves to higher frequencies corresponding to a shift of the basilar membrane vibration pattern of 0.8 mm towards the apex for a given stimulus frequency. Our findings affirm that frequency-position maps in the mammalian cochlea depend on the condition of the inner ear. Damage-induced desensitization in mammalian inner ears results in similar shifts of CF (about 0.5 octaves) but different shifts of the maximum of the vibration pattern towards the base at given frequencies, dependent on the mapping constant of the species, longer basilar membranes showing a larger basal shift. Furthermore, the results substantiate the notion that "crowding" at lower frequencies appears to be a specialization rather than a general feature. Copyright (c) 2010 Elsevier B.V. All rights reserved.

[The Rosenthal experiment or: about the site of productive research - on move of the physiological experimental laboratory of Isidor Rosenthal (1836-1915) from the city to the country].

PubMed

Stahnisch, Frank W

2010-01-01

The disciplinary development of the new science of experimental physiology is often associated with the conditions of cultural development and increasingly technical working contexts of the Industrial Age. Following this perspective, the germ cells of 19th century institutes of experimental physiology were particularly found in the metropolises of Paris, Leipzig or Berlin. Only the major cities sat the revolutionary trends and within this general process, the scientific trends were no exceptions - the provincial research universities simply followed the central ones in their normal science endeavours. Due to this interpretation, the development of the scientific community was pre-formatted as the interplay of innovation (the city) and reception (the periphery). Isidor Rosenthal (1836-1915) was born in Labischin (District of Bromberg/Posen) in 1836 and got his medical training in Berlin. Like not many other experimental physiologists, he can be used as a historiographical testing probe, to follow the conditions of knowledge transfer from center to periphery: After his studies at the Friedrich Wilhelms University and the completion of his dissertation in 1859, Rosenthal entered the newly founded Physiological Institute in Berlin as the first Research Associate of Emil DuBois-Reymond (1818-1896). Rosenthal worked here particularly on the problem of "direct and indirect muscle irritation" in frogs. These neurophysiological investigations led to his growing scientific renown. In 1872, Rosenthal became offered a first professorship in physiology at the Friedrich Alexander University in Bavaria, as one of only few Jewish scientists (and even before Wilhelm Wundt, 1832-1920). But his life and work proved not only exceptional because of his scientific achievements, but also due to his deep rootedness in cultural life--both during his time in Berlin and in Erlangen. By applying a comparative and microhistorical approach in this article, the working conditions of this scientific migrant from Berlin are scrutinized as to the changes that took place between the city and regional university.

Autonomic physiological data associated with simulator discomfort

NASA Technical Reports Server (NTRS)

Miller, James C.; Sharkey, Thomas J.; Graham, Glenna A.; Mccauley, Michael E.

1993-01-01

The development of a physiological monitoring capability for the Army's advanced helicopter simulator facility is reported. Additionally, preliminary physiological data is presented. Our objective was to demonstrate the sensitivity of physiological measures in this simulator to self-reported simulator sickness. The data suggested that heart period, hypergastria, and skin conductance level were more sensitive to simulator sickness than were vagal tone and normal electrogastric activity.

An electromechanical swing-phase-controlled prosthetic knee joint for conversion of physiological energy to electrical energy: feasibility study.

PubMed

Andrysek, Jan; Chau, Gilbert

2007-12-01

Microprocessor-controlled prostheses facilitate a more natural and efficient gait for individuals with above-knee amputations by continually adjusting the level of swing-phase damping. One caveat associated with these technologies is that the user must charge the onboard batteries on a daily basis. It is, therefore, the aim of this study to examine the feasibility of using an electromechanical system to provide prosthetic swing-phase damping and, concomitantly, the function of converting physiological energy that is normally dissipated during the swing phase, to electrical energy. Gait data from a single subject and data from a kinematic simulator were used to develop an empirical model. The findings in this study indicate that an electromagnetic system has appropriate characteristics for use in swing-phase control and also has the potential to recover energy under particular conditions.

[Spatial orientation of the facies patellaris femoris].

PubMed

Hassenpflug, J; Hiss, E; Blauth, W

1987-01-01

The present article reports on the geometrical conditions of the physiological movement of the patella. The geometrical shape of 18 femoral condyles and patella sliding areas was investigated in order to describe basic data for the design of endoprostheses. Surface and direction of the facies patellaris femoris were determined by means of radiographic, mechanical and optical measurements. The curvature of the deepest patella sliding groove proves a constant correlation with the dorsal condylar curvature. In the frontal plane the lowest points of the sliding area run with a dispersion of +/- 4 degrees to the vertical line related to the transverse tangent on the dorsal condylar surface. Considering deviations of leg alignment the measures come close to an angle of about 0 degrees. So the direction of the patella sliding groove differs from the normal valgus position of the distal femur. Therefore in artificial knee replacement a lateral tilt of the patella sliding groove should not be propagated as 'physiological'.

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

PubMed

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

2015-12-01

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

Brain temperature: heat production, elimination and clinical relevance.

PubMed

Bertolizio, Gianluca; Mason, Linda; Bissonnette, Bruno

2011-04-01

Neurological insults are a leading cause of morbidity and mortality, both in adults and especially in children. Among possible therapeutic strategies to limit clinical cerebral damage and improve outcomes, hypothermia remains a promising and beneficial approach. However, its advantages are still debated after decades of use. Studies in adults have generated conflicting results, whereas in children recent data even suggest that hypothermia may be detrimental. Is it because brain temperature physiology is not well understood and/or not applied properly, that hypothermia fails to convince clinicians of its potential benefits? Or is it because hypothermia is not, as believed, the optimal strategy to improve outcome in patients affected with an acute neurological insult? This review article should help to explain the fundamental physiological principles of brain heat production, distribution and elimination under normal conditions and discuss why hypothermia cannot yet be recommended routinely in the management of children affected with various neurological insults. © 2011 Blackwell Publishing Ltd.

Nutritional support of the elderly cancer patient: the role of the nurse.

PubMed

Hopkinson, Jane B

2015-04-01

Cancer in the geriatric population is a growing problem. Malnutrition is common in cancer. A number of factors increase the risk for malnutrition in older people with cancer, including chronic comorbid conditions and normal physiological changes of aging. Nurses have an important role in the nutritional support of older cancer patients. To contribute to the improvement of nutritional support of these patients, nurses need appropriate training to be able to identify risk for malnutrition and offer a range of interventions tailored to individual need. Factors to consider in tailoring interventions include disease status, cancer site, cancer treatment, comorbidity, physiological age, method of facilitating dietary change, and family support. This article identifies ways in which nurses can contribute to the nutritional support of older cancer patients and thus help mitigate the effects of malnutrition. Copyright © 2015 Elsevier Inc. All rights reserved.

Endocannabinoids control vesicle release mode at midbrain periaqueductal grey inhibitory synapses.

PubMed

Aubrey, Karin R; Drew, Geoffrey M; Jeong, Hyo-Jin; Lau, Benjamin K; Vaughan, Christopher W

2017-01-01

The midbrain periaqueductal grey (PAG) forms part of an endogenous analgesic system which is tightly regulated by the neurotransmitter GABA. The role of endocannabinoids in regulating GABAergic control of this system was examined in rat PAG slices. Under basal conditions GABAergic neurotransmission onto PAG output neurons was multivesicular. Activation of the endocannabinoid system reduced GABAergic inhibition by reducing the probability of release and by shifting release to a univesicular mode. Blockade of endocannabinoid system unmasked a tonic control over the probability and mode of GABA release. These findings provides a mechanistic foundation for the control of the PAG analgesic system by disinhibition. The midbrain periaqueductal grey (PAG) has a crucial role in coordinating endogenous analgesic responses to physiological and psychological stressors. Endocannabinoids are thought to mediate a form of stress-induced analgesia within the PAG by relieving GABAergic inhibition of output neurons, a process known as disinhibition. This disinhibition is thought to be achieved by a presynaptic reduction in GABA release probability. We examined whether other mechanisms have a role in endocannabinoid modulation of GABAergic synaptic transmission within the rat PAG. The group I mGluR agonist DHPG ((R,S)-3,5-dihydroxyphenylglycine) inhibited evoked IPSCs and increased their paired pulse ratio in normal external Ca 2+ , and when release probability was reduced by lowering Ca 2+ . However, the effect of DHPG on the coefficient of variation and kinetics of evoked IPSCs differed between normal and low Ca 2+ . Lowering external Ca 2+ had a similar effect on evoked IPSCs to that observed for DHPG in normal external Ca 2+ . The low affinity GABA A receptor antagonist TPMPA ((1,2,5,6-tetrahydropyridin-4-yl)methylphosphinic acid) inhibited evoked IPSCs to a greater extent in low than in normal Ca 2+ . Together these findings indicate that the normal mode of GABA release is multivesicular within the PAG, and that DHPG and lowering external Ca 2+ switch this to a univesicular mode. The effects of DHPG were mediated by mGlu5 receptor engagement of the retrograde endocannabinoid system. Blockade of endocannabinoid breakdown produced a similar shift in the mode of release. We conclude that endocannabinoids control both the mode and the probability of GABA release within the PAG. © 2016 The Authors. The Journal of Physiology © 2016 The Physiological Society.

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

Re-establishment of gap junctional intercellular communication (GJIC) between human endometrial carcinomas by prostaglandin E(2).

PubMed

Schlemmer, Scott R; Kaufman, David G

2012-12-01

Reduced intercellular communication via gap junctions is correlated with carcinogenesis. Gap junctional intercellular communication (GJIC), between normal human endometrial epithelial cells is enhanced when endometrial stromal cells were present in culture. This enhancement of GJIC between normal epithelial cells also occurs when they are cultured in medium conditioned by stromal cells. This observation indicated that a soluble compound (or compounds) produced and secreted by stromal cells mediates GJIC in epithelial cells. Previous studies have shown that endometrial stromal cells release prostaglandin E(2) (PGE(2)) and prostaglandin F(2α) (PGF(2α)) under physiological conditions. When we evaluated the response of normal endometrial epithelial cells to various concentrations of PGE(2,) we found enhanced GJIC with 1nM PGE(2). This is a smaller increase in GJIC than that induced by medium conditioned by stromal cells. When the extracellular concentration of PGE(2) was measured after incubation with stromal cells, it was found to be similar to the concentrations showing maximal GJIC between the normal epithelial cells. When indomethacin was used to inhibit prostaglandin synthesis by stromal cells, GJIC was reduced but not eliminated between normal endometrial epithelial cells. These observations suggest that although PGE(2) secreted by stromal cells is an important mediator of GJIC between the epithelial cells, it is not the sole mediator. Transformed endometrial epithelial cells did not demonstrate GJIC even in the presence of stromal cells. However, we were able to re-establish GJIC in transformed epithelial cells when we added PGE(2) to the cells. Our findings show that PGE(2) may serve as an intercellular mediator between stromal and epithelial cells that regulates GJIC in normal and malignant epithelial cells. This suggests that maintenance of GJIC by preserving or replacing PGE(2) secretion by endometrial stromal cells may have the potential to suppress carcinogenesis in endometrial epithelial cells. Copyright © 2012 Elsevier Inc. All rights reserved.

A Novel Approach for Dynamic Testing of Total Hip Dislocation under Physiological Conditions.

PubMed

Herrmann, Sven; Kluess, Daniel; Kaehler, Michael; Grawe, Robert; Rachholz, Roman; Souffrant, Robert; Zierath, János; Bader, Rainer; Woernle, Christoph

2015-01-01

Constant high rates of dislocation-related complications of total hip replacements (THRs) show that contributing factors like implant position and design, soft tissue condition and dynamics of physiological motions have not yet been fully understood. As in vivo measurements of excessive motions are not possible due to ethical objections, a comprehensive approach is proposed which is capable of testing THR stability under dynamic, reproducible and physiological conditions. The approach is based on a hardware-in-the-loop (HiL) simulation where a robotic physical setup interacts with a computational musculoskeletal model based on inverse dynamics. A major objective of this work was the validation of the HiL test system against in vivo data derived from patients with instrumented THRs. Moreover, the impact of certain test conditions, such as joint lubrication, implant position, load level in terms of body mass and removal of muscle structures, was evaluated within several HiL simulations. The outcomes for a normal sitting down and standing up maneuver revealed good agreement in trend and magnitude compared with in vivo measured hip joint forces. For a deep maneuver with femoral adduction, lubrication was shown to cause less friction torques than under dry conditions. Similarly, it could be demonstrated that less cup anteversion and inclination lead to earlier impingement in flexion motion including pelvic tilt for selected combinations of cup and stem positions. Reducing body mass did not influence impingement-free range of motion and dislocation behavior; however, higher resisting torques were observed under higher loads. Muscle removal emulating a posterior surgical approach indicated alterations in THR loading and the instability process in contrast to a reference case with intact musculature. Based on the presented data, it can be concluded that the HiL test system is able to reproduce comparable joint dynamics as present in THR patients.

A Novel Approach for Dynamic Testing of Total Hip Dislocation under Physiological Conditions

PubMed Central

Herrmann, Sven; Kluess, Daniel; Kaehler, Michael; Grawe, Robert; Rachholz, Roman; Souffrant, Robert; Zierath, János; Bader, Rainer; Woernle, Christoph

2015-01-01

Constant high rates of dislocation-related complications of total hip replacements (THRs) show that contributing factors like implant position and design, soft tissue condition and dynamics of physiological motions have not yet been fully understood. As in vivo measurements of excessive motions are not possible due to ethical objections, a comprehensive approach is proposed which is capable of testing THR stability under dynamic, reproducible and physiological conditions. The approach is based on a hardware-in-the-loop (HiL) simulation where a robotic physical setup interacts with a computational musculoskeletal model based on inverse dynamics. A major objective of this work was the validation of the HiL test system against in vivo data derived from patients with instrumented THRs. Moreover, the impact of certain test conditions, such as joint lubrication, implant position, load level in terms of body mass and removal of muscle structures, was evaluated within several HiL simulations. The outcomes for a normal sitting down and standing up maneuver revealed good agreement in trend and magnitude compared with in vivo measured hip joint forces. For a deep maneuver with femoral adduction, lubrication was shown to cause less friction torques than under dry conditions. Similarly, it could be demonstrated that less cup anteversion and inclination lead to earlier impingement in flexion motion including pelvic tilt for selected combinations of cup and stem positions. Reducing body mass did not influence impingement-free range of motion and dislocation behavior; however, higher resisting torques were observed under higher loads. Muscle removal emulating a posterior surgical approach indicated alterations in THR loading and the instability process in contrast to a reference case with intact musculature. Based on the presented data, it can be concluded that the HiL test system is able to reproduce comparable joint dynamics as present in THR patients. PMID:26717236

Von Hippel-Lindau protein in the RPE is essential for normal ocular growth and vascular development.

PubMed

Lange, Clemens A K; Luhmann, Ulrich F O; Mowat, Freya M; Georgiadis, Anastasios; West, Emma L; Abrahams, Sabu; Sayed, Haroon; Powner, Michael B; Fruttiger, Marcus; Smith, Alexander J; Sowden, Jane C; Maxwell, Patrick H; Ali, Robin R; Bainbridge, James W B

2012-07-01

Molecular oxygen is essential for the development, growth and survival of multicellular organisms. Hypoxic microenvironments and oxygen gradients are generated physiologically during embryogenesis and organogenesis. In the eye, oxygen plays a crucial role in both physiological vascular development and common blinding diseases. The retinal pigment epithelium (RPE) is a monolayer of cells essential for normal ocular development and in the mature retina provides support for overlying photoreceptors and their vascular supply. Hypoxia at the level of the RPE is closely implicated in pathogenesis of age-related macular degeneration. Adaptive tissue responses to hypoxia are orchestrated by sophisticated oxygen sensing mechanisms. In particular, the von Hippel-Lindau tumour suppressor protein (pVhl) controls hypoxia-inducible transcription factor (HIF)-mediated adaptation. However, the role of Vhl/Hif1a in the RPE in the development of the eye and its vasculature is unknown. In this study we explored the function of Vhl and Hif1a in the developing RPE using a tissue-specific conditional-knockout approach. We found that deletion of Vhl in the RPE results in RPE apoptosis, aniridia and microphthalmia. Increased levels of Hif1a, Hif2a, Epo and Vegf are associated with a highly disorganised retinal vasculature, chorioretinal anastomoses and the persistence of embryonic vascular structures into adulthood. Additional inactivation of Hif1a in the RPE rescues the RPE morphology, aniridia, microphthalmia and anterior vasoproliferation, but does not rescue retinal vasoproliferation. These data demonstrate that Vhl-dependent regulation of Hif1a in the RPE is essential for normal RPE and iris development, ocular growth and vascular development in the anterior chamber, whereas Vhl-dependent regulation of other downstream pathways is crucial for normal development and maintenance of the retinal vasculature.

Ischaemic heart disease in pregnancy

PubMed Central

Bondagji, Nabeel S.

2012-01-01

Ischaemic heart disease (IHD) in pregnancy, particularly myocardial infarction (MI), is a rare yet potentially fatal condition for the mother and the foetus. With delays in the age of conception, the changes in some social habits among females including cigarette and shisha smoking in addition to an increased prevalence of diabetes mellitus, IHD may represent a real hazard among pregnant women in the near future. The difficulty in the diagnosis emerges from the similarity of the signs and symptoms of ischaemia and infarct to some of the physiological adaptations that occur in a normal pregnancy. The physiological changes that are normal in pregnancy may aggravate pre-existing disease and may unmask some underlying unrecognized coronary vascular changes; therefore, the diagnosis requires a high index of suspicion and careful assessment of the underlying risk factors. The management of IHD always requires a multidisciplinary team approach. The management of each patient should be individualized according to the clinical condition, the risk factors, and the availability of the necessary support. Pregnancy after MI may be an acceptable and reasonably safe option provided the cited criteria are met. A systematic PubMed search was performed to identify all published data including cases reports, small series and systematic reviews in the existing literature. These publications were comprised of both retrospective and cross sectional population studies to maximize the number of cases considered in order to reach conclusions and make recommendations based on the best available evidence considering the rare occurrence of this event. The epidemiology, diagnosis, medical and surgical treatment, and prognosis of IHD in pregnancy are the subjects of the present review. PMID:23960678

Pro-apoptotic BIM is an essential initiator of physiological endothelial cell death independent of regulation by FOXO3

PubMed Central

Koenig, M N; Naik, E; Rohrbeck, L; Herold, M J; Trounson, E; Bouillet, P; Thomas, T; Voss, A K; Strasser, A; Coultas, L

2014-01-01

The growth of new blood vessels by angiogenesis is essential for normal development, but can also cause or contribute to the pathology of numerous diseases. Recent studies have shown that BIM, a pro-apoptotic BCL2-family protein, is required for endothelial cell apoptosis in vivo, and can contribute to the anti-angiogenic effect of VEGF-A inhibitors in certain tumor models. Despite its importance, the extent to which BIM is autonomously required for physiological endothelial apoptosis remains unknown and its regulation under such conditions is poorly defined. While the transcription factor FOXO3 has been proposed to induce Bim in response to growth factor withdrawal, evidence for this function is circumstantial. We report that apoptosis was reduced in Bim−/− primary endothelial cells, demonstrating a cell-autonomous role for BIM in endothelial death following serum and growth factor withdrawal. In conflict with in vitro studies, BIM-dependent endothelial death in vivo did not require FOXO3. Moreover, endothelial apoptosis proceeded normally in mice lacking FOXO-binding sites in the Bim promoter. Bim mRNA was upregulated in endothelial cells starved of serum and growth factors and this was accompanied by the downregulation of miRNAs of the miR-17∼92 cluster. Bim mRNA levels were also elevated in miR-17∼92+/− endothelial cells cultured under steady-state conditions, suggesting that miR-17∼92 cluster miRNAs may contribute to regulating overall Bim mRNA levels in endothelial cells. PMID:24971484

Thin and open vessel windows for intra-vital fluorescence imaging of murine cochlear blood flow.

PubMed

Shi, Xiaorui; Zhang, Fei; Urdang, Zachary; Dai, Min; Neng, Lingling; Zhang, Jinhui; Chen, Songlin; Ramamoorthy, Sripriya; Nuttall, Alfred L

2014-07-01

Normal microvessel structure and function in the cochlea is essential for maintaining the ionic and metabolic homeostasis required for hearing function. Abnormal cochlear microcirculation has long been considered an etiologic factor in hearing disorders. A better understanding of cochlear blood flow (CoBF) will enable more effective amelioration of hearing disorders that result from aberrant blood flow. However, establishing the direct relationship between CoBF and other cellular events in the lateral wall and response to physio-pathological stress remains a challenge due to the lack of feasible interrogation methods and difficulty in accessing the inner ear. Here we report on new methods for studying the CoBF in a mouse model using a thin or open vessel-window in combination with fluorescence intra-vital microscopy (IVM). An open vessel-window enables investigation of vascular cell biology and blood flow permeability, including pericyte (PC) contractility, bone marrow cell migration, and endothelial barrier leakage, in wild type and fluorescent protein-labeled transgenic mouse models with high spatial and temporal resolution. Alternatively, the thin vessel-window method minimizes disruption of the homeostatic balance in the lateral wall and enables study CoBF under relatively intact physiological conditions. A thin vessel-window method can also be used for time-based studies of physiological and pathological processes. Although the small size of the mouse cochlea makes surgery difficult, the methods are sufficiently developed for studying the structural and functional changes in CoBF under normal and pathological conditions. Copyright © 2014 Elsevier B.V. All rights reserved.

Multiple functions of BCL-2 family proteins.

PubMed

Hardwick, J Marie; Soane, Lucian

2013-02-01

BCL-2 family proteins are the regulators of apoptosis, but also have other functions. This family of interacting partners includes inhibitors and inducers of cell death. Together they regulate and mediate the process by which mitochondria contribute to cell death known as the intrinsic apoptosis pathway. This pathway is required for normal embryonic development and for preventing cancer. However, before apoptosis is induced, BCL-2 proteins have critical roles in normal cell physiology related to neuronal activity, autophagy, calcium handling, mitochondrial dynamics and energetics, and other processes of normal healthy cells. The relative importance of these physiological functions compared to their apoptosis functions in overall organismal physiology is difficult to decipher. Apoptotic and noncanonical functions of these proteins may be intertwined to link cell growth to cell death. Disentanglement of these functions may require delineation of biochemical activities inherent to the characteristic three-dimensional shape shared by distantly related viral and cellular BCL-2 family members.

Cortisol as a Biomarker of Stress in Term Human Labor: Physiological and Methodological Issues

PubMed Central

Newton, Edward R.; Tanner, Charles J.; Heitkemper, Margaret M.

2013-01-01

Literature on the use of plasma cortisol to quantify psychophysiological stress in humans is extensive. However, in parturition at term gestation the use of cortisol as a biomarker of stress is particularly complex. Plasma cortisol levels increase as labor progresses. This increase seems to be important for maintenance of maternal/fetal wellbeing and facilitation of normal labor progress. Unique physiological and methodological issues involved in the use of cortisol as a biomarker of stress in labor present challenges for researchers. This review examines these issues, suggests mixed methods and within-subject repeated measures designs, and offers recommendations for assay procedures for parturient sampling. Documentation of clinical interventions and delivery outcomes may elucidate relationships among psychophysiological stressors, cortisol and normal labor progress. With attention to these methodological issues, analysis of plasma cortisol may lead to clinical interventions that support normal labor physiology. PMID:23338011

Hippo vs. Crab: tissue-specific functions of the mammalian Hippo pathway.

PubMed

Nishio, Miki; Maehama, Tomohiko; Goto, Hiroki; Nakatani, Keisuke; Kato, Wakako; Omori, Hirofumi; Miyachi, Yosuke; Togashi, Hideru; Shimono, Yohei; Suzuki, Akira

2017-01-01

The Hippo signaling pathway is a vital suppressor of tumorigenesis that is often inactivated in human cancers. In normal cells, the Hippo pathway is triggered by external forces such as cell crowding, or changes to the extracellular matrix or cell polarity. Once activated, Hippo signaling down-regulates transcription supported by the paralogous cofactors YAP1 and TAZ. The Hippo pathway's functions in normal and cancer biology have been dissected by studies of mutant mice with null or conditional tissue-specific mutations of Hippo signaling elements. In this review, we attempt to systematically summarize results that have been gleaned from detailed in vivo characterizations of these mutants. Our goal is to describe the physiological roles of Hippo signaling in several normal organ systems, as well as to emphasize how disruption of the Hippo pathway, and particularly hyperactivation of YAP1/TAZ, can be oncogenic. © 2017 The Authors Genes to Cells published by Molecular Biology Society of Japan and John Wiley & Sons Australia, Ltd.

Neural control of renal tubular solute and water transport.

PubMed

DiBona, G F

1989-01-01

The neural control of renal tubular solute and water transport is recognized as an important physiological mechanism in the overall regulation of solute and water homeostasis by the mammalian organism. Recent studies have expanded the understanding of this mechanism concerning the transport of diverse solutes with beginning insight into the precise nature of the cellular transport processes involved. The modulatory roles of both circulating and intrarenal hormonal systems on the responses to alterations in the magnitude of efferent renal sympathetic nerve activity are being understood from the nerve terminal release of neurotransmitter to influences on cellular transport processes which determine the overall effect. When dietary sodium intake is normal or only modestly reduced, intact renal innervation is not essential for normal renal sodium conservation. However, when dietary sodium intake is severely restricted, there is maximum engagement of all mechanisms known to participate in renal sodium conservation and, under these conditions, intact renal innervation is essential for normal renal sodium conservation.

Rectal temperatures, respiratory rates, production, and reproduction performances of crossbred Girolando cows under heat stress in northeastern Brazil

NASA Astrophysics Data System (ADS)

da Costa, Antônio Nélson Lima; Feitosa, José Valmir; Montezuma, Péricles Afonso; de Souza, Priscila Teixeira; de Araújo, Airton Alencar

2015-11-01

This study compared the two breed groups of Girolando (½ Holstein ½ Gyr vs. ¾ Holstein ¼ Gyr) through analysis of the percentages (stressed or non-stressed cows) of rectal temperature (RT), respiratory rate (RR) and pregnancy rate (PR), and means of production and reproduction parameters to determine the group best suited to rearing in semiarid tropical climate. The experiment was conducted at the farm, in the municipality of Umirim, State of Ceará, Brazil. Two hundred and forty cows were used in a 2 × 2 factorial study; 120 of each group were kept under an intensive system during wet and dry seasons. The environmental parameters obtained were relative humidity (RH), air temperature (AT), and the temperature and humidity index (THI). Pregnancy diagnosis (PD) was determined by ultrasonography 30 days after artificial insemination (AI). The milk production of each cow was recorded with automated milkings in the farm. The variables were expressed as mean and standard error, evaluated by ANOVA at 5 % probability using the GLM procedure of SAS. Chi-square test at 5 % probability was applied to data of RT, RR, pregnancy rate (PR), and the number of AIs to obtain pregnancy. The majority of ½ Holstein cows showed mean values of RT and RR within the normal range in both periods and shifts. Most animals of the ¾ Holstein group exhibited the RR means above normal during the afternoon in the rainy and dry periods and RT means above normal during the afternoon in the dry period. After analyses, ½ Holstein crossbred cows are more capable of thermoregulating than ¾ Holstein cows under conditions of thermal stress, and the dry period was more impacting for bovine physiology with significant changes in physiological parameters, even for the first breed group. Knowledge of breed groups adapted to climatic conditions of northeastern Brazil can directly assist cattle farmers in selecting animals best adapted for forming herds.

Rectal temperatures, respiratory rates, production, and reproduction performances of crossbred Girolando cows under heat stress in northeastern Brazil.

PubMed

da Costa, Antônio Nélson Lima; Feitosa, José Valmir; Montezuma, Péricles Afonso; de Souza, Priscila Teixeira; de Araújo, Airton Alencar

2015-11-01

This study compared the two breed groups of Girolando (½ Holstein ½ Gyr vs. ¾ Holstein ¼ Gyr) through analysis of the percentages (stressed or non-stressed cows) of rectal temperature (RT), respiratory rate (RR) and pregnancy rate (PR), and means of production and reproduction parameters to determine the group best suited to rearing in semiarid tropical climate. The experiment was conducted at the farm, in the municipality of Umirim, State of Ceará, Brazil. Two hundred and forty cows were used in a 2 × 2 factorial study; 120 of each group were kept under an intensive system during wet and dry seasons. The environmental parameters obtained were relative humidity (RH), air temperature (AT), and the temperature and humidity index (THI). Pregnancy diagnosis (PD) was determined by ultrasonography 30 days after artificial insemination (AI). The milk production of each cow was recorded with automated milkings in the farm. The variables were expressed as mean and standard error, evaluated by ANOVA at 5% probability using the GLM procedure of SAS. Chi-square test at 5% probability was applied to data of RT, RR, pregnancy rate (PR), and the number of AIs to obtain pregnancy. The majority of ½ Holstein cows showed mean values of RT and RR within the normal range in both periods and shifts. Most animals of the ¾ Holstein group exhibited the RR means above normal during the afternoon in the rainy and dry periods and RT means above normal during the afternoon in the dry period. After analyses, ½ Holstein crossbred cows are more capable of thermoregulating than ¾ Holstein cows under conditions of thermal stress, and the dry period was more impacting for bovine physiology with significant changes in physiological parameters, even for the first breed group. Knowledge of breed groups adapted to climatic conditions of northeastern Brazil can directly assist cattle farmers in selecting animals best adapted for forming herds.

Is Physiology the Locus of Health/Health Promotion?

ERIC Educational Resources Information Center

Zbilut, Joseph P.

2008-01-01

A current trend in physiology education involves the use of clinical vignettes to demonstrate the importance of knowing normal physiology to appreciate pathophysiology. Although laudable, in effect, such tactics promote the so-called "disease" model of medicine while at the same time suggesting that the only utility for the knowledge of physiology…

Physiological responses of Daphnia pulex to acid stress

PubMed Central

Weber, Anna K; Pirow, Ralph

2009-01-01

Background Acidity exerts a determining influence on the composition and diversity of freshwater faunas. While the physiological implications of freshwater acidification have been intensively studied in teleost fish and crayfish, much less is known about the acid-stress physiology of ecologically important groups such as cladoceran zooplankton. This study analyzed the extracellular acid-base state and CO2 partial pressure (PCO2), circulation and ventilation, as well as the respiration rate of Daphnia pulex acclimated to acidic (pH 5.5 and 6.0) and circumneutral (pH 7.8) conditions. Results D. pulex had a remarkably high extracellular pH of 8.33 and extracellular PCO2 of 0.56 kPa under normal ambient conditions (pH 7.8 and normocapnia). The hemolymph had a high bicarbonate concentration of 20.9 mM and a total buffer value of 51.5 meq L-1 pH-1. Bicarbonate covered 93% of the total buffer value. Acidic conditions induced a slight acidosis (ΔpH = 0.16–0.23), a 30–65% bicarbonate loss, and elevated systemic activities (tachycardia, hyperventilation, hypermetabolism). pH 6.0 animals partly compensated the bicarbonate loss by increasing the non-bicarbonate buffer value from 2.0 to 5.1 meq L-1 pH-1. The extracellular PCO2 of pH 5.5 animals was significantly reduced to 0.33 kPa, and these animals showed the highest tolerance to a short-term exposure to severe acid stress. Conclusion Chronic exposure to acidic conditions had a pervasive impact on Daphnia's physiology including acid-base balance, extracellular PCO2, circulation and ventilation, and energy metabolism. Compensatory changes in extracellular non-bicarbonate buffering capacity and the improved tolerance to severe acid stress indicated the activation of defense mechanisms which may result from gene-expression mediated adjustments in hemolymph buffer proteins and in epithelial properties. Mechanistic analyses of the interdependence between extracellular acid-base balance and CO2 transport raised the question of whether a carbonic anhydrase (CA) is involved in the catalysis of the reaction, which led to the discovery of 31 CA-genes in the genome of D. pulex. PMID:19383148

Changes in ganglion cell physiology during retinal degeneration influence excitability by prosthetic electrodes

NASA Astrophysics Data System (ADS)

Cho, Alice; Ratliff, Charles; Sampath, Alapakkam; Weiland, James

2016-04-01

Objective. Here we investigate ganglion cell physiology in healthy and degenerating retina to test its influence on threshold to electrical stimulation. Approach. Age-related Macular Degeneration and Retinitis Pigmentosa cause blindness via outer retinal degeneration. Inner retinal pathways that transmit visual information to the central brain remain intact, so direct electrical stimulation from prosthetic devices offers the possibility for visual restoration. Since inner retinal physiology changes during degeneration, we characterize physiological properties and responses to electrical stimulation in retinal ganglion cells (RGCs) of both wild type mice and the rd10 mouse model of retinal degeneration. Main results. Our aggregate results support previous observations that elevated thresholds characterize diseased retinas. However, a physiology-driven classification scheme reveals distinct sub-populations of ganglion cells with thresholds either normal or strongly elevated compared to wild-type. When these populations are combined, only a weakly elevated threshold with large variance is observed. The cells with normal threshold are more depolarized at rest and exhibit periodic oscillations. Significance. During degeneration, physiological changes in RGCs affect the threshold stimulation currents required to evoke action potentials.

The effects of high temperature and roof modification on physiological responses of swamp buffalo ( Bubalus bubalis) in the tropics

NASA Astrophysics Data System (ADS)

Khongdee, Titaporn; Sripoon, S.; Vajrabukka, C.

2013-05-01

The objective of the experiments reported here was to measure the effects of cooling techniques (Modified roof vs Normal roof) on the performance and physiology of 12 young male buffaloes with a similar live weight of 160 kg. The study was conducted at Chainat Agriculture and Technology College, Chainat Province, Thailand. The animals were divided randomly into two groups, each group comprising six buffaloes, and the two groups were studied to evaluate the effects of modified roofing (normal roof fitted with woven polypropylene shade cloth) on the subjects' physiological responses to heat stress under hot humid conditions. The modified roof resulted in lowered heat stress in buffaloes compared to those under a standard roof. The difference was shown by the buffaloes having a significantly lower mean rectal temperature (39.14 ± 0.07 vs 40.00 ± 0.10°C) and plasma cortisol (2.14 ± 0.24 vs 3.38 ± 0.37 ng/ml). The average daily water consumption was significantly lower in the MR group (MR, 29.71 ± 0.86 vs NR, 34.14 ± 1.06 L head -1 day-1), while there was a tendency for the roughage intake to be higher in the MR group compared to that of the NR group (MR, 5.88 ± 0.18 vs NR, 6.44 ± 0.19 kg head-1 -1 day-1; P = 0.0508). It was concluded that roof modification facilitated a reduction in heat load from roof re-radiation, and was an effective means of alleviating thermal stress in young buffaloes.

Metabolomic strategies to map functions of metabolic pathways.

PubMed

Mulvihill, Melinda M; Nomura, Daniel K

2014-08-01

Genome sequencing efforts have revealed a strikingly large number of unannotated and uncharacterized genes that fall into metabolic enzymes classes, likely indicating that our current knowledge of biochemical pathways in normal physiology, let alone in disease states, remains largely incomplete. This realization presents a daunting challenge for post-genomic-era scientists in deciphering the biochemical and (patho)physiological roles of these enzymes and their metabolites and metabolic networks. This is further complicated by many recent studies showing a rewiring of normal metabolic networks in disease states to give rise to unique pathophysiological functions of enzymes, metabolites, and metabolic pathways. This review focuses on recent discoveries made using metabolic mapping technologies to uncover novel pathways and metabolite-mediated posttranslational modifications and epigenetic alterations and their impact on physiology and disease. Copyright © 2014 the American Physiological Society.

Abnormal Pulmonary Function in Adults with Sickle Cell Anemia

PubMed Central

Klings, Elizabeth S.; Wyszynski, Diego F.; Nolan, Vikki G.; Steinberg, Martin H.

2006-01-01

Rationale: Pulmonary complications of sickle cell anemia (Hb-SS) commonly cause morbidity, yet few large studies of pulmonary function tests (PFTs) in this population have been reported. Objectives: PFTs (spirometry, lung volumes, and diffusion capacity for carbon monoxide [DLCO]) from 310 adults with Hb-SS were analyzed to determine the pattern of pulmonary dysfunction and their association with other systemic complications of sickle cell disease. Methods: Raw PFT data were compared with predicted values. Each subject was subclassified into one of five groups: obstructive physiology, restrictive physiology, mixed obstructive/restrictive physiology, isolated low DLCO, or normal. The association between laboratory data of patients with decreased DLCO or restrictive physiology and those of normal subjects was assessed by multivariate linear regression. Measurements and Main Results: Normal PFTs were present in only 31 of 310 (10%) patients. Overall, adults with Hb-SS were characterized by decreased total lung capacities (70.2 ± 14.7% predicted) and DlCO (64.5 ± 19.9%). The most common PFT patterns were restrictive physiology (74%) and isolated low DlCO (13%). Decreased DLCO was associated with thrombocytosis (p = 0.05), with hepatic dysfunction (elevated alanine aminotransferase; p = 0.07), and a trend toward renal dysfunction (elevated blood urea nitrogen and creatinine; p = 0.05 and 0.07, respectively). Conclusions: Pulmonary function is abnormal in 90% of adult patients with Hb-SS. Common abnormalities include restrictive physiology and decreased DLCO. Decreased DLCO may indicate more severe sickle vasculopathy characterized by impaired hepatic and renal function. PMID:16556694

Physiological and isotopic responses of scleractinian corals to ocean acidification

NASA Astrophysics Data System (ADS)

Krief, Shani; Hendy, Erica J.; Fine, Maoz; Yam, Ruth; Meibom, Anders; Foster, Gavin L.; Shemesh, Aldo

2010-09-01

Uptake of anthropogenic CO 2 by the oceans is altering seawater chemistry with potentially serious consequences for coral reef ecosystems due to the reduction of seawater pH and aragonite saturation state ( Ωarag). The objectives of this long-term study were to investigate the viability of two ecologically important reef-building coral species, massive Porites sp. and Stylophora pistillata, exposed to high pCO 2 (or low pH) conditions and to observe possible changes in physiologically related parameters as well as skeletal isotopic composition. Fragments of Porites sp. and S. pistillata were kept for 6-14 months under controlled aquarium conditions characterized by normal and elevated pCO 2 conditions, corresponding to pH T values of 8.09, 7.49, and 7.19, respectively. In contrast with shorter, and therefore more transient experiments, the long experimental timescale achieved in this study ensures complete equilibration and steady state with the experimental environment and guarantees that the data provide insights into viable and stably growing corals. During the experiments, all coral fragments survived and added new skeleton, even at seawater Ωarag < 1, implying that the coral skeleton is formed by mechanisms under strong biological control. Measurements of boron (B), carbon (C), and oxygen (O) isotopic composition of skeleton, C isotopic composition of coral tissue and symbiont zooxanthellae, along with physiological data (such as skeletal growth, tissue biomass, zooxanthellae cell density, and chlorophyll concentration) allow for a direct comparison with corals living under normal conditions and sampled simultaneously. Skeletal growth and zooxanthellae density were found to decrease, whereas coral tissue biomass (measured as protein concentration) and zooxanthellae chlorophyll concentrations increased under high pCO 2 (low pH) conditions. Both species showed similar trends of δ 11B depletion and δ 18O enrichment under reduced pH, whereas the δ 13C results imply species-specific metabolic response to high pCO 2 conditions. The skeletal δ 11B values plot above seawater δ 11B vs. pH borate fractionation curves calculated using either the theoretically derived α B value of 1.0194 (Kakihana et al. (1977) Bull. Chem. Soc. Jpn.50, 158) or the empirical α B value of 1.0272 (Klochko et al. (2006) EPSL248, 261). However, the effective α B must be greater than 1.0200 in order to yield calculated coral skeletal δ 11B values for pH conditions where Ωarag ⩾ 1. The δ 11B vs. pH offset from the seawater δ 11B vs. pH fractionation curves suggests a change in the ratio of skeletal material laid down during dark and light calcification and/or an internal pH regulation, presumably controlled by ion-transport enzymes. Finally, seawater pH significantly influences skeletal δ 13C and δ 18O. This must be taken into consideration when reconstructing paleo-environmental conditions from coral skeletons.

A Multi-Scale Sampling Strategy for Detecting Physiologically Significant Signals in AVIRIS Imagery

NASA Technical Reports Server (NTRS)

Gamon, John A.; Lee, Lai-Fun; Qiu, Hong-Lie; Davis, Stephen; Roberts, Dar A.; Ustin, Susan L.

1998-01-01

Models of photosynthetic production at ecosystem and global scales require multiple input parameters specifying physical and physiological surface features. While certain physical parameters (e.g., absorbed photosynthetically active radiation) can be derived from current satellite sensors, other physiologically relevant measures (e.g., vegetation type, water status, carboxylation capacity, or photosynthetic light-use efficiency), are not generally directly available from current satellite sensors at the appropriate geographic scale. Consequently, many model parameters must be assumed or derived from independent sources, often at an inappropriate scale. An abundance of ecophysiological studies at the leaf and canopy scales suggests strong physiological control of vegetation-atmosphere CO2 and water vapor fluxes, particularly in evergreen vegetation subjected to diurnal or seasonal stresses. For example hot, dry conditions can lead to stomatal closure, and associated "downregulation" of photosynthetic biochemical processes, a phenomenon often manifested as a "midday photosynthetic depression". A recent study with the revised simple biosphere (SiB2) model demonstrated that photosynthetic downregulation can significantly impact global climate. However, at the global scale, the exact significance of downregulation remains unclear, largely because appropriate physiological measures are generally unavailable at this scale. Clearly, there is a need to develop reliable ways of extracting physiologically relevant information from remote sensing. Narrow-band spectrometers offer many opportunities for deriving physiological parameters needed for ecosystem and global scale photosynthetic models. Experimental studies on the ground at the leaf- to stand-scale have indicated that several narrow-band features can be used to detect plant physiological status. One physiological signal is caused by xanthophyll cycle pigment activity, and is often expressed as the Photochemical Reflectance Index (PRI). Because the xanthophyll cycle pigments are photoregulatory pigments closely linked to photosynthetic function, this index can be used to derive relative photosynthetic rates. An additional signal with physiological significance is the 970 nm water absorption band, which provides a measure of liquid water content. This feature has been quantified both using a simple 2-band ratio (900/970 nm, here referred to as the "Water Band Index" or WBI;), and using the "continuum removal" method. Current atmospheric correction methods for AVIRIS imagery also obtain quantitative expressions of surface liquid water absorption based on the 970 nm water band and may be comparable to ground-based estimates of water content using this feature. However, physiological interpretations of both the PRI and the WBI are best understood at the leaf and canopy scales, where complications of atmospheric interference and complex stand and landscape features can be minimized, and where experimental manipulations can be readily applied. Currently it is not known whether these physiological indices can be used to derive meaningful physiological information from AVIRIS imagery. In addition to the problem of atmospheric interference, another challenge is that any simple physiological index can be confounded by multiple factors unrelated to physiology, and this problem can become more severe at progressively larger spatial scales. For example, previous work has suggested that both the PRI and the WBI, are strongly correlated with other optical measures of canopy structure (e.g., the Normalized Difference Vegetation Index or green vegetation fraction), indicating a confounding effect of structure on physiological signals at the larger, landscape scale. Furthermore, the normal operating mode of most imaging spectrometers does not allow simultaneous, ground truthing at a level of detail needed for physiological sampling. Additionally, manipulative experiments of physiology are difficult to apply at a geographic scale suitable for comparison with remote imagery, which often works at spatial scales that are several orders of magnitude larger than those typically used for physiological studies. These limitations require the consideration of alternative approaches to validating physiological information derived from AVIRIS data. In this report, we present a multi-scale sampling approach to detecting physiologically significant signals in narrow-band spectra. This approach explores the multi-dimensional data space provided by narrow-band spectrometry, and combines AVIRIS imagery at a large scale, with ground spectral sampling at an intermediate scale, and detailed ecophysiological measurements at a fine scale, to examine seasonally and spatially changing relationships between multiple structural and physiological variables. Examples of this approach are provided by simultaneous sampling of the Normalized Difference Vegetation Index (NDVI), an index of fractional PAR interception and green vegetation cover, the Water Band Index (WBI, an index of liquid water absorption, and the Photochemical Reflectance Index (PRI, an index of xanthophyll cycle pigment activity and photosynthetic light-use efficiency. By directly linking changing optical properties sampled on the ground with measurable physiological states, we hope to develop a basis for interpreting similar signals in AVIRIS imagery.

The inhibitory effects of nicotine on physiological sexual arousal in nonsmoking women: results from a randomized, double-blind, placebo-controlled, cross-over trial.

PubMed

Harte, Christopher B; Meston, Cindy M

2008-05-01

Extensive research suggests that long-term cigarette smoking is an independent risk factor for the introduction of sexual dysfunction in men. However, results of limited data investigating this relationship in women are mixed. No studies have examined the acute effects of tobacco or nicotine on physiological sexual response in women. Controlled experimental studies examining acute effects of isolated nicotine intake on female physiological sexual responses are necessary in order to help elucidate tobacco's potential role in the development and/or maintenance of sexual impairment in women. To examine whether isolated nicotine intake acutely affects sexual arousal responses in nonsmoking women. Twenty-five sexually functional women (mean age = 20 years) each with less than 100 direct exposures to nicotine completed two counterbalanced conditions in which they were randomized to received either nicotine gum (6 mg) or placebo gum, both administered double-blind and matched for appearance, taste, and consistency, approximately 40 minutes prior to viewing an erotic film. Physiological (changes in vaginal pulse amplitude via vaginal photoplethysmography) and subjective (continuous self-report) sexual responses to erotic stimuli were examined, as well as changes in mood. Nicotine significantly reduced genital responses to the erotic films (P = 0.05), corresponding to a 30% attenuation in physiological sexual arousal. This occurred in 11 of 18 women with valid physiological assessments. Nicotine had no significant effect on continuous self-report ratings of sexual arousal (P = 0.45), or on mood (all Ps > 0.05). Acute nicotine intake significantly attenuates physiological sexual arousal in healthy nonsmoking women. Our findings provide support to the hypothesis that nicotine may be the primary pharmacological agent responsible for genital hemodynamic disruption, thereby facilitating a cascade of biochemical and vascular events which may impair normal sexual arousal responses.

[Hemolysis Performance Analysis of the Centrifugal Maglev Blood Pump].

PubMed

Wang, Yiwen; Zhang, Fan; Fang, Yuan; Dong, Baichuan; Zhou, Liang

2016-05-01

In order to analyze and study the hemolysis performance of the centrifugal maglev blood pump, which was designed by ourselves, this paper built the mathematical model and computational fluid dynamics analyzed it using Fluent. Then we set up the in vitro hemolysis experiment platform, in case of the design condition, the content of free hemoglobin and hematocrit in plasma were measured in a certain time interval, and calculated the normalized index of hemolysis of the blood pump. The numerical simulation results show the internal static pressure distribution is smooth inside the pump, the wal shear stress inside the pump is less than 150 Pa. Therefore, the red blood cel damage and exposure time is independent. The normalized index of hemolysis is (0.002 9±0.000 7) mg/L, which is in accordance with human physiological requirement.

The Effect of Aging on the Cutaneous Microvasculature

PubMed Central

Bentov, Itay; Reed, May J

2015-01-01

Aging is associated with a progressive loss of function in all organs. Under normal conditions the physiologic compensation for age-related deficits is sufficient, but during times of stress the limitations of this reserve become evident. Explanations for this reduction in reserve include the changes in the microcirculation that occur during the normal aging process. The microcirculation is defined as the blood flow through arterioles, capillaries and venules, which are the smallest vessels in the vasculature and are embedded within organs and tissues. Optimal strategies to maintain the microvasculature following surgery and other stressors must use multifactorial approaches. Using skin as the model organ, we will review the anatomical and functional changes in the microcirculation with aging, and some of the available clinical strategies to potentially mitigate the effect of these changes on important clinical outcomes. PMID:25917013

A physiological model for the investigation of esophageal motility in healthy and pathologic conditions.

PubMed

Carniel, Emanuele Luigi; Frigo, Alessandro; Costantini, Mario; Giuliani, Tommaso; Nicoletti, Loredana; Merigliano, Stefano; Natali, Arturo N

2016-07-15

Recent technological advances in esophageal manometry allowed the definition of new classification methods for the diagnosis of disorders of esophageal motility and the implementation of innovative computational tools for the autonomic, reliable and unbiased detection of different disorders. Computational models can be developed aiming to interpret the mechanical behavior and functionality of the gastrointestinal tract and to summarize the results from clinical measurements, as high-resolution manometry pressure plots, into model parameters. A physiological model was here developed to interpret data from esophageal high-resolution manometry. Such model accounts for parameters related to specific physiological properties of the biological structures involved in the peristaltic mechanism. The identification of model parameters was performed by minimizing the discrepancy between clinical data from high-resolution manometry and model results. Clinical data were collected from both healthy volunteers (n = 35) and patients with different motor disorders, such as achalasia patterns 1 (n = 13), 2 (n = 20) and 3 (n = 5), distal esophageal spasm (n = 69), esophago-gastric junction outflow obstruction (n = 25), nutcracker esophagus (n = 11) and normal motility (n = 42). The physiological model that was formulated in this work can properly explain high-resolution manometry data, as confirmed by the evaluation of the coefficient of determination R 2  = 0.83 - 0.96. The study finally led to identify the statistical distributions of model parameters for each healthy or pathologic conditions considered, addressing the applicability of the achieved results for the implementation of autonomic diagnosis procedures to support the medical staff during the traditional diagnostic process. © IMechE 2016.

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.

Sleep and bodily functions: the physiological interplay between body homeostasis and sleep homeostasis.

PubMed

Amici, R; Bastianini, S; Berteotti, C; Cerri, M; Del Vecchio, F; Lo Martire, V; Luppi, M; Perez, E; Silvani, A; Zamboni, G; Zoccoli, G

2014-01-01

Body homeostasis and sleep homeostasis may both rely on the complex integrative activity carried out by the hypothalamus. Thus, the three main wake-sleep (WS) states (i.e. wakefulness, NREM sleep, and REM sleep) may be better understood if the different cardio-respiratory and metabolic parameters, which are under the integrated control of the autonomic and the endocrine systems, are studied during sleep monitoring. According to this view, many physiological events can be considered as an expression of the activity that physiological regulations should perform in order to cope with the need to fulfill body and sleep homeostasis. This review is aimed at making an assessment of data showing the existence of a physiological interplay between body homeostasis and sleep homeostasis, starting from the spontaneous changes observed in the somatic and autonomic activity during sleep, through evidence showing the deep changes occurring in the central integration of bodily functions during the different WS states, to the changes in the WS states observed when body homeostasis is challenged by the external environment and when the return to normal ambient conditions allows sleep homeo- stasis to run without apparent physiological restrictions. The data summarized in this review suggest that an approach to the dichotomy between NREM and REM sleep based on physiological regulations may offer a framework within which observations that a traditional behavioral approach may overlook can be interpreted. The study of the interplay between body and sleep homeostasis appears, therefore, to be a way to understand the function of complex organisms beyond that of the specific regulations.

Diggin’ on U(biquitin): A Novel Method for the Identification of Physiological E3 Ubiquitin Ligase Substrates

PubMed Central

Rubel, Carrie E.; Schisler, Jonathan C.; Hamlett, Eric D.; DeKroon, Robert M.; Gautel, Mathias; Alzate, Oscar; Patterson, Cam

2013-01-01

The ubiquitin-proteasome system (UPS) plays a central role in maintaining protein homeostasis, emphasized by a myriad of diseases that are associated with altered UPS function such as cancer, muscle-wasting, and neurodegeneration. Protein ubiquitination plays a central role in both the promotion of proteasomal degradation as well as cellular signaling through regulation of the stability of transcription factors and other signaling molecules. Substrate specificity is a critical regulatory step of ubiquitination and is mediated by ubiquitin ligases. Recent studies implicate ubiquitin ligases in multiple models of cardiac diseases such as cardiac hypertrophy, atrophy, and ischemia/reperfusion injury, both in a cardioprotective and maladaptive role. Therefore, identifying physiological substrates of cardiac ubiquitin ligases provides both mechanistic insights into heart disease as well as possible therapeutic targets. Current methods identifying substrates for ubiquitin ligases rely heavily upon non-physiologic in vitro methods, impeding the unbiased discovery of physiological substrates in relevant model systems. Here we describe a novel method for identifying ubiquitin ligase substrates utilizing Tandem Ubiquitin Binding Entities (TUBE) technology, two-dimensional differential in gel electrophoresis (2-D DIGE), and mass spectrometry, validated by the identification of both known and novel physiological substrates of the ubiquitin ligase MuRF1 in primary cardiomyocytes. This method can be applied to any ubiquitin ligase, both in normal and disease model systems, in order to identify relevant physiological substrates under various biological conditions, opening the door to a clearer mechanistic understanding of ubiquitin ligase function and broadening their potential as therapeutic targets. PMID:23695782

Manipulation of heart rate variability can modify response to anger-inducing stimuli.

PubMed

Francis, Heather M; Penglis, Kathryn M; McDonald, Skye

2016-10-01

Research suggests that heart rate variability (HRV) is a physiological indicator of the flexibility of the autonomic nervous system and can provide an objective measure of an individual's ability to appropriately match emotional responses to environmental demands. The present study investigated whether angry response to emotional stimuli was related to HRV, and whether manipulation of HRV using biofeedback could change the anger response in a healthy adult population. Fifty-eight participants received HRV biofeedback (n = 29) or an active control condition (n = 29). HRV measures included standard deviation of normal-to-normal intervals (SDNN), low-frequency (LF) and high-frequency (HF) power, and was recorded across three sessions: baseline, training, and anger induction. The anger induction procedure resulted in increased subjective experience of anger, as well as physiological changes. The biofeedback group had higher HRV than active controls both during the training session (SDNN and LF HRV) and during anger induction (LF HRV). HRV during anger induction was significantly associated with self-reported emotional response for participants receiving biofeedback but not for active controls. Results provide support for HRV as an index of emotion regulation, specifically anger. Further research is needed to determine whether long-term HRV biofeedback can have a lasting effect on managing anger.

Effect of manganese chloride on the neurochemical profile of the rat hypothalamus

PubMed Central

Just, Nathalie; Cudalbu, Cristina; Lei, Hongxia; Gruetter, Rolf

2011-01-01

Manganese (Mn2+)-enhanced magnetic resonance imaging studies of the neuronal pathways of the hypothalamus showed that information about the regulation of food intake and energy balance circulate through specific hypothalamic nuclei. The dehydration-induced anorexia (DIA) model demonstrated to be appropriate for studying the hypothalamus with Mn2+-enhanced magnetic resonance imaging. Manganese is involved in the normal functioning of a variety of physiological processes and is associated with enzymes contributing to neurotransmitter synthesis and metabolism. It also induces psychiatric and motor disturbances. The molecular mechanisms by which Mn2+ produces alterations of the hypothalamic physiological processes are not well understood. 1H-magnetic resonance spectroscopy measurements of the rodent hypothalamus are challenging due to the distant location of the hypothalamus resulting in limited measurement sensitivity. The present study proposed to investigate the effects of Mn2+ on the neurochemical profile of the hypothalamus in normal, DIA, and overnight fasted female rats at 14.1 T. Results provide evidence that γ-aminobutyric acid has an essential role in the maintenance of energy homeostasis in the hypothalamus but is not condition specific. On the contrary, glutamine, glutamate, and taurine appear to respond more accurately to Mn2+ exposure. An increase in glutamine levels could also be a characteristic response of the hypothalamus to DIA. PMID:21712832

Effects of neuroinflammation on the regenerative capacity of brain stem cells.

PubMed

Russo, Isabella; Barlati, Sergio; Bosetti, Francesca

2011-03-01

In the adult brain, neurogenesis under physiological conditions occurs in the subventricular zone and in the dentate gyrus. Although the exact molecular mechanisms that regulate neural stem cell proliferation and differentiation are largely unknown, several factors have been shown to affect neurogenesis. Decreased neurogenesis in the hippocampus has been recognized as one of the mechanisms of age-related brain dysfunction. Furthermore, in pathological conditions of the central nervous system associated with neuroinflammation, inflammatory mediators such as cytokines and chemokines can affect the capacity of brain stem cells and alter neurogenesis. In this review, we summarize the state of the art on the effects of neuroinflammation on adult neurogenesis and discuss the use of the lipopolysaccharide-model to study the effects of inflammation and reactive-microglia on brain stem cells and neurogenesis. Furthermore, we discuss the possible causes underlying reduced neurogenesis with normal aging and potential anti-inflammatory, pro-neurogenic interventions aimed at improving memory deficits in normal and pathological aging and in neurodegenerative diseases. © 2011 The Authors. Journal of Neurochemistry © 2011 International Society for Neurochemistry.

Size-dependent physiological responses of the branching coral Pocillopora verrucosa to elevated temperature and PCO2.

PubMed

Edmunds, Peter J; Burgess, Scott C

2016-12-15

Body size has large effects on organism physiology, but these effects remain poorly understood in modular animals with complex morphologies. Using two trials of a ∼24 day experiment conducted in 2014 and 2015, we tested the hypothesis that colony size of the coral Pocillopora verrucosa affects the response of calcification, aerobic respiration and gross photosynthesis to temperature (∼26.5 and ∼29.7°C) and P CO 2  (∼40 and ∼1000 µatm). Large corals calcified more than small corals, but at a slower size-specific rate; area-normalized calcification declined with size. Whole-colony and area-normalized calcification were unaffected by temperature, P CO 2 , or the interaction between the two. Whole-colony respiration increased with colony size, but the slopes of these relationships differed between treatments. Area-normalized gross photosynthesis declined with colony size, but whole-colony photosynthesis was unaffected by P CO 2 , and showed a weak response to temperature. When scaled up to predict the response of large corals, area-normalized metrics of physiological performance measured using small corals provide inaccurate estimates of the physiological performance of large colonies. Together, these results demonstrate the importance of colony size in modulating the response of branching corals to elevated temperature and high P CO 2 . © 2016. Published by The Company of Biologists Ltd.

Insulin Is a Key Modulator of Fetoplacental Endothelium Metabolic Disturbances in Gestational Diabetes Mellitus

PubMed Central

Sobrevia, Luis; Salsoso, Rocío; Fuenzalida, Bárbara; Barros, Eric; Toledo, Lilian; Silva, Luis; Pizarro, Carolina; Subiabre, Mario; Villalobos, Roberto; Araos, Joaquín; Toledo, Fernando; González, Marcelo; Gutiérrez, Jaime; Farías, Marcelo; Chiarello, Delia I.; Pardo, Fabián; Leiva, Andrea

2016-01-01

Gestational diabetes mellitus (GDM) is a disease of the mother that associates with altered fetoplacental vascular function. GDM-associated maternal hyperglycaemia result in fetal hyperglycaemia, a condition that leads to fetal hyperinsulinemia and altered L-arginine transport and synthesis of nitric oxide, i.e., endothelial dysfunction. These alterations in the fetoplacental endothelial function are present in women with GDM that were under diet or insulin therapy. Since these women and their newborn show normal glycaemia at term, other factors or conditions could be altered and/or not resolved by restoring normal level of circulating D-glucose. GDM associates with metabolic disturbances, such as abnormal handling of the locally released vasodilator adenosine, and biosynthesis and metabolism of cholesterol lipoproteins, or metabolic diseases resulting in endoplasmic reticulum stress and altered angiogenesis. Insulin acts as a potent modulator of all these phenomena under normal conditions as reported in primary cultures of cells obtained from the human placenta; however, GDM and the role of insulin regarding these alterations in this disease are poorly understood. This review focuses on the potential link between insulin and endoplasmic reticulum stress, hypercholesterolemia, and angiogenesis in GDM in the human fetoplacental vasculature. Based in reports in primary culture placental endothelium we propose that insulin is a factor restoring endothelial function in GDM by reversing ERS, hypercholesterolaemia and angiogenesis to a physiological state involving insulin activation of insulin receptor isoforms and adenosine receptors and metabolism in the human placenta from GDM pregnancies. PMID:27065887

Pulp-dentin biology in restorative dentistry. Part 1: normal structure and physiology.

PubMed

Mjör, I A; Sveen, O B; Heyeraas, K J

2001-06-01

Considerable knowledge has accumulated over the years on the structure and function of the dental pulp and dentin. Some of this knowledge has important clinical implications. This review, which is the first of seven articles, will be limited to those parts of the normal structure and physiology of the pulp and dentin that have been shown to result in, or are likely lead to, tissue reactions associated with the clinical treatment of these tissues. Although certain normal structures will be highlighted in some detail, a basic knowledge of pulpal and dentinal development and structure is a prerequisite for an understanding of this text.

Physiological changes in neurodegeneration - mechanistic insights and clinical utility.

PubMed

Ahmed, Rebekah M; Ke, Yazi D; Vucic, Steve; Ittner, Lars M; Seeley, William; Hodges, John R; Piguet, Olivier; Halliday, Glenda; Kiernan, Matthew C

2018-05-01

The effects of neurodegenerative syndromes extend beyond cognitive function to involve key physiological processes, including eating and metabolism, autonomic nervous system function, sleep, and motor function. Changes in these physiological processes are present in several conditions, including frontotemporal dementia, amyotrophic lateral sclerosis, Alzheimer disease and the parkinsonian plus conditions. Key neural structures that mediate physiological changes across these conditions include neuroendocrine and hypothalamic pathways, reward pathways, motor systems and the autonomic nervous system. In this Review, we highlight the key changes in physiological processing in neurodegenerative syndromes and the similarities in these changes between different progressive neurodegenerative brain conditions. The changes and similarities between disorders might provide novel insights into the human neural correlates of physiological functioning. Given the evidence that physiological changes can arise early in the neurodegenerative process, these changes could provide biomarkers to aid in the early diagnosis of neurodegenerative diseases and in treatment trials.

Role of ACTH in the Interactive/Paracrine Regulation of Adrenal Steroid Secretion in Physiological and Pathophysiological Conditions

PubMed Central

Lefebvre, Hervé; Thomas, Michaël; Duparc, Céline; Bertherat, Jérôme; Louiset, Estelle

2016-01-01

In the normal human adrenal gland, steroid secretion is regulated by a complex network of autocrine/paracrine interactions involving bioactive signals released by endothelial cells, nerve terminals, chromaffin cells, immunocompetent cells, and adrenocortical cells themselves. ACTH can be locally produced by medullary chromaffin cells and is, therefore, a major mediator of the corticomedullary functional interplay. Plasma ACTH also triggers the release of angiogenic and vasoactive agents from adrenocortical cells and adrenal mast cells and, thus, indirectly regulates steroid production through modulation of the adrenal blood flow. Adrenocortical neoplasms associated with steroid hypersecretion exhibit molecular and cellular defects that tend to reinforce the influence of paracrine regulatory loops on corticosteroidogenesis. Especially, ACTH has been found to be abnormally synthesized in bilateral macronodular adrenal hyperplasia responsible for hypercortisolism. In these tissues, ACTH is detected in a subpopulation of adrenocortical cells that express gonadal markers. This observation suggests that ectopic production of ACTH may result from impaired embryogenesis leading to abnormal maturation of the adrenogonadal primordium. Globally, the current literature indicates that ACTH is a major player in the autocrine/paracrine processes occurring in the adrenal gland in both physiological and pathological conditions. PMID:27489549

Birth weight and prematurity in infants with single ventricle physiology: pediatric heart network infant single ventricle trial screened population.

PubMed

Williams, Richard V; Ravishankar, Chitra; Zak, Victor; Evans, Frank; Atz, Andrew M; Border, William L; Levine, Jami; Li, Jennifer S; Mahony, Lynn; Mital, Seema; Pearson, Gail D; Prakash, Ashwin; Hsu, Daphne T

2010-01-01

Although congenital heart disease is associated with low birth weight and prematurity, there is little information about these birth outcomes in infants with single ventricle physiology. We describe the birth outcomes (i.e., gestational age and birth weight) in neonates with single ventricle physiology screened for enrollment in the Pediatric Heart Network's Infant Single Ventricle Trial, compare these outcomes with US norms, and examine the association of birth outcomes with anatomic diagnosis and race. All neonates with single ventricle physiology presenting to Infant Single Ventricle Trial centers were screened for enrollment. Demographic data and anatomic diagnoses were obtained from medical records. A total of 1245 neonates with single ventricle physiology were screened at 10 centers (63 to 266 per center). Diagnoses included hypoplastic left heart syndrome in 49%, unbalanced atrioventricular septal defect in 12%, and tricuspid atresia in 9%. Preterm birth occurred in 16% of neonates with single ventricle physiology vs. 12% in normal neonates (P < .001), low birth weight (<2.5 kg) in 18% vs. 8% in normals (P < .001), and small for gestational age (<10th percentile by definition) in 22% vs. 10% in normals (P < .001). A genetic syndrome was reported in 8%. The percentage of preterm birth, low birth weight, and small for gestational age was similar between screened neonates with and without hypoplastic left heart syndrome. In this large, contemporary cohort of neonates with single ventricle physiology, rates of preterm birth, low birth weight, and small for gestational age were higher than in the general population, but similar between screened neonates with and without hypoplastic left heart syndrome.

[Prescribing monitoring in clinical practice: from enlightened empiricism to rational strategies].

PubMed

Buclin, Thierry; Herzig, Lilli

2013-05-15

Monitoring of a medical condition is the periodic measurement of one or several physiological or biological variables to detect a signal regarding its clinical progression or its response to treatment. We distinguish different medical situations between diagnostic, clinical and therapeutic process to apply monitoring. Many clinical, variables can be used for monitoring, once their intrinsic properties (normal range, critical difference, kinetics, reactivity) and external validity (pathophysiological importance, predictive power for clinical outcomes) are established. A formal conceptualization of monitoring is being developed and should support the rational development of monitoring strategies and their validation through appropriate clinical trials.

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.

Microgravity alters the physiological characteristics of Escherichia coli O157:H7 ATCC 35150, ATCC 43889, and ATCC 43895 under different nutrient conditions.

PubMed

Kim, H W; Matin, A; Rhee, M S

2014-04-01

The aim of this study is to provide understanding of microgravity effects on important food-borne bacteria, Escherichia coli O157:H7 ATCC 35150, ATCC 43889, and ATCC 43895, cultured in nutrient-rich or minimal medium. Physiological characteristics, such as growth (measured by optical density and plating), cell morphology, and pH, were monitored under low-shear modeled microgravity (LSMMG; space conditions) and normal gravity (NG; Earth conditions). In nutrient-rich medium, all strains except ATCC 35150 showed significantly higher optical density after 6 h of culture under LSMMG conditions than under NG conditions (P < 0.05). LSMMG-cultured cells were approximately 1.8 times larger than NG-cultured cells at 24 h; therefore, it was assumed that the increase in optical density was due to the size of individual cells rather than an increase in the cell population. The higher pH of the NG cultures relative to that of the LSMMG cultures suggests that nitrogen metabolism was slower in the latter. After 24 h of culturing in minimal media, LSMMG-cultured cells had an optical density 1.3 times higher than that of NG-cultured cells; thus, the higher optical density in the LSMMG cultures may be due to an increase in both cell size and number. Since bacteria actively grew under LSMMG conditions in minimal medium despite the lower pH, it is of some concern that LSMMG-cultured E. coli O157:H7 may be able to adapt well to acidic environments. These changes may be caused by changes in nutrient metabolism under LSMMG conditions, although this needs to be demonstrated in future studies.

Effects of progressive relaxation and classical music on measurements of attention, relaxation, and stress responses.

PubMed

Scheufele, P M

2000-04-01

The present experiment examined relaxation using different experimental conditions to test whether the effects of individual elements of relaxation could be measured, whether specific effects were revealed, or whether relaxation resulted from a generalized "relaxation response." Sixty-seven normal, male volunteers were exposed to a stress manipulation and then to one of two relaxation (Progressive Relaxation, Music) or control (Attention Control, Silence) conditions. Measurements of attention, relaxation, and stress responses were obtained during each phase of the experiment. All four groups exhibited similar performance on behavioral measures of attention that suggested a reduction in physiological arousal following their relaxation or control condition, as well as a decreased heart rate. Progressive Relaxation, however, resulted in the greatest effects on behavioral and self-report measures of relaxation, suggesting that cognitive cues provided by stress management techniques contribute to relaxation.

The gut in iron homeostasis: role of HIF-2 under normal and pathological conditions

PubMed Central

Mastrogiannaki, Maria; Matak, Pavle

2013-01-01

Although earlier, seminal studies demonstrated that the gut per se has the intrinsic ability to regulate the rates of iron absorption, the spotlight in the past decade has been placed on the systemic regulation of iron homeostasis by the hepatic hormone hepcidin and the molecular mechanisms that regulate its expression. Recently, however, attention has returned to the gut based on the finding that hypoxia inducible factor-2 (HIF-2α) regulates the expression of key genes that contribute to iron absorption. Here we review the current understanding of the molecular mechanisms that regulate iron homeostasis in the gut by focusing on the role of HIF-2 under physiological steady-state conditions and in the pathogenesis of iron-related diseases. We also discuss implications for adapting HIF-2–based therapeutic strategies in iron-related pathological conditions. PMID:23678007

Coordinated regulation of photosynthesis in rice increases yield and tolerance to environmental stress

PubMed Central

Ambavaram, Madana M. R.; Basu, Supratim; Krishnan, Arjun; Ramegowda, Venkategowda; Batlang, Utlwang; Rahman, Lutfor; Baisakh, Niranjan; Pereira, Andy

2014-01-01

Plants capture solar energy and atmospheric carbon dioxide (CO2) through photosynthesis, which is the primary component of crop yield, and needs to be increased considerably to meet the growing global demand for food. Environmental stresses, which are increasing with climate change, adversely affect photosynthetic carbon metabolism (PCM) and limit yield of cereals such as rice (Oryza sativa) that feeds half the world. To study the regulation of photosynthesis, we developed a rice gene regulatory network and identified a transcription factor HYR (HIGHER YIELD RICE) associated with PCM, which on expression in rice enhances photosynthesis under multiple environmental conditions, determining a morpho-physiological programme leading to higher grain yield under normal, drought and high-temperature stress conditions. We show HYR is a master regulator, directly activating photosynthesis genes, cascades of transcription factors and other downstream genes involved in PCM and yield stability under drought and high-temperature environmental stress conditions. PMID:25358745

Effects of body temperature on post-anoxic oxidative stress from the perspective of postnatal physiological adaptive processes in rats.

PubMed

Kletkiewicz, H; Rogalska, J; Nowakowska, A; Wozniak, A; Mila-Kierzenkowska, C; Caputa, M

2016-04-01

It is well known that decrease in body temperature provides protection to newborns subjected to anoxia/ischemia. We hypothesized that the normal body temperature of 33°C in neonatal rats (4°C below normal body temperature in adults) is in fact a preadaptation to protect CNS from anoxia and further reductions as well as elevations in temperature may be counterproductive. Our experiments aimed to examine the effect of changes in body temperature on oxidative stress development in newborn rats exposed to anoxia. Two-day-old Wistar rats were divided into 4 temperature groups: i. hypothermic at body temperature of 31°C, ii. maintaining physiological neonatal body temperature of 33°C, iii. forced to maintain hyperthermic temperature of 37°C, and i.v. forced to maintain hyperthermic temperature of 39°C. The temperature was controlled starting 15 minutes before and afterword during 10 minutes of anoxia as well as for 2 hours post-anoxia. Cerebral concentrations of lipid peroxidation products malondialdehyde (MDA) and conjugated dienes (CD) and the activities of antioxidant enzymes had been determined post mortem: immediately after anoxia was finished and 3, 7, and 14 days later. There were no post-anoxic changes in the concentration of MDA, CD and in antioxidant enzymes activity in newborn rats kept at their physiological body temperature of 33°C. In contrast, perinatal anoxia at body temperature elevated to 37°C or 39°C as well as under hypothermic conditions (31°C) intensified post-anoxic oxidative stress and depleted the antioxidant pool. Overall, these findings suggest that elevated body temperature (hyperthermia or fever), as well as exceeding cooling beyond the physiological level of body temperature of newborn rats, may extend perinatal anoxia-induced brain lesions. Our findings provide new insights into the role of body temperature in anoxic insult in vivo.

Right Ventricular Tissue Doppler in Space Flight

NASA Technical Reports Server (NTRS)

Garcia, Kathleen M.; Hamilton, Douglas R.; Sargsyan, Ashot E.; Ebert, Douglas; Martin, David S.; Barratt, Michael R.; Martin, David S.; Bogomolov, Valery V.; Dulchavsky, Scott A.; Duncan, J. Michael

2010-01-01

The presentation slides review normal physiology of the right ventricle in space, general physiology of the right ventricle; difficulties in imaging the heart in space, imaging methods, tissue Doppler spectrum, right ventricle tissue Doppler, and Rt Tei Index.

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

USGS Publications Warehouse

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

2014-01-01

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

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

PubMed

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

2014-01-01

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

Physiological Condition of Juvenile Wading Birds in Relation to Multiple Landscape Stressors in the Florida Everglades: Effects of Hydrology, Prey Availability, and Mercury Bioaccumulation

PubMed Central

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

2014-01-01

The physiological condition of juvenile birds can be influenced by multiple ecological stressors, and few studies have concurrently considered the effects of environmental contaminants in combination with ecological attributes that can influence foraging conditions and prey availability. Using three temporally distinct indices of physiological condition, we compared the physiological response of nestling great egrets (Ardea alba) and white ibises (Eudocimus albus) to changing prey availability, hydrology (water depth, recession rate), and mercury exposure in the Florida Everglades. We found that the physiological response of chicks varied between species and among environmental variables. Chick body condition (short-term index) and fecal corticosterone levels (medium-term) were influenced by wetland water depth, prey availability, region, and age, but not by mercury contamination. However, mercury exposure did influence heat shock protein 70 (HSP70) in egret chicks, indicating a longer-term physiological response to contamination. Our results indicate that the physiological condition of egret and ibis chicks were influenced by several environmental stressors, and the time frame of the effect may depend on the specialized foraging behavior of the adults provisioning the chicks. PMID:25184221

The link between antioxidant enzymes catalase and glutathione S-transferase and physiological condition of a control population of terrestrial isopod (Porcellio scaber).

PubMed

Jemec, Anita; Lešer, Vladka; Drobne, Damjana

2012-05-01

The aim of this work was to investigate if the activities of catalase and glutathione S-transferase in a control population of terrestrial isopods (Porcellio scaber) are correlated with the physiological condition of the isopods. For this purpose, the activities of these enzymes were analysed in isopods from a stock population and in parallel, the physiological condition of the same specimens was assessed using a histological approach based on epithelial thickness and lipid droplets. We found a correlation between antioxidant enzymes and the physiological condition of the isopods. This implies that these enzymes could be used as predictive indicators of the physiological condition in a stock population before comprehensive toxicological studies are conducted and also in control group after the experiment. When a control group is found to be very heterogeneous in terms of physiological condition, the experiment should be repeated with a larger number of experimental animals. The findings of this study will contribute to more accurate experimental design of toxicity tests when using biomarkers. This should encourage other researchers to increase their effort to know the physiological state of their test organisms. Copyright © 2011 Elsevier Inc. All rights reserved.

Tachycardia

MedlinePlus

... normal while at rest. It's normal for your heart rate to rise during exercise or as a physiological ... the heart or both while at rest. Your heart rate is controlled by electrical signals sent across heart ...

Multiorgan insulin sensitivity in lean and obese subjects.

PubMed

Conte, Caterina; Fabbrini, Elisa; Kars, Marleen; Mittendorfer, Bettina; Patterson, Bruce W; Klein, Samuel

2012-06-01

To provide a comprehensive assessment of multiorgan insulin sensitivity in lean and obese subjects with normal glucose tolerance. The hyperinsulinemic-euglycemic clamp procedure with stable isotopically labeled tracer infusions was performed in 40 obese (BMI 36.2 ± 0.6 kg/m(2), mean ± SEM) and 26 lean (22.5 ± 0.3 kg/m(2)) subjects with normal glucose tolerance. Insulin was infused at different rates to achieve low, medium, and high physiological plasma concentrations. In obese subjects, palmitate and glucose R(a) in plasma decreased with increasing plasma insulin concentrations. The decrease in endogenous glucose R(a) was greater during low-, medium-, and high-dose insulin infusions (69 ± 2, 74 ± 2, and 90 ± 2%) than the suppression of palmitate R(a) (52 ± 4, 68 ± 1, and 79 ± 1%). Insulin-mediated increase in glucose disposal ranged from 24 ± 5% at low to 253 ± 19% at high physiological insulin concentrations. The suppression of palmitate R(a) and glucose R(a) were greater in lean than obese subjects during low-dose insulin infusion but were the same in both groups during high-dose insulin infusion, whereas stimulation of glucose R(d) was greater in lean than obese subjects across the entire physiological range of plasma insulin. Endogenous glucose production and adipose tissue lipolytic rate are both very sensitive to small increases in circulating insulin, whereas stimulation of muscle glucose uptake is minimal until high physiological plasma insulin concentrations are reached. Hyperinsulinemia within the normal physiological range can compensate for both liver and adipose tissue insulin resistance, but not skeletal muscle insulin resistance, in obese people who have normal glucose tolerance.

Regulation of food intake and obesity.

PubMed

Mayer, J; Thomas, D W

1967-04-21

This is not the place to consider the medical significance of obesity in terms of conditions such as heart disease and hypertension, diabetes, and arthritis. These very complex interrelationships have been dealt with elsewhere (69). We hope that enough evidence has been presented to demonstrate that energy balance is normally maintained by a precise and reliable physiologic mechanism, and that the energy surplus represented by obesity may reflect direct failure of this mechanism or some combination from a variety of neurological, endocrine, enzymatic, and psychological disorders. Environmental conditions as well as genetic and traumatic factors may contribute to the development of obesity. If increasing mechanization brings tus below the level of energy expenditure at which food intake is properly regulated, appropriate habits of exercise will have to be established and maintained.

Lignocellulosic ethanol production at high-gravity: challenges and perspectives.

PubMed

Koppram, Rakesh; Tomás-Pejó, Elia; Xiros, Charilaos; Olsson, Lisbeth

2014-01-01

In brewing and ethanol-based biofuel industries, high-gravity fermentation produces 10-15% (v/v) ethanol, resulting in improved overall productivity, reduced capital cost, and reduced energy input compared to processing at normal gravity. High-gravity technology ensures a successful implementation of cellulose to ethanol conversion as a cost-competitive process. Implementation of such technologies is possible if all process steps can be performed at high biomass concentrations. This review focuses on challenges and technological efforts in processing at high-gravity conditions and how these conditions influence the physiology and metabolism of fermenting microorganisms, the action of enzymes, and other process-related factors. Lignocellulosic materials add challenges compared to implemented processes due to high inhibitors content and the physical properties of these materials at high gravity. Copyright © 2013 Elsevier Ltd. All rights reserved.

Viral vector-based tools advance knowledge of basal ganglia anatomy and physiology.

PubMed

Sizemore, Rachel J; Seeger-Armbruster, Sonja; Hughes, Stephanie M; Parr-Brownlie, Louise C

2016-04-01

Viral vectors were originally developed to deliver genes into host cells for therapeutic potential. However, viral vector use in neuroscience research has increased because they enhance interpretation of the anatomy and physiology of brain circuits compared with conventional tract tracing or electrical stimulation techniques. Viral vectors enable neuronal or glial subpopulations to be labeled or stimulated, which can be spatially restricted to a single target nucleus or pathway. Here we review the use of viral vectors to examine the structure and function of motor and limbic basal ganglia (BG) networks in normal and pathological states. We outline the use of viral vectors, particularly lentivirus and adeno-associated virus, in circuit tracing, optogenetic stimulation, and designer drug stimulation experiments. Key studies that have used viral vectors to trace and image pathways and connectivity at gross or ultrastructural levels are reviewed. We explain how optogenetic stimulation and designer drugs used to modulate a distinct pathway and neuronal subpopulation have enhanced our mechanistic understanding of BG function in health and pathophysiology in disease. Finally, we outline how viral vector technology may be applied to neurological and psychiatric conditions to offer new treatments with enhanced outcomes for patients. Copyright © 2016 the American Physiological Society.

Unperturbed vs. post-transplantation hematopoiesis: both in vivo but different

PubMed Central

Busch, Katrin; Rodewald, Hans-Reimer

2016-01-01

Purpose of review Hematopoietic stem cell (HSC) transplantation has yielded tremendous information on experimental properties of HSCs. Yet, it remains unclear whether transplantation reflects the physiology of hematopoiesis. A limitation is the difficulty in accessing HSC functions without isolation, in-vitro manipulation and readout for potential. New genetic fate mapping and clonal marking techniques now shed light on hematopoiesis under physiological conditions. Recent findings Transposon-based genetic marks were introduced across the entire hematopoietic system to follow the clonal dynamics of these tags over time. A polyclonal source downstream from stem cells was found responsible for the production of at least granulocytes. In independent experiments, HSCs were genetically marked in adult mice, and the kinetics of label emergence throughout the system was followed over time. These experiments uncovered that during physiological steady-state hematopoiesis large numbers of HSCs yield differentiated progeny. Individual HSCs were active only rarely, indicating their very slow periodicity of differentiation rather than quiescence. Summary Noninvasive genetic experiments in mice have identified a major role of stem and progenitor cells downstream from HSCs as drivers of adult hematopoiesis, and revealed that post-transplantation hematopoiesis differs quantitatively from normal steady-state hematopoiesis. PMID:27213498

Variable stoichiometry in active ion transport: theoretical analysis of physiological consequences.

PubMed

Johnson, E A; Tanford, C; Reynolds, J A

1985-08-01

Active ion transport systems with fixed stoichiometry are subject to a thermodynamic limit on the ion concentration gradients that they can generate and maintain, and their net rates of transport must inevitably decrease as this limit is approached. The capability to vary stoichiometry might thus be physiologically advantageous: a shift to lower stoichiometry (fewer ions pumped per reaction cycle) at increasing thermodynamic load could increase the limit on the supportable concentration gradient and could accelerate the rate of transport under high-load conditions. Here we present a theoretical and numerical analysis of this possibility, using the sarcoplasmic reticulum ATP-driven Ca pump as the example. It is easy to introduce alternate pathways into the reaction cycle for this system to shift the stoichiometry (Ca2+/ATP) from the normal value of 2:1 to 1:1, but it cannot be done without simultaneous generation of a pathway for uncoupled leak of Ca2+ across the membrane. This counteracts the advantageous effect of the change in transport stoichiometry and a physiologically useful rate acceleration cannot be obtained. This result is likely to be generally applicable to most active transport systems.

Variable stoichiometry in active ion transport: theoretical analysis of physiological consequences.

PubMed Central

Johnson, E A; Tanford, C; Reynolds, J A

1985-01-01

Active ion transport systems with fixed stoichiometry are subject to a thermodynamic limit on the ion concentration gradients that they can generate and maintain, and their net rates of transport must inevitably decrease as this limit is approached. The capability to vary stoichiometry might thus be physiologically advantageous: a shift to lower stoichiometry (fewer ions pumped per reaction cycle) at increasing thermodynamic load could increase the limit on the supportable concentration gradient and could accelerate the rate of transport under high-load conditions. Here we present a theoretical and numerical analysis of this possibility, using the sarcoplasmic reticulum ATP-driven Ca pump as the example. It is easy to introduce alternate pathways into the reaction cycle for this system to shift the stoichiometry (Ca2+/ATP) from the normal value of 2:1 to 1:1, but it cannot be done without simultaneous generation of a pathway for uncoupled leak of Ca2+ across the membrane. This counteracts the advantageous effect of the change in transport stoichiometry and a physiologically useful rate acceleration cannot be obtained. This result is likely to be generally applicable to most active transport systems. PMID:3860866

Visualization and contractile activity of cochlear pericytes in the capillaries of the spiral ligament.

PubMed

Dai, Min; Nuttall, Alfred; Yang, Yue; Shi, Xiaorui

2009-08-01

Pericytes, mural cells located on microvessels, are considered to play an important role in the formation of the vasculature and the regulation of local blood flow in some organs. Little is known about the physiology of cochlear pericytes. In order to investigate the function of cochlear pericytes, we developed a method to visualize cochlear pericytes using diaminofluorescein-2 diacetate (DAF-2DA) and intravital fluorescence microscopy. This method can permit the study of the effect of vasoactive agents on pericytes under the in vivo and normal physiological condition. The specificity of the labeling method was verified by the immunofluorescence labeling of pericyte maker proteins such as desmin, neural proteoglycan (NG2), and thymocyte differentiation antigen 1 (Thy-1). Superfused K(+) and Ca(2+) to the cochlear lateral wall resulted in localized constriction of capillaries at pericyte locations both in vivo and in vitro, while there was no obvious change in cochlear capillary diameters with application of the adrenergic neurotransmitter noradrenaline. The method could be an effective way to visualize cochlear pericytes and microvessels and study lateral wall vascular physiology. Moreover, we demonstrate for the first time that cochlear pericytes have contractility, which may be important for regulation of cochlear blood flow.

Magnocellular Neurons and Posterior Pituitary Function.

PubMed

Brown, Colin H

2016-09-15

The posterior pituitary gland secretes oxytocin and vasopressin (the antidiuretic hormone) into the blood system. Oxytocin is required for normal delivery of the young and for delivery of milk to the young during lactation. Vasopressin increases water reabsorption in the kidney to maintain body fluid balance and causes vasoconstriction to increase blood pressure. Oxytocin and vasopressin secretion occurs from the axon terminals of magnocellular neurons whose cell bodies are principally found in the hypothalamic supraoptic nucleus and paraventricular nucleus. The physiological functions of oxytocin and vasopressin depend on their secretion, which is principally determined by the pattern of action potentials initiated at the cell bodies. Appropriate secretion of oxytocin and vasopressin to meet the challenges of changing physiological conditions relies mainly on integration of afferent information on reproductive, osmotic, and cardiovascular status with local regulation of magnocellular neurons by glia as well as intrinsic regulation by the magnocellular neurons themselves. This review focuses on the control of magnocellular neuron activity with a particular emphasis on their regulation by reproductive function, body fluid balance, and cardiovascular status. © 2016 American Physiological Society. Compr Physiol 6:1701-1741, 2016. Copyright © 2016 John Wiley & Sons, Inc.

Non-enzymatic antioxidant accumulations in BR-deficient and BR-insensitive barley mutants under control and drought conditions.

PubMed

Gruszka, Damian; Janeczko, Anna; Dziurka, Michal; Pociecha, Ewa; Fodor, Jozsef

2017-12-07

Drought is one of the most adverse stresses that affect plant growth and yield. Disturbances in metabolic activity resulting from drought cause overproduction of reactive oxygen species. It is postulated that brassinosteroids (BRs) regulate plant tolerance to the stress conditions, but the underlying mechanisms remain largely unknown. An involvement of endogenous BRs in regulation of the antioxidant homeostasis is not fully clarified either. Therefore, the aim of this study was to elucidate the role of endogenous BRs in regulation of non-enzymatic antioxidants in barley (Hordeum vulgare) under control and drought conditions. The plant material included the 'Bowman' cultivar and a group of semi-dwarf near-isogenic lines (NILs), representing mutants deficient in BR biosynthesis or signaling. In general, accumulations of 11 compounds representing various types of non-enzymatic antioxidants were analyzed under both conditions. The analyses of accumulations of reduced and oxidized forms of ascorbate indicated that the BR mutants contain significantly higher contents of dehydroascorbic acid under drought conditions when compared with the 'Bowman' cultivar. The analysis of glutathione accumulation indicated that under the control conditions the BR-insensitive NILs contained significantly lower concentrations of this antioxidant when compared with the rest of genotypes. Therefore, we postulate that BR sensitivity is required for normal accumulation of glutathione. A complete accumulation profile of various tocopherols indicated that functional BR biosynthesis and signaling are required for their normal accumulation under both conditions. Results of this study provided an insight into the role of endogenous BRs in regulation of the non-enzymatic antioxidant homeostasis. © 2017 Scandinavian Plant Physiology Society.

Hypoxia-activated genes from early placenta are elevated in Preeclampsia, but not in Intra-Uterine Growth Retardation

PubMed Central

Vaiman, Daniel; Mondon, Françoise; Garcès-Duran, Alexandra; Mignot, Thérèse-Marie; Robert, Brigitte; Rebourcet, Régis; Jammes, Hélène; Chelbi, Sonia T; Quetin, Frédérique; Marceau, Geoffrey; Sapin, Vincent; Piumi, François; Danan, Jean-Louis; Rigourd, Virginie; Carbonne, Bruno; Ferré, Françoise

2005-01-01

Background As a first step to explore the possible relationships existing between the effects of low oxygen pressure in the first trimester placenta and placental pathologies developing from mid-gestation, two subtracted libraries totaling 2304 cDNA clones were constructed. For achieving this, two reciprocal suppressive/subtractive hybridization procedures (SSH) were applied to early (11 weeks) human placental villi after incubation either in normoxic or in hypoxic conditions. The clones from both libraries (1440 hypoxia-specific and 864 normoxia-specific) were spotted on nylon macroarrays. Complex cDNAs probes prepared from placental villi (either from early pregnancy, after hypoxic or normoxic culture conditions, or near term for controls or pathological placentas) were hybridized to the membranes. Results Three hundred and fifty nine clones presenting a hybridization signal above the background were sequenced and shown to correspond to 276 different genes. Nine of these genes are mitochondrial, while 267 are nuclear. Specific expression profiles characteristic of preeclampsia (PE) could be identified, as well as profiles specific of intra-uterine growth retardation (IUGR). Focusing on the chromosomal distribution of the fraction of genes that responded in at least one hybridization experiment, we could observe a highly significant chromosomal clustering of 54 genes into 8 chromosomal regions, four of which containing imprinted genes. Comparative mapping data indicate that these imprinted clusters are maintained in synteny in mice, and apparently in cattle and pigs, suggesting that the maintenance of such syntenies is requested for achieving a normal placental physiology in eutherian mammals. Conclusion We could demonstrate that genes induced in PE were also genes highly expressed under hypoxic conditions (P = 5.10-5), which was not the case for isolated IUGR. Highly expressed placental genes may be in syntenies conserved interspecifically, suggesting that the maintenance of such clusters is requested for achieving a normal placental physiology in eutherian mammals. PMID:16129025

Intestinal absorption of water-soluble vitamins in health and disease.

PubMed

Said, Hamid M

2011-08-01

Our knowledge of the mechanisms and regulation of intestinal absorption of water-soluble vitamins under normal physiological conditions, and of the factors/conditions that affect and interfere with theses processes has been significantly expanded in recent years as a result of the availability of a host of valuable molecular/cellular tools. Although structurally and functionally unrelated, the water-soluble vitamins share the feature of being essential for normal cellular functions, growth and development, and that their deficiency leads to a variety of clinical abnormalities that range from anaemia to growth retardation and neurological disorders. Humans cannot synthesize water-soluble vitamins (with the exception of some endogenous synthesis of niacin) and must obtain these micronutrients from exogenous sources. Thus body homoeostasis of these micronutrients depends on their normal absorption in the intestine. Interference with absorption, which occurs in a variety of conditions (e.g. congenital defects in the digestive or absorptive system, intestinal disease/resection, drug interaction and chronic alcohol use), leads to the development of deficiency (and sub-optimal status) and results in clinical abnormalities. It is well established now that intestinal absorption of the water-soluble vitamins ascorbate, biotin, folate, niacin, pantothenic acid, pyridoxine, riboflavin and thiamin is via specific carrier-mediated processes. These processes are regulated by a variety of factors and conditions, and the regulation involves transcriptional and/or post-transcriptional mechanisms. Also well recognized now is the fact that the large intestine possesses specific and efficient uptake systems to absorb a number of water-soluble vitamins that are synthesized by the normal microflora. This source may contribute to total body vitamin nutrition, and especially towards the cellular nutrition and health of the local colonocytes. The present review aims to outline our current understanding of the mechanisms involved in intestinal absorption of water-soluble vitamins, their regulation, the cell biology of the carriers involved and the factors that negatively affect these absorptive events. © The Authors Journal compilation © 2011 Biochemical Society

Intestinal absorption of water-soluble vitamins in health and disease

PubMed Central

Said, Hamid M.

2014-01-01

Our knowledge of the mechanisms and regulation of intestinal absorption of water-soluble vitamins under normal physiological conditions, and of the factors/conditions that affect and interfere with theses processes has been significantly expanded in recent years as a result of the availability of a host of valuable molecular/cellular tools. Although structurally and functionally unrelated, the water-soluble vitamins share the feature of being essential for normal cellular functions, growth and development, and that their deficiency leads to a variety of clinical abnormalities that range from anaemia to growth retardation and neurological disorders. Humans cannot synthesize water-soluble vitamins (with the exception of some endogenous synthesis of niacin) and must obtain these micronutrients from exogenous sources. Thus body homoeostasis of these micronutrients depends on their normal absorption in the intestine. Interference with absorption, which occurs in a variety of conditions (e.g. congenital defects in the digestive or absorptive system, intestinal disease/resection, drug interaction and chronic alcohol use), leads to the development of deficiency (and sub-optimal status) and results in clinical abnormalities. It is well established now that intestinal absorption of the water-soluble vitamins ascorbate, biotin, folate, niacin, pantothenic acid, pyridoxine, riboflavin and thiamin is via specific carrier-mediated processes. These processes are regulated by a variety of factors and conditions, and the regulation involves transcriptional and/or post-transcriptional mechanisms. Also well recognized now is the fact that the large intestine possesses specific and efficient uptake systems to absorb a number of water-soluble vitamins that are synthesized by the normal microflora. This source may contribute to total body vitamin nutrition, and especially towards the cellular nutrition and health of the local colonocytes. The present review aims to outline our current understanding of the mechanisms involved in intestinal absorption of water-soluble vitamins, their regulation, the cell biology of the carriers involved and the factors that negatively affect these absorptive events. PMID:21749321

Patient-specific biomechanical model of hypoplastic left heart to predict post-operative cardio-circulatory behaviour.

PubMed

Cutrì, Elena; Meoli, Alessio; Dubini, Gabriele; Migliavacca, Francesco; Hsia, Tain-Yen; Pennati, Giancarlo

2017-09-01

Hypoplastic left heart syndrome is a complex congenital heart disease characterised by the underdevelopment of the left ventricle normally treated with a three-stage surgical repair. In this study, a multiscale closed-loop cardio-circulatory model is created to reproduce the pre-operative condition of a patient suffering from such pathology and virtual surgery is performed. Firstly, cardio-circulatory parameters are estimated using a fully closed-loop cardio-circulatory lumped parameter model. Secondly, a 3D standalone FEA model is build up to obtain active and passive ventricular characteristics and unloaded reference state. Lastly, the 3D model of the single ventricle is coupled to the lumped parameter model of the circulation obtaining a multiscale closed-loop pre-operative model. Lacking any information on the fibre orientation, two cases were simulated: (i) fibre distributed as in the physiological right ventricle and (ii) fibre as in the physiological left ventricle. Once the pre-operative condition is satisfactorily simulated for the two cases, virtual surgery is performed. The post-operative results in the two cases highlighted similar hemodynamic behaviour but different local mechanics. This finding suggests that the knowledge of the patient-specific fibre arrangement is important to correctly estimate the single ventricle's working condition and consequently can be valuable to support clinical decision. Copyright © 2017 IPEM. Published by Elsevier Ltd. All rights reserved.

A pH-responsive carboxymethyl dextran-based conjugate as a carrier of docetaxel for cancer therapy.

PubMed

Han, Hwa Seung; Lee, Minchang; An, Jae Yoon; Son, Soyoung; Ko, Hyewon; Lee, Hansang; Chae, Yee Soo; Kang, Young Mo; Park, Jae Hyung

2016-05-01

Although docetaxel is available for the treatment of various cancers, its clinical applications are limited by its poor water solubility and toxicity to normal cells, resulting in severe adverse effects. In this study, we synthesized a polymeric conjugate with an acid-labile ester linkage, consisting of carboxymethyl dextran (CMD) and docetaxel (DTX), as a potential anticancer drug delivery system. The conjugate exhibited sustained release of DTX in physiological buffer (pH 7.4), whereas its release rate increased remarkably under mildly acidic conditions (pH < 6.5), mimicking the intracellular environment. Cytotoxicity tests conducted in vitro demonstrated that the conjugate exhibited much higher toxicity to cancer cells under mildly acidic conditions than at physiological buffer (pH 7.4). These results implied that the ester linkage in the conjugate allowed for selective release of biologically active DTX under mildly acidic conditions. The in vivo biodistribution of a Cy5.5-labeled conjugate was observed using the noninvasive optical imaging technique after its systemic administration into tumor-bearing mice. The conjugate was effectively accumulated into the tumor site, which may have been because of an enhanced permeability and retention effect. In addition, in vivo antitumor efficacy of the conjugate was significantly higher than that of free DTX. Overall, the CMD-based conjugate might have promising potential as a carrier of DTX for cancer therapy. © 2015 Wiley Periodicals, Inc.

Seasonal variation and meteotropism in various self-rated psychological and physiological features of a normal couple

NASA Astrophysics Data System (ADS)

Maes, Michael; de Meyer, Frans; Peeters, Dirk; Meltzer, Herbert; Cosyns, Paul; Schotte, Chris

1992-12-01

Recently, true seasonal variation with significant periodicities (circannual, semiannual, circatrimensual, circabimensual) and a significant meteotropism have been observed in a number of self-rated characteristics of normal man (arousal, mood, physiology and social behaviour). In order to replicate these findings, two normal controls (a married couple) were asked daily to complete a self-rating scale concerned with the characteristics mentioned above during one calendar year. By means of time series analysis, significant rhythmicities with recurrent cycles in the autorhythmometric data of all of the above characteristics were found. An important part of the variance in these characteristics was found, using multiple regression, to be related to various weather variables, such as mean atmospheric pressure, temperature, relative humidity, wind speed, minutes of sunlight/day and precipitation/day. These results support the hypothesis that temporal variations in human psychological and physiological characteristics may be dictated by the composite effects of past and present atmospheric activity.

Expression of Translationally Controlled Tumor Protein in Human Kidney and in Renal Cell Carcinoma.

PubMed

Ambrosio, Maria R; Rocca, Bruno J; Barone, Aurora; Onorati, Monica; Mundo, Lucia; Crivelli, Filippo; Di Nuovo, Franca; De Falco, Giulia; del Vecchio, Maria T; Tripodi, Sergio A; Tosi, Piero

2015-01-01

Translationally controlled tumor protein is a multifaceted protein involved in several physiological and biological functions. Its expression in normal kidney and in renal carcinomas, once corroborated by functional data, may add elements to elucidate renal physiology and carcinogenesis. In this study, translationally controlled tumor protein expression was evaluated by quantitative real time polymerase chain reaction and western blotting, and its localization was examined by immunohistochemistry on 84 nephrectomies for cancer. In normal kidney protein expression was found in the cytoplasm of proximal and distal tubular cells, in cells of the thick segment of the loop of Henle, and in urothelial cells of the pelvis. It was also detectable in cells of renal carcinoma with different pattern of localization (membranous and cytoplasmic) depending on tumor histotype. Our data may suggest an involvement of translationally controlled tumor protein in normal physiology and carcinogenesis. However, functional in vitro and in vivo studies are needed to verify this hypothesis.

Expression of Translationally Controlled Tumor Protein in Human Kidney and in Renal Cell Carcinoma

PubMed Central

Ambrosio, Maria R.; Rocca, Bruno J.; Barone, Aurora; Onorati, Monica; Mundo, Lucia; Crivelli, Filippo; Di Nuovo, Franca; De Falco, Giulia; del Vecchio, Maria T.; Tripodi, Sergio A.; Tosi, Piero

2015-01-01

Translationally controlled tumor protein is a multifaceted protein involved in several physiological and biological functions. Its expression in normal kidney and in renal carcinomas, once corroborated by functional data, may add elements to elucidate renal physiology and carcinogenesis. In this study, translationally controlled tumor protein expression was evaluated by quantitative real time polymerase chain reaction and western blotting, and its localization was examined by immunohistochemistry on 84 nephrectomies for cancer. In normal kidney protein expression was found in the cytoplasm of proximal and distal tubular cells, in cells of the thick segment of the loop of Henle, and in urothelial cells of the pelvis. It was also detectable in cells of renal carcinoma with different pattern of localization (membranous and cytoplasmic) depending on tumor histotype. Our data may suggest an involvement of translationally controlled tumor protein in normal physiology and carcinogenesis. However, functional in vitro and in vivo studies are needed to verify this hypothesis. PMID:26425551

Acoustic microscopy analyses to determine good vs. failed tissue engineered oral mucosa under normal or thermally stressed culture conditions.

PubMed

Winterroth, Frank; Lee, Junho; Kuo, Shiuhyang; Fowlkes, J Brian; Feinberg, Stephen E; Hollister, Scott J; Hollman, Kyle W

2011-01-01

This study uses scanning acoustic microscopy (SAM) ultrasonic profilometry to determine acceptable vs. failed tissue engineered oral mucosa. Specifically, ex vivo-produced oral mucosal equivalents (EVPOMEs) under normal or thermally stressed culture conditions were scanned with the SAM operator blinded to the culture conditions. As seeded cells proliferate, they fill in and smooth out the surface irregularities; they then stratify and produce a keratinized protective upper layer. Some of these transformations could alter backscatter of ultrasonic signals and in the case of the thermally stressed cells, produce backscatter similar to an unseeded device. If non-invasive ultrasonic monitoring could be developed, then tissue cultivation could be adjusted to measure biological variations in the stratified surface. To create an EVPOME device, oral mucosa keratinocytes were seeded onto acellular cadaveric dermis. Two sets of EVPOMEs were cultured: one at physiological temperature 37 °C and the other at 43 °C. The specimens were imaged with SAM consisting of a single-element transducer: 61 MHz center frequency, 32 MHz bandwidth, 1.52 f#. Profilometry for the stressed and unseeded specimens showed higher surface irregularities compared to unstressed specimens. Elevated thermal stress retards cellular differentiation, increasing root mean square values; these results show that SAM can potentially monitor cell/tissue development.

Comparison of native porcine skin and a dermal substitute using tensiometry and digital image speckle correlation.

PubMed

Fritz, Jason R; Phillips, Brett T; Conkling, Nicole; Fourman, Mitchell; Melendez, Mark M; Bhatnagar, Divya; Simon, Marcia; Rafailovich, Miriam; Dagum, Alexander B

2012-10-01

Dermal substitutes are currently used in plastic surgery to cover various soft tissue defects caused by trauma, burns, or ablative cancer surgery. Little information is available on the biomechanical properties of these dermal substitutes after adequate incorporation as compared to normal skin. Determining parameters such as tensile strength in these skin substitutes will help us further understand their wound healing properties and potential in developing artificial tissue constructs. We hypothesize that a dermal substitute has a lower stress-strain curve and altered stress-induced deformation quantified with tensiometry and digital image speckle correlation (DISC) analysis. Two separate 5×10-cm full-thickness wounds were created on the dorsum of 3 female swine. Fibrin glue was applied before either a full-thickness skin graft (FTSG) or application of artificial dermal matrix. On day 42, cultured autologous keratinocytes were applied as a cell sheet to the wound covered with Integra. On day 56, the wounds were fully excised and fresh tissue specimens, including normal skin, were stored in a physiological solution and prepared for analysis. Rectangular samples were excised from the center of each specimen measuring 4×4×30 mm. Using a tensiometer and DISC analysis, we evaluated the tensile strength of 3 different groups of skin, namely, normal, FTSG, and Integra. There is a significant difference between the Integra specimen when compared to normal skin and FTSG. We found a minimal difference in the stress-strain curves of the latter two. Integra alone shows plastic deformation with continued stretching before ultimate midline fracture. There is significant change between the Young's moduli of the normal skin and the Integra, whereas there is little difference between the FTSG and the normal skin; DISC confirms this analysis. The normal skin and FTSG show a convergence of vectors to a linear plane, whereas Integra shows very little organization. Using 2 different methods of analysis, we have shown a dermal substitute does not display similar biomechanical properties after adequate incorporation. These major tensile strength differences are shown between normal, grafted, and Integra constructs under physiological conditions. These properties will lead to further understanding of artificial tissue and engineered constructs in laboratory and clinical applications.

Microbial communities acclimate to recurring changes in soil redox potential status

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

DeAngelis, Kristen M.; Silver, Whendee; Thompson, Andrew

Rapidly fluctuating environmental conditions can significantly stress organisms, particularly when fluctuations cross thresholds of normal physiological tolerance. Redox potential fluctuations are common in humid tropical soils, and microbial community acclimation or avoidance strategies for survival will in turn shape microbial community diversity and biogeochemistry. To assess the extent to which indigenous bacterial and archaeal communities are adapted to changing in redox potential, soils were incubated under static anoxic, static oxic or fluctuating redox potential conditions, and the standing (DNA-based) and active (RNA-based) communities and biogeochemistry were determined. Fluctuating redox potential conditions permitted simultaneous CO{sub 2} respiration, methanogenesis, N{sub 2}O productionmore » and iron reduction. Exposure to static anaerobic conditions significantly changed community composition, while 4-day redox potential fluctuations did not. Using RNA: DNA ratios as a measure of activity, 285 taxa were more active under fluctuating than static conditions, compared with three taxa that were more active under static compared with fluctuating conditions. These data suggest an indigenous microbialcommunity adapted to fluctuating redox potential.« less

Validation of an integrative mathematical model of dehydration and rehydration in virtual humans.

PubMed

Pruett, W Andrew; Clemmer, John S; Hester, Robert L

2016-11-01

Water homeostasis is one of the body's most critical tasks. Physical challenges to the body, including exercise and surgery, almost always coordinate with some change in water handling reflecting the changing needs of the body. Vasopressin is the most important hormone that contributes to short-term water homeostasis. By manipulating vascular tone and regulating water reabsorption in the collecting duct of the kidneys, vasopressin can mediate the retention or loss of fluids quickly. In this study, we validated HumMod, an integrative mathematical model of human physiology, against six different challenges to water homeostasis with special attention to the secretion of vasopressin and maintenance of electrolyte balance. The studies chosen were performed in normal men and women, and represent a broad spectrum of perturbations. HumMod successfully replicated the experimental results, remaining within 1 standard deviation of the experimental means in 138 of 161 measurements. Only three measurements lay outside of the second standard deviation. Observations were made on serum osmolarity, serum vasopressin concentration, serum sodium concentration, urine osmolarity, serum protein concentration, hematocrit, and cumulative water intake following dehydration. This validation suggests that HumMod can be used to understand water homeostasis under a variety of conditions. © 2016 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

Insulin transport into the brain.

PubMed

Gray, Sarah M; Barrett, Eugene J

2018-05-30

While there is a growing consensus that insulin has diverse and important regulatory actions on the brain, seemingly important aspects of brain insulin physiology are poorly understood. Examples include: what is the insulin concentration within brain interstitial fluid under normal physiologic conditions; whether insulin is made in the brain and acts locally; does insulin from the circulation cross the blood-brain barrier or the blood-CSF barrier in a fashion that facilitates its signaling in brain; is insulin degraded within the brain; do privileged areas with a "leaky" blood-brain barrier serve as signaling nodes for transmitting peripheral insulin signaling; does insulin action in the brain include regulation of amyloid peptides; whether insulin resistance is a cause or consequence of processes involved in cognitive decline. Heretofore, nearly all studies examining brain insulin physiology have employed techniques and methodologies that do not appreciate the complex fluid compartmentation and flow throughout the brain. This review attempts to provide a status report on historical and recent work that begins to address some of these issues. It is undertaken in an effort to suggest a framework for studies going forward. Such studies are inevitably influenced by recent physiologic and genetic studies of insulin accessing and acting in brain, discoveries relating to brain fluid dynamics and the interplay of cerebrospinal fluid, brain interstitial fluid, and brain lymphatics, and advances in clinical neuroimaging that underscore the dynamic role of neurovascular coupling.

Human physiological models of insomnia.

PubMed

Richardson, Gary S

2007-12-01

Despite the wide prevalence and important consequences of insomnia, remarkably little is known about its pathophysiology. Available models exist primarily in the psychological domain and derive from the demonstrated efficacy of behavioral treatment approaches to insomnia management. However, these models offer little specific prediction about the anatomic or physiological foundation of chronic primary insomnia. On the other hand, a growing body of data on the physiology of sleep supports a reasonably circumscribed overview of possible pathophysiological mechanisms, as well as the development of physiological models of insomnia to guide future research. As a pragmatic step, these models focus on primary insomnia, as opposed to comorbid insomnias, because the latter is by its nature a much more heterogeneous presentation, reflecting the effects of the distinct comorbid condition. Current understanding of the regulation of sleep and wakefulness in mammalian brain supports four broad candidate areas: 1) disruption of the sleep homeostat; 2) disruption of the circadian clock; 3) disruption of intrinsic systems responsible for the expression of sleep states; or 4) disruption (hyperactivity) of extrinsic systems capable of over-riding normal sleep-wake regulation. This review examines each of the four candidate pathophysiological mechanisms and the available data in support of each. While studies that directly test the viability of each model are not yet available, descriptive data on primary insomnia favor the involvement of dysfunctional extrinsic stress-response systems in the pathology of primary chronic insomnia.

Modulation of Wolframin Expression in Human Placenta during Pregnancy: Comparison among Physiological and Pathological States

PubMed Central

Perna, Angelica; Iannaccone, Alessandro; Cobellis, Luigi; De Luca, Antonio

2014-01-01

The WFS1 gene, encoding a transmembrane glycoprotein of the endoplasmic reticulum called wolframin, is mutated in Wolfram syndrome, an autosomal recessive disorder defined by the association of diabetes mellitus, optic atrophy, and further organ abnormalities. Disruption of the WFS1 gene in mice causes progressive β-cell loss in the pancreas and impaired stimulus-secretion coupling in insulin secretion. However, little is known about the physiological functions of this protein. We investigated the immunohistochemical expression of wolframin in human placenta throughout pregnancy in normal women and diabetic pregnant women. In normal placenta, there was a modulation of wolframin throughout pregnancy with a strong level of expression during the first trimester and a moderate level in the third trimester of gestation. In diabetic women, wolframin expression was strongly reduced in the third trimester of gestation. The pattern of expression of wolframin in normal placenta suggests that this protein may be required to sustain normal rates of cytotrophoblast cell proliferation during the first trimester of gestation. The decrease in wolframin expression in diabetic placenta suggests that this protein may participate in maintaining the physiologic glucose homeostasis in this organ. PMID:24588001

Probiotics normalize the gut-brain-microbiota axis in immunodeficient mice

PubMed Central

Smith, Carli J.; Emge, Jacob R.; Berzins, Katrina; Lung, Lydia; Khamishon, Rebecca; Shah, Paarth; Rodrigues, David M.; Sousa, Andrew J.; Reardon, Colin; Sherman, Philip M.; Barrett, Kim E.

2014-01-01

The gut-brain-microbiota axis is increasingly recognized as an important regulator of intestinal physiology. Exposure to psychological stress causes activation of the hypothalamic-pituitary-adrenal (HPA) axis and causes altered intestinal barrier function, intestinal dysbiosis, and behavioral changes. The primary aim of this study was to determine whether the effects of psychological stress on intestinal physiology and behavior, including anxiety and memory, are mediated by the adaptive immune system. Furthermore, we wanted to determine whether treatment with probiotics would normalize these effects. Here we demonstrate that B and T cell-deficient Rag1−/− mice displayed altered baseline behaviors, including memory and anxiety, accompanied by an overactive HPA axis, increased intestinal secretory state, dysbiosis, and decreased hippocampal c-Fos expression. Both local (intestinal physiology and microbiota) and central (behavioral and hippocampal c-Fos) changes were normalized by pretreatment with probiotics, indicating an overall benefit on health conferred by changes in the microbiota, independent of lymphocytes. Taken together, these findings indicate a role for adaptive immune cells in maintaining normal intestinal and brain health in mice and show that probiotics can overcome this immune-mediated deficit in the gut-brain-microbiota axis. PMID:25190473

Improved intra-array and interarray normalization of peptide microarray phosphorylation for phosphorylome and kinome profiling by rational selection of relevant spots

PubMed Central

Scholma, Jetse; Fuhler, Gwenny M.; Joore, Jos; Hulsman, Marc; Schivo, Stefano; List, Alan F.; Reinders, Marcel J. T.; Peppelenbosch, Maikel P.; Post, Janine N.

2016-01-01

Massive parallel analysis using array technology has become the mainstay for analysis of genomes and transcriptomes. Analogously, the predominance of phosphorylation as a regulator of cellular metabolism has fostered the development of peptide arrays of kinase consensus substrates that allow the charting of cellular phosphorylation events (often called kinome profiling). However, whereas the bioinformatical framework for expression array analysis is well-developed, no advanced analysis tools are yet available for kinome profiling. Especially intra-array and interarray normalization of peptide array phosphorylation remain problematic, due to the absence of “housekeeping” kinases and the obvious fallacy of the assumption that different experimental conditions should exhibit equal amounts of kinase activity. Here we describe the development of analysis tools that reliably quantify phosphorylation of peptide arrays and that allow normalization of the signals obtained. We provide a method for intraslide gradient correction and spot quality control. We describe a novel interarray normalization procedure, named repetitive signal enhancement, RSE, which provides a mathematical approach to limit the false negative results occuring with the use of other normalization procedures. Using in silico and biological experiments we show that employing such protocols yields superior insight into cellular physiology as compared to classical analysis tools for kinome profiling. PMID:27225531

Effects of Tobacco Smoking on the Degeneration of the Intervertebral Disc: A Finite Element Study

PubMed Central

Elmasry, Shady; Asfour, Shihab; de Rivero Vaccari, Juan Pablo; Travascio, Francesco

2015-01-01

Tobacco smoking is associated with numerous pathological conditions. Compelling experimental evidence associates smoking to the degeneration of the intervertebral disc (IVD). In particular, it has been shown that nicotine down-regulates both the proliferation rate and glycosaminoglycan (GAG) biosynthesis of disc cells. Moreover, tobacco smoking causes the constriction of the vascular network surrounding the IVD, thus reducing the exchange of nutrients and anabolic agents from the blood vessels to the disc. It has been hypothesized that both nicotine presence in the IVD and the reduced solute exchange are responsible for the degeneration of the disc due to tobacco smoking, but their effects on tissue homeostasis have never been quantified. In this study, a previously presented computational model describing the homeostasis of the IVD was deployed to investigate the effects of impaired solute supply and nicotine-mediated down-regulation of cell proliferation and biosynthetic activity on the health of the disc. We found that the nicotine-mediated down-regulation of cell anabolism mostly affected the GAG concentration at the cartilage endplate, reducing it up to 65% of the value attained in normal physiological conditions. In contrast, the reduction of solutes exchange between blood vessels and disc tissue mostly affected the nucleus pulposus, whose cell density and GAG levels were reduced up to 50% of their normal physiological levels. The effectiveness of quitting smoking on the regeneration of a degenerated IVD was also investigated, and showed to have limited benefit on the health of the disc. A cell-based therapy in conjunction with smoke cessation provided significant improvements in disc health, suggesting that, besides quitting smoking, additional treatments should be implemented in the attempt to recover the health of an IVD degenerated by tobacco smoking. PMID:26301590

The knockdown of chloroplastic ascorbate peroxidases reveals its regulatory role in the photosynthesis and protection under photo-oxidative stress in rice.

PubMed

Caverzan, Andréia; Bonifacio, Aurenivia; Carvalho, Fabricio E L; Andrade, Claudia M B; Passaia, Gisele; Schünemann, Mariana; Maraschin, Felipe Dos Santos; Martins, Marcio O; Teixeira, Felipe K; Rauber, Rafael; Margis, Rogério; Silveira, Joaquim Albenisio Gomes; Margis-Pinheiro, Márcia

2014-01-01

The inactivation of the chloroplast ascorbate peroxidases (chlAPXs) has been thought to limit the efficiency of the water-water cycle and photo-oxidative protection under stress conditions. In this study, we have generated double knockdown rice (Oryza sativa L.) plants in both OsAPX7 (sAPX) and OsAPX8 (tAPX) genes, which encode chloroplastic APXs (chlAPXs). By employing an integrated approach involving gene expression, proteomics, biochemical and physiological analyses of photosynthesis, we have assessed the role of chlAPXs in the regulation of the protection of the photosystem II (PSII) activity and CO2 assimilation in rice plants exposed to high light (HL) and methyl violagen (MV). The chlAPX knockdown plants were affected more severely than the non-transformed (NT) plants in the activity and structure of PSII and CO2 assimilation in the presence of MV. Although MV induced significant increases in pigment content in the knockdown plants, the increases were apparently not sufficient for protection. Treatment with HL also caused generalized damage in PSII in both types of plants. The knockdown and NT plants exhibited differences in photosynthetic parameters related to efficiency of utilization of light and CO2. The knockdown plants overexpressed other antioxidant enzymes in response to the stresses and increased the GPX activity in the chloroplast-enriched fraction. Our data suggest that a partial deficiency of chlAPX expression modulate the PSII activity and integrity, reflecting the overall photosynthesis when rice plants are subjected to acute oxidative stress. However, under normal growth conditions, the knockdown plants exhibit normal phenotype, biochemical and physiological performance. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

High concentration of vitamin E decreases thermosensation and thermotaxis learning and the underlying mechanisms in the nematode Caenorhabditis elegans.

PubMed

Li, Yiping; Li, Yinxia; Wu, Qiuli; Ye, Huayue; Sun, Lingmei; Ye, Boping; Wang, Dayong

2013-01-01

α-tocopherol is a powerful liposoluble antioxidant and the most abundant isoform of vitamin E in the body. Under normal physiological conditions, adverse effects of relatively high concentration of vitamin E on organisms and the underlying mechanisms are still largely unclear. In the present study, we used the nematode Caenorhabditis elegans as an in vivo assay system to investigate the possible adverse effects of high concentration of vitamin E on thermosensation and thermotaxis learning and the underlying mechanisms. Our data show that treatment with 100-200 µg/mL of vitamin E did not noticeably influence both thermosensation and thermotaxis learning; however, treatment with 400 µg/mL of vitamin E altered both thermosensation and thermotaxis learning. The observed decrease in thermotaxis learning in 400 µg/mL of vitamin E treated nematodes might be partially due to the moderate but significant deficits in thermosensation, but not due to deficits in locomotion behavior or perception to food and starvation. Treatment with 400 µg/mL of vitamin E did not noticeably influence the morphology of GABAergic neurons, but significantly decreased fluorescent intensities of the cell bodies in AFD sensory neurons and AIY interneurons, required for thermosensation and thermotaxis learning control. Treatment with 400 µg/mL of vitamin E affected presynaptic function of neurons, but had no remarkable effects on postsynaptic function. Moreover, promotion of synaptic transmission by activating PKC-1 effectively retrieved deficits in both thermosensation and thermotaxis learning induced by 400 µg/mL of vitamin E. Therefore, relatively high concentrations of vitamin E administration may cause adverse effects on thermosensation and thermotaxis learning by inducing damage on the development of specific neurons and presynaptic function under normal physiological conditions in C. elegans.

Physiologic Inter-eye Differences in Monkey Optic Nerve Head Architecture and Their Relation to Changes in Early Experimental Glaucoma

PubMed Central

Yang, Hongli; Downs, J. Crawford; Burgoyne, Claude F.

2009-01-01

Purpose To characterize physiologic inter-eye differences in optic nerve head (ONH) architecture within six normal rhesus monkeys and compare them to inter-eye differences within three previously-reported cynomolgus monkeys with early experimental glaucoma (EEG). Methods Trephinated ONH and peripapillary sclera from both eyes of six normal monkeys were serial sectioned, 3D reconstructed, 3D delineated and parameterized. For each normal animal, and each parameter, physiologic inter-eye difference (PID) was calculated (both overall and regionally) by converting all OS data to OD configuration and subtracting the OS from the OD value and Physiologic Inter-eye Percent Difference (PIPD) was calculated as the PID divided by the measurement mean of the two eyes. For each EEG monkey, inter-eye (EEG minus normal) differences and percent differences for each parameter overall and regionally were compared to the PID and PIPD Maximums. Results For all parameters the PID Maximums were relatively small overall. Compared to overall PID maximums, overall inter-eye differences in EEG monkeys were greatest for laminar deformation and thickening, posterior scleral canal enlargement, cupping and prelaminar neural tissue thickening. Compared to the regional PID Maximums, the lamina cribrosa was posteriorly deformed centrally, inferiorly, inferonasally and superiorly and was thickened centrally. The prelaminar neural tissues were thickened inferiorly, inferonasally and superiorly. Conclusion These data provide the first characterization of PID/PIPD maximums for ONH neural and connective tissue parameters in normal monkeys and serve to further clarify the location and character of early ONH change in experimental glaucoma. However, because of the species differences, the findings in EEG need to be confirmed within EEG rhesus monkey eyes. PMID:18775866

Articular cartilage and subchondral bone in the pathogenesis of osteoarthritis.

PubMed

Goldring, Mary B; Goldring, Steven R

2010-03-01

The articular surface plays an essential role in load transfer across the joint, and conditions that produce increased load transfer or altered patterns of load distribution accelerate the development of osteoarthritis (OA). Current knowledge segregates the risk factors into two fundamental mechanisms related to the adverse effects of "abnormal" loading on normal cartilage or "normal" loading on abnormal cartilage. Although chondrocytes can modulate their functional state in response to loading, their capacity to repair and modify the surrounding extracellular matrix is limited in comparison to skeletal cells in bone. This differential adaptive capacity underlies the more rapid appearance of detectable skeletal changes, especially after acute injuries that alter joint mechanics. The imbalance in the adaptation of the cartilage and bone disrupts the physiological relationship between these tissues and further contributes to OA pathology. This review focuses on the specific articular cartilage and skeletal features of OA and the putative mechanisms involved in their pathogenesis.

[The influence of the LK-92 "Adeli" treatment loading suit on electro-neuro-myographic characteristics in patients with infantile cerebral paralysis].

PubMed

Semenova, K A; Antonova, L V

1998-01-01

Treatment-loading costume (LK-92 "Adely") was investigated in terms of its influence on functional state of neuromotor apparatus in 25 children with infantile cerebral paralysis in the form of spastic diplegia. Improvement of motor functions observed may be conditioned by a decrease of an amplitude of bioelectric activity in spastic muscles at physiologic rest and by an increase of an amplitude of agonists' biopotentials at arbitrary movements. Improvement of motor functions may be also caused by normalization of both the coefficients characterizing coordinated muscules' interactions and functional state of spinal motoneurons as well as of the mechanisms of their suprasegmental regulation. It is suggested that such effect may be, realized because of the afferentation normalization as well as by means of the influence of LK-92 "Adely" on both central and segmentary structures of motor analyzer including neuromediator systems.

Food intake in the real world: implications for nutrition and aging.

PubMed

de Castro, John M; Stroebele, Nanette

2002-11-01

Nutrient intakes are affected by two classes of factors, physiological and environmental. In the real world, environmental variables such as social factors, palatability, and the time of eating appear to have large influences on amounts ingested in the short-term. Physiological control mechanisms also operate to regulate intake, and they induce compensatory responses to deviations from the norm. These physiological influences only appear to have weak influences on short-term intake unless there are large deviations from the normal state, but over the long-term they act patiently and persistently to rectify the excesses produced by environmental fluctuations and thereby tend to maintain a relative balance between energy intake and expenditure. As individuals age there is a progressive decline in physiological function including the mechanisms that act to control intake in the young. This should not produce a problem in a healthy individual in a stable environment: however, if that situation should change due to illness or an environmental change such as the death of a spouse, which produces decline in intake, elderly individuals would not have the physiological mechanisms present to compensate. Thus, the deficit in energy intake would not be replaced, and the lower level of intake would be maintained as long as the new health condition or environment remains stable. Hence, the decline in the effectiveness of the physiological systems with age makes the elderly particularly vulnerable and unable to rebound from deficits. Although the elderly have difficulty compensating for deficits automatically by physiologically-induced adjustments, the studies of real world intake reviewed in this article suggest that compensation can be produced by adjustments to the environment. The elderly appear to be as responsive to environmental factors as younger individuals. In particular, they appear to increase intake in response to social facilitation, diurnal rhythms, the eating environment, and palatability to the same extent as their juniors. These data suggest that alterations in the social, temporal, environmental, or hedonic conditions of eating could induce desired alterations in the nutrient intakes of the elderly. The study of real world eating behavior has produced evidence that suggests that this strategy can work. It remains for future applied investigations to ascertain whether or not this strategy is effective in treating undernutrition in the elderly.

The effect of acute maximal exercise on postexercise hemodynamics and central arterial stiffness in obese and normal-weight individuals.

PubMed

Bunsawat, Kanokwan; Ranadive, Sushant M; Lane-Cordova, Abbi D; Yan, Huimin; Kappus, Rebecca M; Fernhall, Bo; Baynard, Tracy

2017-04-01

Central arterial stiffness is associated with incident hypertension and negative cardiovascular outcomes. Obese individuals have higher central blood pressure (BP) and central arterial stiffness than their normal-weight counterparts, but it is unclear whether obesity also affects hemodynamics and central arterial stiffness after maximal exercise. We evaluated central hemodynamics and arterial stiffness during recovery from acute maximal aerobic exercise in obese and normal-weight individuals. Forty-six normal-weight and twenty-one obese individuals underwent measurements of central BP and central arterial stiffness at rest and 15 and 30 min following acute maximal exercise. Central BP and normalized augmentation index (AIx@75) were derived from radial artery applanation tonometry, and central arterial stiffness was obtained via carotid-femoral pulse wave velocity (cPWV) and corrected for central mean arterial pressure (cPWV/cMAP). Central arterial stiffness increased in obese individuals but decreased in normal-weight individuals following acute maximal exercise, after adjusting for fitness. Obese individuals also exhibited an overall higher central BP ( P  <   0.05), with no exercise effect. The increase in heart rate was greater in obese versus normal-weight individuals following exercise ( P  <   0.05), but there was no group differences or exercise effect for AIx@75 In conclusion, obese (but not normal-weight) individuals increased central arterial stiffness following acute maximal exercise. An assessment of arterial stiffness response to acute exercise may serve as a useful detection tool for subclinical vascular dysfunction. © 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

Morphology, physiology, genetics, enigmas, and status of an extremely rare tree: Mutant tanoak

Treesearch

Philip M. McDonald; Jianwei Zhang; Randy S. Senock; Jessica W. Wright

2013-01-01

Important physical characteristics, morphological attributes, physiological functions, and genetic properties of mutant tanoak, Notholithocarpus densiflorus f. attenuato-dentatus (Fagaceae), and normal tanoak, Notholithocarpus densiflorus (Hook. & Arn.) Manos, Cannon & S. H. Oh, were studied on the Challenge...

Individual differences in normal body temperature: longitudinal big data analysis of patient records.

PubMed

Obermeyer, Ziad; Samra, Jasmeet K; Mullainathan, Sendhil

2017-12-13

To estimate individual level body temperature and to correlate it with other measures of physiology and health. Observational cohort study. Outpatient clinics of a large academic hospital, 2009-14. 35 488 patients who neither received a diagnosis for infections nor were prescribed antibiotics, in whom temperature was expected to be within normal limits. Baseline temperatures at individual level, estimated using random effects regression and controlling for ambient conditions at the time of measurement, body site, and time factors. Baseline temperatures were correlated with demographics, medical comorbidities, vital signs, and subsequent one year mortality. In a diverse cohort of 35 488 patients (mean age 52.9 years, 64% women, 41% non-white race) with 243 506 temperature measurements, mean temperature was 36.6°C (95% range 35.7-37.3°C, 99% range 35.3-37.7°C). Several demographic factors were linked to individual level temperature, with older people the coolest (-0.021°C for every decade, P<0.001) and African-American women the hottest (versus white men: 0.052°C, P<0.001). Several comorbidities were linked to lower temperature (eg, hypothyroidism: -0.013°C, P=0.01) or higher temperature (eg, cancer: 0.020, P<0.001), as were physiological measurements (eg, body mass index: 0.002 per m/kg 2 , P<0.001). Overall, measured factors collectively explained only 8.2% of individual temperature variation. Despite this, unexplained temperature variation was a significant predictor of subsequent mortality: controlling for all measured factors, an increase of 0.149°C (1 SD of individual temperature in the data) was linked to 8.4% higher one year mortality (P=0.014). Individuals' baseline temperatures showed meaningful variation that was not due solely to measurement error or environmental factors. Baseline temperatures correlated with demographics, comorbid conditions, and physiology, but these factors explained only a small part of individual temperature variation. Unexplained variation in baseline temperature, however, strongly predicted mortality. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Individual differences in normal body temperature: longitudinal big data analysis of patient records

PubMed Central

Samra, Jasmeet K; Mullainathan, Sendhil

2017-01-01

Abstract Objective To estimate individual level body temperature and to correlate it with other measures of physiology and health. Design Observational cohort study. Setting Outpatient clinics of a large academic hospital, 2009-14. Participants 35 488 patients who neither received a diagnosis for infections nor were prescribed antibiotics, in whom temperature was expected to be within normal limits. Main outcome measures Baseline temperatures at individual level, estimated using random effects regression and controlling for ambient conditions at the time of measurement, body site, and time factors. Baseline temperatures were correlated with demographics, medical comorbidities, vital signs, and subsequent one year mortality. Results In a diverse cohort of 35 488 patients (mean age 52.9 years, 64% women, 41% non-white race) with 243 506 temperature measurements, mean temperature was 36.6°C (95% range 35.7-37.3°C, 99% range 35.3-37.7°C). Several demographic factors were linked to individual level temperature, with older people the coolest (–0.021°C for every decade, P<0.001) and African-American women the hottest (versus white men: 0.052°C, P<0.001). Several comorbidities were linked to lower temperature (eg, hypothyroidism: –0.013°C, P=0.01) or higher temperature (eg, cancer: 0.020, P<0.001), as were physiological measurements (eg, body mass index: 0.002 per m/kg2, P<0.001). Overall, measured factors collectively explained only 8.2% of individual temperature variation. Despite this, unexplained temperature variation was a significant predictor of subsequent mortality: controlling for all measured factors, an increase of 0.149°C (1 SD of individual temperature in the data) was linked to 8.4% higher one year mortality (P=0.014). Conclusions Individuals’ baseline temperatures showed meaningful variation that was not due solely to measurement error or environmental factors. Baseline temperatures correlated with demographics, comorbid conditions, and physiology, but these factors explained only a small part of individual temperature variation. Unexplained variation in baseline temperature, however, strongly predicted mortality. PMID:29237616

Pulmonary arterial distension and vagal afferent nerve activity in anaesthetized dogs.

PubMed

Moore, Jonathan P; Hainsworth, Roger; Drinkhill, Mark J

2004-03-16

Distension of the main pulmonary artery and its bifurcation are known to result in a reflex vasoconstriction and increased respiratory drive; however, these responses are observed at abnormally high distending pressures. In this study we recorded afferent activity from pulmonary arterial baroreceptors to investigate their stimulus-response characteristics and to determine whether they are influenced by physiological changes in intrathoracic pressure. In chloralose-anaesthetized dogs, a cardiopulmonary bypass was established, the pulmonary trunk and its main branches were vascularly isolated and perfused with venous blood at pulsatile pressures designed to simulate the normal pulmonary arterial pressure waveform. Afferent slips of a cervical vagus were dissected and nerve fibres identified that displayed discharge patterns with characteristics expected from pulmonary arterial baroreceptors. Recordings were obtained with (a) chest open (b) chest closed and resealed, and (c) with phasic negative intrathoracic pressures in the resealed chest. Pressure-discharge characteristics obtained in the open-chest animals indicated that the threshold pulmonary pressure (corresponding to 5% of the overall response) was 17.1 +/- 2.9 and the inflexion point of the curve was 29.2 +/- 3.3 mmHg (mean +/-S.E.M). In closed-chest animals the threshold and inflexion pressures were reduced to 12.0 +/- 1.7 and 20.7 +/- 1.8 mmHg. Application of phasic negative intrathoracic pressures further reduced the threshold and inflexion pressures to 9.5 +/- 1.2 mmHg (P < 0.05 vs. open) and 14.7 +/- 0.8 mmHg (P < 0.003 vs. open and P < 0.02 vs. atmospheric). These results indicate that under physiological conditions, with closed-chest and phasic negative intrathoracic pressure changes similar to those associated with normal breathing, activity from pulmonary baroreceptors is obtained at physiological pulmonary arterial pressures in intact animals.

Stress and physiological, behavioral and performance patterns of children under varied air ion levels

NASA Astrophysics Data System (ADS)

Fornof, K. T.; Gilbert, G. O.

1988-12-01

The possibility that individual differences in reactivity to stressors are a major factor underlying discordant results reported for air ion studies prompted an investigation of response patterns in school children under both normal indoor air ion levels and moderately increased negative air ion levels (4000±500/cm3). It was hypothesized that the impact of stressors is reduced with high negative air ionization, and that resultant changes in stress effects would be differentially exhibited according to the children's normal degree of stimulus reactivity. A counter-balanced, replicative, withinssubject design was selected, and the subjects were 12 environmentally sensitive, 1st 4th grade school children. In addition to monitoring stress effects on activity level, attention span, concentration to task and conceptual performance, measures were also made of urinary 5-hydroxyindole acetic acid levels and skin resistance response (SRR) to determine if changes extended to the physiological state. The cold water test was used to add physical stress and enable calculations of Lacey's autonomic lability scores (ALS) as indicators of individual reactivity. The results show main effects for air ions on both physiological parameters, with 48% less change in %SRR ( P<0.01) and 46% less change in urinary 5-HIAA levels ( P<0.055) during negative air ions, indicating increased stress tolerance. Strong interactive effects for ALS x air ion condition appeared, with high and low ALS children reacting oppositely to negative air ions in measures of skin resistance level ( P<0.01), wrist activity ( P<0.01) and digit span backwards ( P<0.004). Thus individual differences in autonomic reactivity and the presence or absence of stressors appear as critical elements for internal validity, and in preventing consequent skewed results from obscuring progress in air ion research.

The anatomy and physiology of the avian endocrine system.

PubMed

Ritchie, Midge; Pilny, Anthony A

2008-01-01

The endocrine system of birds is comparable to that of mammals, although there are many unique aspects to consider when studying the anatomy, physiology, and biochemistry. Avian endocrinology is a field of veterinary medicine that is unfamiliar to many practitioners; however, it is important to have a comprehensive understanding when evaluating companion birds in clinical practice. This article covers the anatomy and physiology of the normal avian, and readers are referred to other articles for a more detailed explanation of altered physiology and pathology.

Physiological regeneration of skin appendages and implications for regenerative medicine

PubMed Central

Chuong, Cheng-Ming; Randall, Valerie A; Widelitz, Randall B.; Wu, Ping; Jiang, Ting-Xin

2013-01-01

The concept of regenerative medicine is relatively new, but animals are well known to remake their hair and feathers regularly by normal regenerative physiological processes. Here we focus on 1) how extra-follicular environments can regulate hair and feather stem cell activities and 2) how different configurations of stem cells can shape organ forms in different body regions to fulfil changing physiological needs. PMID:22505663

Compression Stiffening of Brain and its Effect on Mechanosensing by Glioma Cells

NASA Astrophysics Data System (ADS)

Pogoda, Katarzyna

The stiffness of tissues, often characterized by their time-dependent elastic properties, is tightly controlled under normal condition and central nervous system tissue is among the softest tissues. Changes in tissue and organ stiffness occur in some physiological conditions and are frequently symptoms of diseases such as fibrosis, cardiovascular disease and many forms of cancer. Primary cells isolated from various tissues often respond to changes in the mechanical properties of their substrates, and the range of stiffness over which these responses occur appear to be limited to the tissue elastic modulus from which they are derived. Our goal was to test the hypotheses that the stiffness of tumors derived from CNS tissue differs from that of normal brain, and that transformed cells derived from such tumors exhibit mechanical responses that differ from those of normal glial cells. Unlike breast and some other cancers where the stroma and the tumor itself is substantially stiffer than the surrounding normal tissue, our data suggest that gliomas can arise without a gross change in the macroscopic tissue stiffness when measured at low strains without compression. However, both normal brain and glioma samples stiffen with compression, but not in elongation and increased shear strains. On the other hand, different classes of immortalized cells derived from human glioblastoma show substantially different responses to the stiffness of substrates in vitrowhen grown on soft polyacrylamide and hyaluronic acid gels. This outcome supports the hypothesis that compression stiffening, which might occur with increased vascularization and interstitial pressure gradients that are characteristic of tumors, effectively stiffens the environment of glioma cells, and that in situ, the elastic resistance these cells sense might be sufficient to trigger the same responses that are activated in vitro by increased substrate stiffness.

Low-level infrared laser modulates muscle repair and chromosome stabilization genes in myoblasts.

PubMed

da Silva Neto Trajano, Larissa Alexsandra; Stumbo, Ana Carolina; da Silva, Camila Luna; Mencalha, Andre Luiz; Fonseca, Adenilson S

2016-08-01

Infrared laser therapy is used for skeletal muscle repair based on its biostimulative effect on satellite cells. However, shortening of telomere length limits regenerative potential in satellite cells, which occurs after each cell division cycle. Also, laser therapy could be more effective on non-physiologic tissues. This study evaluated low-level infrared laser exposure effects on mRNA expression from muscle injury repair and telomere stabilization genes in myoblasts in normal and stressful conditions. Laser fluences were those used in clinical protocols. C2C12 myoblast cultures were exposed to low-level infrared laser (10, 35, and 70 J/cm(2)) in standard or normal (10 %) and reduced (2 %) fetal bovine serum concentrations; total RNA was extracted for mRNA expression evaluation from muscle injury repair (MyoD and Pax7) and chromosome stabilization (TRF1 and TRF2) genes by real time quantitative polymerization chain reaction. Data show that low-level infrared laser increases the expression of MyoD and Pax7 in 10 J/cm(2) fluence, TRF1 expression in all fluences, and TRF2 expression in 70 J/cm(2) fluence in both 10 and 2 % fetal bovine serum. Low-level infrared laser increases mRNA expression from genes related to muscle repair and telomere stabilization in myoblasts in standard or normal and stressful conditions.

Autism, Asperger syndrome and brain mechanisms for the attribution of mental states to animated shapes.

PubMed

Castelli, Fulvia; Frith, Chris; Happé, Francesca; Frith, Uta

2002-08-01

Ten able adults with autism or Asperger syndrome and 10 normal volunteers were PET scanned while watching animated sequences. The animations depicted two triangles moving about on a screen in three different conditions: moving randomly, moving in a goal-directed fashion (chasing, fighting), and moving interactively with implied intentions (coaxing, tricking). The last condition frequently elicited descriptions in terms of mental states that viewers attributed to the triangles (mentalizing). The autism group gave fewer and less accurate descriptions of these latter animations, but equally accurate descriptions of the other animations compared with controls. While viewing animations that elicited mentalizing, in contrast to randomly moving shapes, the normal group showed increased activation in a previously identified mentalizing network (medial prefrontal cortex, superior temporal sulcus at the temporo-parietal junction and temporal poles). The autism group showed less activation than the normal group in all these regions. However, one additional region, extrastriate cortex, which was highly active when watching animations that elicited mentalizing, showed the same amount of increased activation in both groups. In the autism group this extrastriate region showed reduced functional connectivity with the superior temporal sulcus at the temporo-parietal junction, an area associated with the processing of biological motion as well as with mentalizing. This finding suggests a physiological cause for the mentalizing dysfunction in autism: a bottleneck in the interaction between higher order and lower order perceptual processes.

Reduction of renal mass is lethal in mice lacking vimentin. Role of endothelin-nitric oxide imbalance.

PubMed Central

Terzi, F; Henrion, D; Colucci-Guyon, E; Federici, P; Babinet, C; Levy, B I; Briand, P; Friedlander, G

1997-01-01

Modulation of vascular tone by chemical and mechanical stimuli is a crucial adaptive phenomenon which involves cytoskeleton elements. Disruption, by homologous recombination, of the gene encoding vimentin, a class III intermediate filament protein mainly expressed in vascular cells, was reported to result in apparently normal phenotype under physiological conditions. In this study, we evaluated whether the lack of vimentin affects vascular adaptation to pathological situations, such as reduction of renal mass, a pathological condition which usually results in immediate and sustained vasodilation of the renal vascular bed. Ablation of 3/4 of renal mass was constantly lethal within 72 h in mice lacking vimentin (Vim-/-), whereas no lethality was observed in wild-type littermates. Death in Vim-/- mice resulted from end-stage renal failure. Kidneys from Vim-/- mice synthesized more endothelin, but less nitric oxide (NO), than kidneys from normal animals. In vitro, renal resistance arteries from Vim-/- mice were selectively more sensitive to endothelin, less responsive to NO-dependent vasodilators, and exhibited an impaired flow (shear stress)- induced vasodilation, which is NO dependent, as compared with those from normal littermates. Finally, in vivo administration of bosentan, an endothelin receptor antagonist, totally prevented lethality in Vim-/- mice. These results suggest that vimentin plays a key role in the modulation of vascular tone, possibly via the tuning of endothelin-nitric oxide balance. PMID:9294120

Transforming Water: Social Influence Moderates Psychological, Physiological, and Functional Response to a Placebo Product

PubMed Central

Crum, Alia J.; Phillips, Damon J.; Goyer, J. Parker; Akinola, Modupe; Higgins, E. Tory

2016-01-01

This paper investigates how social influence can alter physiological, psychological, and functional responses to a placebo product and how such responses influence the ultimate endorsement of the product. Participants consumed a product, “AquaCharge Energy Water,” falsely-labeled as containing 200 mg of caffeine but which was actually plain spring water, in one of three conditions: a no social influence condition, a disconfirming social influence condition, and a confirming social influence condition. Results demonstrated that the effect of the product labeling on physiological alertness (systolic blood pressure), psychological alertness (self-reported alertness), functional alertness (cognitive interference), and product endorsement was moderated by social influence: participants experienced more subjective, physiological and functional alertness and stronger product endorsement when they consumed the product in the confirming social influence condition than when they consumed the product in the disconfirming social influence condition. These results suggest that social influence can alter subjective, physiological, and functional responses to a faux product, in this case transforming the effects of plain water. PMID:27875567

Transforming Water: Social Influence Moderates Psychological, Physiological, and Functional Response to a Placebo Product.

PubMed

Crum, Alia J; Phillips, Damon J; Goyer, J Parker; Akinola, Modupe; Higgins, E Tory

2016-01-01

This paper investigates how social influence can alter physiological, psychological, and functional responses to a placebo product and how such responses influence the ultimate endorsement of the product. Participants consumed a product, "AquaCharge Energy Water," falsely-labeled as containing 200 mg of caffeine but which was actually plain spring water, in one of three conditions: a no social influence condition, a disconfirming social influence condition, and a confirming social influence condition. Results demonstrated that the effect of the product labeling on physiological alertness (systolic blood pressure), psychological alertness (self-reported alertness), functional alertness (cognitive interference), and product endorsement was moderated by social influence: participants experienced more subjective, physiological and functional alertness and stronger product endorsement when they consumed the product in the confirming social influence condition than when they consumed the product in the disconfirming social influence condition. These results suggest that social influence can alter subjective, physiological, and functional responses to a faux product, in this case transforming the effects of plain water.

G6pd Deficiency Does Not Affect the Cytosolic Glutathione or Thioredoxin Antioxidant Defense in Mouse Cochlea.

PubMed

White, Karessa; Kim, Mi-Jung; Ding, Dalian; Han, Chul; Park, Hyo-Jin; Meneses, Zaimary; Tanokura, Masaru; Linser, Paul; Salvi, Richard; Someya, Shinichi

2017-06-07

Glucose-6-phosphate dehydrogenase (G6PD) is the first and rate-limiting enzyme of the pentose phosphate pathway; it catalyzes the conversion of glucose-6-phosphate to 6-phosphogluconate and NADP + to NADPH and is thought to be the principal source of NADPH for the cytosolic glutathione and thioredoxin antioxidant defense systems. We investigated the roles of G6PD in the cytosolic antioxidant defense in the cochlea of G6pd hypomorphic mice that were backcrossed onto normal-hearing CBA/CaJ mice. Young G6pd -deficient mice displayed a significant decrease in cytosolic G6PD protein levels and activities in the inner ears. However, G6pd deficiency did not affect the cytosolic NADPH redox state, or glutathione or thioredoxin antioxidant defense in the inner ears. No histological abnormalities or oxidative damage was observed in the cochlea of G6pd hemizygous males or homozygous females. Furthermore, G6pd deficiency did not affect auditory brainstem response hearing thresholds, wave I amplitudes or wave I latencies in young males or females. In contrast, G6pd deficiency resulted in increased activities and protein levels of cytosolic isocitrate dehydrogenase 1, an enzyme that catalyzes the conversion of isocitrate to α-ketoglutarate and NADP + to NADPH, in the inner ear. In a mouse inner ear cell line, knockdown of Idh1 , but not G6pd , decreased cell growth rates, cytosolic NADPH levels, and thioredoxin reductase activities. Therefore, under normal physiological conditions, G6pd deficiency does not affect the cytosolic glutathione or thioredoxin antioxidant defense in mouse cochlea. Under G6pd deficiency conditions, isocitrate dehydrogenase 1 likely functions as the principal source of NADPH for cytosolic antioxidant defense in the cochlea. SIGNIFICANCE STATEMENT Glucose-6-phosphate dehydrogenase (G6PD) is the first and rate-limiting enzyme of the pentose phosphate pathway; it catalyzes the conversion of glucose-6-phosphate to 6-phosphogluconate and NADP + to NADPH and is thought to be the principal source of NADPH for the cytosolic glutathione and thioredoxin antioxidant defense systems. In the current study, we show that, under normal physiological conditions, G6pd deficiency does not affect the cytosolic glutathione or thioredoxin antioxidant defense in the mouse cochlea. However, under G6pd deficiency conditions, isocitrate dehydrogenase 1 likely functions as the principal source of NADPH for cytosolic antioxidant defense in the cochlea. Copyright © 2017 the authors 0270-6474/17/375770-12$15.00/0.

Anatomy and Physiology of the Blood-Brain Barrier

PubMed Central

Serlin, Yonatan; Shelef, Ilan; Knyazer, Boris; Friedman, Alon

2015-01-01

Essential requisite for the preservation of normal brain activity is to maintain a narrow and stable homeostatic control in the neuronal environment of the CNS. Blood flow alterations and altered vessel permeability are considered key determinants in the pathophysiology of brain injuries. We will review the present-day literature on the anatomy, development and physiological mechanisms of the blood-brain barrier, a distinctive and tightly regulated interface between the CNS and the peripheral circulation, playing a crucial role in the maintenance of the strict environment required for normal brain function. PMID:25681530

Ongoing search for diagnostic biomarkers in idiopathic normal pressure hydrocephalus.

PubMed

Tarnaris, Andrew; Toma, Ahmed K; Kitchen, Neil D; Watkins, Laurence D

2009-12-01

Idiopathic normal pressure hydrocephalus is a syndrome, which typically has a clinical presentation of gait/balance disturbance, often accompanied by cognitive decline and/or urinary incontinence. Its diagnosis is based on relevant history and clinical examination, appropriate imaging findings and physiological testing. The clinical picture of idiopathic normal pressure hydrocephalus may occasionally be difficult to distinguish from that of Alzheimer's dementia, subcortical ischemic vascular dementia and Parkinson's disease. The aim of this article is to systematically review the literature from the last 29 years in order to identify cerebrospinal fluid (CSF) or imaging biomarkers that may aid in the diagnosis of the syndrome. The authors concluded that no CSF or imaging biomarker is currently fulfilling the criteria required to aid in the diagnosis of the condition. However, a few studies have revealed promising CSF and imaging markers that need to be verified by independent groups. The reasons that the progress in this field has been slow so far is also commented on, as well as steps required to apply the current evidence in the design of future studies within the field.

Quantitative Proteomics of the Root of Transgenic Wheat Expressing TaBWPR-1.2 Genes in Response to Waterlogging.

PubMed

Haque, Emdadul; Abe, Fumitaka; Mori, Masahiko; Nanjo, Yohei; Komatsu, Setsuko; Oyanagi, Atsushi; Kawaguchi, Kentaro

2014-11-04

Once candidate genes are available, the application of genetic transformation plays a major part to study their function in plants for adaptation to respective environmental stresses, including waterlogging (WL). The introduction of stress-inducible genes into wheat remains difficult because of low transformation and plant regeneration efficiencies and expression variability and instability. Earlier, we found two cDNAs encoding WL stress-responsive wheat pathogenesis-related proteins 1.2 ( TaBWPR-1.2 ), TaBWPR-1.2#2 and TaBWPR-1.2# 13. Using microprojectile bombardment, both cDNAs were introduced into "Bobwhite". Despite low transformation efficiency, four independent T₂ homozygous lines for each gene were isolated, where transgenes were ubiquitously and variously expressed. The highest transgene expression was obtained in Ubi: TaBWPR-1.2#2 L#11a and Ubi:TaBWPR-1.2#13 L#4a. Using quantitative proteomics, the root proteins of L#11a were analyzed to explore possible physiological pathways regulated by TaBWPR-1.2 under normal and waterlogged conditions. In L#11a, the abundance of proteasome subunit alpha type-3 decreased under normal conditions, whereas that of ferredoxin precursor and elongation factor-2 increased under waterlogged conditions in comparison with normal plants. Proteomic results suggest that L#11a is one of the engineered wheat plants where TaBWPR-1.2#2 is most probably involved in proteolysis, protein synthesis and alteration in the energy pathway in root tissues via the above proteins in order to gain metabolic adjustment to WL.

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.

Existence of Inverted Profile in Chemically Responsive Molecular Pathways in the Zebrafish Liver

PubMed Central

Zhang, Xun; Li, Hu; Ma, Jing; Zhang, Louxin; Li, Baowen; Gong, Zhiyuan

2011-01-01

How a living organism maintains its healthy equilibrium in response to endless exposure of potentially harmful chemicals is an important question in current biology. By transcriptomic analysis of zebrafish livers treated by various chemicals, we defined hubs as molecular pathways that are frequently perturbed by chemicals and have high degree of functional connectivity to other pathways. Our network analysis revealed that these hubs were organized into two groups showing inverted functionality with each other. Intriguingly, the inverted activity profiles in these two groups of hubs were observed to associate only with toxicopathological states but not with physiological changes. Furthermore, these inverted profiles were also present in rat, mouse, and human under certain toxicopathological conditions. Thus, toxicopathological-associated anti-correlated profiles in hubs not only indicate their potential use in diagnosis but also development of systems-based therapeutics to modulate gene expression by chemical approach in order to rewire the deregulated activities of hubs back to normal physiology. PMID:22140468

Effects of Exopolysaccharide Production on Liquid Vegetative Growth, Stress Survival and Stationary Phase Recovery in Myxococcus xanthus

PubMed Central

Hu, Wei; Wang, Jing; McHardy, Ian; Lux, Renate; Yang, Zhe; Li, Yuezhong; Shi, Wenyuan

2013-01-01

Exopolysaccharide (EPS) of Myxococcus xanthus is a well-regulated cell surface component. In addition to its known functions for social motility and fruiting body formation on solid surfaces, EPS has also been proposed to play a role in multi-cellular clumping in liquid medium, though this phenomenon has not been well studied. In this report, we confirmed that M. xanthus clumps formed in liquid were correlated with EPS levels and demonstrated that the EPS encased cell clumps exhibited biofilm-like structures. The clumps protected the cells at physiologically relevant EPS concentrations, while cells lacking EPS exhibited significant reduction in long-term viability and resistance to stressful conditions. However, excess EPS production was counterproductive to vegetative growth and viable cell recovery declined in extended late stationary phase as cells became trapped in the matrix of clumps. Therefore, optimal EPS production by M. xanthus is important for normal physiological functions in liquid. PMID:22538652

Host-Microbe Interactions in Microgravity: Assessment and Implications

PubMed Central

Foster, Jamie S.; Wheeler, Raymond M.; Pamphile, Regine

2014-01-01

Spaceflight imposes several unique stresses on biological life that together can have a profound impact on the homeostasis between eukaryotes and their associated microbes. One such stressor, microgravity, has been shown to alter host-microbe interactions at the genetic and physiological levels. Recent sequencing of the microbiomes associated with plants and animals have shown that these interactions are essential for maintaining host health through the regulation of several metabolic and immune responses. Disruptions to various environmental parameters or community characteristics may impact the resiliency of the microbiome, thus potentially driving host-microbe associations towards disease. In this review, we discuss our current understanding of host-microbe interactions in microgravity and assess the impact of this unique environmental stress on the normal physiological and genetic responses of both pathogenic and mutualistic associations. As humans move beyond our biosphere and undergo longer duration space flights, it will be essential to more fully understand microbial fitness in microgravity conditions in order to maintain a healthy homeostasis between humans, plants and their respective microbiomes. PMID:25370197

Host-microbe interactions in microgravity: assessment and implications.

PubMed

Foster, Jamie S; Wheeler, Raymond M; Pamphile, Regine

2014-05-26

Spaceflight imposes several unique stresses on biological life that together can have a profound impact on the homeostasis between eukaryotes and their associated microbes. One such stressor, microgravity, has been shown to alter host-microbe interactions at the genetic and physiological levels. Recent sequencing of the microbiomes associated with plants and animals have shown that these interactions are essential for maintaining host health through the regulation of several metabolic and immune responses. Disruptions to various environmental parameters or community characteristics may impact the resiliency of the microbiome, thus potentially driving host-microbe associations towards disease. In this review, we discuss our current understanding of host-microbe interactions in microgravity and assess the impact of this unique environmental stress on the normal physiological and genetic responses of both pathogenic and mutualistic associations. As humans move beyond our biosphere and undergo longer duration space flights, it will be essential to more fully understand microbial fitness in microgravity conditions in order to maintain a healthy homeostasis between humans, plants and their respective microbiomes.

Ubiquitinated Sirtuin 1 (SIRT1) Function Is Modulated during DNA Damage-induced Cell Death and Survival*

PubMed Central

Peng, Lirong; Yuan, Zhigang; Li, Yixuan; Ling, Hongbo; Izumi, Victoria; Fang, Bin; Fukasawa, Kenji; Koomen, John; Chen, Jiandong; Seto, Edward

2015-01-01

Downstream signaling of physiological and pathological cell responses depends on post-translational modification such as ubiquitination. The mechanisms regulating downstream DNA damage response (DDR) signaling are not completely elucidated. Sirtuin 1 (SIRT1), the founding member of Class III histone deacetylases, regulates multiple steps in DDR and is closely associated with many physiological and pathological processes. However, the role of post-translational modification or ubiquitination of SIRT1 during DDR is unclear. We show that SIRT1 is dynamically and distinctly ubiquitinated in response to DNA damage. SIRT1 was ubiquitinated by the MDM2 E3 ligase in vitro and in vivo. SIRT1 ubiquitination under normal conditions had no effect on its enzymatic activity or rate of degradation; hypo-ubiquitination, however, reduced SIRT1 nuclear localization. Ubiquitination of SIRT1 affected its function in cell death and survival in response to DNA damage. Our results suggest that ubiquitination is required for SIRT1 function during DDR. PMID:25670865

Psychological and physiological responses during an exam and their relation to personality characteristics.

PubMed

Spangler, G

1997-08-01

The aim of the study was to compare emotional and physiological responses to real and control examinations and to assess their relation to personality characteristics. Emotional responses were assessed by state anxiety and perceived stress. The assessment of physiological responses included the activity of the cardiac system (heart periods, vagal tone), the adrenocortical system (cortisol) and the immune system (immune globulin A, sIgA). Emotional and physiological responses of 23 students (12 males, 11 females) were assessed during an oral exam at the end of a basic course in psychology which was a prerequisite for the students' final exams. For the control condition physiological responses were assessed one week before the examination during a memory test. The findings of the study demonstrate different emotional and physiological response patterns to examinations as compared to the control condition. Heightened anxiety was observed only before the exam. Whereas within-situation physiological responses (higher heart periods, cortisol, and sIgA; lower vagal tone) were observed both under the exam and control condition, responses to exam condition indicated pre-exam anticipatory activation and post-exam restricted recovery responses. With regard to personality characteristics subjects with high ego-resiliency showed more flexible adaptation than subjects with low ego-resiliency both on the emotional level (anxiety down-regulation after exam) and on the physiological level (situation-specific responses, quick recovery). Subjects with high ego-control exhibited a lower physiological reactivity under both conditions, i.e. they seemed to maintain longer their control also on a physiological level independent of the type of situation.

Eppur Si Muove: The Dynamic Nature of Physiological Control of Renal Blood Flow by the Renal Sympathetic Nerves

PubMed Central

Schiller, Alicia M.; Pellegrino, Peter Ricci; Zucker, Irving H.

2016-01-01

Tubuloglomerular feedback and the myogenic response are widely appreciated as important regulators of renal blood flow, but the role of the sympathetic nervous system in physiological renal blood flow control remains controversial. Where classic studies using static measures of renal blood flow failed, dynamic approaches have succeeded in demonstrating sympathetic control of renal blood flow under normal physiological conditions. This review focuses on transfer function analysis of renal pressure-flow, which leverages the physical relationship between blood pressure and flow to assess the underlying vascular control mechanisms. Studies using this approach indicate that the renal nerves are important in the rapid regulation of the renal vasculature. Animals with intact renal innervation show a sympathetic signature in the frequency range associated with sympathetic vasomotion that is eliminated by renal denervation. In conscious rabbits, this sympathetic signature exerts vasoconstrictive, baroreflex control of renal vascular conductance, matching well with the rhythmic, baroreflex-influenced control of renal sympathetic nerve activity and complementing findings from other studies employing dynamic approaches to study renal sympathetic vascular control. In this light, classic studies reporting that nerve stimulation and renal denervation do not affect static measures of renal blood flow provide evidence for the strength of renal autoregulation rather than evidence against physiological renal sympathetic control of renal blood flow. Thus, alongside tubuloglomerular feedback and the myogenic response, renal sympathetic outflow should be considered an important physiological regulator of renal blood flow. Clinically, renal sympathetic vasomotion may be important for solving the problems facing the field of therapeutic renal denervation. PMID:27514571

Eppur Si Muove: The dynamic nature of physiological control of renal blood flow by the renal sympathetic nerves.

PubMed

Schiller, Alicia M; Pellegrino, Peter Ricci; Zucker, Irving H

2017-05-01

Tubuloglomerular feedback and the myogenic response are widely appreciated as important regulators of renal blood flow, but the role of the sympathetic nervous system in physiological renal blood flow control remains controversial. Where classic studies using static measures of renal blood flow failed, dynamic approaches have succeeded in demonstrating sympathetic control of renal blood flow under normal physiological conditions. This review focuses on transfer function analysis of renal pressure-flow, which leverages the physical relationship between blood pressure and flow to assess the underlying vascular control mechanisms. Studies using this approach indicate that the renal nerves are important in the rapid regulation of the renal vasculature. Animals with intact renal innervation show a sympathetic signature in the frequency range associated with sympathetic vasomotion that is eliminated by renal denervation. In conscious rabbits, this sympathetic signature exerts vasoconstrictive, baroreflex control of renal vascular conductance, matching well with the rhythmic, baroreflex-influenced control of renal sympathetic nerve activity and complementing findings from other studies employing dynamic approaches to study renal sympathetic vascular control. In this light, classic studies reporting that nerve stimulation and renal denervation do not affect static measures of renal blood flow provide evidence for the strength of renal autoregulation rather than evidence against physiological renal sympathetic control of renal blood flow. Thus, alongside tubuloglomerular feedback and the myogenic response, renal sympathetic outflow should be considered an important physiological regulator of renal blood flow. Clinically, renal sympathetic vasomotion may be important for solving the problems facing the field of therapeutic renal denervation. Copyright © 2016 Elsevier B.V. All rights reserved.

Devices for noninvasive transcranial electrostimulation of the brain endorphinergic system: application for improvement of human psycho-physiological status.

PubMed

Lebedev, Valery P; Malygin, A V; Kovalevski, A V; Rychkova, S V; Sisoev, V N; Kropotov, S P; Krupitski, E M; Gerasimova, L I; Glukhov, D V; Kozlowski, G P

2002-03-01

It is well known that deficit of endorphins plays an important role in disturbances of human psycho-physiological status. Previously, we revealed that brain endorphinergic structures have quasiresonance characteristics. On the basis of these data, a method of activation of the brain endorphinergic structures by means of noninvasive and rather selective transcranial electrostimulation (TES) as a kind of functional electrical stimulation (FES) was elaborated. New models of TES devices (TRANSAIR) were developed for indoor and outdoor usage. To increase the efficacy of TES, the frequency modulation according to normal distribution in the limits of the quasiresonance characteristics was put into operation. The blind and placebo-controlled (passive and active placebo) study was produced to estimate the TES effects on stress events and accompanied psycho-physiological and autonomic disturbances of different intensities on volunteers and patients in the following groups: everyday stress and fatigue; stress in regular military service and in field conditions; stress in the relatives of those lost in mass disaster; posttraumatic stress (thermal burns); and affective disorders in a postabstinence period. Some subjective verbal and nonverbal tests and objective tests (including heart rate variability) were used for estimation of the initial level of psycho-physiological status, which changes after TES sessions. It was demonstrated that fatigue, stress, and other accompanied psycho-physiological disturbances were significantly improved or abolished after 2-5 TES sessions. The TES effects were more pronounced in cases of heavier disturbances. In conclusion, activation of the brain endorphinergic structures by TES is an effective homeostatic method of FES that sufficiently improves quality of life.

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

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

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

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

Metabolomic strategies to map functions of metabolic pathways

PubMed Central

Mulvihill, Melinda M.

2014-01-01

Genome sequencing efforts have revealed a strikingly large number of unannotated and uncharacterized genes that fall into metabolic enzymes classes, likely indicating that our current knowledge of biochemical pathways in normal physiology, let alone in disease states, remains largely incomplete. This realization presents a daunting challenge for post-genomic-era scientists in deciphering the biochemical and (patho)physiological roles of these enzymes and their metabolites and metabolic networks. This is further complicated by many recent studies showing a rewiring of normal metabolic networks in disease states to give rise to unique pathophysiological functions of enzymes, metabolites, and metabolic pathways. This review focuses on recent discoveries made using metabolic mapping technologies to uncover novel pathways and metabolite-mediated posttranslational modifications and epigenetic alterations and their impact on physiology and disease. PMID:24918200

Zinc and Wound Healing: A Review of Zinc Physiology and Clinical Applications.

PubMed

Kogan, Samuel; Sood, Aditya; Garnick, Mark S

2017-04-01

Our understanding of the role of zinc in normal human physiology is constantly expanding, yet there are major gaps in our knowledge with regard to the function of zinc in wound healing. This review aims to provide the clinician with sufficient understanding of zinc biology and an up-to-date perspective on the role of zinc in wound healing. Zinc is an essential ion that is crucial for maintenance of normal physiology, and zinc deficiency has many manifestations ranging from delayed wound healing to immune dysfunction and impairment of multiple sensory systems. While consensus has been reached regarding the detrimental effects of zinc deficiency on wound healing, there is considerable discord in the literature on the optimal methods and true benefits of zinc supplementation.

Natural thermal adaptation increases heat shock protein levels and decreases oxidative stress.

PubMed

Oksala, Niku K J; Ekmekçi, F Güler; Ozsoy, Ergi; Kirankaya, Serife; Kokkola, Tarja; Emecen, Güzin; Lappalainen, Jani; Kaarniranta, Kai; Atalay, Mustafa

2014-01-01

Heat shock proteins (HSPs), originally identified as heat-inducible gene products, are a family of highly conserved proteins that respond to a wide variety of stress including oxidative stress. Although both acute and chronic oxidative stress have been well demonstrated to induce HSP responses, little evidence is available whether increased HSP levels provide enhanced protection against oxidative stress under elevated yet sublethal temperatures. We studied relationships between oxidative stress and HSPs in a physiological model by using Garra rufa (doctor fish), a fish species naturally acclimatized to different thermal conditions. We compared fish naturally living in a hot spring with relatively high water temperature (34.4±0.6°C) to those living in normal river water temperature (25.4±4.7°C), and found that levels of all the studied HSPs (HSP70, HSP60, HSP90, HSC70 and GRP75) were higher in fish living in elevated water temperature compared with normal river water temperature. In contrast, indicators of oxidative stress, including protein carbonyls and lipid hydroperoxides, were decreased in fish living in the elevated temperature, indicating that HSP levels are inversely associated with oxidative stress. The present results provide evidence that physiologically increased HSP levels provide protection against oxidative stress and enhance cytoprotection. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.

IGFBP-4 and PAPP-A in normal physiology and disease.

PubMed

Hjortebjerg, Rikke

2018-05-30

Insulin-like growth factor (IGF) binding protein-4 (IGFBP-4) is a modulator of the IGF system, exerting both inhibitory and stimulatory effects on IGF-induced cellular growth. IGFBP-4 is the principal substrate for the enzyme pregnancy-associated plasma protein-A (PAPP-A). Through IGF-dependent cleavage of IGFBP-4 in the vicinity of the IGF receptor, PAPP-A is able to increase IGF bioavailability and stimulate IGF-mediated growth. Recently, the stanniocalcins (STCs) were identified as novel inhibitors of PAPP-A proteolytic activity, hereby adding additional members to the seemingly endless list of proteins belonging to the IGF family. Our understanding of these proteins has advanced throughout recent years, and there is evidence to suggest that the role of IGFBP-4 and PAPP-A in defining the relationship between total IGF and IGF bioactivity can be linked to a number of pathological conditions. This review provides an overview of the experimental and clinical findings on the IGFBP-4/PAPP-A/STC axis as a regulator of IGF activity and examines the conundrum surrounding extrapolation of circulating concentrations to tissue action of these proteins. The primary focus will be on the biological significance of IGFBP-4 and PAPP-A in normal physiology and in pathophysiology with emphasis on metabolic disorders, cardiovascular diseases, and cancer. Finally, the review assesses current new trajectories of IGFBP-4 and PAPP-A research. Copyright © 2018. Published by Elsevier Ltd.

Physiology of ejaculation: emphasis on serotonergic control.

PubMed

Giuliano, François; Clément, Pierre

2005-09-01

Ejaculation is constituted by two distinct phases, emission and expulsion. Orgasm, a feature perhaps unique in humans, is a cerebral process that occurs, in normal conditions, concomitantly to expulsion of semen. Normal antegrade ejaculation is a highly coordinated physiological process with emission and expulsion phases being under the control of autonomic and somatic nervous systems respectively. The central command of ejaculation is located at the thoracolumbar and lumbosacral levels of the spinal cord and is activated by stimuli from genital, mainly penile, origin although cerebral descending pathways exert both inhibitory and excitatory regulatory roles. Cerebral structures specifically activated during ejaculation form a tightly interconnected network comprising hypothalamic, diencephalic and pontine areas. A rational neurobiological approach has led to identify several neurotransmitters contributing to the ejaculatory process. Amongst them, serotonin (5-HT) has received strong experimental evidences indicating its inhibitory role in the central control of ejaculation. In particular, 5-HT1A cerebral autoreceptors but also spinal 5-HT1B and, in a lesser extent, 5-HT2C receptors have been shown to mediate the effects of 5-HT on ejaculation. Pharmacological strategies, especially those targeting serotonergic system, for the treatment of ejaculatory disorders in human will undoubtedly benefit from the application of basic and clinical research findings. In this perspective, the use of selective serotonin reuptake inhibitors (SSRIs) which basically increase the amount of central 5-HT and delay ejaculation in humans seems promising.

Modeling road-cycling performance.

PubMed

Olds, T S; Norton, K I; Lowe, E L; Olive, S; Reay, F; Ly, S

1995-04-01

This paper presents a complete set of equations for a "first principles" mathematical model of road-cycling performance, including corrections for the effect of winds, tire pressure and wheel radius, altitude, relative humidity, rotational kinetic energy, drafting, and changed drag. The relevant physiological, biophysical, and environmental variables were measured in 41 experienced cyclists completing a 26-km road time trial. The correlation between actual and predicted times was 0.89 (P < or = 0.0001), with a mean difference of 0.74 min (1.73% of mean performance time) and a mean absolute difference of 1.65 min (3.87%). Multiple simulations were performed where model inputs were randomly varied using a normal distribution about the measured values with a SD equivalent to the estimated day-to-day variability or technical error of measurement in each of the inputs. This analysis yielded 95% confidence limits for the predicted times. The model suggests that the main physiological factors contributing to road-cycling performance are maximal O2 consumption, fractional utilization of maximal O2 consumption, mechanical efficiency, and projected frontal area. The model is then applied to some practical problems in road cycling: the effect of drafting, the advantage of using smaller front wheels, the effects of added mass, the importance of rotational kinetic energy, the effect of changes in drag due to changes in bicycle configuration, the normalization of performances under different conditions, and the limits of human performance.

Classification of lymphoid neoplasms: the microscope as a tool for disease discovery

PubMed Central

Harris, Nancy Lee; Stein, Harald; Isaacson, Peter G.

2008-01-01

In the past 50 years, we have witnessed explosive growth in the understanding of normal and neoplastic lymphoid cells. B-cell, T-cell, and natural killer (NK)–cell neoplasms in many respects recapitulate normal stages of lymphoid cell differentiation and function, so that they can be to some extent classified according to the corresponding normal stage. Likewise, the molecular mechanisms involved the pathogenesis of lymphomas and lymphoid leukemias are often based on the physiology of the lymphoid cells, capitalizing on deregulated normal physiology by harnessing the promoters of genes essential for lymphocyte function. The clinical manifestations of lymphomas likewise reflect the normal function of lymphoid cells in vivo. The multiparameter approach to classification adopted by the World Health Organization (WHO) classification has been validated in international studies as being highly reproducible, and enhancing the interpretation of clinical and translational studies. In addition, accurate and precise classification of disease entities facilitates the discovery of the molecular basis of lymphoid neoplasms in the basic science laboratory. PMID:19029456

Pilot physiology, cognition and flight performance during flight simulation exposed to a 3810-m hypoxic condition.

PubMed

Peacock, Corey A; Weber, Raymond; Sanders, Gabriel J; Seo, Yongsuk; Kean, David; Pollock, Brandon S; Burns, Keith J; Cain, Mark; LaScola, Phillip; Glickman, Ellen L

2017-03-01

Hypoxia is a physiological state defined as a reduction in the distribution of oxygen to the tissues of the body. It has been considered a major factor in aviation safety worldwide because of its potential for pilot disorientation. Pilots are able to operate aircrafts up to 3810 m without the use of supplemental oxygen and may exhibit symptoms associated with hypoxia. To determine the effects of 3810 m on physiology, cognition and performance in pilots during a flight simulation. Ten healthy male pilots engaged in a counterbalanced experimental protocol comparing a 0-m normoxic condition (NORM) with a 3810-m hypoxic condition (HYP) on pilot physiology, cognition and flight performance. Repeated-measures analysis of variance demonstrated a significant (p ≤ 0.05) time by condition interaction for physiological and cognitive alterations during HYP. A paired-samples t test demonstrated no differences in pilot performance (p ≥ 0.05) between conditions. Pilots exhibited physiological and cognitive impairments; however, pilot performance was not affected by HYP.

Catheter based mid-infrared reflectance and reflectance generated absorption spectroscopy

DOEpatents

Holman, Hoi-Ying N

2013-10-29

A method of characterizing conditions in a tissue, by (a) providing a catheter that has a light source that emits light in selected wavenumbers within the range of mid-IR spectrum; (b) directing the light from the catheter to an area of tissue at a location inside a blood vessel of a subject; (c) collecting light reflected from the location and generating a reflectance spectra; and (d) comparing the reflectance spectra to a reference spectra of normal tissue, whereby a location having an increased number of absorbance peaks at said selected wavenumbers indicates a tissue inside the blood vessel containing a physiological marker for atherosclerosis.

Effect of production microclimate on female thermal state with increased temperature and air humidity

NASA Technical Reports Server (NTRS)

Machablishvili, O. G.

1980-01-01

The thermal state of women during the effect of high air temperature and relative humidity with a varying degree of physical loads was studied. Parameters for air temperature, relative humidity, and air movement were established. It was established that in women the thermo-regulatory stress occurs at lower air temperatures and with lower physical loads than in men. The accumulation of heat in women was revealed with lower air temperature than in men. It is concluded that to preserve the normal physiological state of the female organism it is necessary to create more favorable microclimate conditions and decrease the physical loads.

Electrocardiographic consequences of a peripatetic lifestyle in gray wolves (Canis lupus)

USGS Publications Warehouse

Constable, Peter; Hinchcliff, Ken; Demma, Nick; Callahan, Margaret; Dale, Bruce W.; Fox, Kevin; Adams, Layne G.; Wack, Ray; Kramer, Lynn

1998-01-01

Cardiac chamber enlargement and hypertrophy are normal physiologic responses to repetitive endurance exercise activity in human beings and domestic dogs. Whether similar changes occur in wild animals as a consequence of increased activity is unknown. We found that free-ranging gray wolves (Canis lupus, n=11), the archetypical endurance athlete, have electrocardiographic evidence of cardiac chamber enlargement and hypertrophy relative to sedentary captive gray wolves (n=20), as demonstrated by significant increases in QRS duration, QT interval, and QT interval corrected for heart rate, a tendency towards increased Q, R, and S wave voltages in all leads, and a significant decrease in heart rate. We conclude that exercise activity level and therefore lifestyle affects physiologic variables in wild animals. An immediate consequence of this finding is that physiologic measurements obtained from a captive wild-animal population with reduced exercise activity level may not accurately reflect the normal physiologic state for free-ranging members of the same species.

Individual Colorimetric Observer Model

PubMed Central

Asano, Yuta; Fairchild, Mark D.; Blondé, Laurent

2016-01-01

This study proposes a vision model for individual colorimetric observers. The proposed model can be beneficial in many color-critical applications such as color grading and soft proofing to assess ranges of color matches instead of a single average match. We extended the CIE 2006 physiological observer by adding eight additional physiological parameters to model individual color-normal observers. These eight parameters control lens pigment density, macular pigment density, optical densities of L-, M-, and S-cone photopigments, and λmax shifts of L-, M-, and S-cone photopigments. By identifying the variability of each physiological parameter, the model can simulate color matching functions among color-normal populations using Monte Carlo simulation. The variabilities of the eight parameters were identified through two steps. In the first step, extensive reviews of past studies were performed for each of the eight physiological parameters. In the second step, the obtained variabilities were scaled to fit a color matching dataset. The model was validated using three different datasets: traditional color matching, applied color matching, and Rayleigh matches. PMID:26862905

A study on in vitro culture of Trichuris ovis in different physiological solutions at constant temperature, 37°C.

PubMed

Singh, Tikam; Lal, S S

2011-06-01

The primary aim of in vitro culture of whipworms (Trichuris ovis) is to provide artificial conditions under which the life cycle of the parasites completed outside the host under controlled conditions. The physiological solutions used for the present study were sodium chloride (0.64%), Ringer's solution, Tyrode's solution, and Lock-Lewis solution. Parasites were collected from freshly slaughtered intestine of the host. The recovered parasites were washed with running tap water after that with normal saline. After washing parasites were put in four petridishes containing different physiological solutions. Observations were recorded after interval of every 8 h. The hundred percent survival of Trichuris ovis was observed at 32, 40, and 48 h in NaCl (0.64%), Ringer's, Tyrode's, and Lock-Lewis solution, respectively in case of both male and female parasites. In sodium chloride solution (0.64%) cent percent mortality was observed after 64 h of incubation in males and in case of females it was observed 72 h. In Ringer's solution cent percent mortality was observed after 72 in males and in females it was observed 80 h. In Tyrode's solution cent percent mortality was observed after 88 h in males and 96 h in females. In Lock-Lewis solution cent percent mortality was observed after 96 h in case of both the male and female parasites. Present study could be used to understand the effects of various drugs on the above parasites and also other intra-intestinal parasites.

Effects of shoe cleat position on physiology and performance of competitive cyclists.

PubMed

Paton, Carl D

2009-12-01

Aerobic economy is an important factor that affects the performance of competitive cyclists. It has been suggested that placing the foot more anteriorly on the bicycle pedals may improve economy over the traditional foot position by improving pedaling efficiency. The current study examines the effects of changing the anterior-posterior pedal foot position on the physiology and performance of well-trained cyclists. In a crossover study, 10 competitive cyclists completed two maximal incremental and two submaximal tests in either their preferred (control) or a forward (arch) foot position. Maximum oxygen consumption and peak power output were determined from the incremental tests for both foot positions. On two further occasions, cyclists also completed a two-part 60-min submaximal test that required them to maintain a constant power output (equivalent to 60% of their incremental peak power) for 30 min, during which respiratory and blood lactate samples were taken at predetermined intervals. Thereafter, subjects completed a 30-min self-paced maximal effort time trial. Relative to the control, the mean changes (+/-90% confidence limits) in the arch condition were as follows: maximum oxygen consumption, -0.5% (+/-2.0%); incremental peak power output, -0.8% (+/-1.3%); steady-state oxygen consumption at 60%, -2.4% (+/-1.1%); steady-state heart rate 60%, 0.4% (+/-1.7%); lactate concentration 60%, 8.7% (+/-14.4%); and mean time trial power, -1.5% (+/-2.9%). We conclude that there was no substantial physiological or performance advantage in this group using an arch-cleat shoe position in comparison with a cyclist's normal preferred condition.

Creating Simulated Microgravity Patient Models

NASA Technical Reports Server (NTRS)

Hurst, Victor; Doerr, Harold K.; Bacal, Kira

2004-01-01

The Medical Operational Support Team (MOST) has been tasked by the Space and Life Sciences Directorate (SLSD) at the NASA Johnson Space Center (JSC) to integrate medical simulation into 1) medical training for ground and flight crews and into 2) evaluations of medical procedures and equipment for the International Space Station (ISS). To do this, the MOST requires patient models that represent the physiological changes observed during spaceflight. Despite the presence of physiological data collected during spaceflight, there is no defined set of parameters that illustrate or mimic a 'space normal' patient. Methods: The MOST culled space-relevant medical literature and data from clinical studies performed in microgravity environments. The areas of focus for data collection were in the fields of cardiovascular, respiratory and renal physiology. Results: The MOST developed evidence-based patient models that mimic the physiology believed to be induced by human exposure to a microgravity environment. These models have been integrated into space-relevant scenarios using a human patient simulator and ISS medical resources. Discussion: Despite the lack of a set of physiological parameters representing 'space normal,' the MOST developed space-relevant patient models that mimic microgravity-induced changes in terrestrial physiology. These models are used in clinical scenarios that will medically train flight surgeons, biomedical flight controllers (biomedical engineers; BME) and, eventually, astronaut-crew medical officers (CMO).

Interactions of the hormones leptin, ghrelin, adiponectin, resistin, and PYY3-36 with the reproductive system.

PubMed

Budak, Erdal; Fernández Sánchez, Manuel; Bellver, José; Cerveró, Ana; Simón, Carlos; Pellicer, Antonio

2006-06-01

To summarize the effects of novel hormones (leptin, ghrelin, adiponectin, resistin, and PYY3-36) secreted from adipose tissue and the gastrointestinal tract that have been discovered to exert different effects on several reproductive functions, such as the hypothalamic-pituitary-gonadal axis, embryo development, implantation physiology, and clinically relevant conditions. A MEDLINE computer search was performed to identify relevant articles. Leptin and ghrelin exert important roles on body weight regulation, eating behavior, and reproduction, acting on the central nervous system and target reproductive organs. As a marker of adequate nutritional stores, these hormones may act on the central nervous system to initiate the complex process of puberty and maintain normal reproductive function. In addition, leptin and ghrelin and their receptors are involved in reproductive events such as gonadal function, embryo development, and embryo-endometrial interaction. Leptin and ghrelin and other adipose tissue-secreted hormones have significant effects on reproduction. Acting through the brain, these hormones may serve as links between adipose tissue and the reproductive system to supply and regulate energy needs for normal reproduction and pregnancy. Future studies are needed to further clarify the role of these hormones in reproductive events and other related gynecological conditions.

An update on oxidative stress-mediated organ pathophysiology.

PubMed

Rashid, Kahkashan; Sinha, Krishnendu; Sil, Parames C

2013-12-01

Exposure to environmental pollutants and drugs can result in pathophysiological situations in the body. Research in this area is essential as the knowledge on cellular survival and death would help in designing effective therapeutic strategies that are needed for the maintenance of the normal physiological functions of the body. In this regard, naturally occurring bio-molecules can be considered as potential therapeutic targets as they are normally available in commonly consumed foodstuffs and are thought to have minimum side effects. This review article describes the detailed mechanisms of oxidative stress-mediated organ pathophysiology and the ultimate fate of the cells either to survive or to undergo necrotic or apoptotic death. The mechanisms underlying the beneficial role of a number of naturally occurring bioactive molecules in oxidative stress-mediated organ pathophysiology have also been included in the review. The review provides useful information about the recent progress in understanding the mechanism(s) of various types of organ pathophysiology, the complex cross-talk between these pathways, as well as their modulation in stressed conditions. Additionally, it suggests possible therapeutic applications of a number of naturally occurring bioactive molecules in conditions involving oxidative stress. Copyright © 2013 Elsevier Ltd. All rights reserved.

Cellular and molecular mechanisms in the hypoxic tissue: role of HIF-1 and ROS.

PubMed

Zepeda, Andrea B; Pessoa, Adalberto; Castillo, Rodrigo L; Figueroa, Carolina A; Pulgar, Victor M; Farías, Jorge G

2013-08-01

Reactive oxygen species such as superoxide anion radicals (O2 (-) ) and hydrogen peroxide (H2 O2 ) have for long time been recognized as undesirable by-products of the oxidative mitochondrial generation of adenosine triphosphate (ATP). Recently, these highly reactive species have been associated to important signaling pathways in diverse physiological conditions such as those activated in hypoxic microenvironments. The molecular response to hypoxia requires fast-acting mechanisms acting within a wide range of partial pressures of oxygen (O2 ). Intracellular O2 sensing is an evolutionary preserved feature, and the best characterized molecular responses to hypoxia are mediated through transcriptional activation. The transcription factor, hypoxia-inducible factor 1 (HIF-1), is a critical mediator of these adaptive responses, and its activation by hypoxia involves O2 -dependent posttranslational modifications and nuclear translocation. Through the induction of the expression of its target genes, HIF-1 coordinately regulates tissue O2 supply and energetic metabolism. Other transcription factors such as nuclear factor κB are also redox sensitive and are activated in pro-oxidant and hypoxic conditions. The purpose of this review is to summarize new developments in HIF-mediated O2 sensing mechanisms and their interactions with reactive oxygen species-generating pathways in normal and abnormal physiology. Copyright © 2013 John Wiley & Sons, Ltd.

Effect of Topical Iloprost and Nitroglycerin on Gastric Microcirculation and Barrier Function during Hemorrhagic Shock in Dogs.

PubMed

Truse, Richard; Hinterberg, Jonas; Schulz, Jan; Herminghaus, Anna; Weber, Andreas; Mettler-Altmann, Tabea; Bauer, Inge; Picker, Olaf; Vollmer, Christian

2017-01-01

Topical drug application is used to avoid systemic side effects. The aim of this study was to analyze whether locally applied iloprost or nitroglycerin influence gastric mucosal perfusion, oxygenation, and barrier function during physiological and hemorrhagic conditions. In repeated experiments, 5 anesthetized dogs received iloprost, nitroglycerin, or normal saline during physiological and hemorrhagic (-20% blood volume) conditions. Macro- and microcirculatory variables were recorded continuously. Gastric barrier function was assessed via translocation of sucrose into the blood. During hemorrhage, gastric mucosal oxygenation decreased from 77 ± 4 to 37 ± 7%. This effect was attenuated by nitroglycerin (78 ± 6 to 47 ± 13%) and iloprost (82 ± 4 to 54 ± 9%). Sucrose plasma levels increased during hemorrhage from 7 ± 4 to 55 ± 15 relative amounts. This was alleviated by nitroglycerin (5 ± 8 to 29 ± 38 relative amounts). These effects were independent of systemic hemodynamic variables. During hemorrhage, topical nitroglycerin and iloprost improve regional gastric oxygenation without affecting perfusion. Nitroglycerin attenuated the shock-induced impairment of the mucosal barrier integrity. Thus, local drug application improves gastric microcirculation without compromising systemic hemodynamic variables, and it may also protect mucosal barrier function. © 2017 S. Karger AG, Basel.

The Neuroglial Dialog Between Cannabinoids and Hemichannels

PubMed Central

Labra, Valeria C.; Santibáñez, Cristian A.; Gajardo-Gómez, Rosario; Díaz, Esteban F.; Gómez, Gonzalo I.; Orellana, Juan A.

2018-01-01

The formation of gap junctions was initially thought to be the central role of connexins, however, recent evidence had brought to light the high relevance of unopposed hemichannels as an independent mechanism for the selective release of biomolecules during physiological and pathological conditions. In the healthy brain, the physiological opening of astrocyte hemichannels modulates basal excitatory synaptic transmission. At the other end, the release of potentially neurotoxic compounds through astroglial hemichannels and pannexons has been insinuated as one of the functional alterations that negatively affect the progression of multiple brain diseases. Recent insights in this matter have suggested encannabinoids (eCBs) as molecules that could regulate the opening of these channels during diverse conditions. In this review, we discuss and hypothesize the possible interplay between the eCB system and the hemichannel/pannexon-mediated signaling in the inflamed brain and during event of synaptic plasticity. Most findings indicate that eCBs seem to counteract the activation of major neuroinflammatory pathways that lead to glia-mediated production of TNF-α and IL-1β, both well-known triggers of astroglial hemichannel opening. In contrast to the latter, in the normal brain, eCBs apparently elicit the Ca2+-activation of astrocyte hemichannels, which could have significant consequences on eCB-dependent synaptic plasticity. PMID:29662436

Effects of egg incubation condition on the post-hatching growth and performance of the snapping turtle, Chelydra serpentina

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

Ryan, Kathleen M.

1990-12-01

The effect of incubation temperature on the post-hatching growth and performance capacities of the common snapping turtle, Chelydra serpentina was investigated in the laboratory. Turtle eggs were collected from four sites in New York State and randomly assigned to four incubation temperature treatments to produce males (constant 26°C and downshifted 30-26-30°C) and females (constant 30°C and upshifted 26-30-26°C) under constant and altered temperature regimes. The incubation conditions resulted in 92% males from the constant 26°C group and 93% males from the downshifted group. 100% females resulted from both the constant 30°C group and the upshifted group. Turtles hatching from eggsmore » incubated constantly at 26°C were significantly larger than hatchlings from eggs incubated at a constant 30°C or downshifted. Hatchlings were raised in individual aquaria at 25°C and fed earthworms and fish. After a 9-month growth period, turtles which had been incubated at a constant 30°C gained significantly more mass than did turtles from eggs which had been downshifted or upshifted. There was no extended effect of incubation condition on Post-hatching performance and learning ability as measured by righting and feeding responses. Thus, the mass gain differences seen in this study suggest that physiological differences do result as the consequence of incubation condition. However, these physiological differences are not reflected in normal locomotive or feeding behavior.« less

Effects of egg incubation condition on the post-hatching growth and performance of the snapping turtle, Chelydra serpentina

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

Ryan, K.M.

1990-12-01

The effect of incubation temperature on the post-hatching growth and performance capacities of the common snapping turtle, Chelydra serpentina was investigated in the laboratory. Turtle eggs were collected from four sites in New York State and randomly assigned to four incubation temperature treatments to produce males (constant 26[degree]C and downshifted 30-26-30[degree]C) and females (constant 30[degree]C and upshifted 26-30-26[degree]C) under constant and altered temperature regimes. The incubation conditions resulted in 92% males from the constant 26[degree]C group and 93% males from the downshifted group. 100% females resulted from both the constant 30[degree]C group and the upshifted group. Turtles hatching from eggsmore » incubated constantly at 26[degree]C were significantly larger than hatchlings from eggs incubated at a constant 30[degree]C or downshifted. Hatchlings were raised in individual aquaria at 25[degree]C and fed earthworms and fish. After a 9-month growth period, turtles which had been incubated at a constant 30[degree]C gained significantly more mass than did turtles from eggs which had been downshifted or upshifted. There was no extended effect of incubation condition on Post-hatching performance and learning ability as measured by righting and feeding responses. Thus, the mass gain differences seen in this study suggest that physiological differences do result as the consequence of incubation condition. However, these physiological differences are not reflected in normal locomotive or feeding behavior.« less

Quantitative analysis of iris changes after physiologic and pharmacologic mydriasis in a rural Chinese population.

PubMed

Zhang, Ye; Li, Si Zhen; Li, Lei; He, Ming Guang; Thomas, Ravi; Wang, Ning Li

2014-04-24

To estimate and compare the change in iris cross-sectional area (IA) and iris volume (IV) following physiologic and pharmacologic pupil dilation in primary angle closure suspects (PACS) and normal subjects. Anterior segment-optical coherence tomography (AS-OCT) measurements in light, dark, and following pharmacologic dilation were obtained on 186 PACS and 224 normal subjects examined during the 5-year follow-up of the Handan Eye Study. Iris cross-sectional area, IV, and other biometric parameters calculated using the Zhongshan angle assessment program in the right eyes of all subjects were analyzed. The mean IA and IV decreased in dark compared with light and after pharmacologic dilation in both PACS and normal eyes. This change was statistically significant in normal eyes: light versus pharmacologic dilation for IA (P = 0.038) and for IV, both light versus dark (P = 0.031) and light versus pharmacologic dilation (P = 0.012). A longer axial length (P = 0.028) and a greater change in pupil diameter (PD) (P < 0.001) were associated with a larger decrease of IA for the light to dark comparison. A diagnosis of normal eyes (P = 0.011), larger PD in dark (P = 0.001), and a larger change in PD (P = 0.001) were associated with a larger decrease of IV from light to dark. The differences in iris behavior between PACS and normal rural Chinese subjects following physiologic or pharmacologic pupillary dilation may help provide insights into the pathogenesis of angle closure. Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.

Quantitative analysis of the Ca2+‐dependent regulation of delayed rectifier K+ current I Ks in rabbit ventricular myocytes

PubMed Central

Bartos, Daniel C.; Morotti, Stefano; Ginsburg, Kenneth S.; Grandi, Eleonora

2017-01-01

Key points [Ca2+]i enhanced rabbit ventricular slowly activating delayed rectifier K+ current (I Ks) by negatively shifting the voltage dependence of activation and slowing deactivation, similar to perfusion of isoproterenol.Rabbit ventricular rapidly activating delayed rectifier K+ current (I Kr) amplitude and voltage dependence were unaffected by high [Ca2+]i.When measuring or simulating I Ks during an action potential, I Ks was not different during a physiological Ca2+ transient or when [Ca2+]i was buffered to 500 nm. Abstract The slowly activating delayed rectifier K+ current (I Ks) contributes to repolarization of the cardiac action potential (AP). Intracellular Ca2+ ([Ca2+]i) and β‐adrenergic receptor (β‐AR) stimulation modulate I Ks amplitude and kinetics, but details of these important I Ks regulators and their interaction are limited. We assessed the [Ca2+]i dependence of I Ks in steady‐state conditions and with dynamically changing membrane potential and [Ca2+]i during an AP. I Ks was recorded from freshly isolated rabbit ventricular myocytes using whole‐cell patch clamp. With intracellular pipette solutions that controlled free [Ca2+]i, we found that raising [Ca2+]i from 100 to 600 nm produced similar increases in I Ks as did β‐AR activation, and the effects appeared additive. Both β‐AR activation and high [Ca2+]i increased maximally activated tail I Ks, negatively shifted the voltage dependence of activation, and slowed deactivation kinetics. These data informed changes in our well‐established mathematical model of the rabbit myocyte. In both AP‐clamp experiments and simulations, I Ks recorded during a normal physiological Ca2+ transient was similar to I Ks measured with [Ca2+]i clamped at 500–600 nm. Thus, our study provides novel quantitative data as to how physiological [Ca2+]i regulates I Ks amplitude and kinetics during the normal rabbit AP. Our results suggest that micromolar [Ca2+]i, in the submembrane or junctional cleft space, is not required to maximize [Ca2+]i‐dependent I Ks activation during normal Ca2+ transients. PMID:28008618

Effects of wearing aircrew protective clothing on physiological and cognitive responses under various ambient conditions.

PubMed

Faerevik, Hilde; Reinertsen, Randi Eidsmo

2003-06-20

Heat stress can be a significant problem for pilots wearing protective clothing during flights, because they provide extra insulation which prevents evaporative heat loss. Heat stress can influence human cognitive activity, which might be critical in the flying situation, requiring efficient and error-free performance. This study investigated the effect of wearing protective clothing under various ambient conditions on physiological and cognitive performance. On several occasions, eight subjects were exposed for 3 h to three different environmental conditions; 0 degrees C at 80% RH, 23 degrees C at 63% RH and 40 degrees C at 19% RH. The subjects were equipped with thermistors, dressed as they normally do for flights (including helmet, two layers of underwear and an uninsulated survival suit). During three separate exposures the subjects carried out two cognitive performance tests (Vigilance test and DG test). Performance was scored as correct, incorrect, missed reaction and reaction time. Skin temperature, deep body temperature, heart rate, oxygen consumption, temperature and humidity inside the clothing, sweat loss, subjective sensation of temperature and thermal comfort were measured. Rises in rectal temperature, skin temperature, heart rate and body water loss indicated a high level of heat stress in the 40 degrees C ambient temperature condition in comparison with 0 degrees C and 23 degrees C. Performance of the DG test was unaffected by ambient temperature. However, the number of incorrect reactions in the Vigilance test was significantly higher at 40 degrees C than at 23 degrees C (p = 0.006) or 0 degrees C (p = 0.03). The effect on Vigilance performance correlated with changes in deep-body temperature, and this is in accordance with earlier studies that have demonstrated that cognitive performance is virtually unaffected unless environmental conditions are sufficient to change deep body temperature.

It was a first class start which laid the basis for a promising future: Experience from comparative studies on gravity related behavior in animals and consequences for future experiments

NASA Astrophysics Data System (ADS)

Horn, Eberhard R.

2000-01-01

The main title was chosen in imitation of the headline of a lecture given by H. S. Wolff at the ESA-Symposium ``Life Odyssey'' in Maastricht/NL (1999) to contrast his pessimistic view of the science output from biological microgravity studies during the past 25 years with an optimistic view of the author who had the opportunity for studies on the gravity sensory systems of developing vertebrates and insects during the space missions STS-55, STS-84, and STS-90, and who was stimulated by this experience to undertake any effort to extend these studies on the International Space Station ISS. We studied compensatory eye and head movements induced by a lateral roll of the animals, and we found that exposure to both microgravity and hypergravity affect their development. Future studies have to consider long-term exposures to altered gravitational conditions to find answers to two questions, the mechanisms of adaptation during exposure, and the degree of residual effects after becoming an adult animal and also after re-entry to IG-conditions. The main hypothesis on the development of animals in space is that a fertilized egg will be converted to a normal adult animal guided by physiological and morphological set-points which represent the genetic program. In case of developmental retardations or accelerations or otherwise occurring deviations from normal structural and physiological development during specific periods of the embryonic and postembryonic life, these genetically defined supervisors activate readaptive mechanisms which direct the developmental processes towards normality, i.e., stability. Thus, an orbit-stabilized organism will be dramatically disturbed after return to Earth. Because this failure will need support to reach neuronal stability, research has also to consider the analysis of mechanisms which are able to overcome these disturbances. This research will open the door to applications because it forms a bridge to human medicine with its analytical research on control procedures over neuropathological mechanisms. .

Serial biomechanical comparison of edematous, normal, and collagen crosslinked human donor corneas using optical coherence elastography

PubMed Central

Ford, Matthew R.; Roy, Abhijit Sinha; Rollins, Andrew M.; Dupps, William J.

2014-01-01

PURPOSE To noninvasively evaluate the effects of corneal hydration and collagen crosslinking (CXL) on the mechanical behavior of the cornea. SETTING Cleveland Clinic Cole Eye Institute, Cleveland, Ohio, USA. DESIGN Experimental study. METHODS An optical coherence elastography (OCE) technique was used to measure the displacement behavior of 5 pairs of debrided human donor globes in 3 serial states as follows: edematous, normal thickness, and after riboflavin–ultraviolet-A–mediated CXL. During micromotor-controlled axial displacements with a curved goniolens at physiologic intraocular pressure (IOP), serial optical coherence tomography scans were obtained to allow high-resolution intrastromal speckle tracking and displacement measurements over the central 4.0 mm of the cornea. RESULTS With no imposed increase in IOP, the mean lateral to imposed axial displacement ratios were 0.035 μm/μm ± 0.037 (SD) in edematous corneas, 0.021 ± 0.02 μm/μm in normal thickness corneas, and 0.014 ± 0.009 μm/μm in post-CXL corneas. The differences were statistically significant (P<.05, analysis of variance) and indicated a 40% increase in lateral stromal resistance with deturgescence and a further 33% mean increase in relative stiffness with CXL. CONCLUSIONS Serial perturbations of the corneal hydration state and CXL had significant effects on corneal biomechanical behavior. With an axially applied stress from a nonapplanating contact lens, displacements along the direction of the collagen lamellae were 2 orders of magnitude lower than axial deformations. These experiments show the ability of OCE to quantify clinically relevant mechanical property differences under physiologic conditions. Financial Disclosures Proprietary or commercial disclosures are listed after the references. PMID:24767794

Auditory processing assessment suggests that Wistar audiogenic rat neural networks are prone to entrainment.

PubMed

Pinto, Hyorrana Priscila Pereira; Carvalho, Vinícius Rezende; Medeiros, Daniel de Castro; Almeida, Ana Flávia Santos; Mendes, Eduardo Mazoni Andrade Marçal; Moraes, Márcio Flávio Dutra

2017-04-07

Epilepsy is a neurological disease related to the occurrence of pathological oscillatory activity, but the basic physiological mechanisms of seizure remain to be understood. Our working hypothesis is that specific sensory processing circuits may present abnormally enhanced predisposition for coordinated firing in the dysfunctional brain. Such facilitated entrainment could share a similar mechanistic process as those expediting the propagation of epileptiform activity throughout the brain. To test this hypothesis, we employed the Wistar audiogenic rat (WAR) reflex animal model, which is characterized by having seizures triggered reliably by sound. Sound stimulation was modulated in amplitude to produce an auditory steady-state-evoked response (ASSR; -53.71Hz) that covers bottom-up and top-down processing in a time scale compatible with the dynamics of the epileptic condition. Data from inferior colliculus (IC) c-Fos immunohistochemistry and electrographic recordings were gathered for both the control Wistar group and WARs. Under 85-dB SLP auditory stimulation, compared to controls, the WARs presented higher number of Fos-positive cells (at IC and auditory temporal lobe) and a significant increase in ASSR-normalized energy. Similarly, the 110-dB SLP sound stimulation also statistically increased ASSR-normalized energy during ictal and post-ictal periods. However, at the transition from the physiological to pathological state (pre-ictal period), the WAR ASSR analysis demonstrated a decline in normalized energy and a significant increase in circular variance values compared to that of controls. These results indicate an enhanced coordinated firing state for WARs, except immediately before seizure onset (suggesting pre-ictal neuronal desynchronization with external sensory drive). These results suggest a competing myriad of interferences among different networks that after seizure onset converge to a massive oscillatory circuit. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

A unified theory of bone healing and nonunion: BHN theory.

PubMed

Elliott, D S; Newman, K J H; Forward, D P; Hahn, D M; Ollivere, B; Kojima, K; Handley, R; Rossiter, N D; Wixted, J J; Smith, R M; Moran, C G

2016-07-01

This article presents a unified clinical theory that links established facts about the physiology of bone and homeostasis, with those involved in the healing of fractures and the development of nonunion. The key to this theory is the concept that the tissue that forms in and around a fracture should be considered a specific functional entity. This 'bone-healing unit' produces a physiological response to its biological and mechanical environment, which leads to the normal healing of bone. This tissue responds to mechanical forces and functions according to Wolff's law, Perren's strain theory and Frost's concept of the "mechanostat". In response to the local mechanical environment, the bone-healing unit normally changes with time, producing different tissues that can tolerate various levels of strain. The normal result is the formation of bone that bridges the fracture - healing by callus. Nonunion occurs when the bone-healing unit fails either due to mechanical or biological problems or a combination of both. In clinical practice, the majority of nonunions are due to mechanical problems with instability, resulting in too much strain at the fracture site. In most nonunions, there is an intact bone-healing unit. We suggest that this maintains its biological potential to heal, but fails to function due to the mechanical conditions. The theory predicts the healing pattern of multifragmentary fractures and the observed morphological characteristics of different nonunions. It suggests that the majority of nonunions will heal if the correct mechanical environment is produced by surgery, without the need for biological adjuncts such as autologous bone graft. Cite this article: Bone Joint J 2016;98-B:884-91. ©2016 The British Editorial Society of Bone & Joint Surgery.

Investigation of pajama properties on skin under mild cold conditions: the interaction between skin and clothing.

PubMed

Yao, Lei; Gohel, Mayur D I; Li, Yi; Chung, Waiyee J

2011-07-01

Clothing is considered the second skin of the human body. The aim of this study was to determine clothing-wearer interaction on skin physiology under mild cold conditions. Skin physiological parameters, subjective sensory response, stress level, and physical properties of clothing fabric from two longitude parallel-designed wear trials were studied. The wear trials involved four kinds of pajamas made from cotton or polyester material that had hydrophilic or hydrophobic treatment, conducted for three weeks under mild cold conditions. Statistical tools, factor analysis, hierarchical linear regression, and logistic regression were applied to analyze the strong predictors of skin physiological parameters, stress level, and sensory response. A framework was established to illustrate clothing-wearer interactions with clothing fabric properties, skin physiology, stress level, and sensory response under mild cold conditions. Fabric has various effects on the human body under mild cold conditions. A fabric's properties influence skin physiology, sensation, and psychological response. © 2011 The International Society of Dermatology.

Cardiovascular reactivity to acute psychological stress following sleep deprivation.

PubMed

Franzen, Peter L; Gianaros, Peter J; Marsland, Anna L; Hall, Martica H; Siegle, Greg J; Dahl, Ronald E; Buysse, Daniel J

2011-10-01

Psychological stress and sleep disturbances are highly prevalent and are both implicated in the etiology of cardiovascular diseases. Given the common co-occurrence of psychological distress and sleep disturbances including short sleep duration, this study examined the combined effects of these two factors on blood pressure reactivity to immediate mental challenge tasks after well-rested and sleep-deprived experimental conditions. Participants (n = 20) were healthy young adults free from current or past sleep, psychiatric, or major medical disorders. Using a within-subjects crossover design, we examined acute stress reactivity under two experimental conditions: after a night of normal sleep in the laboratory and after a night of total sleep deprivation. Two standardized psychological stress tasks were administered, a Stroop color-word naming interference task and a speech task, which were preceded by a prestress baseline period and followed by a poststress recovery period. Each period was 10 minutes in duration, and blood pressure recordings were collected every 2.5 minutes throughout each period. Mean blood pressure responses during stress and recovery periods were examined with a mixed-effects analysis of covariance, controlling for baseline blood pressure. There was a significant interaction between sleep deprivation and stress on systolic blood pressure (F(2,82.7) = 4.05, p = .02). Systolic blood pressure was higher in the sleep deprivation condition compared with the normal sleep condition during the speech task and during the two baseline periods. Sleep deprivation amplified systolic blood pressure increases to psychological stress. Sleep loss may increase cardiovascular risk by dysregulating stress physiology.

Normal distribution pattern and physiological variants of 68Ga-PSMA-11 PET/CT imaging.

PubMed

Demirci, Emre; Sahin, Onur Erdem; Ocak, Meltem; Akovali, Burak; Nematyazar, Jamal; Kabasakal, Levent

2016-11-01

Ga-PSMA-11 is a novel PET tracer suggested to be used for imaging of advanced prostate cancer. In this study, we aimed to present a detailed biodistribution of Ga-PSMA-11, including physiological and benign variants of prostate-specific membrane antigen (PSMA) imaging. We carried out a retrospective analysis of 40 patients who underwent PSMA PET/computed tomography (CT) imaging and who had no evidence of residual or metastatic disease on the scans. In addition, 16 patients who underwent PSMA PET/CT imaging with any indication other than prostate cancer were included in the study to evaluate physiological uptake in the normal prostate gland. The median, minimum-maximum, and mean standardized uptake value (SUV) values were calculated for visceral organs, bone marrow and lymph nodes, and mucosal areas. Any physiological variants or benign lesions with Ga-PSMA-11 were also noted. Ga-PSMA-11 uptake was noted in the kidneys, parotid and submandibular glands, duodenum, small intestines, spleen, liver, and lacrimal glands, and mucosal uptake in the nasopharynx, vocal cords, pancreas, stomach, mediastinal blood pool, thyroid gland, adrenal gland, rectum, vertebral bone marrow, and testes. Celiac ganglia showed slight Ga-PSMA-11 uptake in 24 of 40 patients without the presence of any other pathologic lymph nodes in abdominal and pelvic areas. Variable uptake of Ga-PSMA-11 was observed in calcified choroid plexus, a thyroid nodule, an adrenal nodule, axillary lymph nodes and celiac ganglia, occasional osteophytes, and gallbladder. The patient group with PSMA PET/CT for indications other than prostate cancer (n=16) showed a slight radiotracer uptake in normal prostate gland (SUVmax: 5.5±1.6, range: 3.5-8.3). This study shows normal distribution pattern, range of SUVs, and physiological variants of Ga-PSMA-11. In addition, several potential pitfalls were documented to prevent misinterpretations of the scan.

Physiological impact of patent foramen ovale on pulmonary gas exchange, ventilatory acclimatization, and thermoregulation.

PubMed

Lovering, Andrew T; Elliott, Jonathan E; Davis, James T

2016-08-01

The foramen ovale, which is part of the normal fetal cardiopulmonary circulation, fails to close after birth in ∼35% of the population and represents a potential source of right-to-left shunt. Despite the prevalence of patent foramen ovale (PFO) in the general population, cardiopulmonary, exercise, thermoregulatory, and altitude physiologists may have underestimated the potential effect of this shunted blood flow on normal physiological processes in otherwise healthy humans. Because this shunted blood bypasses the respiratory system, it would not participate in either gas exchange or respiratory system cooling and may have impacts on other physiological processes that remain undetermined. The consequences of this shunted blood flow in PFO-positive (PFO+) subjects can potentially have a significant, and negative, impact on the alveolar-to-arterial oxygen difference (AaDO2), ventilatory acclimatization to high altitude and respiratory system cooling with PFO+ subjects having a wider AaDO2 at rest, during exercise after acclimatization, blunted ventilatory acclimatization, and a higher core body temperature (∼0.4(°)C) at rest and during exercise. There is also an association of PFO with high-altitude pulmonary edema and acute mountain sickness. These effects on physiological processes are likely dependent on both the presence and size of the PFO, with small PFOs not likely to have significant/measureable effects. The PFO can be an important determinant of normal physiological processes and should be considered a potential confounder to the interpretation of former and future data, particularly in small data sets where a significant number of PFO+ subjects could be present and significantly impact the measured outcomes.

A Physiologically Based Kinetic Model of Rat and Mouse Gestation: Disposition of a Weak Acid

EPA Science Inventory

A physiologically based toxicokinetic model of gestation in the rat mouse has been developed. The model is superimposed on the normal growth curve for nonpregnant females. It describes the entire gestation period including organogenesis. The model consists of uterus, mammary tiss...

Predictable root recession coverage.

PubMed

Hoexter, David L

2006-01-01

Gingival recession, exposure of the tooth's root, is undesirable and, in many situations, contrary to normal physiology. Today's root coverage is predictable. With the use of an acellular dermal matrix membrane (Fasciablast), we can achieve a new blood supply and predictable coverage, with no second surgical procedure. Youth, esthetics and physiology are restored.

A mouse model of high trait anxiety shows reduced heart rate variability that can be reversed by anxiolytic drug treatment.

PubMed

Gaburro, Stefano; Stiedl, Oliver; Giusti, Pietro; Sartori, Simone B; Landgraf, Rainer; Singewald, Nicolas

2011-11-01

Increasing evidence suggests that specific physiological measures may serve as biomarkers for successful treatment to alleviate symptoms of pathological anxiety. Studies of autonomic function investigating parameters such as heart rate (HR), HR variability and blood pressure (BP) indicated that HR variability is consistently reduced in anxious patients, whereas HR and BP data show inconsistent results. Therefore, HR and HR variability were measured under various emotionally challenging conditions in a mouse model of high innate anxiety (high anxiety behaviour; HAB) vs. control normal anxiety-like behaviour (NAB) mice. Baseline HR, HR variability and activity did not differ between mouse lines. However, after cued Pavlovian fear conditioning, both elevated tachycardia and increased fear responses were observed in HAB mice compared to NAB mice upon re-exposure to the conditioning stimulus serving as the emotional stressor. When retention of conditioned fear was tested in the home cage, HAB mice again displayed higher fear responses than NAB mice, while the HR responses were similar. Conversely, in both experimental settings HAB mice consistently exhibited reduced HR variability. Repeated administration of the anxiolytic NK1 receptor antagonist L-822429 lowered the conditioned fear response and shifted HR dynamics in HAB mice to a more regular pattern, similar to that in NAB mice. Additional receiver-operating characteristic (ROC) analysis demonstrated the high specificity and sensitivity of HR variability to distinguish between normal and high anxiety trait. These findings indicate that assessment of autonomic response in addition to freezing might be a useful indicator of the efficacy of novel anxiolytic treatments.

Practical otic anatomy and physiology of the dog and cat.

PubMed

Njaa, Bradley L; Cole, Lynette K; Tabacca, Natalie

2012-11-01

Knowledge of the normal structure and function of the canine and feline ear is critical to be able to diagnose abnormalities that either involve the ear or originate within one or more of the ear compartments. In addition, a veterinarian must be aware of various structures within or associated with the ear so that they are not damaged or destroyed while treating an animal with otic disease. This article provides a brief discussion of the various anatomic features of the ear and normal physiology of portions of the ear. Copyright © 2012 Elsevier Inc. All rights reserved.

Analysis of space-time projection of differential and Michelson-type speckle-interferometer output signal for cardiovibration measurement

NASA Astrophysics Data System (ADS)

Ulyanov, Sergey S.; Tuchin, Valery V.

1993-06-01

The sex differences in cardiovascular system responses to a mild noise stress are established using the physiological and the dynamic systems theory methods. Lower levels of basal systolic arterial pressure and higher rates of its dropping and normalization under influence and after its cessation are typical for women. There are no hypertensive responses to stresses in women in contrast to men. The normalized entropy of the ECG signal, describing the physiological variability, increases in women and decreases in men. The advantages of female cardiovascular system response to mild stresses are discussed.

The energy expenditure of normal and pathologic gait.

PubMed

Waters, R L; Mulroy, S

1999-07-01

Physiological energy expenditure measurement has proven to be a reliable method of quantitatively assessing the penalties imposed by gait disability. The purpose of this review is to outline the basic principles of exercise physiology relevant to human locomotion; detail the energy expenditure of normal walking; and summarize the results of energy expenditure studies performed in patients with specific neurologic and orthopedic disabilities. The magnitude of the disabilities and the patients' capacity to tolerate the increased energy requirements are compared. This paper also will examine the effectiveness of rehabilitation interventions at mitigating the energetic penalties of disability during ambulation.

Low physiological levels of prostaglandins E2 and F2α improve human sperm functions.

PubMed

Rios, Mariana; Carreño, Daniela V; Oses, Carolina; Barrera, Nelson; Kerr, Bredford; Villalón, Manuel

2016-03-01

Prostaglandins (PGs) have been reported to be present in the seminal fluid and cervical mucus, affecting different stages of sperm maturation from spermatogenesis to the acrosome reaction. This study assessed the effects of low physiological PGE2 and PGF2α concentrations on human sperm motility and on the ability of the spermatozoa to bind to the zona pellucida (ZP). Human spermatozoa were isolated from seminal samples with normal concentration and motility parameters and incubated with 1μM PGE2, 1μM PGF2α or control solution to determine sperm motility and the ability to bind to human ZP. The effects of both PGs on intracellular calcium levels were determined. Incubation for 2 or 18h with PGE2 or PGF2α resulted in a significant (P<0.05) increase in the percentage of spermatozoa with progressive motility. In contrast with PGF2α, PGE2 alone induced an increase in sperm intracellular calcium levels; however, the percentage of sperm bound to the human ZP was doubled for both PGs. These results indicate that incubation of human spermatozoa with low physiological levels of PGE2 or PGF2α increases sperm functions and could improve conditions for assisted reproduction protocols.

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.

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

PubMed

Shahabi, Shahram; Kasariyans, Aditya; Noorbakhsh, Farshid

2013-12-01

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

Menstrual physiology: implications for endometrial pathology and beyond

PubMed Central

Maybin, Jacqueline A.; Critchley, Hilary O.D.

2015-01-01

BACKGROUND Each month the endometrium becomes inflamed, and the luminal portion is shed during menstruation. The subsequent repair is remarkable, allowing implantation to occur if fertilization takes place. Aberrations in menstrual physiology can lead to common gynaecological conditions, such as heavy or prolonged bleeding. Increased knowledge of the processes involved in menstrual physiology may also have translational benefits at other tissue sites. METHODS Pubmed and Cochrane databases were searched for all original and review articles published in English until April 2015. Search terms included ‘endometrium’, ‘menstruation’, ‘endometrial repair’, ‘endometrial regeneration’ ‘angiogenesis’, ‘inflammation’ and ‘heavy menstrual bleeding’ or ‘menorrhagia’. RESULTS Menstruation occurs naturally in very few species. Human menstruation is thought to occur as a consequence of preimplantation decidualization, conferring embryo selectivity and the ability to adapt to optimize function. We highlight how current and future study of endometrial inflammation, vascular changes and repair/regeneration will allow us to identify new therapeutic targets for common gynaecological disorders. In addition, we describe how increased knowledge of this endometrial physiology will have many translational applications at other tissue sites. We highlight the clinical applications of what we know, the key questions that remain and the scientific and medical possibilities for the future. CONCLUSIONS The study of menstruation, in both normal and abnormal scenarios, is essential for the production of novel, acceptable medical treatments for common gynaecological complaints. Furthermore, collaboration and communication with specialists in other fields could significantly advance the therapeutic potential of this dynamic tissue. PMID:26253932

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

PubMed

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

2005-12-01

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

Physiological response of some economically important freshwater salmonids to catch-and-release fishing

USGS Publications Warehouse

Wedemeyer, G.A.; Wydoski, R.S.

2008-01-01

Catch-and-release fishing regulations are widely used by fishery resource managers to maintain both the quantity and quality of sport fish populations. We evaluated blood chemistry disturbances in wild brook trout Salvelinus fontinalis, brown trout Salmo trutta, cutthroat trout Oncorhynchus clarkii, and Arctic grayling Thymallus arcticus that had been hooked and played for 1-5 min in waters of the intermountain western United States. A hatchery stock of brown trout was included for comparison. To assess time needed for recovery, additional test groups were played for 5 min and then released into net-pens, where they were held for up to 72 h. The osmoregulatory and metabolic disturbances associated with catch-and-release fishing under the conditions we tested were minimal and judged to be well within normal physiological tolerance limits. In fish that were held for recovery, the blood chemistry alterations that did occur appeared to be related to stress from confinement in the net-pens. Our results confirm the results of previous studies, showing that prerelease air exposure and handling cause more physiological stress than does either hooking per se or playing time. Fishery managers must be aware of the differences in the perceptions, attitudes, and values of different societal groups, some of which feel that catch-and-release fishing should be banned because it is cruel to the animals. On the basis of brain anatomy, it seems highly unlikely that fish experience pain in the same manner as humans experience it, because fish lack a neocortex, the brain structure that enables the sensation of pain in higher vertebrates. However, independent of the neurobiological argument, our results indicate that under conditions similar to those tested, fish subjected to catch and release are neither suffering nor particularly stressed. Improved education programs about the relatively benign physiological effects of catch-and-release fishing as a fishery management practice would be beneficial to anglers and the nonfishing public alike.

Normal venous anatomy and physiology of the lower extremity.

PubMed

Notowitz, L B

1993-06-01

Venous disease of the lower extremities is common but is often misunderstood. It seems that the focus is on the exciting world of arterial anatomy and pathology, while the topic of venous anatomy and pathology comes in second place. However, venous diseases such as chronic venous insufficiency, leg ulcers, and varicose veins affect much of the population and may lead to disability and death. Nurses are often required to answer complex questions from the patients and his or her family about the patient's disease. Patients depend on nurses to provide accurate information in terms they can understand. Therefore it is important to have an understanding of the normal venous system of the legs before one can understand the complexities of venous diseases and treatments. This presents an overview of normal venous anatomy and physiology.

Effects of space flight conditions on the function of the immune system and catecholamine production simulated in a rodent model of hindlimb unloading

NASA Technical Reports Server (NTRS)

Aviles, Hernan; Belay, Tesfaye; Vance, Monique; Sonnenfeld, Gerald

2005-01-01

The rodent model of hindlimb unloading has been successfully used to simulate some of the effects of space flight conditions. Previous studies have indicated that mice exposed to hindlimb-unloading conditions have decreased resistance to infections compared to restrained and normally housed control mice. OBJECTIVE: The purpose of this study was to clarify the mechanisms involved in resistance to infection in this model by examining the effects of hindlimb unloading on the function of the immune system and its impact on the production of catecholamines. METHODS: Female Swiss Webster mice were hindlimb-unloaded during 48 h and the function of the immune system was assessed in spleen and peritoneal cells immediately after this period. In addition, the kinetics of catecholamine production was measured throughout the hindlimb-unloading period. RESULTS: The function of the immune system was significantly suppressed in the hindlimb-unloaded group compared to restrained and normally housed control mice. Levels of catecholamines were increased in the hindlimb-unloaded group and peaked at 12 h following the commencement of unloading. CONCLUSION: These results suggest that physiological responses of mice are altered early after hindlimb unloading and that catecholamines may play a critical role in the modulation of the immune system. These changes may affect the ability of mice to resist infections. Copyright (c) 2005 S. Karger AG, Basel.

Hyperketonemia and ketosis increase the risk of complications in type 1 diabetes

PubMed Central

Kanikarla-Marie, Preeti; Jain, Sushil K.

2016-01-01

Diets that boost ketone production are increasingly used for treating several neurological disorders. Elevation in ketones in most cases is considered favorable, as they provide energy and are efficient in fueling the body’s energy needs. Despite all the benefits from ketones, the above normal elevation in the concentration of ketones in the circulation tend to illicit various pathological complications by activating injurious pathways leading to cellular damage. Recent literature demonstrates a plausible link between elevated levels of circulating ketones and oxidative stress, linking hyperketonemia to innumerable morbid conditions. Ketone bodies are produced by the oxidation of fatty acids in the liver as a source of alternative energy that generally occurs in glucose limiting conditions. Regulation of ketogenesis and ketolysis plays an important role in dictating ketone concentrations in the blood. Hyperketonemia is a condition with elevated blood levels of acetoacetate (AA), 3-β-hydroxybutyrate (BHB), and acetone. Several physiological and pathological triggers, such as fasting, ketogenic diet, and diabetes cause an accumulation and elevation of circulating ketones. Complications of the brain, kidney, liver, and microvasculature were found to be elevated in diabetic patients who had elevated ketones compared to those diabetics with normal ketone levels. This review summarizes the mechanisms by which hyperketonemia and ketoacidosis cause an increase in redox imbalance and thereby increasing the risk of morbidity and mortality in patients. PMID:27036365

Hyperketonemia and ketosis increase the risk of complications in type 1 diabetes.

PubMed

Kanikarla-Marie, Preeti; Jain, Sushil K

2016-06-01

Diets that boost ketone production are increasingly used for treating several neurological disorders. Elevation in ketones in most cases is considered favorable, as they provide energy and are efficient in fueling the body's energy needs. Despite all the benefits from ketones, the above normal elevation in the concentration of ketones in the circulation tend to illicit various pathological complications by activating injurious pathways leading to cellular damage. Recent literature demonstrates a plausible link between elevated levels of circulating ketones and oxidative stress, linking hyperketonemia to innumerable morbid conditions. Ketone bodies are produced by the oxidation of fatty acids in the liver as a source of alternative energy that generally occurs in glucose limiting conditions. Regulation of ketogenesis and ketolysis plays an important role in dictating ketone concentrations in the blood. Hyperketonemia is a condition with elevated blood levels of acetoacetate, 3-β-hydroxybutyrate, and acetone. Several physiological and pathological triggers, such as fasting, ketogenic diet, and diabetes cause an accumulation and elevation of circulating ketones. Complications of the brain, kidney, liver, and microvasculature were found to be elevated in diabetic patients who had elevated ketones compared to those diabetics with normal ketone levels. This review summarizes the mechanisms by which hyperketonemia and ketoacidosis cause an increase in redox imbalance and thereby increase the risk of morbidity and mortality in patients. Copyright © 2016 Elsevier Inc. All rights reserved.

Is shade for horses a comfort resource or a minimum requirement?

PubMed

Holcomb, K E

2017-09-01

Shade or shelter as protection from extremes of weather is required for horses at agricultural research and teaching facilities and is recommended or required by many states, professional organizations, and industry groups. The focus of this paper is the recent research on the responses of horses to hot, sunny weather, which has begun to provide scientific evidence that characterizes how and when shade is used and any benefits shade confers on horses. These behavioral and physiological findings support provision of shade as a resource for thermal comfort and the expression of normal behavior that should be included as a standard of best care practices for healthy adult horses living in the environmental conditions reviewed, rather than an absolute minimum care requirement. Additional research is required for horses living under other environmental conditions, for very young or old horses, horses in very poor body condition, or those with compromised health to determine if their responses to hot, sunny weather differ from those presented here.

Influence of salinity and organic matter on silver accumulation in Gulf toadfish (Opsanus beta).

PubMed

Nichols, Joel W; Brown, Stephanie; Wood, Chris M; Walsh, Patrick J; Playle, Richard C

2006-06-30

To help extend the freshwater based biotic ligand model for silver (Ag) into brackish and saltwater conditions, 50g Gulf toadfish (Opsanus beta) were acclimated to 2.5%, 5%, 10%, 20%, 40%, 80%, or 100% salt water and exposed for 6d to 1.0microM AgNO(3), with or without 10mg C/L organic matter. Suwannee River natural organic matter collected by reverse osmosis was used. Silver accumulation in toadfish gills and plasma decreased as salinity increased, indicating low bioavailability of AgCl complexes. Complexation of Ag by organic matter, normally important in freshwater conditions, was less important as salinity increased. Although relatively little intestinal Ag uptake was observed, both liver and bile accumulated Ag from water imbibed past the isosmotic salinity point ( approximately 1/3 salt water). Toadfish also produced intestinal carbonate pellets, minerals which did not influence Ag accumulation. Our results further stress the importance of Ag speciation, physiological mechanisms, and intestinal Ag uptake when modelling Ag uptake and toxicity beyond freshwater conditions.

Velocity field measurements in oblique static divergent vocal fold models

NASA Astrophysics Data System (ADS)

Erath, Byron

2005-11-01

During normal phonation, the vocal fold cycle is characterized by the glottal opening transitioning from a convergent to a divergent passage and then closing before the cycle is repeated. Under ordinary phonatory conditions, both vocal folds, which form the glottal passage, move in phase with each other, creating a time-varying symmetric opening. However, abnormal pathological conditions, such as unilateral paralysis, and polyps, can result in geometrical asymmetries between the vocal folds throughout the phonatory cycle. This study investigates pulsatile flow fields through 7.5 times life-size vocal fold models with included divergence angles of 5 to 30 degrees, and obliquities between the vocal folds of up to 15 degrees. Flow conditions were scaled to match physiological parameters. Data were taken at the anterior posterior mid-plane using phase-averaged Particle Image Velocimetry (PIV). Viscous flow phenomena including the Coanda effect, flow separation points, and jet "flapping" were investigated. The results are compared to previously reported work of flow through symmetric divergent vocal fold models.

Neuromuscular control of fundamental frequency and glottal posture at phonation onset

PubMed Central

Chhetri, Dinesh K.; Neubauer, Juergen; Berry, David A.

2012-01-01

The laryngeal neuromuscular mechanisms for modulating glottal posture and fundamental frequency are of interest in understanding normal laryngeal physiology and treating vocal pathology. The intrinsic laryngeal muscles in an in vivo canine model were electrically activated in a graded fashion to investigate their effects on onset frequency, phonation onset pressure, vocal fold strain, and glottal distance at the vocal processes. Muscle activation plots for these laryngeal parameters were evaluated for the interaction of following pairs of muscle activation conditions: (1) cricothyroid (CT) versus all laryngeal adductors (TA/LCA/IA), (2) CT versus LCA/IA, (3) CT versus thyroarytenoid (TA) and, (4) TA versus LCA/IA (LCA: lateral cricoarytenoid muscle, IA: interarytenoid). Increases in onset frequency and strain were primarily affected by CT activation. Onset pressure correlated with activation of all adductors in activation condition 1, but primarily with CT activation in conditions 2 and 3. TA and CT were antagonistic for strain. LCA/IA activation primarily closed the cartilaginous glottis while TA activation closed the mid-membranous glottis. PMID:22352513

Dietary sodium influences the effect of mental stress on heart rate variability: a randomized trial in healthy adults.

PubMed

Allen, Alexander R; Gullixson, Leah R; Wolhart, Sarah C; Kost, Susan L; Schroeder, Darrell R; Eisenach, John H

2014-02-01

Dietary sodium influences intermediate physiological traits in healthy adults independent of changes in blood pressure. The purpose of this study was to test the hypothesis that dietary sodium affects cardiac autonomic modulation during mental stress. In a prospective, randomized cross-over design separated by 1 month between diets, 70 normotensive healthy young adults (F/M: 44/26, aged 18-38 years) consumed a 5-day low (10 mmol/day), normal (150 mmol), and high (400 mmol) sodium diet followed by heart rate variability (HRV) recordings at rest and during 5-min computerized mental arithmetic. Women were studied in the low hormone phase of the menstrual cycle following each diet. Diet did not affect resting blood pressure, but heart rate (HR) (mean ± SE) was 66 ± 1, 64 ± 1, and 63 ± 1 bpm in low, normal, and high sodium conditions, respectively (analysis of variance P = 0.02). For HRV, there was a main effect of sodium on resting SD of normalized RR intervals (SDNN), square root of the mean squared difference of successive normalized RR intervals (RMSSD), high frequency, low-frequency normalized units (LFnu), and high-frequency normalized units (HFnu) (P < 0.01 for all). The response to low sodium was most marked and consistent with sympathetic activation and reduced vagal activity, with increased LFnu and decreased SDNN, RMSSD, and HFnu compared to both normal and high sodium conditions (P ≤0.05 for all). Dietary sodium-by-mental stress interactions were significant for mean NN, RMSSD, high-frequency power, LFnu, and low frequency/high frequency ratio (P < 0.05 for all). The interactions signify that sodium restriction evoked an increase in resting sympathetic activity and reduced vagal activity to the extent that mental stress caused modest additional disruptions in autonomic balance. Conversely, normal and high sodium evoked a reduction in resting sympathetic activity and incremental increase in resting vagal activity, which were disrupted to a greater extent during mental stress compared to low sodium. We conclude that autonomic control of HRV at rest and during mental stress is altered by dietary sodium in healthy normotensive young adult men and women.

Influence of Total Knee Arthroplasty on Patellar Kinematics and Patellofemoral Pressure.

PubMed

Tanikawa, Hidenori; Tada, Mitsunori; Harato, Kengo; Okuma, Kazunari; Nagura, Takeo

2017-01-01

Patellofemoral complications are one of the main problems after total knee arthroplasty (TKA). The design of the TKA component may affect the patellar biomechanics, which may be associated with this postoperative complication. The purpose of this study was to assess the influence of TKA and prosthesis designs on the patellar kinematics and patellofemoral pressure. Using fresh-frozen cadavers, we measured the patellofemoral pressure, patella offset, and patella tilt in the following 4 conditions: normal knee (patella replacement only), cruciate-retaining TKA, condylar-stabilizing TKA, and posterior-stabilized TKA. The patellofemoral pressure increased significantly after the cruciate-retaining TKA and condylar-stabilizing TKA compared with the normal knee. The patella offset in the normal knee decreased with increasing knee flexion angles, while the patella offset in the TKA knees did not change significantly through the full range of motion. The amount of lateral patella tilt in the normal knee was significantly larger than the TKA knees in the full range of motion. Although the femoral components are designed to reproduce an anatomical patellar tracking, the physiological patellar kinematics were not observed. Relatively high patellofemoral pressure and kinematic change after TKA may be associated with postoperative complications such as the anterior knee pain. Copyright © 2016 Elsevier Inc. All rights reserved.

Early gut colonizers shape parasite susceptibility and microbiota composition in honey bee workers

PubMed Central

Schwarz, Ryan S.; Moran, Nancy A.; Evans, Jay D.

2016-01-01

Microbial symbionts living within animal guts are largely composed of resident bacterial species, forming communities that often provide benefits to the host. Gut microbiomes of adult honey bees (Apis mellifera) include core residents such as the betaproteobacterium Snodgrassella alvi, alongside transient parasites such as the protozoan Lotmaria passim. To test how these species affect microbiome composition and host physiology, we administered S. alvi and/or L. passim inocula to newly emerged worker bees from four genetic backgrounds (GH) and reared them in normal (within hives) or stressed (protein-deficient, asocial) conditions. Microbiota acquired by normal bees were abundant but quantitatively differed across treatments, indicating treatment-associated dysbiosis. Pretreatment with S. alvi made normal bees more susceptible to L. passim and altered developmental and detoxification gene expression. Stressed bees were more susceptible to L. passim and were depauperate in core microbiota, yet supplementation with S. alvi did not alter this susceptibility. Microbiomes were generally more variable by GH in stressed bees, which also showed opposing and comparatively reduced modulation of gene expression responses to treatments compared with normal bees. These data provide experimental support for a link between altered gut microbiota and increased parasite and pathogen prevalence, as observed from honey bee colony collapse disorder. PMID:27482088

Molecular dynamics study of lipid bilayers modeling the plasma membranes of normal murine thymocytes and leukemic GRSL cells.

PubMed

Andoh, Yoshimichi; Okazaki, Susumu; Ueoka, Ryuichi

2013-04-01

Molecular dynamics (MD) calculations for the plasma membranes of normal murine thymocytes and thymus-derived leukemic GRSL cells in water have been performed under physiological isothermal-isobaric conditions (310.15K and 1 atm) to investigate changes in membrane properties induced by canceration. The model membranes used in our calculations for normal and leukemic thymocytes comprised 23 and 25 kinds of lipids, respectively, including phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, phosphatidylinositol, sphingomyelin, lysophospholipids, and cholesterol. The mole fractions of the lipids adopted here were based on previously published experimental values. Our calculations clearly showed that the membrane area was increased in leukemic cells, and that the isothermal area compressibility of the leukemic plasma membranes was double that of normal cells. The calculated membranes of leukemic cells were thus considerably bulkier and softer in the lateral direction compared with those of normal cells. The tilt angle of the cholesterol and the conformation of the phospholipid fatty acid tails both showed a lower level of order in leukemic cell membranes compared with normal cell membranes. The lateral radial distribution function of the lipids also showed a more disordered structure in leukemic cell membranes than in normal cell membranes. These observations all show that, for the present thymocytes, the lateral structure of the membrane is considerably disordered by canceration. Furthermore, the calculated lateral self-diffusion coefficient of the lipid molecules in leukemic cell membranes was almost double that in normal cell membranes. The calculated rotational and wobbling autocorrelation functions also indicated that the molecular motion of the lipids was enhanced in leukemic cell membranes. Thus, here we have demonstrated that the membranes of thymocyte leukemic cells are more disordered and more fluid than normal cell membranes. Copyright © 2013 Elsevier B.V. All rights reserved.

Stress reactivity, condition, and foraging behavior in zebra finches: effects on boldness, exploration, and sociality.

PubMed

Crino, O L; Buchanan, Katherine L; Trompf, Larissa; Mainwaring, Mark C; Griffith, Simon C

2017-04-01

The arid and semi-arid zones of Australia are characterized by highly variable and unpredictable environmental conditions which affect resources for flora and fauna. Environments which are highly unpredictable in terms of both resource access and distribution are likely to select for a variety of adaptive behavioral strategies, intrinsically linked to the physiological control of behavior. How unpredictable resource distribution has affected the coevolution of behavioral strategies and physiology has rarely been quantified, particularly not in Australian birds. We used a captive population of wild-derived zebra finches to test the relationships between behavioral strategies relating to food access and physiological responses to stress and body condition. We found that individuals that were in poorer body condition and had higher peak corticosterone levels entered baited feeders earlier in the trapping sequence of birds within the colony. We also found that individuals in poorer body condition fed in smaller social groups. Our data show that the foraging decisions which individuals make represent not only a trade-off between food access and risk of exposure, but their underlying physiological response to stress. Our data also suggest fundamental links between social networks and physiological parameters, which largely remain untested. These data demonstrate the fundamental importance of physiological mechanisms in controlling adaptive behavioral strategies and the dynamic interplay between physiological control of behavior and life-history evolution. Copyright © 2016 Elsevier Inc. All rights reserved.

Tissue Doppler Imaging can be useful to distinguish pathological from physiological left ventricular hypertrophy: a study in master athletes and mild hypertensive subjects

PubMed Central

Galanti, Giorgio; Toncelli, Loira; Del Furia, Francesca; Stefani, Laura; Cappelli, Brunello; De Luca, Alessio; Vono, Maria Concetta Roberta

2009-01-01

Background Transthoracic echocardiography left ventricular wall thickness is often increased in master athletes and it results by intense physical training. Left Ventricular Hypertrophy can also be due to a constant pressure overload. Conventional Pulsed Wave (PW) Doppler analysis of diastolic function sometimes fails to distinguish physiological from pathological LVH. The aim of this study is to evaluate the role of Pulsed Wave Tissue Doppler Imaging in differentiating pathological from physiological LVH in the middle-aged population. Methods we selected a group of 80 master athletes, a group of 80 sedentary subjects with essential hypertension and an apparent normal diastolic function at standard PW Doppler analysis. The two groups were comparable for increased left ventricular wall thickness and mass index (134.4 ± 19.7 vs 134.5 ± 22.1 gr/m2; p > .05). Diastolic function indexes using the PW technique were in the normal range for both. Results Pulsed Wave TDI study of diastolic function immediately distinguished the two groups. While in master athletes the diastolic TDI-derived parameters remained within normal range (E' 9.4 ± 3.1 cm/sec; E/E' 7.8 ± 2.1), in the hypertensive group these parameters were found to be constantly altered, with mean values and variation ranges always outside normal validated limits (E' 7.2 ± 2.4 cm/sec; E/E' 10.6 ± 3.2), and with E' and E/E' statistically different in the two groups (p < .001). Conclusion Our study showed that the TDI technique can be an easy and validated method to assess diastolic function in differentiating normal from pseudonormal diastolic patterns and it can distinguish physiological from pathological LVH emphasizing the eligibility certification required by legal medical legislation as in Italy. PMID:19845938

Zebrafish Transgenic Line huORFZ Is an Effective Living Bioindicator for Detecting Environmental Toxicants

PubMed Central

Chu, Chien; Li, Hong-Ping; Tsai, Huai-Jen

2014-01-01

Reliable animal models are invaluable for monitoring the extent of pollution in the aquatic environment. In this study, we demonstrated the potential of huORFZ, a novel transgenic zebrafish line that harbors a human upstream open reading frame of the chop gene fused with GFP reporter, as an animal model for monitoring environmental pollutants and stress-related cellular processes. When huORFZ embryos were kept under normal condition, no leaked GFP signal could be detected. When treated with hazardous chemicals, including heavy metals and endocrine-disrupting chemicals near their sublethal concentrations (LC50), huORFZ embryos exhibited different tissue-specific GFP expression patterns. For further analysis, copper (Cu2+), cadmium (Cd2+) and Chlorpyrifos were applied. Cu2+ triggered GFP responses in skin and muscle, whereas Cd2+ treatment triggered GFP responses in skin, olfactory epithelium and pronephric ducts. Moreover, fluorescence intensity, as exhibited by huORFZ embryos, was dose-dependent. After surviving treated embryos were returned to normal condition, survival rates, as well as TUNEL signals, returned to pretreatment levels with no significant morphological defects observed. Such results indicated the reversibility of treatment conditions used in this study, as long as embryos survived such conditions. Notably, GFP signals decreased along with recovery, suggesting that GFP signaling of huORFZ embryos likely reflected the overall physiological condition of the individual. To examine the performance of the huORFZ line under real-world conditions, we placed huORFZ embryos in different river water samples. We found that the huORFZ embryos correctly detected the presence of various kinds of pollutants. Based on these findings, we concluded that such uORFchop-based system can be integrated into a first-line water alarm system monitoring the discharge of hazardous pollutants. PMID:24594581

Perconditioning and postconditioning: current knowledge, knowledge gaps, barriers to adoption, and future directions.

PubMed

Vinten-Johansen, Jakob; Shi, Weiwei

2011-01-01

The broad definition of "conditioning" is the application of a series of alternating intervals of brief ischemia (hypoxia) and reperfusion (reoxygenation) applied in the setting of prolonged ischemia causing myocardial infarction. While the conditioning stimulus is applied before the major (index) ischemic event in ischemic preconditioning, it is applied during the event in perconditioning, and applied after the event (reperfusion) in postconditioning. Studies on perconditioning have only recently demonstrated a reduction in infarct size by remote ischemia applied during transport of heart attack victims to the hospital before percutaneous coronary interventions (PCIs). The "conditioning" paradigm has been extended to include remote perconditioning and remote postconditioning. However, the biology of perconditioning is virtually unknown. Postconditioning has enjoyed enthusiastic attention from scientists that have done much to demonstrate that the model of triggers, mediators, and effectors used in preconditioning may also apply to postconditioning, with the addition and important contribution of physiological mechanisms resulting in cardioprotection, including gradual normalization of tissue pH, reduction in generation of reactive oxygen species, and avoidance of hypercontracture. This same schema has not been confirmed in perconditioning. However, the unknowns in both conditioning paradigms far outweigh the knowns. Why postconditioning does not exert cardioprotection in experimental models of comorbidities and aging, yet reduces postischemic injury and contractile dysfunction in older patients with multiple comorbidities is a conundrum for which no answers are forthcoming. The optimal algorithm is unknown, as is the interrelationship between the many molecular, cellular, and physiological pathways that purportedly "mediate" or "trigger" the conditioning responses. Whether there are common pathways engaged in all 3 forms of conditioning, and what nuances separate one form of conditioning from another are unanswered questions. Yet, the translational potential of per- and postconditioning will drive further experimental work and clinical trials, which will ask unprecedented cooperation and information sharing between basic and clinician scientists, and creative developments from industry.

The physiological determinants of drug-induced lysosomal stress resistance

PubMed Central

Woldemichael, Tehetina; Rosania, Gus R.

2017-01-01

Many weakly basic, lipophilic drugs accumulate in lysosomes and exert complex, pleiotropic effects on organelle structure and function. Thus, modeling how perturbations of lysosomal physiology affect the maintenance of lysosomal ion homeostasis is necessary to elucidate the key factors which determine the toxicological effects of lysosomotropic agents, in a cell-type dependent manner. Accordingly, a physiologically-based mathematical modeling and simulation approach was used to explore the dynamic, multi-parameter phenomenon of lysosomal stress. With this approach, parameters that are either directly involved in lysosomal ion transportation or lysosomal morphology were transiently altered to investigate their downstream effects on lysosomal physiology reflected by the changes they induce in lysosomal pH, chloride, and membrane potential. In addition, combinations of parameters were simultaneously altered to assess which parameter was most critical for recovery of normal lysosomal physiology. Lastly, to explore the relationship between organelle morphology and induced stress, we investigated the effects of parameters controlling organelle geometry on the restoration of normal lysosomal physiology following a transient perturbation. Collectively, our results indicate a key, interdependent role of V-ATPase number and membrane proton permeability in lysosomal stress tolerance. This suggests that the cell-type dependent regulation of V-ATPase subunit expression and turnover, together with the proton permeability properties of the lysosomal membrane, is critical to understand the differential sensitivity or resistance of different cell types to the toxic effects of lysosomotropic drugs. PMID:29117253

Real-time in vivo uric acid biosensor system for biophysical monitoring of birds.

PubMed

Gumus, A; Lee, S; Karlsson, K; Gabrielson, R; Winkler, D W; Erickson, D

2014-02-21

Research on birds has long played an important role in ecological investigations, as birds are relatively easily observed, and their high metabolic rates and diurnal habits make them quite evidently responsive to changes in their environments. A mechanistic understanding of such avian responses requires a better understanding of how variation in physiological state conditions avian behavior and integrates the effects of recent environmental changes. There is a great need for sensor systems that will allow free-flying birds to interact with their environment and make unconstrained decisions about their spatial location at the same time that their physiological state is being monitored in real time. We have developed a miniature needle-based enzymatic sensor system suitable for continuous real-time amperometric monitoring of uric acid levels in unconstrained live birds. The sensor system was constructed with Pt/Ir wire and Ag/AgCl paste. Uricase enzyme was immobilized on a 0.7 mm sensing cavity of Nafion/cellulose inner membrane to minimize the influences of background interferents. The sensor response was linear from 0.05 to 0.6 mM uric acid, which spans the normal physiological range for most avian species. We developed a two-electrode potentiostat system that drives the biosensor, reads the output current, and wirelessly transmits the data. In addition to extensive characterization of the sensor and system, we also demonstrate autonomous operation of the system by collecting in vivo extracellular uric acid measurements on a domestic chicken. The results confirm our needle-type sensor system's potential for real-time monitoring of birds' physiological state. Successful application of the sensor in migratory birds could open up a new era of studying both the physiological preparation for migration and the consequences of sustained avian flight.

Fructose metabolism in the cerebellum.

PubMed

Funari, Vincent A; Crandall, James E; Tolan, Dean R

2007-01-01

Under normal physiological conditions, the brain utilizes only a small number of carbon sources for energy. Recently, there is growing molecular and biochemical evidence that other carbon sources, including fructose, may play a role in neuro-energetics. Fructose is the number one commercial sweetener in Western civilization with large amounts of fructose being toxic, yet fructose metabolism remains relatively poorly characterized. Fructose is purportedly metabolized via either of two pathways, the fructose-1-phosphate pathway and/or the fructose-6-phosphate pathway. Many early metabolic studies could not clearly discriminate which of these two pathways predominates, nor could they distinguish which cell types in various tissues are capable of fructose metabolism. In addition, the lack of good physiological models, the diet-induced changes in gene expression in many tissues, the involvement of multiple genes in multiple pathways involved in fructose metabolism, and the lack of characterization of some genes involved in fructose metabolism have complicated our understanding of the physiological role of fructose in neuro-energetics. A recent neuro-metabolism study of the cerebellum demonstrated fructose metabolism and co-expression of the genes specific for the fructose 1-phosphate pathway, GLUT5 (glut5) and ketohexokinase (khk), in Purkinje cells suggesting this as an active pathway in specific neurons? Meanwhile, concern over the rapid increase in dietary fructose, particularly among children, has increased awareness about how fructose is metabolized in vivo and what effects a high fructose diet might have. In this regard, establishment of cellular and molecular studies and physiological characterization of the important and/or deleterious roles fructose plays in the brain is critical. This review will discuss the status of fructose metabolism in the brain with special reference to the cerebellum and the physiological roles of the different pathways.

Probing orientation and rotation of red blood cells in optical tweezers by digital holographic microscopy

NASA Astrophysics Data System (ADS)

Cardenas, Nelson; Yu, Lingfeng; Mohanty, Samarendra K.

2011-03-01

Interaction of red blood cells (RBC) with optical tweezers has been found to differ under varied physiological and pathological conditions as compared to its normal conditions. Earlier, we reported difference in rotation of trapped RBC in hypertonic conditions for detection of malaria infection. Disk-like RBC when trapped in optical tweezers get oriented in the vertical plane to maximize interaction with trapping beam. However, classical bright field, phase contrast or epifluorescence microscopy cannot confirm its orientation, thus leading to ambiguous conclusions such as folding of RBC during trapping by some researchers. Now, with use of digital holographic microscopy (DHM), we achieved high axial sensitivity that confirmed orientation of trapped red blood cell. Further, DHM enabled quantitative phase imaging of RBC under hypertonic condition. Dynamic changes of rotating RBC under optical tweezers at different trapping laser power were evaluated by the use of DHM. The deviation from linear dependence of rotation speed of RBC on laser power, was attributed towards deformation of RBC shape due to higher laser power (or speed).

[Features of cholecalciferol hydroxylation in the liver of rats in conditions of D-hypervitaminosis and activity of alpha-tocopherol].

PubMed

Velykyĭ, M M; Apukhovs'ka, L I; Vasylevs'ka, V M; Lotots'ka, O Iu; Besusiak, A I; Khomenko, A V

2010-01-01

It is shown, that hepatocytes contain two (microsomal and mitochondrial) vitamin D3 25-hydroxylase enzymes, which differ as to their activity and function with maximal activity at different concentrations to substrate, namely at 15 microM and 100 microM of vitamin D3, accordingly. Activity of vitamin D3 25-hydroxylase enzymes of hepatocytes is regulated by cholecalciferol and alpha-tocopherol. The general and microsomal vitamin D3 25-hydroxylase enzymes activity of hepatocytes is lowered, but mitochondrial isoform is increased under D-hypervitaminosis conditions. Vitamin E increases microsomal vitamin D3 25-hydroxylase activity and decreases mitochondrial isoform activity of rats hepatocytes under D-hypervitaminosis conditions. It is established that D-hypervitaminosis is accompanied by expressed hypercalcemia and hyperphosphatemia, by decreased contents of mineral components in the bone tissue and high activity of alkaline phosphatase in the blood serum. The physiological doses of vitamin E under these conditions normalized the mineral metabolism, contents of calcium, phosphates and activity of alkaline phosphatase isoform in the blood serum.

Identification of Human HK Genes and Gene Expression Regulation Study in Cancer from Transcriptomics Data Analysis

PubMed Central

Zhang, Zhang; Liu, Jingxing; Wu, Jiayan; Yu, Jun

2013-01-01

The regulation of gene expression is essential for eukaryotes, as it drives the processes of cellular differentiation and morphogenesis, leading to the creation of different cell types in multicellular organisms. RNA-Sequencing (RNA-Seq) provides researchers with a powerful toolbox for characterization and quantification of transcriptome. Many different human tissue/cell transcriptome datasets coming from RNA-Seq technology are available on public data resource. The fundamental issue here is how to develop an effective analysis method to estimate expression pattern similarities between different tumor tissues and their corresponding normal tissues. We define the gene expression pattern from three directions: 1) expression breadth, which reflects gene expression on/off status, and mainly concerns ubiquitously expressed genes; 2) low/high or constant/variable expression genes, based on gene expression level and variation; and 3) the regulation of gene expression at the gene structure level. The cluster analysis indicates that gene expression pattern is higher related to physiological condition rather than tissue spatial distance. Two sets of human housekeeping (HK) genes are defined according to cell/tissue types, respectively. To characterize the gene expression pattern in gene expression level and variation, we firstly apply improved K-means algorithm and a gene expression variance model. We find that cancer-associated HK genes (a HK gene is specific in cancer group, while not in normal group) are expressed higher and more variable in cancer condition than in normal condition. Cancer-associated HK genes prefer to AT-rich genes, and they are enriched in cell cycle regulation related functions and constitute some cancer signatures. The expression of large genes is also avoided in cancer group. These studies will help us understand which cell type-specific patterns of gene expression differ among different cell types, and particularly for cancer. PMID:23382867

Constitutive Uncoupling of Pathways of Gene Expression That Control Growth and Differentiation in Myeloid Leukemia: A Model for the Origin and Progression of Malignancy

NASA Astrophysics Data System (ADS)

Sachs, Leo

1980-10-01

Chemical carcinogens and tumor promoters have pleiotropic effects. Tumor initiators can produce a variety of mutations and tumor promoters can regulate a variety of physiological molecules that control growth and differentiation. The appropriate mutation and the regulation of the appropriate molecules to induce cell growth can initiate and promote the sequence of changes required for transformation of normal cells into malignant cells. After this sequence of changes, some tumors can still be induced to revert with a high frequency from a malignant phenotype to a nonmalignant phenotype. Results obtained from analysis of regulation of growth and differentiation in normal and leukemic myeloid cells, the phenotypic reversion of malignancy by induction of normal differentiation in myeloid leukemia, and the blocks in differentiation-defective leukemic cell mutants have been used to propose a general model for the origin and progression of malignancy. The model states that malignancy originates by changing specific pathways of gene expression required for growth from inducible to constitutive in cells that can still be induced to differentiate normally by the physiological inducer of differentiation. The malignant cells, unlike the normal cells, then no longer require the physiological inducer for growth. This changes the requirements for growth and uncouples growth from differentiation. Constitutive expression of other specific pathways can uncouple other controls, which then causes blocks in differentiation and the further progression of malignancy. The existence of specific constitutive pathways of gene expression that uncouple controls in malignant cells can also explain the expression of fetal proteins, hormones, and some other specialized products of normal development in various types of tumors.

The binding of aluminum to mugineic acid and related compounds as studied by potentiometric titration.

PubMed

Yoshimura, Etsuro; Kohdr, Hicham; Mori, Satoshi; Hider, Robert C

2011-08-01

The phytosiderophores, mugineic acid (MA) and epi-hydroxymugineic acid (HMA), together with a related compound, nicotianamine (NA), were investigated for their ability to bind Al(III). Potentiometric titration analysis demonstrated that MA and HMA bind Al(III), in contrast to NA which does not under normal physiological conditions. With MA and HMA, in addition to the Al complex (AlL), the protonated (AlLH) and deprotonated (AlLH(-1)) complexes were identified from an analysis of titration curves, where L denotes the phytosiderophore form in which all the carboxylate functions are ionized. The equilibrium formation constants of the Al(III) phytosiderophore complexes are much smaller than those of the corresponding Fe(III) complexes. The higher selectivity of phytosiderophores for Fe(III) over Al(III) facilitates Fe(III) acquisition in alkaline conditions where free Al(III) levels are higher than free Fe(III) levels.

Modulating the function of the immune system by thyroid hormones and thyrotropin.

PubMed

Jara, Evelyn L; Muñoz-Durango, Natalia; Llanos, Carolina; Fardella, Carlos; González, Pablo A; Bueno, Susan M; Kalergis, Alexis M; Riedel, Claudia A

2017-04-01

Accumulating evidence suggests a close bidirectional communication and regulation between the neuroendocrine and immune systems. Thyroid hormones (THs) can exert responses in various immune cells, e.g., monocytes, macrophages, natural killer cells, and lymphocytes, affecting several inflammation-related processes (such as, chemotaxis, phagocytosis, reactive oxygen species generation, and cytokines production). The interactions between the endocrine and immune systems have been shown to contribute to pathophysiological conditions, including sepsis, inflammation, autoimmune diseases and viral infections. Under these conditions, TH therapy could contribute to restoring normal physiological functions. Here we discuss the effects of THs and thyroid stimulating hormone (TSH) on the immune system and the contribution to inflammation and pathogen clearance, as well as the consequences of thyroid pathologies over the function of the immune system. Copyright © 2017 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.

Surfing the Big WAVE: Insights into the Role of WAVE3 as a Driving Force in Cancer Progression and Metastasis

PubMed Central

Sossey-Alaoui, Khalid

2014-01-01

WAVE3 belongs to the WASP/WAVE family of actin cytoskeleton remodeling proteins. These proteins are known to be involved in several biological functions ranging from controlling cell shape and movement, to being closely associated with pathological conditions such as cancer progression and metastasis. Last decade has seen an explosion in the literature reporting significant scientific advances on the molecular mechanisms whereby the WASP/WAVE proteins are regulated both in normal physiological as well as pathological conditions. The purpose of this review is to present the major findings pertaining to how WAVE3 has become a critical player in the regulation of signaling pathways involved in cancer progression and metastasis. The review will conclude with suggesting options for the potential use of WAVE3 as a therapeutic target to prevent the progression of cancer to the lethal stage that is the metastatic disease. PMID:23116924

Tinea atypica.

PubMed

Atzori, L; Pau, M; Aste, N

2013-12-01

Although usually simple, the diagnosis of dermatophyte infection is sometimes neglected. Variations in clinical presentation (tinea atypica), mimicking other skin diseases depend on many factors, partially due to the dermatophyte's characteristics, and a combination of patient's pathological but often physiological conditions, such as excessive washing or sun exposure. The physician's misdiagnosis and eventual prescription of steroids or other incongruous treatments further induce pathomorphosis (tinea incognito), longstanding disease and delayed recovery. This review describes the morphology of some atypical dermatophyte infections, in an attempt to compare and correlate changes to the normal features of the disease by site of involvement. The risk factors and predisposing conditions are also analysed to provide a reasoned interpretation of morphology and therefore evoke the diagnostic suspect in atypical cases. Periodical training is the clue to improve dermatologist expertise in what is the first-sight ability to make a diagnosis, perform the correct assessments and consequent therapy in daily practice.

Biomimetic mineralization of metal-organic frameworks as protective coatings for biomacromolecules

NASA Astrophysics Data System (ADS)

Liang, Kang; Ricco, Raffaele; Doherty, Cara M.; Styles, Mark J.; Bell, Stephen; Kirby, Nigel; Mudie, Stephen; Haylock, David; Hill, Anita J.; Doonan, Christian J.; Falcaro, Paolo

2015-06-01

Enhancing the robustness of functional biomacromolecules is a critical challenge in biotechnology, which if addressed would enhance their use in pharmaceuticals, chemical processing and biostorage. Here we report a novel method, inspired by natural biomineralization processes, which provides unprecedented protection of biomacromolecules by encapsulating them within a class of porous materials termed metal-organic frameworks. We show that proteins, enzymes and DNA rapidly induce the formation of protective metal-organic framework coatings under physiological conditions by concentrating the framework building blocks and facilitating crystallization around the biomacromolecules. The resulting biocomposite is stable under conditions that would normally decompose many biological macromolecules. For example, urease and horseradish peroxidase protected within a metal-organic framework shell are found to retain bioactivity after being treated at 80 °C and boiled in dimethylformamide (153 °C), respectively. This rapid, low-cost biomimetic mineralization process gives rise to new possibilities for the exploitation of biomacromolecules.

Inhibition of Monometalated Methionine Aminopeptidase: Inhibitor Discovery and Crystallographic Analysis†

PubMed Central

Huang, Min; Xie, Sheng-Xue; Ma, Ze-Qiang; Huang, Qing-Qing; Nan, Fa-Jun; Ye, Qi-Zhuang

2008-01-01

Two divalent metal ions are commonly seen in the active site cavity of methionine aminopeptidase, and at least one of the metal ions is directly involved in catalysis. Although ample structural and functional information is available for dimetalated enzyme, methionine aminopeptidase likely functions as a monometalated enzyme under physiological conditions. Information on structure, as well as catalysis and inhibition, of the monometalated enzyme is lacking. By improving conditions of high throughput screening, we identified a unique inhibitor with specificity toward the monometalated enzyme. Kinetic characterization indicates a mutual exclusivity in binding between the inhibitor and the second metal ion at the active site. This is confirmed by X-ray structure, and this inhibitor coordinates with the first metal ion and occupies the space normally occupied by the second metal ion. Kinetic and structural analyses of the inhibition by this and other inhibitors provide insight in designing effective inhibitors of methionine aminopeptidase. PMID:17948983

Nonvesicular inhibitory neurotransmission via reversal of the GABA transporter GAT-1

PubMed Central

Wu, Yuanming; Wang, Wengang; Díez-Sampedro, Ana; Richerson, George B.

2007-01-01

SUMMARY GABA transporters play an important but poorly understood role in neuronal inhibition. They can reverse, but this is widely thought to occur only under pathological conditions. Here we use a heterologous expression system to show that the reversal potential of GAT-1 under physiologically relevant conditions is near the normal resting potential of neurons, and that reversal can occur rapidly enough to release GABA during simulated action potentials. We then use paired recordings from cultured hippocampal neurons, and show that GABAergic transmission is not prevented by four methods widely used to block vesicular release. This nonvesicular neurotransmission was potently blocked by GAT-1 antagonists, and was enhanced as predicted by agents that increase cytosolic [GABA] or [Na+]. The results indicate that GAT-1 regulates tonic inhibition by clamping ambient [GABA] at a level high enough to activate high affinity GABAA receptors, and that transporter-mediated GABA release can contribute to phasic inhibition. PMID:18054861

Pathogenesis of Pain.

PubMed

Dinakar, Pradeep; Stillman, Alexandra Marion

2016-08-01

The pathogenesis of pain sensation includes mechanisms that result in acute or chronic pain. Pain itself is described as an unpleasant sensory and emotional experience beginning with a peripheral stimulus that undergoes a physiological process ultimately resulting in the sensation of pain. Biologists recognize pain to be a common sign of potential tissue damage. Hence, pain sensation is protective in function. However, pathologic states of pain exist secondary to disruption of the nociceptive process both peripherally and centrally or secondary to psychological conditions. It is essential to identify these aberrant states of pain and distinguish them from situations of potential tissue damage. Chronic pain is defined as pain that exceeds 3 or 6 months duration. This article is an overview of the essential neuroanatomy and neurophysiology of normal pain nociception, its clinical implications, and the development of persistent and pathological pain conditions following improperly or poorly treated pain. Copyright © 2016. Published by Elsevier Inc.

Developing Physiologic Stress Profiles for School-Age Children Who Stutter

ERIC Educational Resources Information Center

Ortega, Aishah Y.; Ambrose, Nicoline G.

2011-01-01

Purpose: Physiologic reactivity profiles were generated for 9 school-age children with a history of stuttering. Utilizing salivary sampling, stress biomarkers cortisol and alpha-amylase were measured in response to normal daily stressors. Children with a history of stuttering were characterized as high or low autonomic reactors when compared to…

New Ways of Thinking about (and Teaching about) Intestinal Epithelial Function

ERIC Educational Resources Information Center

Barrett, Kim E.

2008-01-01

This article summarizes a presentation made at the Teaching Refresher Course of the American Physiological Society, which was held at the Experimental Biology meeting in 2007. The intestinal epithelium has important ion transport and barrier functions that contribute pivotally to normal physiological functioning of the intestine and other body…

Measurement of Physiologic Glucose Levels Using Raman Spectroscopy in a Rabbit Aqueous Humor Model

NASA Technical Reports Server (NTRS)

Lambert, J.; Storrie-Lombardi, M.; Borchert, M.

1998-01-01

We have elecited a reliable glucose signature in mammalian physiological ranges using near infrared Raman laser excitation at 785 nm and multivariate analysis. In a recent series of experiments we measured glucose levels in an artificial aqueous humor in the range from 0.5 to 13X normal values.

The Influence of Word Frequency on Word Retrieval: Measuring Covert Behaviors

ERIC Educational Resources Information Center

Chih, Yu-Chun; Stierwalt, Julie A. G.; LaPointe, Leonard L.; Chih, Yu-Pin

2017-01-01

Physiological activities (heart rate and respiratory rate) during a word retrieval task were measured in normal participants. Word frequency demonstrated a significant effect on naming accuracy and latencies but not on physiological activities. These data will serve as a basis for comparison for individuals with a compromised language system.

Functional metabolite assemblies—a review

NASA Astrophysics Data System (ADS)

Aizen, Ruth; Tao, Kai; Rencus-Lazar, Sigal; Gazit, Ehud

2018-05-01

Metabolites are essential for the normal operation of cells and fulfill various physiological functions. It was recently found that in several metabolic disorders, the associated metabolites could self-assemble to generate amyloid-like structures, similar to canonical protein amyloids that have a role in neurodegenerative disorders. Yet, assemblies with typical amyloid characteristics are also known to have physiological function. In addition, many non-natural proteins and peptides presenting amyloidal properties have been used for the fabrication of functional nanomaterials. Similarly, functional metabolite assemblies are also found in nature, demonstrating various physiological roles. A notable example is the structural color formed by guanine crystals or fluorescent crystals in feline eyes responsible for enhanced night vision. Moreover, some metabolites have been used for the in vitro fabrication of functional materials, such as glycine crystals presenting remarkable piezoelectric properties or indigo films used to assemble organic semi-conductive electronic devices. Therefore, we believe that the study of metabolite assemblies is not only important in order to understand their role in normal physiology and in pathology, but also paves a new route in exploring the fabrication of organic, bio-compatible materials.

Recent Advances in Type-2-Cell-Mediated Immunity: Insights from Helminth Infection.

PubMed

Harris, Nicola L; Loke, P'ng

2017-12-19

Type-2-cell-mediated immune responses play a critical role in mediating both host-resistance and disease-tolerance mechanisms during helminth infections. Recently, type 2 cell responses have emerged as major regulators of tissue repair and metabolic homeostasis even under steady-state conditions. In this review, we consider how studies of helminth infection have contributed toward our expanding cellular and molecular understanding of type-2-cell-mediated immunity, as well as new areas such as the microbiome. By studying how these successful parasites form chronic infections without overt pathology, we are gaining additional insights into allergic and inflammatory diseases, as well as normal physiology. Copyright © 2017 Elsevier Inc. All rights reserved.

Histopathologic study of the so called 'palpation thyroiditis'.

PubMed Central

Hwang, T. S.; Park, S. H.

1988-01-01

We have reviewed 1066 thyroid lesions and compared the relative incidence of the so called 'palpation thyroiditis' between autoimmune thyroiditis and normal thyroid parenchyme surrounding the nodular thyroid lesion and also discussed the pathogenesis of palpation thyroiditis. The typical histopathologic features of 'palpation thyroiditis' were seen in 275 cases among 467 adenomatous goiters and in none of the autoimmune thyroiditis. We here in this paper suggest that the so called 'palpation thyroiditis' is not merely a secondary phenomenon to mechanical follicular damage by vigorous palpation, but this lesion more likely develops in conditions where certain types of physiologic alteration has occurred in follicular basement membrane, just like a pathogenesis of subacute granulomatous thyroiditis. PMID:3079564

Imaging elemental distribution and ion transport in cultured cells with ion microscopy.

PubMed

Chandra, S; Morrison, G H

1985-06-28

Both elemental distribution and ion transport in cultured cells have been imaged by ion microscopy. Morphological and chemical information was obtained with a spatial resolution of approximately 0.5 micron for sodium, potassium, calcium, and magnesium in freeze-fixed, cryofractured, and freeze-dried normal rat kidney cells and Chinese hamster ovary cells. Ion transport was successfully demonstrated by imaging Na+-K+ fluxes after the inhibition of Na+- and K+ -dependent adenosine triphosphatase with ouabain. This method allows measurements of elemental (isotopic) distribution to be related to cell morphology, thereby providing the means for studying ion distribution and ion transport under different physiological, pathological, and toxicological conditions in cell culture systems.

PubMed Central

Robin, S.; Bonneau, N. H.; Breton, L.; Vandoren, P.

1982-01-01

Cubitus-curvus in a bitch This paper presents a case of cubitus-curvus seen in a five month old female crossbreed dog. There is a description of the clinical and radiological aspects of the case and the corrective surgery is also well described. Special attention was given to the normal anatomy and physiology of the growth plates and to the traumas that can affect these structures. Finally, there is an explanation of the pathogeny of the cubitus-curvus. In our case, the evolution was favorable and the healing of the condition was complete. ImagesFigures 1 et 2.Figures 3 et 4.Figures 5 et 6.Figures 7, 8 et 9.Figures 10 et 11.Figures 12 et 13. PMID:17422108

The study and application of four kinds of organic ion-selective microsensors

NASA Astrophysics Data System (ADS)

Yu, Bi; Zheng, Xiao; Feng, Chu; Hong, Wen-Bing; Liu, Jun-Tao; Wang, Ru-Jiang

1991-09-01

Four kinds of organic ion-selective microelectrodes (two barrels, tip diameter 0.1-0.5 micron) have been developed for the measurement of acetylcholine, histamine, serotonin, and bile acid. Physiological and pathological models on the cellular or sub-cellular level have been established for the purpose of basic and clinical pharmacological research, treatment or diagnosis of certain diseases. The acetylcholine sensitive microelectrode has been applied to the study of acetylcholine activity in single erythrocytes of normal human subjects and patients suffering from manic depressive disorders. The bile acid selective microelectrode has been used for the direct measurement of intracellular bile acid activities both in colorectal cancer and colorectal mucosa in living condition.

Drilling force and temperature of bone under dry and physiological drilling conditions

NASA Astrophysics Data System (ADS)

Xu, Linlin; Wang, Chengyong; Jiang, Min; He, Huiyu; Song, Yuexian; Chen, Hanyuan; Shen, Jingnan; Zhang, Jiayong

2014-11-01

Many researches on drilling force and temperature have been done with the aim to reduce the labour intensiveness of surgery, avoid unnecessary damage and improve drilling quality. However, there has not been a systematic study of mid- and high-speed drilling under dry and physiological conditions(injection of saline). Furthermore, there is no consensus on optimal drilling parameters. To study these parameters under dry and physiological drilling conditions, pig humerus bones are drilled with medical twist drills operated using a wide range of drilling speeds and feed rates. Drilling force and temperature are measured using a YDZ-II01W dynamometer and a NEC TVS-500EX thermal infrared imager, respectively, to evaluate internal bone damage. To evaluate drilling quality, bone debris and hole morphology are observed by SEM(scanning electron microscopy). Changes in drilling force and temperature give similar results during drilling such that the value of each parameter peaks just before the drill penetrates through the osteon of the compact bone into the trabeculae of the spongy bone. Drilling temperatures under physiological conditions are much lower than those observed under dry conditions, while a larger drilling force occurs under physiological conditions than dry conditions. Drilling speed and feed rate have a significant influence on drilling force, temperature, bone debris and hole morphology. The investigation of the effect of drilling force and temperature on internal bone damage reveals that a drilling speed of 4500 r/min and a feed rate of 50 mm/min are recommended for bone drilling under physiological conditions. Drilling quality peaks under these optimal parameter conditions. This paper proposes the optimal drilling parameters under mid- and high-speed surgical drilling, considering internal bone damage and drilling quality, which can be looked as a reference for surgeons performing orthopedic operations.

Growth and physiological responses to surgical and gastric radio transmitter implantation techniques in subyearling chinook salmon (Oncorhynchus tshawytscha)

USGS Publications Warehouse

Martinelli, Theresa L.; Hansel, H.C.; Shively, R.S.

1998-01-01

We examined the effects of surgical and gastric transmitter implantation techniques on the growth, general physiology and behavior of 230 subyearling chinook salmon (Oncorhynchus tshawytscha, Walbaum) (100 mm-154 mm fork length). The transmitter weighed 1.3 g in air (0.9 g in water) and comprised, on average, 6% of the body weight of the fish (in air). Individuals were randomly assigned to an experimental group (control, surgical or gastric) and a sampling period (day 5 or day 21). Relative growth rate was expressed as% body weight gained/day. General condition was assessed by necropsy. Physiological response variables included hematocrit, leucocrit and plasma protein concentration. The mean relative growth rates of control, surgical and gastric fish were not significantly different at day 5. By day 21, the gastric group had a significantly lower relative growth rate (1.3%) as compared to the surgical group (1.8%) and the control group (1.9%) (P = 0.0001). Mean hematocrit values were significantly lower in the surgical (41.8%) and gastric (42.2%) groups as compared to controls (47.3%) at day 5 (P = 0.01), but all were within normal range for salmonids. No significant differences in hematocrit values were detected at day 21. Leucocrit values for all groups were ??? 1% in 99% of the fish. Both tagged groups had significantly lower mean plasma protein levels as compared to controls at day 5 (P = 0.001) and day 21 (P = 0.0001). At day 21 the gastric group (64.4 g 100 m1-1) had significantly lower mean plasma protein levels than the surgical group (68.8 g 100 ml-1) (P = 0.0001). Necropsies showed decreasing condition of gastrically tagged fish over time, and increasing condition of surgical fish. Paired releases of surgically and gastrically implanted yearling chinook salmon in the lower Columbia River in spring, 1996 revealed few significant differences in migration behavior through two reservoirs. We conclude that gastrically implanted fish show decreased growth and condition over a 21 d period. We recommend a surgical implantation method for long-term studies of juvenile salmonids, however, gastric implantation may be suitable for short-term studies.

Coupling gene-based and classic veterinary diagnostics improves interpretation of health and immune function in the Agassiz’s desert tortoise (Gopherus agassizii)

USGS Publications Warehouse

Drake, Karla K.; Bowen, Lizabeth; Lewison, Rebecca L.; Esque, Todd C.; Nussear, Kenneth E.; Braun, Josephine; Waters, Shannon C.; Miles, A. Keith

2017-01-01

The analysis of blood constituents is a widely used tool to aid in monitoring of animal health and disease. However, classic blood diagnostics (i.e. hematologic and plasma biochemical values) often do not provide sufficient information to determine the state of an animal’s health. Field studies on wild tortoises and other reptiles have had limited success in drawing significant inferences between blood diagnostics and physiological and immunological condition. However, recent research using gene transcription profiling in the threatened Mojave desert tortoise (Gopherus agassizii) has proved useful in identifying immune or physiologic responses and overall health. To improve our understanding of health and immune function in tortoises, we evaluated both standard blood diagnostic (body condition, hematologic, plasma biochemistry values, trace elements, plasma proteins, vitamin A levels) and gene transcription profiles in 21 adult tortoises (11 clinically abnormal; 10 clinically normal) from Clark County, NV, USA. Necropsy and histology evaluations from clinically abnormal tortoises revealed multiple physiological complications, with moderate to severe rhinitis or pneumonia being the primary cause of morbidity in all but one of the examined animals. Clinically abnormal tortoises had increased transcription for four genes (SOD, MyD88, CL and Lep), increased lymphocyte production, biochemical enzymes and organics, trace elements of copper, and decreased numbers of leukocytes. We found significant positive correlations between increased transcription for SOD and increased trace elements for copper, as well as genes MyD88 and Lep with increased inflammation and microbial insults. Improved methods for health assessments are an important element of monitoring tortoise population recovery and can support the development of more robust diagnostic measures for ill animals, or individuals directly impacted by disturbance.

Coupling gene-based and classic veterinary diagnostics improves interpretation of health and immune function in the Agassiz’s desert tortoise (Gopherus agassizii)

PubMed Central

Bowen, Lizabeth; Lewison, Rebecca L.; Esque, Todd C.; Nussear, Kenneth E.; Braun, Josephine; Waters, Shannon C.; Miles, A. Keith

2017-01-01

Abstract The analysis of blood constituents is a widely used tool to aid in monitoring of animal health and disease. However, classic blood diagnostics (i.e. hematologic and plasma biochemical values) often do not provide sufficient information to determine the state of an animal’s health. Field studies on wild tortoises and other reptiles have had limited success in drawing significant inferences between blood diagnostics and physiological and immunological condition. However, recent research using gene transcription profiling in the threatened Mojave desert tortoise (Gopherus agassizii) has proved useful in identifying immune or physiologic responses and overall health. To improve our understanding of health and immune function in tortoises, we evaluated both standard blood diagnostic (body condition, hematologic, plasma biochemistry values, trace elements, plasma proteins, vitamin A levels) and gene transcription profiles in 21 adult tortoises (11 clinically abnormal; 10 clinically normal) from Clark County, NV, USA. Necropsy and histology evaluations from clinically abnormal tortoises revealed multiple physiological complications, with moderate to severe rhinitis or pneumonia being the primary cause of morbidity in all but one of the examined animals. Clinically abnormal tortoises had increased transcription for four genes (SOD, MyD88, CL and Lep), increased lymphocyte production, biochemical enzymes and organics, trace elements of copper, and decreased numbers of leukocytes. We found significant positive correlations between increased transcription for SOD and increased trace elements for copper, as well as genes MyD88 and Lep with increased inflammation and microbial insults. Improved methods for health assessments are an important element of monitoring tortoise population recovery and can support the development of more robust diagnostic measures for ill animals, or individuals directly impacted by disturbance. PMID:28835840

Coupling gene-based and classic veterinary diagnostics improves interpretation of health and immune function in the Agassiz's desert tortoise (Gopherus agassizii).

PubMed

Drake, K Kristina; Bowen, Lizabeth; Lewison, Rebecca L; Esque, Todd C; Nussear, Kenneth E; Braun, Josephine; Waters, Shannon C; Miles, A Keith

2017-01-01

The analysis of blood constituents is a widely used tool to aid in monitoring of animal health and disease. However, classic blood diagnostics (i.e. hematologic and plasma biochemical values) often do not provide sufficient information to determine the state of an animal's health. Field studies on wild tortoises and other reptiles have had limited success in drawing significant inferences between blood diagnostics and physiological and immunological condition. However, recent research using gene transcription profiling in the threatened Mojave desert tortoise ( Gopherus agassizii ) has proved useful in identifying immune or physiologic responses and overall health. To improve our understanding of health and immune function in tortoises, we evaluated both standard blood diagnostic (body condition, hematologic, plasma biochemistry values, trace elements, plasma proteins, vitamin A levels) and gene transcription profiles in 21 adult tortoises (11 clinically abnormal; 10 clinically normal) from Clark County, NV, USA. Necropsy and histology evaluations from clinically abnormal tortoises revealed multiple physiological complications, with moderate to severe rhinitis or pneumonia being the primary cause of morbidity in all but one of the examined animals. Clinically abnormal tortoises had increased transcription for four genes (SOD, MyD88, CL and Lep), increased lymphocyte production, biochemical enzymes and organics, trace elements of copper, and decreased numbers of leukocytes. We found significant positive correlations between increased transcription for SOD and increased trace elements for copper, as well as genes MyD88 and Lep with increased inflammation and microbial insults. Improved methods for health assessments are an important element of monitoring tortoise population recovery and can support the development of more robust diagnostic measures for ill animals, or individuals directly impacted by disturbance.

Physiological Factors in Adult Learning and Instruction. Research to Practice Series.

ERIC Educational Resources Information Center

Verner, Coolie; Davison, Catherine V.

The physiological condition of the adult learner as related to his learning capability is discussed. The design of the instructional process, the selection of learning tasks, the rate at which instruction occurs, and the nature of the instructional setting may all be modified by the instructor to accomodate the variable physiological conditions of…

Connexin 43 and ATP-sensitive potassium channels crosstalk: a missing link in hypoxia/ischemia stress.

PubMed

Ahmad Waza, Ajaz; Ahmad Bhat, Shabir; Ul Hussain, Mahboob; Ganai, Bashir A

2018-02-01

Connexin 43 (Cx43) is a gap junction protein expressed in various tissues and organs of vertebrates. Besides functioning as a gap junction, Cx43 also regulates diverse cellular processes like cell growth and differentiation, cell migration, cell survival, etc. Cx43 is critical for normal cardiac functioning and is therefore abundantly expressed in cardiomyocytes. On the other hand, ATP-sensitive potassium (K ATP ) channels are metabolic sensors converting metabolic changes into electrical activity. These channels are important in maintaining the neurotransmitter release, smooth muscle relaxation, cardiac action potential repolarization, normal physiology of cellular repolarization, insulin secretion and immune function. Cx43 and K ATP channels are part of the same signaling pathway, regulating cell survival during stress conditions and ischemia/hypoxia preconditioning. However, the underlying molecular mechanism for their combined role in ischemia/hypoxia preconditioning is largely unknown. The current review focuses on understanding the molecular mechanism responsible for the coordinated role of Cx43 and K ATP channel protein in protecting cardiomyocytes against ischemia/hypoxia stress.

Piezo2 senses airway stretch and mediates lung inflation-induced apnoea

PubMed Central

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

2017-01-01

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

snoU6 and 5S RNAs are not reliable miRNA reference genes in neuronal differentiation.

PubMed

Lim, Q E; Zhou, L; Ho, Y K; Wan, G; Too, H P

2011-12-29

Accurate profiling of microRNAs (miRNAs) is an essential step for understanding the functional significance of these small RNAs in both physiological and pathological processes. Quantitative real-time PCR (qPCR) has gained acceptance as a robust and reliable transcriptomic method to profile subtle changes in miRNA levels and requires reference genes for accurate normalization of gene expression. 5S and snoU6 RNAs are commonly used as reference genes in microRNA quantification. It is currently unknown if these small RNAs are stably expressed during neuronal differentiation. Panels of miRNAs have been suggested as alternative reference genes to 5S and snoU6 in various physiological contexts. To test the hypothesis that miRNAs may serve as stable references during neuronal differentiation, the expressions of eight miRNAs, 5S and snoU6 RNAs in five differentiating neuronal cell types were analyzed using qPCR. The stabilities of the expressions were evaluated using two complementary statistical approaches (geNorm and Normfinder). Expressions of 5S and snoU6 RNAs were stable under some but not all conditions of neuronal differentiation and thus are not suitable reference genes. In contrast, a combination of three miRNAs (miR-103, miR-106b and miR-26b) allowed accurate expression normalization across different models of neuronal differentiation. Copyright © 2011 IBRO. Published by Elsevier Ltd. All rights reserved.

13-cis-retinoic acid metabolism in vivo. The major tissue metabolites in the rat have the all-trans configuration.

PubMed

McCormick, A M; Kroll, K D; Napoli, J L

1983-08-02

The liver and intestinal metabolites of orally dosed 13-cis-[11-3H]retinoic acid were analyzed in normal and 13-cis-retinoic acid treated rats 3 h after administration of the radiolabeled retinoid. all-trans-Retinoic acid was identified as a liver and intestinal mucosa metabolite in normal rats given physiological doses of 13-cis-[3H]retinoic acid. all-trans-Retinoyl glucuronide was identified as the most abundant radiolabeled metabolite in mucosa and a prominent liver metabolite under the same conditions. Thus, the major 13-cis-retinoic acid metabolites retained in liver and mucosa, two retinoid target tissues, had the all-trans configuration. These data indicate that the isomerization of 13-cis-retinoic acid to all-trans-retinoic acid and the subsequent conversion to all-trans-retinoyl glucuronide are central events in the in vivo metabolism of 13-cis-retinoic acid in the rat. Moreover, the all-trans-retinoic acid detected in vivo could account for a significant fraction of the physiological activity of 13-cis-retinoic acid. The tissue disposition and metabolism of orally dosed 13-cis-[3H]retinoic acid are modulated by retinoid treatment. Chronic 13-cis-retinoic acid treatment apparently increased the intestinal accumulation of all-trans-retinoic acid, all-trans-retinoyl glucuronide, and 13-cis-retinoyl glucuronide. The liver concentrations of tritiated all-trans-retinoic acid and all-trans-retinoyl glucuronide were also elevated in 13-cis-retinoic acid treated rats.

A statistical model of diurnal variation in human growth hormone

NASA Technical Reports Server (NTRS)

Klerman, Elizabeth B.; Adler, Gail K.; Jin, Moonsoo; Maliszewski, Anne M.; Brown, Emery N.

2003-01-01

The diurnal pattern of growth hormone (GH) serum levels depends on the frequency and amplitude of GH secretory events, the kinetics of GH infusion into and clearance from the circulation, and the feedback of GH on its secretion. We present a two-dimensional linear differential equation model based on these physiological principles to describe GH diurnal patterns. The model characterizes the onset times of the secretory events, the secretory event amplitudes, as well as the infusion, clearance, and feedback half-lives of GH. We illustrate the model by using maximum likelihood methods to fit it to GH measurements collected in 12 normal, healthy women during 8 h of scheduled sleep and a 16-h circadian constant-routine protocol. We assess the importance of the model components by using parameter standard error estimates and Akaike's Information Criterion. During sleep, both the median infusion and clearance half-life estimates were 13.8 min, and the median number of secretory events was 2. During the constant routine, the median infusion half-life estimate was 12.6 min, the median clearance half-life estimate was 11.7 min, and the median number of secretory events was 5. The infusion and clearance half-life estimates and the number of secretory events are consistent with current published reports. Our model gave an excellent fit to each GH data series. Our analysis paradigm suggests an approach to decomposing GH diurnal patterns that can be used to characterize the physiological properties of this hormone under normal and pathological conditions.

Lack of Plasma Protein Hemopexin Results in Increased Duodenal Iron Uptake.

PubMed

Fiorito, Veronica; Geninatti Crich, Simonetta; Silengo, Lorenzo; Aime, Silvio; Altruda, Fiorella; Tolosano, Emanuela

2013-01-01

The body concentration of iron is regulated by a fine equilibrium between absorption and losses of iron. Iron can be absorbed from diet as inorganic iron or as heme. Hemopexin is an acute phase protein that limits iron access to microorganisms. Moreover, it is the plasma protein with the highest binding affinity for heme and thus it mediates heme-iron recycling. Considering its involvement in iron homeostasis, it was postulated that hemopexin may play a role in the physiological absorption of inorganic iron. Hemopexin-null mice showed elevated iron deposits in enterocytes, associated with higher duodenal H-Ferritin levels and a significant increase in duodenal expression and activity of heme oxygenase. The expression of heme-iron and inorganic iron transporters was normal. The rate of iron absorption was assessed by measuring the amount of (57)Fe retained in tissues from hemopexin-null and wild-type animals after administration of an oral dose of (57)FeSO4 or of (57)Fe-labelled heme. Higher iron retention in the duodenum of hemopexin-null mice was observed as compared with normal mice. Conversely, iron transfer from enterocytes to liver and bone marrow was unaffected in hemopexin-null mice. The increased iron level in hemopexin-null duodenum can be accounted for by an increased iron uptake by enterocytes and storage in ferritins. These data indicate that the lack of hemopexin under physiological conditions leads to an enhanced duodenal iron uptake thus providing new insights to our understanding of body iron homeostasis.

Real-time Continuous Assessment Method for Mental and Physiological Condition using Heart Rate Variability

NASA Astrophysics Data System (ADS)

Yoshida, Yutaka; Yokoyama, Kiyoko; Ishii, Naohiro

It is necessary to monitor the daily health condition for preventing stress syndrome. In this study, it was proposed the method assessing the mental and physiological condition, such as the work stress or the relaxation, using heart rate variability at real time and continuously. The instantanuous heart rate (HR), and the ratio of the number of extreme points (NEP) and the number of heart beats were calculated for assessing mental and physiological condition. In this method, 20 beats heart rate were used to calculate these indexes. These were calculated in one beat interval. Three conditions, which are sitting rest, performing mental arithmetic and watching relaxation movie, were assessed using our proposed algorithm. The assessment accuracies were 71.9% and 55.8%, when performing mental arithmetic and watching relaxation movie respectively. In this method, the mental and physiological condition was assessed using only 20 regressive heart beats, so this method is considered as the real time assessment method.

Decrease of cardiac chaos in congestive heart failure

NASA Astrophysics Data System (ADS)

Poon, Chi-Sang; Merrill, Christopher K.

1997-10-01

The electrical properties of the mammalian heart undergo many complex transitions in normal and diseased states. It has been proposed that the normal heartbeat may display complex nonlinear dynamics, including deterministic chaos,, and that such cardiac chaos may be a useful physiological marker for the diagnosis and management, of certain heart trouble. However, it is not clear whether the heartbeat series of healthy and diseased hearts are chaotic or stochastic, or whether cardiac chaos represents normal or abnormal behaviour. Here we have used a highly sensitive technique, which is robust to random noise, to detect chaos. We analysed the electrocardiograms from a group of healthy subjects and those with severe congestive heart failure (CHF), a clinical condition associated with a high risk of sudden death. The short-term variations of beat-to-beat interval exhibited strongly and consistently chaotic behaviour in all healthy subjects, but were frequently interrupted by periods of seemingly non-chaotic fluctuations in patients with CHF. Chaotic dynamics in the CHF data, even when discernible, exhibited a high degree of random variability over time, suggesting a weaker form of chaos. These findings suggest that cardiac chaos is prevalent in healthy heart, and a decrease in such chaos may be indicative of CHF.

Atomic force microscopy contact, tapping, and jumping modes for imaging biological samples in liquids

NASA Astrophysics Data System (ADS)

Moreno-Herrero, F.; Colchero, J.; Gómez-Herrero, J.; Baró, A. M.

2004-03-01

The capabilities of the atomic force microscope for imaging biomolecules under physiological conditions has been systematically investigated. Contact, dynamic, and jumping modes have been applied to four different biological systems: DNA, purple membrane, Alzheimer paired helical filaments, and the bacteriophage φ29. These samples have been selected to cover a wide variety of biological systems in terms of sizes and substrate contact area, which make them very appropriate for the type of comparative studies carried out in the present work. Although dynamic mode atomic force microscopy is clearly the best choice for imaging soft samples in air, in liquids there is not a leading technique. In liquids, the most appropriate imaging mode depends on the sample characteristics and preparation methods. Contact or dynamic modes are the best choices for imaging molecular assemblies arranged as crystals such as the purple membrane. In this case, the advantage of image acquisition speed predominates over the disadvantage of high lateral or normal force. For imaging individual macromolecules, which are weakly bonded to the substrate, lateral and normal forces are the relevant factors, and hence the jumping mode, an imaging mode which minimizes lateral and normal forces, is preferable to other imaging modes.

[Calcium and vitamin D in bone metabolism: Clinical importance for fracture treatment].

PubMed

Amling, M

2015-12-01

A balanced calcium homeostasis is of critical importance not only for bone remodeling, the physiological process of bone resorption and bone formation that constantly renews bone throughout life but also for normal fracture healing. Given that disturbances of calcium homeostasis are present in 50 % of the German population and that this might result in delayed fracture healing after correct surgical treatment, this paper focusses on calcium and vitamin D in the daily practice in orthopedics and trauma surgery. To ensure the required enteral calcium uptake the following three conditions are required: (1) sufficient calcium intake via the nutrition, (2) a 25-hydroxyvitamin D serum level > 30 µg/l and (3) the presence of sufficient gastric acidification. Given the endemic vitamin D deficiency in Germany as well as the constantly increasing number of people using proton pump inhibitors on a regular basis, it is necessary to closely connect trauma orthopedic surgery and osteological treatment. The first issue to be dealt with is to control and if needed normalize calcium homeostasis in order to allow a normal undisturbed fracture healing process after both conservative as well as operative treatment of fractures.

MicroRNA-200c: A Novel Way to Attack Breast Cancer Metastases by Restoring the Epithelial Phenotype

DTIC Science & Technology

2012-02-01

complex relationships and reveal the extent to whichmiRNAs are involved with SHRs in normal physiology and the pathobiology of steroid hormoneene regulation...proges- terone counteracts estrogen-mediated proliferation. To determine whethermiRNAs play a physiological role inmodulating hormonal control of gene...effect on uterine physiology to ate is the finding that P4/PGR affects uterine contractility during abor via regulation of ZEB1 and the miR-200 family

MELATONIN ENHANCES JUNCTIONAL TRANSFER IN NORMAL C3H/1OT1/2 CELLS

EPA Science Inventory

There is strong evidence that pineal melatonin is involved in controlling neoplastic processes. e have reported that physiological, but not pharmacological or subphysiological, concentrations of melatonin enhance intercellular communication in normal C3H/1OT1/2 fibroblasts. ap ju...

A closed-loop hybrid physiological model relating to subjects under physical stress.

PubMed

El-Samahy, Emad; Mahfouf, Mahdi; Linkens, Derek A

2006-11-01

The objective of this research study is to derive a comprehensive physiological model relating to subjects under physical stress conditions. The model should describe the behaviour of the cardiovascular system, respiratory system, thermoregulation and brain activity in response to physical workload. An experimental testing rig was built which consists of recumbent high performance bicycle for inducing the physical load and a data acquisition system comprising monitors and PCs. The signals acquired and used within this study are the blood pressure, heart rate, respiration, body temperature, and EEG signals. The proposed model is based on a grey-box based modelling approach which was used because of the sufficient level of details it provides. Cardiovascular and EEG Data relating to 16 healthy subject volunteers (data from 12 subjects were used for training/validation and the data from 4 subjects were used for model testing) were collected using the Finapres and the ProComp+ monitors. For model validation, residual analysis via the computing of the confidence intervals as well as related histograms was performed. Closed-loop simulations for different subjects showed that the model can provide reliable predictions for heart rate, blood pressure, body temperature, respiration, and the EEG signals. These findings were also reinforced by the residual analyses data obtained, which suggested that the residuals were within the 90% confidence bands and that the corresponding histograms were of a normal distribution. A higher intelligent level was added to the model, based on neural networks, to extend the capabilities of the model to predict over a wide range of subjects dynamics. The elicited physiological model describing the effect of physiological stress on several physiological variables can be used to predict performance breakdown of operators in critical environments. Such a model architecture lends itself naturally to exploitation via feedback control in a 'reverse-engineering' fashion to control stress via the specification of a safe operating range for the psycho-physiological variables.

Negative Emotions Predict Elevated Interleukin-6 in the United States but not in Japan

PubMed Central

Miyamoto, Yuri; Boylan, Jennifer Morozink; Coe, Christopher L.; Curhan, Katherine B.; Levine, Cynthia S.; Markus, Hazel Rose; Park, Jiyoung; Kitayama, Shinobu; Kawakami, Norito; Karasawa, Mayumi; Love, Gayle D.; Ryff, Carol D.

2013-01-01

Previous studies conducted in Western cultures have shown that negative emotions predict higher levels of pro-inflammatory biomarkers, specifically interleukin-6 (IL-6). This link between negative emotions and IL-6 may be specific to Western cultures where negative emotions are perceived to be problematic and thus may not extend to Eastern cultures where negative emotions are seen as acceptable and normal. Using samples of 1044 American and 382 Japanese middle-aged and older adults, we investigated whether the relationship between negative emotions and IL-6 varies by cultural context. Negative emotions predicted higher IL-6 among American adults, whereas no association was evident among Japanese adults. Furthermore, the interaction between culture and negative emotions remained even after controlling for demographic variables, psychological factors (positive emotions, neuroticism, extraversion), health behaviors (smoking status, alcohol consumption), and health status (chronic conditions, BMI). These findings highlight the role of cultural context in shaping how negative emotions affect inflammatory physiology and underscore the importance of cultural ideas and practices relevant to negative emotions for understanding of the interplay between psychology, physiology, and health. PMID:23911591

How does healthy aging impact on the circadian clock?

PubMed

Popa-Wagner, Aurel; Buga, Ana-Maria; Dumitrascu, Dinu Iuliu; Uzoni, Adriana; Thome, Johannes; Coogan, Andrew N

2017-02-01

Circadian rhythms are recurring patterns in a host of physiological and other parameters that recur with periods of near 24 h. These rhythms reflect the temporal organization of an organism's homeostatic control systems and as such are key processes in ensuring optimal physiological performance. Dysfunction of circadian processes is linked with adverse health conditions. In this review we highlight the evidence that normal, healthy aging is associated with changes in the circadian system; we examine the molecular mechanisms through which such changes may arise, discuss whether more robust circadian function is a predictor of longevity and highlight the role of circadian rhythms in age-related diseases. Overall, the literature shows that aging is associated with marked changes in circadian processes, both at the behavioral and molecular levels, and the molecular mechanisms through which such changes arise remain to be elucidated, but may involve inflammatory process, redox homeostasis and epigenetic modifications. Understanding the nature of age-related circadian dysfunction will allow for the design of chronotherapeutic intervention strategies to attenuate circadian dysfunction and thus improve health and quality of life.

[Development of a glaucoma microstent with drainage into the suprachoroidal space: fluid mechanical model approach].

PubMed

Guthoff, R F; Schmidt, W; Buss, D; Schultze, C; Ruppin, U; Stachs, O; Sternberg, K; Klee, D; Chichkov, B; Schmitz, K-P

2009-09-01

The purpose of this study was to develop a microstent with valve function, which normalizes the intraocular pressure (IOP) and drains into the suprachoroidal space. In comparison to the subconjunctival space the suprachoroidal space is attributed with less fibroblast colonization and activity. Different glaucoma drainage devices were idealized as tubes and the flow rates were calculated according to Hagen-Poiseuille. The dimensions of the ideal glaucoma implant were modified with respect to an aqueous humor production of 2 microl/min and the different outflow pathways. Specific components of glaucoma drainage devices at the inlet and outlet were not included. The volume flow calculation of the tested glaucoma implants showed that the dimensions of all lumina were too large to prevent postoperative hypotension. A maximum inner tube diameter of 53 microm was calculated for drainage into the suprachoroidal space based on an intra-ocular pressure (IOP) of 20 mmHg. The glaucoma microstent has to guarantee an aqueous humor flow for physiological IOP. An increase of IOP has to be regulated to physiological pressure conditions by the microvalve.

Theoretical study on the constricted flow phenomena in arteries

NASA Astrophysics Data System (ADS)

Sen, S.; Chakravarty, S.

2012-12-01

The present study is dealt with the constricted flow characteristics of blood in arteries by making use of an appropriate mathematical model. The constricted artery experiences the generated wall shear stress due to flow disturbances in the presence of constriction. The disturbed flow in the stenosed arterial segment causes malfunction of the cardiovascular system leading to serious health problems in the form of heart attack and stroke. The flowing blood contained in the stenosed artery is considered to be non-Newtonian while the flow is treated to be two-dimensional. The present pursuit also accounts for the motion of the arterial wall and its effect on local fluid mechanics. The flow analysis applies the time-dependent, two-dimensional incompressible nonlinear Navier-Stokes equations for non-Newtonian fluid representing blood. An extensive quantitative analysis presented at the end of the paper based on large scale numerical computations of the quantities of major physiological significance enables one to estimate the constricted flow characteristics in the arterial system under consideration which deviates significantly from that of normal physiological flow conditions.

miRNA as a New Regulatory Mechanism of Estrogen Vascular Action.

PubMed

Pérez-Cremades, Daniel; Mompeón, Ana; Vidal-Gómez, Xavier; Hermenegildo, Carlos; Novella, Susana

2018-02-06

The beneficial effects of estrogen on the cardiovascular system have been reported extensively. In fact, the incidence of cardiovascular diseases in women is lower than in age-matched men during their fertile stage of life, a benefit that disappears after menopause. These sex-related differences point to sexual hormones, mainly estrogen, as possible cardiovascular protective factors. The regulation of vascular function by estrogen is mainly related to the maintenance of normal endothelial function and is mediated by both direct and indirect gene transcription through the activity of specific estrogen receptors. Some of these mechanisms are known, but many remain to be elucidated. In recent years, microRNAs have been established as non-coding RNAs that regulate the expression of a high percentage of protein-coding genes in mammals and are related to the correct function of human physiology. Moreover, within the cardiovascular system, miRNAs have been related to physiological and pathological conditions. In this review, we address what is known about the role of estrogen-regulated miRNAs and their emerging involvement in vascular biology.

Sublethal landrin toxicity: Behavioral and physiological effects on captive vultures

USGS Publications Warehouse

Forthman-Quick, D.L.; Hill, E.F.

1988-01-01

Use of conditioned taste aversion (CTA) has been proposed to reduce consumption of California condor (Gymnogyps californianus) eggs by ravens (Corvus corax). Although landrin has induced aversions in ravens and other birds, no data were available on behavioral and physiological effects of landrin on condors, non-target birds that might consume treated eggs. Because condors are endangered, we selected taxonomically related surrogates to approximate the effects on condors of acute oral doses of landrin. Seven black vultures (Coragyps atratus), 2 turkey vultures (Cathartes aura), and 2 king vultures (Sarcoramphus papa) received landrin and placebo treatments 1 week apart. Plasma cholinesterase (ChE) activity was monitored at zero, 3, and 24 hours posttreatment, and behavioral observations were made for 2 hours posttreatment. The doses tested were nonlethal, and ChE levels approached normal within 24 hours after treatment. Only the frequency of vomiting differed statistically between the placebo and landrin treatment. We conclude that with appropriate precautions, landrin can be used in applications of CTA to discourage consumption of condor eggs by ravens, while posing no apparent risk to reintroduced condors.

Roles of amino acids in preventing and treating intestinal diseases: recent studies with pig models.

PubMed

Liu, Yulan; Wang, Xiuying; Hou, Yongqing; Yin, Yulong; Qiu, Yinsheng; Wu, Guoyao; Hu, Chien-An Andy

2017-08-01

Animal models are needed to study and understand a human complex disease. Because of their similarities in anatomy, structure, physiology, and pathophysiology, the pig has proven its usefulness in studying human gastrointestinal diseases, such as inflammatory bowel disease, ischemia/reperfusion injury, diarrhea, and cancer. To understand the pathogenesis of these diseases, a number of experimental models generated in pigs are available, for example, through surgical manipulation, chemical induction, microbial infection, and genetic engineering. Our interests have been using amino acids as therapeutics in pig and human disease models. Amino acids not only play an important role in protein biosynthesis, but also exert significant physiological effects in regulating immunity, anti-oxidation, redox regulation, energy metabolism, signal transduction, and animal behavior. Recent studies in pigs have shown that specific dietary amino acids can improve intestinal integrity and function under normal and pathological conditions that protect the host from different diseases. In this review, we summarize several pig models in intestinal diseases and how amino acids can be used as therapeutics in treating pig and human diseases.

Anthropogenic pollutants: a threat to ecosystem sustainability?

PubMed

Rhind, S M

2009-11-27

Pollutants, including synthetic organic materials and heavy metals, are known to adversely affect physiological systems in all animal species studied to date. While many individual chemicals can perturb normal functions, the combined actions of multiple pollutants are of particular concern because they can exert effects even when each individual chemical is present at concentrations too low to be individually effective. The biological effects of pollutants differ greatly between species reflecting differences in the pattern of exposure, routes of uptake, metabolism following uptake, rates of accumulation and sensitivity of the target organs. Thus, understanding of the effects of pollutants on wildlife and ecosystems will require detailed study of many different species, representing a wide range of taxa. However, such studies can be informed by knowledge obtained in more controlled conditions which may indicate likely mechanisms of action and suitable endpoint measurements. Responses may be exacerbated by interactions between the effects of pollutants and environmental stressors, such as under-nutrition or osmotic stresses and so changes in such variables associated with climatic changes may exacerbate physiological responses to pollutant burdens.

Recovery of rat alveolar macrophages by bronchoalveolar lavage under normal and activated conditions.

PubMed Central

Rehn, B; Bruch, J; Zou, T; Hobusch, G

1992-01-01

When rat (female Wistar) lungs were lavaged (bronchoalveolar lavage, BAL) six times with physiological saline, approximately the same number of alveolar macrophages (AM) were found in the first and second BAL, whereas in the third fourth, fifth, and sixth BAL, the number of AM decreased exponentially. Morphometric counting of the number of AM in histological sections of lung tissue showed that only 14% of the AM population had been recovered by BAL. Although additives to the BAL fluid such as lidocaine and/or fetal calf serum increased the AM count in the first washing considerably, the total number of AM washed out remained unaltered. Addition of the phagocytosis stimulant zymosan increased the AM count in BAL by a factor of more than 2. On stimulation of the lungs with an inert dust (silicon carbide), the AM count in the BAL and the lung was only slightly increased 8 weeks after intratracheal instillation. In contrast, after exposure to fibrogenic and cytotoxic quartz, the AM count in BAL and lung was significantly increased, and the recovery of AM had also increased by a factor of approximately 2. The experiments show that it is the micromilieu of the alveoli and the condition of the AM (certain physiological activation states, such as phagocytic activity) that essentially determine the degree of recovery. PMID:1396444

Partial gravity reaction experiment sysytem on graund using multi-Copter

NASA Astrophysics Data System (ADS)

Hasegawa, Katsuya; Maeda, Naoko

2016-07-01

In order to enable further space exploration into the space, Moon, Mars, and other planets, it is essential to understand the physiological response to low gravity environments. However, We made low gravity environment for studies using the satellite parabolic flight and drop tower. It is very expensive experiment that low gravity physiological response. Because, it requires rockets and airplanes and dedicated Tower, low gravity conditions test have not been conducted sufficiently due to the extraordinary high cost for conducting experiments. The study present is to develop the radio-controlled multicopter system that is used for the controlled falling flight vehicle (not free fall). During the controlled falling, the payload is exposed to a certain level of low gravity. 1) G profile: low gravity from 0 g to 1 g that will last approximately 5seconds, 50 kg. 2) Supply limited imaging techniques, high-speed or normal video and X ray images. 3) Wireless transmission of up to 64 channels of analog and digital signals. This vehicle is designed for experimentation on various model organisms, from cells to animals and plants. The multicopter flight system enables conducting experiments in low gravity conditions with less than 1% of the budget for spaceflight or parabolic flights. Experiment is possible to perform repeated many times in one day. We can expect reproducible results from many repeated trials at the lowest cost.

Exosomes: From Garbage Bins to Promising Therapeutic Targets

PubMed Central

H. Rashed, Mohammed; Bayraktar, Emine; K. Helal, Gouda; Abd-Ellah, Mohamed F.; Amero, Paola; Chavez-Reyes, Arturo; Rodriguez-Aguayo, Cristian

2017-01-01

Intercellular communication via cell-released vesicles is a very important process for both normal and tumor cells. Cell communication may involve exosomes, small vesicles of endocytic origin that are released by all types of cells and are found in abundance in body fluids, including blood, saliva, urine, and breast milk. Exosomes have been shown to carry lipids, proteins, mRNAs, non-coding RNAs, and even DNA out of cells. They are more than simply molecular garbage bins, however, in that the molecules they carry can be taken up by other cells. Thus, exosomes transfer biological information to neighboring cells and through this cell-to-cell communication are involved not only in physiological functions such as cell-to-cell communication, but also in the pathogenesis of some diseases, including tumors and neurodegenerative conditions. Our increasing understanding of why cells release exosomes and their role in intercellular communication has revealed the very complex and sophisticated contribution of exosomes to health and disease. The aim of this review is to reveal the emerging roles of exosomes in normal and pathological conditions and describe the controversial biological role of exosomes, as it is now understood, in carcinogenesis. We also summarize what is known about exosome biogenesis, composition, functions, and pathways and discuss the potential clinical applications of exosomes, especially as biomarkers and novel therapeutic agents. PMID:28257101

Physiological state influences evaporative water loss and microclimate preference in the snake Vipera aspis.

PubMed

Dupoué, Andréaz; Stahlschmidt, Zachary R; Michaud, Bruno; Lourdais, Olivier

2015-05-15

Animals typically respond to environmental variation by adjusting their physiology, behavior, or both. Ectothermic animals are particularly sensitive to microclimatic conditions and behaviorally thermoregulate to optimize physiological performance. Yet, thermoregulation can be costly and may obligate a physiological tradeoff with water loss. Presumably, this tradeoff intensifies when animals undergo necessary life-history events (e.g., pregnancy or digestion) that impose significant behavioral and physiological changes, including shifts in behavioral thermoregulation and increased metabolic rate. Thus, behavioral responses, such as modified microclimatic preferences, may help mitigate the physiological tradeoff between thermoregulation and water loss. Herein, we examined the influence of major physiological states (specifically, pregnancy, ecdysis, and digestion) on evaporative water loss and on behavioral adjustments in a viviparous snake, Vipera aspis. First, we used open-flow respirometry to measure the effects of physiological states and microclimatic conditions (temperature and humidity) on the rate of total evaporative water loss (TEWL) and metabolic rate (rate of O2 consumption, V˙O2). Then, we experimentally tested the influence of physiological state on microclimate selection. We found that energy-demanding physiological states were associated with i) an increased rate of TEWL and V˙O2 compared to control states and ii) a slight preference (statistically marginal) for both warm and humid conditions compared to controls, suggesting a state-specificity in behavioral response. Overall our results underline the impact of physiological state on water loss and demonstrate the potential for behavior to mitigate the physiological tradeoff between thermoregulation and water balance. Copyright © 2015 Elsevier Inc. All rights reserved.

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

Assessing the Effectiveness of Neurofeedback Training in the Context of Clinical and Social Neuroscience

PubMed Central

Orndorff-Plunkett, Franklin; Singh, Fiza

2017-01-01

Social neuroscience benefits from the experimental manipulation of neuronal activity. One possible manipulation, neurofeedback, is an operant conditioning-based technique in which individuals sense, interact with, and manage their own physiological and mental states. Neurofeedback has been applied to a wide variety of psychiatric illnesses, as well as to treat sub-clinical symptoms, and even to enhance performance in healthy populations. Despite growing interest, there persists a level of distrust and/or bias in the medical and research communities in the USA toward neurofeedback and other functional interventions. As a result, neurofeedback has been largely ignored, or disregarded within social neuroscience. We propose a systematic, empirically-based approach for assessing the effectiveness, and utility of neurofeedback. To that end, we use the term perturbative physiologic plasticity to suggest that biological systems function as an integrated whole that can be perturbed and guided, either directly or indirectly, into different physiological states. When the intention is to normalize the system, e.g., via neurofeedback, we describe it as self-directed neuroplasticity, whose outcome is persistent functional, structural, and behavioral changes. We argue that changes in physiological, neuropsychological, behavioral, interpersonal, and societal functioning following neurofeedback can serve as objective indices and as the metrics necessary for assessing levels of efficacy. In this chapter, we examine the effects of neurofeedback on functional connectivity in a few clinical disorders as case studies for this approach. We believe this broader perspective will open new avenues of investigation, especially within social neuroscience, to further elucidate the mechanisms and effectiveness of these types of interventions, and their relevance to basic research. PMID:28783134

BRAIN REGENERATION IN PHYSIOLOGY AND PATHOLOGY: THE IMMUNE SIGNATURE DRIVING THERAPEUTIC PLASTICITY OF NEURAL STEM CELLS

PubMed Central

Martino, Gianvito; Pluchino, Stefano; Bonfanti, Luca; Schwartz, Michal

2013-01-01

Regenerative processes occurring under physiological (maintenance) and pathological (reparative) conditions are a fundamental part of life and vary greatly among different species, individuals, and tissues. Physiological regeneration occurs naturally as a consequence of normal cell erosion, or as an inevitable outcome of any biological process aiming at the restoration of homeostasis. Reparative regeneration occurs as a consequence of tissue damage. Although the central nervous system (CNS) has been considered for years as a “perennial” tissue, it has recently become clear that both physiological and reparative regeneration occur also within the CNS to sustain tissue homeostasis and repair. Proliferation and differentiation of neural stem/progenitor cells (NPCs) residing within the healthy CNS, or surviving injury, are considered crucial in sustaining these processes. Thus a large number of experimental stem cell-based transplantation systems for CNS repair have recently been established. The results suggest that transplanted NPCs promote tissue repair not only via cell replacement but also through their local contribution to changes in the diseased tissue milieu. This review focuses on the remarkable plasticity of endogenous and exogenous (transplanted) NPCs in promoting repair. Special attention will be given to the cross-talk existing between NPCs and CNS-resident microglia as well as CNS-infiltrating immune cells from the circulation, as a crucial event sustaining NPC-mediated neuroprotection. Finally, we will propose the concept of the context-dependent potency of transplanted NPCs (therapeutic plasticity) to exert multiple therapeutic actions, such as cell replacement, neurotrophic support, and immunomodulation, in CNS repair. PMID:22013212

Growth responses and ion accumulation in the halophytic legume Prosopis strombulifera are determined by Na2SO4 and NaCl.

PubMed

Reginato, M; Sosa, L; Llanes, A; Hampp, E; Vettorazzi, N; Reinoso, H; Luna, V

2014-01-01

Halophytes are potential gene sources for genetic manipulation of economically important crop species. This study addresses the physiological responses of a widespread halophyte, Prosopis strombulifera (Lam.) Benth to salinity. We hypothesised that increasing concentrations of the two major salts present in soils of central Argentina (Na2SO4, NaCl, or their iso-osmotic mixture) would produce distinct physiological responses. We used hydroponically grown P. strombulifera to test this hypothesis, analysing growth parameters, water relations, photosynthetic pigments, cations and anions. These plants showed a halophytic response to NaCl, but strong general inhibition of growth in response to iso-osmotic solutions containing Na2SO4. The explanation for the adaptive success of P. strombulifera in high NaCl conditions seems to be related to a delicate balance between Na(+) accumulation (and its use for osmotic adjustment) and efficient compartmentalisation in vacuoles, the ability of the whole plant to ensure sufficient K(+) supply by maintaining high K(+)/Na(+) discrimination, and maintenance of normal Ca(2+) levels in leaves. The three salt treatments had different effects on the accumulation of ions. Findings in bi-saline-treated plants were of particular interest, where most of the physiological parameters studied showed partial alleviation of SO4(2-)-induced toxicity by Cl(-). Thus, discussions on physiological responses to salinity could be further expanded in a way that more closely mimics natural salt environments. © 2013 German Botanical Society and The Royal Botanical Society of the Netherlands.

Sensing of triacylglycerol in the gut: different mechanisms for fatty acids and 2-monoacylglycerol.

PubMed

Kleberg, Karen; Jacobsen, Anne Katrine; Ferreira, Jozelia G; Windeløv, Johanne Agerlin; Rehfeld, Jens F; Holst, Jens Juul; de Araujo, Ivan E; Hansen, Harald S

2015-04-15

Sensing of dietary triacylglycerol in the proximal small intestine results in physiological, hormonal and behavioural responses. However, the exact physiological pathways linking intestinal fat sensing to food intake and the activation of brain circuits remain to be identified. In this study we examined the role of triacylglycerol digestion for intestinal fat sensing, and compared the effects of the triacylglycerol digestion products, fatty acids and 2-monoacylglycerol, on behavioural, hormonal and dopaminergic responses in behaving mice. Using an operant task in which mice are trained to self-administer lipid emulsions directly into the stomach, we show that inhibiting triacylglycerol digestion disrupts normal behaviour of self-administration in mice, indicating that fat sensing is conditional to digestion. When administered separately, both digestion products, 2-monoacylglycerol and fatty acids, were sensed by the mice, and self-administration patterns of fatty acids were affected by the fatty acid chain length. Peripheral plasma concentrations of the gut hormones GLP-1, GIP, PYY, CCK and insulin did not offer an explanation of the differing behavioural effects produced by 2-monoacylglycerol and fatty acids. However, combined with behavioural responses, striatal dopamine effluxes induced by gut infusions of oleic acid were significantly greater than those produced by equivalent infusions of 2-oleoylglycerol. Our data demonstrate recruitment of different signalling pathways by fatty acids and 2-monoacylglycerol, and suggest that the structural properties of fat rather than total caloric value determine intestinal sensing and the assignment of reward value to lipids. © 2015 The Authors. The Journal of Physiology © 2015 The Physiological Society.

Motivational intensity modulates the effects of positive emotions on set shifting after controlling physiological arousal.

PubMed

Zhou, Ya; Siu, Angela F Y

2015-12-01

Recent research on the construct of emotion suggests the integration of a motivational dimension into the traditional two-dimension (subjective valence and physiological arousal) model. The motivational intensity of an emotional state should be taken into account while investigating the emotion-cognition relationship. This study examined how positive emotional states varying in motivational intensity influenced set shifting, after controlling the potential confounding impacts of physiological arousal. In Experiment 1, 155 volunteers performed a set-shifting task after being randomly assigned to five states: high- vs. low-motivating positive affect (interest vs. serenity), high- vs. low-motivating negative affect (disgust vs. anxiety), and neutral state. Eighty-five volunteers participated in Experiment 2, which further examined the effects of higher vs. lower degree of interest. Both experiments measured and compared participants' physiological arousal (blood pressure and pulse rate) under the normal and experimental conditions as the covariate. Results showed no difference in switching performance between the neutral and serenity groups. As compared with the neutral state, the high-motivating positive affect significantly increased set-switching reaction time costs, but reduced error rate costs; the higher the motivational intensity, the greater the time-costs impairment. This indicates a role of the high-motivating positive affect in regulating the balance between the flexible and stable cognitive control. Motivational intensity also modulated the effects of negative emotional states, i.e., disgust caused a larger increase in time costs than anxiety. Further exploration into neurobiological mechanisms that may mediate the emotional effects on set shifting is warranted. © 2015 Scandinavian Psychological Associations and John Wiley & Sons Ltd.

Assessing the Effectiveness of Neurofeedback Training in the Context of Clinical and Social Neuroscience.

PubMed

Orndorff-Plunkett, Franklin; Singh, Fiza; Aragón, Oriana R; Pineda, Jaime A

2017-08-07

Social neuroscience benefits from the experimental manipulation of neuronal activity. One possible manipulation, neurofeedback, is an operant conditioning-based technique in which individuals sense, interact with, and manage their own physiological and mental states. Neurofeedback has been applied to a wide variety of psychiatric illnesses, as well as to treat sub-clinical symptoms, and even to enhance performance in healthy populations. Despite growing interest, there persists a level of distrust and/or bias in the medical and research communities in the USA toward neurofeedback and other functional interventions. As a result, neurofeedback has been largely ignored, or disregarded within social neuroscience. We propose a systematic, empirically-based approach for assessing the effectiveness, and utility of neurofeedback. To that end, we use the term perturbative physiologic plasticity to suggest that biological systems function as an integrated whole that can be perturbed and guided, either directly or indirectly, into different physiological states. When the intention is to normalize the system, e.g., via neurofeedback, we describe it as self-directed neuroplasticity, whose outcome is persistent functional, structural, and behavioral changes. We argue that changes in physiological, neuropsychological, behavioral, interpersonal, and societal functioning following neurofeedback can serve as objective indices and as the metrics necessary for assessing levels of efficacy. In this chapter, we examine the effects of neurofeedback on functional connectivity in a few clinical disorders as case studies for this approach. We believe this broader perspective will open new avenues of investigation, especially within social neuroscience, to further elucidate the mechanisms and effectiveness of these types of interventions, and their relevance to basic research.

Male hypogonadism: an extended classification based on a developmental, endocrine physiology-based approach.

PubMed

Rey, R A; Grinspon, R P; Gottlieb, S; Pasqualini, T; Knoblovits, P; Aszpis, S; Pacenza, N; Stewart Usher, J; Bergadá, I; Campo, S M

2013-01-01

Normal testicular physiology results from the integrated function of the tubular and interstitial compartments. Serum markers of interstitial tissue function are testosterone and insulin-like factor 3 (INSL3), whereas tubular function can be assessed by sperm count, morphology and motility, and serum anti-Müllerian hormone (AMH) and inhibin B. The classical definition of male hypogonadism refers to testicular failure associated with androgen deficiency, without considering potential deficiencies in germ and Sertoli cells. Furthermore, the classical definition does not consider the fact that low basal serum testosterone cannot be equated to hypogonadism in childhood, because Leydig cells are normally quiescent. A broader clinical definition of hypogonadism that could be applied to male patients in different periods of life requires a comprehensive consideration of the physiology of the hypothalamic-pituitary-testicular axis and its disturbances along development. Here we propose an extended classification of male hypogonadism based on the pathophysiology of the hypothalamic-pituitary-testicular axis in different periods of life. The clinical and biochemical features of male hypogonadism vary according to the following: (i) the level of the hypothalamic-pituitary-testicular axis primarily affected: central, primary or combined; (ii) the testicular cell population initially impaired: whole testis dysfunction or dissociated testicular dysfunction, and: (iii) the period of life when the gonadal function begins to fail: foetal-onset or postnatal-onset. The evaluation of basal testicular function in infancy and childhood relies mainly on the assessment of Sertoli cell markers (AMH and inhibin B). Hypergonadotropism should not be considered a sine qua non condition for the diagnosis of primary hypogonadism in childhood. Finally, the lack of elevation of gonadotropins in adolescents or adults with primary gonadal failure is indicative of a combined hypogonadism involving the gonads and the hypothalamic-pituitary axis. © 2012 American Society of Andrology and European Academy of Andrology.

Interleukin-7 Plasma Levels in Human Differentiate Anorexia Nervosa, Constitutional Thinness and Healthy Obesity.

PubMed

Germain, Natacha; Viltart, Odile; Loyens, Anne; Bruchet, Céline; Nadin, Katia; Wolowczuk, Isabelle; Estour, Bruno; Galusca, Bogdan

2016-01-01

Interleukin-7 (IL-7) is a cytokine involved in energy homeostasis as demonstrated in rodents. Anorexia nervosa is characterized by restrained eating behavior despite adaptive orexigenic regulation profile including high ghrelin plasma levels. Constitutional thinness is a physiological condition of resistance to weight gain with physiological anorexigenic profile including high Peptide YY plasma level. Healthy obesity can be considered as a physiological state of resistance to weight loss with opposite appetite regulating profile to constitutional thinness including low Peptide YY plasma level. No studies in IL-7 are yet available in those populations. Therefore we evaluated circadian plasma levels of IL-7 in anorexia nervosa compared to constitutional thinness, healthy obese and control females. 10 restrictive-type anorexia nervosa women, 5 bingeing/purging anorexia nervosa woman, 5 recovered restrictive anorexia nervosa women, 4 bulimic females, 10 constitutional thinness women, 7 healthy obese females, and 10 normal weight women controls were enrolled in this cross-sectional study, performed in endocrinology unit and academic laboratory. Twelve-point circadian profiles of plasma IL-7 levels were measured in each subject. 24h mean IL-7 plasma levels (pg/ml, mean±SEM) were decreased in restrictive-type anorexia nervosa (123.4±14.4, p<0.0037), bingeing/purging anorexia nervosa (24.2±5.6, p<0.001), recovered restrictive anorexia nervosa (64.2±16.1, p = 0.01) and healthy obese patients (51±3.2, p<0.001) compared to controls (187.7±28.6). Bulimic patients (197.4±42.7) and constitutional thinness patients (264.3±35.8) were similar to controls. Low IL-7 is part of the adaptive profile in restrictive-type anorexia nervosa, confirming its difference with constitutional thinness. Healthy obesity, with low IL-7, is once again in mirror image of constitutional thinness with normal high IL-7.

Metabolic rates and biochemical compositions of Apostichopus japonicus (Selenka) tissue during periods of inactivity

NASA Astrophysics Data System (ADS)

Bao, Jie; Dong, Shuanglin; Tian, Xiangli; Wang, Fang; Gao, Qinfeng; Dong, Yunwei

2010-03-01

Estivation, hibernation, and starvation are indispensable inactive states of sea cucumbers Apostichopus japonicus in nature and in culture ponds. Generally, temperature is the principal factor that induces estivation or hibernation in the sea cucumber. The present study provided insight into the physiological adaptations of A. japonicus during the three types of inactivity (hibernation, estivation, and starvation) by measuring the oxygen consumption rates ( Vo2) and biochemical compositions under laboratory conditions of low (3°C), normal (17°C) and high (24°C) temperature. The results show that the characteristics of A. japonicus in dormancy (hibernation and estivation) states were quite different from higher animals, such as fishes, amphibians, reptiles, and mammals, but more closely resembled a semi-dormant state. It was observed that the shift in the A. japonicus physiological state from normal to dormancy was a chronic rather than acute process, indicated by the gradual depression of metabolic rate. While metabolic rates declined 44.9% for the estivation group and 71.7% for the hibernation group, relative to initial rates, during the 36 d culture period, metabolic rates were not maintained at constant levels during these states. The metabolic depression processes for sea cucumbers in hibernation and estivation appeared to be a passive and an active metabolic suppression, respectively. In contrast, the metabolic rates (128.90±11.70 μg/g h) of estivating sea cucumbers were notably higher (107.85±6.31 μg/g h) than in starving sea cucumbers at 17°C, which indicated that the dormancy mechanism here, as a physiological inhibition, was not as efficient as in higher animals. Finally, the principle metabolic substrate or energy source of sea cucumbers in hibernation was lipid, whereas in estivation they mainly consumed protein in the early times and both protein and lipid thereafter.

A Method of High Throughput Monitoring Crop Physiology Using Chlorophyll Fluorescence and Multispectral Imaging.

PubMed

Wang, Heng; Qian, Xiangjie; Zhang, Lan; Xu, Sailong; Li, Haifeng; Xia, Xiaojian; Dai, Liankui; Xu, Liang; Yu, Jingquan; Liu, Xu

2018-01-01

We present a high throughput crop physiology condition monitoring system and corresponding monitoring method. The monitoring system can perform large-area chlorophyll fluorescence imaging and multispectral imaging. The monitoring method can determine the crop current condition continuously and non-destructively. We choose chlorophyll fluorescence parameters and relative reflectance of multispectral as the indicators of crop physiological status. Using tomato as experiment subject, the typical crop physiological stress, such as drought, nutrition deficiency and plant disease can be distinguished by the monitoring method. Furthermore, we have studied the correlation between the physiological indicators and the degree of stress. Besides realizing the continuous monitoring of crop physiology, the monitoring system and method provide the possibility of machine automatic diagnosis of the plant physiology. Highlights: A newly designed high throughput crop physiology monitoring system and the corresponding monitoring method are described in this study. Different types of stress can induce distinct fluorescence and spectral characteristics, which can be used to evaluate the physiological status of plants.

Psychophysiological investigation of vigilance decrement: boredom or cognitive fatigue?

PubMed

Pattyn, Nathalie; Neyt, Xavier; Henderickx, David; Soetens, Eric

2008-01-28

The vigilance decrement has been described as a slowing in reaction times or an increase in error rates as an effect of time-on-task during tedious monitoring tasks. This decrement has been alternatively ascribed to either withdrawal of the supervisory attentional system, due to underarousal caused by the insufficient workload, or to a decreased attentional capacity and thus the impossibility to sustain mental effort. Furthermore, it has previously been reported that controlled processing is the locus of the vigilance decrement. This study aimed at answering three questions, to better define sustained attention. First, is endogenous attention more vulnerable to time-on-task than exogenous attention? Second, do measures of autonomic arousal provide evidence to support the underload vs overload hypothesis? And third, do these measures show a different effect for endogenous and exogenous attention? We applied a cued (valid vs invalid) conjunction search task, and ECG and respiration recordings were used to compute sympathetic (normalized low frequency power) and parasympathetic tone (respiratory sinus arrhythmia, RSA). Behavioural results showed a dual effect of time-on-task: the usually described vigilance decrement, expressed as increased reaction times (RTs) after 30 min for both conditions; and a higher cost in RTs after invalid cues for the endogenous condition only, appearing after 60 min. Physiological results clearly support the underload hypothesis to subtend the vigilance decrement, since heart period and RSA increased over time-on-task. There was no physiological difference between the endogenous and exogenous conditions. Subjective experience of participants was more compatible with boredom than with high mental effort.

Leptin and reproduction: a review.

PubMed

Moschos, Stergios; Chan, Jean L; Mantzoros, Christos S

2002-03-01

To review recent advances in understanding the role of leptin in the physiology and pathophysiology of reproduction, with a focus on relevant clinical situations. A MEDLINE computer search was performed to identify relevant articles. Leptin, an adipocyte hormone important in regulating energy homeostasis, interacts with the reproductive axis at multiple sites, with stimulatory effects at the hypothalamus and pituitary and inhibitory actions at the gonads. More recently, leptin has been shown to play a role in other target reproductive organs, such as the endometrium, placenta, and mammary gland, with corresponding influences on important physiologic processes such as menstruation, pregnancy, and lactation. As a marker of whether nutritional stores are adequate, leptin may act in concert with gonadotropins and the growth hormone axis to initiate the complex process of puberty. Conditions in which nutritional status is suboptimal, such as eating disorders, exercise-induced amenorrhea, and functional hypothalamic amenorrhea, are associated with low serum leptin levels; and conditions with excess energy stores or metabolic disturbances, such as obesity and polycystic ovarian syndrome, often have elevated serum or follicular fluid leptin levels, raising the possibility that relative leptin deficiency or resistance may be at least partly responsible for the reproductive abnormalities that occur with these conditions. Leptin may act as the critical link between adipose tissue and the reproductive system, indicating whether adequate energy reserves are present for normal reproductive function. Future interventional studies involving leptin administration are expected to further clarify this role of leptin and may provide new therapeutic options for the reproductive dysfunction associated with states of relative leptin deficiency or resistance.

Mathematical model of renal elimination of fluid and small ions during hyper- and hypovolemic conditions.

PubMed

Gyenge, Christina C; Bowen, Bruce D; Reed, Rolf K; Bert, Joel L

2003-02-01

This study is concerned with the formulation of a 'kidney module' linked to the plasma compartment of a larger mathematical model previously developed. Combined, these models can be used to predict, amongst other things, fluid and small ion excretion rates by the kidney; information that should prove useful in evaluating values and trends related to whole-body fluid balance for different clinical conditions to establish fluid administration protocols and for educational purposes. The renal module assumes first-order, negative-feedback responses of the kidney to changes in plasma volume and/or plasma sodium content from their normal physiological set points. Direct hormonal influences are not explicitly formulated in this empiric model. The model also considers that the renal excretion rates of small ions other than sodium are proportional to the excretion rate of sodium. As part of the model development two aspects are emphasized (1): the estimation of parameters related to the renal elimination of fluid and small ions, and (2) model validation via comparisons between the model predictions and selected experimental data. For validation, model predictions of the renal dynamics are compared with new experimental data for two cases: plasma overload resulting from external fluid infusion (e.g. infusions of iso-osmolar solutions and/or hypertonic/hyperoncotic saline solutions), and untreated hypo volemic conditions that result from the external loss of blood. The present study demonstrates that the empiric kidney module presented above can provide good short-term predictions with respect to all renal outputs considered here. Physiological implications of the model are also presented. Copyright Acta Anaesthesiologica Scandinavica 47 (2003)

Exploring the Limits of Cell Adhesion under Shear Stress within Physiological Conditions and beyond on a Chip.

PubMed

Stamp, Melanie E M; Jötten, Anna M; Kudella, Patrick W; Breyer, Dominik; Strobl, Florian G; Geislinger, Thomas M; Wixforth, Achim; Westerhausen, Christoph

2016-10-21

Cell adhesion processes are of ubiquitous importance for biomedical applications such as optimization of implant materials. Here, not only physiological conditions such as temperature or pH, but also topographical structures play crucial roles, as inflammatory reactions after surgery can diminish osseointegration. In this study, we systematically investigate cell adhesion under static, dynamic and physiologically relevant conditions employing a lab-on-a-chip system. We screen adhesion of the bone osteosarcoma cell line SaOs-2 on a titanium implant material for pH and temperature values in the physiological range and beyond, to explore the limits of cell adhesion, e.g., for feverish and acidic conditions. A detailed study of different surface roughness R q gives insight into the correlation between the cells' abilities to adhere and withstand shear flow and the topography of the substrates, finding a local optimum at R q = 22 nm. We use shear stress induced by acoustic streaming to determine a measure for the ability of cell adhesion under an external force for various conditions. We find an optimum of cell adhesion for T = 37 °C and pH = 7.4 with decreasing cell adhesion outside the physiological range, especially for high T and low pH. We find constant detachment rates in the physiological regime, but this behavior tends to collapse at the limits of 41 °C and pH 4.

Selection of reference genes for microRNA analysis associated to early stress response to handling and confinement in Salmo salar.

PubMed

Zavala, Eduardo; Reyes, Daniela; Deerenberg, Robert; Vidal, Rodrigo

2017-05-11

MicroRNAs are key non-coding RNA molecules that play a relevant role in the regulation of gene expression through translational repression and/or transcript cleavage during normal development and physiological adaptation processes like stress. Quantitative reverse transcription polymerase chain reaction (RT-qPCR) has become the approach normally used to determine the levels of microRNAs. However, this approach needs the use of endogenous reference. An improper selection of endogenous references can result in confusing interpretation of data. The aim of this study was to identify and validate appropriate endogenous reference miRNA genes for normalizing RT-qPCR survey of miRNAs expression in four different tissues of Atlantic salmon, under handling and confinement stress conditions associated to early or primary stress response. Nine candidate reference normalizers, including microRNAs and nuclear genes, normally used in vertebrate microRNA expression studies were selected from literature, validated by RT-qPCR and analyzed by the algorithms geNorm and NormFinder. The results revealed that the ssa-miR-99-5p gene was the most stable overall and that ssa-miR-99-5p and ssa-miR-23a-5p genes were the best combination. Moreover, the suitability of ssa-miR-99-5p and ssa-miR-23a-5p as endogeneuos reference genes was demostrated by the expression analysis of ssa-miR-193-5p gene.

Radioimmunoassay of erythropoietin: circulating levels in normal and polycythemic human beings

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

Garcia, J.F.; Ebbe, S.N.; Hollander, L.

1982-05-01

Techniques are described in detail for the RIA of human Ep in unextracted plasma or serum. With 100 ..mu..l of sample, the assay is sensitive at an Ep concentration of approximately 4 mU/ml, and when required, the sensitivity can be increased to 0.4 mU/ml, a range considerably less than the concentration observed in normal human beings. This is approximately 100 times more sensitive than existing in vivo bioassays for this hormone. Studies concerned with the validation of the Ep RIA show a high degree of correlation with the polycythemic mouse bioassay. Dilutions of a variety of human serum samples showmore » a parallel relationship with the standard reference preparation for Ep. Validation of the RIA is further confirmed by observations of appropriate increases or decreases of circulating Ep levels in physiological and clinical conditions known to be associated with stimulation or suppression of Ep secretion. Significantly different mean serum concentrations of 17.2 mU/ml for normal male subjects and 18.8 mU/ml for normal female subjects were observed. Mean plasma Ep concentrations in patients with polycythemia vera are significantly decreased, and those of patients with secondary polycythemia are significantly increased as compared to plasma levels in normal subjects. These results demonstrate an initial practical value of the Ep RA in the hematology clinic, which will most certainly be expanded with its more extensive use.« less