Development and Psychometric Evaluation of a Measure of Intuitive Eating

ERIC Educational Resources Information Center

Tylka, Tracy L.

2006-01-01

Intuitive eating is characterized by eating based on physiological hunger and satiety cues rather than situational and emotional cues and is associated with psychological well-being. This study reports on the development and initial psychometric evaluation of the Intuitive Eating Scale (IES) with data collected in 4 studies from 1,260 college…

A Mechanistic Pharmacokinetic Model for Liver Transporter Substrates Under Liver Cirrhosis Conditions

PubMed Central

Li, R; Barton, HA; Maurer, TS

2015-01-01

Liver cirrhosis is a disease characterized by the loss of functional liver mass. Physiologically based pharmacokinetic (PBPK) modeling was applied to interpret and predict how the interplay among physiological changes in cirrhosis affects pharmacokinetics. However, previous PBPK models under cirrhotic conditions were developed for permeable cytochrome P450 substrates and do not directly apply to substrates of liver transporters. This study characterizes a PBPK model for liver transporter substrates in relation to the severity of liver cirrhosis. A published PBPK model structure for liver transporter substrates under healthy conditions and the physiological changes for cirrhosis are combined to simulate pharmacokinetics of liver transporter substrates in patients with mild and moderate cirrhosis. The simulated pharmacokinetics under liver cirrhosis reasonably approximate observations. This analysis includes meta-analysis to obtain system-dependent parameters in cirrhosis patients and a top-down approach to improve understanding of the effect of cirrhosis on transporter-mediated drug disposition under cirrhotic conditions. PMID:26225262

Physiologically Based Pharmacokinetic Model for Long-Circulating Inorganic Nanoparticles.

PubMed

Liang, Xiaowen; Wang, Haolu; Grice, Jeffrey E; Li, Li; Liu, Xin; Xu, Zhi Ping; Roberts, Michael S

2016-02-10

A physiologically based pharmacokinetic model was developed for accurately characterizing and predicting the in vivo fate of long-circulating inorganic nanoparticles (NPs). This model is built based on direct visualization of NP disposition details at the organ and cellular level. It was validated with multiple data sets, indicating robust inter-route and interspecies predictive capability. We suggest that the biodistribution of long-circulating inorganic NPs is determined by the uptake and release of NPs by phagocytic cells in target organs.

NUCLEAR FACTOR-Y: still complex after all these years?

PubMed

Myers, Zachary A; Holt, Ben F

2018-06-11

The NUCLEAR FACTOR-Y (NF-Y) families of transcription factors are important regulators of plant development and physiology. Though NF-Y regulatory roles have recently been suggested for numerous aspects of plant biology, their roles in flowering time, early seedling development, stress responses, hormone signaling, and nodulation are the best characterized. The past few years have also seen significant advances in our understanding of the mechanistic function of the NF-Y, and as such, increasingly complex and interesting questions are now more approachable. This review will primarily focus on these developmental, physiological, and mechanistic roles of the NF-Y in recent research. Copyright © 2018 Elsevier Ltd. All rights reserved.

Site-directed mutagenesis and PBAN activation of the Helicoverpa zea PBAN-receptor

USDA-ARS?s Scientific Manuscript database

Insect neuropeptides are produced in the central or peripheral nerve tissues, and released to regulate various physiological and behavioral actions during development and reproduction. Pheromone biosynthesis-activating neuropeptide (PBAN)/Pyrokinin is a major neuropeptide family characterized with a...

Physical and Physiological Characteristics of Judo Athletes: An Update

PubMed Central

Torres-Luque, Gema; Hernández-García, Raquel; Escobar-Molina, Raquel; Garatachea, Nuria; Nikolaidis, Pantelis T.

2016-01-01

Judo competition is characterized structurally by weight category, which raises the importance of physiological control training in judo. The aim of the present review was to examine scientific papers on the physiological profile of the judokas, maintenance or loss of weight, framing issues, such as anthropometric parameters (body fat percentage), heart rate responses to training and combat, maximal oxygen uptake, hematological, biological and hormones indicators. The values shown in this review should be used as a reference for the evaluation of physical fitness and the effectiveness of training programs. Hence, this information is expected to contribute to the development of optimal training interventions aiming to achieve maximum athletic performance and to maintain the health of judokas.

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

PubMed

Castellani, John W; Young, Andrew J

2016-04-01

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

Optical approach to the salivary pellicle

NASA Astrophysics Data System (ADS)

Baek, Jae Ho; Krasieva, Tatiana; Tang, Shuo; Ahn, Yehchan; Kim, Chang Soo; Vu, Diana; Chen, Zhongping; Wilder-Smith, Petra

2009-07-01

The salivary pellicle plays an important role in oral physiology, yet noninvasive in situ characterization and mapping of this layer remains elusive. The goal of this study is to develop an optical approach for the real-time, noninvasive mapping and characterization of salivary pellicles using optical coherence tomography (OCT) and optical coherence microscopy (OCM). The long-term goals are to improve diagnostic capabilities in the oral cavity, gain a better understanding of physiological and pathological processes related to the oral hard tissues, and monitor treatment responses. A salivary pellicle is incubated on small enamel cubes using human whole saliva. OCT and OCM imaging occurs at 0, 10, 30, 60 min, and 24 h. For some imaging, spherical gold nanoparticles (15 nm) are added to determine whether this would increase the optical signal from the pellicle. Multiphoton microscopy (MPM) provides the baseline information. In the saliva-incubated samples, a surface signal from the developing pellicle is visible in OCT images. Pellicle ``islands'' form, which increase in complexity over time until they merge to form a continuous layer over the enamel surface. Noninvasive, in situ time-based pellicle formation on the enamel surface is visualized and characterized using optical imaging.

Identification and Evaluation of Integration and Cross Cutting Issues Across HRP Risks

NASA Technical Reports Server (NTRS)

Steinberg, S. L.; Shelhamer, Mark

2015-01-01

The HRP Integrated Research Plan contains the research plans for the 32 risks requiring research to characterize and mitigate. These risks to human health and performance in spaceflight are identified by evidence and each one focuses on a single aspect of human physiology or performance. They are further categorized by aspects of the spaceflight environment, such as altered gravity or space radiation, that that play a major role in their likelihood and consequence. From its inception the "integrate" in the Research Plan has denoted the integrated nature of risks to human health and performance, the connectedness of physiological systems within the human body regardless of the spaceflight environment, and the integrated response of the human body to the spaceflight environment. Common characteristics of the spaceflight environment include altered gravity, atmospheres and light/dark cycles, space radiation, isolation, noise, and periods of high or low workload. Long term exposure to this unique environment produces a suite of physiological effects such as stress; vision, neurocognitive and anthropometric changes; circadian misalignment; fluid shifts, deconditioning; immune dysregulation; and altered nutritional requirements. Matrix diagraming was used to systematically identify, analyze and rate the many-to-many relationships between environmental characteristics and the suite of physiological effects. It was also to identify patterns in the relationships of common physiological effects to each other. Analyses of patterns or relationships in these diagrams help to identify issues that cut across multiple risks. Cross cutting issues benefit from a multidisciplinary approach that synthesizes concepts or data from two or more disciplines to identify and characterize risk factors or develop countermeasures relevant to multiple risks. They also help to illuminate possible problem areas that may arise when a countermeasure impacts risks other than those which it was developed to mitigate, or identify groupings of physiological changes that are likely to occur that may impact the overall risk posture.

Flow pumping system for physiological waveforms.

PubMed

Tsai, William; Savaş, Omer

2010-02-01

A pulsatile flow pumping system is developed to replicate flow waveforms with reasonable accuracy for experiments simulating physiological blood flows at numerous points in the body. The system divides the task of flow waveform generation between two pumps: a gear pump generates the mean component and a piston pump generates the oscillatory component. The system is driven by two programmable servo controllers. The frequency response of the system is used to characterize its operation. The system has been successfully tested in vascular flow experiments where sinusoidal, carotid, and coronary flow waveforms are replicated.

RNA-seq analysis of broiler liver transcriptome reveals novel responses to high ambient temperature.

PubMed

Coble, Derrick J; Fleming, Damarius; Persia, Michael E; Ashwell, Chris M; Rothschild, Max F; Schmidt, Carl J; Lamont, Susan J

2014-12-10

In broilers, high ambient temperature can result in reduced feed consumption, digestive inefficiency, impaired metabolism, and even death. The broiler sector of the U.S. poultry industry incurs approximately $52 million in heat-related losses annually. The objective of this study is to characterize the effects of cyclic high ambient temperature on the transcriptome of a metabolically active organ, the liver. This study provides novel insight into the effects of high ambient temperature on metabolism in broilers, because it is the first reported RNA-seq study to characterize the effect of heat on the transcriptome of a metabolic-related tissue. This information provides a platform for future investigations to further elucidate physiologic responses to high ambient temperature and seek methods to ameliorate the negative impacts of heat. Transcriptome sequencing of the livers of 8 broiler males using Illumina HiSeq 2000 technology resulted in 138 million, 100-base pair single end reads, yielding a total of 13.8 gigabases of sequence. Forty genes were differentially expressed at a significance level of P-value < 0.05 and a fold-change ≥ 2 in response to a week of cyclic high ambient temperature with 27 down-regulated and 13 up-regulated genes. Two gene networks were created from the function-based Ingenuity Pathway Analysis (IPA) of the differentially expressed genes: "Cell Signaling" and "Endocrine System Development and Function". The gene expression differences in the liver transcriptome of the heat-exposed broilers reflected physiological responses to decrease internal temperature, reduce hyperthermia-induced apoptosis, and promote tissue repair. Additionally, the differential gene expression revealed a physiological response to regulate the perturbed cellular calcium levels that can result from high ambient temperature exposure. Exposure to cyclic high ambient temperature results in changes at the metabolic, physiologic, and cellular level that can be characterized through RNA-seq analysis of the liver transcriptome of broilers. The findings highlight specific physiologic mechanisms by which broilers reduce the effects of exposure to high ambient temperature. This information provides a foundation for future investigations into the gene networks involved in the broiler stress response and for development of strategies to ameliorate the negative impacts of heat on animal production and welfare.

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

PubMed

Lira, Matthew E; Gardner, Stephanie M

2017-06-01

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

ENaC/DEG in Tumor Development and Progression

PubMed Central

Liu, Cui; Zhu, Li-Li; Xu, Si-Guang; Ji, Hong-Long; Li, Xiu-Min

2016-01-01

The epithelial Na+ channel/degenerin (ENaC/DEG) superfamily, including the acid-sensing ion channels (ASICs), is characterized by a high degree of similarity in structure but highly diverse in physiological functions. These ion channels have been shown to be important in several physiological functions of normal epithelial cells, including salt homeostasis, fluid transportation and cell mobility. There is increasing evidence suggesting that ENaC/DEG channels are critically engaged in cancer cell biology, such as proliferation, migration, invasion and apoptosis, playing a role in tumor development and progression. In this review, we will discuss recent studies showing the role of ENaC and ASIC channels in epithelial cells and its relationship to the oncogenesis. PMID:27698929

Physiological and biochemical characterization of Azospirillum brasilense strains commonly used as plant growth-promoting rhizobacteria.

PubMed

Di Salvo, Luciana P; Silva, Esdras; Teixeira, Kátia R S; Cote, Rosalba Esquivel; Pereyra, M Alejandra; García de Salamone, Inés E

2014-12-01

Azospirillum is a plant growth-promoting rhizobacteria (PGPR) genus vastly studied and utilized as agriculture inoculants. Isolation of new strains under different environmental conditions allows the access to the genetic diversity and improves the success of inoculation procedures. Historically, the isolation of this genus has been performed by the use of some traditional culture media. In this work we characterized the physiology and biochemistry of five different A. brasilense strains, commonly used as cereal inoculants. The aim of this work is to contribute to pose into revision some concepts concerning the most used protocols to isolate and characterize this bacterium. We characterized their growth in different traditional and non-traditional culture media, evaluated some PGPR mechanisms and characterized their profiles of fatty acid methyl esters and carbon-source utilization. This work shows, for the first time, differences in both profiles, and ACC deaminase activity of A. brasilense strains. Also, we show unexpected results obtained in some of the evaluated culture media. Results obtained here and an exhaustive knowledge revision revealed that it is not appropriate to conclude about bacterial species without analyzing several strains. Also, it is necessary to continue developing studies and laboratory techniques to improve the isolation and characterization protocols. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Functional characterization of Anaphase Promoting Complex/Cyclosome (APC/C) E3 ubiquitin ligases in tumorigenesis

PubMed Central

Zhang, Jinfang; Wan, Lixin; Dai, Xiangpeng; Sun, Yi; Wei, Wenyi

2014-01-01

The Anaphase Promoting Complex/Cyclosome (APC/C) is a multi-subunit E3 ubiquitin ligase that primarily governs cell cycle progression. APC/C is composed of at least 14 core subunits and recruits its substrates for ubiquitination via one of the two adaptor proteins, Cdc20 or Cdh1, in M or M/early G1 phase, respectively. Furthermore, recent studies have shed light on crucial functions for APC/C in maintaining genomic integrity, neuronal differentiation, cellular metabolism and tumorigenesis. To gain better insight into the in vivo physiological functions of APC/C in regulating various cellular processes, particularly development and tumorigenesis, a number of mouse models of APC/C core subunits, coactivators or inhibitors have been established and characterized. However, due to their essential role in cell cycle regulation, most of the germline knockout mice targeting the APC/C pathway are embryonic lethal, indicating the need for generating conditional knockout mouse models to assess the role in tumorigenesis for each APC/C signaling component in specific tissues. In this review, we will first provide a brief introduction of the ubiquitin-proteasome system (UPS) and the biochemical activities and cellular functions of the APC/C E3 ligase. We will then focus primarily on characterizing genetic mouse models used to understand the physiological roles of each APC/C signaling component in embryogenesis, cell proliferation, development and carcinogenesis. Finally, we discuss future research directions to further elucidate the physiological contributions of APC/C components during tumorigenesis and validate their potentials as a novel class of anti-cancer targets. PMID:24569229

Identification and characterization of contrasting sunflower genotypes to early leaf senescence process combining molecular and physiological studies (Helianthus annuus L.).

PubMed

López Gialdi, A I; Moschen, S; Villán, C S; López Fernández, M P; Maldonado, S; Paniego, N; Heinz, R A; Fernandez, P

2016-09-01

Leaf senescence is a complex mechanism ruled by multiple genetic and environmental variables that affect crop yields. It is the last stage in leaf development, is characterized by an active decline in photosynthetic rate, nutrients recycling and cell death. The aim of this work was to identify contrasting sunflower inbred lines differing in leaf senescence and to deepen the study of this process in sunflower. Ten sunflower genotypes, previously selected by physiological analysis from 150 inbred genotypes, were evaluated under field conditions through physiological, cytological and molecular analysis. The physiological measurement allowed the identification of two contrasting senescence inbred lines, R453 and B481-6, with an increase in yield in the senescence delayed genotype. These findings were confirmed by cytological and molecular analysis using TUNEL, genomic DNA gel electrophoresis, flow sorting and gene expression analysis by qPCR. These results allowed the selection of the two most promising contrasting genotypes, which enables future studies and the identification of new biomarkers associated to early senescence in sunflower. In addition, they allowed the tuning of cytological techniques for a non-model species and its integration with molecular variables. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

On-Line Analysis of Physiologic and Neurobehavioral Variables During Long-Duration Space Missions

NASA Technical Reports Server (NTRS)

Brown, Emery N.

1999-01-01

The goal of this project is to develop reliable statistical algorithms for on-line analysis of physiologic and neurobehavioral variables monitored during long-duration space missions. Maintenance of physiologic and neurobehavioral homeostasis during long-duration space missions is crucial for ensuring optimal crew performance. If countermeasures are not applied, alterations in homeostasis will occur in nearly all-physiologic systems. During such missions data from most of these systems will be either continually and/or continuously monitored. Therefore, if these data can be analyzed as they are acquired and the status of these systems can be continually assessed, then once alterations are detected, appropriate countermeasures can be applied to correct them. One of the most important physiologic systems in which to maintain homeostasis during long-duration missions is the circadian system. To detect and treat alterations in circadian physiology during long duration space missions requires development of: 1) a ground-based protocol to assess the status of the circadian system under the light-dark environment in which crews in space will typically work; and 2) appropriate statistical methods to make this assessment. The protocol in Project 1, Circadian Entrainment, Sleep-Wake Regulation and Neurobehavioral will study human volunteers under the simulated light-dark environment of long-duration space missions. Therefore, we propose to develop statistical models to characterize in near real time circadian and neurobehavioral physiology under these conditions. The specific aims of this project are to test the hypotheses that: 1) Dynamic statistical methods based on the Kronauer model of the human circadian system can be developed to estimate circadian phase, period, amplitude from core-temperature data collected under simulated light- dark conditions of long-duration space missions. 2) Analytic formulae and numerical algorithms can be developed to compute the error in the estimates of circadian phase, period and amplitude determined from the data in Specific Aim 1. 3) Statistical models can detect reliably in near real- time (daily) significant alternations in the circadian physiology of individual subjects by analyzing the circadian and neurobehavioral data collected in Project 1. 4) Criteria can be developed using the Kronauer model and the recently developed Jewett model of cognitive -performance and subjective alertness to define altered circadian and neurobehavioral physiology and to set conditions for immediate administration of countermeasures.

Drawing on student knowledge in human anatomy and physiology

NASA Astrophysics Data System (ADS)

Slominski, Tara Nicole

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

Different physiological stages and breeding systems related to the variability of meat quality of indigenous Pantaneiro sheep

PubMed Central

Burin, Poliana Campos; Leonardo, Ariadne Patricia; Fausto, Daiane Aparecido; da Silva, Adrielly Lais Alves; Ricardo, Hélio de Almeida; Corrêa da Silva, Marcelo; de Souza, Márcio Rodrigues; de Vargas Junior, Fernando Miranda

2018-01-01

This study configures a first report regarding the variability of meat quality of locally adapted Pantaneiro sheep depending on different physiological stages and breeding systems. Pantaneiro sheep are raised in Brazil under a tropical wetland ecosystem denominated Pantanal. Twenty-nine Pantaneiro sheep from different sex and physiological stages were sorted into three groups, simulating three of the most representative ovine meat products commercialized by South American industries: a) non castrated male lambs (n = 11); b) wethers (n = 9); c) cull ewes (n = 9). Animals from each physiological stage were submitted to different breeding systems, resembling farming strategies adopted in several developing countries of South America. The effect of physiological stages on the quality of meat was accessed using 16 variables measured in the longissimus thoracis et lumborum (LM) and the semimembranosus (SM) muscles. The variables were related to brightness, color, physical aspects, soluble and total collagen as well as chemical traits. The physiological stage was defined as a classification variable in order to proceed ANOVA tests and comparison of means (P<0.05). Multivariate analysis was used to identify patterns of similarity and differentiation between samples of different physiological stages (a, b, c). The results revealed that meat quality varies according to different physiological stages, especially between lambs (a) and cull ewes (c). As a consequence, the physiological stage at slaughter should be taken into consideration to cote the quality of meat from indigenous sheep raised in tropical regions. The results contribute towards sensorial evaluation and the characterization of potential food products derived from indigenous sheep bred under tropical climate in developing countries. PMID:29432430

Mechanical and biocompatible characterizations of a readily available multilayer vascular graft

PubMed Central

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

2013-01-01

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

Community level physiological profiles (CLPP), characterization and microbial activity of soil amended with dairy sewage sludge.

PubMed

Frąc, Magdalena; Oszust, Karolina; Lipiec, Jerzy

2012-01-01

The aim of the present work was to assess the influence of organic amendment applications compared to mineral fertilization on soil microbial activity and functional diversity. The field experiment was set up on a soil classified as an Eutric Cambisol developed from loess (South-East Poland). Two doses of both dairy sewage sludge (20 Mg·ha(-1) and 26 Mg·ha(-1)) and of mineral fertilizers containing the same amount of nutrients were applied. The same soil without any amendment was used as a control. The soil under undisturbed native vegetation was also included in the study as a representative background sample. The functional diversity (catabolic potential) was assessed using such indices as Average Well Color Development (AWCD), Richness (R) and Shannon-Weaver index (H). These indices were calculated, following the community level physiological profiling (CLPP) using Biolog Eco Plates. Soil dehydrogenase and respiratory activity were also evaluated. The indices were sensitive enough to reveal changes in community level physiological profiles due to treatment effects. It was shown that dairy sewage amended soil was characterized by greater AWCD, R, H and dehydrogenase and respiratory activity as compared to control or mineral fertilized soil. Analysis of variance (ANOVA) and principal component analysis (PCA) were used to depict the differences of the soil bacterial functional diversity between the treatments.

Community Level Physiological Profiles (CLPP), Characterization and Microbial Activity of Soil Amended with Dairy Sewage Sludge

PubMed Central

Frąc, Magdalena; Oszust, Karolina; Lipiec, Jerzy

2012-01-01

The aim of the present work was to assess the influence of organic amendment applications compared to mineral fertilization on soil microbial activity and functional diversity. The field experiment was set up on a soil classified as an Eutric Cambisol developed from loess (South-East Poland). Two doses of both dairy sewage sludge (20 Mg·ha−1 and 26 Mg·ha−1) and of mineral fertilizers containing the same amount of nutrients were applied. The same soil without any amendment was used as a control. The soil under undisturbed native vegetation was also included in the study as a representative background sample. The functional diversity (catabolic potential) was assessed using such indices as Average Well Color Development (AWCD), Richness (R) and Shannon–Weaver index (H). These indices were calculated, following the community level physiological profiling (CLPP) using Biolog Eco Plates. Soil dehydrogenase and respiratory activity were also evaluated. The indices were sensitive enough to reveal changes in community level physiological profiles due to treatment effects. It was shown that dairy sewage amended soil was characterized by greater AWCD, R, H and dehydrogenase and respiratory activity as compared to control or mineral fertilized soil. Analysis of variance (ANOVA) and principal component analysis (PCA) were used to depict the differences of the soil bacterial functional diversity between the treatments. PMID:22737006

A Liver-centric Multiscale Modeling Framework for Xenobiotics ...

EPA Pesticide Factsheets

We describe a multi-scale framework for modeling acetaminophen-induced liver toxicity. Acetaminophen is a widely used analgesic. Overdose of acetaminophen can result in liver injury via its biotransformation into toxic product, which further induce massive necrosis. Our study focuses on developing a multi-scale computational model to characterize both phase I and phase II metabolism of acetaminophen, by bridging Physiologically Based Pharmacokinetic (PBPK) modeling at the whole body level, cell movement and blood flow at the tissue level and cell signaling and drug metabolism at the sub-cellular level. To validate the model, we estimated our model parameters by fi?tting serum concentrations of acetaminophen and its glucuronide and sulfate metabolites to experiments, and carried out sensitivity analysis on 35 parameters selected from three modules. Our study focuses on developing a multi-scale computational model to characterize both phase I and phase II metabolism of acetaminophen, by bridging Physiologically Based Pharmacokinetic (PBPK) modeling at the whole body level, cell movement and blood flow at the tissue level and cell signaling and drug metabolism at the sub-cellular level. This multiscale model bridges the CompuCell3D tool used by the Virtual Tissue project with the httk tool developed by the Rapid Exposure and Dosimetry project.

Structural dynamics of the skeletal muscle fiber by second harmonic generation

NASA Astrophysics Data System (ADS)

Nucciotti, V.; Stringari, C.; Sacconi, L.; Vanzi, F.; Linari, M.; Piazzesi, G.; Lombardi, V.; Pavone, F. S.

2008-02-01

The high degree of structural order in skeletal muscle allows imaging of this tissue by Second Harmonic Generation (SHG). As previously found (Vanzi et al., J. Muscle Cell Res. Motil. 2006) by fractional extraction of proteins, myosin is the source of SHG signal. A full characterization of the polarization-dependence of the SHG signal can provide very selective information on the orientation of the emitting proteins and their dynamics during contraction. We developed a line scan polarization method, allowing measurements of a full polarization curve in intact muscle fibers from skeletal muscle of the frog to characterize the SHG polarization dependence on different physiological states (resting, rigor and isometric tetanic contraction). The polarization data have been interpreted by means of a model in terms of the average orientation of SHG emitters.The different physiological states are characterized by distinct patterns of SHG polarization. The variation of the orientation of emitting molecules in relation to the physiological state of the muscle demonstrates that one part of SHG signal arises from the globular head of the myosin molecule that cross-links actin and myosin filaments. The dependence of the SHG modulation on the degree of overlap between actin and myosin filaments during an isometric contraction, provides the constraints to estimate the fraction of myosin heads generating the isometric force in the active muscle fiber.

Polybrominated diphenyl ethers in human placenta associated with neonatal physiological development at a typical e-waste recycling area in China.

PubMed

Xu, Long; Huo, Xia; Zhang, Yuling; Li, Weiqiu; Zhang, Jianqing; Xu, Xijin

2015-01-01

Our aim of this study was to characterize the exposure pattern of polybrominated diphenyl ethers(PBDEs) in human placenta and assess their potential effects on neonates. Placenta samples were obtained from a typical e-waste area in Guiyu and a reference area in Haojiang, China. The median ΣPBDE concentration was 32.25 ng/g lipid weight (lw) in placenta samples from Guiyu, and 5.13 ng/g lw from Haojiang. BDE-209 predominated in placenta samples, followed by BDE-28, -47, -99 -153, -183. Residence in Guiyu contributed the most to elevated PDBE levels. Neonatal physiological indices, including bodymass index (BMI), Apgar 1 score and head circumference, were reduced in Guiyu group. No significant difference was found in neonatal weight between the two groups, but neonatal body length in Guiyu was increased. Our data suggest prenatal exposure to PBDEs is high at the e-waste recycling area, and may lead to adverse physiological development in the fetus.

Local corticotropin releasing hormone (CRH) signals to its receptor CRHR1 during postnatal development of the mouse olfactory bulb.

PubMed

Garcia, Isabella; Bhullar, Paramjit K; Tepe, Burak; Ortiz-Guzman, Joshua; Huang, Longwen; Herman, Alexander M; Chaboub, Lesley; Deneen, Benjamin; Justice, Nicholas J; Arenkiel, Benjamin R

2016-01-01

Neuropeptides play important physiological functions during distinct behaviors such as arousal, learning, memory, and reproduction. However, the role of local, extrahypothalamic neuropeptide signaling in shaping synapse formation and neuronal plasticity in the brain is not well understood. Here, we characterize the spatiotemporal expression profile of the neuropeptide corticotropin-releasing hormone (CRH) and its receptor CRHR1 in the mouse OB throughout development. We found that CRH-expressing interneurons are present in the external plexiform layer, that its cognate receptor is expressed by granule cells, and show that both CRH and CRHR1 expression enriches in the postnatal period when olfaction becomes important towards olfactory-related behaviors. Further, we provide electrophysiological evidence that CRHR1-expressing granule cells functionally respond to CRH ligand, and that the physiological circuitry of CRHR1 knockout mice is abnormal, leading to impaired olfactory behaviors. Together, these data suggest a physiologically relevant role for local CRH signaling towards shaping the neuronal circuitry within the mouse OB.

Prediction and diagnosis of apple fruit physiological disorders

USDA-ARS?s Scientific Manuscript database

Apple postharvest physiological disorders, characterized by peel or flesh necrosis, result in significant yearly financial losses in commercial operations. Stakeholders have identified the need for effective, consistent control measures for apple postharvest physiological disorders and the developme...

Lab-on-a-brane: A novel physiologically relevant planar arterial model to study transendothelial transport

NASA Astrophysics Data System (ADS)

Budhwani, Karim Ismail

The tremendous quality of life impact notwithstanding, cardiovascular diseases and Cancer add up to over US$ 700bn each year in financial costs alone. Aging and population growth are expected to further expand the problem space while drug research and development remain expensive. However, preclinical costs can be substantially mitigated by substituting animal models with in vitro devices that accurately model human cardiovascular transport. Here we present a novel physiologically relevant lab-on-a-brane that simulates in vivo pressure, flow, strain, and shear waveforms associated with normal and pathological conditions in large and small blood vessels for studying molecular transport across the endothelial monolayer. The device builds upon previously demonstrated integrated microfluidic loop design by: (a) introducing nanoscale pores in the substrate membrane to enable transmembrane molecular transport, (b) transforming the substrate membrane into a nanofibrous matrix for 3D smooth muscle cell (SMC) tissue culture, (c) integrating electrospinning fabrication methods, (d) engineering an invertible sandwich cell culture device architecture, and (e) devising a healthy co-culture mechanism for human arterial endothelial cell (HAEC) monolayer and multiple layers of human smooth muscle cells (HSMC) to accurately mimic arterial anatomy. Structural and mechanical characterization was conducted using confocal microscopy, SEM, stress/strain analysis, and infrared spectroscopy. Transport was characterized using FITC-Dextran hydraulic permeability protocol. Structure and transport characterization successfully demonstrate device viability as a physiologically relevant arterial mimic for testing transendothelial transport. Thus, our lab-on-a-brane provides a highly effective and efficient, yet considerably inexpensive, physiologically relevant alternative for pharmacokinetic evaluation; possibly reducing animals used in pre-clinical testing, clinical trials cost from false starts, and time-to-market. Furthermore, this platform can be easily configured for testing targeted therapeutic delivery and in multiple simultaneous arrays for personalized and precision medicine applications.

The trajectory of life. Decreasing physiological network complexity through changing fractal patterns

PubMed Central

Sturmberg, Joachim P.; Bennett, Jeanette M.; Picard, Martin; Seely, Andrew J. E.

2015-01-01

In this position paper, we submit a synthesis of theoretical models based on physiology, non-equilibrium thermodynamics, and non-linear time-series analysis. Based on an understanding of the human organism as a system of interconnected complex adaptive systems, we seek to examine the relationship between health, complexity, variability, and entropy production, as it might be useful to help understand aging, and improve care for patients. We observe the trajectory of life is characterized by the growth, plateauing and subsequent loss of adaptive function of organ systems, associated with loss of functioning and coordination of systems. Understanding development and aging requires the examination of interdependence among these organ systems. Increasing evidence suggests network interconnectedness and complexity can be captured/measured/associated with the degree and complexity of healthy biologic rhythm variability (e.g., heart and respiratory rate variability). We review physiological mechanisms linking the omics, arousal/stress systems, immune function, and mitochondrial bioenergetics; highlighting their interdependence in normal physiological function and aging. We argue that aging, known to be characterized by a loss of variability, is manifested at multiple scales, within functional units at the small scale, and reflected by diagnostic features at the larger scale. While still controversial and under investigation, it appears conceivable that the integrity of whole body complexity may be, at least partially, reflected in the degree and variability of intrinsic biologic rhythms, which we believe are related to overall system complexity that may be a defining feature of health and it's loss through aging. Harnessing this information for the development of therapeutic and preventative strategies may hold an opportunity to significantly improve the health of our patients across the trajectory of life. PMID:26082722

In vitro microfluidic models of tumor microenvironment to screen transport of drugs and nanoparticles.

PubMed

Ozcelikkale, Altug; Moon, Hye-Ran; Linnes, Michael; Han, Bumsoo

2017-09-01

Advances in nanotechnology have enabled numerous types of nanoparticles (NPs) to improve drug delivery to tumors. While many NP systems have been proposed, their clinical translation has been less than anticipated primarily due to failure of current preclinical evaluation techniques to adequately model the complex interactions between the NP and physiological barriers of tumor microenvironment. This review focuses on microfluidic tumor models for characterization of delivery efficacy and toxicity of cancer nanomedicine. Microfluidics offer significant advantages over traditional macroscale cell cultures by enabling recapitulation of tumor microenvironment through precise control of physiological cues such as hydrostatic pressure, shear stress, oxygen, and nutrient gradients. Microfluidic systems have recently started to be adapted for screening of drugs and NPs under physiologically relevant settings. So far the two primary application areas of microfluidics in this area have been high-throughput screening using traditional culture settings such as single cells or multicellular tumor spheroids, and mimicry of tumor microenvironment for study of cancer-related cell-cell and cell-matrix interactions. These microfluidic technologies are also useful in modeling specific steps in NP delivery to tumor and characterize NP transport properties and outcomes by systematic variation of physiological conditions. Ultimately, it will be possible to design drug-screening platforms uniquely tailored for individual patient physiology using microfluidics. These in vitro models can contribute to development of precision medicine by enabling rapid and patient-specific evaluation of cancer nanomedicine. WIREs Nanomed Nanobiotechnol 2017, 9:e1460. doi: 10.1002/wnan.1460 For further resources related to this article, please visit the WIREs website. © 2017 Wiley Periodicals, Inc.

Personalized physiological medicine.

PubMed

Ince, Can

2017-12-28

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

Physiological significance of TRPV2 as a mechanosensor, thermosensor and lipid sensor.

PubMed

Shibasaki, Koji

2016-09-01

This review provides a summary of the physiological significance of the TRPV2 ion channel. While TRPV2 was initially characterized as a noxious heat sensor, we found that TRPV2 can also act as a mechanosensor in embryonic neurons or adult myenteric neurons. Here, we summarize the newly characterized functions of TRPV2, including the research progress that has been made toward our understanding of TRPV2 physiology, and discuss other recent data pertaining to TRPV2. It is thought that TRPV2 may be an important drug target based on its broad expression patterns and important physiological roles. The possible associations between diseases and TRPV2 are also discussed.

Large-Scale Bioinformatics Analysis of Bacillus Genomes Uncovers Conserved Roles of Natural Products in Bacterial Physiology.

PubMed

Grubbs, Kirk J; Bleich, Rachel M; Santa Maria, Kevin C; Allen, Scott E; Farag, Sherif; Shank, Elizabeth A; Bowers, Albert A

2017-01-01

Bacteria possess an amazing capacity to synthesize a diverse range of structurally complex, bioactive natural products known as specialized (or secondary) metabolites. Many of these specialized metabolites are used as clinical therapeutics, while others have important ecological roles in microbial communities. The biosynthetic gene clusters (BGCs) that generate these metabolites can be identified in bacterial genome sequences using their highly conserved genetic features. We analyzed an unprecedented 1,566 bacterial genomes from Bacillus species and identified nearly 20,000 BGCs. By comparing these BGCs to one another as well as a curated set of known specialized metabolite BGCs, we discovered that the majority of Bacillus natural products are comprised of a small set of highly conserved, well-distributed, known natural product compounds. Most of these metabolites have important roles influencing the physiology and development of Bacillus species. We identified, in addition to these characterized compounds, many unique, weakly conserved BGCs scattered across the genus that are predicted to encode unknown natural products. Many of these "singleton" BGCs appear to have been acquired via horizontal gene transfer. Based on this large-scale characterization of metabolite production in the Bacilli , we go on to connect the alkylpyrones, natural products that are highly conserved but previously biologically uncharacterized, to a role in Bacillus physiology: inhibiting spore development. IMPORTANCE Bacilli are capable of producing a diverse array of specialized metabolites, many of which have gained attention for their roles as signals that affect bacterial physiology and development. Up to this point, however, the Bacillus genus's metabolic capacity has been underexplored. We undertook a deep genomic analysis of 1,566 Bacillus genomes to understand the full spectrum of metabolites that this bacterial group can make. We discovered that the majority of the specialized metabolites produced by Bacillus species are highly conserved, known compounds with important signaling roles in the physiology and development of this bacterium. Additionally, there is significant unique biosynthetic machinery distributed across the genus that might lead to new, unknown metabolites with diverse biological functions. Inspired by the findings of our genomic analysis, we speculate that the highly conserved alkylpyrones might have an important biological activity within this genus. We go on to validate this prediction by demonstrating that these natural products are developmental signals in Bacillus and act by inhibiting sporulation.

Assessment of Renal Hemodynamics and Oxygenation by Simultaneous Magnetic Resonance Imaging (MRI) and Quantitative Invasive Physiological Measurements.

PubMed

Cantow, Kathleen; Arakelyan, Karen; Seeliger, Erdmann; Niendorf, Thoralf; Pohlmann, Andreas

2016-01-01

In vivo assessment of renal perfusion and oxygenation under (patho)physiological conditions by means of noninvasive diagnostic imaging is conceptually appealing. Blood oxygen level-dependent (BOLD) magnetic resonance imaging (MRI) and quantitative parametric mapping of the magnetic resonance (MR) relaxation times T 2* and T 2 are thought to provide surrogates of renal tissue oxygenation. The validity and efficacy of this technique for quantitative characterization of local tissue oxygenation and its changes under different functional conditions have not been systematically examined yet and remain to be established. For this purpose, the development of an integrative multimodality approaches is essential. Here we describe an integrated hybrid approach (MR-PHYSIOL) that combines established quantitative physiological measurements with T 2* (T 2) mapping and MR-based kidney size measurements. Standardized reversible (patho)physiologically relevant interventions, such as brief periods of aortic occlusion, hypoxia, and hyperoxia, are used for detailing the relation between the MR-PHYSIOL parameters, in particular between renal T 2* and tissue oxygenation.

REACTIONS OF BENZO[A]PYRENE-7,8-QUINONE WITH DEOXYGUANOSINE AND DEOXYADENOSINE AT PHYSIOLOGICAL pH: IDENTIFICATION AND CHARACTERIZATION OF STABLE ADDUCTS

EPA Science Inventory

Reactions of Benzo[a]pyrene-7,8-quinone with Deoxyguanosine and Deoxyadenosine at Physiological pH: Identification and Characterization of Stable Adducts

Narayanan Balu, William T. Padgett, Guy Lambert, Adam E. Swank,
Ann M. Richard, and Stephen Nesnow

Environmen...

Challenges in breeding for yield increase for drought.

PubMed

Sinclair, Thomas R

2011-06-01

Crop genetic improvement for environmental stress at the molecular and physiological level is very complex and challenging. Unlike the example of the current major commercial transgenic crops for which biotic stress tolerance is based on chemicals alien to plants, the complex, redundant and homeostatic molecular and physiological systems existing in plants must be altered for drought tolerance improvement. Sophisticated tools must be developed to monitor phenotype expression at the crop level to characterize variation among genotypes across a range of environments. Once stress-tolerant cultivars are developed, regional probability distributions describing yield response across years will be necessary. This information can then aid in identifying environmental conditions for positive and negative responses to genetic modification to guide farmer selection of stress-tolerant cultivars. Copyright © 2011 Elsevier Ltd. All rights reserved.

The conservation physiology toolbox: status and opportunities

PubMed Central

Love, Oliver P; Hultine, Kevin R

2018-01-01

Abstract For over a century, physiological tools and techniques have been allowing researchers to characterize how organisms respond to changes in their natural environment and how they interact with human activities or infrastructure. Over time, many of these techniques have become part of the conservation physiology toolbox, which is used to monitor, predict, conserve, and restore plant and animal populations under threat. Here, we provide a summary of the tools that currently comprise the conservation physiology toolbox. By assessing patterns in articles that have been published in ‘Conservation Physiology’ over the past 5 years that focus on introducing, refining and validating tools, we provide an overview of where researchers are placing emphasis in terms of taxa and physiological sub-disciplines. Although there is certainly diversity across the toolbox, metrics of stress physiology (particularly glucocorticoids) and studies focusing on mammals have garnered the greatest attention, with both comprising the majority of publications (>45%). We also summarize the types of validations that are actively being completed, including those related to logistics (sample collection, storage and processing), interpretation of variation in physiological traits and relevance for conservation science. Finally, we provide recommendations for future tool refinement, with suggestions for: (i) improving our understanding of the applicability of glucocorticoid physiology; (ii) linking multiple physiological and non-physiological tools; (iii) establishing a framework for plant conservation physiology; (iv) assessing links between environmental disturbance, physiology and fitness; (v) appreciating opportunities for validations in under-represented taxa; and (vi) emphasizing tool validation as a core component of research programmes. Overall, we are confident that conservation physiology will continue to increase its applicability to more taxa, develop more non-invasive techniques, delineate where limitations exist, and identify the contexts necessary for interpretation in captivity and the wild. PMID:29942517

The Fragile X Syndrome: From Molecular Genetics to Neurobiology

ERIC Educational Resources Information Center

Willemsen, Rob; Oostra, Ben A.; Bassell, Gary J.; Dictenberg, Jason

2004-01-01

Since the identification of the FMR1 gene basic research has been focused on the molecular characterization of the FMR1 gene product, the fragile X mental retardation protein (FMRP). Recent developments in fragile X research have provided new insights and knowledge about the physiological function of FMRP in the cell and the nerve cell in…

A systematic review of physiological reactivity to stimuli in autism.

PubMed

Lydon, Sinéad; Healy, Olive; Reed, Phil; Mulhern, Teresa; Hughes, Brian M; Goodwin, Matthew S

2016-12-01

The prevalence of abnormal behavioural responses to a variety of stimuli among individuals with autism has led researchers to examine whether physiological reactivity (PR) is typical in this population. This article reviewed studies assessing PR to sensory, social and emotional, and stressor stimuli in individuals with autism. Systematic searches of electronic databases identified 57 studies that met our inclusion criteria. Studies were analysed to determine: (a) participant characteristics; (b) physiological measures used; (c) PR to sensory, social and emotional or stressor stimuli; (d) the relation between PR and behavioural or psychological variables and (e) baseline physiological activity. A novel measure of methodological quality suitable for use with non-randomized, non-interventional, psychophysiological studies was also developed and applied. Individuals with autism were found to respond differently than typically developing controls in 78.6%, 66.7% and 71.4% of sensory, social and emotional, and stressor stimulus classes, respectively. However, this extant literature is characterized by variable and inconsistent findings, which do not appear to be accounted for by varying methodological quality, making it difficult to determine what specific factors differentiate individuals with autism who present with atypical PR from those who do not. Despite this uncertainty, individual differences in PR are clearly present in autism, suggesting additional research is needed to determine the variables relating to PR among those with ASD and to examine the possible existence of physiological subtype responders in the population.

Developing Hydrogeological Site Characterization Strategies based on Human Health Risk

NASA Astrophysics Data System (ADS)

de Barros, F.; Rubin, Y.; Maxwell, R. M.

2013-12-01

In order to provide better sustainable groundwater quality management and minimize the impact of contamination in humans, improved understanding and quantification of the interaction between hydrogeological models, geological site information and human health are needed. Considering the joint influence of these components in the overall human health risk assessment and the corresponding sources of uncertainty aid decision makers to better allocate resources in data acquisition campaigns. This is important to (1) achieve remediation goals in a cost-effective manner, (2) protect human health and (3) keep water supplies clean in order to keep with quality standards. Such task is challenging since a full characterization of the subsurface is unfeasible due to financial and technological constraints. In addition, human exposure and physiological response to contamination are subject to uncertainty and variability. Normally, sampling strategies are developed with the goal of reducing uncertainty, but less often they are developed in the context of their impacts on the overall system uncertainty. Therefore, quantifying the impact from each of these components (hydrogeological, behavioral and physiological) in final human health risk prediction can provide guidance for decision makers to best allocate resources towards minimal prediction uncertainty. In this presentation, a multi-component human health risk-based framework is presented which allows decision makers to set priorities through an information entropy-based visualization tool. Results highlight the role of characteristic length-scales characterizing flow and transport in determining data needs within an integrated hydrogeological-health framework. Conditions where uncertainty reduction in human health risk predictions may benefit from better understanding of the health component, as opposed to a more detailed hydrogeological characterization, are also discussed. Finally, results illustrate how different dose-response models can impact the probability of human health risk exceeding a regulatory threshold.

Understanding How Adolescents with Autism Respond to Facial Expressions in Virtual Reality Environments

PubMed Central

Bekele, Esubalew; Zheng, Zhi; Swanson, Amy; Crittendon, Julie; Warren, Zachary; Sarkar, Nilanjan

2013-01-01

Autism Spectrum Disorders (ASD) are characterized by atypical patterns of behaviors and impairments in social communication. Among the fundamental social impairments in the ASD population are challenges in appropriately recognizing and responding to facial expressions. Traditional intervention approaches often require intensive support and well-trained therapists to address core deficits, with many with ASD having tremendous difficulty accessing such care due to lack of available trained therapists as well as intervention costs. As a result, emerging technology such as virtual reality (VR) has the potential to offer useful technology-enabled intervention systems. In this paper, an innovative VR-based facial emotional expression presentation system was developed that allows monitoring of eye gaze and physiological signals related to emotion identification to explore new efficient therapeutic paradigms. A usability study of this new system involving ten adolescents with ASD and ten typically developing adolescents as a control group was performed. The eye tracking and physiological data were analyzed to determine intragroup and intergroup variations of gaze and physiological patterns. Performance data, eye tracking indices and physiological features indicated that there were differences in the way adolescents with ASD process and recognize emotional faces compared to their typically developing peers. These results will be used in the future for an online adaptive VR-based multimodal social interaction system to improve emotion recognition abilities of individuals with ASD. PMID:23428456

Understanding how adolescents with autism respond to facial expressions in virtual reality environments.

PubMed

Bekele, Esubalew; Zheng, Zhi; Swanson, Amy; Crittendon, Julie; Warren, Zachary; Sarkar, Nilanjan

2013-04-01

Autism Spectrum Disorders (ASD) are characterized by atypical patterns of behaviors and impairments in social communication. Among the fundamental social impairments in the ASD population are challenges in appropriately recognizing and responding to facial expressions. Traditional intervention approaches often require intensive support and well-trained therapists to address core deficits, with many with ASD having tremendous difficulty accessing such care due to lack of available trained therapists as well as intervention costs. As a result, emerging technology such as virtual reality (VR) has the potential to offer useful technology-enabled intervention systems. In this paper, an innovative VR-based facial emotional expression presentation system was developed that allows monitoring of eye gaze and physiological signals related to emotion identification to explore new efficient therapeutic paradigms. A usability study of this new system involving ten adolescents with ASD and ten typically developing adolescents as a control group was performed. The eye tracking and physiological data were analyzed to determine intragroup and intergroup variations of gaze and physiological patterns. Performance data, eye tracking indices and physiological features indicated that there were differences in the way adolescents with ASD process and recognize emotional faces compared to their typically developing peers. These results will be used in the future for an online adaptive VR-based multimodal social interaction system to improve emotion recognition abilities of individuals with ASD.

Cryptococcus neoformans Mediator Protein Ssn8 Negatively Regulates Diverse Physiological Processes and Is Required for Virulence

PubMed Central

Wang, Lin-Ing; Lin, Yu-Sheng; Liu, Kung-Hung; Jong, Ambrose Y.; Shen, Wei-Chiang

2011-01-01

Cryptococcus neoformans is a ubiquitously distributed human pathogen. It is also a model system for studying fungal virulence, physiology and differentiation. Light is known to inhibit sexual development via the evolutionarily conserved white collar proteins in C. neoformans. To dissect molecular mechanisms regulating this process, we have identified the SSN8 gene whose mutation suppresses the light-dependent CWC1 overexpression phenotype. Characterization of sex-related phenotypes revealed that Ssn8 functions as a negative regulator in both heterothallic a-α mating and same-sex mating processes. In addition, Ssn8 is involved in the suppression of other physiological processes including invasive growth, and production of capsule and melanin. Interestingly, Ssn8 is also required for the maintenance of cell wall integrity and virulence. Our gene expression studies confirmed that deletion of SSN8 results in de-repression of genes involved in sexual development and melanization. Epistatic and yeast two hybrid studies suggest that C. neoformans Ssn8 plays critical roles downstream of the Cpk1 MAPK cascade and Ste12 and possibly resides at one of the major branches downstream of the Cwc complex in the light-mediated sexual development pathway. Taken together, our studies demonstrate that the conserved Mediator protein Ssn8 functions as a global regulator which negatively regulates diverse physiological and developmental processes and is required for virulence in C. neoformans. PMID:21559476

Paradoxical physiological transitions from aging to late life in Drosophila.

PubMed

Shahrestani, Parvin; Quach, Julie; Mueller, Laurence D; Rose, Michael R

2012-02-01

In a variety of organisms, adulthood is divided into aging and late life, where aging is a period of exponentially increasing mortality rates and late life is a period of roughly plateaued mortality rates. In this study we used ∼57,600 Drosophila melanogaster from six replicate populations to examine the physiological transitions from aging to late life in four functional characters that decline during aging: desiccation resistance, starvation resistance, time spent in motion, and negative geotaxis. Time spent in motion and desiccation resistance declined less quickly in late life compared to their patterns of decline during aging. Negative geotaxis declined at a faster rate in late life compared to its rate of decline during aging. These results yield two key findings: (1) Late-life physiology is distinct from the physiology of aging, in that there is not simply a continuation of the physiological trends which characterize aging; and (2) late life physiology is complex, in that physiological characters vary with respect to their stabilization, deceleration, or acceleration in the transition from aging to late life. These findings imply that a correct understanding of adulthood requires identifying and appropriately characterizing physiology during properly delimited late-life periods as well as aging periods.

Paradoxical Physiological Transitions from Aging to Late Life in Drosophila

PubMed Central

Quach, Julie; Mueller, Laurence D.; Rose, Michael R.

2012-01-01

Abstract In a variety of organisms, adulthood is divided into aging and late life, where aging is a period of exponentially increasing mortality rates and late life is a period of roughly plateaued mortality rates. In this study we used ∼57,600 Drosophila melanogaster from six replicate populations to examine the physiological transitions from aging to late life in four functional characters that decline during aging: desiccation resistance, starvation resistance, time spent in motion, and negative geotaxis. Time spent in motion and desiccation resistance declined less quickly in late life compared to their patterns of decline during aging. Negative geotaxis declined at a faster rate in late life compared to its rate of decline during aging. These results yield two key findings: (1) Late-life physiology is distinct from the physiology of aging, in that there is not simply a continuation of the physiological trends which characterize aging; and (2) late life physiology is complex, in that physiological characters vary with respect to their stabilization, deceleration, or acceleration in the transition from aging to late life. These findings imply that a correct understanding of adulthood requires identifying and appropriately characterizing physiology during properly delimited late-life periods as well as aging periods. PMID:22233126

Molecular bases of circadian rhythmicity in renal physiology and pathology

PubMed Central

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

2013-01-01

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

Age-Related Change in Mobility: Perspectives From Life Course Epidemiology and Geroscience

PubMed Central

Cooper, Rachel; Shardell, Michelle; Simonsick, Eleanor M.; Schrack, Jennifer A.; Kuh, Diana

2016-01-01

Mobility is the most studied and most relevant physical ability affecting quality of life with strong prognostic value for disability and survival. Natural selection has built the “engine” of mobility with great robustness, redundancy, and functional reserve. Efficient patterns of mobility can be acquired during development even by children affected by severe impairments. Analogously, age-associated impairments in mobility-related physiological systems are compensated and overt limitations of mobility only occur when the severity can no longer be compensated. Mobility loss in older persons usually results from multiple impairments in the central nervous system, muscles, joints, and energetic and sensory physiological systems. Early preclinical changes in these physiological systems that precede mobility loss have been poorly studied. Peak performance, rate of decline, compensatory behaviors, or subclinical deterioration of physiological resources may cumulatively influence both timing of mobility loss and chances of recovery, but their role as risk factors has not been adequately characterized. Understanding the natural history of these early changes and intervening on them would likely be the most effective strategy to reduce the burden of disability in the population. For example, young women with low bone peak mass could be counseled to start strength resistance exercise to reduce their high risk of developing osteoporosis and fracture later in life. Expanding this approach to other physiological domains requires collecting and interpreting data from life course epidemiological studies, establishing normative measures of mobility, physical function, and physical activity, and connecting them with life course trajectories of the mobility-relevant physiological domains. PMID:26975983

Increased leaf mesophyll porosity following transient retinoblastoma-related protein silencing is revealed by microcomputed tomography imaging and leads to a system-level physiological response to the altered cell division pattern

PubMed Central

Dorca-Fornell, Carmen; Pajor, Radoslaw; Lehmeier, Christoph; Pérez-Bueno, Marísa; Bauch, Marion; Sloan, Jen; Osborne, Colin; Rolfe, Stephen; Sturrock, Craig; Mooney, Sacha; Fleming, Andrew

2013-01-01

The causal relationship between cell division and growth in plants is complex. Although altered expression of cell-cycle genes frequently leads to altered organ growth, there are many examples where manipulation of the division machinery leads to a limited outcome at the level of organ form, despite changes in constituent cell size. One possibility, which has been under-explored, is that altered division patterns resulting from manipulation of cell-cycle gene expression alter the physiology of the organ, and that this has an effect on growth. We performed a series of experiments on retinoblastoma-related protein (RBR), a well characterized regulator of the cell cycle, to investigate the outcome of altered cell division on leaf physiology. Our approach involved combination of high-resolution microCT imaging and physiological analysis with a transient gene induction system, providing a powerful approach for the study of developmental physiology. Our investigation identifies a new role for RBR in mesophyll differentiation that affects tissue porosity and the distribution of air space within the leaf. The data demonstrate the importance of RBR in early leaf development and the extent to which physiology adapts to modified cellular architecture resulting from altered cell-cycle gene expression. PMID:24118480

The paranasal sinuses: the last frontier in craniofacial biology.

PubMed

Márquez, Samuel

2008-11-01

This special issue of the Anatomical Record explores the presence and diversity of paranasal sinuses in distinct vertebrate groups. The following topics are addressed in particular: dinosaur physiology; development; physiology; adaptation; imaging; and primate systematics. A variety of approaches and techniques are used to examine and characterize the diversity of paranasal sinus pneumatization in a wide spectrum of vertebrates. These range from dissection to histology, from plain X-rays to computer tomography, from comparative anatomy to natural experimental settings, from mathematical computation to computer model simulation, and 2D to 3D reconstructions. The articles in this issue are a combination of literature review and new, hypothesis-driven anatomical research that highlights the complexities of paranasal sinus growth and development; ontogenetic and disease processes; physiology; paleontology; primate systematics; and human evolution. The issue incorporates a wide variety of vertebrates, encompassing a period of over 65 million years, in an effort to offer insight into the diversity of the paranasal sinus complexes through time and space, and thereby providing a greater understanding and appreciation of these special spaces within the cranium. Copyright 2008 Wiley-Liss, Inc.

Form(ul)ation of adipocytes by lipids.

PubMed

Lapid, Kfir; Graff, Jonathan M

2017-07-03

Lipids have the potential to serve as bio-markers, which allow us to analyze and to identify cells under various experimental settings, and to serve as a clinical diagnostic tool. For example, diagnosis according to specific lipids that are associated with diabetes and obesity. The rapid development of mass-spectrometry techniques enables identification and profiling of multiple types of lipid species. Together, lipid profiling and data interpretation forge the new field of lipidomics. Lipidomics can be used to characterize physiologic and pathophysiological processes in adipocytes, since lipid metabolism is at the core of adipocyte physiology and energy homeostasis. A significant bulk of lipids are stored in adipocytes, which can be released and used to produce energy, used to build membranes, or used as signaling molecules that regulate metabolism. In this review, we discuss how exhaust of lipidomes can be used to study adipocyte differentiation, physiology and pathophysiology.

Manometric characterization of rectal dysfunction following radical hysterectomy.

PubMed

Barnes, W; Waggoner, S; Delgado, G; Maher, K; Potkul, R; Barter, J; Benjamin, S

1991-08-01

Bladder dysfunction thought to be due to partial denervation has been described following radical hysterectomy. Some patients experience acute and chronic rectal dysfunction characterized by difficulty with defecation and loss of defecatory urge. To define this abnormality, anorectal pressure profiles were examined in 15 patients with Stage I carcinoma of the cervix before and after radical hysterectomy. Profiles were done using standard anorectal manometry with a water-infused system. In all patients preoperative manometric profiles were normal; postoperative studies were abnormal in all patients. Features seen include altered relaxation of the internal sphincter, increased distension needed to trigger relaxation, and decreased rectal sensation; external sphincters and resting internal sphincters were unchanged. Postoperatively, 12 patients reported problems with rectal function. A physiologic defect is definable in patients undergoing radical hysterectomy; this suggests disruption of the spinal reflex arcs controlling rectal emptying. These physiologic abnormalities correlate with the clinical symptomatology experienced by some patients. Continuing definition and evaluation of management options in this situation should be useful in developing effective therapy for rectal dysfunction following radical hysterectomy.

Quantitative characterization of mechanically indented in vivo human skin in adults and infants using optical coherence tomography

NASA Astrophysics Data System (ADS)

Huang, Pin-Chieh; Pande, Paritosh; Shelton, Ryan L.; Joa, Frank; Moore, Dave; Gillman, Elisa; Kidd, Kimberly; Nolan, Ryan M.; Odio, Mauricio; Carr, Andrew; Boppart, Stephen A.

2017-03-01

Influenced by both the intrinsic viscoelasticity of the tissue constituents and the time-evolved redistribution of fluid within the tissue, the biomechanical response of skin can reflect not only localized pathology but also systemic physiology of an individual. While clinical diagnosis of skin pathologies typically relies on visual inspection and manual palpation, a more objective and quantitative approach for tissue characterization is highly desirable. Optical coherence tomography (OCT) is an interferometry-based imaging modality that enables in vivo assessment of cross-sectional tissue morphology with micron-scale resolution, which surpasses those of most standard clinical imaging tools, such as ultrasound imaging and magnetic resonance imaging. This pilot study investigates the feasibility of characterizing the biomechanical response of in vivo human skin using OCT. OCT-based quantitative metrics were developed and demonstrated on the human subject data, where a significant difference between deformed and nondeformed skin was revealed. Additionally, the quantified postindentation recovery results revealed differences between aged (adult) and young (infant) skin. These suggest that OCT has the potential to quantitatively assess the mechanically perturbed skin as well as distinguish different physiological conditions of the skin, such as changes with age or disease.

Advanced continuous cultivation methods for systems microbiology.

PubMed

Adamberg, Kaarel; Valgepea, Kaspar; Vilu, Raivo

2015-09-01

Increasing the throughput of systems biology-based experimental characterization of in silico-designed strains has great potential for accelerating the development of cell factories. For this, analysis of metabolism in the steady state is essential as only this enables the unequivocal definition of the physiological state of cells, which is needed for the complete description and in silico reconstruction of their phenotypes. In this review, we show that for a systems microbiology approach, high-resolution characterization of metabolism in the steady state--growth space analysis (GSA)--can be achieved by using advanced continuous cultivation methods termed changestats. In changestats, an environmental parameter is continuously changed at a constant rate within one experiment whilst maintaining cells in the physiological steady state similar to chemostats. This increases the resolution and throughput of GSA compared with chemostats, and, moreover, enables following of the dynamics of metabolism and detection of metabolic switch-points and optimal growth conditions. We also describe the concept, challenge and necessary criteria of the systematic analysis of steady-state metabolism. Finally, we propose that such systematic characterization of the steady-state growth space of cells using changestats has value not only for fundamental studies of metabolism, but also for systems biology-based metabolic engineering of cell factories.

Physiologic and endocrinologic characterization of male sex-biased diabetes in C57BLKS/J mice congenic for the fat mutation at the carboxypeptidease E locus.

PubMed

Leiter, E H; Kintner, J; Flurkey, K; Beamer, W G; Naggert, J K

1999-02-01

The fat gene in mice represents a recessive mutation at the carboxypeptidase E (Cpe) locus. The mutant allele (Cpe(fat)) encodes a highly unstable enzyme and produces an obesity phenotype characterized by attenuated processing of prohormones such as proinsulin that require this exopeptidase for full maturation. This article presents a preliminary physiologic and endocrinologic characterization of the stock of C57BLKS/LtJ-Cpe(fat)/Cpe(fat) mice at the backcross generation (N10) currently distributed by The Jackson Laboratory. Although previously reported not to be diabetogenic at N5, an additional five backcrosses to the C57BLKS/J background resulted in a male-biased development of both obesity and diabetes. Major differences distinguishing this mutant stock from the phenotypes produced by either the diabetes (Lepr(db)) or obese (Lep(ob)) mutations on the same inbred strain background are lack of hyperphagia and hypercorticism, sensitivity of diabetic males to exogenous insulin, and a milder and male-biased diabetes syndrome that is not associated with widespread beta-cell necrosis and islet atrophy, and that often remits with age.

Analysis of cardiovascular regulation.

PubMed

Wilhelm, F H; Grossman, P; Roth, W T

1999-01-01

Adequate characterization of hemodynamic and autonomic responses to physical and mental stress can elucidate underlying mechanisms of cardiovascular disease or anxiety disorders. We developed a physiological signal processing system for analysis of continuously recorded ECG, arterial blood pressure (BP), and respiratory signals using the programming language Matlab. Data collection devices are a 16-channel digital, physiological recorder (Vitaport), a finger arterial pressure transducer (Finapres), and a respiratory inductance plethysmograph (Respitrace). Besides the conventional analysis of the physiological channels, power spectral density and transfer functions of respiration, heart rate, and blood pressure variability are used to characterize respiratory sinus arrhythmia (RSA), 0.10-Hz BP oscillatory activity (Mayer-waves), and baroreflex sensitivity. The arterial pressure transducer waveforms permit noninvasive estimation of stroke volume, cardiac output, and systemic vascular resistance. Time trends in spectral composition of indices are assessed using complex demodulation. Transient dynamic changes of cardiovascular parameters at the onset of stress and recovery periods are quantified using a regression breakpoint model that optimizes piecewise linear curve fitting. Approximate entropy (ApEn) is computed to quantify the degree of chaos in heartbeat dynamics. Using our signal processing system we found distinct response patterns in subgroups of patients with coronary artery disease or anxiety disorders, which were related to specific pharmacological and behavioral factors.

Membranes to achieve immunoprotection of transplanted islets

PubMed Central

Schweicher, Julien; Nyitray, Crystal; Desai, Tejal A.

2014-01-01

Transplantation of islet or beta cells is seen as the cure for type 1 diabetes since it allows physiological regulation of blood glucose levels without requiring any compliance from the patients. In order to circumvent the use of immunosuppressive drugs (and their side effects), semipermeable membranes have been developed to encapsulate and immunoprotect transplanted cells. This review presents the historical developments of immunoisolation and provides an update on the current research in this field. A particular emphasis is laid on the fabrication, characterization and performance of membranes developed for immunoisolation applications. PMID:24389172

Characterization of dynamic physiology of the bladder by optical coherence tomography

NASA Astrophysics Data System (ADS)

Yuan, Zhijia; Keng, Kerri; Pan, Rubin; Ren, Hugang; Du, Congwu; Kim, Jason; Pan, Yingtian

2012-03-01

Because of its high spatial resolution and noninvasive imaging capabilities, optical coherence tomography has been used to characterize the morphological details of various biological tissues including urinary bladder and to diagnose their alternations (e.g., cancers). In addition to static morphology, the dynamic features of tissue morphology can provide important information that can be used to diagnose the physiological and functional characteristics of biological tissues. Here, we present the imaging studies based on optical coherence tomography to characterize motion related physiology and functions of rat bladder detrusor muscles and compared the results with traditional biomechanical measurements. Our results suggest that optical coherence tomography is capable of providing quantitative evaluation of contractile functions of intact bladder (without removing bladder epithelium and connective tissue), which is potentially of more clinical relevance for future clinical diagnosis - if incorporated with cystoscopic optical coherence tomography.

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.

MRI EVALUATION OF KNEE CARTILAGE

PubMed Central

Rodrigues, Marcelo Bordalo; Camanho, Gilberto Luís

2015-01-01

Through the ability of magnetic resonance imaging (MRI) to characterize soft tissue noninvasively, it has become an excellent method for evaluating cartilage. The development of new and faster methods allowed increased resolution and contrast in evaluating chondral structure, with greater diagnostic accuracy. In addition, physiological techniques for cartilage assessment that can detect early changes before the appearance of cracks and erosion have been developed. In this updating article, the various techniques for chondral assessment using knee MRI will be discussed and demonstrated. PMID:27022562

Physiologically based pharmacokinetic modeling of PLGA nanoparticles with varied mPEG content

PubMed Central

Li, Mingguang; Panagi, Zoi; Avgoustakis, Konstantinos; Reineke, Joshua

2012-01-01

Biodistribution of nanoparticles is dependent on their physicochemical properties (such as size, surface charge, and surface hydrophilicity). Clear and systematic understanding of nanoparticle properties’ effects on their in vivo performance is of fundamental significance in nanoparticle design, development and optimization for medical applications, and toxicity evaluation. In the present study, a physiologically based pharmacokinetic model was utilized to interpret the effects of nanoparticle properties on previously published biodistribution data. Biodistribution data for five poly(lactic-co-glycolic) acid (PLGA) nanoparticle formulations prepared with varied content of monomethoxypoly (ethyleneglycol) (mPEG) (PLGA, PLGA-mPEG256, PLGA-mPEG153, PLGA-mPEG51, PLGA-mPEG34) were collected in mice after intravenous injection. A physiologically based pharmacokinetic model was developed and evaluated to simulate the mass-time profiles of nanoparticle distribution in tissues. In anticipation that the biodistribution of new nanoparticle formulations could be predicted from the physiologically based pharmacokinetic model, multivariate regression analysis was performed to build the relationship between nanoparticle properties (size, zeta potential, and number of PEG molecules per unit surface area) and biodistribution parameters. Based on these relationships, characterized physicochemical properties of PLGA-mPEG495 nanoparticles (a sixth formulation) were used to calculate (predict) biodistribution profiles. For all five initial formulations, the developed model adequately simulates the experimental data indicating that the model is suitable for description of PLGA-mPEG nanoparticle biodistribution. Further, the predicted biodistribution profiles of PLGA-mPEG495 were close to experimental data, reflecting properly developed property–biodistribution relationships. PMID:22419876

Harnessing glycomics technologies: integrating structure with function for glycan characterization

PubMed Central

Robinson, Luke N.; Artpradit, Charlermchai; Raman, Rahul; Shriver, Zachary H.; Ruchirawat, Mathuros; Sasisekharan, Ram

2013-01-01

Glycans, or complex carbohydrates, are a ubiquitous class of biological molecules which impinge on a variety of physiological processes ranging from signal transduction to tissue development and microbial pathogenesis. In comparison to DNA and proteins, glycans present unique challenges to the study of their structure and function owing to their complex and heterogeneous structures and the dominant role played by multivalency in their sequence-specific biological interactions. Arising from these challenges, there is a need to integrate information from multiple complementary methods to decode structure-function relationships. Focusing on acidic glycans, we describe here key glycomics technologies for characterizing their structural attributes, including linkage, modifications, and topology, as well as for elucidating their role in biological processes. Two cases studies, one involving sialylated branched glycans and the other sulfated glycosaminoglycans, are used to highlight how integration of orthogonal information from diverse datasets enables rapid convergence of glycan characterization for development of robust structure-function relationships. PMID:22522536

Characterization of the pH and Temperature in the Rabbit, Pig, and Monkey Eye: Key Parameters for the Development of Long-Acting Delivery Ocular Strategies.

PubMed

Lorget, Florence; Parenteau, Audrey; Carrier, Michel; Lambert, Daniel; Gueorguieva, Ana; Schuetz, Chris; Bantseev, Vlad; Thackaberry, Evan

2016-09-06

Many long-acting delivery strategies for ocular indications rely on pH- and/or temperature-driven release of the therapeutic agent and degradation of the drug carrier. Yet, these physiological parameters are poorly characterized in ocular animal models. These strategies aim at reducing the frequency of dosing, which is of particular interest for the treatment of chronic disorders affecting the posterior segment of the eye, such as macular degeneration that warrants monthly or every other month intravitreal injections. We used anesthetized white New Zealand rabbits, Yucatan mini pigs, and cynomolgus monkeys to characterize pH and temperature in several vitreous locations and the central aqueous location. We also established post mortem pH changes in the vitreous. Our data showed regional and species differences, which need to be factored into strategies for developing biodegradable long-acting delivery systems.

Physiologically based pharmacokinetic model of amphotericin B disposition in rats following administration of deoxycholate formulation (Fungizone®): pooled analysis of published data.

PubMed

Kagan, Leonid; Gershkovich, Pavel; Wasan, Kishor M; Mager, Donald E

2011-06-01

The time course of tissue distribution of amphotericin B (AmB) has not been sufficiently characterized despite its therapeutic importance and an apparent disconnect between plasma pharmacokinetics and clinical outcomes. The goals of this work were to develop and evaluate a physiologically based pharmacokinetic (PBPK) model to characterize the disposition properties of AmB administered as deoxycholate formulation in healthy rats and to examine the utility of the PBPK model for interspecies scaling of AmB pharmacokinetics. AmB plasma and tissue concentration-time data, following single and multiple intravenous administration of Fungizone® to rats, from several publications were combined for construction of the model. Physiological parameters were fixed to literature values. Various structural models for single organs were evaluated, and the whole-body PBPK model included liver, spleen, kidney, lung, heart, gastrointestinal tract, plasma, and remainder compartments. The final model resulted in a good simultaneous description of both single and multiple dose data sets. Incorporation of three subcompartments for spleen and kidney tissues was required for capturing a prolonged half-life in these organs. The predictive performance of the final PBPK model was assessed by evaluating its utility in predicting pharmacokinetics of AmB in mice and humans. Clearance and permeability-surface area terms were scaled with body weight. The model demonstrated good predictions of plasma AmB concentration-time profiles for both species. This modeling framework represents an important basis that may be further utilized for characterization of formulation- and disease-related factors in AmB pharmacokinetics and pharmacodynamics.

Teleosts as Model Organisms To Understand Host-Microbe Interactions.

PubMed

Lescak, Emily A; Milligan-Myhre, Kathryn C

2017-08-01

Host-microbe interactions are influenced by complex host genetics and environment. Studies across animal taxa have aided our understanding of how intestinal microbiota influence vertebrate development, disease, and physiology. However, traditional mammalian studies can be limited by the use of isogenic strains, husbandry constraints that result in small sample sizes and limited statistical power, reliance on indirect characterization of gut microbial communities from fecal samples, and concerns of whether observations in artificial conditions are actually reflective of what occurs in the wild. Fish models are able to overcome many of these limitations. The extensive variation in the physiology, ecology, and natural history of fish enriches studies of the evolution and ecology of host-microbe interactions. They share physiological and immunological features common among vertebrates, including humans, and harbor complex gut microbiota, which allows identification of the mechanisms driving microbial community assembly. Their accelerated life cycles and large clutch sizes and the ease of sampling both internal and external microbial communities make them particularly well suited for robust statistical studies of microbial diversity. Gnotobiotic techniques, genetic manipulation of the microbiota and host, and transparent juveniles enable novel insights into mechanisms underlying development of the digestive tract and disease states. Many diseases involve a complex combination of genes which are difficult to manipulate in homogeneous model organisms. By taking advantage of the natural genetic variation found in wild fish populations, as well as of the availability of powerful genetic tools, future studies should be able to identify conserved genes and pathways that contribute to human genetic diseases characterized by dysbiosis. Copyright © 2017 Lescak and Milligan-Myhre.

Instrumentation for Non-Invasive Assessment of Cardiovascular Regulation

NASA Technical Reports Server (NTRS)

Cohen, Richard J.

1999-01-01

It is critically important to be able to assess alterations in cardiovascular regulation during and after space flight. We propose to develop an instrument for the non-invasive assessment of such alterations that can be used on the ground and potentially during space flight. This instrumentation would be used by the Cardiovascular Alterations Team at multiple sites for the study of the effects of space flight on the cardiovascular system and the evaluation of countermeasures. In particular, the Cardiovascular Alterations Team will use this instrumentation in conjunction with ground-based human bed-rest studies and during application of acute stresses e.g., tilt, lower body negative pressure, and exercise. In future studies, the Cardiovascular Alterations Team anticipates using this instrumentation to study astronauts before and after space flight and ultimately, during space flight. The instrumentation may also be used by the Bone Demineralization/Calcium Metabolism Team, the Neurovestibular Team and the Human Performance Factors, Sleep and Chronobiology Team to measure changes in autonomic nervous function. The instrumentation will be based on a powerful new technology - cardiovascular system identification (CSI) - which has been developed in our laboratory. CSI provides a non-invasive approach for the study of alterations in cardiovascular regulation. This approach involves the analysis of second-to-second fluctuations in physiologic signals such as heart rate and non-invasively measured arterial blood pressure in order to characterize quantitatively the physiologic mechanisms responsible for the couplings between these signals. Through the characterization of multiple physiologic mechanisms, CSI provides a closed-loop model of the cardiovascular regulatory state in an individual subject.

Teleosts as Model Organisms To Understand Host-Microbe Interactions

PubMed Central

2017-01-01

ABSTRACT Host-microbe interactions are influenced by complex host genetics and environment. Studies across animal taxa have aided our understanding of how intestinal microbiota influence vertebrate development, disease, and physiology. However, traditional mammalian studies can be limited by the use of isogenic strains, husbandry constraints that result in small sample sizes and limited statistical power, reliance on indirect characterization of gut microbial communities from fecal samples, and concerns of whether observations in artificial conditions are actually reflective of what occurs in the wild. Fish models are able to overcome many of these limitations. The extensive variation in the physiology, ecology, and natural history of fish enriches studies of the evolution and ecology of host-microbe interactions. They share physiological and immunological features common among vertebrates, including humans, and harbor complex gut microbiota, which allows identification of the mechanisms driving microbial community assembly. Their accelerated life cycles and large clutch sizes and the ease of sampling both internal and external microbial communities make them particularly well suited for robust statistical studies of microbial diversity. Gnotobiotic techniques, genetic manipulation of the microbiota and host, and transparent juveniles enable novel insights into mechanisms underlying development of the digestive tract and disease states. Many diseases involve a complex combination of genes which are difficult to manipulate in homogeneous model organisms. By taking advantage of the natural genetic variation found in wild fish populations, as well as of the availability of powerful genetic tools, future studies should be able to identify conserved genes and pathways that contribute to human genetic diseases characterized by dysbiosis. PMID:28439034

[Modeling of experimental hypertension by chronic salt loading combined with a low-protein diet in Wistar rats].

PubMed

Strekalova, V V; Khachirov, D G; Dedenkov, A N; Suvorov, Iu I; Shvatsabaia, I K

1989-01-01

Combination of chronic salt loading with protein-poor diet produces experimental hypertension with natrium consumption near to physiological. The present model is characterized, compared to the existing one, by stage development, moderate arterial blood pressure elevation and absence of "salt toxicosis" and may be thus considered more adequate for experimental investigation of primary arterial hypertension pathophysiology.

Whole tree xylem sap flow responses to multiple environmental variables in a wet tropical forest

Treesearch

J.J. O' Brien; S.F. Oberbauer; D.B. Clark

2004-01-01

In order to quantify and characterize the variance in rain-forest tree physiology, whole tree sap flow responses to local environmental conditions were investigated in 10 species of trees with diverse traits at La Selva Biological Station, Costa Rica. A simple model was developed to predict tree sap flow responses to a synthetic environmental variable generated by a...

Investigation of Sclerotinia sclerotiorum strains variability in Brazil.

PubMed

Abreu, M J; Souza, E A

2015-06-18

White mold is a common bean disease caused by the fungus Sclerotinia sclerotiorum, resulting in economic losses in Brazil and worldwide. Lack of knowledge about the population structure of the pathogen makes it difficult to control the disease. The aim of this study was to characterize strains of S. sclerotiorum obtained from ex-perimental and commercial common bean fields in Brazil. We analyzed 50 strains of S. sclerotiorum collected at several locations in the state of Minas Gerais. The strains were characterized according to their ability and time for developing apothecia. Morphological and physiological analyses such as the mycelial growth index, colony color, the time re-quired to form the first sclerotia on media, the number of sclerotia per plate, average sclerotium size, and sclerotium shape were performed. We determined the mycelial compatibility, conducted molecular analy-sis of microsatellites, and evaluated the aggressiveness of 28 strains. Most strains had the ability to form apothecia. A small group of strains showed mycelial compatibility, and the strains showed different aggres-siveness levels. Overall, the population studied here demonstrated wide variability based on the morphological, physiological, and molecular traits analyzed. The average size and shape of sclerotia presented a cor-relation of 0.617, whereas the times required to form sclerotia and the number of sclerotia per plate showed a correlation of -0.455. The char-acterization of the pathogen population described herein will provide an important tool for promoting the development of bean cultivars re-sistant to white mold.

Transient CD15-positive endothelial phenotype in the human placenta correlates with physiological and pathological fetoplacental immaturity.

PubMed

Seidmann, L; Suhan, T; Unger, R; Gerein, V; Kirkpatrick, C J

2014-09-01

Placental growth and villous maturation are critical parameters of placental function at the end of pregnancy. A failure in these processes leads to the development of placental dysfunction, as well as fetal and neonatal mortality and morbidity. The aim of the study was to determine the relevant diagnostic markers associated with pathological placental development. Forty tissue samples from normal placentas of different gestational age and 68 pathological term placentas with defective villous maturation (GDM, idiopathic IUFD, preeclamsia, HELLP syndrome) comprised the comparative immunohistochemical study (CD15, CD45 and CD34). Positive immunohistochemical reactions were quantitatively assessed in the chorionic plate and vessels of the villi of different histological type. Physiologically immature placentas of the first and second trimester and pathologically immature term placentas were characterized by marked endothelial CD15-immunostaining. A significant loss of CD15-positive endothelium of the placentas was associated with a physiological and accelerated villous maturity. A spatio-temporal correlation was shown for CD15+ endothelial cells (ECs) and the number of CD45+ stromal cells (SCs). A negative temporal correlation was shown for CD15+ ECs and CD15+ myelomonocytes in the fetal blood. CD34 expression in the ECs was stable during the pregnancy. A correlation between a transient CD15-positive endothelial phenotype and a physiological and pathological fetoplacental immaturity was demonstrated. Physiological and accelerated placental maturation was accompanied by a significant disappearance of CD15-positive endothelium. We propose that "immature" CD15+ endothelium is an important diagnostic marker of the physiological and pathological fetoplacental immaturity. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Development of an anaesthetized-rat model of exercise hyperpnoea: an integrative model of respiratory control using an equilibrium diagram.

PubMed

Miyamoto, Tadayoshi; Manabe, Kou; Ueda, Shinya; Nakahara, Hidehiro

2018-05-01

What is the central question of this study? The lack of useful small-animal models for studying exercise hyperpnoea makes it difficult to investigate the underlying mechanisms of exercise-induced ventilatory abnormalities in various disease states. What is the main finding and its importance? We developed an anaesthetized-rat model for studying exercise hyperpnoea, using a respiratory equilibrium diagram for quantitative characterization of the respiratory chemoreflex feedback system. This experimental model will provide an opportunity to clarify the major determinant mechanisms of exercise hyperpnoea, and will be useful for understanding the mechanisms responsible for abnormal ventilatory responses to exercise in disease models. Exercise-induced ventilatory abnormalities in various disease states seem to arise from pathological changes of respiratory regulation. Although experimental studies in small animals are essential to investigate the pathophysiological basis of various disease models, the lack of an integrated framework for quantitatively characterizing respiratory regulation during exercise prevents us from resolving these problems. The purpose of this study was to develop an anaesthetized-rat model for studying exercise hyperpnoea for quantitative characterization of the respiratory chemoreflex feedback system. In 24 anaesthetized rats, we induced muscle contraction by stimulating bilateral distal sciatic nerves at low and high voltage to mimic exercise. We recorded breath-by-breath respiratory gas analysis data and cardiorespiratory responses while running two protocols to characterize the controller and plant of the respiratory chemoreflex. The controller was characterized by determining the linear relationship between end-tidal CO 2 pressure (P ETC O2) and minute ventilation (V̇E), and the plant by the hyperbolic relationship between V̇E and P ETC O2. During exercise, the controller curve shifted upward without change in controller gain, accompanying increased oxygen uptake. The hyperbolic plant curve shifted rightward and downward depending on exercise intensity as predicted by increased metabolism. Exercise intensity-dependent changes in operating points (V̇E and P ETC O2) were estimated by integrating the controller and plant curves in a respiratory equilibrium diagram. In conclusion, we developed an anaesthetized-rat model for studying exercise hyperpnoea, using systems analysis for quantitative characterization of the respiratory system. This novel experimental model will be useful for understanding the mechanisms responsible for abnormal ventilatory responses to exercise in disease models. © 2018 Morinomiya University of Medical Sciences. Experimental Physiology © 2018 The Physiological Society.

3D modeling and characterization of a calorimetric flow rate sensor for sweat rate sensing applications

NASA Astrophysics Data System (ADS)

Iftekhar, Ahmed Tashfin; Ho, Jenny Che-Ting; Mellinger, Axel; Kaya, Tolga

2017-03-01

Sweat-based physiological monitoring has been intensively explored in the last decade with the hopes of developing real-time hydration monitoring devices. Although the content of sweat (electrolytes, lactate, urea, etc.) provides significant information about the physiology, it is also very important to know the rate of sweat at the time of sweat content measurements because the sweat rate is known to alter the concentrations of sweat compounds. We developed a calorimetric based flow rate sensor using PolydimethylSiloxane that is suitable for sweat rate applications. Our simple approach on using temperature-based flow rate detection can easily be adapted to multiple sweat collection and analysis devices. Moreover, we have developed a 3D finite element analysis model of the device using COMSOL Multiphysics™ and verified the flow rate measurements. The experiment investigated flow rate values from 0.3 μl/min up to 2.1 ml/min, which covers the human sweat rate range (0.5 μl/min-10 μl/min). The 3D model simulations and analytical model calculations covered an even wider range in order to understand the main physical mechanisms of the device. With a verified 3D model, different environmental heat conditions could be further studied to shed light on the physiology of the sweat rate.

Success stories and emerging themes in conservation physiology.

PubMed

Madliger, Christine L; Cooke, Steven J; Crespi, Erica J; Funk, Jennifer L; Hultine, Kevin R; Hunt, Kathleen E; Rohr, Jason R; Sinclair, Brent J; Suski, Cory D; Willis, Craig K R; Love, Oliver P

2016-01-01

The potential benefits of physiology for conservation are well established and include greater specificity of management techniques, determination of cause-effect relationships, increased sensitivity of health and disturbance monitoring and greater capacity for predicting future change. While descriptions of the specific avenues in which conservation and physiology can be integrated are readily available and important to the continuing expansion of the discipline of 'conservation physiology', to date there has been no assessment of how the field has specifically contributed to conservation success. However, the goal of conservation physiology is to foster conservation solutions and it is therefore important to assess whether physiological approaches contribute to downstream conservation outcomes and management decisions. Here, we present eight areas of conservation concern, ranging from chemical contamination to invasive species to ecotourism, where physiological approaches have led to beneficial changes in human behaviour, management or policy. We also discuss the shared characteristics of these successes, identifying emerging themes in the discipline. Specifically, we conclude that conservation physiology: (i) goes beyond documenting change to provide solutions; (ii) offers a diversity of physiological metrics beyond glucocorticoids (stress hormones); (iii) includes approaches that are transferable among species, locations and times; (iv) simultaneously allows for human use and benefits to wildlife; and (v) is characterized by successes that can be difficult to find in the primary literature. Overall, we submit that the field of conservation physiology has a strong foundation of achievements characterized by a diversity of conservation issues, taxa, physiological traits, ecosystem types and spatial scales. We hope that these concrete successes will encourage the continued evolution and use of physiological tools within conservation-based research and management plans.

Evaluation of a patient with suspected chronic demyelinating polyneuropathy.

PubMed

Jani-Acsadi, Agnes; Lewis, Richard A

2013-01-01

Demyelinating neuropathies are typically characterized by physiological slowing of conduction velocity and pathologically by segmental loss of myelin and in some instances, evidence of remyelination. Clinically, patients with demyelinating neuropathy can be seen with inherited disorders (Charcot-Marie-Tooth disease) or acquired disorders, typically immune-mediated or inflammatory. The acquired disorders can be either acute or subacute as seen in the acute inflammatory demyelinating polyneuropathy (AIDP) form of Guillain-Barré syndrome or chronic progressive or relapsing disorders such as chronic inflammatory demyelinating polyneuropathy. It is important to develop a logical approach to diagnosing these disorders. This requires an understanding of the clinical, genetic, physiological, and pathological features of these neuropathies. Clinically, important features to consider are the temporal progression, degree of symmetry, and involvement of proximal as well as distal muscles. Genetically, recognizing the different inheritance patterns and age of onset allow for a coordinated approach to determining a specific genotype. Physiologically, besides nerve conduction slowing, other physiological hallmarks of demyelination include temporal dispersion of compound motor action potentials (CMAP) on proximal stimulation, conduction block, and distal CMAP duration prolongation with certain patterns of involvement pointing to specific disorders. This chapter focuses on these various aspects of the evaluation of patients with chronic acquired demyelinating neuropathies to develop a comprehensive and thoughtful diagnostic concept. Copyright © 2013 Elsevier B.V. All rights reserved.

Drosophila development, physiology, behavior, and lifespan are influenced by altered dietary composition

PubMed Central

Ormerod, Kiel G.; LePine, Olivia K.; Abbineni, Prabhodh S.; Bridgeman, Justin M.; Mercier, A. Joffre; Tattersall, Glenn J.

2017-01-01

ABSTRACT Diet profoundly influences the behavior of animals across many phyla. Despite this, most laboratories using model organisms, such as Drosophila, use multiple, different, commercial or custom-made media for rearing their animals. In addition to measuring growth, fecundity and longevity, we used several behavioral and physiological assays to determine if and how altering food media influence wild-type (Canton S) Drosophila melanogaster, at larval, pupal, and adult stages. Comparing 2 commonly used commercial food media we observed several key developmental and morphological differences. Third-instar larvae and pupae developmental timing, body weight and size, and even lifespan significantly differed between the 2 diets, and some of these differences persisted into adulthood. Diet was also found to produce significantly different thermal preference, locomotory capacity for geotaxis, feeding rates, and lower muscle response to hormonal stimulation. There were no differences, however, in adult thermal preferences, in the number or viability of eggs laid, or in olfactory learning and memory between the diets. We characterized the composition of the 2 diets and found particularly significant differences in cholesterol and (phospho)lipids between them. Notably, diacylglycerol (DAG) concentrations vary substantially between the 2 diets, and may contribute to key phenotypic differences, including lifespan. Overall, the data confirm that 2 different diets can profoundly influence the behavior, physiology, morphology and development of wild-type Drosophila, with greater behavioral and physiologic differences occurring during the larval stages. PMID:28277941

Optoacoustic Monitoring of Physiologic Variables

PubMed Central

Esenaliev, Rinat O.

2017-01-01

Optoacoustic (photoacoustic) technique is a novel diagnostic platform that can be used for noninvasive measurements of physiologic variables, functional imaging, and hemodynamic monitoring. This technique is based on generation and time-resolved detection of optoacoustic (thermoelastic) waves generated in tissue by short optical pulses. This provides probing of tissues and individual blood vessels with high optical contrast and ultrasound spatial resolution. Because the optoacoustic waves carry information on tissue optical and thermophysical properties, detection, and analysis of the optoacoustic waves allow for measurements of physiologic variables with high accuracy and specificity. We proposed to use the optoacoustic technique for monitoring of a number of important physiologic variables including temperature, thermal coagulation, freezing, concentration of molecular dyes, nanoparticles, oxygenation, and hemoglobin concentration. In this review we present origin of contrast and high spatial resolution in these measurements performed with optoacoustic systems developed and built by our group. We summarize data obtained in vitro, in experimental animals, and in humans on monitoring of these physiologic variables. Our data indicate that the optoacoustic technology may be used for monitoring of cerebral blood oxygenation in patients with traumatic brain injury and in neonatal patients, central venous oxygenation monitoring, total hemoglobin concentration monitoring, hematoma detection and characterization, monitoring of temperature, and coagulation and freezing boundaries during thermotherapy. PMID:29311964

Optoacoustic Monitoring of Physiologic Variables.

PubMed

Esenaliev, Rinat O

2017-01-01

Optoacoustic (photoacoustic) technique is a novel diagnostic platform that can be used for noninvasive measurements of physiologic variables, functional imaging, and hemodynamic monitoring. This technique is based on generation and time-resolved detection of optoacoustic (thermoelastic) waves generated in tissue by short optical pulses. This provides probing of tissues and individual blood vessels with high optical contrast and ultrasound spatial resolution. Because the optoacoustic waves carry information on tissue optical and thermophysical properties, detection, and analysis of the optoacoustic waves allow for measurements of physiologic variables with high accuracy and specificity. We proposed to use the optoacoustic technique for monitoring of a number of important physiologic variables including temperature, thermal coagulation, freezing, concentration of molecular dyes, nanoparticles, oxygenation, and hemoglobin concentration. In this review we present origin of contrast and high spatial resolution in these measurements performed with optoacoustic systems developed and built by our group. We summarize data obtained in vitro , in experimental animals, and in humans on monitoring of these physiologic variables. Our data indicate that the optoacoustic technology may be used for monitoring of cerebral blood oxygenation in patients with traumatic brain injury and in neonatal patients, central venous oxygenation monitoring, total hemoglobin concentration monitoring, hematoma detection and characterization, monitoring of temperature, and coagulation and freezing boundaries during thermotherapy.

Carbon nanopipettes characterize calcium release pathways in breast cancer cells

NASA Astrophysics Data System (ADS)

Schrlau, Michael G.; Brailoiu, Eugen; Patel, Sandip; Gogotsi, Yury; Dun, Nae J.; Bau, Haim H.

2008-08-01

Carbon-based nanoprobes are attractive for minimally invasive cell interrogation but their application in cell physiology has thus far been limited. We have developed carbon nanopipettes (CNPs) with nanoscopic tips and used them to inject calcium-mobilizing messengers into cells without compromising cell viability. We identify pathways sensitive to cyclic adenosine diphosphate ribose (cADPr) and nicotinic acid adenine dinucleotide phosphate (NAADP) in breast carcinoma cells. Our findings demonstrate the superior utility of CNPs for intracellular delivery of impermeant molecules and, more generally, for cell physiology studies. The CNPs do not appear to cause any lasting damage to cells. Their advantages over commonly used glass pipettes include smaller size, breakage and clogging resistance, and potential for multifunctionality such as in concurrent injection and electrical measurements.

Carbon nanopipettes characterize calcium release pathways in breast cancer cells.

PubMed

Schrlau, Michael G; Brailoiu, Eugen; Patel, Sandip; Gogotsi, Yury; Dun, Nae J; Bau, Haim H

2008-08-13

Carbon-based nanoprobes are attractive for minimally invasive cell interrogation but their application in cell physiology has thus far been limited. We have developed carbon nanopipettes (CNPs) with nanoscopic tips and used them to inject calcium-mobilizing messengers into cells without compromising cell viability. We identify pathways sensitive to cyclic adenosine diphosphate ribose (cADPr) and nicotinic acid adenine dinucleotide phosphate (NAADP) in breast carcinoma cells. Our findings demonstrate the superior utility of CNPs for intracellular delivery of impermeant molecules and, more generally, for cell physiology studies. The CNPs do not appear to cause any lasting damage to cells. Their advantages over commonly used glass pipettes include smaller size, breakage and clogging resistance, and potential for multifunctionality such as in concurrent injection and electrical measurements.

Physiology of Hyperuricemia and Urate-Lowering Treatments.

PubMed

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

2018-01-01

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

What do we know about the transient receptor potential vanilloid 2 (TRPV2) ion channel?

PubMed

Perálvarez-Marín, Alex; Doñate-Macian, Pau; Gaudet, Rachelle

2013-11-01

Transient receptor potential (TRP) ion channels are emerging as a new set of membrane proteins involved in a vast array of cellular processes and regulated by a large number of physical and chemical stimuli, which involves them with sensory cell physiology. The vanilloid TRP subfamily (TRPV) named after the vanilloid receptor 1 (TRPV1) consists of six members, and at least four of them (TRPV1-TRPV4) have been related to thermal sensation. One of the least characterized members of the TRP subfamily is TRPV2. Although initially characterized as a noxious heat sensor, TRPV2 now seems to have little to do with temperature sensing but a much more complex physiological profile. Here we review the available information and research progress on the structure, physiology and pharmacology of TRPV2 in an attempt to shed some light on the physiological and pharmacological deorphanization of TRPV2. © 2013 FEBS.

What do we know about the Transient Receptor Potential Vanilloid 2 (TRPV2) ion channel?

PubMed Central

Perálvarez-Marín, Alex; Doñate-Macian, Pau; Gaudet, Rachelle

2013-01-01

Transient receptor potential (TRP) ion channels are emerging as a new set of membrane proteins involved in a vast array of cellular processes and regulated by a large number of physical and chemical stimuli, which involves them with sensory cell physiology. The vanilloid TRP subfamily (TRPV) named after the vanilloid receptor 1 (TRPV1) consists of six members, and at least four of them (TRPV1-TRPV4) have been related to thermal sensation. One of the least characterized members of the TRP subfamily is TRPV2. Although initially characterized as a noxious heat sensor, TRPV2 now seems to have little to do with temperature sensing, but a much more complex physiological profile. Here we review the available information and research progress on the structure, physiology and pharmacology of TRPV2 in an attempt to shed some light on the physiological and pharmacological deorphanization of TRPV2. PMID:23615321

Discovery of potent and selective small-molecule PAR-2 agonists.

PubMed

Seitzberg, Jimmi Gerner; Knapp, Anne Eeg; Lund, Birgitte Winther; Mandrup Bertozzi, Sine; Currier, Erika A; Ma, Jian-Nong; Sherbukhin, Vladimir; Burstein, Ethan S; Olsson, Roger

2008-09-25

Proteinase activated receptor-2 plays a crucial role in a wide variety of conditions with a strong inflammatory component. We present the discovery and characterization of two structurally different, potent, selective, and metabolically stable small-molecule PAR-2 agonists. These ligands may be useful as pharmacological tools for elucidating the complex physiological role of the PAR-2 receptors as well as for the development of PAR-2 antagonists.

Tunable Collagen I Hydrogels for Engineered Physiological Tissue Micro-Environments

PubMed Central

Antoine, Elizabeth E.; Vlachos, Pavlos P.; Rylander, Marissa N.

2015-01-01

Collagen I hydrogels are commonly used to mimic the extracellular matrix (ECM) for tissue engineering applications. However, the ability to design collagen I hydrogels similar to the properties of physiological tissues has been elusive. This is primarily due to the lack of quantitative correlations between multiple fabrication parameters and resulting material properties. This study aims to enable informed design and fabrication of collagen hydrogels in order to reliably and reproducibly mimic a variety of soft tissues. We developed empirical predictive models relating fabrication parameters with material and transport properties. These models were obtained through extensive experimental characterization of these properties, which include compression modulus, pore and fiber diameter, and diffusivity. Fabrication parameters were varied within biologically relevant ranges and included collagen concentration, polymerization pH, and polymerization temperature. The data obtained from this study elucidates previously unknown fabrication-property relationships, while the resulting equations facilitate informed a priori design of collagen hydrogels with prescribed properties. By enabling hydrogel fabrication by design, this study has the potential to greatly enhance the utility and relevance of collagen hydrogels in order to develop physiological tissue microenvironments for a wide range of tissue engineering applications. PMID:25822731

Success stories and emerging themes in conservation physiology

PubMed Central

Madliger, Christine L.; Cooke, Steven J.; Crespi, Erica J.; Funk, Jennifer L.; Hultine, Kevin R.; Hunt, Kathleen E.; Rohr, Jason R.; Sinclair, Brent J.; Suski, Cory D.; Willis, Craig K. R.; Love, Oliver P.

2016-01-01

The potential benefits of physiology for conservation are well established and include greater specificity of management techniques, determination of cause–effect relationships, increased sensitivity of health and disturbance monitoring and greater capacity for predicting future change. While descriptions of the specific avenues in which conservation and physiology can be integrated are readily available and important to the continuing expansion of the discipline of ‘conservation physiology’, to date there has been no assessment of how the field has specifically contributed to conservation success. However, the goal of conservation physiology is to foster conservation solutions and it is therefore important to assess whether physiological approaches contribute to downstream conservation outcomes and management decisions. Here, we present eight areas of conservation concern, ranging from chemical contamination to invasive species to ecotourism, where physiological approaches have led to beneficial changes in human behaviour, management or policy. We also discuss the shared characteristics of these successes, identifying emerging themes in the discipline. Specifically, we conclude that conservation physiology: (i) goes beyond documenting change to provide solutions; (ii) offers a diversity of physiological metrics beyond glucocorticoids (stress hormones); (iii) includes approaches that are transferable among species, locations and times; (iv) simultaneously allows for human use and benefits to wildlife; and (v) is characterized by successes that can be difficult to find in the primary literature. Overall, we submit that the field of conservation physiology has a strong foundation of achievements characterized by a diversity of conservation issues, taxa, physiological traits, ecosystem types and spatial scales. We hope that these concrete successes will encourage the continued evolution and use of physiological tools within conservation-based research and management plans. PMID:27382466

Does fingerprinting truly represent the diversity of wine yeasts? A case study with interdelta genotyping of Saccharomyces cerevisiae strains.

PubMed

Pfliegler, W P; Sipiczki, M

2016-12-01

Simple and efficient genotyping methods are widely used to assess the diversity of a large number of microbial strains, e.g. wine yeasts isolated from a specific geographical area or a vintage. Such methods are often also the first to be applied, to decrease the number of strains deemed interesting for a more time-consuming physiological characterization. Here, we aimed to use a physiologically characterized strain collection of 69 Saccharomyces cerevisiae strains from Hungarian wine regions to determine whether geographical origin or physiological similarity can be recovered by clustering the strains with one or two simultaneously used variations of interdelta genotyping. Our results indicate that although a detailed clustering with high resolution can be achieved with this method, the clustering of strains is largely contrasting when different primer sets are used and it does not recover geographical or physiological groups. Genotyping is routinely used for assessing the diversity of a large number of isolates/strains of a single species, e.g. a collection of wine yeasts. We tested the efficiency of interdelta genotyping on a collection of Saccharomyces wine yeasts from four wine regions of Hungary that was previously characterized physiologically. Interdelta fingerprinting recovered neither physiological nor geographical similarities, and in addition, the two different primer pairs widely used for this method showed conflicting and barely comparable results. Thus, this method does not necessarily represent the true diversity of a strain collection, but detailed clustering may be achieved by the combined use of primer sets. © 2016 The Society for Applied Microbiology.

Identification and Characterization of Pheasant and Quail Avian Beta Defensin 2

USDA-ARS?s Scientific Manuscript database

Peptides play significant roles in physiology as hormones, neurotransmitters, growth, antimicrobial, and signal transducing factors. Identification of their tissue specific occurrence and abundance may lead to a better understanding of their physiological significance. Previously, we identified matu...

Kinematic Characterization of Left Ventricular Chamber Stiffness and Relaxation

NASA Astrophysics Data System (ADS)

Mossahebi, Sina

Heart failure is the most common cause of hospitalization today, and diastolic heart failure accounts for 40-50% of cases. Therefore, it is critical to identify diastolic dysfunction at a subclinical stage so that appropriate therapy can be administered before ventricular function is further, and perhaps irreversibly impaired. Basic concepts in physics such as kinematic modeling provide a unique method with which to characterize cardiovascular physiology, specifically diastolic function (DF). The advantage of an approach that is standard in physics, such as the kinematic modeling is its causal formulation that functions in contrast to correlative approaches traditionally utilized in the life sciences. Our research group has pioneered theoretical and experimental quantitative analysis of DF in humans, using both non-invasive (echocardiography, cardiac MRI) and invasive (simultaneous catheterization-echocardiography) methods. Our group developed and validated the Parametrized Diastolic Filling (PDF) formalism which is motivated by basic physiologic principles (LV is a mechanical suction pump at the mitral valve opening) that obey Newton's Laws. PDF formalism is a kinematic model of filling employing an equation of motion, the solution of which accurately predicts all E-wave contours in accordance with the rules of damped harmonic oscillatory motion. The equation's lumped parameters---ventricular stiffness, ventricular viscoelasticity/relaxation and ventricular load---are obtained by solving the 'inverse problem'. The parameters' physiologic significance and clinical utility have been repeatedly demonstrated in multiple clinical settings. In this work we apply our kinematic modeling approach to better understand how the heart works as it fills in order to advance the relationship between physiology and mathematical modeling. Through the use of this modeling, we thereby define and validate novel, causal indexes of diastolic function such as early rapid filling energy, diastatic stiffness, and relaxation and stiffness components of E-wave deceleration time.

Physiological and biochemical characterization of Trichoderma harzianum, a biological control agent against soilborne fungal plant pathogens.

PubMed Central

Grondona, I; Hermosa, R; Tejada, M; Gomis, M D; Mateos, P F; Bridge, P D; Monte, E; Garcia-Acha, I

1997-01-01

Monoconidial cultures of 15 isolates of Trichoderma harzianum were characterized on the basis of 82 morphological, physiological, and biochemical features and 99 isoenzyme bands from seven enzyme systems. The results were subjected to numerical analysis which revealed four distinct groups. Representative sequences of the internal transcribed spacer 1 (ITS 1)-ITS 2 region in the ribosomal DNA gene cluster were compared between groups confirming this distribution. The utility of the groupings generated from the morphological, physiological, and biochemical data was assessed by including an additional environmental isolate in the electrophoretic analysis. The in vitro antibiotic activity of the T. harzianum isolates was assayed against 10 isolates of five different soilborne fungal plant pathogens: Aphanomyces cochlioides, Rhizoctonia solani, Phoma betae, Acremonium cucurbitacearum, and Fusarium oxysporum f. sp. radicis lycopersici. Similarities between levels and specificities of biological activity and the numerical characterization groupings are both discussed in relation to antagonist-specific populations in known and potential biocontrol species. PMID:9251205

Development and characterization of a voltammetric carbon-fiber microelectrode pH sensor.

PubMed

Makos, Monique A; Omiatek, Donna M; Ewing, Andrew G; Heien, Michael L

2010-06-15

This work describes the development and characterization of a modified carbon-fiber microelectrode sensor capable of measuring real-time physiological pH changes in biological microenvironments. The reagentless sensor was fabricated under ambient conditions from voltammetric reduction of the diazonium salt Fast Blue RR onto a carbon-fiber surface in aprotic media. Fast-scan cyclic voltammetry was used to probe redox activity of the p-quinone moiety of the surface-bound molecule as a function of pH. In vitro calibration of the sensor in solutions ranging from pH 6.5 to 8.0 resulted in a pH-dependent anodic peak potential response. Flow-injection analysis was used to characterize the modified microelectrode, revealing sensitivity to acidic and basic changes discernible to 0.005 pH units. Furthermore, the modified electrode was used to measure dynamic in vivo pH changes evoked during neurotransmitter release in the central nervous system of the microanalytical model organism Drosophila melanogaster.

Development and Characterization of a Voltammetric Carbon-fiber Microelectrode pH Sensor

PubMed Central

Makos, Monique A.; Omiatek, Donna M.; Ewing, Andrew G.; Heien, Michael L.

2010-01-01

This work describes the development and characterization of a modified carbon-fiber microelectrode sensor capable of measuring real-time physiological pH changes in biological microenvironments. The reagentless sensor was fabricated under ambient conditions from voltammetric reduction of the diazonium salt Fast Blue RR onto a carbon-fiber surface in aprotic media. Fast-scan cyclic voltammetry was used to probe redox activity of the p-quinone moiety of the surface-bound molecule as a function of pH. In vitro calibration of the sensor in solutions ranging from pH 6.5 to 8.0 resulted in a pH-dependent anodic peak potential response. Flow-injection analysis was used to characterize the modified microelectrode, revealing sensitivity to acidic and basic changes discernable to 0.005 pH units. Furthermore, the modified electrode was used to measure dynamic in vivo pH changes evoked during neurotransmitter release in the central nervous system of the microanalytical model organism Drosophila melanogaster. PMID:20380393

Morphological, Physiological, and Taxonomic Characterization of Actinobacterial Isolates Living as Endophytes of Cacao Pods and Cacao Seeds

PubMed Central

Tchinda, Romaric Armel Mouafo; Boudjeko, Thaddée; Simao-Beaunoir, Anne-Marie; Lerat, Sylvain; Tsala, Éric; Monga, Ernest; Beaulieu, Carole

2016-01-01

Vascular plants are commonly colonized by endophytic actinobacteria. However, very little is known about the relationship between these microorganisms and cacao fruits. In order to determine the physiological and taxonomic relationships between the members of this community, actinobacteria were isolated from cacao fruits and seeds. Among the 49 isolates recovered, 11 morphologically distinct isolates were selected for further characterization. Sequencing of the 16S rRNA gene allowed the partition of the selected isolates into three phylogenetic clades. Most of the selected endophytic isolates belonged to the Streptomyces violaceusniger clade. Physiological characterization was carried out and a similarity index was used to cluster the isolates. However, clustering based on physiological properties did not match phylogenetic lineages. Isolates were also characterized for traits commonly associated with plant growth-promoting bacteria, including antibiosis and auxin biosynthesis. All isolates exhibited resistance to geldanamycin, whereas only two isolates were shown to produce this antibiotic. Endophytes were inoculated on radish seedlings and most isolates were found to possess plant growth-promoting abilities. These endophytic actinobacteria inhibited the growth of various plant pathogenic fungi and/or bacteria. The present study showed that S. violaceusniger clade members represent a significant part of the actinobacterial community living as endophytes in cacao fruits and seeds. While several members of this clade are known to be geldanamycin producers and efficient biocontrol agents of plant diseases, we herein established the endophytic lifestyle of some of these microorganisms, demonstrating their potential as plant health agents. PMID:26947442

Morphological, Physiological, and Taxonomic Characterization of Actinobacterial Isolates Living as Endophytes of Cacao Pods and Cacao Seeds.

PubMed

Tchinda, Romaric Armel Mouafo; Boudjeko, Thaddée; Simao-Beaunoir, Anne-Marie; Lerat, Sylvain; Tsala, Éric; Monga, Ernest; Beaulieu, Carole

2016-01-01

Vascular plants are commonly colonized by endophytic actinobacteria. However, very little is known about the relationship between these microorganisms and cacao fruits. In order to determine the physiological and taxonomic relationships between the members of this community, actinobacteria were isolated from cacao fruits and seeds. Among the 49 isolates recovered, 11 morphologically distinct isolates were selected for further characterization. Sequencing of the 16S rRNA gene allowed the partition of the selected isolates into three phylogenetic clades. Most of the selected endophytic isolates belonged to the Streptomyces violaceusniger clade. Physiological characterization was carried out and a similarity index was used to cluster the isolates. However, clustering based on physiological properties did not match phylogenetic lineages. Isolates were also characterized for traits commonly associated with plant growth-promoting bacteria, including antibiosis and auxin biosynthesis. All isolates exhibited resistance to geldanamycin, whereas only two isolates were shown to produce this antibiotic. Endophytes were inoculated on radish seedlings and most isolates were found to possess plant growth-promoting abilities. These endophytic actinobacteria inhibited the growth of various plant pathogenic fungi and/or bacteria. The present study showed that S. violaceusniger clade members represent a significant part of the actinobacterial community living as endophytes in cacao fruits and seeds. While several members of this clade are known to be geldanamycin producers and efficient biocontrol agents of plant diseases, we herein established the endophytic lifestyle of some of these microorganisms, demonstrating their potential as plant health agents.

Physiology-based modelling approaches to characterize fish habitat suitability: Their usefulness and limitations

NASA Astrophysics Data System (ADS)

Teal, Lorna R.; Marras, Stefano; Peck, Myron A.; Domenici, Paolo

2018-02-01

Models are useful tools for predicting the impact of global change on species distribution and abundance. As ectotherms, fish are being challenged to adapt or track changes in their environment, either in time through a phenological shift or in space by a biogeographic shift. Past modelling efforts have largely been based on correlative Species Distribution Models, which use known occurrences of species across landscapes of interest to define sets of conditions under which species are likely to maintain populations. The practical advantages of this correlative approach are its simplicity and the flexibility in terms of data requirements. However, effective conservation management requires models that make projections beyond the range of available data. One way to deal with such an extrapolation is to use a mechanistic approach based on physiological processes underlying climate change effects on organisms. Here we illustrate two approaches for developing physiology-based models to characterize fish habitat suitability. (i) Aerobic Scope Models (ASM) are based on the relationship between environmental factors and aerobic scope (defined as the difference between maximum and standard (basal) metabolism). This approach is based on experimental data collected by using a number of treatments that allow a function to be derived to predict aerobic metabolic scope from the stressor/environmental factor(s). This function is then integrated with environmental (oceanographic) data of current and future scenarios. For any given species, this approach allows habitat suitability maps to be generated at various spatiotemporal scales. The strength of the ASM approach relies on the estimate of relative performance when comparing, for example, different locations or different species. (ii) Dynamic Energy Budget (DEB) models are based on first principles including the idea that metabolism is organised in the same way within all animals. The (standard) DEB model aims to describe empirical relationships which can be found consistently within physiological data across the animal kingdom. The advantages of the DEB models are that they make use of the generalities found in terms of animal physiology and can therefore be applied to species for which little data or empirical observations are available. In addition, the limitations as well as useful potential refinements of these and other physiology-based modelling approaches are discussed. Inclusion of the physiological response of various life stages and modelling the patterns of extreme events observed in nature are suggested for future work.

Development of a physiology-directed population pharmacokinetic and pharmacodynamic model for characterizing the impact of genetic and demographic factors on clopidogrel response in healthy adults.

PubMed

Jiang, Xi-Ling; Samant, Snehal; Lewis, Joshua P; Horenstein, Richard B; Shuldiner, Alan R; Yerges-Armstrong, Laura M; Peletier, Lambertus A; Lesko, Lawrence J; Schmidt, Stephan

2016-01-20

Clopidogrel (Plavix®), is a widely used antiplatelet agent, which shows high inter-individual variability in treatment response in patients following the standard dosing regimen. In this study, a physiology-directed population pharmacokinetic/pharmacodynamic (PK/PD) model was developed based on clopidogrel and clopidogrel active metabolite (clop-AM) data from the PAPI and the PGXB2B studies using a step-wise approach in NONMEM (version 7.2). The developed model characterized the in vivo disposition of clopidogrel, its bioactivation into clop-AM in the liver and subsequent platelet aggregation inhibition in the systemic circulation reasonably well. It further allowed the identification of covariates that significantly impact clopidogrel's dose-concentration-response relationship. In particular, CYP2C19 intermediate and poor metabolizers converted 26.2% and 39.5% less clopidogrel to clop-AM, respectively, compared to extensive metabolizers. In addition, CES1 G143E mutation carriers have a reduced CES1 activity (82.9%) compared to wild-type subjects, which results in a significant increase in clop-AM formation. An increase in BMI was found to significantly decrease clopidogrel's bioactivation, whereas increased age was associated with increased platelet reactivity. Our PK/PD model analysis suggests that, in order to optimize clopidogrel dosing on a patient-by-patient basis, all of these factors have to be considered simultaneously, e.g. by using quantitative clinical pharmacology tools. Copyright © 2015 Elsevier B.V. All rights reserved.

Development of a physiology-directed population pharmacokinetic and pharmacodynamic model for characterizing the impact of genetic and demographic factors on clopidogrel response in healthy adults

PubMed Central

Jiang, Xi-Ling; Samant, Snehal; Lewis, Joshua P.; Horenstein, Richard B.; Shuldiner, Alan R.; Yerges-Armstrong, Laura M.; Peletier, Lambertus A.; Lesko, Lawrence J.; Schmidt, Stephan

2018-01-01

Clopidogrel (Plavix®), is a widely used antiplatelet agent, which shows high inter-individual variability in treatment response in patients following the standard dosing regimen. In this study, a physiology-directed population pharmacokinetic/pharmacodynamic (PK/PD) model was developed based on clopidogrel and clopidogrel active metabolite (clop-AM) data from the PAPI and the PGXB2B studies using a step-wise approach in NONMEM (version 7.2). The developed model characterized the in vivo disposition of clopidogrel, its bioactivation into clop-AM in the liver and subsequent platelet aggregation inhibition in the systemic circulation reasonably well. It further allowed the identification of covariates that significantly impact clopidogrel’s dose–concentration–response relationship. In particular, CYP2C19 intermediate and poor metabolizers converted 26.2% and 39.5% less clopidogrel to clop-AM, respectively, compared to extensive metabolizers. In addition, CES1 G143E mutation carriers have a reduced CES1 activity (82.9%) compared to wild-type subjects, which results in a significant increase in clop-AM formation. An increase in BMI was found to significantly decrease clopidogrel’s bioactivation, whereas increased age was associated with increased platelet reactivity. Our PK/PD model analysis suggests that, in order to optimize clopidogrel dosing on a patient-by-patient basis, all of these factors have to be considered simultaneously, e.g. by using quantitative clinical pharmacology tools. PMID:26524713

Animal Models for Dysphagia Studies: What Have We Learnt So Far.

PubMed

German, Rebecca Z; Crompton, A W; Gould, Francois D H; Thexton, Allan J

2017-02-01

Research using animal models has contributed significantly to realizing the goal of understanding dysfunction and improving the care of patients who suffer from dysphagia. But why should other researchers and the clinicians who see patients day in and day out care about this work? Results from studies of animal models have the potential to change and grow how we think about dysphagia research and practice in general, well beyond applying specific results to human studies. Animal research provides two key contributions to our understanding of dysphagia. The first is a more complete characterization of the physiology of both normal and pathological swallow than is possible in human subjects. The second is suggesting of specific, physiological, targets for development and testing of treatment interventions to improve dysphagia outcomes.

Animal Models for Dysphagia Studies: What have we learnt so far

PubMed Central

German, Rebecca Z.; Crompton, A.W.; Gould, Francois D. H.; Thexton, Allan J.

2017-01-01

Research using animal models has contributed significantly to realizing the goal of understanding dysfunction and improving the care of patients who suffer from dysphagia. But why should other researchers and the clinicians who see patients day in and day out care about this work? Results from studies of animal models have the potential to change and grow how we think about dysphagia research and practice in general, well beyond applying specific results to human studies. Animal research provides two key contributions to our understanding of dysphagia. The first is a more complete characterization of the physiology of both normal and pathological swallow than is possible in human subjects. The second is suggesting of specific, physiological, targets for development and testing of treatment interventions to improve dysphagia outcomes. PMID:28132098

The development of contour processing: evidence from physiology and psychophysics

PubMed Central

Taylor, Gemma; Hipp, Daniel; Moser, Alecia; Dickerson, Kelly; Gerhardstein, Peter

2014-01-01

Object perception and pattern vision depend fundamentally upon the extraction of contours from the visual environment. In adulthood, contour or edge-level processing is supported by the Gestalt heuristics of proximity, collinearity, and closure. Less is known, however, about the developmental trajectory of contour detection and contour integration. Within the physiology of the visual system, long-range horizontal connections in V1 and V2 are the likely candidates for implementing these heuristics. While post-mortem anatomical studies of human infants suggest that horizontal interconnections reach maturity by the second year of life, psychophysical research with infants and children suggests a considerably more protracted development. In the present review, data from infancy to adulthood will be discussed in order to track the development of contour detection and integration. The goal of this review is thus to integrate the development of contour detection and integration with research regarding the development of underlying neural circuitry. We conclude that the ontogeny of this system is best characterized as a developmentally extended period of associative acquisition whereby horizontal connectivity becomes functional over longer and longer distances, thus becoming able to effectively integrate over greater spans of visual space. PMID:25071681

Advancements in remote physiological measurement and applications in human-computer interaction

NASA Astrophysics Data System (ADS)

McDuff, Daniel

2017-04-01

Physiological signals are important for tracking health and emotional states. Imaging photoplethysmography (iPPG) is a set of techniques for remotely recovering cardio-pulmonary signals from video of the human body. Advances in iPPG methods over the past decade combined with the ubiquity of digital cameras presents the possibility for many new, lowcost applications of physiological monitoring. This talk will highlight methods for recovering physiological signals, work characterizing the impact of video parameters and hardware on these measurements, and applications of this technology in human-computer interfaces.

Physiological status of naturally reared juvenile spring chinook salmon in the Yakima River: Seasonal dynamics and changes associated with smolting

USGS Publications Warehouse

Beckman, B.R.; Larsen, D.A.; Sharpe, C.; Lee-Pawlak, B.; Schreck, C.B.; Dickhoff, Walton W.

2000-01-01

Two year-classes of juvenile spring chinook salmon Oncorhynchus tshawytscha from the Yakima River, Washington, were sampled from July (3-4 months postemergence) through May (yearling smolt out-migration). Physiological characters measured included liver glycogen, body lipid, gill Na+-K+ ATPase, plasma thyroxine (T4), and plasma insulin-like growth factor-I (IGF-I). Distinct physiological changes were found that corresponded to season. Summer and fall were characterized by relatively high body lipid and condition factor. Winter was characterized by decreases in body lipid, condition factor, and plasma hormones. An increase in condition factor and body lipid was found in February and March. Finally, April and May were characterized by dramatic changes characteristic of smolting, including increased gill Na+-K+ ATPase activity, plasma T4, and IGF-I and decreased condition factor, body lipid, and liver glycogen. These results create a physiological template for juvenile spring chinook salmon in the drainage that provides a baseline for comparison with other years, populations, and life history types. In addition, this baseline provides a standard for controlled laboratory experiments and a target for fish culturists who rear juvenile spring chinook salmon for release from conservation hatcheries. The implications of these results for juvenile chinook salmon ecology and life history are discussed.

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.

The esophagiome: integrated anatomical, mechanical, and physiological analysis of the esophago-gastric segment.

PubMed

Zhao, Jingbo; McMahon, Barry; Fox, Mark; Gregersen, Hans

2018-06-10

Esophageal diseases are highly prevalent and carry significant socioeconomic burden. Despite the apparently simple function of the esophagus, we still struggle to better understand its physiology and pathophysiology. The assessment of large data sets and application of multiscale mathematical organ models have gained attention as part of the Physiome Project. This has long been recognized in cardiology but has only recently gained attention for the gastrointestinal(GI) tract. The term "esophagiome" implies a holistic assessment of esophageal function, from cellular and muscle physiology to the mechanical responses that transport and mix fluid contents. These anatomical, mechanical, and physiological models underlie the development of a "virtual esophagus" modeling framework to characterize and analyze function and disease. Functional models incorporate anatomical details with sensory-motor responses, especially related to biomechanical functions such as bolus transport. Our review builds on previous reviews and focuses on assessment of detailed anatomical and geometric data using advanced imaging technology for evaluation of gastro-esophageal reflux disease (GERD), and on esophageal mechanophysiology assessed using technologies that distend the esophagus. Integration of mechanics- and physiology-based analysis is a useful characteristic of the esophagiome. Experimental data on pressures and geometric characteristics are useful for the validation of mathematical and computer models of the esophagus that may provide predictions of novel endoscopic, surgical, and pharmaceutical treatment options. © 2018 New York Academy of Sciences.

Development and Feasibility Testing of Image-Guided Minimally Invasive Tissue for Diagnosis Treatment of Benign and Malignant Breast Disease

NASA Technical Reports Server (NTRS)

Jeffrey, Stefanie S.

1999-01-01

Dr. Robert Mah and Dr. Stefanie Jeffrey worked on the development of the NASA Smart Probe in its application as a device to measure and interpret physiologic and image-based parameters of breast tissue. To date the following has been achieved: 1 . Choice of candidate sensors to be tested in breast tissue. 2. Preliminary designs for probe tip, specifically use of different tip shapes, cutting edges, and sensor configuration. 3. Design of sonographic guidance system. 4. Design of data extraction and analysis tool using scanned information of images of the breast tissue to provide a higher dimension of information for breast tissue characterization and interpretation. 5. Initial ex-vivo (fruit and tofu) and in-vivo (rodent) testing to confirm unique substance and tissue characterization by the Smart Probe software.

Characterizing endophytic competence and plant growth promotion of bacterial endophytes inhabiting the seed endosphere of Rice.

PubMed

Walitang, Denver I; Kim, Kiyoon; Madhaiyan, Munusamy; Kim, Young Kee; Kang, Yeongyeong; Sa, Tongmin

2017-10-26

Rice (Oryza sativa L. ssp. indica) seeds as plant microbiome present both an opportunity and a challenge to colonizing bacterial community living in close association with plants. Nevertheless, the roles and activities of bacterial endophytes remain largely unexplored and insights into plant-microbe interaction are compounded by its complexity. In this study, putative functions or physiological properties associated with bacterial endophytic nature were assessed. Also, endophytic roles in plant growth and germination that may allow them to be selectively chosen by plants were also studied. The cultivable seed endophytes were dominated by Proteobacteria particularly class Gammaproteobacteria. Highly identical type strains were isolated from the seed endosphere regardless of the rice host's physiological tolerance to salinity. Among the type strains, Flavobacterium sp., Microbacterium sp. and Xanthomonas sp. were isolated from the salt-sensitive and salt-tolerant cultivars. PCA-Biplot ordination also showed that specific type strains isolated from different rice cultivars have distinguishing similar characteristics. Flavobacterium sp. strains are phosphate solubilizers and indole-3-acetic acid producers with high tolerance to salinity and osmotic stress. Pseudomonas strains are characterized as high siderophore producers while Microbacterium sp. and Xanthomonas sp. strains have very high pectinase and cellulase activity. Among the physiological traits of the seed endophytes, bacterial pectinase and cellulase activity are positively correlated as well as salt and osmotic tolerance. Overall characterization shows that majority of the isolates could survive in 4-8% salt concentration as well as in 0.6 M and 1.2 M sucrose solution. The activities of catalase, pectinase and cellulase were also observed in almost all of the isolates indicating the importance of these characteristics for survival and colonization into the seed endosphere. Seed bacterial endophytes also showed promising plant growth promoting activities including hormone modulation, nitrogen fixation, siderophore production and phosphate solubilization. Though many of the isolates possess similar PGP and endophytic physiological traits, this study shows some prominent and distinguishing traits among bacterial groups indicating key determinants for their success as endophytes in the rice seed endosphere. Rice seeds are also inhabited by bacterial endophytes that promote growth during early seedling development.

Emerging roles of gut microbiota and the immune system in the development of the enteric nervous system

PubMed Central

Kabouridis, Panagiotis S.; Pachnis, Vassilis

2015-01-01

The enteric nervous system (ENS) consists of neurons and glial cells that differentiate from neural crest progenitors. During embryogenesis, development of the ENS is controlled by the interplay of neural crest cell–intrinsic factors and instructive cues from the surrounding gut mesenchyme. However, postnatal ENS development occurs in a different context, which is characterized by the presence of microbiota and an extensive immune system, suggesting an important role of these factors on enteric neural circuit formation and function. Initial reports confirm this idea while further studies in this area promise new insights into ENS physiology and pathophysiology. PMID:25729852

Role of Thyroid Hormones in Skeletal Development and Bone Maintenance

PubMed Central

Bassett, J. H. Duncan

2016-01-01

The skeleton is an exquisitely sensitive and archetypal T3-target tissue that demonstrates the critical role for thyroid hormones during development, linear growth, and adult bone turnover and maintenance. Thyrotoxicosis is an established cause of secondary osteoporosis, and abnormal thyroid hormone signaling has recently been identified as a novel risk factor for osteoarthritis. Skeletal phenotypes in genetically modified mice have faithfully reproduced genetic disorders in humans, revealing the complex physiological relationship between centrally regulated thyroid status and the peripheral actions of thyroid hormones. Studies in mutant mice also established the paradigm that T3 exerts anabolic actions during growth and catabolic effects on adult bone. Thus, the skeleton represents an ideal physiological system in which to characterize thyroid hormone transport, metabolism, and action during development and adulthood and in response to injury. Future analysis of T3 action in individual skeletal cell lineages will provide new insights into cell-specific molecular mechanisms and may ultimately identify novel therapeutic targets for chronic degenerative diseases such as osteoporosis and osteoarthritis. This review provides a comprehensive analysis of the current state of the art. PMID:26862888

Zolpidem efficacy and safety in disorders of consciousness.

PubMed

Machado, Calixto; Estévez, Mario; Rodriguez-Rojas, Rafael

2018-01-01

Sutton and Clauss presented a detailed review about the effectiveness of zolpidem, discussing recoveries from brain damage due to strokes, trauma and hypoxia. A significant finding has been the unexpected and paradoxical increment of brain activity in vegetative state/unresponsive wakefulness syndrome (VS/UWS). On the contrary, zolpidem is considered one of the best sleep inducers in normal subjects. We have studied series of VS/UWS cases after zolpidem intake. We have demonstrated EEG activation, increment of BOLD signal in different brain regions, and an autonomic influence, mainly characterized by a vagolytic chronotropic effect without a significant increment of the vasomotor sympathetic tone. As this autonomic imbalance might induce cardio- circulatory complications, which we didn't find in any of our patients, we suggest developing future trials under control of physiological indices by bedside monitoring. However, considering that the paradoxical arousing zolpidem effect might be certainly related to brain function improvement, we agree with Sutton and Clauss that future multicentre and multinational clinical trials should be developed, but under control of physiological indices.

Early molecular events involved in Pinus pinaster Ait. somatic embryo development under reduced water availability: transcriptomic and proteomic analyses.

PubMed

Morel, Alexandre; Teyssier, Caroline; Trontin, Jean-François; Eliášová, Kateřina; Pešek, Bedřich; Beaufour, Martine; Morabito, Domenico; Boizot, Nathalie; Le Metté, Claire; Belal-Bessai, Leila; Reymond, Isabelle; Harvengt, Luc; Cadene, Martine; Corbineau, Françoise; Vágner, Martin; Label, Philippe; Lelu-Walter, Marie-Anne

2014-09-01

Maritime pine somatic embryos (SEs) require a reduction in water availability (high gellan gum concentration in the maturation medium) to reach the cotyledonary stage. This key switch, reported specifically for pine species, is not yet well understood. To facilitate the use of somatic embryogenesis for mass propagation of conifers, we need a better understanding of embryo development. Comparison of both transcriptome (Illumina RNA sequencing) and proteome [two-dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis with mass spectrometry (MS) identification] of immature SEs, cultured on either high (9G) or low (4G) gellan gum concentration, was performed, together with analysis of water content, fresh and dry mass, endogenous abscisic acid (ABA; gas chromatography-MS), soluble sugars (high-pressure liquid chromatography), starch and confocal laser microscope observations. This multiscale, integrated analysis was used to unravel early molecular and physiological events involved in SE development. Under unfavorable conditions (4G), the glycolytic pathway was enhanced, possibly in relation to cell proliferation that may be antagonistic to SE development. Under favorable conditions (9G), SEs adapted to culture constraint by activating specific protective pathways, and ABA-mediated molecular and physiological responses promoting embryo development. Our results suggest that on 9G, germin-like protein and ubiquitin-protein ligase could be used as predictive markers of SE development, whereas protein phosphatase 2C could be a biomarker for culture adaptive responses. This is the first characterization of early molecular mechanisms involved in the development of pine SEs following an increase in gellan gum concentration in the maturation medium, and it is also the first report on somatic embryogenesis in conifers combining transcriptomic and proteomic datasets. © 2014 Scandinavian Plant Physiology Society.

Differences between Helianthus winteri and Helianthus annuus are deeper than physiology

USDA-ARS?s Scientific Manuscript database

Winter’s sunflower (Helianthus winteri, Hw), a new sunflower species, is found on rocky, un-grazed, south facing slopes of the Southern Sierra Nevada foothills between the valley edge and several hundred feet upslope. This study characterized physiological differences between Helianthus winteri (Hw)...

Uncertainty and Variability in Physiologically-Based Pharmacokinetic (PBPK) Models: Key Issues and Case Studies (Final Report)

EPA Science Inventory

EPA announced the availability of the final report, Uncertainty and Variability in Physiologically-Based Pharmacokinetic (PBPK) Models: Key Issues and Case Studies. This report summarizes some of the recent progress in characterizing uncertainty and variability in physi...

Cytokinin induces genome-wide binding of the type-B response regulator ARR10 to regulate growth and development in Arabidopsis

PubMed Central

Zubo, Yan O.; Blakley, Ivory Clabaugh; Yamburenko, Maria V.; Worthen, Jennifer M.; Street, Ian H.; Franco-Zorrilla, José M.; Zhang, Wenjing; Raines, Tracy; Kieber, Joseph J.; Loraine, Ann E.

2017-01-01

The plant hormone cytokinin affects a diverse array of growth and development processes and responses to the environment. How a signaling molecule mediates such a diverse array of outputs and how these response pathways are integrated with other inputs remain fundamental questions in plant biology. To this end, we characterized the transcriptional network initiated by the type-B ARABIDOPSIS RESPONSE REGULATORs (ARRs) that mediate the cytokinin primary response, making use of chromatin immunoprecipitation sequencing (ChIP-seq), protein-binding microarrays, and transcriptomic approaches. By ectopic overexpression of ARR10, Arabidopsis lines hypersensitive to cytokinin were generated and used to clarify the role of cytokinin in regulation of various physiological responses. ChIP-seq was used to identify the cytokinin-dependent targets for ARR10, thereby defining a crucial link between the cytokinin primary-response pathway and the transcriptional changes that mediate physiological responses to this phytohormone. Binding of ARR10 was induced by cytokinin with binding sites enriched toward the transcriptional start sites for both induced and repressed genes. Three type-B ARR DNA-binding motifs, determined by use of protein-binding microarrays, were enriched at ARR10 binding sites, confirming their physiological relevance. WUSCHEL was identified as a direct target of ARR10, with its cytokinin-enhanced expression resulting in enhanced shooting in tissue culture. Results from our analyses shed light on the physiological role of the type-B ARRs in regulating the cytokinin response, mechanism of type-B ARR activation, and basis by which cytokinin regulates diverse aspects of growth and development as well as responses to biotic and abiotic factors. PMID:28673986

Current Topics in Canine and Feline Obesity.

PubMed

Hamper, Beth

2016-09-01

The domestication and urbanization of dogs and cats has dramatically altered their environment and behavior. Human and pet obesity is a global concern, particularly in developed countries. An increased incidence of chronic disease is associated with obesity secondary to low-grade systemic inflammation. This article reviews current research into the genetic, dietary, and physiologic factors associated with obesity, along with use of "omics" technology to better understand and characterize this disease. Copyright © 2016 Elsevier Inc. All rights reserved.

Characterization of Prostate-Specific Membrane Antigen (PSMA) for Use in Therapeutic and Diagnostic Strategies against Prostate Cancer

DTIC Science & Technology

2000-07-01

Copenhagen, Copenhagen, Denmark To develop adjuvant therapy for glioma patients vaccination by autologous Neovascularization of blood vessels is...on the physiology of solid Vaccines : Novel Antigens and Vectors I tumors and their response to treatment. #5056 DNA VACCINATION OF BRAIN TUMOR...involvement of Mtsl(S1 0OA4) Cal’-binding protein in DNA vaccination with irradiation of tumor. The induced immunological processes tumour progression and

Lecithin based lamellar liquid crystals as a physiologically acceptable dermal delivery system for ascorbyl palmitate.

PubMed

Gosenca, Mirjam; Bešter-Rogač, Marija; Gašperlin, Mirjana

2013-09-27

Liquid crystalline systems with a lamellar structure have been extensively studied as dermal delivery systems. Ascorbyl palmitate (AP) is one of the most studied and used ascorbic acid derivatives and is employed as an antioxidant to prevent skin aging. The aim of this study was to develop and characterize skin-compliant dermal delivery systems with a liquid crystalline structure for AP. First, a pseudoternary phase diagram was constructed using Tween 80/lecithin/isopropyl myristate/water at a Tween 80/lecithin mass ratio of 1/1, and the region of lamellar liquid crystals was identified. Second, selected unloaded and AP-loaded lamellar liquid crystal systems were physicochemically characterized with polarizing optical microscopy, small-angle X-ray scattering, differential scanning calorimetry, and rheology techniques. The interlayer spacing and rheological parameters differ regarding quantitative composition, whereas the microstructure of the lamellar phase was affected by the AP incorporation, resulting either in additional micellar structures (at 25 and 32 °C) or being completely destroyed at higher temperature (37°C). After this, the study was oriented towards in vitro cytotoxicity evaluation of lamellar liquid crystal systems on a keratinocyte cell line. The results suggest that the lamellar liquid crystals that were developed could be used as a physiologically acceptable dermal delivery system. Copyright © 2013 Elsevier B.V. All rights reserved.

Amateur boxing: physical and physiological attributes.

PubMed

Chaabène, Helmi; Tabben, Montassar; Mkaouer, Bessem; Franchini, Emerson; Negra, Yassine; Hammami, Mehrez; Amara, Samiha; Chaabène, Raja Bouguezzi; Hachana, Younés

2015-03-01

Boxing is one of the oldest combat sports. The aim of the current review is to critically analyze the amateur boxer's physical and physiological characteristics and to provide practical recommendations for training as well as new areas of scientific research. High-level male and female boxers show a propensity for low body fat levels. Although studies on boxer somatotypes are limited, the available information shows that elite-level male boxers are characterized by a higher proportion of mesomorphy with a well-developed muscle mass and a low body fat level. To help support the overall metabolic demands of a boxing match and to accelerate the recovery process between rounds, athletes of both sexes require a high level of cardiorespiratory fitness. International boxers show a high peak and mean anaerobic power output. Muscle strength in both the upper and lower limbs is paramount for a fighter's victory and is one of the keys to success in boxing. As boxing punches are brief actions and very dynamic, high-level boxing performance requires well-developed muscle power in both the upper and lower limbs. Albeit limited, the available studies reveal that isometric strength is linked to high-level boxing performance. Future investigations into the physical and physiological attributes of boxers are required to enrich the current data set and to help create a suitable training program.

Myocardial T2* Mapping at Ultrahigh Field: Physics and Frontier Applications

NASA Astrophysics Data System (ADS)

Huelnhagen, Till; Paul, Katharina; Ku, Min-Chi; Serradas Duarte, Teresa; Niendorf, Thoralf

2017-06-01

Cardiovascular magnetic resonance imaging (CMR) has become an indispensable clinical tool for the assessment of morphology, function and structure of the heart muscle. By exploiting quantification of the effective transverse relaxation time (T2*) CMR also affords myocardial tissue characterization and probing of cardiac physiology, both being in the focus of ongoing research. These developments are fueled by the move to ultrahigh magnetic field strengths, which permits enhanced sensitivity and spatial resolution that help to overcome limitations of current clinical MR systems with the goal to contribute to a better understanding of myocardial (patho)physiology in vivo. In this context, the aim of this report is to introduce myocardial T2* mapping at ultrahigh magnetic fields as a promising technique to non-invasively assess myocardial (patho)physiology. For this purpose the basic principles of T2* assessment, the biophysical mechanisms determining T2* and (pre)clinical applications of myocardial T2* mapping are presented. Technological challenges and solutions for T2* sensitized CMR at ultrahigh magnetic field strengths are discussed followed by a review of acquisition techniques and post processing approaches. Preliminary results derived from myocardial T2* mapping in healthy subjects and cardiac patients at 7.0 Tesla are presented. A concluding section discusses remaining questions and challenges and provides an outlook on future developments and potential clinical applications.

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

PubMed

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

2013-09-01

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

Methodology for quantitative rapid multi-tracer PET tumor characterizations.

PubMed

Kadrmas, Dan J; Hoffman, John M

2013-10-04

Positron emission tomography (PET) can image a wide variety of functional and physiological parameters in vivo using different radiotracers. As more is learned about the molecular basis for disease and treatment, the potential value of molecular imaging for characterizing and monitoring disease status has increased. Characterizing multiple aspects of tumor physiology by imaging multiple PET tracers in a single patient provides additional complementary information, and there is a significant body of literature supporting the potential value of multi-tracer PET imaging in oncology. However, imaging multiple PET tracers in a single patient presents a number of challenges. A number of techniques are under development for rapidly imaging multiple PET tracers in a single scan, where signal-recovery processing algorithms are employed to recover various imaging endpoints for each tracer. Dynamic imaging is generally used with tracer injections staggered in time, and kinetic constraints are utilized to estimate each tracers' contribution to the multi-tracer imaging signal. This article summarizes past and ongoing work in multi-tracer PET tumor imaging, and then organizes and describes the main algorithmic approaches for achieving multi-tracer PET signal-recovery. While significant advances have been made, the complexity of the approach necessitates protocol design, optimization, and testing for each particular tracer combination and application. Rapid multi-tracer PET techniques have great potential for both research and clinical cancer imaging applications, and continued research in this area is warranted.

Methodology for Quantitative Rapid Multi-Tracer PET Tumor Characterizations

PubMed Central

Kadrmas, Dan J.; Hoffman, John M.

2013-01-01

Positron emission tomography (PET) can image a wide variety of functional and physiological parameters in vivo using different radiotracers. As more is learned about the molecular basis for disease and treatment, the potential value of molecular imaging for characterizing and monitoring disease status has increased. Characterizing multiple aspects of tumor physiology by imaging multiple PET tracers in a single patient provides additional complementary information, and there is a significant body of literature supporting the potential value of multi-tracer PET imaging in oncology. However, imaging multiple PET tracers in a single patient presents a number of challenges. A number of techniques are under development for rapidly imaging multiple PET tracers in a single scan, where signal-recovery processing algorithms are employed to recover various imaging endpoints for each tracer. Dynamic imaging is generally used with tracer injections staggered in time, and kinetic constraints are utilized to estimate each tracers' contribution to the multi-tracer imaging signal. This article summarizes past and ongoing work in multi-tracer PET tumor imaging, and then organizes and describes the main algorithmic approaches for achieving multi-tracer PET signal-recovery. While significant advances have been made, the complexity of the approach necessitates protocol design, optimization, and testing for each particular tracer combination and application. Rapid multi-tracer PET techniques have great potential for both research and clinical cancer imaging applications, and continued research in this area is warranted. PMID:24312149

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

PubMed

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

2010-07-01

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

Techniques for physicochemical characterization of nanomaterials

PubMed Central

Lin, Ping-Chang; Lin, Stephen; Wang, Paul C.; Sridhar, Rajagopalan

2014-01-01

Advances in nanotechnology have opened up a new era of diagnosis, prevention and treatment of diseases and traumatic injuries. Nanomaterials, including those with potential for clinical applications, possess novel physicochemical properties that have an impact on their physiological interactions, from the molecular level to the systemic level. There is a lack of standardized methodologies or regulatory protocols for detection or characterization of nanomaterials. This review summarizes the techniques that are commonly used to study the size, shape, surface properties, composition, purity and stability of nanomaterials, along with their advantages and disadvantages. At present there are no FDA guidelines that have been developed specifically for nanomaterial based formulations for diagnostic or therapeutic use. There is an urgent need for standardized protocols and procedures for the characterization of nanoparticles, especially those that are intended for use as theranostics. PMID:24252561

Sex peptides and MIPs can activate the same G protein-coupled receptor

USDA-ARS?s Scientific Manuscript database

In many animal species, copulation elicits a number of physiological and behavioral changes in the female partner. In Drosophila melanogaster, the main molecular effector of these physiological responses has been identified as sex peptide (SP). The sex peptide receptor (SPR) has been characterized a...

Asymmetrical Interhemispheric Connections Develop in Cat Visual Cortex after Early Unilateral Convergent Strabismus: Anatomy, Physiology, and Mechanisms

PubMed Central

Bui Quoc, Emmanuel; Ribot, Jérôme; Quenech’Du, Nicole; Doutremer, Suzette; Lebas, Nicolas; Grantyn, Alexej; Aushana, Yonane; Milleret, Chantal

2011-01-01

In the mammalian primary visual cortex, the corpus callosum contributes to the unification of the visual hemifields that project to the two hemispheres. Its development depends on visual experience. When this is abnormal, callosal connections must undergo dramatic anatomical and physiological changes. However, data concerning these changes are sparse and incomplete. Thus, little is known about the impact of abnormal postnatal visual experience on the development of callosal connections and their role in unifying representation of the two hemifields. Here, the effects of early unilateral convergent strabismus (a model of abnormal visual experience) were fully characterized with respect to the development of the callosal connections in cat visual cortex, an experimental model for humans. Electrophysiological responses and 3D reconstruction of single callosal axons show that abnormally asymmetrical callosal connections develop after unilateral convergent strabismus, resulting from an extension of axonal branches of specific orders in the hemisphere ipsilateral to the deviated eye and a decreased number of nodes and terminals in the other (ipsilateral to the non-deviated eye). Furthermore this asymmetrical organization prevents the establishment of a unifying representation of the two visual hemifields. As a general rule, we suggest that crossed and uncrossed retino-geniculo-cortical pathways contribute successively to the development of the callosal maps in visual cortex. PMID:22275883

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.

Understanding the physiology and adaptation of staphylococci: a post-genomic approach.

PubMed

Becker, Karsten; Bierbaum, Gabriele; von Eiff, Christof; Engelmann, Susanne; Götz, Friedrich; Hacker, Jörg; Hecker, Michael; Peters, Georg; Rosenstein, Ralf; Ziebuhr, Wilma

2007-11-01

Staphylococcus aureus as well as coagulase-negative staphylococci are medically highly important pathogens characterized by an increasing resistance rate toward many antibiotics. Although normally being skin and mucosa commensals, some staphylococcal species and strains have the capacity to cause a wide range of infectious diseases. Many of these infections affect immunocompromised patients in hospitals. However, community-acquired staphylococcal infections due to resistant strains are also currently on the rise. In the light of this development, there is an urgent need for novel anti-staphylococcal therapeutic and prevention strategies for which a better understanding of the physiology of these bacteria is an essential prerequisite. Within the past years, staphylococci have been in the focus of genomic research, resulting in the determination and publication of a range of full-genome sequences of different staphylococcal species and strains which provided the basis for the design and application of DNA microarrays and other genomic tools. Here we summarize the results of the project group 'Staphylococci' within the research network 'Pathogenomics' giving new insights into the genome structure, molecular epidemiology, physiology, and genetic adaptation of both S. aureus and coagulase-negative staphylococci.

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.

A New Approach to Predict Microbial Community Assembly and Function Using a Stochastic, Genome-Enabled Modeling Framework

NASA Astrophysics Data System (ADS)

King, E.; Brodie, E.; Anantharaman, K.; Karaoz, U.; Bouskill, N.; Banfield, J. F.; Steefel, C. I.; Molins, S.

2016-12-01

Characterizing and predicting the microbial and chemical compositions of subsurface aquatic systems necessitates an understanding of the metabolism and physiology of organisms that are often uncultured or studied under conditions not relevant for one's environment of interest. Cultivation-independent approaches are therefore important and have greatly enhanced our ability to characterize functional microbial diversity. The capability to reconstruct genomes representing thousands of populations from microbial communities using metagenomic techniques provides a foundation for development of predictive models for community structure and function. Here, we discuss a genome-informed stochastic trait-based model incorporated into a reactive transport framework to represent the activities of coupled guilds of hypothetical microorganisms. Metabolic pathways for each microbe within a functional guild are parameterized from metagenomic data with a unique combination of traits governing organism fitness under dynamic environmental conditions. We simulate the thermodynamics of coupled electron donor and acceptor reactions to predict the energy available for cellular maintenance, respiration, biomass development, and enzyme production. While `omics analyses can now characterize the metabolic potential of microbial communities, it is functionally redundant as well as computationally prohibitive to explicitly include the thousands of recovered organisms into biogeochemical models. However, one can derive potential metabolic pathways from genomes along with trait-linkages to build probability distributions of traits. These distributions are used to assemble groups of microbes that couple one or more of these pathways. From the initial ensemble of microbes, only a subset will persist based on the interaction of their physiological and metabolic traits with environmental conditions, competing organisms, etc. Here, we analyze the predicted niches of these hypothetical microbes and assess the ability of a stochastically assembled community of organisms to predict subsurface biogeochemical dynamics.

Anti-angiogenic activities of snake venom CRISP isolated from Echis carinatus sochureki.

PubMed

Lecht, Shimon; Chiaverelli, Rachel A; Gerstenhaber, Jonathan; Calvete, Juan J; Lazarovici, Philip; Casewell, Nicholas R; Harrison, Robert; Lelkes, Peter I; Marcinkiewicz, Cezary

2015-06-01

Cysteine-rich secretory protein (CRISP) is present in majority of vertebrate including human. The physiological role of this protein is not characterized. We report that a CRISP isolated from Echis carinatus sochureki venom (ES-CRISP) inhibits angiogenesis. The anti-angiogenic activity of purified ES-CRISP from snake venom was investigated in vitro using endothelial cells assays such as proliferation, migration and tube formation in Matrigel, as well as in vivo in quail embryonic CAM system. The modulatory effect of ES-CRISP on the expression of major angiogenesis factors and activation of angiogenesis pathways was tested by qRT-PCR and Western blot. The amino acid sequence of ES-CRISP was found highly similar to other members of this snake venom protein family, and shares over 50% identity with human CRISP-3. ES-CRISP supported adhesion to endothelial cells, although it was also internalized into the cytoplasm in a granule-like manner. It blocked EC proliferation, migration and tube formation in Matrigel. In the embryonic quail CAM system, ES-CRISP abolished neovascularization process induced by exogenous growth factors (bFGF, vpVEGF) and by developing gliomas. CRISP modulates the expression of several factors at the mRNA level, which were characterized as regulators of angiogenesis and blocked activation of MAPK Erk1/2 induced by VEGF. ES-CRISP was characterized as a negative regulator of the angiogenesis, by direct interaction with endothelial cells. The presented work may lead to the development of novel angiostatic therapy, as well as contribute to the identification of the physiological relevance of this functionally uncharacterized protein. Copyright © 2015 Elsevier B.V. All rights reserved.

A novel method for multiparameter physiological phenotype characterization at the single-cell level

NASA Astrophysics Data System (ADS)

Kelbauskas, Laimonas; Ashili, Shashanka; Houkal, Jeff; Smith, Dean; Mohammadreza, Aida; Lee, Kristen; Kumar, Ashok; Anis, Yasser; Paulson, Tom; Youngbull, Cody; Tian, Yanqing; Johnson, Roger; Holl, Mark; Meldrum, Deirdre

2011-02-01

Non-genetic intercellular heterogeneity has been increasingly recognized as one of the key factors in a variety of core cellular processes including proliferation, stimulus response, carcinogenesis and drug resistance. Many diseases, including cancer, originate in a single or a few cells. Early detection and characterization of these abnormal cells can provide new insights into the pathogenesis and serve as a tool for better disease diagnosis and treatment. We report on a novel technology for multiparameter physiological phenotype characterization at the single-cell level. It is based on real-time measurements of concentrations of several metabolites by means of extracellular optical sensors in microchambers of sub-nL volume containing single cells. In its current configuration, the measurement platform features the capability to detect oxygen consumption rate and pH changes under normoxic and hypoxic conditions at the single-cell level. We have conceived, designed and developed a semi-automated method for single-cell manipulation and loading into microwells utilizing custom, high-precision fluid handling at the nanoliter scale. We present the results of a series of measurements of oxygen consumption rates (OCRs) of single human metaplastic esophageal epithelial cells. In addition, to assess the effects of cell-to-cell interactions, we have measured OCRs of two and three cells placed in a single well. The major advantages of the approach are a) multiplexed characterization of cell phenotype at the single-cell level, b) minimal invasiveness due to the distant positioning of sensors, and c) flexibility in terms of accommodating measurements of other metabolites or biomolecules of interest.

A facile route to glycated albumin detection.

PubMed

Bohli, Nadra; Meilhac, Olivier; Rondeau, Philippe; Gueffrache, Syrine; Mora, Laurence; Abdelghani, Adnane

2018-07-01

In this paper we propose an easy way to detect the glycated form of human serum albumin which is biomarker for several diseases such as diabetes and Alzheimer. The detection platform is a label free impedimetric immunosensor, in which we used a monoclonal human serum albumin antibody as a bioreceptor and electrochemical impedance as a transducing method. The antibody was deposited onto a gold surface by simple physisorption technique. Bovine serum albumin was used as a blocking agent for non-specific binding interactions. Cyclic voltammetry and electrochemical impedance spectroscopy were used for the characterization of each layer. Human serum albumin was glycated at different levels with several concentrations of glucose ranging from 0 mM to 500 mM representing physiological, pathological (diabetic albumin) and suprapathological concentration of glucose. Through the calibration curves, we could clearly distinguish between two different areas related to physiological and pathological albumin glycation levels. The immunosensor displayed a linear range from 7.49% to 15.79% of glycated albumin to total albumin with a good sensitivity. Surface plasmon resonance imaging was also used to characterize the developed immunosensor. Copyright © 2018 Elsevier B.V. All rights reserved.

Development and characterization of a microfluidic model of the tumour microenvironment.

PubMed

Ayuso, Jose M; Virumbrales-Muñoz, María; Lacueva, Alodia; Lanuza, Pilar M; Checa-Chavarria, Elisa; Botella, Pablo; Fernández, Eduardo; Doblare, Manuel; Allison, Simon J; Phillips, Roger M; Pardo, Julián; Fernandez, Luis J; Ochoa, Ignacio

2016-10-31

The physical microenvironment of tumours is characterized by heterotypic cell interactions and physiological gradients of nutrients, waste products and oxygen. This tumour microenvironment has a major impact on the biology of cancer cells and their response to chemotherapeutic agents. Despite this, most in vitro cancer research still relies primarily on cells grown in 2D and in isolation in nutrient- and oxygen-rich conditions. Here, a microfluidic device is presented that is easy to use and enables modelling and study of the tumour microenvironment in real-time. The versatility of this microfluidic platform allows for different aspects of the microenvironment to be monitored and dissected. This is exemplified here by real-time profiling of oxygen and glucose concentrations inside the device as well as effects on cell proliferation and growth, ROS generation and apoptosis. Heterotypic cell interactions were also studied. The device provides a live 'window' into the microenvironment and could be used to study cancer cells for which it is difficult to generate tumour spheroids. Another major application of the device is the study of effects of the microenvironment on cellular drug responses. Some data is presented for this indicating the device's potential to enable more physiological in vitro drug screening.

Physiological enzymology: The next frontier in understanding protein structure and function at the cellular level.

PubMed

Lee, Irene; Berdis, Anthony J

2016-01-01

Historically, the study of proteins has relied heavily on characterizing the activity of a single purified protein isolated from other cellular components. This classic approach allowed scientists to unambiguously define the intrinsic kinetic and chemical properties of that protein. The ultimate hope was to extrapolate this information toward understanding how the enzyme or receptor behaves within its native cellular context. These types of detailed in vitro analyses were necessary to reduce the innate complexities of measuring the singular activity and biochemical properties of a specific enzyme without interference from other enzymes and potential competing substrates. However, recent developments in fields encompassing cell biology, molecular imaging, and chemical biology now provide the unique chemical tools and instrumentation to study protein structure, function, and regulation in their native cellular environment. These advancements provide the foundation for a new field, coined physiological enzymology, which quantifies the function and regulation of enzymes and proteins at the cellular level. In this Special Edition, we explore the area of Physiological Enzymology and Protein Function through a series of review articles that focus on the tools and techniques used to measure the cellular activity of proteins inside living cells. This article is part of a Special Issue entitled: Physiological Enzymology and Protein Functions. Copyright © 2015 Elsevier B.V. All rights reserved.

Neonatal NMDA Receptor Blockade Disrupts Spike Timing and Glutamatergic Synapses in Fast Spiking Interneurons in a NMDA Receptor Hypofunction Model of Schizophrenia

PubMed Central

Jones, Kevin S.; Corbin, Joshua G.; Huntsman, Molly M.

2014-01-01

The dysfunction of parvalbumin-positive, fast-spiking interneurons (FSI) is considered a primary contributor to the pathophysiology of schizophrenia (SZ), but deficits in FSI physiology have not been explicitly characterized. We show for the first time, that a widely-employed model of schizophrenia minimizes first spike latency and increases GluN2B-mediated current in neocortical FSIs. The reduction in FSI first-spike latency coincides with reduced expression of the Kv1.1 potassium channel subunit which provides a biophysical explanation for the abnormal spiking behavior. Similarly, the increase in NMDA current coincides with enhanced expression of the GluN2B NMDA receptor subunit, specifically in FSIs. In this study mice were treated with the NMDA receptor antagonist, MK-801, during the first week of life. During adolescence, we detected reduced spike latency and increased GluN2B-mediated NMDA current in FSIs, which suggests transient disruption of NMDA signaling during neonatal development exerts lasting changes in the cellular and synaptic physiology of neocortical FSIs. Overall, we propose these physiological disturbances represent a general impairment to the physiological maturation of FSIs which may contribute to schizophrenia-like behaviors produced by this model. PMID:25290690

Micro-patterned graphene-based sensing skins for human physiological monitoring

NASA Astrophysics Data System (ADS)

Wang, Long; Loh, Kenneth J.; Chiang, Wei-Hung; Manna, Kausik

2018-03-01

Ultrathin, flexible, conformal, and skin-like electronic transducers are emerging as promising candidates for noninvasive and nonintrusive human health monitoring. In this work, a wearable sensing membrane is developed by patterning a graphene-based solution onto ultrathin medical tape, which can then be attached to the skin for monitoring human physiological parameters and physical activity. Here, the sensor is validated for monitoring finger bending/movements and for recognizing hand motion patterns, thereby demonstrating its future potential for evaluating athletic performance, physical therapy, and designing next-generation human-machine interfaces. Furthermore, this study also quantifies the sensor’s ability to monitor eye blinking and radial pulse in real-time, which can find broader applications for the healthcare sector. Overall, the printed graphene-based sensing skin is highly conformable, flexible, lightweight, nonintrusive, mechanically robust, and is characterized by high strain sensitivity.

Sex Differences in Androgen Regulation of Metabolism in Nonhuman Primates.

PubMed

True, Cadence; Abbott, David H; Roberts, Charles T; Varlamov, Oleg

2017-01-01

The in-depth characterization of sex differences relevant to human physiology requires the judicious use of a variety of animal models and human clinical data. Nonhuman primates (NHPs) represent an important experimental system that bridges rodent studies and clinical investigations. NHP studies have been especially useful in understanding the role of sex hormones in development and metabolism and also allow the elucidation of the effects of pertinent dietary influences on physiology pertinent to disease states such as obesity and diabetes. This chapter summarizes the current state of our understanding of androgen effects on male and female NHP metabolism relevant to hypogonadism in human males and polycystic ovary syndrome in human females. This review will also focus on the interaction between altered androgen levels and dietary restriction and excess, in particular the Western-style diet that underlies significant human pathophysiology.

SEX DIFFERENCES IN ANDROGEN REGULATION OF METABOLISM IN NONHUMAN PRIMATES

PubMed Central

True, Cadence; Abbott, David H.; Roberts, Charles T.; Varlamov, Oleg

2018-01-01

The in-depth characterization of sex differences relevant to human physiology requires the judicious use of a variety of animal models and human clinical data. Nonhuman primates (NHPs) represent an important experimental system that bridges rodent studies and clinical investigations. NHP studies have been especially useful in understanding the role of sex hormones in development and metabolism and also allow the elucidation of the effects of pertinent dietary influences on physiology pertinent to disease states such as obesity and diabetes. This chapter summarizes the current state of our understanding of androgen effects on male and female NHP metabolism relevant to hypogonadism in human males and polycystic ovary syndrome in human females, as well as the interaction between altered androgen levels and dietary restriction and excess, in particular the western-style diet that underlies significant human pathophysiology. PMID:29224110

Experimental characterization and analysis of the BITalino platforms against a reference device.

PubMed

Batista, Diana; Silva, Hugo; Fred, Ana

2017-07-01

Low-cost hardware platforms for biomedical engineering are becoming increasingly available, which empower the research community in the development of new projects in a wide range of areas related with physiological data acquisition. Building upon previous work by our group, this work compares the quality of the data acquired by means of two different versions of the multimodal physiological computing platform BITalino, with a device that can be considered a reference. We acquired data from 5 sensors, namely Accelerometry (ACC), Electrocardiography (ECG), Electroencephalography (EEG), Electrodermal Activity (EDA) and Electromyography (EMG). Experimental evaluation shows that ACC, ECG and EDA data are highly correlated with the reference in what concerns the raw waveforms. When compared by means of their commonly used features, EEG and EMG data are also quite similar across the different devices.

Rodent models of insomnia: a review of experimental procedures that induce sleep disturbances.

PubMed

Revel, Florent G; Gottowik, Juergen; Gatti, Sylvia; Wettstein, Joseph G; Moreau, Jean-Luc

2009-06-01

Insomnia, the most common sleep disorder, is characterized by persistent difficulty in falling or staying asleep despite adequate opportunity to sleep, leading to daytime fatigue and mental dysfunction. As sleep is a sophisticated physiological process generated by a network of neuronal systems that cannot be reproduced in-vitro, pre-clinical development of hypnotic drugs requires in-vivo investigations. Accordingly, this review critically evaluates current and putative rodent models of insomnia which could be used to screen novel hypnotics. Only few valid insomnia models are currently available, although many experimental conditions lead to disturbance of physiological sleep. We categorized these conditions as a function of the procedure used to induce perturbation of sleep, and we discuss their respective advantages and pitfalls with respect to validity, feasibility and translational value to human research.

Physiological Characterization of the SynCardia Total Artificial Heart in a Mock Circulation System

PubMed Central

Crosby, Jessica R.; DeCook, Katrina J.; Tran, Phat L.; Smith, Richard G.; Larson, Douglas F.; Khalpey, Zain I.; Burkhoff, Daniel; Slepian, Marvin J.

2014-01-01

The SynCardia total artificial heart (TAH) has emerged as an effective, life-saving bi-ventricular replacement system for a wide variety of patients with end-stage heart failure. While the clinical performance of the TAH is established, modern physiologic characterization, in terms of elastance behavior and pressure-volume characterization has not been defined. Herein we examine the TAH in terms of elastance using a non-ejecting left-ventricle, and then characterize the pressure-volume relationship of the TAH by varying preload and afterload parameters using a Donovan Mock Circulatory System. We demonstrate that the TAH does not operate with time-varying elastance, differing from the human heart. Further, we show that the TAH has a pressure-volume relationship behavior that also differs from that of the human heart. The TAH does exhibit Starling-like behavior, with output increasing via preload dependent mechanisms, without reliance on an alteration of inotropic state within the operating window of the TAH. Within our testing range, the TAH is insensitive to variations in afterload, however this insensitivity has a limit, the limit being the maximum driving pressure of the pneumatic driver. Understanding the physiology of the TAH affords insight into the functional parameters that govern artificial heart behavior providing perspective on differences compared to the human heart. PMID:25551416

Physiological characterization of the SynCardia total artificial heart in a mock circulation system.

PubMed

Crosby, Jessica R; DeCook, Katrina J; Tran, Phat L; Smith, Richard G; Larson, Douglas F; Khalpey, Zain I; Burkhoff, Daniel; Slepian, Marvin J

2015-01-01

The SynCardia total artificial heart (TAH) has emerged as an effective, life-saving biventricular replacement system for a wide variety of patients with end-stage heart failure. Although the clinical performance of the TAH is established, modern physiological characterization, in terms of elastance behavior and pressure-volume (PV) characterization has not been defined. Herein, we examine the TAH in terms of elastance using a nonejecting left ventricle, and then characterize the PV relation of the TAH by varying preload and afterload parameters using a Donovan Mock Circulatory System. We demonstrate that the TAH does not operate with time-varying elastance, differing from the human heart. Furthermore, we show that the TAH has a PV relation behavior that also differs from that of the human heart. The TAH does exhibit Starling-like behavior, with output increasing via preload-dependent mechanisms, without reliance on an alteration of inotropic state within the operating window of the TAH. Within our testing range, the TAH is insensitive to variations in afterload; however, this insensitivity has a limit, the limit being the maximum driving pressure of the pneumatic driver. Understanding the physiology of the TAH affords insight into the functional parameters that govern artificial heart behavior providing perspective on differences compared with the human heart.

Select Neuropeptides and their G-Protein Coupled Receptors in Caenorhabditis Elegans and Drosophila Melanogaster

PubMed Central

Bendena, William G.; Campbell, Jason; Zara, Lian; Tobe, Stephen S.; Chin-Sang, Ian D.

2012-01-01

The G-protein coupled receptor (GPCR) family is comprised of seven transmembrane domain proteins and play important roles in nerve transmission, locomotion, proliferation and development, sensory perception, metabolism, and neuromodulation. GPCR research has been targeted by drug developers as a consequence of the wide variety of critical physiological functions regulated by this protein family. Neuropeptide GPCRs are the least characterized of the GPCR family as genetic systems to characterize their functions have lagged behind GPCR gene discovery. Drosophila melanogaster and Caenorhabditis elegans are genetic model organisms that have proved useful in characterizing neuropeptide GPCRs. The strength of a genetic approach leads to an appreciation of the behavioral plasticity that can result from subtle alterations in GPCRs or regulatory proteins in the pathways that GPCRs control. Many of these invertebrate neuropeptides, GPCRs, and signaling pathway components serve as models for mammalian counterparts as they have conserved sequences and function. This review provides an overview of the methods to match neuropeptides to their cognate receptor and a state of the art account of neuropeptide GPCRs that have been characterized in D. melanogaster and C. elegans and the behaviors that have been uncovered through genetic manipulation. PMID:22908006

Deep-Diving California Sea Lions: Are They Pushing Their Physiological Limit?

DTIC Science & Technology

2014-09-30

were 55 + 8, 51 + 6, and 40 + bpm. As illustrated in Figs. 1 and 2, the heart rate profile was characterized by rapid development of a bradycardia ...slow heart rate), and a gradual increase in heart rate during the bottom phase of the dive and during ascent. The degree of bradycardia was more...deeper dives of longer duration, and the degree of bradycardia increases with maximum depth and duration of dives. 4 0 20 40 60 80 100 120 140 0

Noninvasive photoacoustic identification and imaging of gut microbes.

PubMed

Huang, Xiaoxiao; Shi, Ying; Liu, Yajing; Xu, Hongzhi; Liu, Yu; Xiao, Chuanxing; Ren, Jianlin; Nie, Liming

2017-08-01

Homeostasis of the gut microbiota is indispensable for various physiological functions. Its composition and activity co-develop with the host, and especially associate with human colorectal cancer. However, current composition identification methods are complicated and not timely without spatial distribution information. In this Letter, we explored the photoacoustic imaging (PAI) technique to characterize the composition and quantify the proportions of the gut microbes after optical probe labeling. Our experimental results demonstrated that PAI has the potential to identify different gut bacterial species on the spot.

Deep-Diving California Sea Lions: Are They Pushing Their Physiological Limit

DTIC Science & Technology

2015-09-30

resting heart rate (70 bpm ) (Ponganis et al. 1997) is reached, and e) duration of and heart rate during the ascent tachycardia. If possible, heart rate...Resting heart rates were 54 + 6 beats min-1 ( bpm ), and in dives of 1-3 min, 3-5 min, and > 5 min, dive heart rates (number of beats/dive duration...were 55 + 8, 51 + 6, and 40 + bpm . As illustrated in Figs. 1 and 2, the heart rate profile was characterized by rapid development of a bradycardia

Complex degree of mutual anisotropy in diagnostics of biological tissues physiological changes

NASA Astrophysics Data System (ADS)

Ushenko, Yu. A.; Dubolazov, O. V.; Karachevtcev, A. O.; Zabolotna, N. I.

2011-05-01

To characterize the degree of consistency of parameters of the optically uniaxial birefringent protein nets of blood plasma a new parameter - complex degree of mutual anisotropy is suggested. The technique of polarization measuring the coordinate distributions of the complex degree of mutual anisotropy of blood plasma is developed. It is shown that statistic approach to the analysis of complex degree of mutual anisotropy distributions of blood plasma is effective in the diagnosis and differentiation of acute inflammation - acute and gangrenous appendicitis.

Complex degree of mutual anisotropy in diagnostics of biological tissues physiological changes

NASA Astrophysics Data System (ADS)

Ushenko, Yu. A.; Dubolazov, A. V.; Karachevtcev, A. O.; Zabolotna, N. I.

2011-09-01

To characterize the degree of consistency of parameters of the optically uniaxial birefringent protein nets of blood plasma a new parameter - complex degree of mutual anisotropy is suggested. The technique of polarization measuring the coordinate distributions of the complex degree of mutual anisotropy of blood plasma is developed. It is shown that statistic approach to the analysis of complex degree of mutual anisotropy distributions of blood plasma is effective in the diagnosis and differentiation of acute inflammation - acute and gangrenous appendicitis.

Quantitative biology of single neurons

PubMed Central

Eberwine, James; Lovatt, Ditte; Buckley, Peter; Dueck, Hannah; Francis, Chantal; Kim, Tae Kyung; Lee, Jaehee; Lee, Miler; Miyashiro, Kevin; Morris, Jacqueline; Peritz, Tiina; Schochet, Terri; Spaethling, Jennifer; Sul, Jai-Yoon; Kim, Junhyong

2012-01-01

The building blocks of complex biological systems are single cells. Fundamental insights gained from single-cell analysis promise to provide the framework for understanding normal biological systems development as well as the limits on systems/cellular ability to respond to disease. The interplay of cells to create functional systems is not well understood. Until recently, the study of single cells has concentrated primarily on morphological and physiological characterization. With the application of new highly sensitive molecular and genomic technologies, the quantitative biochemistry of single cells is now accessible. PMID:22915636

Cadherins and Their Partners in the Nematode Worm Caenorhabditis elegans

PubMed Central

Hardin, Jeff; Lynch, Allison; Loveless, Timothy; Pettitt, Jonathan

2018-01-01

The extreme simplicity of Caenorhabditis elegans makes it an ideal system to study the basic principles of cadherin function at the level of single cells within the physiologically relevant context of a developing animal. The genetic tractability of C. elegans also means that components of cadherin complexes can be identified through genetic modifier screens, allowing a comprehensive in vivo characterization of the macromolecular assemblies involved in cadherin function during tissue formation and maintenance in C. elegans. This work shows that a single cadherin system, the classical cadherin–catenin complex, is essential for diverse morphogenetic events during embryogenesis through its interactions with a range of mostly conserved proteins that act to modulate its function. The role of other members of the cadherin family in C. elegans, including members of the Fat-like, Flamingo/CELSR and calsyntenin families is less well characterized, but they have clear roles in neuronal development and function. PMID:23481198

The job analysis of Korean nurses as a strategy to improve the Korean Nursing Licensing Examination.

PubMed

Park, In Sook; Suh, Yeon Ok; Park, Hae Sook; Ahn, Soo Yeon; Kang, So Young; Ko, Il Sun

2016-01-01

This study aimed at characterizing Korean nurses' occupational responsibilities to apply the results for improvement of the Korean Nursing Licensing Examination. First, the contents of nursing job were defined based on a focus group interview of 15 nurses. Developing a Curriculum (DACOM) method was used to examine those results and produce the questionnaire by 13 experts. After that, the questionnaire survey to 5,065 hospital nurses was done. The occupational responsibilities of nurses were characterized as involving 8 duties, 49 tasks, and 303 task elements. Those 8 duties are nursing management and professional development, safety and infection control, the management of potential risk factors, basic nursing and caring, the maintenance of physiological integrity, medication and parenteral treatments, socio-psychological integrity, and the maintenance and improvement of health. The content of Korean Nursing Licensing Examination should be improved based on 8 duties and 49 tasks of the occupational responsibilities of Korean nurses.

Aerophagia and rumination: recognition and therapy.

PubMed

Chitkara, Denesh K; Bredenoord, Albert J; Talley, Nicholas J; Whitehead, William E

2006-07-01

Aerophagia and rumination syndrome are functional upper gastrointestinal disorders that are becoming increasingly recognized in otherwise-healthy children and adults. Aerophagia is primarily characterized by troublesome repetitive belching and abdominal symptoms that result from air sucking and swallowing. Rumination syndrome is primarily characterized by regurgitation occurring shortly after meal intake. Physiologic studies suggest that both disorders are a result of habitual behavior with associated esophageal and gastric physiologic deviations. However, the underlying etiology of these disorders remains unclear. Studies examining optimal treatments are lacking. However, therapeutic approaches utilizing biofeedback may be helpful in alleviating symptoms for patients with these conditions.

Development and characterization of a 3D multicell microtissue culture model of airway smooth muscle.

PubMed

West, Adrian R; Zaman, Nishat; Cole, Darren J; Walker, Matthew J; Legant, Wesley R; Boudou, Thomas; Chen, Christopher S; Favreau, John T; Gaudette, Glenn R; Cowley, Elizabeth A; Maksym, Geoffrey N

2013-01-01

Airway smooth muscle (ASM) cellular and molecular biology is typically studied with single-cell cultures grown on flat 2D substrates. However, cells in vivo exist as part of complex 3D structures, and it is well established in other cell types that altering substrate geometry exerts potent effects on phenotype and function. These factors may be especially relevant to asthma, a disease characterized by structural remodeling of the airway wall, and highlights a need for more physiologically relevant models of ASM function. We utilized a tissue engineering platform known as microfabricated tissue gauges to develop a 3D culture model of ASM featuring arrays of ∼0.4 mm long, ∼350 cell "microtissues" capable of simultaneous contractile force measurement and cell-level microscopy. ASM-only microtissues generated baseline tension, exhibited strong cellular organization, and developed actin stress fibers, but lost structural integrity and dissociated from the cantilevers within 3 days. Addition of 3T3-fibroblasts dramatically improved survival times without affecting tension development or morphology. ASM-3T3 microtissues contracted similarly to ex vivo ASM, exhibiting reproducible responses to a range of contractile and relaxant agents. Compared with 2D cultures, microtissues demonstrated identical responses to acetylcholine and KCl, but not histamine, forskolin, or cytochalasin D, suggesting that contractility is regulated by substrate geometry. Microtissues represent a novel model for studying ASM, incorporating a physiological 3D structure, realistic mechanical environment, coculture of multiple cells types, and comparable contractile properties to existing models. This new model allows for rapid screening of biochemical and mechanical factors to provide insight into ASM dysfunction in asthma.

An experimental model of allergic asthma in cats sensitized to house dust mite or bermuda grass allergen.

PubMed

Norris Reinero, Carol R; Decile, Kendra C; Berghaus, Roy D; Williams, Kurt J; Leutenegger, Christian M; Walby, William F; Schelegle, Edward S; Hyde, Dallas M; Gershwin, Laurel J

2004-10-01

Animal models are used to mimic human asthma, however, not all models replicate the major characteristics of the human disease. Spontaneous development of asthma with hallmark features similar to humans has been documented to occur with relative frequency in only one animal species, the cat. We hypothesized that we could develop an experimental model of feline asthma using clinically relevant aeroallergens identified from cases of naturally developing feline asthma, and characterize immunologic, physiologic, and pathologic changes over 1 year. House dust mite (HDMA) and Bermuda grass (BGA) allergen were selected by screening 10 privately owned pet cats with spontaneous asthma using a serum allergen-specific IgE ELISA. Parenteral sensitization and aerosol challenges were used to replicate the naturally developing disease in research cats. The asthmatic phenotype was characterized using intradermal skin testing, serum allergen-specific IgE ELISA, serum and bronchoalveolar lavage fluid (BALF) IgG and IgA ELISAs, airway hyperresponsiveness testing, BALF cytology, cytokine profiles using TaqMan PCR, and histopathologic evaluation. Sensitization with HDMA or BGA in cats led to allergen-specific IgE production, allergen-specific serum and BALF IgG and IgA production, airway hyperreactivity, airway eosinophilia, an acute T helper 2 cytokine profile in peripheral blood mononuclear cells and BALF cells, and histologic evidence of airway remodeling. Using clinically relevant aeroallergens to sensitize and challenge the cat provides an additional animal model to study the immunopathophysiologic mechanisms of allergic asthma. Chronic exposure to allergen in the cat leads to a variety of immunologic, physiologic, and pathologic changes that mimic the features seen in human asthma.

Interactive effects on CO2, drought, and ultraviolet-B radiation on maize growth and development.

PubMed

Wijewardana, Chathurika; Henry, W Brien; Gao, Wei; Reddy, K Raja

2016-07-01

Crop growth and development are highly responsive to global climate change components such as elevated carbon dioxide (CO2), drought, and ultraviolet-B (UV-B) radiation. Plant tolerance to these environmental stresses comprises its genetic potential, physiological changes, metabolism, and signaling pathways. An inclusive understanding of morphological, physiological, and biochemical responses to these abiotic stresses is imperative for the development of stress tolerant varieties for future environments. The objectives of this study were to characterize the changes in vegetative and physiological traits in maize hybrids in their response to multiple environmental factors of (CO2) [400 and 750μmolmol(-1) (+(CO2)], irrigation treatments based evapotranspiration (ET) [100 and 50% (-ET)], and UV-B radiation [0 and 10kJm(-2)d(-1) (+UV-B)] and to identify the multiple stress tolerant hybrids aid in mitigating projected climate change for shaping future agriculture. Six maize hybrids (P1498, DKC 65-81, N75H-GTA, P1319, DKC 66-97, and N77P-3111) with known drought tolerance variability were grown in eight sunlit, controlled environment chambers in which control treatment consisted of 400μmolmol(-1) [CO2], 100% ET-based irrigation, and 0kJ UV-B. Plants grown at +UV-B alone or combination with 50% ET produced shorter plants and smaller leaf area while elevated CO2 treatments ameliorated the damaging effects of drought and higher UV-B levels on maize hybrids. Plant height, leaf area, total dry matter chlorophyll, carotenoids, and net photosynthesis measured were increased in response to CO2 enrichment. Total stress response index (TSRI) for each hybrid, developed from the cumulative sum of response indices of vegetative and physiological parameters, varied among the maize hybrids. The hybrids were classified as tolerant (P1498), intermediate (DKC 65-81, N75H-GTA, N77P-3111) and sensitive (P1319 and DKC 66-97) to multiple environmental stresses. The positive correlation between TSRI and vegetative and physiological index developed in this study demonstrates that a combination of vegetative and physiological traits is an effective screening tool to identify germplasm best suited to cope with future changing climates. Furthermore, the tolerant hybrids identified in this study indicate that the possibility of cultivar selection for enhanced agronomic performance and stability in a water limited environment with higher UV-B, anticipated to occur in future climates. Copyright © 2016 Elsevier B.V. All rights reserved.

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

PubMed

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

2015-01-01

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

16S rRNA Gene Sequencing for Deciphering the Colorectal Cancer Gut Microbiome: Current Protocols and Workflows.

PubMed

Osman, Muhammad-Afiq; Neoh, Hui-Min; Ab Mutalib, Nurul-Syakima; Chin, Siok-Fong; Jamal, Rahman

2018-01-01

The human gut holds the densest microbiome ecosystem essential in maintaining a healthy host physiology, whereby disruption of this ecosystem has been linked to the development of colorectal cancer (CRC). The advent of next-generation sequencing technologies such as the 16S rRNA gene sequencing has enabled characterization of the CRC gut microbiome architecture in an affordable and culture-free approach. Nevertheless, the lack of standardization in handling and storage of biospecimens, nucleic acid extraction, 16S rRNA gene primer selection, length, and depth of sequencing and bioinformatics analyses have contributed to discrepancies found in various published studies of this field. Accurate characterization of the CRC microbiome found in different stages of CRC has the potential to be developed into a screening tool in the clinical setting. This mini review aims to concisely compile all available CRC microbiome studies performed till end of 2016 and to suggest standardized protocols that are crucial in developing a gut microbiome screening panel for CRC.

Characterization of the metabolic and physiologic response to chromium supplementation in subjects with type 2 diabetes mellitus

USDA-ARS?s Scientific Manuscript database

The objective of this study was to provide a comprehensive evaluation of chromium (Cr) supplementation on metabolic, physiologic, and phenotypic parameters in subjects with Type 2 DM and evaluate changes in “responders” and “non-responders”. After pre-intervention testing to assess glycemia, insuli...

Behaviour, Physiology and Experience of Pathological Laughing and Crying in Amyotrophic Lateral Sclerosis

ERIC Educational Resources Information Center

Olney, Nicholas T.; Goodkind, Madeleine S.; Lomen-Hoerth, Catherine; Whalen, Patrick K.; Williamson, Craig A.; Holley, Deborah E.; Verstaen, Alice; Brown, Laurel M.; Miller, Bruce L.; Kornak, John; Levenson, Robert W.; Rosen, Howard J.

2011-01-01

Pathological laughing and crying is a disorder of emotional expression seen in a number of neurological diseases. The aetiology is poorly understood, but clinical descriptions suggest a disorder of emotion regulation. The goals of this study were: (i) to characterize the subjective, behavioural and physiological emotional reactions that occur…

Swim-exercised mice show a decreased level of protein O-GlcNAcylation and expression of O-GlcNAc transferase in heart.

PubMed

Belke, Darrell D

2011-07-01

Swim-training exercise in mice leads to cardiac remodeling associated with an improvement in contractile function. Protein O-linked N-acetylglucosamine (O-GlcNAcylation) is a posttranslational modification of serine and threonine residues capable of altering protein-protein interactions affecting gene transcription, cell signaling pathways, and general cell physiology. Increased levels of protein O-GlcNAcylation in the heart have been associated with pathological conditions such as diabetes, ischemia, and hypertrophic heart failure. In contrast, the impact of physiological exercise on protein O-GlcNAcylation in the heart is currently unknown. Swim-training exercise in mice was associated with the development of a physiological hypertrophy characterized by an improvement in contractile function relative to sedentary mice. General protein O-GlcNAcylation was significantly decreased in swim-exercised mice. This effect was mirrored in the level of O-GlcNAcylation of individual proteins such as SP1. The decrease in protein O-GlcNAcylation was associated with a decrease in the expression of O-GlcNAc transferase (OGT) and glutamine-fructose amidotransferase (GFAT) 2 mRNA. O-GlcNAcase (OGA) activity was actually lower in swim-trained than sedentary hearts, suggesting that it did not contribute to the decreased protein O-GlcNAcylation. Thus it appears that exercise-induced physiological hypertrophy is associated with a decrease in protein O-GlcNAcylation, which could potentially contribute to changes in gene expression and other physiological changes associated with exercise.

Development of tactile sensory circuits in the CNS.

PubMed

Iwasato, Takuji; Erzurumlu, Reha S

2018-06-13

Molecular identification of neuronal types and genetic and imaging approaches to characterize their properties reveal morphological, physiological and dynamic aspects of sensory circuit development. Here we focus on the mouse tactile sensory circuitry, with particular emphasis on the main trigeminal pathway that connects the whiskers, the major tactile organ in rodents, to the neocortex. At each level of this pathway, neurogenesis, axonal elongation, pathfinding, target recognition and circuit reorganization including dendritic refinement of cortical layer 4 neurons occur contemporaneously and a multitude of molecular signals are used in differing combinations. We highlight recent advances in development of tactile circuitry and note gaps in our understanding. Copyright © 2018 Elsevier Ltd. All rights reserved.

Biomimetics of fetal alveolar flow phenomena using microfluidics.

PubMed

Tenenbaum-Katan, Janna; Fishler, Rami; Rothen-Rutishauser, Barbara; Sznitman, Josué

2015-01-01

At the onset of life in utero, the respiratory system begins as a liquid-filled tubular organ and undergoes significant morphological changes during fetal development towards establishing a respiratory organ optimized for gas exchange. As airspace morphology evolves, respiratory alveolar flows have been hypothesized to exhibit evolving flow patterns. In the present study, we have investigated flow topologies during increasing phases of embryonic life within an anatomically inspired microfluidic device, reproducing real-scale features of fetal airways representative of three distinct phases of in utero gestation. Micro-particle image velocimetry measurements, supported by computational fluid dynamics simulations, reveal distinct respiratory alveolar flow patterns throughout different stages of fetal life. While attached, streamlined flows characterize the shallow structures of premature alveoli indicative of the onset of saccular stage, separated recirculating vortex flows become the signature of developed and extruded alveoli characteristic of the advanced stages of fetal development. To further mimic physiological aspects of the cellular environment of developing airways, our biomimetic devices integrate an alveolar epithelium using the A549 cell line, recreating a confluent monolayer that produces pulmonary surfactant. Overall, our in vitro biomimetic fetal airways model delivers a robust and reliable platform combining key features of alveolar morphology, flow patterns, and physiological aspects of fetal lungs developing in utero.

Bacterial diversity in Adélie penguin, Pygoscelis adeliae, guano: molecular and morpho-physiological approaches.

PubMed

Zdanowski, Marek K; Weglenski, Piotr; Golik, Pawel; Sasin, Joanna M; Borsuk, Piotr; Zmuda, Magdalena J; Stankovic, Anna

2004-11-01

The total number of bacteria and culturable bacteria in Adélie penguin (Pygoscelis adeliae) guano was determined during 42 days of decomposition in a location adjacent to the rookery in Admiralty Bay, King George Island, Antarctica. Of the culturable bacteria, 72 randomly selected colonies were described using 49 morpho-physiological tests, 27 of which were subsequently considered significant in characterizing and differentiating the isolates. On the basis of the nucleotide sequence of a fragment of the 16S rRNA gene in each of 72 pure isolates, three major phylogenetic groups were identified, namely the Moraxellaceae/Pseudomonadaceae (29 isolates), the Flavobacteriaceae (14), and the Micrococcaceae (29). Grouping of the isolates on the basis of morpho-physiological tests (whether 49 or 27 parameters) showed similar results to those based on 16S rRNA gene sequences. Clusters were characterized by considerable intra-cluster variation in both 16S rRNA gene sequences and morpho-physiological responses. High diversity in abundance and morphometry of total bacterial communities during penguin guano decomposition was supported by image analysis of epifluorescence micrographs. The results indicate that the bacterial community in penguin guano is not only one of the richest in Antarctica, but is extremely diverse, both phylogenetically and morpho-physiologically.

Myth and Reality in Hydrogeological Site Characterization at DD and R Sites

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

Rubin, Yoram

2008-01-15

The science of hydrogeological site characterization has made significant progress over the last twenty years. Progress has been made in modeling of flow and transport in the heterogeneous subsurface, in understanding of the complex patterns of geological heterogeneity and in measurement technologies. Modeling of uncertainty has also advanced significantly, in recognition of the inherent limitations of subsurface characterization. Much less progress has been made in transforming this progress into practice, where characterization is determined to a large extent by regulations. Environmental regulations have not progressed as much as the science, for example, in recognizing uncertainty. As such, practitioners are lessmore » inclined to adopt advanced, science-based solutions, this opening the door for myths and conflicts. Myths develop where the science base is perceived to be weak, whereas conflicts arise in the face of a disconnect between the science and the regulations. Myths translate to ad-hoc solutions and misplaced empiricism, as well as to unjustified reliance on field experience, to the detriment of D and DR. This paper explores the roots for this situation and identifies ideas that may help in bridging the gap between research and applications. A rational approach for DD and R is needed that will encourage innovation in site characterization, reduce costs and accelerate completion. Such an approach needs to include several elements. DD and R regulations need to recognize the various aspects of uncertainty inherent to site characterization, and as such, should be formulated using probabilistic concepts. One of the immediate benefits will be in allowing a gradual approach for data acquisition in DD and R sites: decisions can be made even under the most severe data limitations, and can be modified as additional data become available. The definition of risk is another major element. There is no universal definition of risk or of a methodology to define risk. Different sites justify different definitions, depending on many environmental, economical and social factors. Despite the lack of consensus, it seems that a good place to start is in fact to recognize that there is a room for all these factors, and a need to balance between them. As experience is gained, through research and discussions among DD and R stakeholders, this may become less of a challenge. Regulations need to recognize the possibility of developing alternative, site-specific characterization strategies based on the various length and time scales that define specific environmental problems, including length scales of heterogeneity, source dimensions and distance to environmental targets. For example, point and distributed sources justify different characterization strategies. Development of problem- or site-specific strategies will create the context for defining innovative efficient DD and R strategies. Innovation in characterization can will also follow from recognizing the specific physiological aspects of the toxins and the related uncertainty. This will open the door for improving risk characterization not only from the hydrologic perspective, but also form the physiologic one.« less

Expression, purification, and characterization of an enzymatically active truncated human rho-kinase I (ROCK I) domain expressed in Sf-9 insect cells.

PubMed

Khandekar, Sanjay S; Yi, Tracey; Dul, Ed; Wright, Lois L; Chen, Susan; Scott, Gilbert F; Smith, Gary K; Lee, Dennis; Hu, Erding; Kirkpatrick, Robert B

2006-01-01

Rho Kinase I (ROCK I) is a serine/threonine kinase that is involved in diverse cellular signaling. To further understand the physiological role of ROCK I and to identify and develop potent and selective inhibitors of ROCK I, we have overexpressed and purified a constitutively active dimeric human ROCK I (3-543) kinase domain using the Sf9-baculovirus expression system. In addition, using a limited proteolysis technique, we have identified a minimal functional subdomain of ROCK I that can be used in crystallization studies. The availability of multimilligram amounts of purified and well characterized functional human ROCK I kinase domains will be useful in screening and structural studies.

Fabrication and characterization of an inorganic gold and silica nanoparticle mediated drug delivery system for nitric oxide

NASA Astrophysics Data System (ADS)

Das, Amitava; Mukherjee, Priyabrata; Singla, Sumit K.; Guturu, Praveen; Frost, Megan C.; Mukhopadhyay, Debabrata; Shah, Vijay H.; Ranjan Patra, Chitta

2010-07-01

Nitric oxide (NO) plays an important role in inhibiting the development of hepatic fibrosis and its ensuing complication of portal hypertension by inhibiting human hepatic stellate cell (HSC) activation. Here we have developed a gold nanoparticle and silica nanoparticle mediated drug delivery system containing NO donors, which could be used for potential therapeutic application in chronic liver disease. The gold nanoconjugates were characterized using several physico-chemical techniques such as UV-visible spectroscopy and transmission electron microscopy. Silica nanoconjugates were synthesized and characterized as reported previously. NO released from gold and silica nanoconjugates was quantified under physiological conditions (pH = 7.4 at 37 °C) for a substantial period of time. HSC proliferation and the vascular tube formation ability, manifestations of their activation, were significantly attenuated by the NO released from these nanoconjugates. This study indicates that gold and silica nanoparticle mediated drug delivery systems for introducing NO could be used as a strategy for the treatment of hepatic fibrosis or chronic liver diseases, by limiting HSC activation.

Metabolic, Reproductive, and Neurologic Abnormalities in Agpat1-Null Mice.

PubMed

Agarwal, Anil K; Tunison, Katie; Dalal, Jasbir S; Nagamma, Sneha S; Hamra, F Kent; Sankella, Shireesha; Shao, Xinli; Auchus, Richard J; Garg, Abhimanyu

2017-11-01

Defects in the biosynthesis of phospholipids and neutral lipids are associated with cell membrane dysfunction, disrupted energy metabolism, and diseases including lipodystrophy. In these pathways, the 1-acylglycerol-3-phosphate O-acyltransferase (AGPAT) enzymes transfer a fatty acid to the sn-2 carbon of sn-1-acylglycerol-3-phosphate (lysophosphatidic acid) to form sn-1, 2-acylglycerol-3-phosphate [phosphatidic acid (PA)]. PA is a precursor for key phospholipids and diacylglycerol. AGPAT1 and AGPAT2 are highly homologous isoenzymes that are both expressed in adipocytes. Genetic defects in AGPAT2 cause congenital generalized lipodystrophy, indicating that AGPAT1 cannot compensate for loss of AGPAT2 in adipocytes. To further explore the physiology of AGPAT1, we characterized a loss-of-function mouse model (Agpat1-/-). The majority of Agpat1-/- mice died before weaning and had low body weight and low plasma glucose levels, independent of plasma insulin and glucagon levels, with reduced percentage of body fat but not generalized lipodystrophy. These mice also had decreased hepatic messenger RNA expression of Igf-1 and Foxo1, suggesting a decrease in gluconeogenesis. In male mice, sperm development was impaired, with a late meiotic arrest near the onset of round spermatid production, and gonadotropins were elevated. Female mice showed oligoanovulation yet retained responsiveness to gonadotropins. Agpat1-/- mice also demonstrated abnormal hippocampal neuron development and developed audiogenic seizures. In summary, Agpat1-/- mice developed widespread disturbances of metabolism, sperm development, and neurologic function resulting from disrupted phospholipid homeostasis. AGPAT1 appears to serve important functions in the physiology of multiple organ systems. The Agpat1-deficient mouse provides an important model in which to study the contribution of phospholipid and triacylglycerol synthesis to physiology and diseases. Copyright © 2017 Endocrine Society.

[Variability patterns of nest construction, physiological state, and morphometric traits in honey bee].

PubMed

Es'kov, E K; Es'kova, M D

2014-01-01

High variability of cells size is used selectively for reproduction of working bees and drones. A decrease in both distance between cells and cells size themselves causes similar effects to body mass and morphometric traits of developing individuals. Adaptation of honey bees to living in shelters has led to their becoming tolerant to hypoxia. Improvement of ethological and physiological mechanisms of thermal regulation is associated with limitation of ecological valence and acquiring of stenothermic features by breed. Optimal thermal conditions for breed are limited by the interval 33-34.5 degrees C. Deviations of temperature by 3-4 degrees C beyond this range have minimum lethal effect at embryonic stage of development and medium effect at the stage of pre-pupa and pupa. Developing at the low bound of the vital range leads to increasing, while developing at the upper bound--to decreasing of body mass, mandibular and hypopharyngeal glands, as well as other organs, which, later, affects the variability of these traits during the adult stage of development. Eliminative and teratogenic efficiency of ecological factors that affect a breed is most often manifested in underdevelopment of wings. However, their size (in case of wing laminas formation). is characterized by relatively low variability and size-dependent asymmetry. Asymmetry variability of wings and other pair organs is expressed through realignment of size excess from right- to left-side one with respect to their increase. Selective elimination by those traits whose emerging probability increases as developmental conditions deviate from the optimal ones promotes restrictions on individual variability. Physiological mechanisms that facilitate adaptability enhancement under conditions of increasing anthropogenic contamination of eivironment and trophic substrates consumed by honey bees, arrear to be toxicants accumulation in rectum and crops' ability to absorb contaminants from nectar in course of its processing to honey.

Cellular and Physiological Effects of Anthrax Exotoxin and Its Relevance to Disease

PubMed Central

Lowe, David E.; Glomski, Ian J.

2012-01-01

Bacillus anthracis, the causative agent of anthrax, secretes a tri-partite exotoxin that exerts pleiotropic effects on the host. The purification of the exotoxin components, protective antigen, lethal factor, and edema factor allowed the rapid characterization of their physiologic effects on the host. As molecular biology matured, interest focused on the molecular mechanisms and cellular alterations induced by intoxication. Only recently have researchers begun to connect molecular and cellular knowledge back to the broader physiological effects of the exotoxin. This review focuses on the progress that has been made bridging molecular knowledge back to the exotoxin’s physiological effects on the host. PMID:22919667

Creating homogenous strain distribution within 3D cell-encapsulated constructs using a simple and cost-effective uniaxial tensile bioreactor: Design and validation study.

PubMed

Subramanian, Gayathri; Elsaadany, Mostafa; Bialorucki, Callan; Yildirim-Ayan, Eda

2017-08-01

Mechanical loading bioreactors capable of applying uniaxial tensile strains are emerging to be a valuable tool to investigate physiologically relevant cellular signaling pathways and biochemical expression. In this study, we have introduced a simple and cost-effective uniaxial tensile strain bioreactor for the application of precise and homogenous uniaxial strains to 3D cell-encapsulated collagen constructs at physiological loading strains (0-12%) and frequencies (0.01-1 Hz). The bioreactor employs silicone-based loading chambers specifically designed to stretch constructs without direct gripping to minimize stress concentration at the ends of the construct and preserve its integrity. The loading chambers are driven by a versatile stepper motor ball-screw actuation system to produce stretching of the constructs. Mechanical characterization of the bioreactor performed through Finite Element Analysis demonstrated that the constructs experienced predominantly uniaxial tensile strain in the longitudinal direction. The strains produced were found to be homogenous over a 15 × 4 × 2 mm region of the construct equivalent to around 60% of the effective region of characterization. The strain values were also shown to be consistent and reproducible during cyclic loading regimes. Biological characterization confirmed the ability of the bioreactor to promote cell viability, proliferation, and matrix organization of cell-encapsulated collagen constructs. This easy-to-use uniaxial tensile strain bioreactor can be employed for studying morphological, structural, and functional responses of cell-embedded matrix systems in response to physiological loading of musculoskeletal tissues. It also holds promise for tissue-engineered strategies that involve delivery of mechanically stimulated cells at the site of injury through a biological carrier to develop a clinically useful therapy for tissue healing. Biotechnol. Bioeng. 2017;114: 1878-1887. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Insights into the Evolution of Host Association through the Isolation and Characterization of a Novel Human Periodontal Pathobiont, Desulfobulbus oralis.

PubMed

Cross, Karissa L; Chirania, Payal; Xiong, Weili; Beall, Clifford J; Elkins, James G; Giannone, Richard J; Griffen, Ann L; Guss, Adam M; Hettich, Robert L; Joshi, Snehal S; Mokrzan, Elaine M; Martin, Roman K; Zhulin, Igor B; Leys, Eugene J; Podar, Mircea

2018-03-13

The human oral microbiota encompasses representatives of many bacterial lineages that have not yet been cultured. Here we describe the isolation and characterization of previously uncultured Desulfobulbus oralis , the first human-associated representative of its genus. As mammalian-associated microbes rarely have free-living close relatives, D. oralis provides opportunities to study how bacteria adapt and evolve within a host. This sulfate-reducing deltaproteobacterium has adapted to the human oral subgingival niche by curtailing its physiological repertoire, losing some biosynthetic abilities and metabolic independence, and by dramatically reducing environmental sensing and signaling capabilities. The genes that enable free-living Desulfobulbus to synthesize the potent neurotoxin methylmercury were also lost by D. oralis , a notably positive outcome of host association. However, horizontal gene acquisitions from other members of the microbiota provided novel mechanisms of interaction with the human host, including toxins like leukotoxin and hemolysins. Proteomic and transcriptomic analysis revealed that most of those factors are actively expressed, including in the subgingival environment, and some are secreted. Similar to other known oral pathobionts, D. oralis can trigger a proinflammatory response in oral epithelial cells, suggesting a direct role in the development of periodontal disease. IMPORTANCE Animal-associated microbiota likely assembled as a result of numerous independent colonization events by free-living microbes followed by coevolution with their host and other microbes. Through specific adaptation to various body sites and physiological niches, microbes have a wide range of contributions, from beneficial to disease causing. Desulfobulbus oralis provides insights into genomic and physiological transformations associated with transition from an open environment to a host-dependent lifestyle and the emergence of pathogenicity. Through a multifaceted mechanism triggering a proinflammatory response, D. oralis is a novel periodontal pathobiont. Even though culture-independent approaches can provide insights into the potential role of the human microbiome "dark matter," cultivation and experimental characterization remain important to studying the roles of individual organisms in health and disease.

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.

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

PubMed

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

2017-03-01

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

Physiologically-Based Toxicokinetic Modeling of Zearalenone and Its Metabolites: Application to the Jersey Girl Study

PubMed Central

Mukherjee, Dwaipayan; Royce, Steven G.; Alexander, Jocelyn A.; Buckley, Brian; Isukapalli, Sastry S.; Bandera, Elisa V.; Zarbl, Helmut; Georgopoulos, Panos G.

2014-01-01

Zearalenone (ZEA), a fungal mycotoxin, and its metabolite zeranol (ZAL) are known estrogen agonists in mammals, and are found as contaminants in food. Zeranol, which is more potent than ZEA and comparable in potency to estradiol, is also added as a growth additive in beef in the US and Canada. This article presents the development and application of a Physiologically-Based Toxicokinetic (PBTK) model for ZEA and ZAL and their primary metabolites, zearalenol, zearalanone, and their conjugated glucuronides, for rats and for human subjects. The PBTK modeling study explicitly simulates critical metabolic pathways in the gastrointestinal and hepatic systems. Metabolic events such as dehydrogenation and glucuronidation of the chemicals, which have direct effects on the accumulation and elimination of the toxic compounds, have been quantified. The PBTK model considers urinary and fecal excretion and biliary recirculation and compares the predicted biomarkers of blood, urinary and fecal concentrations with published in vivo measurements in rats and human subjects. Additionally, the toxicokinetic model has been coupled with a novel probabilistic dietary exposure model and applied to the Jersey Girl Study (JGS), which involved measurement of mycoestrogens as urinary biomarkers, in a cohort of young girls in New Jersey, USA. A probabilistic exposure characterization for the study population has been conducted and the predicted urinary concentrations have been compared to measurements considering inter-individual physiological and dietary variability. The in vivo measurements from the JGS fall within the high and low predicted distributions of biomarker values corresponding to dietary exposure estimates calculated by the probabilistic modeling system. The work described here is the first of its kind to present a comprehensive framework developing estimates of potential exposures to mycotoxins and linking them with biologically relevant doses and biomarker measurements, including a systematic characterization of uncertainties in exposure and dose estimation for a vulnerable population. PMID:25474635

Sexual dimorphic floral development in dioecious plants revealed by transcriptome, phytohormone, and DNA methylation analysis in Populus tomentosa.

PubMed

Song, Yuepeng; Ma, Kaifeng; Ci, Dong; Chen, Qingqing; Tian, Jiaxing; Zhang, Deqiang

2013-12-01

Dioecious plants have evolved sex-specific floral development mechanisms. However, the precise gene expression patterns in dioecious plant flower development remain unclear. Here, we used andromonoecious poplar, an exceptional model system, to eliminate the confounding effects of genetic background of dioecious plants. Comparative transcriptome and physiological analysis allowed us to characterize sex-specific development of female and male flowers. Transcriptome analysis identified genes significantly differentially expressed between the sexes, including genes related to floral development, phytohormone synthesis and metabolism, and DNA methylation. Correlation analysis revealed a significant correlation between phytohormone signaling and gene expression, identifying specific phytohormone-responsive genes and their cis-regulatory elements. Two genes related to DNA methylation, METHYLTRANSFERASE1 (MET1) and DECREASED DNA METHYLATION 1 (DDM1), which are located in the sex determination region of Chromosome XIX, have differential expression between female and male flowers. A time-course analysis revealed that MET1 and DDM1 expression may produce different DNA methylation levels in female and male flowers. Understanding the interactions of phytohormone signaling, DNA methylation and target gene expression should lead to a better understanding of sexual differences in floral development. Thus, this study identifies a set of candidate genes for further studies of poplar sexual dimorphism and relates sex-specific floral development to physiological and epigenetic changes.

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

Adolescent brain development, substance use, and psychotherapeutic change.

PubMed

Wetherill, Reagan; Tapert, Susan F

2013-06-01

Adolescence is a unique developmental period characterized by major physiological, psychological, social, and brain changes, as well as an increased incidence of maladaptive, addictive behaviors. With the use of MRI techniques, researchers have been able to provide a better understanding of adolescent brain maturation and how neurodevelopment affects cognition and behavior. This review discusses adolescent brain development and its potential influence on psychotherapeutic change. We focus on cognitive-behavioral and mindfulness-based approaches for treating substance use and highlight potential brain mechanisms underlying response to psychotherapy. Finally, we discuss integrative neuroimaging and treatment studies and potential opportunities for advancing the treatment of adolescent addictive behaviors. 2013 APA, all rights reserved

Biotechnology in Food Production and Processing

NASA Astrophysics Data System (ADS)

Knorr, Dietrich; Sinskey, Anthony J.

1985-09-01

The food processing industry is the oldest and largest industry using biotechnological processes. Further development of food products and processes based on biotechnology depends upon the improvement of existing processes, such as fermentation, immobilized biocatalyst technology, and production of additives and processing aids, as well as the development of new opportunities for food biotechnology. Improvements are needed in the characterization, safety, and quality control of food materials, in processing methods, in waste conversion and utilization processes, and in currently used food microorganism and tissue culture systems. Also needed are fundamental studies of the structure-function relationship of food materials and of the cell physiology and biochemistry of raw materials.

Physiological Expression of AMPKγ2RG Mutation Causes Wolff-Parkinson-White Syndrome and Induces Kidney Injury in Mice*

PubMed Central

Yang, Xiaodong; Mudgett, John; Bou-About, Ghina; Champy, Marie-France; Jacobs, Hugues; Monassier, Laurent; Pavlovic, Guillaume; Sorg, Tania; Herault, Yann; Petit-Demoulière, Benoit; Lu, Ku; Feng, Wen; Wang, Hongwu; Ma, Li-Jun; Askew, Roger; Erion, Mark D.; Kelley, David E.; Myers, Robert W.; Li, Cai

2016-01-01

Mutations of the AMP-activated kinase gamma 2 subunit (AMPKγ2), N488I (AMPKγ2NI) and R531G (AMPKγ2RG), are associated with Wolff-Parkinson-White (WPW) syndrome, a cardiac disorder characterized by ventricular pre-excitation in humans. Cardiac-specific transgenic overexpression of human AMPKγ2NI or AMPKγ2RG leads to constitutive AMPK activation and the WPW phenotype in mice. However, overexpression of these mutant proteins also caused profound, non-physiological increase in cardiac glycogen, which might abnormally alter the true phenotype. To investigate whether physiological levels of AMPKγ2NI or AMPKγ2RG mutation cause WPW syndrome and metabolic changes in other organs, we generated two knock-in mouse lines on the C57BL/6N background harboring mutations of human AMPKγ2NI and AMPKγ2RG, respectively. Similar to the reported phenotypes of mice overexpressing AMPKγ2NI or AMPKγ2RG in the heart, both lines developed WPW syndrome and cardiac hypertrophy; however, these effects were independent of cardiac glycogen accumulation. Compared with AMPKγ2WT mice, AMPKγ2NI and AMPKγ2RG mice exhibited reduced body weight, fat mass, and liver steatosis when fed with a high fat diet (HFD). Surprisingly, AMPKγ2RG but not AMPKγ2NI mice fed with an HFD exhibited severe kidney injury characterized by glycogen accumulation, inflammation, apoptosis, cyst formation, and impaired renal function. These results demonstrate that expression of AMPKγ2NI and AMPKγ2RG mutations at physiological levels can induce beneficial metabolic effects but that this is accompanied by WPW syndrome. Our data also reveal an unexpected effect of AMPKγ2RG in the kidney, linking lifelong constitutive activation of AMPK to a potential risk for kidney dysfunction in the context of an HFD. PMID:27621313

Physiological Expression of AMPKγ2RG Mutation Causes Wolff-Parkinson-White Syndrome and Induces Kidney Injury in Mice.

PubMed

Yang, Xiaodong; Mudgett, John; Bou-About, Ghina; Champy, Marie-France; Jacobs, Hugues; Monassier, Laurent; Pavlovic, Guillaume; Sorg, Tania; Herault, Yann; Petit-Demoulière, Benoit; Lu, Ku; Feng, Wen; Wang, Hongwu; Ma, Li-Jun; Askew, Roger; Erion, Mark D; Kelley, David E; Myers, Robert W; Li, Cai; Guan, Hong-Ping

2016-11-04

Mutations of the AMP-activated kinase gamma 2 subunit (AMPKγ2), N488I (AMPKγ2 NI ) and R531G (AMPKγ2 RG ), are associated with Wolff-Parkinson-White (WPW) syndrome, a cardiac disorder characterized by ventricular pre-excitation in humans. Cardiac-specific transgenic overexpression of human AMPKγ2 NI or AMPKγ2 RG leads to constitutive AMPK activation and the WPW phenotype in mice. However, overexpression of these mutant proteins also caused profound, non-physiological increase in cardiac glycogen, which might abnormally alter the true phenotype. To investigate whether physiological levels of AMPKγ2 NI or AMPKγ2 RG mutation cause WPW syndrome and metabolic changes in other organs, we generated two knock-in mouse lines on the C57BL/6N background harboring mutations of human AMPKγ2 NI and AMPKγ2 RG , respectively. Similar to the reported phenotypes of mice overexpressing AMPKγ2 NI or AMPKγ2 RG in the heart, both lines developed WPW syndrome and cardiac hypertrophy; however, these effects were independent of cardiac glycogen accumulation. Compared with AMPKγ2 WT mice, AMPKγ2 NI and AMPKγ2 RG mice exhibited reduced body weight, fat mass, and liver steatosis when fed with a high fat diet (HFD). Surprisingly, AMPKγ2 RG but not AMPKγ2 NI mice fed with an HFD exhibited severe kidney injury characterized by glycogen accumulation, inflammation, apoptosis, cyst formation, and impaired renal function. These results demonstrate that expression of AMPKγ2 NI and AMPKγ2 RG mutations at physiological levels can induce beneficial metabolic effects but that this is accompanied by WPW syndrome. Our data also reveal an unexpected effect of AMPKγ2 RG in the kidney, linking lifelong constitutive activation of AMPK to a potential risk for kidney dysfunction in the context of an HFD. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Sleep: a physiological "cerveau isolé" stage?

PubMed

Gottesmann, C; User, P; Gioanni, H

1980-01-01

Rapid or paradoxical sleep in the rat is usually preceded and often followed by a stage of short duration characterized by large spindles in the frontal cortex and theta rhythm in the hippocampus. The midbrain transection induces for hours the same electrophysiological patterns suggesting the existence in the rat of a short physiologically isolated, forebrain stage during sleep.

Beyond triglyceride synthesis: the dynamic functional roles of MGAT and DGAT enzymes in energy metabolism.

PubMed

Shi, Yuguang; Cheng, Dong

2009-07-01

Monoacyglycerol acyltransferases (MGATs) and diacylglycerol acyltransferases (DGATs) catalyze two consecutive steps of enzyme reactions in the synthesis of triacylglycerols (TAGs). The metabolic complexity of TAG synthesis is reflected by the presence of multiple isoforms of MGAT and DGAT enzymes that differ in catalytic properties, subcellular localization, tissue distribution, and physiological functions. MGAT and DGAT enzymes play fundamental roles in the metabolism of monoacylglycerol (MAG), diacylglycerol (DAG), and triacylglycerol (TAG) that are involved in many aspects of physiological functions, such as intestinal fat absorption, lipoprotein assembly, adipose tissue formation, signal transduction, satiety, and lactation. The recent progress in the phenotypic characterization of mice deficient in MGAT and DGAT enzymes and the development of chemical inhibitors have revealed important roles of these enzymes in the regulation of energy homeostasis and insulin sensitivity. Consequently, selective inhibition of MGAT or DGAT enzymes by synthetic compounds may provide novel treatment for obesity and its related metabolic complications.

Real-time monitoring of cardiovascular function in rhesus macaques infected with Zaire ebolavirus.

PubMed

Kortepeter, Mark G; Lawler, James V; Honko, Anna; Bray, Mike; Johnson, Joshua C; Purcell, Bret K; Olinger, Gene G; Rivard, Robert; Hepburn, Matthew J; Hensley, Lisa E

2011-11-01

Nine rhesus macaques were implanted with multisensor telemetry devices and internal jugular vein catheters before being infected with Zaire ebolavirus. All animals developed viremia, fever, a hemorrhagic rash, and typical changes of Ebola hemorrhagic fever in clinical laboratory tests. Three macaques unexpectedly survived this usually lethal disease, making it possible to compare physiological parameters in lethally challenged animals and survivors. After the onset of fever, lethal illness was characterized by a decline in mean arterial blood pressure, an increase in pulse and respiratory rate, lactic acidosis, and renal failure. Survivors showed less pronounced change in these parameters. Four macaques were randomized to receive supplemental volumes of intravenous normal saline when they became hypotensive. Although those animals had less severe renal compromise, no apparent survival benefit was observed. This is the first report of continuous physiologic monitoring in filovirus-infected nonhuman primates and the first to attempt cardiovascular support with intravenous fluids.

Genetic, physiologic and ecogeographic factors contributing to variation in Homo sapiens: Homo floresiensis reconsidered.

PubMed

Richards, Gary D

2006-11-01

A new species, Homo floresiensis, was recently named for Pleistocene hominid remains on Flores, Indonesia. Significant controversy has arisen regarding this species. To address controversial issues and refocus investigations, I examine the affinities of these remains with Homo sapiens. Clarification of problematic issues is sought through an integration of genetic and physiological data on brain ontogeny and evolution. Clarification of the taxonomic value of various 'primitive' traits is possible given these data. Based on this evidence and using a H. sapiens morphological template, models are developed to account for the combination of features displayed in the Flores fossils. Given this overview, I find substantial support for the hypothesis that the remains represent a variant of H. sapiens possessing a combined growth hormone-insulin-like growth factor I axis modification and mutation of the MCPH gene family. Further work will be required to determine the extent to which this variant characterized the population.

Improved physiologically based pharmacokinetic model for oral exposures to chromium in mice, rats, and humans to address temporal variation and sensitive populations.

PubMed

Kirman, C R; Suh, M; Proctor, D M; Hays, S M

2017-06-15

A physiologically based pharmacokinetic (PBPK) model for hexavalent chromium [Cr(VI)] in mice, rats, and humans developed previously (Kirman et al., 2012, 2013), was updated to reflect an improved understanding of the toxicokinetics of the gastrointestinal tract following oral exposures. Improvements were made to: (1) the reduction model, which describes the pH-dependent reduction of Cr(VI) to Cr(III) in the gastrointestinal tract under both fasted and fed states; (2) drinking water pattern simulations, to better describe dosimetry in rodents under the conditions of the NTP cancer bioassay; and (3) parameterize the model to characterize potentially sensitive human populations. Important species differences, sources of non-linear toxicokinetics, and human variation are identified and discussed within the context of human health risk assessment. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Anxiety Sensitivity in Bereaved Adults with and without Complicated Grief

PubMed Central

Robinaugh, Donald J.; McNally, Richard J.; LeBlanc, Nicole J.; Pentel, Kimberly Z.; Schwarz, Noah R.; Shah, Riva M.; Nadal-Vicens, Mireya F.; Moore, Cynthia W.; Marques, Luana; Bui, Eric; Simon, Naomi M.

2014-01-01

Complicated grief (CG) is a bereavement specific syndrome chiefly characterized by symptoms of persistent separation distress. Physiological reactivity to reminders of the loss and repeated acute pangs or waves of severe anxiety and psychological pain are prominent features of CG. Fear of this grief-related physiological arousal may contribute to CG by increasing the distress associated with grief reactions and increasing the likelihood of maladaptive coping strategies and grief-related avoidance. Here, we examined anxiety sensitivity (i.e., the fear of anxiety-related sensations; AS) in two studies of bereaved adults with and without CG. In both studies, bereaved adults with CG exhibited elevated AS relative to those without CG. In Study 2, AS was positively associated with CG symptom severity among those with CG. These findings are consistent with the possibility that AS contributes to the development or maintenance of CG symptoms. PMID:25075646

Median nerve trauma in a rat model of work-related musculoskeletal disorder.

PubMed

Clark, Brian D; Barr, Ann E; Safadi, Fayez F; Beitman, Lisa; Al-Shatti, Talal; Amin, Mamta; Gaughan, John P; Barbe, Mary F

2003-07-01

Anatomical and physiological changes were evaluated in the median nerves of rats trained to perform repetitive reaching. Motor degradation was evident after 4 weeks. ED1-immunoreactive macrophages were seen in the transcarpal region of the median nerve of both forelimbs by 5-6 weeks. Fibrosis, characterized by increased immunoexpression of collagen type I by 8 weeks and connective tissue growth factor by 12 weeks, was evident. The conduction velocity (NCV) within the carpal tunnel showed a modest but significant decline after 9-12 weeks. The lowest NCV values were found in animals that refused to participate in the task for the full time available. Thus, both anatomical and physiological signs of progressive tissue damage were present in this model. These results, together with other recent findings indicate that work-related carpal tunnel syndrome develops through mechanisms that include injury, inflammation, fibrosis and subsequent nerve compression.

Characteristic Sizes of Life in the Oceans, from Bacteria to Whales.

PubMed

Andersen, K H; Berge, T; Gonçalves, R J; Hartvig, M; Heuschele, J; Hylander, S; Jacobsen, N S; Lindemann, C; Martens, E A; Neuheimer, A B; Olsson, K; Palacz, A; Prowe, A E F; Sainmont, J; Traving, S J; Visser, A W; Wadhwa, N; Kiørboe, T

2016-01-01

The size of an individual organism is a key trait to characterize its physiology and feeding ecology. Size-based scaling laws may have a limited size range of validity or undergo a transition from one scaling exponent to another at some characteristic size. We collate and review data on size-based scaling laws for resource acquisition, mobility, sensory range, and progeny size for all pelagic marine life, from bacteria to whales. Further, we review and develop simple theoretical arguments for observed scaling laws and the characteristic sizes of a change or breakdown of power laws. We divide life in the ocean into seven major realms based on trophic strategy, physiology, and life history strategy. Such a categorization represents a move away from a taxonomically oriented description toward a trait-based description of life in the oceans. Finally, we discuss life forms that transgress the simple size-based rules and identify unanswered questions.

Characterization and Reclassification of Yeasts Used for Biological Control of Postharvest Diseases of Fruits and Vegetables

PubMed Central

McLaughlin, R. J.; Wilson, C. L.; Chalutz, E.; Kurtzman, C. P.; Fett, W. F.; Osman, S. F.

1990-01-01

In previous studies workers have shown that three yeast strains (strains US-7, 82, and 101) have biological control activity against various postharvest fungal pathogens of fruits and vegetables, including Penicillium rots of apples and citrus and Botrytis rot of apples. In these reports the researchers have described these strains as Debaryomyces hansenii (anamorph, Candida famata) or Candida sp. strains. In this study we performed additional physiological, DNA reassociation, and mannan characterization tests that clearly established a new taxonomic classification for these strains, Candida guilliermondii. We also propose amendment of the physiological test profile in the taxonomic description of C. guilliermondii. PMID:16348361

Dynamical analysis of uterine cell electrical activity model.

PubMed

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

2006-01-01

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

Design, Fabrication and Characterization of an In Silico Cell Physiology lab for Bio Sensing Applications

NASA Astrophysics Data System (ADS)

Haque, A. ul; Rokkam, M.; DeCarlo, A. R.; Wereley, S. T.; Wells, H. W.; McLamb, W. T.; Roux, S. J.; Irazoqui, P. P.; Porterfield, D. M.

2006-04-01

In this paper, we report the design, fabrication and characterization of an In Silico cell physiology biochip for measuring Ca2+ ion concentrations and currents around single cells. This device has been designed around specific science objectives of measuring real time multidimensional calcium flux patterns around sixteen Ceratopteris richardii fern spores in microgravity flight experiments and ground studies. The sixteen microfluidic cell holding pores are 150 by 150 µm each and have 4 Ag/AgCl electrodes leading into them. An SU-8 structural layer is used for insulation and packaging purposes. The In Silico cell physiology lab is wire bonded on to a custom PCB for easy interface with a state of the art data acquisition system. The electrodes are coated with a Ca2+ ion selective membrane based on ETH-5234 ionophore and operated against an Ag/AgCl reference electrode. Initial characterization results have shown Nernst slopes of 30mv/decade that were stable over a number of measurement cycles. While this work is focused on technology to enable basic research on the Ceratopteris richardii spores, we anticipate that this type of cell physiology lab-on-a-chip will be broadly applied in biomedical and pharmacological research by making minor modifications to the electrode material and the measurement technique. Future applications include detection of glucose, hormones such as plant auxin, as well as multiple analyte detection on the same chip.

Adult pituitary stem cells: from pituitary plasticity to adenoma development.

PubMed

Florio, Tullio

2011-01-01

The pituitary needs high plasticity of the hormone-producing cell compartment to generate the continuously changing hormonal signals that govern the key physiological processes it is involved in, as well as homeostatic cell turnover. However, the underlying mechanisms are still poorly understood. It was proposed that adult stem cells direct the generation of newborn cells with a hormonal phenotype according to the physiological requirements. However, only in recent years adult pituitary stem cells have begun to be phenotypically characterized in several studies that identified multiple stem/progenitor cell candidates. Also considering the incompletely defined features of this cell subpopulation, some discrepancies among the different reports are clearly apparent and long-term self-renewal remains to be unequivocally demonstrated. Here, all the recently published evidence is analyzed, trying, when possible, to reconcile the results of the different studies. Finally, with the perspective of shedding light on pituitary tumorigenesis and the development of potentially new pharmacological approaches directed against these cells, very recent evidence on the presence of putative cancer stem cells in human pituitary adenomas is discussed. Copyright © 2011 S. Karger AG, Basel.

Improved physiologically based pharmacokinetic model for oral exposures to chromium in mice, rats, and humans to address temporal variation and sensitive populations

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

Kirman, C.R., E-mail: ckirman@summittoxicology.com

A physiologically based pharmacokinetic (PBPK) model for hexavalent chromium [Cr(VI)] in mice, rats, and humans developed previously (Kirman et al., 2012, 2013), was updated to reflect an improved understanding of the toxicokinetics of the gastrointestinal tract following oral exposures. Improvements were made to: (1) the reduction model, which describes the pH-dependent reduction of Cr(VI) to Cr(III) in the gastrointestinal tract under both fasted and fed states; (2) drinking water pattern simulations, to better describe dosimetry in rodents under the conditions of the NTP cancer bioassay; and (3) parameterize the model to characterize potentially sensitive human populations. Important species differences, sourcesmore » of non-linear toxicokinetics, and human variation are identified and discussed within the context of human health risk assessment. - Highlights: • An improved version of the PBPK model for Cr(VI) toxicokinetics was developed. • The model incorporates data collected to fill important data gaps. • Model predictions for specific age groups and sensitive subpopulations are provided. • Implications to human health risk assessment are discussed.« less

Correlation between vortices and wall shear stress in a curved artery model under pulsatile flow conditions

NASA Astrophysics Data System (ADS)

Cox, Christopher; Plesniak, Michael W.

2017-11-01

One of the most physiologically relevant factors within the cardiovascular system is the wall shear stress. The wall shear stress affects endothelial cells via mechanotransduction and atherosclerotic regions are strongly correlated with curvature and branching in the human vasculature, where the shear stress is both oscillatory and multidirectional. Also, the combined effect of curvature and pulsatility in cardiovascular flows produces unsteady vortices. In this work, our goal is to assess the correlation between multiple vortex pairs and wall shear stress. To accomplish this, we use an in-house high-order flux reconstruction Navier-Stokes solver to simulate pulsatile flow of a Newtonian blood-analog fluid through a rigid 180° curved artery model. We use a physiologically relevant flow rate and generate results using both fully developed and uniform entrance conditions, the latter motivated by the fact that flow upstream to a curved artery may not be fully developed. Under these two inflow conditions, we characterize the evolution of various vortex pairs and their subsequent effect on several wall shear stress metrics. Supported by GW Center for Biomimetics and Bioinspired Engineering.

Nutrition in adolescents: physiology, metabolism, and nutritional needs.

PubMed

Das, Jai K; Salam, Rehana A; Thornburg, Kent L; Prentice, Andrew M; Campisi, Susan; Lassi, Zohra S; Koletzko, Berthold; Bhutta, Zulfiqar A

2017-04-01

Adolescence is the period of development that begins at puberty and ends in early adulthood. Most commonly, adolescence is divided into three developmental periods: early adolescence (10-14 years of age), late adolescence (15-19 years of age), and young adulthood (20-24 years of age). Adolescence is marked by physical and sexual maturation, social and economic independence, development of identity, acquisition of skills needed to carry out adult relationships and roles, and the capacity for abstract reasoning. Adolescence is characterized by a rapid pace of growth that is second only to that of infancy. Nutrition and the adolescent transition are closely intertwined, since eating patterns and behaviors are influenced by many factors, including peer influences, parental modeling, food availability, food preferences, cost, convenience, personal and cultural beliefs, mass media, and body image. Here, we describe the physiology, metabolism, and nutritional requirements for adolescents and pregnant adolescents, as well as nutrition-related behavior and current trends in adolescent nutrition. We conclude with thoughts on the implications for nutrition interventions and priority areas that would require further investigation. © 2017 New York Academy of Sciences.

Development of concept-based physiology lessons for biomedical engineering undergraduate students.

PubMed

Nelson, Regina K; Chesler, Naomi C; Strang, Kevin T

2013-06-01

Physiology is a core requirement in the undergraduate biomedical engineering curriculum. In one or two introductory physiology courses, engineering students must learn physiology sufficiently to support learning in their subsequent engineering courses and careers. As preparation for future learning, physiology instruction centered on concepts may help engineering students to further develop their physiology and biomedical engineering knowledge. Following the Backward Design instructional model, a series of seven concept-based lessons was developed for undergraduate engineering students. These online lessons were created as prerequisite physiology training to prepare students to engage in a collaborative engineering challenge activity. This work is presented as an example of how to convert standard, organ system-based physiology content into concept-based content lessons.

Aberrant patterns of X chromosome inactivation in a new line of human embryonic stem cells established in physiological oxygen concentrations.

PubMed

de Oliveira Georges, Juliana Andrea; Vergani, Naja; Fonseca, Simone Aparecida Siqueira; Fraga, Ana Maria; de Mello, Joana Carvalho Moreira; Albuquerque, Maria Cecília R Maciel; Fujihara, Litsuko Shimabukuro; Pereira, Lygia Veiga

2014-08-01

One of the differences between murine and human embryonic stem cells (ESCs) is the epigenetic state of the X chromosomes in female lines. Murine ESCs (mESCs) present two transcriptionally active Xs that will undergo the dosage compensation process of XCI upon differentiation, whereas most human ESCs (hESCs) spontaneously inactivate one X while keeping their pluripotency. Whether this reflects differences in embryonic development of mice and humans, or distinct culture requirements for the two kinds of pluripotent cells is not known. Recently it has been shown that hESCs established in physiological oxygen levels are in a stable pre-XCI state equivalent to that of mESCs, suggesting that culture in low oxygen concentration is enough to preserve that epigenetic state of the X chromosomes. Here we describe the establishment of two new lines of hESCs under physiological oxygen level and the characterization of the XCI state in the 46,XX line BR-5. We show that a fraction of undifferentiated cells present XIST RNA accumulation and single H3K27me foci, characteristic of the inactive X. Moreover, analysis of allele specific gene expression suggests that pluripotent BR-5 cells present completely skewed XCI. Our data indicate that physiological levels of oxygen are not sufficient for the stabilization of the pre-XCI state in hESCs.

Mining functionally relevant gene sets for analyzing physiologically novel clinical expression data.

PubMed

Turcan, Sevin; Vetter, Douglas E; Maron, Jill L; Wei, Xintao; Slonim, Donna K

2011-01-01

Gene set analyses have become a standard approach for increasing the sensitivity of transcriptomic studies. However, analytical methods incorporating gene sets require the availability of pre-defined gene sets relevant to the underlying physiology being studied. For novel physiological problems, relevant gene sets may be unavailable or existing gene set databases may bias the results towards only the best-studied of the relevant biological processes. We describe a successful attempt to mine novel functional gene sets for translational projects where the underlying physiology is not necessarily well characterized in existing annotation databases. We choose targeted training data from public expression data repositories and define new criteria for selecting biclusters to serve as candidate gene sets. Many of the discovered gene sets show little or no enrichment for informative Gene Ontology terms or other functional annotation. However, we observe that such gene sets show coherent differential expression in new clinical test data sets, even if derived from different species, tissues, and disease states. We demonstrate the efficacy of this method on a human metabolic data set, where we discover novel, uncharacterized gene sets that are diagnostic of diabetes, and on additional data sets related to neuronal processes and human development. Our results suggest that our approach may be an efficient way to generate a collection of gene sets relevant to the analysis of data for novel clinical applications where existing functional annotation is relatively incomplete.

Characterizing Uncertainty and Variability in PBPK Models: State of the Science and Needs for Research and Implementation

EPA Science Inventory

Mode-of-action based risk and safety assessments can rely upon tissue dosimetry estimates in animals and humans obtained from physiologically-based pharmacokinetic (PBPK) modeling. However, risk assessment also increasingly requires characterization of uncertainty and variabilit...

Characterization of Lactobacillus from Algerian Goat’S Milk Based on Phenotypic, 16S rDNA Sequencing and their Technological Properties

PubMed Central

Marroki, Ahmed; Zúñiga, Manuel; Kihal, Mabrouk; Pérez- Martínez, Gaspar

2011-01-01

Nineteen strains of Lactobacillus isolated from goat’s milk from farms in north-west of Algeria were characterized. Isolates were identified by phenotypic, physiological and genotypic methods and some of their important technological properties were studied. Phenotypic characterization was carried out by studying physiological, morphological characteristics and carbohydrate fermentation patterns using API 50 CHL system. Isolates were also characterized by partial 16S rDNA sequencing. Results obtained with phenotypic methods were correlated with the genotypic characterization and 13 isolates were identified as L. plantarum, two isolates as L. rhamnosus and one isolate as L. fermentum. Three isolates identified as L. plantarum by phenotypic characterization were found to be L. pentosus by the genotypic method. A large diversity in technological properties (acid production in skim milk, exopolysaccharide production, aminopeptidase activity, antibacterial activity and antibiotic susceptibility) was observed. Based on these results, two strains of L. plantarum (LbMS16 and LbMS21) and one strain of L. rhamnosus (LbMF25) have been tentatively selected for use as starter cultures in the manufacture of artisanal fermented dairy products in Algeria. PMID:24031617

Novel imaging technologies for characterization of microbial extracellular polysaccharides.

PubMed

Lilledahl, Magnus B; Stokke, Bjørn T

2015-01-01

Understanding of biology is underpinned by the ability to observe structures at various length scales. This is so in a historical context and is also valid today. Evolution of novel insight often emerges from technological advancement. Recent developments in imaging technologies that is relevant for characterization of extraceullar microbiological polysaccharides are summarized. Emphasis is on scanning probe and optical based techniques since these tools offers imaging capabilities under aqueous conditions more closely resembling the physiological state than other ultramicroscopy imaging techniques. Following the demonstration of the scanning probe microscopy principle, novel operation modes to increase data capture speed toward video rate, exploitation of several cantilever frequencies, and advancement of utilization of specimen mechanical properties as contrast, also including their mode of operation in liquid, have been developed on this platform. Combined with steps in advancing light microscopy with resolution beyond the far field diffraction limit, non-linear methods, and combinations of the various imaging modalities, the potential ultramicroscopy toolbox available for characterization of exopolysaccharides (EPS) are richer than ever. Examples of application of such ultramicroscopy strategies range from imaging of isolated microbial polysaccharides, structures being observed when they are involved in polyelectrolyte complexes, aspects of their enzymatic degradation, and cell surface localization of secreted polysaccharides. These, and other examples, illustrate that the advancement in imaging technologies relevant for EPS characterization supports characterization of structural aspects.

Transformation of a Dwarf "Arabidopsis" Mutant Illustrates Gibberellin Hormone Physiology and the Function of a Green Revolution Gene

ERIC Educational Resources Information Center

Molina, Isabel; Weber, Katrin; Alves Cursino dos Santos, Deborah Y.; Ohlrogge, John

2009-01-01

The introduction of dwarfing traits into crops was a major factor in increased grain yields during the "Green Revolution." In most cases those traits were the consequence of altered synthesis or response to the gibberellin (GA) plant hormones. Our current understanding of GA synthesis and physiology has been facilitated by the characterization of…

An oral multiparticulate, modified-release, hydrocortisone replacement therapy that provides physiological cortisol exposure.

PubMed

Whitaker, Martin; Debono, Miguel; Huatan, Hiep; Merke, Deborah; Arlt, Wiebke; Ross, Richard J

2014-04-01

It is not possible with current hydrocortisone replacement to mimic the diurnal cortisol profile in patients with adrenal insufficiency. Previous attempts with modified-release technology were unsuccessful. Our objective was to develop hydrocortisone formulations that recreate the diurnal cortisol profile using multiparticulate technology. Screening by in vitro dissolution profiles, pharmacokinetic (PK) testing in dexamethasone-suppressed dogs and humans, and comparison with a reference population. Field laboratories and clinical research facility. Formulations were generated using an enteric (delayed release) design configuration with an extended (sustained release) dissolution profile. In vitro dissolution confirmed delayed and sustained hydrocortisone release. However, in dogs and humans, sustained release resulted in reduced bioavailability. A formulation, DIURF-006, was developed that maintained delayed release but omitted the sustained-release functionality. PK characterization of DIURF-006 showed that, despite absence of a sustained-release component, absorption was sufficiently sustained to deliver extended hydrocortisone absorption. In dexamethasone-suppressed volunteers (n = 16) receiving a twice-daily 'toothbrush' regimen (20 mg at 23:00 h and 10 mg at 07:00 h), DIURF-006 gave a similar cortisol profile to physiological cortisol levels: DIURF-006 vs physiological, Geomean AUC 5610 vs 4706 h * nmol/l, Geomean Cmax 665 vs 594 nmol/l and Median Tmax 8·5 h vs clock time 08:12 h for peak cortisol. The relative bioavailability of DIURF-006 vs hydrocortisone was 89%, and cortisol levels increased linearly with doses between 5 and 30 mg. A multiparticulate oral hydrocortisone formulation with only an enteric coat provides delayed and sustained absorption and when given in a 'toothbrush' regimen provides physiological cortisol exposure. © 2013 John Wiley & Sons Ltd.

A mobile system for assessment of physiological response to posture transitions.

PubMed

Jovanov, Emil; Milosevic, Mladen; Milenković, Aleksandar

2013-01-01

Posture changes initiate a dynamic physiological response that can be used as an indicator of the overall health status. We introduce an inconspicuous mobile wellness monitoring system (imWell) that continuously assesses the dynamic physiological response to posture transitions during activities of daily living. imWell utilizes a Zephyr BioHarness 3 physiological monitor that continually reports heart activity and physical activity via Bluetooth to a personal device (e.g. smartphone). The personal device processes the reported activity data in real-time to recognize posture transitions from the accelerometer data and to characterize dynamic heart response to posture changes. It annotates, logs, and uploads the heart activity data to our mHealth server. In this paper we present algorithms for detection of posture transitions and heart activity characterization during a sit-to-stand transition. The proposed system was tested on seven healthy subjects performing a predefined protocol. The total average and standard deviation for sit-to-stand transition time is 2.7 ± 0.69 s, resulting in the change of heart rate of 27.36 ± 9.30 bpm (from 63.3 ± 9.02 bpm to 90.66 ± 10.09 bpm).

Conceptual framework of the eco-physiological phases of insect diapause development justified by transcriptomic profiling

PubMed Central

Štětina, Tomáš; Poupardin, Rodolphe; Korbelová, Jaroslava; Bruce, Alexander William

2017-01-01

Insects often overcome unfavorable seasons in a hormonally regulated state of diapause during which their activity ceases, development is arrested, metabolic rate is suppressed, and tolerance of environmental stress is bolstered. Diapausing insects pass through a stereotypic succession of eco-physiological phases termed “diapause development.” The phasing is varied in the literature, and the whole concept is sometimes criticized as being too artificial. Here we present the results of transcriptional profiling using custom microarrays representing 1,042 genes in the drosophilid fly, Chymomyza costata. Fully grown, third-instar larvae programmed for diapause by a photoperiodic (short-day) signal were assayed as they traversed the diapause developmental program. When analyzing the gradual dynamics in the transcriptomic profile, we could readily distinguish distinct diapause developmental phases associated with induction/initiation, maintenance, cold acclimation, and termination by cold or by photoperiodic signal. Accordingly, each phase is characterized by a specific pattern of gene expression, supporting the physiological relevance of the concept of diapause phasing. Further, we have dissected in greater detail the changes in transcript levels of elements of several signaling pathways considered critical for diapause regulation. The phase of diapause termination is associated with enhanced transcript levels in several positive elements stimulating direct development (the 20-hydroxyecdysone pathway: Ecr, Shd, Broad; the Wnt pathway: basket, c-jun) that are countered by up-regulation in some negative elements (the insulin-signaling pathway: Ilp8, PI3k, Akt; the target of rapamycin pathway: Tsc2 and 4EBP; the Wnt pathway: shaggy). We speculate such up-regulations may represent the early steps linked to termination of diapause programming. PMID:28720705

GPER/GPR30 knockout mice: effects of GPER on metabolism

PubMed Central

Sharma, Geetanjali; Prossnitz, Eric R.

2015-01-01

i. Summary Endogenous estrogens, predominantly 17β-estradiol (E2), mediate various very diverse effects throughout the body in both normal physiology and disease. Actions include development (including puberty) and reproduction as well as additional effects throughout life in the metabolic, endocrine, musculoskeletal, nervous, cardiovascular and immune systems. The actions of E2 have traditionally been attributed to the classical nuclear estrogen receptors (ERα and ERβ) that largely mediate transcriptional/genomic activities. However, more recently the G protein-coupled estrogen receptor GPER/GPR30 has become recognized as an essential mediator of certain, and particularly rapid, signaling events in response to E2. Murine genetic knockout (KO) models represent an important approach to understand the mechanisms of E2 action in physiology and disease. Studies of GPER KO mice over the last years have revealed functions for GPER in the regulation of obesity, insulin resistance and glucose intolerance, among other areas of (patho)physiology. This chapter focuses on methods for the evaluation of metabolic parameters in vivo and ex vivo with an emphasis on glucose homeostasis and metabolism through the use of glucose and insulin tolerance tests, pancreatic islet and adipocyte isolation and characterization. PMID:26585159

GPER/GPR30 Knockout Mice: Effects of GPER on Metabolism.

PubMed

Sharma, Geetanjali; Prossnitz, Eric R

2016-01-01

Endogenous estrogens, predominantly 17β-estradiol (E2), mediate various diverse effects throughout the body in both normal physiology and disease. Actions include development (including puberty) and reproduction as well as additional effects throughout life in the metabolic, endocrine, musculoskeletal, nervous, cardiovascular, and immune systems. The actions of E2 have traditionally been attributed to the classical nuclear estrogen receptors (ERα and ERβ) that largely mediate transcriptional/genomic activities. However, more recently the G protein-coupled estrogen receptor GPER/GPR30 has become recognized as an essential mediator of certain, and particularly rapid, signaling events in response to E2. Murine genetic knockout (KO) models represent an important approach to understand the mechanisms of E2 action in physiology and disease. Studies of GPER KO mice over the last years have revealed functions for GPER in the regulation of obesity, insulin resistance and glucose intolerance, among other areas of (patho)physiology. This chapter focuses on methods for the evaluation of metabolic parameters in vivo and ex vivo with an emphasis on glucose homeostasis and metabolism through the use of glucose and insulin tolerance tests, pancreatic islet and adipocyte isolation and characterization.

Integrating 4-d light-sheet imaging with interactive virtual reality to recapitulate developmental cardiac mechanics and physiology

NASA Astrophysics Data System (ADS)

Ding, Yichen; Yu, Jing; Abiri, Arash; Abiri, Parinaz; Lee, Juhyun; Chang, Chih-Chiang; Baek, Kyung In; Sevag Packard, René R.; Hsiai, Tzung K.

2018-02-01

There currently is a limited ability to interactively study developmental cardiac mechanics and physiology. We therefore combined light-sheet fluorescence microscopy (LSFM) with virtual reality (VR) to provide a hybrid platform for 3- dimensional (3-D) architecture and time-dependent cardiac contractile function characterization. By taking advantage of the rapid acquisition, high axial resolution, low phototoxicity, and high fidelity in 3-D and 4-D (3-D spatial + 1-D time or spectra), this VR-LSFM hybrid methodology enables interactive visualization and quantification otherwise not available by conventional methods such as routine optical microscopes. We hereby demonstrate multi-scale applicability of VR-LSFM to 1) interrogate skin fibroblasts interacting with a hyaluronic acid-based hydrogel, 2) navigate through the endocardial trabecular network during zebrafish development, and 3) localize gene therapy-mediated potassium channel expression in adult murine hearts. We further combined our batch intensity normalized segmentation (BINS) algorithm with deformable image registration (DIR) to interface a VR environment for the analysis of cardiac contraction. Thus, the VR-LSFM hybrid platform demonstrates an efficient and robust framework for creating a user-directed microenvironment in which we uncovered developmental cardiac mechanics and physiology with high spatiotemporal resolution.

Ambulatory diffuse optical tomography and multimodality physiological monitoring system for muscle and exercise applications

NASA Astrophysics Data System (ADS)

Hu, Gang; Zhang, Quan; Ivkovic, Vladimir; Strangman, Gary E.

2016-09-01

Ambulatory diffuse optical tomography (aDOT) is based on near-infrared spectroscopy (NIRS) and enables three-dimensional imaging of regional hemodynamics and oxygen consumption during a person's normal activities. Although NIRS has been previously used for muscle assessment, it has been notably limited in terms of the number of channels measured, the extent to which subjects can be ambulatory, and/or the ability to simultaneously acquire synchronized auxiliary data such as electromyography (EMG) or electrocardiography (ECG). We describe the development of a prototype aDOT system, called NINscan-M, capable of ambulatory tomographic imaging as well as simultaneous auxiliary multimodal physiological monitoring. Powered by four AA size batteries and weighing 577 g, the NINscan-M prototype can synchronously record 64-channel NIRS imaging data, eight channels of EMG, ECG, or other analog signals, plus force, acceleration, rotation, and temperature for 24+ h at up to 250 Hz. We describe the system's design, characterization, and performance characteristics. We also describe examples of isometric, cycle ergometer, and free-running ambulatory exercise to demonstrate tomographic imaging at 25 Hz. NINscan-M represents a multiuse tool for muscle physiology studies as well as clinical muscle assessment.

Mechanical Characterization of Microengineered Epithelial Cysts by Using Atomic Force Microscopy.

PubMed

Shen, Yusheng; Guan, Dongshi; Serien, Daniela; Takeuchi, Shoji; Tong, Penger; Yobas, Levent; Huang, Pingbo

2017-01-24

Most organs contain interconnected tubular tissues that are one-cell-thick, polarized epithelial monolayers enclosing a fluid-filled lumen. Such tissue organization plays crucial roles in developmental and normal physiology, and the proper functioning of these tissues depends on their regulation by complex biochemical perturbations and equally important, but poorly understood, mechanical perturbations. In this study, by combining micropatterning techniques and atomic force microscopy, we developed a simple in vitro experimental platform for characterizing the mechanical properties of the MDCK II cyst, the simplest model of lumen-enclosing epithelial monolayers. By using this platform, we estimated the elasticity of the cyst monolayer and showed that the presence of a luminal space influences cyst mechanics substantially, which could be attributed to polarization and tissue-level coordination. More interestingly, the results from force-relaxation experiments showed that the cysts also displayed tissue-level poroelastic characteristics that differed slightly from those of single cells. Our study provides the first quantitative findings, to our knowledge, on the tissue-level mechanics of well-polarized epithelial cysts and offers new insights into the interplay between cyst mechanics and cyst physiology. Moreover, our simple platform is a potentially useful tool for enhancing the current understanding of cyst mechanics in health and disease. Copyright © 2017 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Raman spectroscopy: in vivo quick response code of skin physiological status

NASA Astrophysics Data System (ADS)

Vyumvuhore, Raoul; Tfayli, Ali; Piot, Olivier; Le Guillou, Maud; Guichard, Nathalie; Manfait, Michel; Baillet-Guffroy, Arlette

2014-11-01

Dermatologists need to combine different clinically relevant characteristics for a better understanding of skin health. These characteristics are usually measured by different techniques, and some of them are highly time consuming. Therefore, a predicting model based on Raman spectroscopy and partial least square (PLS) regression was developed as a rapid multiparametric method. The Raman spectra collected from the five uppermost micrometers of 11 healthy volunteers were fitted to different skin characteristics measured by independent appropriate methods (transepidermal water loss, hydration, pH, relative amount of ceramides, fatty acids, and cholesterol). For each parameter, the obtained PLS model presented correlation coefficients higher than R2=0.9. This model enables us to obtain all the aforementioned parameters directly from the unique Raman signature. In addition to that, in-depth Raman analyses down to 20 μm showed different balances between partially bound water and unbound water with depth. In parallel, the increase of depth was followed by an unfolding process of the proteins. The combinations of all these information led to a multiparametric investigation, which better characterizes the skin status. Raman signal can thus be used as a quick response code (QR code). This could help dermatologic diagnosis of physiological variations and presents a possible extension to pathological characterization.

Raman spectroscopy: in vivo quick response code of skin physiological status.

PubMed

Vyumvuhore, Raoul; Tfayli, Ali; Piot, Olivier; Le Guillou, Maud; Guichard, Nathalie; Manfait, Michel; Baillet-Guffroy, Arlette

2014-01-01

Dermatologists need to combine different clinically relevant characteristics for a better understanding of skin health. These characteristics are usually measured by different techniques, and some of them are highly time consuming. Therefore, a predicting model based on Raman spectroscopy and partial least square (PLS) regression was developed as a rapid multiparametric method. The Raman spectra collected from the five uppermost micrometers of 11 healthy volunteers were fitted to different skin characteristics measured by independent appropriate methods (transepidermal water loss, hydration, pH, relative amount of ceramides, fatty acids, and cholesterol). For each parameter, the obtained PLS model presented correlation coefficients higher than R2=0.9. This model enables us to obtain all the aforementioned parameters directly from the unique Raman signature. In addition to that, in-depth Raman analyses down to 20 μm showed different balances between partially bound water and unbound water with depth. In parallel, the increase of depth was followed by an unfolding process of the proteins. The combinations of all these information led to a multiparametric investigation, which better characterizes the skin status. Raman signal can thus be used as a quick response code (QR code). This could help dermatologic diagnosis of physiological variations and presents a possible extension to pathological characterization.

Broadband attenuation measurements of phospholipid-shelled ultrasound contrast agents.

PubMed

Raymond, Jason L; Haworth, Kevin J; Bader, Kenneth B; Radhakrishnan, Kirthi; Griffin, Joseph K; Huang, Shao-Ling; McPherson, David D; Holland, Christy K

2014-02-01

The aim of this study was to characterize the frequency-dependent acoustic attenuation of three phospholipid-shelled ultrasound contrast agents (UCAs): Definity, MicroMarker and echogenic liposomes. A broadband through-transmission technique allowed for measurement over 2 to 25 MHz with a single pair of transducers. Viscoelastic shell parameters of the UCAs were estimated using a linearized model developed by N. de Jong, L. Hoff, T. Skotland and N. Bom (Ultrasonics 1992; 30:95-103). The effect of diluent on the attenuation of these UCA suspensions was evaluated by performing attenuation measurements in 0.5% (w/v) bovine serum albumin and whole blood. Changes in attenuation and shell parameters of the UCAs were investigated at room temperature (25°C) and physiologic temperature (37°C). The attenuation of the UCAs diluted in 0.5% (w/v) bovine serum albumin was found to be identical to the attenuation of UCAs in whole blood. For each UCA, attenuation was higher at 37°C than at 25°C, underscoring the importance of conducting characterization studies at physiologic temperature. Echogenic liposomes exhibited a larger increase in attenuation at 37°C versus 25°C than either Definity or MicroMarker. Copyright © 2014 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

Measurement of cortical functional activation in awake mice using two-photon microscopy and a novel pO2-sensitive probe(Conference Presentation)

NASA Astrophysics Data System (ADS)

Sencan, Ikbal; Esipova, Tatiana V.; Kilic, Kivilcim; Li, Baoqiang; Desjardins, Michèle; Yaseen, Mohammad A.; Wang, Hui; Jaswal, Rajeshwer S.; Kura, Sreekanth; Fu, Buyin; Boas, David A.; Devor, Anna; Sakadžić, Sava; Vinogradov, Sergei A.

2017-02-01

We characterized cortical microvascular PO2 and blood flow changes in response to whisker stimulation in awake mice. The measurements were performed by combining two-photon microscopy imaging of the cortical oxygenation and optical coherence tomography imaging of the cerebral blood flow. In order to perform fast spatio-temporally resolved measurements of PO2, we used a newly-developed oxygen-sensitive probe PtG-2P, which has significantly higher brightness than the established two-photon-enhanced oxygen sensor PtP-C343. We characterized the performance of the new probe in vivo and mapped the amplitudes and shapes (e.g. initial dip, overshoot, and post stimulus undershoot) of the PO2 changes as a function of the vessel type (e.g., arterioles, capillaries, and venules) and a distance from the activation center. The measurements in the awake mice are not affected by the confounding factors of anesthesia on the animal physiology, including the level of cerebral metabolism and the amplitude and speed of neuronal and vascular responses. Our results will help to understand changes in oxygenation and blood flow on the cortical microvascular scale, will lead to improved understanding of the cerebral physiology, pathophysiology and will improve quantitative interpretation of fMRI signals.

Characterizing the in vivo role of trehalose in Saccharomyces cerevisiae using the AGT1 transporter

DOE PAGES

Gibney, Patrick A.; Schieler, Ariel; Chen, Jonathan C.; ...

2015-04-27

Trehalose is a highly stable, nonreducing disaccharide of glucose. A large body of research exists implicating trehalose in a variety of cellular phenomena, notably response to stresses of various kinds. However, in very few cases has the role of trehalose been examined directly in vivo. Here, we describe the development and characterization of a system in Saccharomyces cerevisiae that allows us to manipulate intracellular trehalose concentrations independently of the biosynthetic enzymes and independently of any applied stress. We found that many physiological roles heretofore ascribed to intracellular trehalose, including heat resistance, are not due to the presence of trehalose permore » se. We also found that many of the metabolic and growth defects associated with mutations in the trehalose biosynthesis pathway are not abolished by providing abundant intracellular trehalose. Instead, we made the observation that intracellular accumulation of trehalose or maltose (another disaccharide of glucose) is growth-inhibitory in a carbon source-specific manner. We conclude that the physiological role of the trehalose pathway is fundamentally metabolic: i.e., more complex than simply the consequence of increased concentrations of the sugar and its attendant physical properties (with the exception of the companion paper where demonstrate a direct role for trehalose in protecting cells against desiccation).« less

Development and characterization of a microfluidic model of the tumour microenvironment

PubMed Central

Ayuso, Jose M.; Virumbrales-Muñoz, María; Lacueva, Alodia; Lanuza, Pilar M.; Checa-Chavarria, Elisa; Botella, Pablo; Fernández, Eduardo; Doblare, Manuel; Allison, Simon J.; Phillips, Roger M.; Pardo, Julián; Fernandez, Luis J.; Ochoa, Ignacio

2016-01-01

The physical microenvironment of tumours is characterized by heterotypic cell interactions and physiological gradients of nutrients, waste products and oxygen. This tumour microenvironment has a major impact on the biology of cancer cells and their response to chemotherapeutic agents. Despite this, most in vitro cancer research still relies primarily on cells grown in 2D and in isolation in nutrient- and oxygen-rich conditions. Here, a microfluidic device is presented that is easy to use and enables modelling and study of the tumour microenvironment in real-time. The versatility of this microfluidic platform allows for different aspects of the microenvironment to be monitored and dissected. This is exemplified here by real-time profiling of oxygen and glucose concentrations inside the device as well as effects on cell proliferation and growth, ROS generation and apoptosis. Heterotypic cell interactions were also studied. The device provides a live ‘window’ into the microenvironment and could be used to study cancer cells for which it is difficult to generate tumour spheroids. Another major application of the device is the study of effects of the microenvironment on cellular drug responses. Some data is presented for this indicating the device’s potential to enable more physiological in vitro drug screening. PMID:27796335

Development and validation of an open source O2-sensitive gel for physiological profiling of soil microbial communities.

PubMed

McLamore, E S; Garland, J L; Mackowiak, C; Desaunay, A; Garland, N; Chaturvedi, P; Taguchi, M; Dreaden, K; Catechis, John; Ullman, J L

2014-01-01

Community level physiological profiling is a simple, high-throughput technique for assessing microbial community physiology. Initial methods relying on redox-dye based detection of respiration were subject to strong enrichment bias, but subsequent development of a microtiter assay using an oxygen-quenched dye reduced this bias and improved the versatility of the approach. Commercial production of the oxygen microplates recently stopped, which led to the present effort to develop and validate a system using a luminophore dye (platinum tetrakis pentafluorophenyl) immobilized at the bottom of wells within a 96 well microtiter plate. The technique was used to analyze three well-characterized Florida soils: oak saw palmetto scrub, coastal mixed hardwood, and soil from an agricultural field used to grow corn silage. Substrate induced respiration was monitored by measuring respiration rates in soils under basal conditions and comparing to soils supplemented with nitrogen and various carbon sources (mannose, casein, asparagine, coumaric acid). All data was compared to a previously available commercial assay. There were no significant differences in the maximum peak intensity or the time to peak response for all soils tested (p<0.001, α=0.05). The experimental assay plates can be reused on soils up to four times (based on a deviation of less than 5%), where the commercial assay should not be reused. The results indicate that the new oxygen-based bioassay is a cost effective, open source tool for functional profiling of microbial communities. Copyright © 2013 Elsevier B.V. All rights reserved.

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

PubMed Central

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

2014-01-01

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

Type 2 diabetes and obesity in adults.

PubMed

Whitmore, Catherine

There are approximately 2.5 million people in the UK with diabetes; 85-95% of whom have type 2 diabetes. Type 2 diabetes mellitus is characterized by insulin resistance and impaired insulin secretion. As approximately 90% of people with type 2 diabetes are overweight or obese, obesity is seen as a significant contributory factor in its development. This article aims to examine some of the physiological mechanisms by which overweight and obesity contribute to the development of type 2 diabetes, and review some of the approaches to managing overweight and obesity in the person with established type 2 diabetes, including dietary management, the use of reduced carbohydrate diets on glycamic control, anti-diabetes and anti-obesity drugs both in use and in development, and bariatric surgery.

The ALK receptor in sympathetic neuron development and neuroblastoma.

PubMed

Janoueix-Lerosey, Isabelle; Lopez-Delisle, Lucille; Delattre, Olivier; Rohrer, Hermann

2018-05-01

The ALK gene encodes a tyrosine kinase receptor characterized by an expression pattern mainly restricted to the developing central and peripheral nervous systems. In 2008, the discovery of ALK activating mutations in neuroblastoma, a tumor of the sympathetic nervous system, represented a breakthrough in the understanding of the pathogenesis of this pediatric cancer and established mutated ALK as a tractable therapeutic target for precision medicine. Subsequent studies addressed the identity of ALK ligands, as well as its physiological function in the sympathoadrenal lineage, its role in neuroblastoma development and the signaling pathways triggered by mutated ALK. This review focuses on these different aspects of the ALK biology and summarizes the various therapeutic strategies relying on ALK inhibition in neuroblastoma, either as monotherapies or combinatory treatments.

REV-ERB and ROR nuclear receptors as drug targets

PubMed Central

Kojetin, Douglas J.; Burris, Thomas P.

2016-01-01

The nuclear receptors REV-ERB (consisting of REV-ERBα and REV-ERBβ) and retinoic acid receptor-related orphan receptors (RORs; consisting of RORα, RORβ and RORγ) are involved in many physiological processes, including regulation of metabolism, development and immunity as well as the circadian rhythm. The recent characterization of endogenous ligands for these former orphan nuclear receptors has stimulated the development of synthetic ligands and opened up the possibility of targeting these receptors to treat several diseases, including diabetes, atherosclerosis, autoimmunity and cancer. This Review focuses on the latest developments in ROR and REV-ERB pharmacology indicating that these nuclear receptors are druggable targets and that ligands targeting these receptors may be useful in the treatment of several disorders. PMID:24577401

A New Conditionally Immortalized Human Fetal Brain Pericyte Cell Line: Establishment and Functional Characterization as a Promising Tool for Human Brain Pericyte Studies.

PubMed

Umehara, Kenta; Sun, Yuchen; Hiura, Satoshi; Hamada, Koki; Itoh, Motoyuki; Kitamura, Keita; Oshima, Motohiko; Iwama, Atsushi; Saito, Kosuke; Anzai, Naohiko; Chiba, Kan; Akita, Hidetaka; Furihata, Tomomi

2018-07-01

While pericytes wrap around microvascular endothelial cells throughout the human body, their highest coverage rate is found in the brain. Brain pericytes actively contribute to various brain functions, including the development and stabilization of the blood-brain barrier (BBB), tissue regeneration, and brain inflammation. Accordingly, detailed characterization of the functional nature of brain pericytes is important for understanding the mechanistic basis of brain physiology and pathophysiology. Herein, we report on the development of a new human brain pericyte cell line, hereafter referred to as the human brain pericyte/conditionally immortalized clone 37 (HBPC/ci37). Developed via the cell conditionally immortalization method, these cells exhibited excellent proliferative ability at 33 °C. However, when cultured at 37 °C, HBPC/ci37 cells showed a differentiated phenotype that was marked by morphological alterations and increases in several pericyte-enriched marker mRNA levels, such as platelet-derived growth factor receptor β. It was also found that HBPC/ci37 cells possessed the facilitative ability of in vitro BBB formation and differentiation into a neuronal lineage. Furthermore, HBPC/ci37 cells exhibited the typical "reactive" features of brain pericytes in response to pro-inflammatory cytokines. To summarize, our results clearly demonstrate that HBPC/ci37 cells possess the ability to perform several key brain pericyte functions while also showing the capacity for extensive and continuous proliferation. Based on these findings, it can be expected that, as a unique human brain pericyte model, HBPC/ci37 cells have the potential to contribute to significant advances in the understanding of human brain pericyte physiology and pathophysiology.

Transcriptomic response of sea urchin larvae Strongylocentrotus purpuratus to CO2-driven seawater acidification.

PubMed

Todgham, Anne E; Hofmann, Gretchen E

2009-08-01

Ocean acidification from the uptake of anthropogenic CO(2) is expected to have deleterious consequences for many calcifying marine animals. Forecasting the vulnerability of these marine organisms to climate change is linked to an understanding of whether species possess the physiological capacity to compensate for the potentially adverse effects of ocean acidification. We carried out a microarray-based transcriptomic analysis of the physiological response of larvae of a calcifying marine invertebrate, the purple sea urchin, Strongylocentrotus purpuratus, to CO(2)-driven seawater acidification. In lab-based cultures, larvae were raised under conditions approximating current ocean pH conditions (pH 8.01) and at projected, more acidic pH conditions (pH 7.96 and 7.88) in seawater aerated with CO(2) gas. Targeting expression of approximately 1000 genes involved in several biological processes, this study captured changes in gene expression patterns that characterize the transcriptomic response to CO(2)-driven seawater acidification of developing sea urchin larvae. In response to both elevated CO(2) scenarios, larvae underwent broad scale decreases in gene expression in four major cellular processes: biomineralization, cellular stress response, metabolism and apoptosis. This study underscores that physiological processes beyond calcification are impacted greatly, suggesting that overall physiological capacity and not just a singular focus on biomineralization processes is essential for forecasting the impact of future CO(2) conditions on marine organisms. Conducted on targeted and vulnerable species, genomics-based studies, such as the one highlighted here, have the potential to identify potential ;weak links' in physiological function that may ultimately determine an organism's capacity to tolerate future ocean conditions.

Metabolic and functional characterization of effects of developmental temperature in Drosophila melanogaster.

PubMed

Schou, Mads F; Kristensen, Torsten N; Pedersen, Anders; Karlsson, B Göran; Loeschcke, Volker; Malmendal, Anders

2017-02-01

The ability of ectotherms to respond to changes in their thermal environment through plastic mechanisms is central to their adaptive capability. However, we still lack knowledge on the physiological and functional responses by which ectotherms acclimate to temperatures during development, and in particular, how physiological stress at extreme temperatures may counteract beneficial acclimation responses at benign temperatures. We exposed Drosophila melanogaster to 10 developmental temperatures covering their entire permissible temperature range. We obtained metabolic profiles and reaction norms for several functional traits: egg-to-adult viability, developmental time, and heat and cold tolerance. Females were more heat tolerant than males, whereas no sexual dimorphism was found in cold tolerance. A group of metabolites, mainly free amino acids, had linear reaction norms. Several energy-carrying molecules, as well as some sugars, showed distinct inverted U-shaped norms of reaction across the thermal range, resulting in a positive correlation between metabolite intensities and egg-to-adult viability. At extreme temperatures, low levels of these metabolites were interpreted as a response characteristic of costs of homeostatic perturbations. Our results provide novel insights into a range of metabolites reported to be central for the acclimation response and suggest several new candidate metabolites. Low and high temperatures result in different adaptive physiological responses, but they also have commonalities likely to be a result of the failure to compensate for the physiological stress. We suggest that the regulation of metabolites that are tightly connected to the performance curve is important for the ability of ectotherms to cope with variation in temperature. Copyright © 2017 the American Physiological Society.

Genetic and Physiological Studies of Bacillus Anthracis Related to Development of an Improved Vaccine

DTIC Science & Technology

1990-07-01

charartorization of the conjugative pl&a.dd, PLS2O, of Baci~llu sbtllis ( natto ) amd its ability to tranisfer pla&iuids v" iitrains of B. inthraci~s, B...2-r-ich atms;hwre. A smll amount of effort wa spent on further’ characterization of the Bacillus subtilis ( natto ) fertility plasmid. pLS2I, which...previously cured of pX02. All transcipients that inherited the pXO2::Tn9l7 derivatives exhibited the donor phenotype. The 64.2-kb Bacillus subtilis ( natto

Optical medical imaging: from glass to man

NASA Astrophysics Data System (ADS)

Bradley, Mark

2016-11-01

A formidable challenge in modern respiratory healthcare is the accurate and timely diagnosis of lung infection and inflammation. The EPSRC Interdisciplinary Research Collaboration (IRC) `Proteus' seeks to address this challenge by developing an optical fibre based healthcare technology platform that combines physiological sensing with multiplexed optical molecular imaging. This technology will enable in situ measurements deep in the human lung allowing the assessment of tissue function and characterization of the unique signatures of pulmonary disease and is illustrated here with our in-man application of Optical Imaging SmartProbes and our first device Versicolour.

Laser induced fluorescence technique for environmental applications

NASA Astrophysics Data System (ADS)

Utkin, Andrei B.; Felizardo, Rui; Gameiro, Carla; Matos, Ana R.; Cartaxana, Paulo

2014-08-01

We discuss the development of laser induced fluorescence sensors and their application in the evaluation of water pollution and physiological status of higher plants and algae. The sensors were built on the basis of reliable and robust solid-state Nd:YAG lasers. They demonstrated good efficiency in: i) detecting and characterizing oil spills and dissolved organic matter; ii) evaluating the impact of stress on higher plants (cork oak, maritime pine, and genetically modified Arabidopsis); iii) tracking biomass changes in intertidal microphytobenthos; and iv) mapping macroalgal communities in the Tagus Estuary.

In vivo observation of transient photoreceptor movement correlated with oblique light stimulation

NASA Astrophysics Data System (ADS)

Lu, Yiming; Liu, Changgeng; Yao, Xincheng

2018-02-01

Rod-dominated transient retinal phototropism (TRP) has been observed in freshly isolated retinas, promising a noninvasive biomarker for high resolution assessment of retinal physiology. However, in vivo mapping of TRP is challenging due to its fast time course and sub-cellular signal magnitude. By developing a line-scanning and virtually structured detection based super-resolution ophthalmoscope, we report here in vivo observation of TRP in frog retina. In vivo characterization of TRP time course and magnitude were implemented by using variable light stimulus intensities.

Mass Determination of Entire Amyloid Fibrils by Using Mass Spectrometry.

PubMed

Doussineau, Tristan; Mathevon, Carole; Altamura, Lucie; Vendrely, Charlotte; Dugourd, Philippe; Forge, Vincent; Antoine, Rodolphe

2016-02-12

Amyloid fibrils are self-assembled protein structures with important roles in biology (either pathogenic or physiological), and are attracting increasing interest in nanotechnology. However, because of their high aspect ratio and the presence of some polymorphism, that is, the possibility to adopt various structures, their characterization is challenging and basic information such as their mass is unknown. Here we show that charge-detection mass spectrometry, recently developed for large self-assembled systems such as viruses, provides such information in a straightforward manner. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Zebrafish Bone and General Physiology Are Differently Affected by Hormones or Changes in Gravity.

PubMed

Aceto, Jessica; Nourizadeh-Lillabadi, Rasoul; Marée, Raphael; Dardenne, Nadia; Jeanray, Nathalie; Wehenkel, Louis; Aleström, Peter; van Loon, Jack J W A; Muller, Marc

2015-01-01

Teleost fish such as zebrafish (Danio rerio) are increasingly used for physiological, genetic and developmental studies. Our understanding of the physiological consequences of altered gravity in an entire organism is still incomplete. We used altered gravity and drug treatment experiments to evaluate their effects specifically on bone formation and more generally on whole genome gene expression. By combining morphometric tools with an objective scoring system for the state of development for each element in the head skeleton and specific gene expression analysis, we confirmed and characterized in detail the decrease or increase of bone formation caused by a 5 day treatment (from 5dpf to 10 dpf) of, respectively parathyroid hormone (PTH) or vitamin D3 (VitD3). Microarray transcriptome analysis after 24 hours treatment reveals a general effect on physiology upon VitD3 treatment, while PTH causes more specifically developmental effects. Hypergravity (3g from 5dpf to 9 dpf) exposure results in a significantly larger head and a significant increase in bone formation for a subset of the cranial bones. Gene expression analysis after 24 hrs at 3g revealed differential expression of genes involved in the development and function of the skeletal, muscular, nervous, endocrine and cardiovascular systems. Finally, we propose a novel type of experimental approach, the "Reduced Gravity Paradigm", by keeping the developing larvae at 3g hypergravity for the first 5 days before returning them to 1g for one additional day. 5 days exposure to 3g during these early stages also caused increased bone formation, while gene expression analysis revealed a central network of regulatory genes (hes5, sox10, lgals3bp, egr1, edn1, fos, fosb, klf2, gadd45ba and socs3a) whose expression was consistently affected by the transition from hyper- to normal gravity.

Zebrafish Bone and General Physiology Are Differently Affected by Hormones or Changes in Gravity

PubMed Central

Aceto, Jessica; Nourizadeh-Lillabadi, Rasoul; Marée, Raphael; Dardenne, Nadia; Jeanray, Nathalie; Wehenkel, Louis; Aleström, Peter

2015-01-01

Teleost fish such as zebrafish (Danio rerio) are increasingly used for physiological, genetic and developmental studies. Our understanding of the physiological consequences of altered gravity in an entire organism is still incomplete. We used altered gravity and drug treatment experiments to evaluate their effects specifically on bone formation and more generally on whole genome gene expression. By combining morphometric tools with an objective scoring system for the state of development for each element in the head skeleton and specific gene expression analysis, we confirmed and characterized in detail the decrease or increase of bone formation caused by a 5 day treatment (from 5dpf to 10 dpf) of, respectively parathyroid hormone (PTH) or vitamin D3 (VitD3). Microarray transcriptome analysis after 24 hours treatment reveals a general effect on physiology upon VitD3 treatment, while PTH causes more specifically developmental effects. Hypergravity (3g from 5dpf to 9 dpf) exposure results in a significantly larger head and a significant increase in bone formation for a subset of the cranial bones. Gene expression analysis after 24 hrs at 3g revealed differential expression of genes involved in the development and function of the skeletal, muscular, nervous, endocrine and cardiovascular systems. Finally, we propose a novel type of experimental approach, the "Reduced Gravity Paradigm", by keeping the developing larvae at 3g hypergravity for the first 5 days before returning them to 1g for one additional day. 5 days exposure to 3g during these early stages also caused increased bone formation, while gene expression analysis revealed a central network of regulatory genes (hes5, sox10, lgals3bp, egr1, edn1, fos, fosb, klf2, gadd45ba and socs3a) whose expression was consistently affected by the transition from hyper- to normal gravity. PMID:26061167

Emission Computed Tomography: A New Technique for the Quantitative Physiologic Study of Brain and Heart in Vivo

DOE R&D Accomplishments Database

Phelps, M. E.; Hoffman, E. J.; Huang, S. C.; Schelbert, H. R.; Kuhl, D. E.

1978-01-01

Emission computed tomography can provide a quantitative in vivo measurement of regional tissue radionuclide tracer concentrations. This facility when combined with physiologic models and radioactively labeled physiologic tracers that behave in a predictable manner allow measurement of a wide variety of physiologic variables. This integrated technique has been referred to as Physiologic Tomography (PT). PT requires labeled compounds which trace physiologic processes in a known and predictable manner, and physiologic models which are appropriately formulated and validated to derive physiologic variables from ECT data. In order to effectively achieve this goal, PT requires an ECT system that is capable of performing truly quantitative or analytical measurements of tissue tracer concentrations and which has been well characterized in terms of spatial resolution, sensitivity and signal to noise ratios in the tomographic image. This paper illustrates the capabilities of emission computed tomography and provides examples of physiologic tomography for the regional measurement of cerebral and myocardial metabolic rate for glucose, regional measurement of cerebral blood volume, gated cardiac blood pools and capillary perfusion in brain and heart. Studies on patients with stroke and myocardial ischemia are also presented.

Comparative Transcriptomic Characterization of the Early Development in Pacific White Shrimp Litopenaeus vannamei

PubMed Central

Wei, Jiankai; Zhang, Xiaojun; Yu, Yang; Huang, Hao; Li, Fuhua; Xiang, Jianhai

2014-01-01

Penaeid shrimp has a distinctive metamorphosis stage during early development. Although morphological and biochemical studies about this ontogeny have been developed for decades, researches on gene expression level are still scarce. In this study, we have investigated the transcriptomes of five continuous developmental stages in Pacific white shrimp (Litopenaeus vannamei) with high throughput Illumina sequencing technology. The reads were assembled and clustered into 66,815 unigenes, of which 32,398 have putative homologues in nr database, 14,981 have been classified into diverse functional categories by Gene Ontology (GO) annotation and 26,257 have been associated with 255 pathways by KEGG pathway mapping. Meanwhile, the differentially expressed genes (DEGs) between adjacent developmental stages were identified and gene expression patterns were clustered. By GO term enrichment analysis, KEGG pathway enrichment analysis and functional gene profiling, the physiological changes during shrimp metamorphosis could be better understood, especially histogenesis, diet transition, muscle development and exoskeleton reconstruction. In conclusion, this is the first study that characterized the integrated transcriptomic profiles during early development of penaeid shrimp, and these findings will serve as significant references for shrimp developmental biology and aquaculture research. PMID:25197823

Biomechanics of the Chick Embryonic Heart Outflow Tract at HH18 Using 4D Optical Coherence Tomography Imaging and Computational Modeling

PubMed Central

Liu, Aiping; Yin, Xin; Shi, Liang; Li, Peng; Thornburg, Kent L.; Wang, Ruikang; Rugonyi, Sandra

2012-01-01

During developmental stages, biomechanical stimuli on cardiac cells modulate genetic programs, and deviations from normal stimuli can lead to cardiac defects. Therefore, it is important to characterize normal cardiac biomechanical stimuli during early developmental stages. Using the chicken embryo model of cardiac development, we focused on characterizing biomechanical stimuli on the Hamburger–Hamilton (HH) 18 chick cardiac outflow tract (OFT), the distal portion of the heart from which a large portion of defects observed in humans originate. To characterize biomechanical stimuli in the OFT, we used a combination of in vivo optical coherence tomography (OCT) imaging, physiological measurements and computational fluid dynamics (CFD) modeling. We found that, at HH18, the proximal portion of the OFT wall undergoes larger circumferential strains than its distal portion, while the distal portion of the OFT wall undergoes larger wall stresses. Maximal wall shear stresses were generally found on the surface of endocardial cushions, which are protrusions of extracellular matrix onto the OFT lumen that later during development give rise to cardiac septa and valves. The non-uniform spatial and temporal distributions of stresses and strains in the OFT walls provide biomechanical cues to cardiac cells that likely aid in the extensive differential growth and remodeling patterns observed during normal development. PMID:22844414

W' expenditure and reconstitution during severe intensity constant power exercise: mechanistic insight into the determinants of W'.

PubMed

Broxterman, Ryan M; Skiba, Phillip F; Craig, Jesse C; Wilcox, Samuel L; Ade, Carl J; Barstow, Thomas J

2016-10-01

The sustainable duration of severe intensity exercise is well-predicted by critical power (CP) and the curvature constant (W'). The development of the W'BAL model allows for the pattern of W' expenditure and reconstitution to be characterized and this model has been applied to intermittent exercise protocols. The purpose of this investigation was to assess the influence of relaxation phase duration and exercise intensity on W' reconstitution during dynamic constant power severe intensity exercise. Six men (24.6 ± 0.9 years, height: 173.5 ± 1.9 cm, body mass: 78.9 ± 5.6 kg) performed severe intensity dynamic handgrip exercise to task failure using 50% and 20% duty cycles. The W'BAL model was fit to each exercise test and the time constant for W' reconstitution (τW') was determined. The τW' was significantly longer for the 50% duty cycle (1640 ± 262 sec) than the 20% duty cycle (863 ± 84 sec, P = 0.02). Additionally, the relationship between τW' and CP was well described as an exponential decay (r(2) = 0.90, P < 0.0001). In conclusion, the W'BAL model is able to characterize the expenditure and reconstitution of W' across the contraction-relaxation cycles comprising severe intensity constant power handgrip exercise. Moreover, the reconstitution of W' during constant power severe intensity exercise is influenced by the relative exercise intensity, the duration of relaxation between contractions, and CP. © 2016 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

Consequences of advanced aging on renal function in chronic hyperandrogenemic female rat model: implications for aging women with polycystic ovary syndrome.

PubMed

Patil, Chetan N; Racusen, Lorraine C; Reckelhoff, Jane F

2017-11-01

Polycystic ovary syndrome (PCOS) is the most common endocrine and reproductive disorder in premenopausal women, characterized by hyperandrogenemia, metabolic syndrome, and inflammation. Women who had PCOS during their reproductive years remain hyperandrogenemic after menopause. The consequence of chronic hyperandrogenemia with advanced aging has not been studied to our knowledge. We have characterized a model of hyperandrogenemia in female rats and have aged them to 22-25 months to mimic advanced aging in hyperandrogenemic women, and tested the hypothesis that chronic exposure to hyperandrogenemia with aging has a deleterious effect on renal function. Female rats were chronically implanted with dihydrotestosterone pellets (DHT 7.5 mg/90 days) that were changed every 85 days or placebo pellets, and renal function was measured by clearance methods. Aging DHT-treated females had a threefold higher level of DHT with significantly higher body weight, mean arterial pressure, left kidney weight, proteinuria, and kidney injury molecule-1 (KIM-1), than did age-matched controls. In addition, DHT-treated-old females had a 60% reduction in glomerular filtration rate, 40% reduction in renal plasma flow, and significant reduction in urinary nitrate and nitrite excretion (UNOxV), an index of nitric oxide production. Morphological examination of kidneys showed that old DHT-treated females had significant focal segmental glomerulosclerosis, global sclerosis, and interstitial fibrosis compared to controls. Thus chronic hyperandrogenemia that persists into old age in females is associated with renal injury. These data suggest that women with chronic hyperandrogenemia such as in PCOS may be at increased risk for development of chronic kidney disease with advanced age. © 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

Genome-wide expression analysis of soybean NF-Y genes reveals potential function in development and drought response.

PubMed

Quach, Truyen N; Nguyen, Hanh T M; Valliyodan, Babu; Joshi, Trupti; Xu, Dong; Nguyen, Henry T

2015-06-01

Nuclear factor-Y (NF-Y), a heterotrimeric transcription factor, is composed of NF-YA, NF-YB and NF-YC proteins. In plants, there are usually more than 10 genes for each family and their members have been identified to be key regulators in many developmental and physiological processes controlling gametogenesis, embryogenesis, nodule development, seed development, abscisic acid (ABA) signaling, flowering time, primary root elongation, blue light responses, endoplasmic reticulum (ER) stress response and drought tolerance. Taking the advantages of the recent soybean genome draft and information on functional characterizations of nuclear factor Y (NF-Y) transcription factor family in plants, we identified 21 GmNF-YA, 32 GmNF-YB, and 15 GmNF-YC genes in the soybean (Glycine max) genome. Phylogenetic analyses show that soybean's proteins share strong homology to Arabidopsis and many of them are closely related to functionally characterized NF-Y in plants. Expression analysis in various tissues of flower, leaf, root, seeds of different developmental stages, root hairs under rhizobium inoculation, and drought-treated roots and leaves revealed that certain groups of soybean NF-Y are likely involved in specific developmental and stress responses. This study provides extensive evaluation of the soybean NF-Y family and is particularly useful for further functional characterization of GmNF-Y proteins in seed development, nodulation and drought adaptation of soybean.

Emotional and physiological responses of fluent listeners while watching the speech of adults who stutter.

PubMed

Guntupalli, Vijaya K; Everhart, D Erik; Kalinowski, Joseph; Nanjundeswaran, Chayadevie; Saltuklaroglu, Tim

2007-01-01

People who stutter produce speech that is characterized by intermittent, involuntary part-word repetitions and prolongations. In addition to these signature acoustic manifestations, those who stutter often display repetitive and fixated behaviours outside the speech producing mechanism (e.g. in the head, arm, fingers, nares, etc.). Previous research has examined the attitudes and perceptions of those who stutter and people who frequently interact with them (e.g. relatives, parents, employers). Results have shown an unequivocal, powerful and robust negative stereotype despite a lack of defined differences in personality structure between people who stutter and normally fluent individuals. However, physiological investigations of listener responses during moments of stuttering are limited. There is a need for data that simultaneously examine physiological responses (e.g. heart rate and galvanic skin conductance) and subjective behavioural responses to stuttering. The pairing of these objective and subjective data may provide information that casts light on the genesis of negative stereotypes associated with stuttering, the development of compensatory mechanisms in those who stutter, and the true impact of stuttering on senders and receivers alike. To compare the emotional and physiological responses of fluent speakers while listening and observing fluent and severe stuttered speech samples. Twenty adult participants (mean age = 24.15 years, standard deviation = 3.40) observed speech samples of two fluent speakers and two speakers who stutter reading aloud. Participants' skin conductance and heart rate changes were measured as physiological responses to stuttered or fluent speech samples. Participants' subjective responses on arousal (excited-calm) and valence (happy-unhappy) dimensions were assessed via the Self-Assessment Manikin (SAM) rating scale with an additional questionnaire comprised of a set of nine bipolar adjectives. Results showed significantly increased skin conductance and lower mean heart rate during the presentation of stuttered speech relative to the presentation of fluent speech samples (p<0.05). Listeners also self-rated themselves as being more aroused, unhappy, nervous, uncomfortable, sad, tensed, unpleasant, avoiding, embarrassed, and annoyed while viewing stuttered speech relative to the fluent speech. These data support the notion that stutter-filled speech can elicit physiological and emotional responses in listeners. Clinicians who treat stuttering should be aware that listeners show involuntary physiological responses to moderate-severe stuttering that probably remain salient over time and contribute to the evolution of negative stereotypes of people who stutter. With this in mind, it is hoped that clinicians can work with people who stutter to develop appropriate coping strategies. The role of amygdala and mirror neural mechanism in physiological and subjective responses to stuttering is discussed.

Vasculogenesis and Angiogenesis: Molecular and Cellular Controls

PubMed Central

Kubis, N.; Levy, B.I.

2003-01-01

Summary Angiogenesis characterizes embryonic development, but also occurs in adulthood in physiological situations such as adaptation to muscle exercise, and in pathological conditions like cancer. Major advances have been made in understanding the molecular mechanisms responsible for vasculogenesis and angiogenesis, largely due to the use of “knock-out mice”, i.e. mice in which the gene coding for the protein under investigation has been inactivated. Interestingly, the same growth factors and their receptors are equally involved in the different aspects of vasculogenesis and angiogenesis during development and in adulthood. This review aims to describe in detail their respective roles and how interactions between them lead to a newly formed vessel. PMID:20591248

Novel adducts from the reaction of 1-chloro-3-buten-2-one with 2'-deoxyguanosine. Structural characterization and potential as tools to investigate 1,3-butadiene carcinogenicity.

PubMed

Zheng, Jin; Li, Yan; Yu, Ying-Xin; An, Jing; Zhang, Xin-Yu; Elfarra, Adnan A

2015-01-25

1-Chloro-3-buten-2-one (CBO) is a potential reactive metabolite of 1,3-butadiene (BD), a carcinogenic air pollutant. To develop tools that may help investigate the role of CBO in BD carcinogenicity and to develop biomarkers that can be used to assess BD exposure, the reaction of CBO with 2'-deoxyguanosine (dG) under in vitro physiological conditions (pH 7.4, 37°C) was investigated and the products (designated as CG-1, CG-2, CG-3, CG-4, CG-5, and CG-6 based on their retention times on HPLC) were characterized by MS and NMR spectroscopy. The structures of CG-1, CG-2, CG-3, and CG-4 were 1,N2-(3-hydroxy-3-hydroxymethylpropan-1,3-diyl)-2'-deoxyguanosine, N7-(4-chloro-3-oxobutyl)-2'-deoxyguanosine, N7,8-(3-hydroxy-3-chloromethylpropan-1,3-diyl)guanine and N2-(4-chloro-3-oxobutyl)-2'-deoxyguanosine, respectively. CG-5 and CG-6, a pair of diastereomers, were characterized as 1,N2-(3-hydroxy-3-chloromethylpropan-1,3-diyl)-2'-deoxyguanosine. CG-1 was stable under in vitro physiological conditions, whereas CG-2, CG-3, CG-4, and CG-5/6 were unstable and exhibited the half-lives at <1.0, 4.8±0.1, 6.7±0.3, and 2.7±0.1 h, respectively. CG-2 decomposed primarily via a retro-Michael reaction to produce dG and CBO, with only a small fraction of CG-2 degrading to CG-3. Decomposition of CG-4 proceeded via a cyclization reaction and/or replacement of the chlorine atom by a hydroxyl group to form 1,N2-(1-hydroxy-1-hydroxymethylpropan-1,3-diyl)-2'-deoxyguanosine (CG-4D1) and N(2)-(4-hydroxy-3-oxobutyl)-2'-deoxyguanosine (CG-4D2), whereas decomposition of CG-5/6 yielded CG-1. Collectively, the newly characterized CBO adducts could be used to investigate the role of CBO in the mechanism of BD carcinogenicity and could also be used to develop biomarkers for BD exposure. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Mapping Epileptic Activity: Sources or Networks for the Clinicians?

PubMed Central

Pittau, Francesca; Mégevand, Pierre; Sheybani, Laurent; Abela, Eugenio; Grouiller, Frédéric; Spinelli, Laurent; Michel, Christoph M.; Seeck, Margitta; Vulliemoz, Serge

2014-01-01

Epileptic seizures of focal origin are classically considered to arise from a focal epileptogenic zone and then spread to other brain regions. This is a key concept for semiological electro-clinical correlations, localization of relevant structural lesions, and selection of patients for epilepsy surgery. Recent development in neuro-imaging and electro-physiology and combinations, thereof, have been validated as contributory tools for focus localization. In parallel, these techniques have revealed that widespread networks of brain regions, rather than a single epileptogenic region, are implicated in focal epileptic activity. Sophisticated multimodal imaging and analysis strategies of brain connectivity patterns have been developed to characterize the spatio-temporal relationships within these networks by combining the strength of both techniques to optimize spatial and temporal resolution with whole-brain coverage and directional connectivity. In this paper, we review the potential clinical contribution of these functional mapping techniques as well as invasive electrophysiology in human beings and animal models for characterizing network connectivity. PMID:25414692

Characterizing the stress/defense transcriptome of Arabidopsis

PubMed Central

Mahalingam, Ramamurthy; Gomez-Buitrago, AnaMaria; Eckardt, Nancy; Shah, Nigam; Guevara-Garcia, Angel; Day, Philip; Raina, Ramesh; Fedoroff, Nina V

2003-01-01

Background To understand the gene networks that underlie plant stress and defense responses, it is necessary to identify and characterize the genes that respond both initially and as the physiological response to the stress or pathogen develops. We used PCR-based suppression subtractive hybridization to identify Arabidopsis genes that are differentially expressed in response to ozone, bacterial and oomycete pathogens and the signaling molecules salicylic acid (SA) and jasmonic acid. Results We identified a total of 1,058 differentially expressed genes from eight stress cDNA libraries. Digital northern analysis revealed that 55% of the stress-inducible genes are rarely transcribed in unstressed plants and 17% of them were not previously represented in Arabidopsis expressed sequence tag databases. More than two-thirds of the genes in the stress cDNA collection have not been identified in previous studies as stress/defense response genes. Several stress-responsive cis-elements showed a statistically significant over-representation in the promoters of the genes in the stress cDNA collection. These include W- and G-boxes, the SA-inducible element, the abscisic acid response element and the TGA motif. Conclusions The stress cDNA collection comprises a broad repertoire of stress-responsive genes encoding proteins that are involved in both the initial and subsequent stages of the physiological response to abiotic stress and pathogens. This set of stress-, pathogen- and hormone-modulated genes is an important resource for understanding the genetic interactions underlying stress signaling and responses and may contribute to the characterization of the stress transcriptome through the construction of standardized specialized arrays. PMID:12620105

A coupled photometric assay for characterization of S-adenosyl-l-homocysteine hydrolases in the physiological hydrolytic direction.

PubMed

Kailing, Lyn L; Bertinetti, Daniela; Herberg, Friedrich W; Pavlidis, Ioannis V

2017-10-25

S-Adenosyl-l-homocysteine hydrolases (SAHases) are important metabolic enzymes and their dysregulation is associated with some severe diseases. In vivo they catalyze the hydrolysis of S-adenosyl-l-homocysteine (SAH), the by-product of methylation reactions in various organisms. SAH is a potent inhibitor of methyltransferases, thus its removal from the equilibrium is an important requirement for methylation reactions. SAH hydrolysis is also the first step in the cellular regeneration process of the methyl donor S-adenosyl-l-methionine (SAM). However, in vitro the equilibrium lies towards the synthetic direction. To enable characterization of SAHases in the physiologically relevant direction, we have developed a coupled photometric assay that shifts the equilibrium towards hydrolysis by removing the product adenosine, using a high affinity adenosine kinase (AK). This converts adenosine to AMP and thereby forms equimolar amounts of ADP, which is phosphorylated by a pyruvate kinase (PK), in turn releasing pyruvate. The readout of the assay is the consumption of NADH during the lactate dehydrogenase (LDH) catalyzed reduction of pyruvate to lactic acid. The applicability of the assay is showcased for the determination of the kinetic constants of an SAHase from Bradyrhizobium elkanii (K M,SAH 41±5μM, v max,SAH 25±1μM/min with 0.13mg/mL enzyme). This assay is a valuable tool for in vitro characterization of SAHases with biotechnological potential, and for monitoring SAHase activity in diagnostics. Copyright © 2017 Elsevier B.V. All rights reserved.

Panel 2: Anatomy (Eustachian Tube, Middle Ear, and Mastoid-Anatomy, Physiology, Pathophysiology, and Pathogenesis).

PubMed

Alper, Cuneyt M; Luntz, Michal; Takahashi, Haruo; Ghadiali, Samir N; Swarts, J Douglas; Teixeira, Miriam S; Csákányi, Zsuzsanna; Yehudai, Noam; Kania, Romain; Poe, Dennis S

2017-04-01

Objective In this report, we review the recent literature (ie, past 4 years) to identify advances in our understanding of the middle ear-mastoid-eustachian tube system. We use this review to determine whether the short-term goals elaborated in the last report were achieved, and we propose updated goals to guide future otitis media research. Data Sources PubMed, Web of Science, Medline. Review Methods The panel topic was subdivided, and each contributor performed a literature search within the given time frame. The keywords searched included middle ear, eustachian tube, and mastoid for their intersection with anatomy, physiology, pathophysiology, and pathology. Preliminary reports from each panel member were consolidated and discussed when the panel met on June 11, 2015. At that meeting, the progress was evaluated and new short-term goals proposed. Conclusions Progress was made on 13 of the 20 short-term goals proposed in 2011. Significant advances were made in the characterization of middle ear gas exchange pathways, modeling eustachian tube function, and preliminary testing of treatments for eustachian tube dysfunction. Implications for Practice In the future, imaging technologies should be developed to noninvasively assess middle ear/eustachian tube structure and physiology with respect to their role in otitis media pathogenesis. The new data derived from these structure/function experiments should be integrated into computational models that can then be used to develop specific hypotheses concerning otitis media pathogenesis and persistence. Finally, rigorous studies on medical or surgical treatments for eustachian tube dysfunction should be undertaken.

Cytotoxicity and Physiological Effects of Silver Nanoparticles on Marine Invertebrates.

PubMed

Magesky, Adriano; Pelletier, Émilien

2018-01-01

Silver nanoparticles (AgNPs) incorporation in commercial products is increasing due to their remarkable physical and chemical properties and their low cost on the market. Silver has been known for a long time to be highly toxic to bacterial communities, aquatic organisms, and particularly to marine biota. Strong chloro-complexes dominate Ag speciation in seawater and facilitate its persistence in dissolved form. It has a great impact on marine organisms because low concentration of silver can lead to strong bioaccumulation, partly because the neutral silver chloro complex (AgCl 0 ) is highly bioavailable. Owing to the fact that estuaries and coastal areas are considered as the ultimate fate for AgNPs, the study of their toxic effects on marine invertebrates can reveal some environmental risks related to nanosilver exposure. In an attempt to reach this goal, many invertebrate taxa including mollusks, crustaceans, echinoderms and polychaetes have been used as biological models. The main findings related to AgNP toxicity and marine invertebrates are summarized hereafter. Some cellular mechanisms involving nano-internalization (cellular uptake, distribution and elimination), DNA damaging, antioxidant cellular defenses and protein expression are discussed. Physiological effects on early stage development, silver metabolic speciation, immune response, tissue damaging, anti-oxidant effects and nano-depuration are also described. Finally, we paid attention to some recent interesting findings using sea urchin developmental stages and their cells as models for nanotoxicity investigation. Cellular and physiological processes characterizing sea urchin development revealed new and multiple toxicity mechanisms of both soluble and nano forms of silver.

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.

Sensorimotor coordination and the structure of space.

PubMed

McCollum, Gin

2003-01-01

Embedded in neural and behavioral organization is a structure of sensorimotor space. Both this embedded spatial structure and the structure of physical space inform sensorimotor control. This paper reviews studies in which the gravitational vertical and horizontal are crucial. The mathematical expressions of spatial geometry in these studies indicate methods for investigating sensorimotor control in freefall. In freefall, the spatial structure introduced by gravitation - the distinction between vertical and horizontal - does not exist. However, an astronaut arriving in space carries the physiologically-embedded distinction between horizontal and vertical learned on earth. The physiological organization based on this distinction collapses when the strong otolith activity and other gravitational cues for sensorimotor behavior become unavailable. The mathematical methods in this review are applicable in understanding the changes in physiological organization as an astronaut adapts to sensorimotor control in freefall. Many mathematical languages are available for characterizing the logical structures in physiological organization. Here, group theory is used to characterize basic structure of physical and physiological spaces. Dynamics and topology allow the grouping of trajectory ranges according to the outcomes or attractors. The mathematics of ordered structures express complex orderings, such as in multiphase movements in which different parts of the body are moving in different phase sequences. Conditional dynamics, which combines dynamics with the mathematics of ordered structures, accommodates the parsing of movement sequences into trajectories and transitions. Studies reviewed include those of the sit-to-stand movement and early locomotion, because of the salience of gravitation in those behaviors. Sensorimotor transitions and the conditions leading to them are characterized in conditional dynamic control structures that do not require thinking of an organism as an input-output device. Conditions leading to sensorimotor transitions on earth assume the presence of a gravitational vertical which is lacking in space. Thus, conditions used on earth for sensorimotor transitions may become ambiguous in space. A platform study in which sensorimotor transition conditions are ambiguous and are related to motion sickness is reviewed.

Dissimilarity measure based on ordinal pattern for physiological signals

NASA Astrophysics Data System (ADS)

Wang, Jing; Shang, Pengjian; Shi, Wenbin; Cui, Xingran

2016-08-01

Complex physiologic signals may carry information of their underlying mechanisms. In this paper, we introduce a dissimilarity measure to capture the features of underlying dynamics from various types of physiologic signals based on rank order statistics of ordinal patterns. Simulated 1/f noise and white noise are used to evaluate the effect of data length, embedding dimension and time delay on this measure. We then apply this measure to different physiologic signals. The method can successfully characterize the unique underlying patterns of subjects at similar physiologic states. It can also serve as a good discriminative tool for the healthy young, healthy elderly, congestive heart failure, atrial fibrilation and white noise groups. Furthermore, when investigated into the details of underlying ordinal patterns for each group, it is found that the distributions of ordinal patterns varies significantly for healthy and pathologic states, as well as aging.

Molecular physiology of weight regulation in mice and humans

PubMed Central

Leibel, RL

2009-01-01

Evolutionary considerations relating to efficiency in reproduction, and survival in hostile environments, suggest that body energy stores are sensed and actively regulated, with stronger physiological and behavioral responses to loss than gain of stored energy. Many physiological studies support this inference, and suggest that a critical axis runs between body fat and the hypothalamus. The molecular cloning of leptin and its receptor—projects based explicitly on the search for elements in this axis—confirmed the existence of this axis and provided important tools with which to understand its molecular physiology. Demonstration of the importance of this soma-brain reciprocal connection in body weight regulation in humans has been pursued using both classical genetic approaches and studies of physiological responses to experimental weight perturbation. This paper reviews the history of the rationale and methodology of the cloning of leptin (Lep) and the leptin receptor (Lepr), and describes some of the clinical investigation characterizing this axis. PMID:19136999

Mapping differential interactomes by affinity purification coupled with data-independent mass spectrometry acquisition.

PubMed

Lambert, Jean-Philippe; Ivosev, Gordana; Couzens, Amber L; Larsen, Brett; Taipale, Mikko; Lin, Zhen-Yuan; Zhong, Quan; Lindquist, Susan; Vidal, Marc; Aebersold, Ruedi; Pawson, Tony; Bonner, Ron; Tate, Stephen; Gingras, Anne-Claude

2013-12-01

Characterizing changes in protein-protein interactions associated with sequence variants (e.g., disease-associated mutations or splice forms) or following exposure to drugs, growth factors or hormones is critical to understanding how protein complexes are built, localized and regulated. Affinity purification (AP) coupled with mass spectrometry permits the analysis of protein interactions under near-physiological conditions, yet monitoring interaction changes requires the development of a robust and sensitive quantitative approach, especially for large-scale studies in which cost and time are major considerations. We have coupled AP to data-independent mass spectrometric acquisition (sequential window acquisition of all theoretical spectra, SWATH) and implemented an automated data extraction and statistical analysis pipeline to score modulated interactions. We used AP-SWATH to characterize changes in protein-protein interactions imparted by the HSP90 inhibitor NVP-AUY922 or melanoma-associated mutations in the human kinase CDK4. We show that AP-SWATH is a robust label-free approach to characterize such changes and propose a scalable pipeline for systems biology studies.

Atomic Force Microscopy in Characterizing Cell Mechanics for Biomedical Applications: A Review.

PubMed

Li, Mi; Dang, Dan; Liu, Lianqing; Xi, Ning; Wang, Yuechao

2017-09-01

Cell mechanics is a novel label-free biomarker for indicating cell states and pathological changes. The advent of atomic force microscopy (AFM) provides a powerful tool for quantifying the mechanical properties of single living cells in aqueous conditions. The wide use of AFM in characterizing cell mechanics in the past two decades has yielded remarkable novel insights in understanding the development and progression of certain diseases, such as cancer, showing the huge potential of cell mechanics for practical applications in the field of biomedicine. In this paper, we reviewed the utilization of AFM to characterize cell mechanics. First, the principle and method of AFM single-cell mechanical analysis was presented, along with the mechanical responses of cells to representative external stimuli measured by AFM. Next, the unique changes of cell mechanics in two types of physiological processes (stem cell differentiation, cancer metastasis) revealed by AFM were summarized. After that, the molecular mechanisms guiding cell mechanics were analyzed. Finally the challenges and future directions were discussed.

Transcript Analysis and Regulative Events during Flower Development in Olive (Olea europaea L.).

PubMed

Alagna, Fiammetta; Cirilli, Marco; Galla, Giulio; Carbone, Fabrizio; Daddiego, Loretta; Facella, Paolo; Lopez, Loredana; Colao, Chiara; Mariotti, Roberto; Cultrera, Nicolò; Rossi, Martina; Barcaccia, Gianni; Baldoni, Luciana; Muleo, Rosario; Perrotta, Gaetano

2016-01-01

The identification and characterization of transcripts involved in flower organ development, plant reproduction and metabolism represent key steps in plant phenotypic and physiological pathways, and may generate high-quality transcript variants useful for the development of functional markers. This study was aimed at obtaining an extensive characterization of the olive flower transcripts, by providing sound information on the candidate MADS-box genes related to the ABC model of flower development and on the putative genetic and molecular determinants of ovary abortion and pollen-pistil interaction. The overall sequence data, obtained by pyrosequencing of four cDNA libraries from flowers at different developmental stages of three olive varieties with distinct reproductive features (Leccino, Frantoio and Dolce Agogia), included approximately 465,000 ESTs, which gave rise to more than 14,600 contigs and approximately 92,000 singletons. As many as 56,700 unigenes were successfully annotated and provided gene ontology insights into the structural organization and putative molecular function of sequenced transcripts and deduced proteins in the context of their corresponding biological processes. Differentially expressed genes with potential regulatory roles in biosynthetic pathways and metabolic networks during flower development were identified. The gene expression studies allowed us to select the candidate genes that play well-known molecular functions in a number of biosynthetic pathways and specific biological processes that affect olive reproduction. A sound understanding of gene functions and regulatory networks that characterize the olive flower is provided.

Transcript Analysis and Regulative Events during Flower Development in Olive (Olea europaea L.)

PubMed Central

Alagna, Fiammetta; Cirilli, Marco; Galla, Giulio; Carbone, Fabrizio; Daddiego, Loretta; Facella, Paolo; Lopez, Loredana; Colao, Chiara; Mariotti, Roberto; Cultrera, Nicolò; Rossi, Martina; Barcaccia, Gianni; Baldoni, Luciana; Muleo, Rosario; Perrotta, Gaetano

2016-01-01

The identification and characterization of transcripts involved in flower organ development, plant reproduction and metabolism represent key steps in plant phenotypic and physiological pathways, and may generate high-quality transcript variants useful for the development of functional markers. This study was aimed at obtaining an extensive characterization of the olive flower transcripts, by providing sound information on the candidate MADS-box genes related to the ABC model of flower development and on the putative genetic and molecular determinants of ovary abortion and pollen-pistil interaction. The overall sequence data, obtained by pyrosequencing of four cDNA libraries from flowers at different developmental stages of three olive varieties with distinct reproductive features (Leccino, Frantoio and Dolce Agogia), included approximately 465,000 ESTs, which gave rise to more than 14,600 contigs and approximately 92,000 singletons. As many as 56,700 unigenes were successfully annotated and provided gene ontology insights into the structural organization and putative molecular function of sequenced transcripts and deduced proteins in the context of their corresponding biological processes. Differentially expressed genes with potential regulatory roles in biosynthetic pathways and metabolic networks during flower development were identified. The gene expression studies allowed us to select the candidate genes that play well-known molecular functions in a number of biosynthetic pathways and specific biological processes that affect olive reproduction. A sound understanding of gene functions and regulatory networks that characterize the olive flower is provided. PMID:27077738

Application of Physiologically Based Absorption Modeling to Characterize the Pharmacokinetic Profiles of Oral Extended Release Methylphenidate Products in Adults

PubMed Central

Yang, Xiaoxia; Duan, John; Fisher, Jeffrey

2016-01-01

A previously presented physiologically-based pharmacokinetic model for immediate release (IR) methylphenidate (MPH) was extended to characterize the pharmacokinetic behaviors of oral extended release (ER) MPH formulations in adults for the first time. Information on the anatomy and physiology of the gastrointestinal (GI) tract, together with the biopharmaceutical properties of MPH, was integrated into the original model, with model parameters representing hepatic metabolism and intestinal non-specific loss recalibrated against in vitro and in vivo kinetic data sets with IR MPH. A Weibull function was implemented to describe the dissolution of different ER formulations. A variety of mathematical functions can be utilized to account for the engineered release/dissolution technologies to achieve better model performance. The physiological absorption model tracked well the plasma concentration profiles in adults receiving a multilayer-release MPH formulation or Metadate CD, while some degree of discrepancy was observed between predicted and observed plasma concentration profiles for Ritalin LA and Medikinet Retard. A local sensitivity analysis demonstrated that model parameters associated with the GI tract significantly influenced model predicted plasma MPH concentrations, albeit to varying degrees, suggesting the importance of better understanding the GI tract physiology, along with the intestinal non-specific loss of MPH. The model provides a quantitative tool to predict the biphasic plasma time course data for ER MPH, helping elucidate factors responsible for the diverse plasma MPH concentration profiles following oral dosing of different ER formulations. PMID:27723791

Development of a computational model of glucose toxicity in the progression of diabetes mellitus.

PubMed

Perez-Rivera, Danilo T; Torres-Torres, Veronica L; Torres-Colon, Abraham E; Cruz-Aponte, Maytee

2016-10-01

Diabetes mellitus is a disease characterized by a range of metabolic complications involving an individual's blood glucose levels, and its main regulator, insulin. These complications can vary largely from person to person depending on their current biophysical state. Biomedical research day-by-day makes strides to impact the lives of patients of a variety of diseases, including diabetes. One large stride that is being made is the generation of techniques to assist physicians to ``personalize medicine''. From available physiological data, biological understanding of the system, and dimensional analysis, a differential equation-based mathematical model was built in a sequential matter, to be able to elucidate clearly how each parameter correlates to the patient's current physiological state. We developed a simple mathematical model that accurately simulates the dynamics between glucose, insulin, and pancreatic $\\beta$-cells throughout disease progression with constraints to maintain biological relevance. The current framework is clearly capable of tracking the patient's current progress through the disease, dependent on factors such as latent insulin resistance or an attrite $\\beta$-cell population. Further interests would be to develop tools that allow the direct and feasible testing of how effective a given plan of treatment would be at returning the patient to a desirable biophysical state.

Abstracts of Review Articles and Educational Materials in Physiology

ERIC Educational Resources Information Center

Physiology Teacher, 1977

1977-01-01

Contained are 99 abstracts of review articles, texts, books, manuals, learning programs, and audiovisual material used in teaching physiology. Specific fields include cell physiology, circulation, comparative physiology, development and aging, endocrinology and metabolism, environmental and exercise physiology, gastrointestinal physiology, muscle…

Delayed response to cold stress is characterized by successive metabolic shifts culminating in apple fruit peel necrosis

USDA-ARS?s Scientific Manuscript database

Superficial scald is a physiological disorder of apple fruit characterized by sunken, necrotic lesions appearing after prolonged cold storage, although initial injury occurs much earlier in the storage period. To determine the degree to which the transition to cell death is an active process and sp...

A strain of Serratia marcescens pathogenic for larvae of Lymantria dispar: Characterization

Treesearch

J.D. Podgwaite; B.J. Cosenza

1976-01-01

A gram-negative bacillus, pathogenic for gypsy moth larvae, was characterized culturally, morphologically, and physiologically as a member of the Serratia group of the family Enterobacteriaceae. The microorganism lacked the pigmentation characteristic of the group but was generally distinguished from closely related members of the family by its...

Sickle cell anemia mice develop a unique cardiomyopathy with restrictive physiology

PubMed Central

Bakeer, Nihal; James, Jeanne; Roy, Swarnava; Wansapura, Janaka; Shanmukhappa, Shiva Kumar; Lorenz, John N.; Osinska, Hanna; Backer, Kurt; Huby, Anne-Cecile; Shrestha, Archana; Niss, Omar; Fleck, Robert; Quinn, Charles T.; Taylor, Michael D.; Purevjav, Enkhsaikhan; Aronow, Bruce J.; Towbin, Jeffrey A.; Malik, Punam

2016-01-01

Cardiopulmonary complications are the leading cause of mortality in sickle cell anemia (SCA). Elevated tricuspid regurgitant jet velocity, pulmonary hypertension, diastolic, and autonomic dysfunction have all been described, but a unifying pathophysiology and mechanism explaining the poor prognosis and propensity to sudden death has been elusive. Herein, SCA mice underwent a longitudinal comprehensive cardiac analysis, combining state-of-the-art cardiac imaging with electrocardiography, histopathology, and molecular analysis to determine the basis of cardiac dysfunction. We show that in SCA mice, anemia-induced hyperdynamic physiology was gradually superimposed with restrictive physiology, characterized by progressive left atrial enlargement and diastolic dysfunction with preserved systolic function. This phenomenon was absent in WT mice with experimentally induced chronic anemia of similar degree and duration. Restrictive physiology was associated with microscopic cardiomyocyte loss and secondary fibrosis detectable as increased extracellular volume by cardiac-MRI. Ultrastructural mitochondrial changes were consistent with severe chronic hypoxia/ischemia and sarcomere diastolic-length was shortened. Transcriptome analysis revealed up-regulation of genes involving angiogenesis, extracellular-matrix, circadian-rhythm, oxidative stress, and hypoxia, whereas ion-channel transport and cardiac conduction were down-regulated. Indeed, progressive corrected QT prolongation, arrhythmias, and ischemic changes were noted in SCA mice before sudden death. Sudden cardiac death is common in humans with restrictive cardiomyopathies and long QT syndromes. Our findings may thus provide a unifying cardiac pathophysiology that explains the reported cardiac abnormalities and sudden death seen in humans with SCA. PMID:27503873

The Impact of Protein Phosphorylation on Chlamydial Physiology

PubMed Central

Claywell, Ja E.; Matschke, Lea M.; Fisher, Derek J.

2016-01-01

Chlamydia are Gram negative bacterial pathogens responsible for disease in humans and economically important domesticated animals. As obligate intracellular bacteria, they must gain entry into a host cell where they propagate within a parasitophorous organelle that serves as an interactive interface between the bacterium and the host. Nutrient acquisition, growth, and evasion of host defense mechanisms occur from this location. In addition to these cellular and bacterial dynamics, Chlamydia differentiate between two morphologically distinct forms, the elementary body and reticulate body, that are optimized for either extracellular or intracellular survival, respectively. The mechanisms regulating and mediating these diverse physiological events remain largely unknown. Reversible phosphorylation, including classical two-component signaling systems, partner switching mechanisms, and the more recently appreciated bacterial Ser/Thr/Tyr kinases and phosphatases, has gained increasing attention for its role in regulating important physiological processes in bacteria including metabolism, development, and virulence. Phosphorylation modulates these events via rapid and reversible modification of protein substrates leading to changes in enzyme activity, protein oligomerization, cell signaling, and protein localization. The characterization of several conserved chlamydial protein kinases and phosphatases along with phosphoproteome analysis suggest that Chlamydia are capable of global and growth stage-specific protein phosphorylation. This mini review will highlight the current knowledge of protein phosphorylation in Chlamydia and its potential role in chlamydial physiology and, consequently, virulence. Comparisons with other minimal genome intracellular bacterial pathogens also will be addressed with the aim of illustrating the importance of this understudied regulatory mechanism on pathogenesis and the principle questions that remain unanswered. PMID:28066729

Hypertension and obstructive sleep apnea

PubMed Central

Phillips, Craig L; O’Driscoll, Denise M

2013-01-01

Obstructive sleep apnea (OSA) is increasingly being recognized as a major health burden with strong focus on the associated cardiovascular risk. Studies from the last two decades have provided strong evidence for a causal role of OSA in the development of systemic hypertension. The acute physiological changes that occur during apnea promote nocturnal hypertension and may lead to the development of sustained daytime hypertension via the pathways of sympathetic activation, inflammation, oxidative stress, and endothelial dysfunction. This review will focus on the acute hemodynamic disturbances and associated intermittent hypoxia that characterize OSA and the potential pathophysiological mechanisms responsible for the development of hypertension in OSA. In addition the epidemiology of OSA and hypertension, as well as the role of treatment of OSA, in improving blood pressure control will be examined. PMID:23750107

eUnaG: a new ligand-inducible fluorescent reporter to detect drug transporter activity in live cells

PubMed Central

Yeh, Johannes T.-H.; Nam, Kwangho; Yeh, Joshua T.-H.; Perrimon, Norbert

2017-01-01

The absorption, distribution, metabolism and excretion (ADME) of metabolites and toxic organic solutes are orchestrated by the ATP-binding cassette (ABC) transporters and the organic solute carrier family (SLC) proteins. A large number of ABC and SLC transpoters exist; however, only a small number have been well characterized. To facilitate the analysis of these transporters, which is important for drug safety and physiological studies, we developed a sensitive genetically encoded bilirubin (BR)-inducible fluorescence sensor (eUnaG) to detect transporter-coupled influx/efflux of organic compounds. This sensor can be used in live cells to measure transporter activity, as excretion of BR depends on ABC and SLC transporters. Applying eUnaG in functional RNAi screens, we characterize l(2)03659 as a Drosophila multidrug resistant-associated ABC transporter. PMID:28176814

A physiome interoperability roadmap for personalized drug development

PubMed Central

2016-01-01

The goal of developing therapies and dosage regimes for characterized subgroups of the general population can be facilitated by the use of simulation models able to incorporate information about inter-individual variability in drug disposition (pharmacokinetics), toxicity and response effect (pharmacodynamics). Such observed variability can have multiple causes at various scales, ranging from gross anatomical differences to differences in genome sequence. Relevant data for many of these aspects, particularly related to molecular assays (known as ‘-omics’), are available in online resources, but identification and assignment to appropriate model variables and parameters is a significant bottleneck in the model development process. Through its efforts to standardize annotation with consequent increase in data usability, the human physiome project has a vital role in improving productivity in model development and, thus, the development of personalized therapy regimes. Here, we review the current status of personalized medicine in clinical practice, outline some of the challenges that must be overcome in order to expand its applicability, and discuss the relevance of personalized medicine to the more widespread challenges being faced in drug discovery and development. We then review some of (i) the key data resources available for use in model development and (ii) the potential areas where advances made within the physiome modelling community could contribute to physiologically based pharmacokinetic and physiologically based pharmacokinetic/pharmacodynamic modelling in support of personalized drug development. We conclude by proposing a roadmap to further guide the physiome community in its on-going efforts to improve data usability, and integration with modelling efforts in the support of personalized medicine development. PMID:27051513

Mycochemical Characterization of Agaricus subrufescens considering Their Morphological and Physiological Stage of Maturity on the Traceability Process

PubMed Central

Pardo, Jose E; Tomaz, Rafael Simões; Miasaki, Celso Tadao; Pardo-Giménez, Arturo

2017-01-01

Agaricus subrufescens Peck is a basidiomycete with immunomodulatory compounds and antitumor activities. This research evaluated the mycochemical composition of A. subrufescens, considering their morphological and physiological stage of maturity, with a particular focus on the development of a traceability process for the formulation of new nutritional products based on fungal foods. The stipes contained a high amount of dry matter (10.33%), total carbohydrate (69.56%), available carbohydrate (63.89%), and energy value (363.97 kcal 100 g−1 DM). The pilei contained a high amount of moisture (90.66%), nitrogen (7.75%), protein (33.96%), ash (8.24), crude fat (2.44%), acid detergent fiber (16.75 g kg−1), neutral detergent fiber (41.82 g kg−1), hemicellulose (25.07 g kg−1), and lignin (9.77 g kg−1). Stipes with mature physiological stage had higher values of dry matter (10.50%), crude fiber (5.94%), total carbohydrate (72.82%), AC (66.88%), and energy value (364.91 kcal 100 g−1 DM). Pilei of the mushrooms in the immature physiological stage had higher values of P (36.83%), N (8.41%), and A (8.44%). Due to the differences between the mycochemical compositions of the morphological parts of mushrooms linked to their physiological stage of maturity, such characteristics have immense potential to be considered for a traceability process. This study can be used for the purpose of providing the consumer with more product diversity, optimizing bioactivities of composts, and allowing farmers an efficient and profitable use of the mushroom biomass. PMID:29082241

Space Physiology within an Exercise Physiology Curriculum

ERIC Educational Resources Information Center

Carter, Jason R.; West, John B.

2013-01-01

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

Cardiovascular Deconditioning in Humans: Alteration in Cardiovascular Regulation and Function During Simulated Microgravity

NASA Technical Reports Server (NTRS)

Cohen, Richard

1999-01-01

Alterations in cardiovascular regulation and function that occur during and after space flight have been reported. These alterations are manifested, for example, by reduced orthostatic tolerance upon reentry to the earth's gravity from space. However, the precise physiologic mechanisms responsible for these alterations remain to be fully elucidated. Perhaps, as a result, effective countermeasures have yet to be developed. In this project we apply a powerful, new method - cardiovascular system identification (CSI) - for the study of the effects of space flight on the cardiovascular system so that effective countermeasures can be developed. CSI involves the mathematical analysis of second-to-second fluctuations in non-invasively measured heart rate, arterial blood pressure (ABP), and instantaneous lung volume (ILV - respiratory activity) in order to characterize quantitatively the physiologic mechanisms responsible for the couplings between these signals. Through the characterization of all the physiologic mechanisms coupling these signals, CSI provides a model of the closed-loop cardiovascular regulatory state in an individual subject. The model includes quantitative descriptions of the heart rate baroreflex, autonomic function, as well as other important physiologic mechanisms. We are in the process of incorporating beat-to-beat fluctuations of stroke volume into the CSI technique in order to quantify additional physiologic mechanisms such as those involved in control of peripheral vascular resistance and alterations in cardiac contractility. We apply CSI in conjunction with the two general protocols of the Human Studies Core project. The first protocol involves ground-based, human head down tilt bed rest to simulate microgravity and acute stressors - upright tilt, standing and bicycle exercise - to provide orthostatic and exercise challenges. The second protocol is intended to be the same as the first but with the addition of sleep deprivation to determine whether this contributes to cardiovascular alterations. In these studies, we focus on the basic physiologic mechanisms responsible for the alterations in cardiovascular regulation and function during the simulated microgravity in order to formulate hypotheses regarding what countermeasures are likely to be most effective. Compared to our original proposal, the protocol we are using has been slightly modified to lengthen the bed rest period to 16 days and streamline the data collection. These modifications provide us data on a longer bed rest period and have enabled us to increase our subject throughput. Based on review of our preliminary data we have decided to test a countermeasure which is applied the very end of the bed rest period. We will use the same bed rest protocol to test this countermeasure. We anticipate completing the baseline data collection in our first protocol plus testing of the countermeasure in an additional eight subjects, at which time we plan to initiate the second protocol which includes sleep deprivation. In future studies, we plan to apply CSI to test other potential countermeasures in conjunction with the same bed rest, sleep deprivation and acute stressor models. We also anticipate applying CSI for studying astronauts before and after space flight and ultimately, during space flight. The application of CSI is providing information relevant to the development and evaluation of effective countermeasures allowing humans to adapt appropriately upon re-exposure to a gravity field, and to live and work for longer periods of time in microgravity.

Insights into the Evolution of Host Association through the Isolation and Characterization of a Novel Human Periodontal Pathobiont, Desulfobulbus oralis

DOE PAGES

Cross, Karissa L.; Chirania, Payal; Xiong, Weili; ...

2018-03-13

The human oral microbiota encompasses representatives of many bacterial lineages that have not yet been cultured. Here we describe the isolation and characterization of previously unculturedDesulfobulbus oralis , the first human-associated representative of its genus. As mammalian-associated microbes rarely have free-living close relatives,D. oralis provides opportunities to study how bacteria adapt and evolve within a host. This sulfate-reducing deltaproteobacterium has adapted to the human oral subgingival niche by curtailing its physiological repertoire, losing some biosynthetic abilities and metabolic independence, and by dramatically reducing environmental sensing and signaling capabilities. The genes that enable free-living Desulfobulbus to synthesize the potent neurotoxin methylmercury weremore » also lost byD. oralis, a notably positive outcome of host association. However, horizontal gene acquisitions from other members of the microbiota provided novel mechanisms of interaction with the human host, including toxins like leukotoxin and hemolysins. Proteomic and transcriptomic analysis revealed that most of those factors are actively expressed, including in the subgingival environment, and some are secreted. Similar to other known oral pathobionts, D. oralis can trigger a proinflammatory response in oral epithelial cells, suggesting a direct role in the development of periodontal disease. Animal-associated microbiota likely assembled as a result of numerous independent colonization events by free-living microbes followed by coevolution with their host and other microbes. Through specific adaptation to various body sites and physiological niches, microbes have a wide range of contributions, from beneficial to disease causing.Desulfobulbus oralis provides insights into genomic and physiological transformations associated with transition from an open environment to a host-dependent lifestyle and the emergence of pathogenicity. Through a multifaceted mechanism triggering a proinflammatory response, D. oralis is a novel periodontal pathobiont. Even though culture-independent approaches can provide insights into the potential role of the human microbiome “dark matter,” cultivation and experimental characterization remain important to studying the roles of individual organisms in health and disease.« less

Insights into the Evolution of Host Association through the Isolation and Characterization of a Novel Human Periodontal Pathobiont, Desulfobulbus oralis

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

Cross, Karissa L.; Chirania, Payal; Xiong, Weili

The human oral microbiota encompasses representatives of many bacterial lineages that have not yet been cultured. Here we describe the isolation and characterization of previously unculturedDesulfobulbus oralis , the first human-associated representative of its genus. As mammalian-associated microbes rarely have free-living close relatives,D. oralis provides opportunities to study how bacteria adapt and evolve within a host. This sulfate-reducing deltaproteobacterium has adapted to the human oral subgingival niche by curtailing its physiological repertoire, losing some biosynthetic abilities and metabolic independence, and by dramatically reducing environmental sensing and signaling capabilities. The genes that enable free-living Desulfobulbus to synthesize the potent neurotoxin methylmercury weremore » also lost byD. oralis, a notably positive outcome of host association. However, horizontal gene acquisitions from other members of the microbiota provided novel mechanisms of interaction with the human host, including toxins like leukotoxin and hemolysins. Proteomic and transcriptomic analysis revealed that most of those factors are actively expressed, including in the subgingival environment, and some are secreted. Similar to other known oral pathobionts, D. oralis can trigger a proinflammatory response in oral epithelial cells, suggesting a direct role in the development of periodontal disease. Animal-associated microbiota likely assembled as a result of numerous independent colonization events by free-living microbes followed by coevolution with their host and other microbes. Through specific adaptation to various body sites and physiological niches, microbes have a wide range of contributions, from beneficial to disease causing.Desulfobulbus oralis provides insights into genomic and physiological transformations associated with transition from an open environment to a host-dependent lifestyle and the emergence of pathogenicity. Through a multifaceted mechanism triggering a proinflammatory response, D. oralis is a novel periodontal pathobiont. Even though culture-independent approaches can provide insights into the potential role of the human microbiome “dark matter,” cultivation and experimental characterization remain important to studying the roles of individual organisms in health and disease.« less

Inflammation-sensitive in situ smart scaffolding for regenerative medicine.

PubMed

Patra, Hirak K; Sharma, Yashpal; Islam, Mohammad Mirazul; Jafari, Mohammad Javad; Murugan, N Arul; Kobayashi, Hisatoshi; Turner, Anthony P F; Tiwari, Ashutosh

2016-10-06

To cope with the rapid evolution of the tissue engineering field, it is now essential to incorporate the use of on-site responsive scaffolds. Therefore, it is of utmost importance to find new 'Intelligent' biomaterials that can respond to the physicochemical changes in the microenvironment. In this present report, we have developed biocompatible stimuli responsive polyaniline-multiwalled carbon nanotube/poly(N-isopropylacrylamide), (PANI-MWCNT/PNIPAm) composite nanofiber networks and demonstrated the physiological temperature coordinated cell grafting phenomenon on its surface. The composite nanofibers were prepared by a two-step process initiated with an assisted in situ polymerization followed by electrospinning. To obtain a smooth surface in individual nanofibers with the thinnest diameter, the component ratios and electrospinning conditions were optimized. The temperature-gated rearrangements of the molecular structure are characterized by FTIR spectroscopy with simultaneous macromolecular architecture changes reflected on the surface morphology, average diameter and pore size as determined by scanning electron microscopy. The stimuli responsiveness of the nanofibers has first been optimized with computational modeling of temperature sensitive components (coil-like and globular conformations) to tune the mechanism for temperature dependent interaction during in situ scaffolding with the cell membrane. The nanofiber networks show excellent biocompatibility, tested with fibroblasts and also show excellent sensitivity to inflammation to combat loco-regional acidosis that delay the wound healing process by an in vitro model that has been developed for testing the proposed responsiveness of the composite nanofiber networks. Cellular adhesion and detachment are regulated through physiological temperature and show normal proliferation of the grafted cells on the composite nanofibers. Thus, we report for the first time, the development of physiological temperature gated inflammation-sensitive smart biomaterials for advanced tissue regeneration and regenerative medicine.

Improving and accelerating the differentiation and functional maturation of human stem cell-derived neurons: role of extracellular calcium and GABA.

PubMed

Kemp, Paul J; Rushton, David J; Yarova, Polina L; Schnell, Christian; Geater, Charlene; Hancock, Jane M; Wieland, Annalena; Hughes, Alis; Badder, Luned; Cope, Emma; Riccardi, Daniela; Randall, Andrew D; Brown, Jonathan T; Allen, Nicholas D; Telezhkin, Vsevolod

2016-11-15

Neurons differentiated from pluripotent stem cells using established neural culture conditions often exhibit functional deficits. Recently, we have developed enhanced media which both synchronize the neurogenesis of pluripotent stem cell-derived neural progenitors and accelerate their functional maturation; together these media are termed SynaptoJuice. This pair of media are pro-synaptogenic and generate authentic, mature synaptic networks of connected forebrain neurons from a variety of induced pluripotent and embryonic stem cell lines. Such enhanced rate and extent of synchronized maturation of pluripotent stem cell-derived neural progenitor cells generates neurons which are characterized by a relatively hyperpolarized resting membrane potential, higher spontaneous and induced action potential activity, enhanced synaptic activity, more complete development of a mature inhibitory GABA A receptor phenotype and faster production of electrical network activity when compared to standard differentiation media. This entire process - from pre-patterned neural progenitor to active neuron - takes 3 weeks or less, making it an ideal platform for drug discovery and disease modelling in the fields of human neurodegenerative and neuropsychiatric disorders, such as Huntington's disease, Parkinson's disease, Alzheimer's disease and Schizophrenia. © 2016 The Authors. The Journal of Physiology © 2016 The Physiological Society.

Zebrafish Models of Prader-Willi Syndrome: Fast Track to Pharmacotherapeutics

PubMed Central

Spikol, Emma D.; Laverriere, Caroline E.; Robnett, Maya; Carter, Gabriela; Wolfe, Erin; Glasgow, Eric

2016-01-01

Prader-Willi syndrome (PWS) is a rare genetic neurodevelopmental disorder characterized by an insatiable appetite, leading to chronic overeating and obesity. Additional features include short stature, intellectual disability, behavioral problems and incomplete sexual development. Although significant progress has been made in understanding the genetic basis of PWS, the mechanisms underlying the pathogenesis of the disorder remain poorly understood. Treatment for PWS consists mainly of palliative therapies; curative therapies are sorely needed. Zebrafish, Danio rerio, represent a promising way forward for elucidating physiological problems such as obesity and identifying new pharmacotherapeutic options for PWS. Over the last decade, an increased appreciation for the highly conserved biology among vertebrates and the ability to perform high-throughput drug screening has seen an explosion in the use of zebrafish for disease modeling and drug discovery. Here, we review recent advances in developing zebrafish models of human disease. Aspects of zebrafish genetics and physiology that are relevant to PWS will be discussed, and the advantages and disadvantages of zebrafish models will be contrasted with current animal models for this syndrome. Finally, we will present a paradigm for drug screening in zebrafish that is potentially the fastest route for identifying and delivering curative pharmacotherapies to PWS patients. PMID:27857842

MELiSSA Food Characterization general approach and current status

NASA Astrophysics Data System (ADS)

Weihreter, Martin; Chaerle, Laury; Secco, Benjamin; Molders, Katrien; van der Straeten, Dominique; Duliere, Eric; Pieters, Serge; Maclean, Heather; Dochain, Denis; Quinet, Muriel; Lutts, Stanley; Graham, Thomas; Stasiak, Michael; Rondeau Vuk, Theresa; Zheng, Youbin; Dixon, Mike; Laniau, Martine; Larreture, Alain; Timsit, Michel; Aronne, Giovanna; Barbieri, Giancarlo; Buonomo, Roberta; Veronica; Paradiso, Roberta; de Pascale, Stafania; Galbiati, Massimo; Troia, A. R.; Nobili, Matteo; Bucchieri, Lorenzo; Page, Valérie; Feller, Urs; Lasseur, Christophe

Higher plants play an important role in closed ecological life support systems as oxygen pro-ducers, carbon dioxide and water recyclers, and as a food source. For an integration of higher plant chambers into the MELiSSA (Micro Ecological Life Support System Alternative) loop, a detailed characterization and optimization of the full food production and preparation chain is needed. This implies the prediction and control of the nutritional quality of the final products consumed by the crew, the prediction of the wastes quality and quantity produced along the chain for further waste treatment (MELiSSA waste treatment) and the optimization of overall efficiencies. To reach this goal several issues have to be studied in an integrated manner: the physiological responses of crops to a range of environmental parameters, crop yield efficiencies and respective ratio and composition of edible and inedible biomass, the processability and storability of the produced food and last but not least composition of wastes in view of further degradation (fiber content). Within the Food Characterization (FC) project several compar-ative plant growth bench tests were carried out to obtain preliminary data regarding these aspects. Four pre-selected cultivars of each of the four energy-rich crops with worldwide usage -wheat, durum wheat, potato and soybean -were grown under well-characterized environmental conditions. The different cultivars of each species are screened for their performance in view of a closed loop application by parameter ranking. This comprises the characterization of edi-ble/inedible biomass ratio, nutritional quality, processability and overall performance under the specific conditions of hydroponic cultivation and artificial illumination. A second closely linked goal of the FC project is to develop a mechanistic physiological plant model, which will ease the integration of higher plants compartments in the MELiSSA concept by virtue of its predictive abilities. Available MELiSSA closed environment crop growth data were used to develop a first photosynthetic model representing the basic carbon fixation mechanisms. This model will be further elaborated in the course of this study to predict yield, oxygen production and transpi-ration. As an ultimate goal the model is intended to simulate the composition of the different plant organs (root, shoot, fruit/seed or tuber) for each crop under various conditions. For the validation of this model an extensive amount of data sets are needed. Current plant growth bench test setups will provide part of the required data. To gain more precise and detailed datasets, a highly closed plant growth chamber (Plant Characterization Unit, PCU) is under development. The PCU will provide accurate mass balances for carbon, water, oxygen and other elements with statistical reliability. This reliability is achieved through a high degree of closure and environment homogeneity. The PCU will also provide data for the above described plant characterization studies. The general work approach, the current status and future steps will be illustrated.

Flow Cytometry of Extracellular Vesicles: Potential, Pitfalls, and Prospects.

PubMed

Nolan, John P

2015-07-01

Evidence suggests that extracellular vesicles (EVs) can play roles in physiology and pathology, providing impetus to explore their use as diagnostic and therapeutic targets. However, EVs are also small, heterogeneous, and difficult to measure, and so this potential has not yet been realized. The development of improved approaches to EV detection and characterization will be critical to further understanding their roles in physiology and disease. Flow cytometry has been a popular tool for measuring cell-derived EVs, but has often been used in an uncritical manner in which fundamental principles and limitations of the instrument are ignored. Recent efforts to standardize procedures and document the effects of different methodologies have helped to address this shortcoming, but much work remains. In this paper, I address some of the instrument, reagent, and analysis considerations relevant to measurement of individual EVs in flow, with the aim of clarifying a path to quantitative and standardized measurement of these interesting and potentially important biological nanoparticles. Copyright © 2015 John Wiley & Sons, Inc.

Cell-specific STORM superresolution imaging reveals nanoscale organization of cannabinoid signaling

PubMed Central

Szabó, Szilárd I.; Szabadits, Eszter; Pintér, Balázs; Woodhams, Stephen G.; Henstridge, Christopher M.; Balla, Gyula Y.; Nyilas, Rita; Varga, Csaba; Lee, Sang-Hun; Matolcsi, Máté; Cervenak, Judit; Kacskovics, Imre; Watanabe, Masahiko; Sagheddu, Claudia; Melis, Miriam; Pistis, Marco; Soltesz, Ivan; Katona, István

2014-01-01

A major challenge in neuroscience is to determine the nanoscale position and quantity of signaling molecules in a cell-type-, and subcellular compartment-specific manner. We therefore developed a novel approach combining cell-specific physiological and anatomical characterization with superresolution imaging, and studied the molecular and structural parameters shaping the physiological properties of synaptic endocannabinoid signaling in the mouse hippocampus. We found that axon terminals of perisomatically-projecting GABAergic interneurons possess increased CB1 receptor number, active-zone complexity, and receptor/effector ratio compared to dendritically-projecting interneurons, in agreement with higher efficiency of cannabinoid signaling at somatic versus dendritic synapses. Furthermore, chronic Δ9-tetrahydrocannabinol administration, which reduces cannabinoid efficacy on GABA release, evoked dramatic CB1-downregulation in a dose-dependent manner. Full receptor recovery required several weeks after cessation of Δ9-tetrahydrocannabinol treatment. These findings demonstrate that cell-type-specific nanoscale analysis of endogenous protein distribution is possible in brain circuits, and identify novel molecular properties controlling endocannabinoid signaling and cannabis-induced cognitive dysfunction. PMID:25485758

Beyond triglyceride synthesis: the dynamic functional roles of MGAT and DGAT enzymes in energy metabolism

PubMed Central

Shi, Yuguang; Cheng, Dong

2009-01-01

Monoacyglycerol acyltransferases (MGATs) and diacylglycerol acyltransferases (DGATs) catalyze two consecutive steps of enzyme reactions in the synthesis of triacylglycerols (TAGs). The metabolic complexity of TAG synthesis is reflected by the presence of multiple isoforms of MGAT and DGAT enzymes that differ in catalytic properties, subcellular localization, tissue distribution, and physiological functions. MGAT and DGAT enzymes play fundamental roles in the metabolism of monoacylglycerol (MAG), diacylglycerol (DAG), and triacylglycerol (TAG) that are involved in many aspects of physiological functions, such as intestinal fat absorption, lipoprotein assembly, adipose tissue formation, signal transduction, satiety, and lactation. The recent progress in the phenotypic characterization of mice deficient in MGAT and DGAT enzymes and the development of chemical inhibitors have revealed important roles of these enzymes in the regulation of energy homeostasis and insulin sensitivity. Consequently, selective inhibition of MGAT or DGAT enzymes by synthetic compounds may provide novel treatment for obesity and its related metabolic complications. PMID:19116371

Systems identification and application systems development for monitoring the physiological and health status of crewmen in space

NASA Technical Reports Server (NTRS)

Leonard, J. I.; Furukawa, S.; Vannordstrand, P. C.

1975-01-01

The use of automated, analytical techniques to aid medical support teams is suggested. Recommendations are presented for characterizing crew health in terms of: (1) wholebody function including physiological, psychological and performance factors; (2) a combination of critical performance indexes which consist of multiple factors of measurable parameters; (3) specific responses to low noise level stress tests; and (4) probabilities of future performance based on present and periodic examination of past performance. A concept is proposed for a computerized real time biomedical monitoring and health care system that would have the capability to integrate monitored data, detect off-nominal conditions based on current knowledge of spaceflight responses, predict future health status, and assist in diagnosis and alternative therapies. Mathematical models could play an important role in this approach, especially when operating in a real time mode. Recommendations are presented to update the present health monitoring systems in terms of recent advances in computer technology and biomedical monitoring systems.

Cracking the ANP32 whips: Important functions, unequal requirement, and hints at disease implications

PubMed Central

Reilly, Patrick T; Yu, Yun; Hamiche, Ali; Wang, Lishun

2014-01-01

The acidic (leucine-rich) nuclear phosphoprotein 32 kDa (ANP32) family is composed of small, evolutionarily conserved proteins characterized by an N-terminal leucine-rich repeat domain and a C-terminal low-complexity acidic region. The mammalian family members (ANP32A, ANP32B, and ANP32E) are ascribed physiologically diverse functions including chromatin modification and remodelling, apoptotic caspase modulation, protein phosphatase inhibition, as well as regulation of intracellular transport. In addition to reviewing the widespread literature on the topic, we present a concept of the ANP32s as having a whip-like structure. We also present hypotheses that ANP32C and other intronless sequences should not currently be considered bona fide family members, that their disparate necessity in development may be due to compensatory mechanisms, that their contrasting roles in cancer are likely context-dependent, along with an underlying hypothesis that ANP32s represent an important node of physiological regulation by virtue of their diverse biochemical activities. PMID:25156960

Metaphors of mind and society. The origins of German psychiatry in the revolutionary era.

PubMed

Hansen, L

1998-09-01

Johann Christian Reil's long polemic, Rhapsodieen über die Anwendung der psychischen Curmethode der Geisteszerrütungen (1803), is a call for the reform of the treatment of the insane. It also marks a transition from the Kantian approach to physiology of his earlier work to the Naturphilosophie that increasingly characterized his publications after this time. In this essay I first survey the historiographical debates of recent years concerning society and the emergence of psychiatry. I then examine the social-cultural context of the late Aufklärung in Prussia, out of which Reil's work emerged, before sketching the intellectual background of the Rhapsodieen, which lies in the development of German physiology since the 1750s. The heart of my work is a close analysis of Reil's theory of mental illness. Here I tease out his political and cultural imagery and note the ways in which his originally Enlightenment assumptions shifted toward the Romantic amid the anxieties of the revolutionary era.

[Ineffective sexuality pattern in an adolescent: nursing approach in primary health care].

PubMed

Martín-García, Angel; Oter-Quintana, Cristina; Brito-Brito, Pedro Ruymán; Martín-Iglesias, Susana; Alcolea-Cosín, M Teresa

2013-01-01

Adolescent is a phase of continual physiological, psychological and social adaptation. It is during this time that young people tend to have their first sexual experiences. Sexual dysfunctions are characterized by important clinical changes in sexual desire and/or by psycho-physiological changes in the sexual response cycle. Premature ejaculation is one of the most frequent sexual dysfunction amongst men, with a higher prevalence in the younger population compared to other populations. The clinical case is presented of a 17 year-old male who experienced difficulties during his sexual relations. It is discussed whether his condition was a sexual dysfunction or ineffective sexual pattern. The care plan which was developed in nursing consultation was described for ineffective sexual pattern; the pending nursing treatment incorporated activities recommended by scientific evidence. Finally, the role of primary health care nursing professionals is pointed out in the detection and approach of sexual problems in adolescents. Copyright © 2013 Elsevier España, S.L. All rights reserved.

Downregulation of vitellogenin gene activity increases the gustatory responsiveness of honey bee workers (Apis mellifera)

PubMed Central

Amdam, Gro V.; Norberg, Kari; Page, Robert E.; Erber, Joachim; Scheiner, Ricarda

2008-01-01

In the honey bee (Apis mellifera), young workers usually perform tasks in the nest while older workers forage in the field. The behavioral shift from nest-task to foraging activity is accompanied by physiological and sensory changes so that foragers can be characterized by a higher juvenile hormone (JH) level, a lower vitellogenin protein titer, and an increased responsiveness to water and sucrose stimuli. JH was hypothesized to be the key mediator of behavioral development, physiology, and sensory sensitivity in honey bee workers. Recent research, however, has shown that JH is controlled by the hemolymph vitellogenin level, which implies that the fat body specific vitellogenin gene can be a key regulator of behavioral change. Here, we show that downregulation of vitellogenin activity by RNA interference (RNAi) causes an increase in the gustatory responsiveness of worker bees. Our observations suggest that vitellogenin is an important regulator of long-term changes in honey bee behavior. PMID:16466813

BXR, an embryonic orphan nuclear receptor activated by a novel class of endogenous benzoate metabolites

PubMed Central

Blumberg, Bruce; Kang, Heonjoong; Bolado, Jack; Chen, Hongwu; Craig, A. Grey; Moreno, Tanya A.; Umesono, Kazuhiko; Perlmann, Thomas; De Robertis, Eddy M.; Evans, Ronald M.

1998-01-01

Nuclear receptors are ligand-modulated transcription factors that respond to steroids, retinoids, and thyroid hormones to control development and body physiology. Orphan nuclear receptors, which lack identified ligands, provide a unique, and largely untapped, resource to discover new principles of physiologic homeostasis. We describe the isolation and characterization of the vertebrate orphan receptor, BXR, which heterodimerizes with RXR and binds high-affinity DNA sites composed of a variant thyroid hormone response element. A bioactivity-guided screen of embryonic extracts revealed that BXR is activatable by low-molecular-weight molecules with spectral patterns distinct from known nuclear receptor ligands. Mass spectrometry and 1H NMR analysis identified alkyl esters of amino and hydroxy benzoic acids as potent, stereoselective activators. In vitro cofactor association studies, along with competable binding of radiolabeled compounds, establish these molecules as bona fide ligands. Benzoates comprise a new molecular class of nuclear receptor ligand and their activity suggests that BXR may control a previously unsuspected vertebrate signaling pathway. PMID:9573044

Bayesian parameter estimation for stochastic models of biological cell migration

NASA Astrophysics Data System (ADS)

Dieterich, Peter; Preuss, Roland

2013-08-01

Cell migration plays an essential role under many physiological and patho-physiological conditions. It is of major importance during embryonic development and wound healing. In contrast, it also generates negative effects during inflammation processes, the transmigration of tumors or the formation of metastases. Thus, a reliable quantification and characterization of cell paths could give insight into the dynamics of these processes. Typically stochastic models are applied where parameters are extracted by fitting models to the so-called mean square displacement of the observed cell group. We show that this approach has several disadvantages and problems. Therefore, we propose a simple procedure directly relying on the positions of the cell's trajectory and the covariance matrix of the positions. It is shown that the covariance is identical with the spatial aging correlation function for the supposed linear Gaussian models of Brownian motion with drift and fractional Brownian motion. The technique is applied and illustrated with simulated data showing a reliable parameter estimation from single cell paths.

Mycobacterial lipolytic enzymes: a gold mine for tuberculosis research.

PubMed

Dedieu, L; Serveau-Avesque, C; Kremer, L; Canaan, S

2013-01-01

Tuberculosis (TB) is one of the deadliest infectious diseases worldwide with a strong impact in developing countries. Mycobacterium tuberculosis, the etiological agent of TB, has a high capacity to evade the host immune system and establish a chronic, asymptomatic and latent infection. In a latent TB infection, persistent bacilli are present in a non-replicating dormant state within host granulomas. During reactivation, bacilli start replicating again leading to an active TB infection that can be highly contagious. Mycobacterial lipids and lipolytic enzymes are thought to play important physiological roles during dormancy and reactivation. The role of lipolytic enzymes in the physiology of M. tuberculosis and physiopathology of the disease will be discussed in this review, with an emphasis on the secreted or cell wall-associated, surface exposed lipolytic enzymes characterized to date. Studies on the localization, enzymatic activity and immunological properties of these enzymes highlighted their possible usefulness as new diagnostic markers in the fight against TB. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

Transcendental experiences during meditation practice.

PubMed

Travis, Frederick

2014-01-01

This article explores transcendental experiences during meditation practice and the integration of transcendental experiences and the unfolding of higher states of consciousness with waking, dreaming, and sleeping. The subject/object relationship during transcendental experiences is characterized by the absence of time, space, and body sense--the framework that gives meaning to waking experiences. Physiologically, transcendental experiences during Transcendental Meditation practice are marked by slow inhalation, along with autonomic orientation at the onset of breath changes and heightened α1 (8-10 Hz) frontal coherence. The integration of transcendental experiences with waking, dreaming, and sleeping is also marked by distinct subjective and objective markers. This integrated state, called Cosmic Consciousness in the Vedic tradition, is subjectively marked by inner self-awareness coexisting with waking, sleeping, and dreaming. Physiologically, Cosmic Consciousness is marked by the coexistence of α1 electroencephalography (EEG) with delta EEG during deep sleep, and higher brain integration, greater emotional stability, and decreased anxiety during challenging tasks. Transcendental experiences may be the engine that fosters higher human development. © 2013 New York Academy of Sciences.

Analysis of the proteolysis of bioactive peptides using a peptidomics approach

PubMed Central

Kim, Yun-Gon; Lone, Anna Mari; Saghatelian, Alan

2014-01-01

Identifying the peptidases that inactivate bioactive peptides (e.g. peptide hormones and neuropeptides) in mammals is an important unmet challenge. This protocol describes a recent approach that combines liquid chromatography-mass spectrometry peptidomics to identify endogenous cleavage sites of a bioactive peptide, the subsequent biochemical purification of a candidate peptidase based on these cleavage sites, and validation of the candidate peptidase’s role in the physiological regulation of the bioactive peptide by examining a peptidase knockout mouse. We highlight successful application of this protocol to discover that insulin-degrading enzyme (IDE) regulates physiological calcitonin gene-related peptide (CGRP) levels and detail the key stages and steps in this approach. This protocol requires 7 days of work; however, the total time for this protocol is highly variable because of its dependence on the availability of biological reagents, namely purified enzymes and knockout mice. The protocol is valuable because it expedites the characterization of mammalian peptidases, such as IDE, which in certain instances can be used to develop novel therapeutics. PMID:23949379

Genetic Code Expansion: A Powerful Tool for Understanding the Physiological Consequences of Oxidative Stress Protein Modifications.

PubMed

Porter, Joseph J; Mehl, Ryan A

2018-01-01

Posttranslational modifications resulting from oxidation of proteins (Ox-PTMs) are present intracellularly under conditions of oxidative stress as well as basal conditions. In the past, these modifications were thought to be generic protein damage, but it has become increasingly clear that Ox-PTMs can have specific physiological effects. It is an arduous task to distinguish between the two cases, as multiple Ox-PTMs occur simultaneously on the same protein, convoluting analysis. Genetic code expansion (GCE) has emerged as a powerful tool to overcome this challenge as it allows for the site-specific incorporation of an Ox-PTM into translated protein. The resulting homogeneously modified protein products can then be rigorously characterized for the effects of individual Ox-PTMs. We outline the strengths and weaknesses of GCE as they relate to the field of oxidative stress and Ox-PTMs. An overview of the Ox-PTMs that have been genetically encoded and applications of GCE to the study of Ox-PTMs, including antibody validation and therapeutic development, is described.

Acute Modulation of Mycobacterial Cell Envelope Biogenesis by Front-Line Tuberculosis Drugs.

PubMed

Rodriguez-Rivera, Frances P; Zhou, Xiaoxue; Theriot, Julie A; Bertozzi, Carolyn R

2018-05-04

Front-line tuberculosis (TB) drugs have been characterized extensively in vitro and in vivo with respect to gene expression and cell viability. However, little work has been devoted to understanding their effects on the physiology of the cell envelope, one of the main targets of this clinical regimen. Herein, we use metabolic labeling methods to visualize the effects of TB drugs on cell envelope dynamics in mycobacterial species. We developed a new fluorophore-trehalose conjugate to visualize trehalose monomycolates of the mycomembrane using super-resolution microscopy. We also probed the relationship between mycomembrane and peptidoglycan dynamics using a dual metabolic labeling strategy. Finally, we found that metabolic labeling of both cell envelope structures reports on drug effects on cell physiology in two hours, far faster than a genetic sensor of cell envelope stress. Our work provides insight into acute drug effects on cell envelope biogenesis in live mycobacteria. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Porifera Lectins: Diversity, Physiological Roles and Biotechnological Potential.

PubMed

Gardères, Johan; Bourguet-Kondracki, Marie-Lise; Hamer, Bojan; Batel, Renato; Schröder, Heinz C; Müller, Werner E G

2015-08-07

An overview on the diversity of 39 lectins from the phylum Porifera is presented, including 38 lectins, which were identified from the class of demosponges, and one lectin from the class of hexactinellida. Their purification from crude extracts was mainly performed by using affinity chromatography and gel filtration techniques. Other protocols were also developed in order to collect and study sponge lectins, including screening of sponge genomes and expression in heterologous bacterial systems. The characterization of the lectins was performed by Edman degradation or mass spectrometry. Regarding their physiological roles, sponge lectins showed to be involved in morphogenesis and cell interaction, biomineralization and spiculogenesis, as well as host defense mechanisms and potentially in the association between the sponge and its microorganisms. In addition, these lectins exhibited a broad range of bioactivities, including modulation of inflammatory response, antimicrobial and cytotoxic activities, as well as anticancer and neuromodulatory activity. In view of their potential pharmacological applications, sponge lectins constitute promising molecules of biotechnological interest.

Investigating a holobiont: Microbiota perturbations and transkingdom networks.

PubMed

Greer, Renee; Dong, Xiaoxi; Morgun, Andrey; Shulzhenko, Natalia

2016-01-01

The scientific community has recently come to appreciate that, rather than existing as independent organisms, multicellular hosts and their microbiota comprise a complex evolving superorganism or metaorganism, termed a holobiont. This point of view leads to a re-evaluation of our understanding of different physiological processes and diseases. In this paper we focus on experimental and computational approaches which, when combined in one study, allowed us to dissect mechanisms (traditionally named host-microbiota interactions) regulating holobiont physiology. Specifically, we discuss several approaches for microbiota perturbation, such as use of antibiotics and germ-free animals, including advantages and potential caveats of their usage. We briefly review computational approaches to characterize the microbiota and, more importantly, methods to infer specific components of microbiota (such as microbes or their genes) affecting host functions. One such approach called transkingdom network analysis has been recently developed and applied in our study. (1) Finally, we also discuss common methods used to validate the computational predictions of host-microbiota interactions using in vitro and in vivo experimental systems.

Porifera Lectins: Diversity, Physiological Roles and Biotechnological Potential

PubMed Central

Gardères, Johan; Bourguet-Kondracki, Marie-Lise; Hamer, Bojan; Batel, Renato; Schröder, Heinz C.; Müller, Werner E. G.

2015-01-01

An overview on the diversity of 39 lectins from the phylum Porifera is presented, including 38 lectins, which were identified from the class of demosponges, and one lectin from the class of hexactinellida. Their purification from crude extracts was mainly performed by using affinity chromatography and gel filtration techniques. Other protocols were also developed in order to collect and study sponge lectins, including screening of sponge genomes and expression in heterologous bacterial systems. The characterization of the lectins was performed by Edman degradation or mass spectrometry. Regarding their physiological roles, sponge lectins showed to be involved in morphogenesis and cell interaction, biomineralization and spiculogenesis, as well as host defense mechanisms and potentially in the association between the sponge and its microorganisms. In addition, these lectins exhibited a broad range of bioactivities, including modulation of inflammatory response, antimicrobial and cytotoxic activities, as well as anticancer and neuromodulatory activity. In view of their potential pharmacological applications, sponge lectins constitute promising molecules of biotechnological interest. PMID:26262628

HyCCAPP as a tool to characterize promoter DNA-protein interactions in Saccharomyces cerevisiae.

PubMed

Guillen-Ahlers, Hector; Rao, Prahlad K; Levenstein, Mark E; Kennedy-Darling, Julia; Perumalla, Danu S; Jadhav, Avinash Y L; Glenn, Jeremy P; Ludwig-Kubinski, Amy; Drigalenko, Eugene; Montoya, Maria J; Göring, Harald H; Anderson, Corianna D; Scalf, Mark; Gildersleeve, Heidi I S; Cole, Regina; Greene, Alexandra M; Oduro, Akua K; Lazarova, Katarina; Cesnik, Anthony J; Barfknecht, Jared; Cirillo, Lisa A; Gasch, Audrey P; Shortreed, Michael R; Smith, Lloyd M; Olivier, Michael

2016-06-01

Currently available methods for interrogating DNA-protein interactions at individual genomic loci have significant limitations, and make it difficult to work with unmodified cells or examine single-copy regions without specific antibodies. In this study, we describe a physiological application of the Hybridization Capture of Chromatin-Associated Proteins for Proteomics (HyCCAPP) methodology we have developed. Both novel and known locus-specific DNA-protein interactions were identified at the ENO2 and GAL1 promoter regions of Saccharomyces cerevisiae, and revealed subgroups of proteins present in significantly different levels at the loci in cells grown on glucose versus galactose as the carbon source. Results were validated using chromatin immunoprecipitation. Overall, our analysis demonstrates that HyCCAPP is an effective and flexible technology that does not require specific antibodies nor prior knowledge of locally occurring DNA-protein interactions and can now be used to identify changes in protein interactions at target regions in the genome in response to physiological challenges. Copyright © 2016 Elsevier Inc. All rights reserved.

[Progress on salt resistance in autopolyploid plants].

PubMed

Zhu, Hong Ju; Liu, Wen Ge

2018-04-20

Polyploidization is a key driving force that plays a vital role in the evolution of higher plants. Autopolyploid plants often demonstrate altered physiology phenomena due to the different genome composition and gene expression patterns. For example, autopolyploid plants are more resistant to stresses than their homologous diploid ancestors. Soil salinity and secondary salinization are two vital factors affecting crop production which severely limit the sustainable development of agriculture in China. Polyploid plants are important germplasm resources in crop genetic improvement due to their higher salt tolerance. Revealing the mechanism of salt tolerance in homologous plants will provide a foundation for breeding new plants with improved salt resistance. In this review, we describe the existing and ongoing characterization of the mechanism of salt tolerance in autopolyploid plants, including the salt tolerance evolution, physiology, biochemistry, cell structure and molecular level researches. Finally, we also discuss the prospects in this field by using polyploid watermelon as an example, which will be helpful in polyploid research and plant breeding.

Linkage of within vineyard soil properties, grapevine physiology, grape composition and sensory characteristics in a premium wine grape vineyard.

NASA Astrophysics Data System (ADS)

Smart, David; Hess, Sallie; Ebeler, Susan; Heymann, Hildegarde; Plant, Richard

2014-05-01

Analysis of numerous vineyards has revealed a very high degree of variation exists at the within vineyard scale and may outweigh in some cases broader mesoclimatic and geological factors. For this reason, selective harvest of high quality wine grapes is often conducted and based on subjective field sensory analysis (taste). This is an established practice in many wine growing regions. But the relationships between these subjective judgments to principle soil and grapevine physiological characteristics are not well understood. To move toward greater understanding of the physiological factors related to field sensory evaluation, physiological data was collected over the 2007 and 2008 growing seasons in a selectively harvested premium production Napa Valley estate vineyard, with a history of selective harvesting based on field sensory evaluation. Data vines were established and remained as individual study units throughout the data gathering and analysis phase, and geographic information systems science (GIS) was used to geographically scale physiological and other data at the vineyard level. Areas yielding grapes with perceived higher quality (subjective analysis) were characterized by vines with 1) statistically significantly lower (P < 0.05) leaf water potential (LWP) both pre-dawn (PD) and midday (MD), 2) smaller berry diameter and weight, 3) lower pruning weights, and 4) higher soluble solids (Brix). Strong positive correlations emerged between June ψPD and pre-harvest grape berry diameter (R2 = 0.616 in 2007 and 0.413 in 2008) and similar strong correlations existed for berry weight (R2 = 0.626 in 2007 and 0.554 in 2008). A trained sensory panel performed a sensory analysis and characterized fruit using and a multivariate, principal components, analysis (PCA). This approach indicated that grapes from vines with lowest midday leaf water potential at veraison (< -1.5 MPa) had sweeter and softer pulp, absence of vegetal characteristics, and browner and crunchier seeds, while grapes from vines of > -1.5 MPa were characterized by vegetal flavors and astringent and bitter seeds and skins. Data from vines were grouped into vines experiencing MD at veraison of < -1.5 MPa versus vines with MD > -1.5 MPa and subjected to single factor analysis of variance. This analysis revealed statistically significant differences (P less than 0.05) in many of the above properties - berry diameter, weight, pulp, and fruity versus vegetal characteristic. The groupings corresponded to the areas described as producing higher and lower quality fruit, respectively, based on field taste evaluation. Metabolomic analysis of grape skins from these two groups showed statistically significant differences in accumulation of amino acids and organic acids. Our results suggest there is not a continuous relationship between physiological water status (stress) and grape sensory characteristics, but rather the presence of an inflection point that may be related to early season PD in controlling grape development as well as composition. Soils analyses revealed the preferred fruit was on vines in areas where soils were shallower rather than any definitive characteristic related to particle size distribution or nutrient availability, suggesting that in this vineyard soil available water is the major controlling factor.

Metabolic studies of transient tyrosinemia in premature infants

NASA Technical Reports Server (NTRS)

Fernbach, S. A.; Summons, R. E.; Pereira, W. E.; Duffield, A. M.

1975-01-01

The recently developed technique of gas chromatography-mass spectrometry supported by computer has considerably improved the analysis of physiologic fluids. This study attempted to demonstrate the value of this system in the investigation of metabolite patterns in urine in two metabolic problems of prematurity, transient tyrosinemia and late metabolic acidosis. Serial 24-hr urine specimens were analyzed in 9 infants. Transient tyrosinemia, characterized by 5- 10-fold increases over basal excretion of tyrosine, p-hydroxyphenyllactate, and p-hydroxyphenylpyruvate in urine, was noted in five of the infants. Late metabolic acidosis was seen in four infants, but bore no relation to transient tyrosinemia.

Modeling the Pulse Signal by Wave-Shape Function and Analyzing by Synchrosqueezing Transform

PubMed Central

Wang, Chun-Li; Yang, Yueh-Lung; Wu, Wen-Hsiang; Tsai, Tung-Hu; Chang, Hen-Hong

2016-01-01

We apply the recently developed adaptive non-harmonic model based on the wave-shape function, as well as the time-frequency analysis tool called synchrosqueezing transform (SST) to model and analyze oscillatory physiological signals. To demonstrate how the model and algorithm work, we apply them to study the pulse wave signal. By extracting features called the spectral pulse signature, and based on functional regression, we characterize the hemodynamics from the radial pulse wave signals recorded by the sphygmomanometer. Analysis results suggest the potential of the proposed signal processing approach to extract health-related hemodynamics features. PMID:27304979

Modeling the Pulse Signal by Wave-Shape Function and Analyzing by Synchrosqueezing Transform.

PubMed

Wu, Hau-Tieng; Wu, Han-Kuei; Wang, Chun-Li; Yang, Yueh-Lung; Wu, Wen-Hsiang; Tsai, Tung-Hu; Chang, Hen-Hong

2016-01-01

We apply the recently developed adaptive non-harmonic model based on the wave-shape function, as well as the time-frequency analysis tool called synchrosqueezing transform (SST) to model and analyze oscillatory physiological signals. To demonstrate how the model and algorithm work, we apply them to study the pulse wave signal. By extracting features called the spectral pulse signature, and based on functional regression, we characterize the hemodynamics from the radial pulse wave signals recorded by the sphygmomanometer. Analysis results suggest the potential of the proposed signal processing approach to extract health-related hemodynamics features.

Brain development during the preschool years

PubMed Central

Brown, Timothy T.; Jernigan, Terry L.

2012-01-01

The preschool years represent a time of expansive psychological growth, with the initial expression of many psychological abilities that will continue to be refined into young adulthood. Likewise, brain development during this age is characterized by its “blossoming” nature, showing some of its most dynamic and elaborative anatomical and physiological changes. In this article, we review human brain development during the preschool years, sampling scientific evidence from a variety of sources. First, we cover neurobiological foundations of early postnatal development, explaining some of the primary mechanisms seen at a larger scale within neuroimaging studies. Next, we review evidence from both structural and functional imaging studies, which now accounts for a large portion of our current understanding of typical brain development. Within anatomical imaging, we focus on studies of developing brain morphology and tissue properties, including diffusivity of white matter fiber tracts. We also present new data on changes during the preschool years in cortical area, thickness, and volume. Physiological brain development is then reviewed, touching on influential results from several different functional imaging and recording modalities in the preschool and early school-age years, including positron emission tomography (PET), electroencephalography (EEG) and event-related potentials (ERP), functional magnetic resonance imaging (fMRI), magnetoencephalography (MEG), and near-infrared spectroscopy (NIRS). Here, more space is devoted to explaining some of the key methodological factors that are required for interpretation. We end with a section on multimodal and multidimensional imaging approaches, which we believe will be critical for increasing our understanding of brain development and its relationship to cognitive and behavioral growth in the preschool years and beyond. PMID:23007644

Vascular physiology and protein disposition in a preclinical model of neurodegeneration.

PubMed

Boswell, C Andrew; Mundo, Eduardo E; Johnstone, Bernadette; Ulufatu, Sheila; Schweiger, Michelle G; Bumbaca, Daniela; Fielder, Paul J; Prabhu, Saileta; Khawli, Leslie A

2013-05-06

The development of clinically relevant preclinical models that mimic the hallmarks of neurodegenerative disease is an ongoing pursuit in early drug development. In particular, robust physiological characterization of central nervous system (CNS) disease models is necessary to predict drug delivery to target tissues and to correctly interpret pharmacodynamic responses to disease-modifying therapeutic candidates. Efficient drug delivery across the blood-CNS barrier is a particularly daunting task, prompting our strategy to evaluate the biodistribution of five distinct molecular probes in a well-characterized mouse model of neurodegeneration. A transgenic mouse model of amyotrophic lateral sclerosis was selected based on a phenotype resembling clinical symptoms, including loss of motor neurons from the spinal cord and paralysis in one or more limbs, due to expression of a G93A mutant form of human superoxide dismutase (SOD1). The tissue distributions of two proteins, albumin and a representative immunoglobulin G antibody, as well as two blood flow markers, the lipophilic blood flow marker Ceretec (i.e., (99m)Tc-HMPAO) and the polar ionic tracer, rubidium-86 chloride ((86)RbCl), were measured following intravenous injection in SOD1(G93A) and age-matched control mice. The radiopharmaceutical TechneScan PYP was also used to measure the distribution of (99m)Tc-labeled red blood cells as a blood pool marker. Both the antibody and (86)Rb were able to cross the blood-spinal cord barrier in SOD1(G93A) mice to a greater extent than in control mice. Although the biodistribution patterns of antibody, albumin, and RBCs were largely similar, notable differences were detected in muscle and skin. Moreover, vastly different biodistribution patterns were observed for a lipophilic and polar perfusion agent, with SOD1(G93A) mutation resulting in reduced renal filtration rates for the former but not the latter. Overall, the multiprobe strategy provided an opportunity to efficiently collect an abundance of physiological information, including the degree and regional extent of blood-CNS barrier permeability, in a preclinical model of neurodegeneration.

2014 SRP Integration Transcript

NASA Technical Reports Server (NTRS)

Steinberg, Susan

2014-01-01

HRP's mission is to reduce the risks to human health and performance during long-duration spaceflight. The HRP Integrated Research Plan (IRP) contains the research plans for the 32 risks that require research to characterize and mitigate. From its inception the "integrate" aspect of the IRP has denoted the integrated nature of risks to human health and performance. Even though each risk in the IRP has its own research plan and is tracked separately, the interrelated nature of health and performance requires that they be addressed in an integrative or holistic fashion so that the connectedness of physiological systems within the human body and the integrated response to spaceflight can be addressed. Common characteristics of the spaceflight environment include altered gravity, atmospheres, and light/dark cycles; space radiation; isolation; noise; and periods of high or low workload. Long-term exposure to this unique environment produces a suite of physiological effects such as stress; vision, neurocognitive, and anthropometric changes; circadian misalignment; fluid shifts; cardiovascular deconditioning; immune dysregulation; and altered nutritional requirements. Expanding cross-disciplinary integrative approaches that synthesize concepts or data from two or more disciplines would improve the identification and characterization risk factors, and enable the development of countermeasures relevant to multiple risks. Cross-disciplinary approaches might also help to illuminate problem areas that may arise when a countermeasure adversely impacts risks other than those which it was developed to mitigate, or to identify groupings of physiological changes that are likely to occur that may impact the overall risk posture. In 2014 HRP embarked on a pilot study that combined four SRPs (and 12 HRP risks) - Behavioral Health, Sensorimotor, Cardiovascular, and Bone/Muscle - specifically to discuss cross-disciplinary integration. The points outlined below were suggested to seed the discussion, within the bounding constraint that research plans must be feasible and relevant to the HRP mission. While these were suggested starting points, the overall guiding principle was to allow free discussion from panel members on any aspect of integrated research that they felt was important, Existing cross-disciplinary integration as documented in the IRP (HRR), Existing or needed integration already identified by HRP, but not yet well defined within the IRP, Areas of integration that are missing.

Developmental trajectories of cerebrovascular reactivity in healthy children and young adults assessed with magnetic resonance imaging.

PubMed

Leung, Jackie; Kosinski, Przemyslaw D; Croal, Paula L; Kassner, Andrea

2016-05-15

Cerebrovascular reactivity (CVR) reflects the vasodilatory reserve of cerebral resistance vessels. Normal development in children is associated with significant changes in blood pressure, cerebral blood flow (CBF) and cerebral oxygen metabolism. Therefore, it stands to reason that CVR will also undergo changes during this period. The study acquired magnetic resonance imaging measures of CVR and CBF in healthy children and young adults to trace their changes with age. We found that CVR changes in two phases, increasing with age until the mid-teens, followed by a decrease. Baseline CBF declined steadily with age. We conclude that CVR varies with age during childhood, which prompts future CVR studies involving children to take into account the effect of development. Cerebrovascular reactivity (CVR) reflects the vasculature's ability to accommodate changes in blood flow demand thereby serving as a critical imaging tool for mapping vascular reserve. Normal development is associated with extensive physiological changes in blood pressure, cerebral blood flow and cerebral metabolic rate of oxygen, all of which can affect CVR. Moreover, the evolution of these physiological parameters is most prominent during childhood. Therefore, the aim of this study was to use non-invasive magnetic resonance imaging (MRI) to characterize the developmental trajectories of CVR in healthy children and young adults, and relate them to changes in cerebral blood flow (CBF). Thirty-four healthy subjects (17 males, 17 females; age 9-30 years) underwent CVR assessment using blood oxygen level-dependent MRI in combination with a computer controlled CO2 stimulus. In addition, baseline CBF was measured with a pulsed arterial spin labelling sequence. CVR exhibited a gradual increase with age in both grey and white matter up to 14.7 years. After this break point, a negative correlation with age was detected. Baseline CBF maintained a consistent negative linear correlation across the entire age range. The significant age-dependent changes in CVR and CBF demonstrate the evolution of cerebral haemodynamics in children and should be taken into consideration. The shift in developmental trajectory of CVR from increasing to decreasing suggests that physiological factors beyond baseline CBF also influence CVR. © 2016 The Authors. The Journal of Physiology © 2016 The Physiological Society.

Functional imaging of skeletal muscle fiber in different physiological states by second harmonic generation

NASA Astrophysics Data System (ADS)

Nucciotti, V.; Stringari, C.; Sacconi, L.; Vanzi, F.; Tesi, C.; Piroddi, N.; Poggesi, C.; Castiglioni, C.; Milani, A.; Linari, M.; Piazzesi, G.; Lombardi, V.; Pavone, F. S.

2007-07-01

The intrinsically ordered arrays of proteins in skeletal muscle allows imaging of this tissue by Second Harmonic Generation (SHG). Biochemical and colocalization studies have gathered an increasing wealth of clues for the attribution of the molecular origin of the muscle SHG signal to the motor protein myosin. Thus, SHG represents a potentially very powerful tool in the investigation of structural dynamics occurring in muscle during active production of force. A full characterization of the polarization-dependence of the SHG signal represents a very selective information on the orientation of the emitting proteins and their dynamics during contraction, provided that different physiological states of muscle (relaxed, rigor and active) exhibit distinct patterns of SHG polarization dependence. Here polarization data are obtained from single frog muscle fibers at rest and during isometric contraction and interpreted, by means of a model, in terms of an average orientation of the SHG emitters which are structured with a cylindrical symmetry about the fiber axis. Optimizing the setup for accurate polarization measurements with SHG, we developed a line scan imaging method allowing measurement of SHG polarization curves in different physiological states. We demonstrate that muscle fiber displays a measurable variation of the orientation of SHG emitters with the transition from rest to isometric contraction.

A Modern Understanding of the Traditional and Nontraditional Biological Functions of Angiotensin-Converting Enzyme

PubMed Central

Ong, Frank S.; Blackwell, Wendell-Lamar B.; Shah, Kandarp H.; Giani, Jorge F.; Gonzalez-Villalobos, Romer A.; Shen, Xiao Z.; Fuchs, Sebastien

2013-01-01

Angiotensin-converting enzyme (ACE) is a zinc-dependent peptidase responsible for converting angiotensin I into the vasoconstrictor angiotensin II. However, ACE is a relatively nonspecific peptidase that is capable of cleaving a wide range of substrates. Because of this, ACE and its peptide substrates and products affect many physiologic processes, including blood pressure control, hematopoiesis, reproduction, renal development, renal function, and the immune response. The defining feature of ACE is that it is composed of two homologous and independently catalytic domains, the result of an ancient gene duplication, and ACE-like genes are widely distributed in nature. The two ACE catalytic domains contribute to the wide substrate diversity of ACE and, by extension, the physiologic impact of the enzyme. Several studies suggest that the two catalytic domains have different biologic functions. Recently, the X-ray crystal structure of ACE has elucidated some of the structural differences between the two ACE domains. This is important now that ACE domain-specific inhibitors have been synthesized and characterized. Once widely available, these reagents will undoubtedly be powerful tools for probing the physiologic actions of each ACE domain. In turn, this knowledge should allow clinicians to envision new therapies for diseases not currently treated with ACE inhibitors. PMID:23257181

A strategy for in-flight measurements of physiology of pilots of high-performance fighter aircraft.

PubMed

West, John B

2013-07-01

Some pilots flying modern high-performance fighter aircraft develop "hypoxia-like" incidents characterized by short periods of confusion and cognitive impairment. The problem is serious and recently led to the grounding of a fleet of aircraft. Extensive discussions of the incidents have taken place but some people believe that there is inadequate data to determine the cause. There is a tremendous disconnect between what is known about the function of the aircraft and the function of the pilot. This paper describes a plan for measuring the inspired and expired Po2 and Pco2 in the pilot's mask, the inspiratory flow rate, and pressure in the mask. A critically important requirement is that the interference with the function of the pilot is minimal. Although extensive physiological measurements were previously made on pilots in ground-based experiments such as rapid decompression in an altitude chamber and increased acceleration on a centrifuge, in-flight measurements of gas exchange have not been possible until now primarily because of the lack of suitable equipment. The present paper shows how the recent availability of small, rapidly responding oxygen and carbon dioxide analyzers make sophisticated in-flight measurements feasible. The added information has the potential of greatly improving our knowledge of pilot physiology, which could lead to an explanation for the incidents.

Proteinase-activated receptors (PARs) – focus on receptor-receptor-interactions and their physiological and pathophysiological impact

PubMed Central

2013-01-01

Proteinase-activated receptors (PARs) are a subfamily of G protein-coupled receptors (GPCRs) with four members, PAR1, PAR2, PAR3 and PAR4, playing critical functions in hemostasis, thrombosis, embryonic development, wound healing, inflammation and cancer progression. PARs are characterized by a unique activation mechanism involving receptor cleavage by different proteinases at specific sites within the extracellular amino-terminus and the exposure of amino-terminal “tethered ligand“ domains that bind to and activate the cleaved receptors. After activation, the PAR family members are able to stimulate complex intracellular signalling networks via classical G protein-mediated pathways and beta-arrestin signalling. In addition, different receptor crosstalk mechanisms critically contribute to a high diversity of PAR signal transduction and receptor-trafficking processes that result in multiple physiological effects. In this review, we summarize current information about PAR-initiated physical and functional receptor interactions and their physiological and pathological roles. We focus especially on PAR homo- and heterodimerization, transactivation of receptor tyrosine kinases (RTKs) and receptor serine/threonine kinases (RSTKs), communication with other GPCRs, toll-like receptors and NOD-like receptors, ion channel receptors, and on PAR association with cargo receptors. In addition, we discuss the suitability of these receptor interaction mechanisms as targets for modulating PAR signalling in disease. PMID:24215724

HyspIRI Measurements of Agricultural Systems in California: 2013-2015

NASA Astrophysics Data System (ADS)

Townsend, P. A.; Kruger, E. L.; Singh, A.; Jablonski, A. D.; Kochaver, S.; Serbin, S.

2015-12-01

During 2013-2015, NASA collected high-altitude AVIRIS hyperspectral and MASTER thermal infrared imagery across large swaths of California in support of the HyspIRI planning and prototyping activities. During these campaigns, we made extensive measurements of photosynthetic capacity—Vcmax and Jmax—and their temperature sensitivities across a range of sites, crop types and environmental conditions. Our objectives were to characterize the physiological diversity of agricultural vegetation in California and develop generalizable algorithms to map these physiological parameters across several image acquisitions, regardless of crop type and canopy temperatures. We employed AVIRIS imagery to scale and estimate the vegetation parameters and MASTER surface temperature to provide context, since physiology responds exponentially to leaf temperature. We demonstrate a segmentation approach to disentangling leaf and background soil temperature, and then illustrate our retrievals of Vcmax and Jmax during overflight conditions across a large number of the 2013-2015 HyspIRI acquisitions. Our results show >80% repeatability (R2) across split sample jack-knifing, with RMSEs within 15% of the range of our data. The approach was robust across crop types (e.g., grape, almond, pistachio, avocado, pomegranate, oats, peppers, citrus, date palm, alfalfa, melons, beets) and leaf temperatures. A global imaging spectroscopy system such as HyspIRI will offer unprecedented ability to monitor agricultural crop performance under widely varying surface conditions.

Metabotropic glutamate receptors in auditory processing

PubMed Central

Lu, Yong

2014-01-01

As the major excitatory neurotransmitter used in the vertebrate brain, glutamate activates ionotropic and metabotropic glutamate receptors (mGluRs), which mediate fast and slow neuronal actions, respectively. Important modulatory roles of mGluRs have been shown in many brain areas, and drugs targeting mGluRs have been developed for treatment of brain disorders. Here, I review the studies on mGluRs in the auditory system. Anatomical expression of mGluRs in the cochlear nucleus has been well characterized, while data for other auditory nuclei await more systematic investigations at both the light and electron microscopy levels. The physiology of mGluRs has been extensively studied using in vitro brain slice preparations, with a focus on the lower auditory brainstem in both mammals and birds. These in vitro physiological studies have revealed that mGluRs participate in neurotransmission, regulate ionic homeostasis, induce synaptic plasticity, and maintain the balance between excitation and inhibition in a variety of auditory structures. However, very few in vivo physiological studies on mGluRs in auditory processing have been undertaken at the systems level. Many questions regarding the essential roles of mGluRs in auditory processing still remain unanswered and more rigorous basic research is warranted. PMID:24909898

Movement, migration, and smolting of Atlantic salmon (Salmo salar)

USGS Publications Warehouse

McCormick, S.D.; Hansen, Lonnie P.; Quinn, T.P.; Saunders, R.L.

1998-01-01

A variety of movements characterize the behavioral plasticity of Atlantic salmon (Salmo salar) in fresh water, including movements of fry from redds, establishment of feeding territories, spawning movements of sexually mature male parr, movement to and from winter habitat, and smolt migration in spring. Smolting is an adaptive specialization for downstream migration, seawater entry, and marine residence. While still in fresh water, smolts become silvery and streamlined, lose their positive rheotaxis and territoriality, and begin schooling. Physiological changes include increased salinity tolerance, olfactory sensitivity, metabolic rate, scope for growth, and altered hemoglobin and visual pigments. Through their impact on the neuroendocrine system, photoperiod and temperature regulate physiological changes, whereas temperature and water flow may initiate migration. Smolt survival is affected by a limited period of readiness (a physiological 'smolt window') and the timing of seawater entry with environmental conditions such as temperature, food, and predators (an ecological 'smolt window'). Smolt development is adversely affected by acidity, pollutants, and improper rearing conditions, and is often more sensitive than other life stages. Unfortunately, the migration corridor of smolts (mainstems of rivers and estuaries) are the most heavily impacted by pollution, dams, and other anthropogenic activities that may be directly lethal or increase mortality by delaying or inhibiting smolt migration.

Patient Characterization Protocols for Psychophysiological Studies of Traumatic Brain Injury and Post-TBI Psychiatric Disorders

PubMed Central

Rapp, Paul E.; Rosenberg, Brenna M.; Keyser, David O.; Nathan, Dominic; Toruno, Kevin M.; Cellucci, Christopher J.; Albano, Alfonso M.; Wylie, Scott A.; Gibson, Douglas; Gilpin, Adele M. K.; Bashore, Theodore R.

2013-01-01

Psychophysiological investigations of traumatic brain injury (TBI) are being conducted for several reasons, including the objective of learning more about the underlying physiological mechanisms of the pathological processes that can be initiated by a head injury. Additional goals include the development of objective physiologically based measures that can be used to monitor the response to treatment and to identify minimally symptomatic individuals who are at risk of delayed-onset neuropsychiatric disorders following injury. Research programs studying TBI search for relationships between psychophysiological measures, particularly ERP (event-related potential) component properties (e.g., timing, amplitude, scalp distribution), and a participant’s clinical condition. Moreover, the complex relationships between brain injury and psychiatric disorders are receiving increased research attention, and ERP technologies are making contributions to this effort. This review has two objectives supporting such research efforts. The first is to review evidence indicating that TBI is a significant risk factor for post-injury neuropsychiatric disorders. The second objective is to introduce ERP researchers who are not familiar with neuropsychiatric assessment to the instruments that are available for characterizing TBI, post-concussion syndrome, and psychiatric disorders. Specific recommendations within this very large literature are made. We have proceeded on the assumption that, as is typically the case in an ERP laboratory, the investigators are not clinically qualified and that they will not have access to participant medical records. PMID:23885250

Characterizing the in vivo role of trehalose in Saccharomyces cerevisiae using the AGT1 transporter

PubMed Central

Gibney, Patrick A.; Schieler, Ariel; Chen, Jonathan C.; Rabinowitz, Joshua D.; Botstein, David

2015-01-01

Trehalose is a highly stable, nonreducing disaccharide of glucose. A large body of research exists implicating trehalose in a variety of cellular phenomena, notably response to stresses of various kinds. However, in very few cases has the role of trehalose been examined directly in vivo. Here, we describe the development and characterization of a system in Saccharomyces cerevisiae that allows us to manipulate intracellular trehalose concentrations independently of the biosynthetic enzymes and independently of any applied stress. We found that many physiological roles heretofore ascribed to intracellular trehalose, including heat resistance, are not due to the presence of trehalose per se. We also found that many of the metabolic and growth defects associated with mutations in the trehalose biosynthesis pathway are not abolished by providing abundant intracellular trehalose. Instead, we made the observation that intracellular accumulation of trehalose or maltose (another disaccharide of glucose) is growth-inhibitory in a carbon source-specific manner. We conclude that the physiological role of the trehalose pathway is fundamentally metabolic: i.e., more complex than simply the consequence of increased concentrations of the sugar and its attendant physical properties (with the exception of the companion paper where Tapia et al. [Tapia H, et al. (2015) Proc Natl Acad Sci USA, 10.1073/pnas.1506415112] demonstrate a direct role for trehalose in protecting cells against desiccation). PMID:25918382

In vitro Differentiation of Functional Human Skeletal Myotubes in a Defined System

PubMed Central

Guo, Xiufang; Greene, Keshel; Akanda, Nesar; Smith, Alec; Stancescu, Maria; Lambert, Stephen; Vandenburgh, Herman; Hickman, James

2013-01-01

In vitro human skeletal muscle systems are valuable tools for the study of human muscular development, disease and treatment. However, published in vitro human muscle systems have so far only demonstrated limited differentiation capacities. Advanced differentiation features such as cross-striations and contractility have only been observed in co-cultures with motoneurons. Furthermore, it is commonly regarded that cultured human myotubes do not spontaneously contract, and any contraction has been considered to originate from innervation. This study developed a serum-free culture system in which human skeletal myotubes demonstrated advanced differentiation. Characterization by immunocytochemistry, electrophysiology and analysis of contractile function revealed these major features: A) well defined sarcomeric development, as demonstrated by the presence of cross-striations. B) finely developed excitation-contraction coupling apparatus characterized by the close apposition of dihydropyridine receptors on T-tubules and Ryanodine receptors on sarcoplasmic reticulum membranes. C) spontaneous and electrically controlled contractility. This report not only demonstrates an improved level of differentiation of cultured human skeletal myotubes, but also provides the first published evidence that such myotubes are capable of spontaneous contraction. Use of this functional in vitro human skeletal muscle system would advance studies concerning human skeletal muscle development and physiology, as well as muscle-related disease and therapy. PMID:24516722

In vitro Differentiation of Functional Human Skeletal Myotubes in a Defined System.

PubMed

Guo, Xiufang; Greene, Keshel; Akanda, Nesar; Smith, Alec; Stancescu, Maria; Lambert, Stephen; Vandenburgh, Herman; Hickman, James

2014-01-01

In vitro human skeletal muscle systems are valuable tools for the study of human muscular development, disease and treatment. However, published in vitro human muscle systems have so far only demonstrated limited differentiation capacities. Advanced differentiation features such as cross-striations and contractility have only been observed in co-cultures with motoneurons. Furthermore, it is commonly regarded that cultured human myotubes do not spontaneously contract, and any contraction has been considered to originate from innervation. This study developed a serum-free culture system in which human skeletal myotubes demonstrated advanced differentiation. Characterization by immunocytochemistry, electrophysiology and analysis of contractile function revealed these major features: A) well defined sarcomeric development, as demonstrated by the presence of cross-striations. B) finely developed excitation-contraction coupling apparatus characterized by the close apposition of dihydropyridine receptors on T-tubules and Ryanodine receptors on sarcoplasmic reticulum membranes. C) spontaneous and electrically controlled contractility. This report not only demonstrates an improved level of differentiation of cultured human skeletal myotubes, but also provides the first published evidence that such myotubes are capable of spontaneous contraction. Use of this functional in vitro human skeletal muscle system would advance studies concerning human skeletal muscle development and physiology, as well as muscle-related disease and therapy.

Genome-wide identification of jasmonate biosynthetic genes and their characterization of their expression profiles during apple (Malus x domestica) fruit maturation

USDA-ARS?s Scientific Manuscript database

The plant hormones regulate many physiological processes including apple fruit ripening by integrating diverse developmental cues and environmental signals. In addition to the well-characterized role of ethylene, jasmonic acid (JA) and its derivatives have also been suggested to play an important ro...

An evaluation of seed scarification methods of four native Lupinus species

Treesearch

C. D. Jones; S. L. Jensen; M. R. Stevens

2010-01-01

Seed dormancy is a survival strategy that better ensures the persistence of a species. Dormancy is characterized as exogenous if caused by factors outside the embryo or endogenous if caused by factors within the embryo. Exogenous dormancy is further characterized as physical, mechanical or chemical, while endogenous dormancy may be physiological or morphological....

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

NASA Technical Reports Server (NTRS)

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

1997-01-01

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

Hallmarks of progeroid syndromes: lessons from mice and reprogrammed cells

PubMed Central

López-Otín, Carlos

2016-01-01

ABSTRACT Ageing is a process that inevitably affects most living organisms and involves the accumulation of macromolecular damage, genomic instability and loss of heterochromatin. Together, these alterations lead to a decline in stem cell function and to a reduced capability to regenerate tissue. In recent years, several genetic pathways and biochemical mechanisms that contribute to physiological ageing have been described, but further research is needed to better characterize this complex biological process. Because premature ageing (progeroid) syndromes, including progeria, mimic many of the characteristics of human ageing, research into these conditions has proven to be very useful not only to identify the underlying causal mechanisms and identify treatments for these pathologies, but also for the study of physiological ageing. In this Review, we summarize the main cellular and animal models used in progeria research, with an emphasis on patient-derived induced pluripotent stem cell models, and define a series of molecular and cellular hallmarks that characterize progeroid syndromes and parallel physiological ageing. Finally, we describe the therapeutic strategies being investigated for the treatment of progeroid syndromes, and their main limitations. PMID:27482812

The role of retinal bipolar cell in early vision: an implication with analogue networks and regularization theory.

PubMed

Yagi, T; Ohshima, S; Funahashi, Y

1997-09-01

A linear analogue network model is proposed to describe the neuronal circuit of the outer retina consisting of cones, horizontal cells, and bipolar cells. The model reflects previous physiological findings on the spatial response properties of these neurons to dim illumination and is expressed by physiological mechanisms, i.e., membrane conductances, gap-junctional conductances, and strengths of chemical synaptic interactions. Using the model, we characterized the spatial filtering properties of the bipolar cell receptive field with the standard regularization theory, in which the early vision problems are attributed to minimization of a cost function. The cost function accompanying the present characterization is derived from the linear analogue network model, and one can gain intuitive insights on how physiological mechanisms contribute to the spatial filtering properties of the bipolar cell receptive field. We also elucidated a quantitative relation between the Laplacian of Gaussian operator and the bipolar cell receptive field. From the computational point of view, the dopaminergic modulation of the gap-junctional conductance between horizontal cells is inferred to be a suitable neural adaptation mechanism for transition between photopic and mesopic vision.

Physiological serum copper concentrations found in malignancies cause unfolding induced aggregation of human serum albumin in vitro.

PubMed

Rizvi, Asim; Furkan, Mohd; Naseem, Imrana

2017-12-15

Malignancies are characterized by several drastic metabolic changes, one of which is a progressive rise in the levels of serum copper. This rise in serum copper is documented across all malignancies and across malignancies in several species. This study aims to explore in vitro the effect of increased copper levels on the structure of the blood protein human serum albumin. Exposure of human serum albumin to physiologically relevant copper concentrations for 21 days resulted in structural modifications in the protein which were evident by changes in the intrinsic florescence. A loss of the predominantly alpha helical structure of human serum albumin was recorded along with a tendency to form protein aggregates. This aggregation was characterized by Thioflavin T and Congo Red assays. Rayleigh light scattering and turbidity assays confirmed aggregation. The aggregates were visually confirmed using transmission electron microscopy. This is the first report implicating increased copper levels as a cause of aggregation of blood proteins in malignancies. The physiological and biochemical implications of this phenomenon are discussed. Copyright © 2017. Published by Elsevier Inc.

Space-time codependence of retinal ganglion cells can be explained by novel and separable components of their receptive fields.

PubMed

Cowan, Cameron S; Sabharwal, Jasdeep; Wu, Samuel M

2016-09-01

Reverse correlation methods such as spike-triggered averaging consistently identify the spatial center in the linear receptive fields (RFs) of retinal ganglion cells (GCs). However, the spatial antagonistic surround observed in classical experiments has proven more elusive. Tests for the antagonistic surround have heretofore relied on models that make questionable simplifying assumptions such as space-time separability and radial homogeneity/symmetry. We circumvented these, along with other common assumptions, and observed a linear antagonistic surround in 754 of 805 mouse GCs. By characterizing the RF's space-time structure, we found the overall linear RF's inseparability could be accounted for both by tuning differences between the center and surround and differences within the surround. Finally, we applied this approach to characterize spatial asymmetry in the RF surround. These results shed new light on the spatiotemporal organization of GC linear RFs and highlight a major contributor to its inseparability. © 2016 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

Development of sensors for monitoring oxygen and free radicals in plant physiology

NASA Astrophysics Data System (ADS)

Chaturvedi, Prachee

Oxygen plays a critical role in the physiology of photosynthetic organisms, including bioenergetics, metabolism, development, and stress response. Oxygen levels affect photosynthesis, respiration, and alternative oxidase pathways. Likewise, the metabolic rate of spatially distinct plant cells (and therefore oxygen flux) is known to be affected by biotic stress (e.g., herbivory) and environmental stress (e.g., salt/nutrient stress). During aerobic metabolism, cells produce reactive oxygen species (ROS) as a by product. Plants also produce ROS during adaptation to stress (e.g., abscisic acid (ABA) mediated stress responses). If stress conditions are prolonged, ROS levels surpass the capacity of detoxifying mechanisms within the cell, resulting in oxidative damage. While stress response pathways such as ABA-mediated mechanisms have been well characterized (e.g., water stress, inhibited shoot growth, synthesis of storage proteins in seeds), the connection between ROS production, oxygen metabolism and stress response remains unknown. In part, this is because details of oxygen transport at the interface of cell(s) and the surrounding microenvironment remains nebulous. The overall goal of this research was to develop oxygen and Free radical sensors for studying stress signaling in plants. Recent developments in nanomaterials and data acquisition systems were integrated to develop real-time, non-invasive oxygen and Free radical sensors. The availability of these sensors for plant physiologists is an exciting opportunity to probe the functional realm of cells and tissues in ways that were not previously possible.

Hypoxic Switch in Mitochondrial Myeloid Cell Leukemia Factor-1/Mtd Apoptotic Rheostat Contributes to Human Trophoblast Cell Death in Preeclampsia

PubMed Central

Soleymanlou, Nima; Jurisicova, Andrea; Wu, Yuanhong; Chijiiwa, Mari; Ray, Jocelyn E.; Detmar, Jacqui; Todros, Tullia; Zamudio, Stacy; Post, Martin; Caniggia, Isabella

2007-01-01

Preeclampsia, a disorder of pregnancy, is characterized by increased trophoblast cell death and altered trophoblast-mediated remodeling of myometrial spiral arteries resulting in reduced uteroplacental perfusion. Mitochondria-associated Bcl-2 family members are important regulators of programed cell death. The mechanism whereby hypoxia alters the mitochondrial apoptotic rheostat is essential to our understanding of placental disease. Herein, myeloid cell leukemia factor-1 (Mcl-1) isoform expression was examined in physiological/pathological models of placental hypoxia. Preeclamptic placentae were characterized by caspase-dependent cleavage of death-suppressing Mcl-1L and switch toward cell death-inducing Mcl-1S. In vitro, Mcl-1L cleavage was induced by hypoxia-reoxygenation in villous explants, whereas Mcl-1L overexpression under hypoxia-reoxygenation rescued trophoblast cells from undergoing apoptosis. Cleavage was mediated by caspase-3/-7 because pharmacological caspase inhibition prevented this process. Altitude-induced chronic hypoxia was characterized by expression of Mcl-1L; resulting in a reduction of apoptotic markers (cleaved caspase-3/-8 and p85 poly-ADP-ribose polymerase). Moreover, in both physiological (explants and high altitude) and pathological (preeclampsia) placental hypoxia, decreased trophoblast syncytin expression was observed. Hence, although both pathological and physiological placental hypoxia are associated with slowed trophoblast differentiation, trophoblast apoptosis is only up-regulated in preeclampsia, because of a hypoxia-reoxygenation-induced switch in generation of proapoptotic Mcl-1 isoforms. PMID:17600131

Direct measurement and characterization of active photosynthesis zones inside biofuel producing and wastewater remediating microalgal biofilms

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

Bernstein, Hans C.; Kesaano, Maureen; Moll, Karen

2014-03-01

Abstract: Microalgal biofilm based technologies are of keen interest due to their high biomass concentrations and ability to utilize renewable resources, such as light and CO2. While photoautotrophic biofilms have long been used for wastewater remediation applications, biofuel production represents a relatively new and under-represented focus area. However, the direct measurement and characterization of fundamental parameters required for physiological analyses are challenging due to biofilm heterogeneity. This study evaluated oxygenic photosynthesis and biofuel precursor molecule production using a novel rotating algal biofilm reactor (RABR) operated at field- and laboratory-scales for wastewater remediation and biofuel production, respectively. Clear differences in oxygenic-photosynthesis,more » respiration and biofuel-precursor capacities were observed between the two systems and different conditions based on light and nitrogen availability. Nitrogen depletion was not found to have the same effect on lipid accumulation compared to prior planktonic studies. Physiological characterizations of these microalgal biofilms identify potential areas for future process optimization.« less

The electrocardiogram signal of Seba's short-tailed bat, Carollia perspicillata.

PubMed

Mihova, Diana; Hechavarría, Julio C

2016-07-01

A number of studies have successfully used electrocardiogram (ECG) signals to characterize complex physiological phenomena such as associative learning in bats. However, at present, no thorough characterization of the structure of ECG signals is available for these animals. The aim of the present study was to quantitatively characterize features of the ECG signals in the bat species Carollia perspicillata, a species that is commonly used in neuroethology studies. Our results show that the ECG signals of C. perspicillata follow the typical mammalian pattern, in that they are composed by a P wave, QRS complex and a T wave. Peak-to-peak amplitudes in the bats' ECG signals were larger in measuring configurations in which one of the electrodes was attached to the right thumb. In addition, large differences in the instantaneous heart rate (HR) distributions were observed between ketamine/xylazine anesthetized and awake bats. Ketamine/xylazine might target the neural circuits that control HR, therefore, instantaneous HR measurements should only be used as physiological marker in awake animals.

Physiological assessment of task underload

NASA Technical Reports Server (NTRS)

Comstock, J. Raymond, Jr.; Harris, Randall L., Sr.; Pope, Alan T.

1988-01-01

The ultimate goal of research efforts directed at underload, boredom, or complacency in high-technology work environments is to detect conditions or states of the operator that can be demonstrated to lead to performance degradation, and then to intervene in the environment to restore acceptable system performance. Physiological measures may provide indices of changes in condition or state of the operator that may be of value in high-technology work environments. The focus of the present study was on the use of physiological measures in the assessment of operator condition or state in a task underload scenario. A fault acknowledgement task characterized by simple repetitive responses with minimal novelty, complexity, and uncertainty was employed to place subjects in a task underload situation. Physiological measures (electrocardiogram (ECG), electroencephalogram (EEG), and pupil diameter) were monitored during task performance over a one-hour test session for 12 subjects. Each of the physiological measures exhibited changes over the test session indicative of decrements in subject arousal level. While high correlations between physiological measures were found across subjects, individual differences between subjects support the use of profiling techniques to establish baselines unique to each subject.

[Diastolic dysfunction in the elderly subjects. Disease or a physiological manifestation of ageing?].

PubMed

Meluzín, J; Podroužková, H; Gregorová, Z; Panovský, R

2013-05-01

The purpose of this summary paper is to discuss the current knowledge of the impact of age on diastolic function of the left ventricle. Data from the literature: Reports published till this time have convincingly demonstrated a significant relationship of age to diastolic function of the left ventricle. Ageing is a physiological process accompanied by structural changes in both myocardium and arterial bed resulting in worsening of parameters characterizing the left ventricular diastolic function. This "physiological" diastolic dysfunction in the elderly subjects can be explained by the deterioration of passive left ventricular filling properties and by worsening of left ventricular relaxation. The detailed analysis of published reports shows problems in distiguishing this "physiological" diastolic dysfunction resulting from physiological tissue ageing from "pathological" diastolic dysfunction reflecting a disease of cardiovascular system. To interprete correctly values of parameters quantifying diastolic function of the left ventricle, one should take into account the age of subjects under the examination. Further studies are necessary to distinguish exactly "physiological" deterioration of diastolic function associated with ageing from really "pathological" diastolic dysfunction in the elderly subjects.

Genetic ablation of P65 subunit of NF-κB in mdx mice to improve muscle physiological function.

PubMed

Yin, Xi; Tang, Ying; Li, Jian; Dzuricky, Anna T; Pu, Chuanqiang; Fu, Freddie; Wang, Bing

2017-10-01

Duchenne muscular dystrophy (DMD) is a genetic muscle disease characterized by dystrophin deficiency. Beyond gene replacement, the question of whether ablation of the p65 gene of nuclear factor-kappa B (NF-κB) in DMD can improve muscle physiology function is unknown. In this study, we investigated muscle physiological improvement in mdx mice (DMD model) with a genetic reduction of NF-κB. Muscle physiological function and histology were studied in 2-month-old mdx/p65 +/- , wild-type, mdx, and human minidystrophin gene transgenic mdx (TghΔDys/mdx) mice. Improved muscle physiological function was found in mdx/p65 +/- mice when compared with mdx mice; however, it was similar to TghΔDys/mdx mice. The results indicate that genetic reduction of p65 levels diminished chronic inflammation in dystrophic muscle, thus leading to amelioration of muscle pathology and improved muscle physiological function. The results show that inhibition of NF-κB may be a promising therapy when combined with gene therapy for DMD. Muscle Nerve 56: 759-767, 2017. © 2016 Wiley Periodicals, Inc.

Physiological and Molecular Characterization of Cephaleuros virescens Occurring in Mango Trees.

PubMed

Vasconcelos, Camila Vilela; Pereira, Fabíola Teodoro; Duarte, Elizabeth Amélia Alves; de Oliveira, Thiago Alves Santos; Peixoto, Nei; Carvalho, Daniel Diego Costa

2018-06-01

The objective of this work was to accomplish the isolation, molecular identification and characterizing the physiology of the causal agent of the algal spot in mango trees. For this purpose, the pathogen growth was assessed in different culture media, with subsequent observation and measurements of the filamentous cells. The molecular identification was made using mycelium obtained from leaf lesions and pure algae colonies grown in culture medium. Descriptions based on DNA sequencing indicated that the algae is Cephaleuros virescens . The algae must be isolated primarily in liquid medium for further pricking into agar medium. The highest mycelial growth average in Petri dishes occurred when the algae were grown in Trebouxia and BBM. Trebouxia enabled larger cells in the filamentous cells when compared to other culture media.

Stem cells and bone: a historical perspective.

PubMed

Bianco, Paolo

2015-01-01

Bone physiology and stem cells were tightly intertwined with one another, both conceptually and experimentally, long before the current explosion of interest in stem cells and so-called regenerative medicine. Bone is home to the two best known and best characterized systems of postnatal stem cells, and it is the only organ in which two stem cells and their dependent lineages coordinate the overall adaptive responses of two major physiological systems. All along, the nature and the evolutionary significance of the interplay of bone and hematopoiesis have remained a major scientific challenge, but also allowed for some of the most spectacular developments in cell biology-based medicine, such as hematopoietic stem cell transplantation. This question recurs in novel forms at multiple turning points over time: today, it finds in the biology of the "niche" its popular phrasing. Entirely new avenues of investigation emerge as a new view of bone in physiology and medicine is progressively established. Looking at bone and stem cells in a historical perspective provides a unique case study to highlight the general evolution of science in biomedicine since the end of World War II to the present day. A paradigm shift in science and in its relation to society and policies occurred in the second half of the XXth century, with major implications thereof for health, industry, drug development, market and society. Current interest in stem cells in bone as in other fields is intertwined with that shift. New opportunities and also new challenges arise. This article is part of a Special Issue entitled "Stem cells and bone". Copyright © 2014. Published by Elsevier Inc.

Neuro-psychopharmacological perspective of Orphan receptors of Rhodopsin (class A) family of G protein-coupled receptors.

PubMed

Khan, Muhammad Zahid; He, Ling

2017-04-01

In the central nervous system (CNS), G protein-coupled receptors (GPCRs) are the most fruitful targets for neuropsychopharmacological drug development. Rhodopsin (class A) is the most studied class of GPCR and includes orphan receptors for which the endogenous ligand is not known or is unclear. Characterization of orphan GPCRs has proven to be challenging, and the production pace of GPCR-based drugs has been incredibly slow. Determination of the functions of these receptors may provide unexpected insight into physiological and neuropathological processes. Advances in various methods and techniques to investigate orphan receptors including in situ hybridization and knockdown/knockout (KD/KO) showed extensive expression of these receptors in the mammalian brain and unmasked their physiological and neuropathological roles. Due to these rapid progress and development, orphan GPCRs are rising as a new and promising class of drug targets for neurodegenerative diseases and psychiatric disorders. This review presents a neuropsychopharmacological perspective of 26 orphan receptors of rhodopsin (class A) family, namely GPR3, GPR6, GPR12, GPR17, GPR26, GPR35, GPR39, GPR48, GPR49, GPR50, GPR52, GPR55, GPR61, GPR62, GPR63, GPR68, GPR75, GPR78, GPR83, GPR84, GPR85, GPR88, GPR153, GPR162, GPR171, and TAAR6. We discussed the expression of these receptors in mammalian brain and their physiological roles. Furthermore, we have briefly highlighted their roles in neurodegenerative diseases and psychiatric disorders including Alzheimer's disease, Parkinson's disease, neuroinflammation, inflammatory pain, bipolar and schizophrenic disorders, epilepsy, anxiety, and depression.

The development of peripartum depressive symptoms is associated with gene polymorphisms of MAOA, 5-HTT and COMT.

PubMed

Doornbos, Bennard; Dijck-Brouwer, D A Janneke; Kema, Ido P; Tanke, Marit A C; van Goor, Saskia A; Muskiet, Frits A J; Korf, Jakob

2009-10-01

Polymorphisms of monoamine-related genes have been associated with depression following life events. The peripartum is a physiologically and psychologically challenging period, characterized by fluctuations in depressive symptoms, therefore facilitating prospective investigations in this gene x environment (G x E) interaction. Eighty nine pregnant women filled in two Edinburgh Postpartum Depression Scale (EPDS) questionnaires during pregnancy and two in the postpartum period. MAOA, COMT and 5-HTT polymorphisms were analyzed. We found a significant interaction between the development of depressive symptoms in the course of pregnancy and polymorphisms in 5-HTT (p=0.019); MAOA (p=0.044) and COMT (p=0.026), and MAOA x COMT (p<0.001). Particularly, women carrying the combination of low activity variants of MAOA and COMT showed increased EPDS scores at week 36 of pregnancy and 6 weeks postpartum, but not during early pregnancy or 12 weeks postpartum. We found that MAOA in combination with COMT appears to regulate not only the stress response in laboratory experiments, but also seems to influence the stress-evoked onset of mood during normal, mild, stressful events, such as experienced in the peripartum period. These findings support the GxE concept for depression, but they underline the complexity of this concept, as the cumulating effects of these polymorphic genes (i.e. MAOA+COMT) might be needed and the effects of these polymorphic genes becomes apparent in special environmental or physiological conditions (i.e. the peripartum period). We therefore suggest that G x E interactions become especially noticeable from longitudinal study designs in specific physiological or social challenging periods.

Culturing and Characterization of Gut Symbiont Burkholderia spp. from the Southern Chinch Bug, Blissus insularis (Hemiptera: Blissidae)

PubMed Central

Buss, Eileen A.; Boucias, Drion G.

2016-01-01

ABSTRACT The phloem-feeding Southern chinch bug, Blissus insularis, harbors a high density of the exocellular bacterial symbiont Burkholderia in the lumen of specialized midgut crypts. Here we developed an organ culture method that initially involved incubating the B. insularis crypts in osmotically balanced insect cell culture medium. This approach enabled the crypt-inhabiting Burkholderia spp. to make a transition to an in vitro environment and to be subsequently cultured in standard bacteriological media. Examinations using ribotyping and BOX-PCR fingerprinting techniques demonstrated that most in vitro-produced bacterial cultures were identical to their crypt-inhabiting Burkholderia counterparts. Genomic and physiological analyses of gut-symbiotic Burkholderia spp. that were isolated individually from two separate B. insularis laboratory colonies revealed that the majority of individual insects harbored a single Burkholderia ribotype in their midgut crypts, resulting in a diverse Burkholderia community within each colony. The diversity was also exhibited by the phenotypic and genotypic characteristics of these Burkholderia cultures. Access to cultures of crypt-inhabiting bacteria provides an opportunity to investigate the interaction between symbiotic Burkholderia spp. and the B. insularis host. Furthermore, the culturing method provides an alternative strategy for establishing in vitro cultures of other fastidious insect-associated bacterial symbionts. IMPORTANCE An organ culture method was developed to establish in vitro cultures of a fastidious Burkholderia symbiont associated with the midgut crypts of the Southern chinch bug, Blissus insularis. The identities of the resulting cultures were confirmed using the genomic and physiological features of Burkholderia cultures isolated from B. insularis crypts, showing that host insects maintained the diversity of Burkholderia spp. over multiple generations. The availability of characterized gut-symbiotic Burkholderia cultures provides a resource for genetic manipulation of these bacteria and for examination of the mechanisms underlying insect-bacterium symbiosis. PMID:27016568

Automated fiber tracking and tissue characterization of the anterior cruciate ligament with optical coherence tomography

NASA Astrophysics Data System (ADS)

Balasubramanian, Priya S.; Guo, Jiaqi; Yao, Xinwen; Qu, Dovina; Lu, Helen H.; Hendon, Christine P.

2017-02-01

The directionality of collagen fibers across the anterior cruciate ligament (ACL) as well as the insertion of this key ligament into bone are important for understanding the mechanical integrity and functionality of this complex tissue. Quantitative analysis of three-dimensional fiber directionality is of particular interest due to the physiological, mechanical, and biological heterogeneity inherent across the ACL-to-bone junction, the behavior of the ligament under mechanical stress, and the usefulness of this information in designing tissue engineered grafts. We have developed an algorithm to characterize Optical Coherence Tomography (OCT) image volumes of the ACL. We present an automated algorithm for measuring ligamentous fiber angles, and extracting attenuation and backscattering coefficients of ligament, interface, and bone regions within mature and immature bovine ACL insertion samples. Future directions include translating this algorithm for real time processing to allow three-dimensional volumetric analysis within dynamically moving samples.

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

PubMed

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

2014-01-01

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

IMART software for correction of motion artifacts in images collected in intravital microscopy

PubMed Central

Dunn, Kenneth W; Lorenz, Kevin S; Salama, Paul; Delp, Edward J

2014-01-01

Intravital microscopy is a uniquely powerful tool, providing the ability to characterize cell and organ physiology in the natural context of the intact, living animal. With the recent development of high-resolution microscopy techniques such as confocal and multiphoton microscopy, intravital microscopy can now characterize structures at subcellular resolution and capture events at sub-second temporal resolution. However, realizing the potential for high resolution requires remarkable stability in the tissue. Whereas the rigid structure of the skull facilitates high-resolution imaging of the brain, organs of the viscera are free to move with respiration and heartbeat, requiring additional apparatus for immobilization. In our experience, these methods are variably effective, so that many studies are compromised by residual motion artifacts. Here we demonstrate the use of IMART, a software tool for removing motion artifacts from intravital microscopy images collected in time series or in three dimensions. PMID:26090271

Structural characterization of a D-isomer specific 2-hydroxyacid dehydrogenase from Lactobacillus delbrueckii ssp. bulgaricus.

PubMed

Holton, Simon J; Anandhakrishnan, Madhankumar; Geerlof, Arie; Wilmanns, Matthias

2013-02-01

Hydroxyacid dehydrogenases, responsible for the stereospecific conversion of 2-keto acids to 2-hydroxyacids in lactic acid producing bacteria, have a range of biotechnology applications including antibiotic synthesis, flavor development in dairy products and the production of valuable synthons. The genome of Lactobacillus delbrueckii ssp. bulgaricus, a member of the heterogeneous group of lactic acid bacteria, encodes multiple hydroxyacid dehydrogenases whose structural and functional properties remain poorly characterized. Here, we report the apo and coenzyme NAD⁺ complexed crystal structures of the L. bulgaricusD-isomer specific 2-hydroxyacid dehydrogenase, D2-HDH. Comparison with closely related members of the NAD-dependent dehydrogenase family reveals that whilst the D2-HDH core fold is structurally conserved, the substrate-binding site has a number of non-canonical features that may influence substrate selection and thus dictate the physiological function of the enzyme. Copyright © 2012 Elsevier Inc. All rights reserved.

Parametric Characterization of Flow Inside Cererbal Aneurysms Treated with Flow-Diverting Stents

NASA Astrophysics Data System (ADS)

Barbour, Michael; Levitt, Michael; Geindreau, Christian; Johnson, Luke; Chivukula, Keshav; Aliseda, Alberto

2017-11-01

Cerebral aneurysms are often treated with a flow-diverting stent (FDS) to reduce blood flow into the aneurysm sac, promoting the development of a stable thrombus. Successful treatment is highly dependent on the degree of flow reduction and the altered hemodynamics inside the aneurysm sac following treatment. Establishing a causal connection between hemodynamic metrics of FDS-treated CAs and long-term clinical outcomes requires a rigorous parametric characterization of this flow environment. We use 3D particle image velocimetry (PIV) to measure the flow inside idealized aneurysm models treated with FDS. Physiologically realistic Reynolds numbers and increasing levels of parent vessel curvature are analyzed to understand the effect of inertia on flow development. The flow velocity into the aneurysm and the topology of the flow inside the sac is shown to be highly dependent on parent vessel Dean number (De). The role of flow pulsatility is then added to the study via time-dependent waveforms. Velocity measurements at 2 values of parent vessel Womersley number (Wo) allow us to parameterize flow inside of CAs treated with FDS as a function of De, Re and Wo, improving the fundamental understanding of how FDS alter CA hemodynamics and aiding in the development of new treatments.

A high throughput array microscope for the mechanical characterization of biomaterials

NASA Astrophysics Data System (ADS)

Cribb, Jeremy; Osborne, Lukas D.; Hsiao, Joe Ping-Lin; Vicci, Leandra; Meshram, Alok; O'Brien, E. Tim; Spero, Richard Chasen; Taylor, Russell; Superfine, Richard

2015-02-01

In the last decade, the emergence of high throughput screening has enabled the development of novel drug therapies and elucidated many complex cellular processes. Concurrently, the mechanobiology community has developed tools and methods to show that the dysregulation of biophysical properties and the biochemical mechanisms controlling those properties contribute significantly to many human diseases. Despite these advances, a complete understanding of the connection between biomechanics and disease will require advances in instrumentation that enable parallelized, high throughput assays capable of probing complex signaling pathways, studying biology in physiologically relevant conditions, and capturing specimen and mechanical heterogeneity. Traditional biophysical instruments are unable to meet this need. To address the challenge of large-scale, parallelized biophysical measurements, we have developed an automated array high-throughput microscope system that utilizes passive microbead diffusion to characterize mechanical properties of biomaterials. The instrument is capable of acquiring data on twelve-channels simultaneously, where each channel in the system can independently drive two-channel fluorescence imaging at up to 50 frames per second. We employ this system to measure the concentration-dependent apparent viscosity of hyaluronan, an essential polymer found in connective tissue and whose expression has been implicated in cancer progression.

Delayed response to cold stress is characterized by successive metabolic shifts culminating in apple fruit peel necrosis.

PubMed

Gapper, Nigel E; Hertog, Maarten L A T M; Lee, Jinwook; Buchanan, David A; Leisso, Rachel S; Fei, Zhangjun; Qu, Guiqin; Giovannoni, James J; Johnston, Jason W; Schaffer, Robert J; Nicolaï, Bart M; Mattheis, James P; Watkins, Christopher B; Rudell, David R

2017-04-21

Superficial scald is a physiological disorder of apple fruit characterized by sunken, necrotic lesions appearing after prolonged cold storage, although initial injury occurs much earlier in the storage period. To determine the degree to which the transition to cell death is an active process and specific metabolism involved, untargeted metabolic and transcriptomic profiling was used to follow metabolism of peel tissue over 180 d of cold storage. The metabolome and transcriptome of peel destined to develop scald began to diverge from peel where scald was controlled using antioxidant (diphenylamine; DPA) or rendered insensitive to ethylene using 1-methylcyclopropene (1-MCP) beginning between 30 and 60 days of storage. Overall metabolic and transcriptomic shifts, representing multiple pathways and processes, occurred alongside α-farnesene oxidation and, later, methanol production alongside symptom development. Results indicate this form of peel necrosis is a product of an active metabolic transition involving multiple pathways triggered by chilling temperatures at cold storage inception rather than physical injury. Among multiple other pathways, enhanced methanol and methyl ester levels alongside upregulated pectin methylesterases are unique to peel that is developing scald symptoms similar to injury resulting from mechanical stress and herbivory in other plants.

Physiological and transcriptional analyses of developmental stages along sugarcane leaf.

PubMed

Mattiello, Lucia; Riaño-Pachón, Diego Mauricio; Martins, Marina Camara Mattos; da Cruz, Larissa Prado; Bassi, Denis; Marchiori, Paulo Eduardo Ribeiro; Ribeiro, Rafael Vasconcelos; Labate, Mônica T Veneziano; Labate, Carlos Alberto; Menossi, Marcelo

2015-12-29

Sugarcane is one of the major crops worldwide. It is cultivated in over 100 countries on 22 million ha. The complex genetic architecture and the lack of a complete genomic sequence in sugarcane hamper the adoption of molecular approaches to study its physiology and to develop new varieties. Investments on the development of new sugarcane varieties have been made to maximize sucrose yield, a trait dependent on photosynthetic capacity. However, detailed studies on sugarcane leaves are scarce. In this work, we report the first molecular and physiological characterization of events taking place along a leaf developmental gradient in sugarcane. Photosynthetic response to CO2 indicated divergence in photosynthetic capacity based on PEPcase activity, corroborated by activity quantification (both in vivo and in vitro) and distinct levels of carbon discrimination on different segments along leaf length. Additionally, leaf segments had contrasting amount of chlorophyll, nitrogen and sugars. RNA-Seq data indicated a plethora of biochemical pathways differentially expressed along the leaf. Some transcription factors families were enriched on each segment and their putative functions corroborate with the distinct developmental stages. Several genes with higher expression in the middle segment, the one with the highest photosynthetic rates, were identified and their role in sugarcane productivity is discussed. Interestingly, sugarcane leaf segments had a different transcriptional behavior compared to previously published data from maize. This is the first report of leaf developmental analysis in sugarcane. Our data on sugarcane is another source of information for further studies aiming to understand and/or improve C4 photosynthesis. The segments used in this work were distinct in their physiological status allowing deeper molecular analysis. Although limited in some aspects, the comparison to maize indicates that all data acquired on one C4 species cannot always be easily extrapolated to other species. However, our data indicates that some transcriptional factors were segment-specific and the sugarcane leaf undergoes through the process of suberizarion, photosynthesis establishment and senescence.

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

NASA Technical Reports Server (NTRS)

Lange, K. A.

1980-01-01

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

Development of a physiologically based pharmacokinetic model of actinomycin D in children with cancer

PubMed Central

Walsh, Christopher; Bonner, Jennifer J.; Johnson, Trevor N.; Neuhoff, Sibylle; Ghazaly, Essam A.; Gribben, John G.; Boddy, Alan V.

2016-01-01

Aims Use of the anti‐tumour antibiotic actinomycin D is associated with development of hepatotoxicity, particularly in young children. A paucity of actinomycin D pharmacokinetic data make it challenging to develop a sound rationale for defining dosing regimens in younger patients. The study aim was to develop a physiologically based pharmacokinetic (PBPK) model using a combination of data from the literature and generated from experimental analyses. Methods Assays to determine actinomycin D Log P, blood:plasma partition ratio and ABCB1 kinetics were conducted. These data were combined with physiochemical properties sourced from the literature to generate a compound file for use within the modelling‐simulation software Simcyp (version 14 release 1). For simulation, information was taken from two datasets, one from 117 patients under the age of 21 and one from 20 patients aged 16–48. Results The final model incorporated clinical renal and biliary clearance data and an additional systemic clearance value. The mean AUC0‐26h of simulated subjects was within 1.25‐fold of the observed AUC0‐26h (84 ng h ml−1 simulated vs. 93 ng h ml−1 observed). For the younger age ranges, AUC predictions were within two‐fold of observed values, with simulated data from six of the eight age/dose ranges falling within 15% of observed data. Simulated values for actinomycin D AUC0‐26h and clearance in infants aged 0–12 months ranged from 104 to 115 ng h ml−1 and 3.5–3.8 l h−1, respectively. Conclusions The model has potential utility for prediction of actinomycin D exposure in younger patients and may help guide future dosing. However, additional independent data from neonates and infants is needed for further validation. Physiological differences between paediatric cancer patients and healthy children also need to be further characterized and incorporated into PBPK models. PMID:26727248

Developing a Nationwide K-12 Outreach Model: Physiology Understanding (PhUn) Week 10 Years Later

ERIC Educational Resources Information Center

Stieben, Margaret; Halpin, Patricia A.; Matyas, Marsha Lakes

2017-01-01

Since 2005, nearly 600 Physiology Understanding Week (PhUn Week) events have taken place across the U.S., involving American Physiological Society (APS) members in K-12 outreach. The program seeks to build student understanding of physiology and physiology careers, assist teachers in recognizing physiology in their standards-based curriculum, and…

DOE Research and Development Accomplishments Nobels in Medicine Associated

Science.gov Websites

Wells Beadle 1958 Physiology or Medicine Sir Peter Mansfield Physiology or Medicine C 1997 Allan M . Cormack 1979 Physiology or Medicine Stanley Prusiner Physiology or Medicine M 1983 Sir Peter Mansfield 2003 Physiology or Medicine Barbara McClintock Physiology or Medicine Barbara McClintock 1983

Keeping the right time in space: importance of circadian clock and sleep for physiology and performance of astronauts.

PubMed

Guo, Jin-Hu; Qu, Wei-Min; Chen, Shan-Guang; Chen, Xiao-Ping; Lv, Ke; Huang, Zhi-Li; Wu, Yi-Lan

2014-01-01

The circadian clock and sleep are essential for human physiology and behavior; deregulation of circadian rhythms impairs health and performance. Circadian clocks and sleep evolved to adapt to Earth's environment, which is characterized by a 24-hour light-dark cycle. Changes in gravity load, lighting and work schedules during spaceflight missions can impact circadian clocks and disrupt sleep, in turn jeopardizing the mood, cognition and performance of orbiting astronauts. In this review, we summarize our understanding of both the influence of the space environment on the circadian timing system and sleep and the impact of these changes on astronaut physiology and performance.

Physiological reactivity to faces via live and video-mediated communication in typical and atypical development.

PubMed

Riby, Deborah M; Whittle, Lisa; Doherty-Sneddon, Gwyneth

2012-01-01

The human face is a powerful elicitor of emotion, which induces autonomic nervous system responses. In this study, we explored physiological arousal and reactivity to affective facial displays shown in person and through video-mediated communication. We compared measures of physiological arousal and reactivity in typically developing individuals and those with the developmental disorders Williams syndrome (WS) and autism spectrum disorder (ASD). Participants attended to facial displays of happy, sad, and neutral expressions via live and video-mediated communication. Skin conductance level (SCL) indicated that live faces, but not video-mediated faces, increased arousal, especially for typically developing individuals and those with WS. There was less increase of SCL, and physiological reactivity was comparable for live and video-mediated faces in ASD. In typical development and WS, physiological reactivity was greater for live than for video-mediated communication. Individuals with WS showed lower SCL than typically developing individuals, suggesting possible hypoarousal in this group, even though they showed an increase in arousal for faces. The results are discussed in terms of the use of video-mediated communication with typically and atypically developing individuals and atypicalities of physiological arousal across neurodevelopmental disorder groups.

State of the Art of Interpersonal Physiology in Psychotherapy: A Systematic Review.

PubMed

Kleinbub, Johann R

2017-01-01

Introduction: The fast expanding field of Interpersonal Physiology (IP) focuses on the study of co-ordination or synchronization dynamics between the physiological activities of two, or more, individuals. IP has been associated with various relational features (e.g., empathy, attachment security, rapport, closeness…) that overlap with desirable characteristics of clinical relationships, suggesting that the relevant studies might provide objective, economical, and theory-free techniques to investigate the clinical process. The goal of the present work is to systematically retrieve and review the literature on IP in the field of psychotherapy and psychological intervention, in order to consolidate the knowledge of this research domain, highlight its critical issues, and delineate possible developments. Method: Following the guidelines by Okoli and Schabram (2010), a systematic literature search was performed in Scopus, Web of Science, PsycINFO, and PubMed databases by means of multiple keyword combinations; the results were integrated with references to the retrieved articles' bibliography as well as to other published reviews on IP. Results: All the retrieved documents reported clinical interactions that are characterized, at least partially, by IP phenomena. They appear to use fragmented and sometimes ambiguous terminology and show a lack of both specific theory-informed hypotheses and sound analytical procedures. Conclusion: Although the psychological nature of IP and its role in the clinical relationship are still mostly unknown, the potential value of a physiology-based measure of implicit exchanges in psychotherapy drives an acceleration in this research field. On the basis of the highlighted critical issues, possible future directions for clinical IP researchers are discussed.

New insights into globoids of protein storage vacuoles in wheat aleurone using synchrotron soft X-ray microscopy

PubMed Central

Regvar, Marjana; Eichert, Diane; Kaulich, Burkhard; Gianoncelli, Alessandra; Pongrac, Paula; Vogel-Mikuš, Katarina; Kreft, Ivan

2011-01-01

Mature developed seeds are physiologically and biochemically committed to store nutrients, principally as starch, protein, oils, and minerals. The composition and distribution of elements inside the aleurone cell layer reflect their biogenesis, structural characteristics, and physiological functions. It is therefore of primary importance to understand the mechanisms underlying metal ion accumulation, distribution, storage, and bioavailability in aleurone subcellular organelles for seed fortification purposes. Synchrotron radiation soft X-ray full-field imaging mode (FFIM) and low-energy X-ray fluorescence (LEXRF) spectromicroscopy were applied to characterize major structural features and the subcellular distribution of physiologically important elements (Zn, Fe, Na, Mg, Al, Si, and P). These direct imaging methods reveal the accumulation patterns between the apoplast and symplast, and highlight the importance of globoids with phytic acid mineral salts and walls as preferential storage structures. C, N, and O chemical topographies are directly linked to the structural backbone of plant substructures. Zn, Fe, Na, Mg, Al, and P were linked to globoid structures within protein storage vacuoles with variable levels of co-localization. Si distribution was atypical, being contained in the aleurone apoplast and symplast, supporting a physiological role for Si in addition to its structural function. These results reveal that the immobilization of metals within the observed endomembrane structures presents a structural and functional barrier and affects bioavailability. The combination of high spatial and chemical X-ray microscopy techniques highlights how in situ analysis can yield new insights into the complexity of the wheat aleurone layer, whose precise biochemical composition, morphology, and structural characteristics are still not unequivocally resolved. PMID:21447756

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

PubMed

Kelliher, Kevin R; Wersinger, Scott R

2009-01-01

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

Gynecomastia in Infants, Children, and Adolescents.

PubMed

Leung, Alexander K C; Leung, Alexander A C

2017-01-01

Gynecomastia may occur physiologically in the neonatal period, during puberty, and in old age. It may also develop in association with various pathologic states. The challenge for the physician is to distinguish physiological gynecomastia from those with an underlying pathology. To review in depth the pathophysiology, clinical manifestations, and treatment of gynecomastia. A PubMed search was completed in Clinical Queries using the key term "gynecomastia". Patents were searched using the key term "gynecomastia" from www.google.com/patents, www.uspto.gov, and www.freepatentsonline.com. Gynecomastia is caused by an imbalance between the stimulatory effect of estrogen and the inhibitory effect of androgen at the breast tissue level. Clinically, gynecomastia is characterized by the presence of a firm or rubbery, discrete, subareolar ridge of glandular tissue that is symmetrical in shape, freely movable, and nonadherent to skin or underlying tissue. Since most cases of physiological gynecomastia regress spontaneously with time, reassurance is all that is necessary. For pathological gynecomastia, treatment should be directed at the underlying cause, if possible. If gynecomastia persists in spite of the above measures, pharmacologic therapy and reduction mammoplasty may be considered. Recent patents related to the management of gynecomastia are discussed. The majority of cases are physiological and do not require treatment other than reassurance. For pathological cases, the underlying cause should be treated if possible. If gynecomastia persists in spite of the above measures and treatment becomes necessary, tamoxifen is the treatment of choice. Reduction mammoplasty may be considered for resistant cases. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Cenozoic climate change shaped the evolutionary ecophysiology of the Cupressaceae conifers

PubMed Central

Pittermann, Jarmila; Stuart, Stephanie A.; Dawson, Todd E.; Moreau, Astrid

2012-01-01

The Cupressaceae clade has the broadest diversity in habitat and morphology of any conifer family. This clade is characterized by highly divergent physiological strategies, with deciduous swamp-adapted genera-like Taxodium at one extreme, and evergreen desert genera-like Cupressus at the other. The size disparity within the Cupressaceae is equally impressive, with members ranging from 5-m-tall juniper shrubs to 100-m-tall redwood trees. Phylogenetic studies demonstrate that despite this variation, these taxa all share a single common ancestor; by extension, they also share a common ancestral habitat. Here, we use a common-garden approach to compare xylem and leaf-level physiology in this family. We then apply comparative phylogenetic methods to infer how Cenozoic climatic change shaped the morphological and physiological differences between modern-day members of the Cupressaceae. Our data show that drought-resistant crown clades (the Cupressoid and Callitroid clades) most likely evolved from drought-intolerant Mesozoic ancestors, and that this pattern is consistent with proposed shifts in post-Eocene paleoclimates. We also provide evidence that within the Cupressaceae, the evolution of drought-resistant xylem is coupled to increased carbon investment in xylem tissue, reduced xylem transport efficiency, and at the leaf level, reduced photosynthetic capacity. Phylogenetically based analyses suggest that the ancestors of the Cupressaceae were dependent upon moist habitats, and that drought-resistant physiology developed along with increasing habitat aridity from the Oligocene onward. We conclude that the modern biogeography of the Cupressaceae conifers was shaped in large part by their capacity to adapt to drought. PMID:22628565

Cenozoic climate change shaped the evolutionary ecophysiology of the Cupressaceae conifers.

PubMed

Pittermann, Jarmila; Stuart, Stephanie A; Dawson, Todd E; Moreau, Astrid

2012-06-12

The Cupressaceae clade has the broadest diversity in habitat and morphology of any conifer family. This clade is characterized by highly divergent physiological strategies, with deciduous swamp-adapted genera-like Taxodium at one extreme, and evergreen desert genera-like Cupressus at the other. The size disparity within the Cupressaceae is equally impressive, with members ranging from 5-m-tall juniper shrubs to 100-m-tall redwood trees. Phylogenetic studies demonstrate that despite this variation, these taxa all share a single common ancestor; by extension, they also share a common ancestral habitat. Here, we use a common-garden approach to compare xylem and leaf-level physiology in this family. We then apply comparative phylogenetic methods to infer how Cenozoic climatic change shaped the morphological and physiological differences between modern-day members of the Cupressaceae. Our data show that drought-resistant crown clades (the Cupressoid and Callitroid clades) most likely evolved from drought-intolerant Mesozoic ancestors, and that this pattern is consistent with proposed shifts in post-Eocene paleoclimates. We also provide evidence that within the Cupressaceae, the evolution of drought-resistant xylem is coupled to increased carbon investment in xylem tissue, reduced xylem transport efficiency, and at the leaf level, reduced photosynthetic capacity. Phylogenetically based analyses suggest that the ancestors of the Cupressaceae were dependent upon moist habitats, and that drought-resistant physiology developed along with increasing habitat aridity from the Oligocene onward. We conclude that the modern biogeography of the Cupressaceae conifers was shaped in large part by their capacity to adapt to drought.

Physiological time model of Scirpophaga incertulas (Lepidoptera: Pyralidae) in rice in Guandong Province, People's Republic of China.

PubMed

Stevenson, Douglass E; Feng, Ge; Zhang, Runjie; Harris, Marvin K

2005-08-01

Scirpophaga incertulas (Walker) (Lepidoptera: Pyralidae) is autochthonous and monophagous on rice, Oryza spp., which favors the development of a physiological time model using degree-days (degrees C) to establish a well defined window during which adults will be present in fields. Model development of S. incertulas adult flight phenology used climatic data and historical field observations of S. incertulas from 1962 through 1988. Analysis of variance was used to evaluate 5,203 prospective models with starting dates ranging from 1 January (day 1) to 30 April (day 121) and base temperatures ranging from -3 through 18.5 degrees C. From six candidate models, which shared the lowest standard deviation of prediction error, a model with a base temperature of 10 degrees C starting on 19 January was selected for validation. Validation with linear regression evaluated the differences between predicted and observed events and showed the model consistently predicted phenological events of 10 to 90% cumulative flight activity within a 3.5-d prediction interval regarded as acceptable for pest management decision making. The degree-day phenology model developed here is expected to find field application in Guandong Province. Expansion to other areas of rice production will require field validation. We expect the degree-day characterization of the activity period will remain essentially intact, but the start day may vary based on climate and geographic location. The development and validation of the phenology model of the S. incertulas by using procedures originally developed for pecan nut casebearer, Acrobasis nuxvorella Neunzig, shows the fungibility of this approach to developing prediction models for other insects.

Proteome regulation during Olea europaea fruit development.

PubMed

Bianco, Linda; Alagna, Fiammetta; Baldoni, Luciana; Finnie, Christine; Svensson, Birte; Perrotta, Gaetano

2013-01-01

Widespread in the Mediterranean basin, Olea europaea trees are gaining worldwide popularity for the nutritional and cancer-protective properties of the oil, mechanically extracted from ripe fruits. Fruit development is a physiological process with remarkable impact on the modulation of the biosynthesis of compounds affecting the quality of the drupes as well as the final composition of the olive oil. Proteomics offers the possibility to dig deeper into the major changes during fruit development, including the important phase of ripening, and to classify temporal patterns of protein accumulation occurring during these complex physiological processes. In this work, we started monitoring the proteome variations associated with olive fruit development by using comparative proteomics coupled to mass spectrometry. Proteins extracted from drupes at three different developmental stages were separated on 2-DE and subjected to image analysis. 247 protein spots were revealed as differentially accumulated. Proteins were identified from a total of 121 spots and discussed in relation to olive drupe metabolic changes occurring during fruit development. In order to evaluate if changes observed at the protein level were consistent with changes of mRNAs, proteomic data produced in the present work were compared with transcriptomic data elaborated during previous studies. This study identifies a number of proteins responsible for quality traits of cv. Coratina, with particular regard to proteins associated to the metabolism of fatty acids, phenolic and aroma compounds. Proteins involved in fruit photosynthesis have been also identified and their pivotal contribution in oleogenesis has been discussed. To date, this study represents the first characterization of the olive fruit proteome during development, providing new insights into fruit metabolism and oil accumulation process.

Contribution of Phenological and Physiological Variations on Northern Vegetation Productivity Changes over Last Three Decades

NASA Technical Reports Server (NTRS)

Ganguly, Sangram

2015-01-01

Plant phenology and maximum photosynthetic state determine spatiotemporal variability of gross primary productivity (GPP) of vegetation. Recent warming induced impacts accelerate shifts of phenology and physiological status over Northern vegetated land. Thus, understanding and quantifying these changes are very important. Here, we investigate 1) how vegetation phenology and physiological status (maximum photosynthesis) are evolved over last three decades and 2) how such components (phenology and physiological status) contribute on inter-annual variation of the GPP during the last three decades. We utilized both long-term remotely sensed (GIMMS (Global Inventory Modeling and Mapping Studies), NDVI3g (Normalized Difference Vegetation Index 3rd generation) and MODIS (Moderate Resolution Imaging Spectroradiometer)) to extract larger scale phenology metrics (growing season start, end and duration); and productivity (i.e., growing season integrated vegetation index, GSIVI) to answer these questions. For evaluation purpose, we also introduced field-measured phenology and productivity datasets (e.g., FLUXNET) and possible remotely-sensed and modeled metrics at continental and regional scales. From this investigation, we found that onset of the growing season has advanced by 1.61 days per decade and the growing season end has delayed by 0.67 days per decade over the circumpolar region. This asymmetric extension of growing season results in a longer growing-season trend (2.96 days per decade) and widespread increasing vegetation-productivity trend (2.96 GSIVI per decade) over Northern land. However, the regionally-diverged phenology shift and maximum photosynthetic state contribute differently characterized productivity, inter-annual variability and trend. We quantified that about 50 percent, 13 percent and 6.5 percent of Northern land's inter-annual variability are dominantly controlled by the onset of the growing season, the end of the growing season and the maximum photosynthetic state, respectively. Productivity characterization over the other approximately 30 percent region has been driven by these co-dominant drivers. Our study clearly shows that regionally different contribution of phenological and physiological components on characterizing vegetation production over the last three decades.

Convergence of goals: phylogenetical, morphological, and physiological characterization of tolerance to drought stress in tall fescue (Festuca arundinacea Schreb.).

PubMed

Salehi, Mohammadreza; Salehi, Hassan; xNiazi, Hassan; Ghobadi, Cyrus

2014-03-01

The aim of this study is to find Iranian tall fescue accessions that tolerate drought stress and investigation on phylogenetical, morphological, and physiological characterization of them. For this propose, inter-simple sequence repeats (ISSR) markers were used to examine the genetic variability of accessions from different provinces of Iran. Of 21 primers, 20 primers generated highly reproducible fragments. Using these primers, 390 discernible DNA fragments were produced with 367 (93.95 %) being polymorphic. The polymorphic information content (PIC) values ranged from 0.948 to 0.976, with a mean PIC value of 0.969. Probability identity (PI) and discriminating power (D = 1-PI) among the primers ranged from 0.001 to 0.004 and 0.998 to 0.995, respectively. A binary qualitative data matrix was constructed. Data analyses were performed using the NTSYS software and the similarity values were used to generate a dendrogram via UPGMA. To study the drought stress, plants were irrigated at 25 % FC condition for three times. Fresh leaves were collected to measure physiological characters including: superoxide dismutase, catalase, and peroxidase activities and proline and total chlorophyll content at two times, before and after stress application. Relative water content, fresh and dry weight ratio, survival percentage, and visual quality were evaluated after stress. Morphological and physiological characters were assessed in order to classify accessions as either tolerant or sensitive using Ward's method of Hierarchical cluster analysis in SPSS software. The results of present study demonstrated that the ISSR markers are useful for studying tall fescue genetic diversity. Convergence of morphological and physiological characterizations during drought stress and phylogenetic relationship results showed that accessions can be grouped into four clusters; drought-tolerant accessions that collected from west of Iran, drought-tolerant accessions collected from northwest of Iran, drought semi-tolerant accessions collected from center of Iran, and drought-sensitive accessions collected from north of Iran. Data presented could be used to classify the tall fescue accessions based on suitability of cultivation in the regions studied or the regions with the similar environmental condition.

Hyaluronic Acid in Vascular and Immune Homeostasis during Normal Pregnancy and Preeclampsia

PubMed Central

Ziganshina, M. M.; Pavlovich, S. V.; Bovin, N. V.; Sukhikh, G. T.

2016-01-01

Preeclampsia (PE) is a multisystem pathologic state that clinically manifests itself after the 20th week of pregnancy. It is characterized by high maternal and perinatal morbidity and mortality. According to modern concepts, the impairment of trophoblast invasion into maternal spiral arteries, leading to the development of ischemia in placenta, is considered to be the major pathogenetic factor of PE development. Ischemic lesions initiate the development of a systemic inflammatory response (SIR) and endothelial dysfunction, which is the main cause of the multiple organ failure in PE. Some data has appear indicating the importance of a glycans-forming endothelial glycocalyx and extracellular matrix (ECM) for placenta morphogenesis, as well as their role in the regulation of vascular permeability and vascular tone in hypertension disorders and, in particular, PE. Since intact glycocalyx and ECM are considered to be the major factors that maintain the physiological vascular tone and adequate intercellular interactions, their value in PE pathogenesis is underestimated. This review is focused on hyaluronic acid (HA) as the key glycan providing the organization and stabilization of the ECM and glycocalyx, its distribution in tissues in the case of presence or absence of placental pathology, as well as on the regulatory function of hyaluronic acids of various molecular weights in different physiological and pathophysiological processes. The summarized data will provide a better understanding of the PE pathogenesis, with the main focus on glycopathology. PMID:27795844

Isolation, Characterization, and Ecology of Sulfur-Respiring Crenarchaea Inhabiting Acid-Sulfate-Chloride-Containing Geothermal Springs in Yellowstone National Park▿ †

PubMed Central

Boyd, Eric S.; Jackson, Robert A.; Encarnacion, Gem; Zahn, James A.; Beard, Trevor; Leavitt, William D.; Pi, Yundan; Zhang, Chuanlun L.; Pearson, Ann; Geesey, Gill G.

2007-01-01

Elemental sulfur (S0) is associated with many geochemically diverse hot springs, yet little is known about the phylogeny, physiology, and ecology of the organisms involved in its cycling. Here we report the isolation, characterization, and ecology of two novel, S0-reducing Crenarchaea from an acid geothermal spring referred to as Dragon Spring. Isolate 18U65 grows optimally at 70 to 72°C and at pH 2.5 to 3.0, while isolate 18D70 grows optimally at 81°C and pH 3.0. Both isolates are chemoorganotrophs, dependent on complex peptide-containing carbon sources, S0, and anaerobic conditions for respiration-dependent growth. Glycerol dialkyl glycerol tetraethers (GDGTs) containing four to six cyclopentyl rings were present in the lipid fraction of isolates 18U65 and 18D70. Physiological characterization suggests that the isolates are adapted to the physicochemical conditions of Dragon Spring and can utilize the natural organic matter in the spring as a carbon and energy source. Quantitative PCR analysis of 16S rRNA genes associated with the S0 flocs recovered from several acid geothermal springs using isolate-specific primers indicates that these two populations together represent 17 to 37% of the floc-associated DNA. The physiological characteristics of isolates 18U65 and 18D70 are consistent with their potential widespread distribution and putative role in the cycling of sulfur in acid geothermal springs throughout the Yellowstone National Park geothermal complex. Based on phenotypic and genetic characterization, the designations Caldisphaera draconis sp. nov. and Acidilobus sulfurireducens sp. nov. are proposed for isolates 18U65 and 18D70, respectively. PMID:17720836

Exercise Is More Effective at Altering Gut Microbial Composition and Producing Stable Changes in Lean Mass in Juvenile versus Adult Male F344 Rats

PubMed Central

Mika, Agnieszka; Van Treuren, Will; González, Antonio; Herrera, Jonathan J.; Knight, Rob; Fleshner, Monika

2015-01-01

The mammalian intestine harbors a complex microbial ecosystem that influences many aspects of host physiology. Exposure to specific microbes early in development affects host metabolism, immune function, and behavior across the lifespan. Just as the physiology of the developing organism undergoes a period of plasticity, the developing microbial ecosystem is characterized by instability and may also be more sensitive to change. Early life thus presents a window of opportunity for manipulations that produce adaptive changes in microbial composition. Recent insights have revealed that increasing physical activity can increase the abundance of beneficial microbial species. We therefore investigated whether six weeks of wheel running initiated in the juvenile period (postnatal day 24) would produce more robust and stable changes in microbial communities versus exercise initiated in adulthood (postnatal day 70) in male F344 rats. 16S rRNA gene sequencing was used to characterize the microbial composition of juvenile versus adult runners and their sedentary counterparts across multiple time points during exercise and following exercise cessation. Alpha diversity measures revealed that the microbial communities of young runners were less even and diverse, a community structure that reflects volatility and malleability. Juvenile onset exercise altered several phyla and, notably, increased Bacteroidetes and decreased Firmicutes, a configuration associated with leanness. At the genus level of taxonomy, exercise altered more genera in juveniles than in the adults and produced patterns associated with adaptive metabolic consequences. Given the potential of these changes to contribute to a lean phenotype, we examined body composition in juvenile versus adult runners. Interestingly, exercise produced persistent increases in lean body mass in juvenile but not adult runners. Taken together, these results indicate that the impact of exercise on gut microbiota composition as well as body composition may depend on the developmental stage during which exercise is initiated. PMID:26016739

Systems pharmacology - Towards the modeling of network interactions.

PubMed

Danhof, Meindert

2016-10-30

Mechanism-based pharmacokinetic and pharmacodynamics (PKPD) and disease system (DS) models have been introduced in drug discovery and development research, to predict in a quantitative manner the effect of drug treatment in vivo in health and disease. This requires consideration of several fundamental properties of biological systems behavior including: hysteresis, non-linearity, variability, interdependency, convergence, resilience, and multi-stationarity. Classical physiology-based PKPD models consider linear transduction pathways, connecting processes on the causal path between drug administration and effect, as the basis of drug action. Depending on the drug and its biological target, such models may contain expressions to characterize i) the disposition and the target site distribution kinetics of the drug under investigation, ii) the kinetics of target binding and activation and iii) the kinetics of transduction. When connected to physiology-based DS models, PKPD models can characterize the effect on disease progression in a mechanistic manner. These models have been found useful to characterize hysteresis and non-linearity, yet they fail to explain the effects of the other fundamental properties of biological systems behavior. Recently systems pharmacology has been introduced as novel approach to predict in vivo drug effects, in which biological networks rather than single transduction pathways are considered as the basis of drug action and disease progression. These models contain expressions to characterize the functional interactions within a biological network. Such interactions are relevant when drugs act at multiple targets in the network or when homeostatic feedback mechanisms are operative. As a result systems pharmacology models are particularly useful to describe complex patterns of drug action (i.e. synergy, oscillatory behavior) and disease progression (i.e. episodic disorders). In this contribution it is shown how physiology-based PKPD and disease models can be extended to account for internal systems interactions. It is demonstrated how SP models can be used to predict the effects of multi-target interactions and of homeostatic feedback on the pharmacological response. In addition it is shown how DS models may be used to distinguish symptomatic from disease modifying effects and to predict the long term effects on disease progression, from short term biomarker responses. It is concluded that incorporation of expressions to describe the interactions in biological network analysis opens new avenues to the understanding of the effects of drug treatment on the fundamental aspects of biological systems behavior. Copyright © 2016 The Author. Published by Elsevier B.V. All rights reserved.

Heterogeneous Optimization Framework: Reproducible Preprocessing of Multi-Spectral Clinical MRI for Neuro-Oncology Imaging Research.

PubMed

Milchenko, Mikhail; Snyder, Abraham Z; LaMontagne, Pamela; Shimony, Joshua S; Benzinger, Tammie L; Fouke, Sarah Jost; Marcus, Daniel S

2016-07-01

Neuroimaging research often relies on clinically acquired magnetic resonance imaging (MRI) datasets that can originate from multiple institutions. Such datasets are characterized by high heterogeneity of modalities and variability of sequence parameters. This heterogeneity complicates the automation of image processing tasks such as spatial co-registration and physiological or functional image analysis. Given this heterogeneity, conventional processing workflows developed for research purposes are not optimal for clinical data. In this work, we describe an approach called Heterogeneous Optimization Framework (HOF) for developing image analysis pipelines that can handle the high degree of clinical data non-uniformity. HOF provides a set of guidelines for configuration, algorithm development, deployment, interpretation of results and quality control for such pipelines. At each step, we illustrate the HOF approach using the implementation of an automated pipeline for Multimodal Glioma Analysis (MGA) as an example. The MGA pipeline computes tissue diffusion characteristics of diffusion tensor imaging (DTI) acquisitions, hemodynamic characteristics using a perfusion model of susceptibility contrast (DSC) MRI, and spatial cross-modal co-registration of available anatomical, physiological and derived patient images. Developing MGA within HOF enabled the processing of neuro-oncology MR imaging studies to be fully automated. MGA has been successfully used to analyze over 160 clinical tumor studies to date within several research projects. Introduction of the MGA pipeline improved image processing throughput and, most importantly, effectively produced co-registered datasets that were suitable for advanced analysis despite high heterogeneity in acquisition protocols.

Design and characterization of a novel multimodal fiber-optic probe and spectroscopy system for skin cancer applications

PubMed Central

Sharma, Manu; Marple, Eric; Reichenberg, Jason; Tunnell, James W.

2014-01-01

The design and characterization of an instrument combining Raman, fluorescence, and reflectance spectroscopic modalities is presented. Instrument development has targeted skin cancer applications as a novel fiber-optic probe has been specially designed to interrogate cutaneous lesions. The instrument is modular and both its software and hardware components are described in depth. Characterization of the fiber-optic probe is also presented, which details the probe's ability to measure diagnostically important parameters such as intrinsic fluorescence and absorption and reduced scattering coefficients along with critical performance metrics such as high Raman signal-to-noise ratios at clinically practical exposure times. Validation results using liquid phantoms show that the probe and system can extract absorption and scattering coefficients with less than 10% error. As the goal is to use the instrument for the clinical early detection of skin cancer, preliminary clinical data are also presented, which indicates our system's ability to measure physiological quantities such as relative collagen and nicotinamide adenine dinucleotide concentration, oxygen saturation, blood volume fraction, and mean vessel diameter. PMID:25173240

Discovery and characterization of proteins associated with aflatoxin-resistance: evaluating their potential as breeding markers.

PubMed

Brown, Robert L; Chen, Zhi-Yuan; Warburton, Marilyn; Luo, Meng; Menkir, Abebe; Fakhoury, Ahmad; Bhatnagar, Deepak

2010-04-01

Host resistance has become a viable approach to eliminating aflatoxin contamination of maize since the discovery of several maize lines with natural resistance. However, to derive commercial benefit from this resistance and develop lines that can aid growers, markers need to be identified to facilitate the transfer of resistance into commercially useful genetic backgrounds without transfer of unwanted traits. To accomplish this, research efforts have focused on the identification of kernel resistance-associated proteins (RAPs) including the employment of comparative proteomics to investigate closely-related maize lines that vary in aflatoxin accumulation. RAPs have been identified and several further characterized through physiological and biochemical investigations to determine their causal role in resistance and, therefore, their suitability as breeding markers. Three RAPs, a 14 kDa trypsin inhibitor, pathogenesis-related protein 10 and glyoxalase I are being investigated using RNAi gene silencing and plant transformation. Several resistant lines have been subjected to QTL mapping to identify loci associated with the aflatoxin-resistance phenotype. Results of proteome and characterization studies are discussed.

Fast-scan Cyclic Voltammetry for the Characterization of Rapid Adenosine Release.

PubMed

Nguyen, Michael D; Venton, B Jill

2015-01-01

Adenosine is a signaling molecule and downstream product of ATP that acts as a neuromodulator. Adenosine regulates physiological processes, such as neurotransmission and blood flow, on a time scale of minutes to hours. Recent developments in electrochemical techniques, including fast-scan cyclic voltammetry (FSCV), have allowed direct detection of adenosine with sub-second temporal resolution. FSCV studies have revealed a novel mode of rapid signaling that lasts only a few seconds. This rapid release of adenosine can be evoked by electrical or mechanical stimulations or it can be observed spontaneously without stimulation. Adenosine signaling on this time scale is activity dependent; however, the mode of release is not fully understood. Rapid adenosine release modulates oxygen levels and evoked dopamine release, indicating that adenosine may have a rapid modulatory role. In this review, we outline how FSCV can be used to detect adenosine release, compare FSCV with other techniques used to measure adenosine, and present an overview of adenosine signaling that has been characterized using FSCV. These studies point to a rapid mode of adenosine modulation, whose mechanism and function will continue to be characterized in the future.

As-yet-uncultivated oral bacteria: breadth and association with oral and extra-oral diseases

PubMed Central

Siqueira, José F.; Rôças, Isabela N.

2013-01-01

It has been shown that 40–60% of the bacteria found in different healthy and diseased oral sites still remain to be grown in vitro, phenotypically characterized, and formally named as species. The possibility exists that these as-yet-uncultivated bacteria play important ecological roles in oral bacterial communities and may participate in the pathogenesis of several oral infectious diseases. There is also a potential for these as-yet-uncultivated oral bacteria to take part in extra-oral infections. For a comprehensive characterization of physiological and pathogenic properties as well as antimicrobial susceptibility of individual bacterial species, strains need to be grown in pure culture. Advances in culturing techniques have allowed the cultivation of several oral bacterial taxa only previously known by a 16S rRNA gene sequence signature, and novel species have been proposed. There is a growing need for developing improved methods to cultivate and characterize the as-yet-uncultivated portion of the oral microbiome so as to unravel its role in health and disease. PMID:23717756

Replicable in vivo physiological and behavioral phenotypes of the Shank3B null mutant mouse model of autism.

PubMed

Dhamne, Sameer C; Silverman, Jill L; Super, Chloe E; Lammers, Stephen H T; Hameed, Mustafa Q; Modi, Meera E; Copping, Nycole A; Pride, Michael C; Smith, Daniel G; Rotenberg, Alexander; Crawley, Jacqueline N; Sahin, Mustafa

2017-01-01

Autism spectrum disorder (ASD) is a clinically and biologically heterogeneous condition characterized by social, repetitive, and sensory behavioral abnormalities. No treatments are approved for the core diagnostic symptoms of ASD. To enable the earliest stages of therapeutic discovery and development for ASD, robust and reproducible behavioral phenotypes and biological markers are essential to establish in preclinical animal models. The goal of this study was to identify electroencephalographic (EEG) and behavioral phenotypes that are replicable between independent cohorts in a mouse model of ASD. The larger goal of our strategy is to empower the preclinical biomedical ASD research field by generating robust and reproducible behavioral and physiological phenotypes in animal models of ASD, for the characterization of mechanistic underpinnings of ASD-relevant phenotypes, and to ensure reliability for the discovery of novel therapeutics. Genetic disruption of the SHANK3 gene, a scaffolding protein involved in the stability of the postsynaptic density in excitatory synapses, is thought to be responsible for a relatively large number of cases of ASD. Therefore, we have thoroughly characterized the robustness of ASD-relevant behavioral phenotypes in two cohorts, and for the first time quantified translational EEG activity in Shank3B null mutant mice. In vivo physiology and behavioral assays were conducted in two independently bred and tested full cohorts of Shank3B null mutant ( Shank3B KO) and wildtype littermate control (WT) mice. EEG was recorded via wireless implanted telemeters for 7 days of baseline followed by 20 min of recording following pentylenetetrazol (PTZ) challenge. Behaviors relevant to the diagnostic and associated symptoms of ASD were tested on a battery of established behavioral tests. Assays were designed to reproduce and expand on the original behavioral characterization of Shank3B KO mice. Two or more corroborative tests were conducted within each behavioral domain, including social, repetitive, cognitive, anxiety-related, sensory, and motor categories of assays. Relative to WT mice, Shank3B KO mice displayed a dramatic resistance to PTZ seizure induction and an enhancement of gamma band oscillatory EEG activity indicative of enhanced inhibitory tone. These findings replicated in two separate cohorts. Behaviorally, Shank3B KO mice exhibited repetitive grooming, deficits in aspects of reciprocal social interactions and vocalizations, and reduced open field activity, as well as variable deficits in sensory responses, anxiety-related behaviors, learning and memory. Robust animal models and quantitative, replicable biomarkers of neural dysfunction are needed to decrease risk and enable successful drug discovery and development for ASD and other neurodevelopmental disorders. Complementary to the replicated behavioral phenotypes of the Shank3B mutant mouse is the new identification of a robust, translational in vivo neurophysiological phenotype. Our findings provide strong evidence for robustness and replicability of key translational phenotypes in Shank3B mutant mice and support the usefulness of this mouse model of ASD for therapeutic discovery.

Detection and Evaluation of Early Breast Cancer via Magnetic Resonance Imaging: Studies of Mouse Models and Clinical Implementation

DTIC Science & Technology

2009-03-01

compartment modeling on breast 3D DCE-MRI data, to relate kinetic curves to the underlying physiology of the lesions (14–18). However, for low time...classification provided high sensitivity and low specificity in diagnosing malignant lesions. The results demonstrated that the modified EMM fit the 3D...lesion localization and characterization.11 However, for low time resolution 3D DCEMRI data, the accuracy of physiological parameters ob- tained from

Differences in autonomic physiological responses between good and poor inductive reasoners.

PubMed

Melis, C; van Boxtel, A

2001-11-01

We investigated individual- and task-related differences in autonomic physiological responses induced by time limited figural and verbal inductive reasoning tasks. In a group of 52 participants, the percentage of correctly responded task items was evaluated together with nine different autonomic physiological response measures and respiration rate (RR). Weighted multidimensional scaling analyses of the physiological responses revealed three underlying dimensions, primarily characterized by RR, parasympathetic, and sympathetic activity. RR and sympathetic activity appeared to be relatively more important response dimensions for poor reasoners, whereas parasympathetic responsivity was relatively more important for good reasoners. These results suggest that poor reasoners showed higher levels of cognitive processing intensity than good reasoners. Furthermore, for the good reasoners, the dimension of sympathetic activity was relatively more important during the figural than during the verbal reasoning task, which was explained in terms of hemispheric lateralization in autonomic function.

The physiology of invasive plants in low-resource environments

PubMed Central

Funk, Jennifer L.

2013-01-01

While invasive plant species primarily occur in disturbed, high-resource environments, many species have invaded ecosystems characterized by low nutrient, water, and light availability. Species adapted to low-resource systems often display traits associated with resource conservation, such as slow growth, high tissue longevity, and resource-use efficiency. This contrasts with our general understanding of invasive species physiology derived primarily from studies in high-resource environments. These studies suggest that invasive species succeed through high resource acquisition. This review examines physiological and morphological traits of native and invasive species in low-resource environments. Existing data support the idea that species invading low-resource environments possess traits associated with resource acquisition, resource conservation or both. Disturbance and climate change are affecting resource availability in many ecosystems, and understanding physiological differences between native and invasive species may suggest ways to restore invaded ecosystems. PMID:27293610

Physiological reactivity to phobic stimuli in people with fear of flying.

PubMed

Busscher, Bert; van Gerwen, Lucas J; Spinhoven, Philip; de Geus, Eco J C

2010-09-01

The nature of the relationship between physiological and subjective responses in phobic subjects remains unclear. Phobics have been thought to be characterized by a heightened physiological response (physiological perspective) or by a heightened perception of a normal physiological response (psychological perspective). In this study, we examined subjective measures of anxiety, heart rate (HR), and cardiac autonomic responses to flight-related stimuli in 127 people who applied for fear-of-flying therapy at a specialized treatment center and in 36 controls without aviophobia. In keeping with the psychological perspective, we found a large increase in subjective distress (eta(2)=.43) during exposure to flight-related stimuli in the phobics and no change in subjective distress in the controls, whereas the physiological responses of both groups were indiscriminate. However, in keeping with the physiological perspective, we found that, within the group of phobics, increases in subjective fear during exposure were moderately strong coupled to HR (r =.208, P=.022) and cardiac vagal (r =.199, P=.028) reactivity. In contrast to predictions by the psychological perspective, anxiety sensitivity did not modulate this coupling. We conclude that subjective fear responses and autonomic responses are only loosely coupled during mildly threatening exposure to flight-related stimuli. More ecologically valid exposure to phobic stimuli may be needed to test the predictions from the physiological and psychological perspectives. Copyright (c) 2010 Elsevier Inc. All rights reserved.

Biomolecule recognition using piezoresistive nanomechanical force probes

NASA Astrophysics Data System (ADS)

Tosolini, Giordano; Scarponi, Filippo; Cannistraro, Salvatore; Bausells, Joan

2013-06-01

Highly sensitive sensors are one of the enabling technologies for the biomarker detection in early stage diagnosis of pathologies. We have developed a self-sensing nanomechanical force probe able for detecting the unbinding of single couples of biomolecular partners in nearly physiological conditions. The embedding of a piezoresistive transducer into a nanomechanical cantilever enabled high force measurement capability with sub 10-pN resolution. Here, we present the design, microfabrication, optimization, and complete characterization of the sensor. The exceptional electromechanical performance obtained allowed us to detect biorecognition specific events underlying the biotin-avidin complex formation, by integrating the sensor in a commercial atomic force microscope.

Genome-scale reconstruction of the metabolic network in Yersinia pestis CO92

NASA Astrophysics Data System (ADS)

Navid, Ali; Almaas, Eivind

2007-03-01

The gram-negative bacterium Yersinia pestis is the causative agent of bubonic plague. Using publicly available genomic, biochemical and physiological data, we have developed a constraint-based flux balance model of metabolism in the CO92 strain (biovar Orientalis) of this organism. The metabolic reactions were appropriately compartmentalized, and the model accounts for the exchange of metabolites, as well as the import of nutrients and export of waste products. We have characterized the metabolic capabilities and phenotypes of this organism, after comparing the model predictions with available experimental observations to evaluate accuracy and completeness. We have also begun preliminary studies into how cellular metabolism affects virulence.

Chemical ecology: studies from East Africa.

PubMed

Meinwald, J; Prestwich, G D; Nakanishi, K; Kubo, I

1978-03-17

The International Centre of Insect Physiology and Ecology (ICIPE), in Nairobi, provides a laboratory at which a multinational group of scientists pursues interdisciplinary research. In collaboration with their colleagues in biology, ICIPE chemists have characterized the sex pheromones of the tick which serves as a vector of East Coast fever and have identified a termite queen-cell-building pheromone. The structure of many anthropod defensive chemicals have been determined; most interesting of these are the trinervitenes, structurally novel diterpenoids from nasute termites. Several highly active insect antifeedants were discovered using a simple bioassay to screen selected East African plants. These antifeedants may provide leads for the development of new insect-control techniques.

Is applicable thermodynamics of negative temperature for living organisms?

NASA Astrophysics Data System (ADS)

Atanasov, Atanas Todorov

2017-11-01

During organismal development the moment of sexual maturity can be characterizes by nearly maximum basal metabolic rate and body mass. Once the living organism reaches extreme values of the mass and the basal metabolic rate, it reaches near equilibrium thermodynamic steady state physiological level with maximum organismal complexity. Such thermodynamic systems that reach equilibrium steady state level at maximum mass-energy characteristics can be regarded from the prospective of thermodynamics of negative temperature. In these systems the increase of the internal and free energy is accompanied with decrease of the entropy. In our study we show the possibility the living organisms to regard as thermodynamic system with negative temperature

Endocannabinoid signalling and the deteriorating brain

PubMed Central

Di Marzo, Vincenzo; Stella, Nephi; Zimmer, Andreas

2015-01-01

Ageing is characterized by the progressive impairment of physiological functions and increased risk of developing debilitating disorders, including chronic inflammation and neurodegenerative diseases. These disorders have common molecular mechanisms that can be targeted therapeutically. In the wake of the approval of the first cannabinoid-based drug for the symptomatic treatment of multiple sclerosis, we examine how endocannabinoid (eCB) signalling controls — and is affected by — normal ageing and neuroinflammatory and neurodegenerative disorders. We propose a conceptual framework linking eCB signalling to the control of the cellular and molecular hallmarks of these processes, and categorize the key components of endocannabinoid signalling that may serve as targets for novel therapeutics. PMID:25524120

Physiology modulates social flexibility and collective behaviour in equids and other large ungulates.

PubMed

Gersick, Andrew S; Rubenstein, Daniel I

2017-08-19

Though morphologically very similar, equids across the extant species occupy ecological niches that are surprisingly non-overlapping. Occupancy of these distinct niches appears related to subtle physiological and behavioural adaptations which, in turn, correspond to significant differences in the social behaviours and emergent social systems characterizing the different species. Although instances of intraspecific behavioural variation in equids demonstrate that the same body plan can support a range of social structures, each of these morphologically similar species generally shows robust fidelity to its evolved social system. The pattern suggests a subtle relationship between physiological phenotypes and behavioural flexibility. While environmental conditions can vary widely within relatively short temporal or spatial scales, physiological changes and changes to the behaviours that regulate physiological processes, are constrained to longer cycles of adaptation. Physiology is then the limiting variable in the interaction between ecological variation and behavioural and socio-structural flexibility. Behavioural and socio-structural flexibility, in turn, will generate important feedbacks that will govern physiological function, thus creating a coupled web of interactions that can lead to changes in individual and collective behaviour. Longitudinal studies of equid and other large-bodied ungulate populations under environmental stress, such as those discussed here, may offer the best opportunities for researchers to examine, in real time, the interplay between individual behavioural plasticity, socio-structural flexibility, and the physiological and genetic changes that together produce adaptive change.This article is part of the themed issue 'Physiological determinants of social behaviour in animals'. © 2017 The Author(s).

State-of-the-Art Review on Physiologically Based Pharmacokinetic Modeling in Pediatric Drug Development.

PubMed

Yellepeddi, Venkata; Rower, Joseph; Liu, Xiaoxi; Kumar, Shaun; Rashid, Jahidur; Sherwin, Catherine M T

2018-05-18

Physiologically based pharmacokinetic modeling and simulation is an important tool for predicting the pharmacokinetics, pharmacodynamics, and safety of drugs in pediatrics. Physiologically based pharmacokinetic modeling is applied in pediatric drug development for first-time-in-pediatric dose selection, simulation-based trial design, correlation with target organ toxicities, risk assessment by investigating possible drug-drug interactions, real-time assessment of pharmacokinetic-safety relationships, and assessment of non-systemic biodistribution targets. This review summarizes the details of a physiologically based pharmacokinetic modeling approach in pediatric drug research, emphasizing reports on pediatric physiologically based pharmacokinetic models of individual drugs. We also compare and contrast the strategies employed by various researchers in pediatric physiologically based pharmacokinetic modeling and provide a comprehensive overview of physiologically based pharmacokinetic modeling strategies and approaches in pediatrics. We discuss the impact of physiologically based pharmacokinetic models on regulatory reviews and product labels in the field of pediatric pharmacotherapy. Additionally, we examine in detail the current limitations and future directions of physiologically based pharmacokinetic modeling in pediatrics with regard to the ability to predict plasma concentrations and pharmacokinetic parameters. Despite the skepticism and concern in the pediatric community about the reliability of physiologically based pharmacokinetic models, there is substantial evidence that pediatric physiologically based pharmacokinetic models have been used successfully to predict differences in pharmacokinetics between adults and children for several drugs. It is obvious that the use of physiologically based pharmacokinetic modeling to support various stages of pediatric drug development is highly attractive and will rapidly increase, provided the robustness and reliability of these techniques are well established.

Flowers under pressure: ins and outs of turgor regulation in development

PubMed Central

Beauzamy, Léna; Nakayama, Naomi; Boudaoud, Arezki

2014-01-01

Background Turgor pressure is an essential feature of plants; however, whereas its physiological importance is unequivocally recognized, its relevance to development is often reduced to a role in cell elongation. Scope This review surveys the roles of turgor in development, the molecular mechanisms of turgor regulation and the methods used to measure turgor and related quantities, while also covering the basic concepts associated with water potential and water flow in plants. Three key processes in flower development are then considered more specifically: flower opening, anther dehiscence and pollen tube growth. Conclusions Many molecular determinants of turgor and its regulation have been characterized, while a number of methods are now available to quantify water potential, turgor and hydraulic conductivity. Data on flower opening, anther dehiscence and lateral root emergence suggest that turgor needs to be finely tuned during development, both spatially and temporally. It is anticipated that a combination of biological experiments and physical measurements will reinforce the existing data and reveal unexpected roles of turgor in development. PMID:25288632

Development of Concept-Based Physiology Lessons for Biomedical Engineering Undergraduate Students

ERIC Educational Resources Information Center

Nelson, Regina K.; Chesler, Naomi C.; Strang, Kevin T.

2013-01-01

engineering curriculum. In one or two introductory physiology courses, engineering students must learn physiology sufficiently to support learning in their subsequent engineering courses and careers. As preparation for future learning, physiology instruction centered on concepts may…

A GRFa2/Prop1/stem (GPS) cell niche in the pituitary.

PubMed

Garcia-Lavandeira, Montse; Quereda, Víctor; Flores, Ignacio; Saez, Carmen; Diaz-Rodriguez, Esther; Japon, Miguel A; Ryan, Aymee K; Blasco, Maria A; Dieguez, Carlos; Malumbres, Marcos; Alvarez, Clara V

2009-01-01

The adult endocrine pituitary is known to host several hormone-producing cells regulating major physiological processes during life. Some candidates to progenitor/stem cells have been proposed. However, not much is known about pituitary cell renewal throughout life and its homeostatic regulation during specific physiological changes, such as puberty or pregnancy, or in pathological conditions such as tumor development. We have identified in rodents and humans a niche of non-endocrine cells characterized by the expression of GFRa2, a Ret co-receptor for Neurturin. These cells also express b-Catenin and E-cadherin in an oriented manner suggesting a planar polarity organization for the niche. In addition, cells in the niche uniquely express the pituitary-specific transcription factor Prop1, as well as known progenitor/stem markers such as Sox2, Sox9 and Oct4. Half of these GPS (GFRa2/Prop1/Stem) cells express S-100 whereas surrounding elongated cells in contact with GPS cells express Vimentin. GFRa2+-cells form non-endocrine spheroids in culture. These spheroids can be differentiated to hormone-producing cells or neurons outlining the neuroectoderm potential of these progenitors. In vivo, GPSs cells display slow proliferation after birth, retain BrdU label and show long telomeres in its nuclei, indicating progenitor/stem cell properties in vivo. Our results suggest the presence in the adult pituitary of a specific niche of cells characterized by the expression of GFRa2, the pituitary-specific protein Prop1 and stem cell markers. These GPS cells are able to produce different hormone-producing and neuron-like cells and they may therefore contribute to postnatal pituitary homeostasis. Indeed, the relative abundance of GPS numbers is altered in Cdk4-deficient mice, a model of hypopituitarism induced by the lack of this cyclin-dependent kinase. Thus, GPS cells may display functional relevance in the physiological expansion of the pituitary gland throughout life as well as protection from pituitary disease.

A GRFa2/Prop1/Stem (GPS) Cell Niche in the Pituitary

PubMed Central

Garcia-Lavandeira, Montse; Quereda, Víctor; Flores, Ignacio; Saez, Carmen; Diaz-Rodriguez, Esther; Japon, Miguel A.; Ryan, Aymee K.; Blasco, Maria A.; Dieguez, Carlos; Malumbres, Marcos; Alvarez, Clara V.

2009-01-01

Background The adult endocrine pituitary is known to host several hormone-producing cells regulating major physiological processes during life. Some candidates to progenitor/stem cells have been proposed. However, not much is known about pituitary cell renewal throughout life and its homeostatic regulation during specific physiological changes, such as puberty or pregnancy, or in pathological conditions such as tumor development. Principal Findings We have identified in rodents and humans a niche of non-endocrine cells characterized by the expression of GFRa2, a Ret co-receptor for Neurturin. These cells also express b-Catenin and E-cadherin in an oriented manner suggesting a planar polarity organization for the niche. In addition, cells in the niche uniquely express the pituitary-specific transcription factor Prop1, as well as known progenitor/stem markers such as Sox2, Sox9 and Oct4. Half of these GPS (GFRa2/Prop1/Stem) cells express S-100 whereas surrounding elongated cells in contact with GPS cells express Vimentin. GFRa2+-cells form non-endocrine spheroids in culture. These spheroids can be differentiated to hormone-producing cells or neurons outlining the neuroectoderm potential of these progenitors. In vivo, GPSs cells display slow proliferation after birth, retain BrdU label and show long telomeres in its nuclei, indicating progenitor/stem cell properties in vivo. Significance Our results suggest the presence in the adult pituitary of a specific niche of cells characterized by the expression of GFRa2, the pituitary-specific protein Prop1 and stem cell markers. These GPS cells are able to produce different hormone-producing and neuron-like cells and they may therefore contribute to postnatal pituitary homeostasis. Indeed, the relative abundance of GPS numbers is altered in Cdk4-deficient mice, a model of hypopituitarism induced by the lack of this cyclin-dependent kinase. Thus, GPS cells may display functional relevance in the physiological expansion of the pituitary gland throughout life as well as protection from pituitary disease. PMID:19283075

Physicochemical characterization of engineered nanoparticles under physiological conditions: effect of culture media components and particle surface coating.

PubMed

Fatisson, Julien; Quevedo, Ivan R; Wilkinson, Kevin J; Tufenkji, Nathalie

2012-03-01

The use of engineered nanoparticles (ENPs) in commercial products has increased substantially over the last few years. Some research has been conducted in order to determine whether or not such materials are cytotoxic, but questions remain regarding the role that physiological media and sera constituents play in ENP aggregation or stabilization. In this study, several characterization methods were used to evaluate the particle size and surface potential of 6 ENPs suspended in a number of culture media and in the presence of different culture media constituents. Dynamic light scattering (DLS) and fluorescence correlation spectroscopy (FCS) were employed for size determinations. Results were interpreted on the basis of ENP surface potentials evaluated from particle electrophoretic mobilities (EPM). Measurements made after 24h of incubation at 37°C showed that the cell culture medium constituents had only moderate impact on the physicochemical properties of the ENP, although incubation in bovine serum albumin destabilized the colloidal system. In contrast, most of the serum proteins increased colloidal stabilization. Moreover, the type of ENP surface modification played a significant role in ENP behavior whereby the complexity of interactions between the ENPs and the medium components generally decreased with increasing complexity of the particle surface. This investigation emphasizes the importance of ENP characterization under conditions that are representative of cell culture media or physiological conditions for improved assessments of nanoparticle cytotoxicity. Copyright © 2011 Elsevier B.V. All rights reserved.

Genetic approaches in comparative and evolutionary physiology.

PubMed

Storz, Jay F; Bridgham, Jamie T; Kelly, Scott A; Garland, Theodore

2015-08-01

Whole animal physiological performance is highly polygenic and highly plastic, and the same is generally true for the many subordinate traits that underlie performance capacities. Quantitative genetics, therefore, provides an appropriate framework for the analysis of physiological phenotypes and can be used to infer the microevolutionary processes that have shaped patterns of trait variation within and among species. In cases where specific genes are known to contribute to variation in physiological traits, analyses of intraspecific polymorphism and interspecific divergence can reveal molecular mechanisms of functional evolution and can provide insights into the possible adaptive significance of observed sequence changes. In this review, we explain how the tools and theory of quantitative genetics, population genetics, and molecular evolution can inform our understanding of mechanism and process in physiological evolution. For example, lab-based studies of polygenic inheritance can be integrated with field-based studies of trait variation and survivorship to measure selection in the wild, thereby providing direct insights into the adaptive significance of physiological variation. Analyses of quantitative genetic variation in selection experiments can be used to probe interrelationships among traits and the genetic basis of physiological trade-offs and constraints. We review approaches for characterizing the genetic architecture of physiological traits, including linkage mapping and association mapping, and systems approaches for dissecting intermediary steps in the chain of causation between genotype and phenotype. We also discuss the promise and limitations of population genomic approaches for inferring adaptation at specific loci. We end by highlighting the role of organismal physiology in the functional synthesis of evolutionary biology. Copyright © 2015 the American Physiological Society.

Fluid and electrolyte homeostasis during spaceflight: Elucidation of mechanisms in a primate

NASA Technical Reports Server (NTRS)

Churchill, Susanne

1990-01-01

Although it is now well accepted that exposure to the hypogravic environment of space induces a shift of fluid from the lower extremities toward the upper body, the actual physiological responses to this central volume expansion have not been well characterized. Because it is likely that the fluid and electrolyte response to hypogravity plays a critical role in the development of Cardiovascular Deconditioning, elucidation of these mechanisms is of critical importance. The goal of flight experiment 223, scheduled to fly on SLS-2, is the definition of the basic renal, fluid and electrolyte response to spaceflight in four instrumented squirrel monkeys. The studies were those required to support the development of flight hardware and optimal inflight procedures, and to evaluate a ground-based model for weightlessness, lower body positive pressure (LBPP).

Physiology of fish endocrine pancreas.

PubMed

Plisetskaya, E M

1989-06-01

From the very beginning of physiological studies on the endocine pancreas, fish have been used as experimental subjects. Fish insulin was one of the first vertebrate insulins isolated and one of the first insulins whose primary and then tertiary structures were reported. Before a second pancreatic hormone, glucagon, was characterized, a physiologically active 'impurity', similar to that in mammalian insulin preparations, was found in fish insulins.Fish have become the most widely used model for studies of biosynthesis and processing of the pancreatic hormones. It seems inconceivable, therefore, that until the recent past cod and tuna insulins have been the only purified piscine islet hormones available for physiological experiments. The situation has changed remarkably during the last decade.In this review the contemporary status of physiological studies on the fish pancreas is outlined with an emphasis on the following topics: 1) contents of pancreatic peptides in plasma and in islet tissue; 2) actions of piscine pancreatic hormones in fish; 3) specific metabolic consequences of an acute insufficiency of pancreatic peptides; 4) functional interrelations among pancreatic peptides which differ from those of mammals. The pitfalls, lacunae and the perspectives of contemporary physiological studies on fish endocrine pancreas are outlined.

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.

Microparticles: A New Perspective in Central Nervous System Disorders

PubMed Central

Schindler, Stephanie M.; Little, Jonathan P.

2014-01-01

Microparticles (MPs) are a heterogeneous population of small cell-derived vesicles, ranging in size from 0.1 to 1 μm. They contain a variety of bioactive molecules, including proteins, biolipids, and nucleic acids, which can be transferred between cells without direct cell-to-cell contact. Consequently, MPs represent a novel form of intercellular communication, which could play a role in both physiological and pathological processes. Growing evidence indicates that circulating MPs contribute to the development of cancer, inflammation, and autoimmune and cardiovascular diseases. Most cell types of the central nervous system (CNS) have also been shown to release MPs, which could be important for neurodevelopment, CNS maintenance, and pathologies. In disease, levels of certain MPs appear elevated; therefore, they may serve as biomarkers allowing for the development of new diagnostic tools for detecting the early stages of CNS pathologies. Quantification and characterization of MPs could also provide useful information for making decisions on treatment options and for monitoring success of therapies, particularly for such difficult-to-treat diseases as cerebral malaria, multiple sclerosis, and Alzheimer's disease. Overall, studies on MPs in the CNS represent a novel area of research, which promises to expand the knowledge on the mechanisms governing some of the physiological and pathophysiological processes of the CNS. PMID:24860829

A high performance biometric signal and image processing method to reveal blood perfusion towards 3D oxygen saturation mapping

NASA Astrophysics Data System (ADS)

Imms, Ryan; Hu, Sijung; Azorin-Peris, Vicente; Trico, Michaël.; Summers, Ron

2014-03-01

Non-contact imaging photoplethysmography (PPG) is a recent development in the field of physiological data acquisition, currently undergoing a large amount of research to characterize and define the range of its capabilities. Contact-based PPG techniques have been broadly used in clinical scenarios for a number of years to obtain direct information about the degree of oxygen saturation for patients. With the advent of imaging techniques, there is strong potential to enable access to additional information such as multi-dimensional blood perfusion and saturation mapping. The further development of effective opto-physiological monitoring techniques is dependent upon novel modelling techniques coupled with improved sensor design and effective signal processing methodologies. The biometric signal and imaging processing platform (bSIPP) provides a comprehensive set of features for extraction and analysis of recorded iPPG data, enabling direct comparison with other biomedical diagnostic tools such as ECG and EEG. Additionally, utilizing information about the nature of tissue structure has enabled the generation of an engineering model describing the behaviour of light during its travel through the biological tissue. This enables the estimation of the relative oxygen saturation and blood perfusion in different layers of the tissue to be calculated, which has the potential to be a useful diagnostic tool.

Physiology of Developing Gravity Receptors and Otolith-Ocular Reflexes in Rat

NASA Technical Reports Server (NTRS)

Blanks, Robert H.

1997-01-01

This proposal had the long-term objective of examining the effects of microgravity on the physiology of the adult and developing mammalian gravity receptors. The grant outlined three-years of ground-based studies to examine. 1) the physiologic responses or otolith afferents in the adult rat and during postnatal development, and 2) the otolith organ contributions to the vertical vestibulo-ocular (VOR) and postural reflexes.

Physiological Measures of Emotion from a Developmental Perspective: State of the Science

ERIC Educational Resources Information Center

Dennis, Tracy A.; Buss, Kristin A.; Hastings, Paul D.; Bell, Martha Ann; Diaz, Anjolii; Adam, Emma K.; Miskovic, Vladimir; Schmidt, Louis A.; Feldman, Ruth; Katz, Lynn Fainsilber; Rigterink, Tami; Strang, Nicole M.; Hanson, Jamie L.; Pollak, Seth D.; Dahl, Ronald E.; Silk, Jennifer S.; Siegle, Greg J.; Beauchaine, Theodore P.; Cicchetti, Dante; Rogosch, Fred A.; Fox, Nathan A.; Kirwan, Michael; Reeb-Sutherland, Bethany; Gunnar, Megan R.; Obradovic, Jelena; Boyce, W. Thomas; Molenaar, Peter C. M.; Gates, Kathleen M.

2012-01-01

In the past decade, there has been a dramatic growth in research examining the development of emotion from a physiological perspective. However, this widespread use of physiological measures to study emotional development coexists with relatively few guiding principles, thus reducing opportunities to move the field forward in innovative ways. The…

Teaching Acid/Base Physiology in the Laboratory

ERIC Educational Resources Information Center

Friis, Ulla G.; Plovsing, Ronni; Hansen, Klaus; Laursen, Bent G.; Wallstedt, Birgitta

2010-01-01

Acid/base homeostasis is one of the most difficult subdisciplines of physiology for medical students to master. A different approach, where theory and practice are linked, might help students develop a deeper understanding of acid/base homeostasis. We therefore set out to develop a laboratory exercise in acid/base physiology that would provide…

Post-Translational Modification of Constitutive Nitric Oxide Synthase in the Penis

PubMed Central

Musicki, Biljana; Ross, Ashley E.; Champion, Hunter C.; Burnett, Arthur L.; Bivalacqua, Trinity J.

2009-01-01

Erectile dysfunction (ED) is a common men's health problem characterized by the consistent inability to sustain an erection sufficient for sexual intercourse. Basic science research on erectile physiology has been devoted to investigating the pathogenesis of ED and has led to the conclusion that ED is predominately a disease of vascular origin and/or neurogenic dysfunction. The constitutive forms of nitric oxide synthase [NOS; endothelial NOS (eNOS) and neuronal NOS (nNOS)] are important enzymes involved in the production of nitric oxide (NO) and thus regulate penile vascular homeostasis. Given the impact of endothelial- and neuronal-derived NO in penile vascular biology, a great deal of research over the past decade has focused on the role of NO synthesis from the endothelium and nitrergic nerve terminal in normal erectile physiology as well as in disease states. Loss of the functional integrity of the endothelium and subsequent endothelial dysfunction plays an integral role in the occurrence of ED. Therefore, molecular mechanisms involved in dysregulation of these NOS isoforms in the development of ED are essential to discovering the pathogenesis of ED in various disease states. This communication reviews the role of eNOS and nNOS in erectile physiology and discusses the alterations in eNOS and nNOS via post-translation modification in various vascular diseases of the penis. PMID:19342700

Physiological effects of light on the human circadian pacemaker

NASA Technical Reports Server (NTRS)

Shanahan, T. L.; Czeisler, C. A.

2000-01-01

The physiology of the human circadian pacemaker and its influence and on the daily organization of sleep, endocrine and behavioral processes is an emerging interest in science and medicine. Understanding the development, organization and fundamental properties underlying the circadian timing system may provide insight for the application of circadian principles to the practice of clinical medicine, both diagnostically (interpretation of certain clinical tests are dependent on time of day) and therapeutically (certain pharmacological responses vary with the time of day). The light-dark cycle is the most powerful external influence acting upon the human circadian pacemaker. It has been shown that timed exposure to light can both synchronize and reset the phase of the circadian pacemaker in a predictable manner. The emergence of detectable circadian rhythmicity in the neonatal period is under investigation (as described elsewhere in this issue). Therefore, the pattern of light exposure provided in the neonatal intensive care setting has implications. One recent study identified differences in both amount of sleep time and weight gain in infants maintained in a neonatal intensive care environment that controlled the light-dark cycle. Unfortunately, neither circadian phase nor the time of day has been considered in most clinical investigations. Further studies with knowledge of principles characterizing the human circadian timing system, which governs a wide array of physiological processes, are required to integrate these findings with the practice of clinical medicine.

Advances in Management of Esophageal Motility Disorders.

PubMed

Kahrilas, Peter J; Bredenoord, Albert J; Carlson, Dustin A; Pandolfino, John E

2018-04-24

The widespread adoption of high-resolution manometry (HRM) has led to a restructuring in the classification of esophageal motility disorder classification summarized in the Chicago Classification, currently in version 3.0. It has become apparent that the cardinal feature of achalasia, impaired lower esophageal sphincter relaxation, can occur in several disease phenotypes: without peristalsis, with premature (spastic) distal esophageal contractions, with panesophageal pressurization, or even with preserved peristalsis. Furthermore, despite these advances in diagnostics, no single manometric pattern is perfectly sensitive or specific for idiopathic achalasia and complimentary assessments with provocative maneuvers during HRM or interrogating the esophagogastric junction with the functional luminal imaging probe during endoscopy can be useful in clarifying equivocal or inexplicable HRM findings. Using these tools, we have come to conceptualize esophageal motility disorders as characterized by obstructive physiology at the esophagogastric junction, smooth muscle esophagus, or both. Recognizing obstructive physiology as a primary target of therapy has become particularly relevant with the development of a minimally invasive technique for performing a calibrated myotomy of the esophageal circular muscle, the POEM procedure. Now and going forward, optimal management is to render treatment in a phenotype-specific manner: e.g. POEM calibrated to patient-specific physiology for spastic achalasia and spastic disorders of the smooth muscle esophagus, more conservative strategies (pneumatic dilation) for the disorders limited to the sphincter. Copyright © 2018 AGA Institute. Published by Elsevier Inc. All rights reserved.

FT-IR spectroscopy as a tool for rapid identification and intra-species characterization of airborne filamentous fungi.

PubMed

Fischer, Guido; Braun, Silvia; Thissen, Ralf; Dott, Wolfgang

2006-01-01

Identification of microfungi is time-consuming due to cultivation and microscopic examination and can be influenced by the interpretation of the macro- and micro-morphological characters observed. Fungal conidia contain mycotoxins that may be present in bioaerosols and thus the capacity for production of mycotoxins (and allergens) needs to be investigated to create a basis for reliable risk assessment in environmental and occupational hygiene. The present investigation aimed to create a simple but sophisticated method for the preparation of samples and the identification of airborne fungi by FT-IR spectroscopy. The method was suited to reproducibly differentiate Aspergillus and Penicillium species on the generic, the species, and the strain level. There are strong indications that strains of one taxon differing in metabolite production can be reliably distinguished by FT-IR spectroscopy (e.g. Aspergillus parasiticus). On the other hand, species from different taxa being similar in secondary metabolite production showed comparably higher similarities. The results obtained here can serve as a basis for the development of a database for species identification and strain characterization of microfungi. The method presented here will improve and facilitate the risk assessment in case of bioaerosol exposure, as strains with different physiological properties (e.g. toxic, non-toxic) could be differentiated. Moreover, it has the potential to significantly improve the identification of microfungi in various fields of applied microbiological research, e.g. high throughput screening in view of specific physiological properties, biodiversity studies, inventories in environmental microbiology, and quality control measures.

Quantitative Measurement of GPCR Endocytosis via Pulse-Chase Covalent Labeling

PubMed Central

Fujishiro, Mitsuhiro; Okamura, Tomohisa; Fujio, Keishi; Okazaki, Hiroaki; Nomura, Seitaro; Takeda, Norifumi; Harada, Mutsuo; Toko, Haruhiro; Takimoto, Eiki; Akazawa, Hiroshi; Morita, Hiroyuki; Suzuki, Jun-ichi; Yamazaki, Tsutomu; Yamamoto, Kazuhiko; Komuro, Issei; Yanagisawa, Masashi

2015-01-01

G protein-coupled receptors (GPCRs) play a critical role in many physiological systems and represent one of the largest families of signal-transducing receptors. The number of GPCRs at the cell surface regulates cellular responsiveness to their cognate ligands, and the number of GPCRs, in turn, is dynamically controlled by receptor endocytosis. Recent studies have demonstrated that GPCR endocytosis, in addition to affecting receptor desensitization and resensitization, contributes to acute G protein-mediated signaling. Thus, endocytic GPCR behavior has a significant impact on various aspects of physiology. In this study, we developed a novel GPCR internalization assay to facilitate characterization of endocytic GPCR behavior. We genetically engineered chimeric GPCRs by fusing HaloTag (a catalytically inactive derivative of a bacterial hydrolase) to the N-terminal end of the receptor (HT-GPCR). HaloTag has the ability to form a stable covalent bond with synthetic HaloTag ligands that contain fluorophores or a high-affinity handle (such as biotin) and the HaloTag reactive linker. We selectively labeled HT-GPCRs at the cell surface with a HaloTag PEG ligand, and this pulse-chase covalent labeling allowed us to directly monitor the relative number of internalized GPCRs after agonist stimulation. Because the endocytic activities of GPCR ligands are not necessarily correlated with their agonistic activities, applying this novel methodology to orphan GPCRs, or even to already characterized GPCRs, will increase the likelihood of identifying currently unknown ligands that have been missed by conventional pharmacological assays. PMID:26020647

Physiological Characterization and Comparative Transcriptome Analysis of White and Green Leaves of Ananas comosus var. bracteatus

PubMed Central

Li, Xia; Kanakala, Surapathrudu; He, Yehua; Zhong, Xiaolan; Yu, Sanmiao; Li, Ruixue; Sun, Lingxia; Ma, Jun

2017-01-01

Leaf coloration is one of the most important and attractive characteristics of Ananas comosus var. bracteatus. The chimeric character is not stable during the in vitro tissue culturing. Many regenerated plants lost economic values for the loss of the chimeric character of leaves. In order to reveal the molecular mechanisms involved in the albino phenotype of the leaf cells, the physiological and transcriptional differences between complete white (CWh) and green (CGr) leaf cells of A. comosus var. bracteatus were analyzed. A total of 1,431 differentially expressed unigenes (DEGs) in CGr and CWh leaves were identified using RNA-seq. A comparison to the COG, GO and KEGG annotations revealed DEGs involved in chlorophyll biosynthesis, chloroplast development and photosynthesis. Furthermore, the measurement of main precursors of chlorophyll in the CWh leaves confirmed that the rate-limiting step in chlorophyll biosynthesis, and thus the cause of the albino phenotype of the white cells, was the conversion of pyrrole porphobilinogen (PBG) to uroporphyrinogen III (Uro III). The enzyme activity of porphobilinogen deaminase (PBGD) and uroporporphyrinogn III synthase (UROS), which catalyze the transition of PBG to Uro III, was significantly decreased in the CWh leaves. Our data showed the transcriptional differences between the CWh and CGr plants and characterized key steps in chlorophyll biosynthesis of the CWh leaves. These results contribute to our understanding of the mechanisms and regulation of pigment biosynthesis in the CWh leaf cells of A. comosus var. bracteatus. PMID:28095462

Physiological Characterization and Comparative Transcriptome Analysis of White and Green Leaves of Ananas comosus var. bracteatus.

PubMed

Li, Xia; Kanakala, Surapathrudu; He, Yehua; Zhong, Xiaolan; Yu, Sanmiao; Li, Ruixue; Sun, Lingxia; Ma, Jun

2017-01-01

Leaf coloration is one of the most important and attractive characteristics of Ananas comosus var. bracteatus. The chimeric character is not stable during the in vitro tissue culturing. Many regenerated plants lost economic values for the loss of the chimeric character of leaves. In order to reveal the molecular mechanisms involved in the albino phenotype of the leaf cells, the physiological and transcriptional differences between complete white (CWh) and green (CGr) leaf cells of A. comosus var. bracteatus were analyzed. A total of 1,431 differentially expressed unigenes (DEGs) in CGr and CWh leaves were identified using RNA-seq. A comparison to the COG, GO and KEGG annotations revealed DEGs involved in chlorophyll biosynthesis, chloroplast development and photosynthesis. Furthermore, the measurement of main precursors of chlorophyll in the CWh leaves confirmed that the rate-limiting step in chlorophyll biosynthesis, and thus the cause of the albino phenotype of the white cells, was the conversion of pyrrole porphobilinogen (PBG) to uroporphyrinogen III (Uro III). The enzyme activity of porphobilinogen deaminase (PBGD) and uroporporphyrinogn III synthase (UROS), which catalyze the transition of PBG to Uro III, was significantly decreased in the CWh leaves. Our data showed the transcriptional differences between the CWh and CGr plants and characterized key steps in chlorophyll biosynthesis of the CWh leaves. These results contribute to our understanding of the mechanisms and regulation of pigment biosynthesis in the CWh leaf cells of A. comosus var. bracteatus.

Stabilization of gene expression and cell morphology after explant recycling during fin explant culture in goldfish.

PubMed

Chenais, Nathalie; Lareyre, Jean-Jacques; Le Bail, Pierre-Yves; Labbe, Catherine

2015-07-01

The development of fin primary cell cultures for in vitro cellular and physiological studies is hampered by slow cell outgrowth, low proliferation rate, poor viability, and sparse cell characterization. Here, we investigated whether the recycling of fresh explants after a first conventional culture could improve physiological stability and sustainability of the culture. The recycled explants were able to give a supplementary cell culture showing faster outgrowth, cleaner cell layers and higher net cell production. The cells exhibited a highly stabilized profile for marker gene expression including a low cytokeratin 49 (epithelial marker) and a high collagen 1a1 (mesenchymal marker) expression. Added to the cell spindle-shaped morphology, motility behavior, and actin organization, this suggests that the cells bore stable mesenchymal characteristics. This contrast with the time-evolving expression pattern observed in the control fresh explants during the first 2 weeks of culture: a sharp decrease in cytokeratin 49 expression was concomitant with a gradual increase in col1a1. We surmise that such loss of epithelial features for the benefit of mesenchymal ones was triggered by an epithelial to mesenchymal transition (EMT) process or by way of a progressive population replacement process. Overall, our findings provide a comprehensive characterization of this new primary culture model bearing mesenchymal features and whose stability over culture time makes those cells good candidates for cell reprogramming prior to nuclear transfer, in a context of fish genome preservation. Copyright © 2015 Elsevier Inc. All rights reserved.

Development of Animal Physiology Practical Guidance Oriented Guided Inquiry for Student of Biology Department

NASA Astrophysics Data System (ADS)

Putra, Z. A. Z.; Sumarmin, R.; Violita, V.

2018-04-01

The guides used for practicing animal physiology need to be revised and adapted to the lecture material. This is because in the subject of Animal Physiology. The guidance of animal physiology practitioners is still conventional with prescription model instructions and is so simple that it is necessary to develop a practical guide that can lead to the development of scientific work. One of which is through practice guided inquiry guided practicum guide. This study aims to describe the process development of the practical guidance and reveal the validity, practicality, and effectiveness Guidance Physiology Animals guided inquiry inferior to the subject of Animal Physiology for students Biology Department State University of Padang. This type of research is development research. This development research uses the Plomp model. Stages performed are problem identification and analysis stage, prototype development and prototyping stage, and assessment phase. Data analysis using descriptive analysis. The instrument of data collection using validation and practical questionnaires, competence and affective field of competence observation and psychomotor and cognitive domain competence test. The result of this research shows that guidance of Inquiry Guided Initiative Guided Physiology with 3.23 valid category, practicality by lecturer with value 3.30 practical category, student with value 3.37 practical criterion. Affective effectiveness test with 93,00% criterion is very effective, psychomotor aspect 89,50% with very effective criteria and cognitive domain with value of 67, pass criterion. The conclusion of this research is Guided Inquiry Student Guided Protoxial Guidance For Students stated valid, practical and effective.

Potential effects of physiological plastic responses to salinity on population networks of the estuarine crab Chasmagnathus granulata

NASA Astrophysics Data System (ADS)

Giménez, Luis

2002-12-01

Chasmagnathus granulata is a South American crab occurring in estuarine salt marshes of the Brazilian, Uruguayan and Argentine coasts. Life history is characterized by an export strategy of its larval stages. I reviewed information on experimental manipulation of salinity during embryonic and larval development (pre- and posthatching salinities), and on habitat characteristics of C. granulata in order to determine potential effects of larval response to salinity in the field and to suggest consequences for the population structure. Local populations are spread over coastal areas with different physical characteristics. Benthic phases occupy estuaries characterized by different patterns of salinity variation, and release larvae to coastal waters characterized by strong salinity gradients. The zoea 1 of C. granulata showed a strong acclimatory response to low salinity. This response operated only during the first weeks of development (during zoeae 1 and 2) since subsequent larval survival at low posthatching salinities was consistently low. Larvae developing at low salinity frequently followed a developmental pathway with five instead of four zoeal stages. The ability to acclimate and the variability in larval development (i.e. the existence of alternative developmental pathways) could be interpreted as a strategy to buffer environmental variability at spatial scales of local or population networks. Early survivorship and production of larvae may be relatively high across a rather wide range of variability in salinity (5-32‰). Plastic responses to low salinity would therefore contribute to maintain a certain degree of population connectivity and persistence regardless of habitat heterogeneity.

Potential effects of physiological plastic responses to salinity on population networks of the estuarine crab Chasmagnathus granulata

NASA Astrophysics Data System (ADS)

Giménez, Luis

2003-01-01

Chasmagnathus granulata is a South American crab occurring in estuarine salt marshes of the Brazilian, Uruguayan and Argentine coasts. Life history is characterized by an export strategy of its larval stages. I reviewed information on experimental manipulation of salinity during embryonic and larval development (pre- and posthatching salinities), and on habitat characteristics of C. granulata in order to determine potential effects of larval response to salinity in the field and to suggest consequences for the population structure. Local populations are spread over coastal areas with different physical characteristics. Benthic phases occupy estuaries characterized by different patterns of salinity variation, and release larvae to coastal waters characterized by strong salinity gradients. The zoea 1 of C. granulata showed a strong acclimatory response to low salinity. This response operated only during the first weeks of development (during zoeae 1 and 2) since subsequent larval survival at low posthatching salinities was consistently low. Larvae developing at low salinity frequently followed a developmental pathway with five instead of four zoeal stages. The ability to acclimate and the variability in larval development (i.e. the existence of alternative developmental pathways) could be interpreted as a strategy to buffer environmental variability at spatial scales of local or population networks. Early survivorship and production of larvae may be relatively high across a rather wide range of variability in salinity (5-32‰). Plastic responses to low salinity would therefore contribute to maintain a certain degree of population connectivity and persistence regardless of habitat heterogeneity.

Network Physiology: How Organ Systems Dynamically Interact

PubMed Central

Bartsch, Ronny P.; Liu, Kang K. L.; Bashan, Amir; Ivanov, Plamen Ch.

2015-01-01

We systematically study how diverse physiologic systems in the human organism dynamically interact and collectively behave to produce distinct physiologic states and functions. This is a fundamental question in the new interdisciplinary field of Network Physiology, and has not been previously explored. Introducing the novel concept of Time Delay Stability (TDS), we develop a computational approach to identify and quantify networks of physiologic interactions from long-term continuous, multi-channel physiological recordings. We also develop a physiologically-motivated visualization framework to map networks of dynamical organ interactions to graphical objects encoded with information about the coupling strength of network links quantified using the TDS measure. Applying a system-wide integrative approach, we identify distinct patterns in the network structure of organ interactions, as well as the frequency bands through which these interactions are mediated. We establish first maps representing physiologic organ network interactions and discover basic rules underlying the complex hierarchical reorganization in physiologic networks with transitions across physiologic states. Our findings demonstrate a direct association between network topology and physiologic function, and provide new insights into understanding how health and distinct physiologic states emerge from networked interactions among nonlinear multi-component complex systems. The presented here investigations are initial steps in building a first atlas of dynamic interactions among organ systems. PMID:26555073

Characterization of Electrocardiogram Changes Throughout a Marathon

PubMed Central

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

2014-01-01

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

NMR-Based Metabonomic Analysis of Physiological Responses to Starvation and Refeeding in the Rat.

PubMed

Serrano-Contreras, José I; García-Pérez, Isabel; Meléndez-Camargo, María E; Zepeda, L Gerardo

2016-09-02

Starvation is a postabsorptive condition derived from a limitation on food resources by external factors. Energy homeostasis is maintained under this condition by using sources other than glucose via adaptive mechanisms. After refeeding, when food is available, other adaptive processes are linked to energy balance. However, less has been reported about the physiological mechanisms present as a result of these conditions, considering the rat as a supraorganism. Metabolic profiling using (1)H nuclear magnetic resonance spectroscopy was used to characterize the physiological metabolic differences in urine specimens collected under starved, refed, and recovered conditions. In addition, because starvation induced lack of faecal production and not all animals produced faeces during refeeding, 24 h pooled faecal water samples were also analyzed. Urinary metabolites upregulated by starvation included 2-butanamidoacetate, 3-hydroxyisovalerate, ketoleucine, methylmalonate, p-cresyl glucuronide, p-cresyl sulfate, phenylacetylglycine, pseudouridine, creatinine, taurine, and N-acetyl glycoprotein, which were related to renal and skeletal muscle function, β-oxidation, turnover of proteins and RNA, and host-microbial interactions. Food-derived metabolites, including gut microbial cometabolites, and tricarboxylic acid cycle intermediates were upregulated under refed and recovered conditions, which characterized anabolic urinary metabotypes. The upregulation of creatine and pantothenate indicated an absorptive state after refeeding. Fecal short chain fatty acids, 3-(3-hydroxyphenyl)propionate, lactate, and acetoin provided additional information about the combinatorial metabolism between the host and gut microbiota. This investigation contributes to allow a deeper understanding of physiological responses associated with starvation and refeeding.

Instantaneous Transfer Entropy for the Study of Cardiovascular and Cardiorespiratory Nonstationary Dynamics.

PubMed

Valenza, Gaetano; Faes, Luca; Citi, Luca; Orini, Michele; Barbieri, Riccardo

2018-05-01

Measures of transfer entropy (TE) quantify the direction and strength of coupling between two complex systems. Standard approaches assume stationarity of the observations, and therefore are unable to track time-varying changes in nonlinear information transfer with high temporal resolution. In this study, we aim to define and validate novel instantaneous measures of TE to provide an improved assessment of complex nonstationary cardiorespiratory interactions. We here propose a novel instantaneous point-process TE (ipTE) and validate its assessment as applied to cardiovascular and cardiorespiratory dynamics. In particular, heartbeat and respiratory dynamics are characterized through discrete time series, and modeled with probability density functions predicting the time of the next physiological event as a function of the past history. Likewise, nonstationary interactions between heartbeat and blood pressure dynamics are characterized as well. Furthermore, we propose a new measure of information transfer, the instantaneous point-process information transfer (ipInfTr), which is directly derived from point-process-based definitions of the Kolmogorov-Smirnov distance. Analysis on synthetic data, as well as on experimental data gathered from healthy subjects undergoing postural changes confirms that ipTE, as well as ipInfTr measures are able to dynamically track changes in physiological systems coupling. This novel approach opens new avenues in the study of hidden, transient, nonstationary physiological states involving multivariate autonomic dynamics in cardiovascular health and disease. The proposed method can also be tailored for the study of complex multisystem physiology (e.g., brain-heart or, more in general, brain-body interactions).

Purification and sequence of rat oxyntomodulin.

PubMed Central

Collie, N L; Walsh, J H; Wong, H C; Shively, J E; Davis, M T; Lee, T D; Reeve, J R

1994-01-01

Structural information about rat enteroglucagon, intestinal peptides containing the pancreatic glucagon sequence, has been based previously on cDNA, immunologic, and chromatographic data. Our interests in testing the physiological actions of synthetic enteroglucagon peptides in rats required that we identify precisely the forms present in vivo. From knowledge of the proglucagon gene sequence, we synthesized an enteroglucagon C-terminal octapeptide common to both proposed enteroglucagon forms, glicentin and oxyntomodulin, but sharing no sequence overlap with glucagon. We then developed a radioimmunoassay using antibodies raised against the octapeptide that was specific for enteroglucagon peptides without cross-reacting with glucagon. Rat intestine was extracted, and one presumptive enteroglucagon form was purified by following the enteroglucagon C-terminal octapeptide-like immunoreactivity through several HPLC purification steps. Structural characterization of the material by amino acid composition, microsequence, and mass spectral analyses identified the peptide as rat oxyntomodulin. The 37-residue peptide consists of pancreatic glucagon plus the C-terminal extension, Lys-Arg-Asn-Arg-Asn-Asn-Ile-Ala. This now permits synthesis of an unambiguous duplicate of endogenous rat oxyntomodulin for physiological studies. Images PMID:7937770

GPR30: a novel therapeutic target in estrogen-related disease.

PubMed

Prossnitz, Eric R; Sklar, Larry A; Oprea, Tudor I; Arterburn, Jeffrey B

2008-03-01

Estrogen is a crucial hormone in human physiology that regulates a multitude of biological processes. It is also an important target in many diseases such as cancer and skeletal, neurological and immunological conditions. The actions of estrogen have traditionally been ascribed to one of two closely related classical nuclear hormone receptors, ERalpha and ERbeta, which are best characterized for regulating gene expression. Recent studies have revealed the contribution of a novel estrogen receptor GPR30, which belongs to the family of seven-transmembrane G-protein-coupled receptors, to many of the rapid biological responses to estrogen. Many drugs, such as tamoxifen and fulvestrant, which seem to selectively inhibit the activities of the classical estrogen receptors, are in widespread clinical use. However, recent results indicate that these same drugs activate multiple cellular-signaling pathways via GPR30. Unraveling the pharmacological profiles and specificities of ERalpha, ERbeta and GPR30 will be vital for understanding not only the physiological roles of each receptor but also for the development of the next generation of receptor-specific drugs.

Obesity and diabetes in vulnerable populations: reflection on proximal and distal causes.

PubMed

Candib, Lucy M

2007-01-01

Around the world obesity and diabetes are climbing to epidemic proportion, even in countries previously characterized by scarcity. Likewise, people from low-income and minority communities, as well as immigrants from the developing world, increasingly visit physicians in North America with obesity, metabolic syndrome, or diabetes. Explanations limited to lifestyle factors such as diet and exercise are inadequate to explain the universality of what can be called a syndemic, a complex and widespread phenomenon in population health produced by multiple reinforcing conditions. Underlying the problem are complex factors-genetic, physiological, psychological, familial, social, economic, and political-coalescing to overdetermine these conditions. These interacting factors include events occurring during fetal life, maternal physiology and life context, the thrifty genotype, the nutritional transition, health impact of urbanization and immigration, social attributions and cultural perceptions of increased weight, and changes in food costs and availability resulting from globalization. Better appreciation of the complexity of causation underlying the worldwide epidemic of obesity and diabetes can refocus the work of clinicians and researchers to work at multiple levels to address prevention and treatment for these conditions among vulnerable populations.

Predicting Insulin Absorption and Glucose Uptake during Exercise in Type 1 Diabetes

NASA Astrophysics Data System (ADS)

Frank, Spencer; Hinshaw, Ling; Basu, Rita; Szeri, Andrew; Basu, Ananda

2017-11-01

A dose of insulin infused into subcutaneous tissue has been shown to absorb more quickly during exercise, potentially causing hypoglycemia in persons with type 1 diabetes. We develop a model that relates exercise-induced physiological changes to enhanced insulin-absorption (k) and glucose uptake (GU). Drawing on concepts of the microcirculation we derive a relationship that reveals that k and GU are mainly determined by two physiological parameters that characterize the tissue: the tissue perfusion rate (Q) and the capillary permeability surface area (PS). Independently measured values of Q and PS from the literature are used in the model to make predictions of k and GU. We compare these predictions to experimental observations of healthy and diabetic patients that are given a meal followed by rest or exercise. The experiments show that during exercise insulin concentrations significantly increase and that glucose levels fall rapidly. The model predictions are consistent with the experiments and show that increases in Q and PS directly increase k and GU. This mechanistic understanding provides a basis for handling exercise in control algorithms for an artificial pancreas. Now at University of British Columbia.

Guards at the gate: physiological and pathological roles of tissue-resident innate lymphoid cells in the lung.

PubMed

Cheng, Hang; Jin, Chengyan; Wu, Jing; Zhu, Shan; Liu, Yong-Jun; Chen, Jingtao

2017-12-01

The lung is an important open organ and the primary site of respiration. Many life-threatening diseases develop in the lung, e.g., pneumonia, asthma, chronic obstructive pulmonary diseases (COPDs), pulmonary fibrosis, and lung cancer. In the lung, innate immunity serves as the frontline in both anti-irritant response and anti-tumor defense and is also critical for mucosal homeostasis; thus, it plays an important role in containing these pulmonary diseases. Innate lymphoid cells (ILCs), characterized by their strict tissue residence and distinct function in the mucosa, are attracting increased attention in innate immunity. Upon sensing the danger signals from damaged epithelium, ILCs activate, proliferate, and release numerous cytokines with specific local functions; they also participate in mucosal immune-surveillance, immune-regulation, and homeostasis. However, when their functions become uncontrolled, ILCs can enhance pathological states and induce diseases. In this review, we discuss the physiological and pathological functions of ILC subsets 1 to 3 in the lung, and how the pathogenic environment affects the function and plasticity of ILCs.

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

PubMed

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

2013-06-01

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

Visualization of protein interactions in living Drosophila embryos by the bimolecular fluorescence complementation assay.

PubMed

Hudry, Bruno; Viala, Séverine; Graba, Yacine; Merabet, Samir

2011-01-28

Protein interactions control the regulatory networks underlying developmental processes. The understanding of developmental complexity will, therefore, require the characterization of protein interactions within their proper environment. The bimolecular fluorescence complementation (BiFC) technology offers this possibility as it enables the direct visualization of protein interactions in living cells. However, its potential has rarely been applied in embryos of animal model organisms and was only performed under transient protein expression levels. Using a Hox protein partnership as a test case, we investigated the suitability of BiFC for the study of protein interactions in the living Drosophila embryo. Importantly, all BiFC parameters were established with constructs that were stably expressed under the control of endogenous promoters. Under these physiological conditions, we showed that BiFC is specific and sensitive enough to analyse dynamic protein interactions. We next used BiFC in a candidate interaction screen, which led to the identification of several Hox protein partners. Our results establish the general suitability of BiFC for revealing and studying protein interactions in their physiological context during the rapid course of Drosophila embryonic development.

Genetic Code Expansion: A Powerful Tool for Understanding the Physiological Consequences of Oxidative Stress Protein Modifications

PubMed Central

2018-01-01

Posttranslational modifications resulting from oxidation of proteins (Ox-PTMs) are present intracellularly under conditions of oxidative stress as well as basal conditions. In the past, these modifications were thought to be generic protein damage, but it has become increasingly clear that Ox-PTMs can have specific physiological effects. It is an arduous task to distinguish between the two cases, as multiple Ox-PTMs occur simultaneously on the same protein, convoluting analysis. Genetic code expansion (GCE) has emerged as a powerful tool to overcome this challenge as it allows for the site-specific incorporation of an Ox-PTM into translated protein. The resulting homogeneously modified protein products can then be rigorously characterized for the effects of individual Ox-PTMs. We outline the strengths and weaknesses of GCE as they relate to the field of oxidative stress and Ox-PTMs. An overview of the Ox-PTMs that have been genetically encoded and applications of GCE to the study of Ox-PTMs, including antibody validation and therapeutic development, is described. PMID:29849913

Cell-specific STORM super-resolution imaging reveals nanoscale organization of cannabinoid signaling.

PubMed

Dudok, Barna; Barna, László; Ledri, Marco; Szabó, Szilárd I; Szabadits, Eszter; Pintér, Balázs; Woodhams, Stephen G; Henstridge, Christopher M; Balla, Gyula Y; Nyilas, Rita; Varga, Csaba; Lee, Sang-Hun; Matolcsi, Máté; Cervenak, Judit; Kacskovics, Imre; Watanabe, Masahiko; Sagheddu, Claudia; Melis, Miriam; Pistis, Marco; Soltesz, Ivan; Katona, István

2015-01-01

A major challenge in neuroscience is to determine the nanoscale position and quantity of signaling molecules in a cell type- and subcellular compartment-specific manner. We developed a new approach to this problem by combining cell-specific physiological and anatomical characterization with super-resolution imaging and studied the molecular and structural parameters shaping the physiological properties of synaptic endocannabinoid signaling in the mouse hippocampus. We found that axon terminals of perisomatically projecting GABAergic interneurons possessed increased CB1 receptor number, active-zone complexity and receptor/effector ratio compared with dendritically projecting interneurons, consistent with higher efficiency of cannabinoid signaling at somatic versus dendritic synapses. Furthermore, chronic Δ(9)-tetrahydrocannabinol administration, which reduces cannabinoid efficacy on GABA release, evoked marked CB1 downregulation in a dose-dependent manner. Full receptor recovery required several weeks after the cessation of Δ(9)-tetrahydrocannabinol treatment. These findings indicate that cell type-specific nanoscale analysis of endogenous protein distribution is possible in brain circuits and identify previously unknown molecular properties controlling endocannabinoid signaling and cannabis-induced cognitive dysfunction.

Measuring Apoptosis by Microscopy and Flow Cytometry.

PubMed

Hollville, Emilie; Martin, Seamus J

2016-02-02

Apoptosis is a mode of programmed cell death that plays an important role during development and in the maintenance of tissue homeostasis. Numerous physiological as well as pathological stimuli trigger apoptosis such as engagement of Fas, TRAIL, or TNF receptors, growth factor deprivation, hypoxia, or exposure to cytotoxic drugs. Apoptosis is coordinated from within by members of the caspase family of cysteine proteases that, upon activation, trigger a series of morphological changes including cell shrinkage, extensive plasma membrane blebbing, chromatin condensation, DNA hydrolysis, and nuclear fragmentation. These dramatic structural and biochemical alterations result not only in the controlled dismantling of the cell, but also in the efficient recognition and removal of apoptotic cells by phagocytes. Necrosis, which is typically nonprogrammed or imposed upon the cell by overwhelming membrane or organelle damage, is characterized by rapid plasma membrane rupture followed by organelle and cell swelling. Necrosis is often provoked by infectious agents or a severe departure from physiological conditions. This unit describes protocols for the measurement of apoptosis and for distinguishing apoptosis from necrosis. Copyright © 2016 John Wiley & Sons, Inc.

Crystallization and preliminary X-ray diffraction analysis of the phosphate-binding protein PhoX from Xanthomonas citri

PubMed Central

Pegos, Vanessa R.; Medrano, Francisco Javier; Balan, Andrea

2014-01-01

Xanthomonas axonopodis pv. citri (X. citri) is an important bacterium that causes citrus canker disease in plants in Brazil and around the world, leading to significant economic losses. Determination of the physiology and mechanisms of pathogenesis of this bacterium is an important step in the development of strategies for its containment. Phosphate is an essential ion in all microrganisms owing its importance during the synthesis of macromolecules and in gene and protein regulation. Interestingly, X. citri has been identified to present two periplasmic binding proteins that have not been further characterized: PstS, from an ATP-binding cassette for high-affinity uptake and transport of phosphate, and PhoX, which is encoded by an operon that also contains a putative porin for the transport of phosphate. Here, the expression, purification and crystallization of the phosphate-binding protein PhoX and X-ray data collection at 3.0 Å resolution are described. Biochemical, biophysical and structural data for this protein will be helpful in the elucidation of its function in phosphate uptake and the physiology of the bacterium. PMID:25484207

Endochondral bone formation in embryonic mouse pre-metatarsals

NASA Technical Reports Server (NTRS)

Klement, B. J.; Spooner, B. S.

1992-01-01

Long term exposure to a reduced gravitational environment has a deleterious effect on bone. The developmental events which occur prior to initial bone deposition will provide insight into the regulation of mature bone physiology. We have characterized a system in which the events preceding bone formation take place in an isolated in vitro organ culture environment. We show that cultured pre-metatarsal tissue parallels development of pre-metatarsal tissue in the embryo. Both undergo mesenchyme differentiation and morphogenesis to form a cartilage rod, which resembles the future bone, followed by terminal chondrocyte differentiation in a definite morphogenetic pattern. These sequential steps occur prior to osteoblast maturation and bone matrix deposition in the developing organism. Alkaline phosphatase (ALP) activity is a distinctive enzymatic marker for mineralizing tissues. We have measured this activity throughout pre-metatarsal development and show (a) where in the tissue it is predominantly found, and (b) that this is indeed the mineralizing isoform of the enzyme.

Development of physical and mathematical models for the Porous Ceramic Tube Plant Nutrification System (PCTPNS)

NASA Technical Reports Server (NTRS)

Tsao, D. Teh-Wei; Okos, M. R.; Sager, J. C.; Dreschel, T. W.

1992-01-01

A physical model of the Porous Ceramic Tube Plant Nutrification System (PCTPNS) was developed through microscopic observations of the tube surface under various operational conditions. In addition, a mathematical model of this system was developed which incorporated the effects of the applied suction pressure, surface tension, and gravitational forces as well as the porosity and physical dimensions of the tubes. The flow of liquid through the PCTPNS was thus characterized for non-biological situations. One of the key factors in the verification of these models is the accurate and rapid measurement of the 'wetness' or holding capacity of the ceramic tubes. This study evaluated a thermistor based moisture sensor device and recommendations for future research on alternative sensing devices are proposed. In addition, extensions of the physical and mathematical models to include the effects of plant physiology and growth are also discussed for future research.

The response of transgenic Brassica species to salt stress: a review.

PubMed

Shah, Nadil; Anwar, Sumera; Xu, Jingjing; Hou, Zhaoke; Salah, Akram; Khan, Shahbaz; Gong, Jianfang; Shang, Zhengwei; Qian, Li; Zhang, Chunyu

2018-06-01

Salt stress is considered one of the main abiotic factors to limit crop growth and productivity by affecting morpho-physiological and biochemical processes. Genetically, a number of salt tolerant Brassica varieties have been developed and introduced, but breeding of such varieties is time consuming. Therefore, current focus is on transgenic technology, which plays an important role in the development of salt tolerant varieties. Various salt tolerant genes have been characterized and incorporated into Brassica. Therefore, such genetic transformation of Brassica species is a significant step for improvement of crops, as well as conferring salt stress resistance qualities to Brassica species. Complete genome sequencing has made the task of genetically transforming Brassica species easier, by identifying desired candidate genes. The present review discusses relevant information about the principles which should be employed to develop transgenic Brassica species, and also will recommend tools for improved tolerance to salinity.

The Developmental Process of the Growing Motile Ciliary Tip Region.

PubMed

Reynolds, Matthew J; Phetruen, Tanaporn; Fisher, Rebecca L; Chen, Ke; Pentecost, Brian T; Gomez, George; Ounjai, Puey; Sui, Haixin

2018-05-22

Eukaryotic motile cilia/flagella play vital roles in various physiological processes in mammals and some protists. Defects in cilia formation underlie multiple human disorders, known as ciliopathies. The detailed processes of cilia growth and development are still far from clear despite extensive studies. In this study, we characterized the process of cilium formation (ciliogenesis) by investigating the newly developed motile cilia of deciliated protists using complementary techniques in electron microscopy and image analysis. Our results demonstrated that the distal tip region of motile cilia exhibit progressive morphological changes as cilia develop. This developmental process is time-dependent and continues after growing cilia reach their full lengths. The structural analysis of growing ciliary tips revealed that B-tubules of axonemal microtubule doublets terminate far away from the tip end, which is led by the flagellar tip complex (FTC), demonstrating that the FTC might not directly mediate the fast turnover of intraflagellar transport (IFT).

Genetically Encoded Biosensors in Plants: Pathways to Discovery.

PubMed

Walia, Ankit; Waadt, Rainer; Jones, Alexander M

2018-04-29

Genetically encoded biosensors that directly interact with a molecule of interest were first introduced more than 20 years ago with fusion proteins that served as fluorescent indicators for calcium ions. Since then, the technology has matured into a diverse array of biosensors that have been deployed to improve our spatiotemporal understanding of molecules whose dynamics have profound influence on plant physiology and development. In this review, we address several types of biosensors with a focus on genetically encoded calcium indicators, which are now the most diverse and advanced group of biosensors. We then consider the discoveries in plant biology made by using biosensors for calcium, pH, reactive oxygen species, redox conditions, primary metabolites, phytohormones, and nutrients. These discoveries were dependent on the engineering, characterization, and optimization required to develop a successful biosensor; they were also dependent on the methodological developments required to express, detect, and analyze the readout of such biosensors.

Wearable physiological sensors and real-time algorithms for detection of acute mountain sickness.

PubMed

Muza, Stephen R

2018-03-01

This is a minireview of potential wearable physiological sensors and algorithms (process and equations) for detection of acute mountain sickness (AMS). Given the emerging status of this effort, the focus of the review is on the current clinical assessment of AMS, known risk factors (environmental, demographic, and physiological), and current understanding of AMS pathophysiology. Studies that have examined a range of physiological variables to develop AMS prediction and/or detection algorithms are reviewed to provide insight and potential technological roadmaps for future development of real-time physiological sensors and algorithms to detect AMS. Given the lack of signs and nonspecific symptoms associated with AMS, development of wearable physiological sensors and embedded algorithms to predict in the near term or detect established AMS will be challenging. Prior work using [Formula: see text], HR, or HRv has not provided the sensitivity and specificity for useful application to predict or detect AMS. Rather than using spot checks as most prior studies have, wearable systems that continuously measure SpO 2 and HR are commercially available. Employing other statistical modeling approaches such as general linear and logistic mixed models or time series analysis to these continuously measured variables is the most promising approach for developing algorithms that are sensitive and specific for physiological prediction or detection of AMS.

New Perspectives on Acetate and One-Carbon Metabolism in the Methanoarchaea

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

Ferry, James

Carbonic anhydrases catalyze the reversible hydration of carbon dioxide to bicarbonate. Although widespread in prokaryotes of the domains Bacteria and Archaea, few have been investigated and the physiological functions are largely unknown. Carbonic anhydrases are of biotechnological interest for carbon dioxide capture and sequestration at point sources. Prokaryotes encode three independently evolved classes. The alpha-class is restricted to a few pathogens and the other two are uniformly distributed in phylogenetically and physiologically diverse species. Although wide-spread in prokaryotes, only three gamma-class enzymes have been biochemically characterized and the physiological functions have not been investigated. The gamma-class is prominent in anaerobicmore » acetate-utilizing methane-producing species of the genus Methanosarcina that encode three subclasses. Enzymes from two of the subclasses, Cam and CamH from Methanosarcina thermophila, have been characterized and found to utilize iron in the active site which is the first example of an iron-containing carbonic anhydrase. No representative of the third subclass has been isolated, although this subclass constitutes the great majority of the β-class. This grant application proposed to characterize gamma-class carbonic anhydrases from diverse anaerobic prokaryotes from the domains Bacteria and Archaea to broaden the understanding of this enzyme. In particular, the three subclasses present the genetically tractable acetate-utilizing methanogen Methanosarcina acetivorans will be investigated to extend studies of acetate and one-carbon metabolism in this species. A genetic approach will be taken to ascertain the physiological functions. It is also proposed to delve deeper into the mechanism of Cam from M. thermophila, the archetype of the gamma-class, via a high resolution neutron structure and kinetic analysis of site-specific amino acid replacement variants. In the course of the investigation, goals were added to take advantage of discoveries on enzymes responding to oxidative stress.« less

Characterization and fine mapping of qkc7.03: a major locus for kernel cracking in maize.

PubMed

Yang, Mingtao; Chen, Lin; Wu, Xun; Gao, Xing; Li, Chunhui; Song, Yanchun; Zhang, Dengfeng; Shi, Yunsu; Li, Yu; Li, Yong-Xiang; Wang, Tianyu

2018-02-01

A major locus conferring kernel cracking in maize was characterized and fine mapped to an interval of 416.27 kb. Meanwhile, combining the results of transcriptomic analysis, the candidate gene was inferred. Seed development requires a proper structural and physiological balance between the maternal tissues and the internal structures of the seeds. In maize, kernel cracking is a disorder in this balance that seriously limits quality and yield and is characterized by a cracked pericarp at the kernel top and endosperm everting. This study elucidated the genetic basis and characterization of kernel cracking. Primarily, a near isogenic line (NIL) with a B73 background exhibited steady kernel cracking across environments. Therefore, deprived mapping populations were developed from this NIL and its recurrent parent B73. A major locus on chromosome 7, qkc7.03, was identified to be associated with the cracking performance. According to a progeny test of recombination events, qkc7.03 was fine mapped to a physical interval of 416.27 kb. In addition, obvious differences were observed in embryo development and starch granule arrangement within the endosperm between the NIL and its recurrent parent upon the occurrence of kernel cracking. Moreover, compared to its recurrent parent, the transcriptome of the NIL showed a significantly down-regulated expression of genes related to zeins, carbohydrate synthesis and MADS-domain transcription factors. The transcriptomic analysis revealed ten annotated genes within the target region of qkc7.03, and only GRMZM5G899476 was differently expressed between the NIL and its recurrent parent, indicating that this gene might be a candidate gene for kernel cracking. The results of this study facilitate the understanding of the potential mechanism underlying kernel cracking in maize.

Retrospective Analysis of Inflight Exercise Loading and Physiological Outcomes

NASA Technical Reports Server (NTRS)

Ploutz-Snyder, L. L.; Buxton, R. E.; De Witt, J. K.; Guilliams, M. E.; Hanson, A. M.; Peters, B. T.; Pandorf, M. M. Scott; Sibonga, J. D.

2014-01-01

Astronauts perform exercise throughout their missions to counter the health declines that occur as a result of long-term exposure to weightlessness. Although all astronauts perform exercise during their missions, the specific prescriptions, and thus the mechanical loading, differs among individuals. For example, inflight ground reaction force data indicate that subject-specific differences exist in foot forces created when exercising on the second-generation treadmill (T2) [1]. The current exercise devices allow astronauts to complete prescriptions at higher intensities, resulting in greater benefits with increased efficiency. Although physiological outcomes have improved, the specific factors related to the increased benefits are unknown. In-flight exercise hardware collect data that allows for exploratory analyses to determine if specific performance factors relate to physiological outcomes. These analyses are vital for understanding which components of exercise are most critical for optimal human health and performance. The relationship between exercise performance variables and physiological changes during flight has yet to be fully investigated. Identifying the critical performance variables that relate to improved physiological outcomes is vital for creating current and future exercise prescriptions to optimize astronaut health. The specific aims of this project are: 1) To quantify the exercise-related mechanical loading experienced by crewmembers on T2 and ARED during their mission on ISS; 2) To explore relationships between exercise loading variables, bone, and muscle health changes during the mission; 3) To determine if specific mechanical loading variables are more critical than others in protecting physiology; 4) To develop methodology for operational use in monitoring accumulated training loads during crew exercise programs. This retrospective analysis, which is currently in progress, is being conducted using data from astronauts that have flown long-duration missions onboard the ISS and have had access to exercise on the T2 and the Advanced Resistive Exercise Device (ARED). The specific exercise prescriptions vary for each astronaut. General exercise summary metrics will be developed to quantify exercise intensities, volumes, and durations for each subject. Where available, ground reaction force data will be used to quantify mechanical loading experienced by each astronaut. These inflight exercise metrics will be investigated relative to changes in pre- to post-flight bone and muscle health to identify which specific variables are related with improved or degraded physiological outcomes. The information generated from this analysis will fill gaps related to typical bone loading characterization, exercise performance capability, exercise volume and efficiency, and importance of exercise hardware. In addition, methods for quantification of exercise loading for use in monitoring the exercise programs during future space missions will be explored with the intent to inform exercise scientists and trainers as to the critical aspects of inflight exercise prescriptions.

Determinants of physiological and perceived physiological stress reactivity in children and adolescents.

PubMed

Evans, Brittany E; Greaves-Lord, Kirstin; Euser, Anja S; Tulen, Joke H M; Franken, Ingmar H A; Huizink, Anja C

2013-01-01

Abnormal physiological stress reactivity is increasingly investigated as a vulnerability marker for various physical and psychological health problems. However, studies are inconsistent in taking into account potential covariates that may influence the developing stress system. We systematically tested determinants (individual, developmental, environmental and substance use-related) of physiological and perceived physiological stress reactivity. We also examined the relation between physiological and perceived physiological stress reactivity. In a stratified sample of 363 children (7-12 years) and 344 adolescents (13-20 years) from the general population, we examined cortisol, heart rate, respiratory sinus arrhythmia and perceived physiological stress reactivity to a psychosocial stress procedure. Using multivariate linear regression models, we found that individual, developmental, environmental and substance use-related factors were related to each of the stress response indices. These determinant factors were different for each of the stress reactivity indices, and different in children versus adolescents. Perceived physiological stress reactivity predicted cortisol reactivity in adolescents only. All other relations between perceived physiological and physiological stress reactivity were not significant. As physiological stress variables are often examined as vulnerability markers for the development of health problems, we maintain that it is essential that future studies take into consideration factors that may account for found relations. Our study provides an overview and indication of which variables should be considered in the investigation of the relation between physiological stress indices and illness.

Proteome Comparisons between Hemolymph of Two Honeybee Strains (Apis mellifera ligustica) Reveal Divergent Molecular Basis in Driving Hemolymph Function and High Royal Jelly Secretion.

PubMed

Ararso, Zewdu; Ma, Chuan; Qi, Yuping; Feng, Mao; Han, Bin; Hu, Han; Meng, Lifeng; Li, Jianke

2018-01-05

Hemolymph is vital for the immunity of honeybees and offers a way to investigate their physiological status. To gain novel insight into the functionality and molecular details of the hemolymph in driving increased Royal Jelly (RJ) production, we characterized and compared hemolymph proteomes across the larval and adult ages of Italian bees (ITbs) and Royal Jelly bees (RJbs), a stock selected from ITbs for increasing RJ output. Unprecedented in-depth proteome was attained with the identification of 3394 hemolymph proteins in both bee lines. The changes in proteome support the general function of hemolymph to drive development and immunity across different ages. However, age-specific proteome settings have adapted to prime the distinct physiology for larvae and adult bees. In larvae, the proteome is thought to drive temporal immunity, rapid organogenesis, and reorganization of larval structures. In adults, the proteome plays key roles in prompting tissue development and immune defense in newly emerged bees, in gland maturity in nurse bees, and in carbohydrate energy production in forager bees. Between larval and adult samples of the same age, RJbs and ITbs have tailored distinct hemolymph proteome programs to drive their physiology. In particular, in day 4 larvae and nurse bees, a large number of highly abundant proteins are enriched in protein synthesis and energy metabolism in RJbs. This implies that they have adapted their proteome to initiate different developmental trajectories and high RJ secretion in response to selection for enhanced RJ production. Our hitherto unexplored in-depth proteome coverage provides novel insight into molecular details that drive hemolymph function and high RJ production by RJbs.

ATM activation in normal human tissues and testicular cancer.

PubMed

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

2005-06-01

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

Myocardial dysfunction occurs prior to changes in ventricular geometry in mice with chronic kidney disease (CKD).

PubMed

Winterberg, Pamela D; Jiang, Rong; Maxwell, Josh T; Wang, Bo; Wagner, Mary B

2016-03-01

Uremic cardiomyopathy is responsible for high morbidity and mortality rates among patients with chronic kidney disease (CKD), but the underlying mechanisms contributing to this complex phenotype are incompletely understood. Myocardial deformation analyses (ventricular strain) of patients with mild CKD have recently been reported to predict adverse clinical outcome. We aimed to determine if early myocardial dysfunction in a mouse model of CKD could be detected using ventricular strain analyses. CKD was induced in 5-week-old male 129X1/SvJ mice through partial nephrectomy (5/6Nx) with age-matched mice undergoing bilateral sham surgeries serving as controls. Serial transthoracic echocardiography was performed over 16 weeks following induction of CKD. Invasive hemodynamic measurements were performed at 8 weeks. Gene expression and histology was performed on hearts at 8 and 16 weeks. CKD mice developed decreased longitudinal strain (-25 ± 4.2% vs. -29 ± 2.3%; P = 0.01) and diastolic dysfunction (E/A ratio 1.2 ± 0.15 vs. 1.9 ± 0.18; P < 0.001) compared to controls as early as 2 weeks following 5/6Nx. In contrast, ventricular hypertrophy was not apparent until 4 weeks. Hearts from CKD mice developed progressive fibrosis at 8 and 16 weeks with gene signatures suggestive of evolving heart failure with elevated expression of natriuretic peptides. Uremic cardiomyopathy in this model is characterized by early myocardial dysfunction which preceded observable changes in ventricular geometry. The model ultimately resulted in myocardial fibrosis and increased expression of natriuretic peptides suggestive of progressive heart failure. © 2016 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

Adaptation to Life in the High Andes: Nocturnal Oxyhemoglobin Saturation in Early Development.

PubMed

Hill, Catherine Mary; Baya, Ana; Gavlak, Johanna; Carroll, Annette; Heathcote, Kate; Dimitriou, Dagmara; L'Esperance, Veline; Webster, Rebecca; Holloway, John; Virues-Ortega, Javier; Kirkham, Fenella Jane; Bucks, Romola Starr; Hogan, Alexandra Marie

2016-05-01

Physiological adaptation to high altitude hypoxia may be impaired in Andeans with significant European ancestry. The respiratory 'burden' of sleep may challenge adaptation, leading to relative nocturnal hypoxia. Developmental aspects of sleep-related breathing in high-altitude native children have not previously been reported. We aimed to determine the influence of development on diurnal-nocturnal oxyhemoglobin differences in children living at high altitude. This was a cross-sectional, observational study. Seventy-five healthy Bolivian children aged 6 mo to 17 y, native to low altitude (500 m), moderate high altitude (2,500 m), and high altitude (3,700 m) were recruited. Daytime resting pulse oximetry was compared to overnight recordings using Masimo radical oximeters. Genetic ancestry was determined from DNA samples. Children had mixed European/Amerindian ancestry, with no significant differences between altitudes. Sixty-two participants had ≥ 5 h of nocturnal, artifact-free data. As predicted, diurnal mean oxyhemoglobin saturation decreased across altitudes (infants and children, both P < 0.001), with lowest diurnal values at high altitude in infants. At high altitude, there was a greater drop in nocturnal mean oxyhemoglobin saturation (infants, P < 0.001; children, P = 0.039) and an increase in variability (all P ≤ 0.001) compared to low altitude. Importantly, diurnal to nocturnal altitude differences diminished (P = 0.036), from infancy to childhood, with no further change during adolescence. Physiological adaptation to high-altitude living in native Andeans is unlikely to compensate for the significant differences we observed between diurnal and nocturnal oxyhemoglobin saturation, most marked in infancy. This vulnerability to sleep-related hypoxia in early childhood has potential lifespan implications. Future studies should characterize the sleep- related respiratory physiology underpinning our observations. © 2016 Associated Professional Sleep Societies, LLC.

Periodontal Ligament Entheses and their Adaptive Role in the Context of Dentoalveolar Joint Function

PubMed Central

Lin, Jeremy D.; Jang, Andrew T.; Kurylo, Michael P.; Hurng, Jonathan; Yang, Feifei; Yang, Lynn; Pal, Arvin; Chen, Ling; Ho, Sunita P.

2017-01-01

Objectives The dynamic bone-periodontal ligament (PDL)-tooth fibrous joint consists of two adaptive functionally graded interfaces (FGI), the PDL-bone and PDL-cementum that respond to mechanical strain transmitted during mastication. In general, from a materials and mechanics perspective, FGI prevent catastrophic failure during prolonged cyclic loading. This review is a discourse of results gathered from literature to illustrate the dynamic adaptive nature of the fibrous joint in response to physiologic and pathologic simulated functions, and experimental tooth movement. Methods Historically, studies have investigated soft to hard tissue transitions through analytical techniques that provided insights into structural, biochemical, and mechanical characterization methods. Experimental approaches included two dimensional to three dimensional advanced in situ imaging and analytical techniques. These techniques allowed mapping and correlation of deformations to physicochemical and mechanobiological changes within volumes of the complex subjected to concentric and eccentric loading regimes respectively. Results Tooth movement is facilitated by mechanobiological activity at the interfaces of the fibrous joint and generates elastic discontinuities at these interfaces in response to eccentric loading. Both concentric and eccentric loads mediated cellular responses to strains, and prompted self-regulating mineral forming and resorbing zones that in turn altered the functional space of the joint. Significance A multiscale biomechanics and mechanobiology approach is important for correlating joint function to tissue-level strain-adaptive properties with overall effects on joint form as related to physiologic and pathologic functions. Elucidating the shift in localization of biomolecules specifically at interfaces during development, function, and therapeutic loading of the joint is critical for developing “functional regeneration and adaptation” strategies with an emphasis on restoring physiologic joint function. PMID:28476202

Legacy of Biomedical Research During the Space Shuttle Program

NASA Technical Reports Server (NTRS)

Hayes, Judith C.

2011-01-01

The Space Shuttle Program provided many opportunities to study the role of spaceflight on human life for over 30 years and represented the longest and largest US human spaceflight program. Outcomes of the research were understanding the effect of spaceflight on human physiology and performance, countermeasures, operational protocols, and hardware. The Shuttle flights were relatively short, < 16 days and routinely had 4 to 6 crewmembers for a total of 135 flights. Biomedical research was conducted on the Space Shuttle using various vehicle resources. Specially constructed pressurized laboratories called Spacelab and SPACEHAB housed many laboratory instruments to accomplish experiments in the Shuttle s large payload bay. In addition to these laboratory flights, nearly every mission had dedicated human life science research experiments conducted in the Shuttle middeck. Most Shuttle astronauts participated in some life sciences research experiments either as test subjects or test operators. While middeck experiments resulted in a low sample per mission compared to many Earth-based studies, this participation allowed investigators to have repetition of tests over the years on successive Shuttle flights. In addition, as a prelude to the International Space Station (ISS), NASA used the Space Shuttle as a platform for assessing future ISS hardware systems and procedures. The purpose of this panel is to provide an understanding of science integration activities required to implement Shuttle research, review biomedical research, characterize countermeasures developed for Shuttle and ISS as well as discuss lessons learned that may support commercial crew endeavors. Panel topics include research integration, cardiovascular physiology, neurosciences, skeletal muscle, and exercise physiology. Learning Objective: The panel provides an overview from the Space Shuttle Program regarding research integration, scientific results, lessons learned from biomedical research and countermeasure development.

Non-targeted Metabolomics in Diverse Sorghum Breeding Lines Indicates Primary and Secondary Metabolite Profiles Are Associated with Plant Biomass Accumulation and Photosynthesis

DOE PAGES

Turner, Marie F.; Heuberger, Adam L.; Kirkwood, Jay S.; ...

2016-07-11

Metabolomics is an emerging method to improve our understanding of how genetic diversity affects phenotypic variation in plants. Recent studies have demonstrated that genotype has a major influence on biochemical variation in several types of plant tissues, however, the association between metabolic variation and variation in morphological and physiological traits is largely unknown. Sorghum bicolor (L.) is an important food and fuel crop with extensive genetic and phenotypic variation. Sorghum lines have been bred for differing phenotypes beneficial for production of grain (food), stem sugar (food, fuel), and cellulosic biomass (forage, fuel), and these varying phenotypes are the end productsmore » of innate metabolic programming which determines how carbon is allocated during plant growth and development. Further, sorghum has been adapted among highly diverse environments. Because of this geographic and phenotypic variation, the sorghum metabolome is expected to be highly divergent; however, metabolite variation in sorghum has not been characterized. Here, we utilize a phenotypically diverse panel of sorghum breeding lines to identify associations between leaf metabolites and morpho-physiological traits. The panel (11 lines) exhibited significant variation for 21 morpho-physiological traits, as well as broader trends in variation by sorghum type (grain vs. biomass types). Variation was also observed for cell wall constituents (glucan, xylan, lignin, ash). Non-targeted metabolomics analysis of leaf tissue showed that 956 of 1181 metabolites varied among the lines (81%, ANOVA, FDR adjusted p < 0.05). Both univariate and multivariate analyses determined relationships between metabolites and morpho-physiological traits, and 384 metabolites correlated with at least one trait (32%, p < 0.05), including many secondary metabolites such as glycosylated flavonoids and chlorogenic acids. The use of metabolomics to explain relationships between two or more morpho-physiological traits was explored and showed chlorogenic and shikimic acid to be associated with photosynthesis, early plant growth and final biomass measures in sorghum. In conclusion, taken together, this study demonstrates the integration of metabolomics with morpho-physiological datasets to elucidate links between plant metabolism, growth, and architecture.« less

Non-targeted Metabolomics in Diverse Sorghum Breeding Lines Indicates Primary and Secondary Metabolite Profiles Are Associated with Plant Biomass Accumulation and Photosynthesis

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

Turner, Marie F.; Heuberger, Adam L.; Kirkwood, Jay S.

Metabolomics is an emerging method to improve our understanding of how genetic diversity affects phenotypic variation in plants. Recent studies have demonstrated that genotype has a major influence on biochemical variation in several types of plant tissues, however, the association between metabolic variation and variation in morphological and physiological traits is largely unknown. Sorghum bicolor (L.) is an important food and fuel crop with extensive genetic and phenotypic variation. Sorghum lines have been bred for differing phenotypes beneficial for production of grain (food), stem sugar (food, fuel), and cellulosic biomass (forage, fuel), and these varying phenotypes are the end productsmore » of innate metabolic programming which determines how carbon is allocated during plant growth and development. Further, sorghum has been adapted among highly diverse environments. Because of this geographic and phenotypic variation, the sorghum metabolome is expected to be highly divergent; however, metabolite variation in sorghum has not been characterized. Here, we utilize a phenotypically diverse panel of sorghum breeding lines to identify associations between leaf metabolites and morpho-physiological traits. The panel (11 lines) exhibited significant variation for 21 morpho-physiological traits, as well as broader trends in variation by sorghum type (grain vs. biomass types). Variation was also observed for cell wall constituents (glucan, xylan, lignin, ash). Non-targeted metabolomics analysis of leaf tissue showed that 956 of 1181 metabolites varied among the lines (81%, ANOVA, FDR adjusted p < 0.05). Both univariate and multivariate analyses determined relationships between metabolites and morpho-physiological traits, and 384 metabolites correlated with at least one trait (32%, p < 0.05), including many secondary metabolites such as glycosylated flavonoids and chlorogenic acids. The use of metabolomics to explain relationships between two or more morpho-physiological traits was explored and showed chlorogenic and shikimic acid to be associated with photosynthesis, early plant growth and final biomass measures in sorghum. In conclusion, taken together, this study demonstrates the integration of metabolomics with morpho-physiological datasets to elucidate links between plant metabolism, growth, and architecture.« less

Physiological effects of weightlessness: countermeasure system development for a long-term Chinese manned spaceflight.

PubMed

Wang, Linjie; Li, Zhili; Tan, Cheng; Liu, Shujuan; Zhang, Jianfeng; He, Siyang; Zou, Peng; Liu, Weibo; Li, Yinghui

2018-04-25

The Chinese space station will be built around 2020. As a national space laboratory, it will offer unique opportunities for studying the physiological effects of weightlessness and the efficacy of the countermeasures against such effects. In this paper, we described the development of countermeasure systems in the Chinese space program. To emphasize the need of the Chinese space program to implement its own program for developing countermeasures, we reviewed the literature on the negative physiological effects of weightlessness, the challenges of completing missions, the development of countermeasure devices, the establishment of countermeasure programs, and the efficacy of the countermeasure techniques in American and Russian manned spaceflights. In addition, a brief overview was provided on the Chinese research and development on countermeasures to discuss the current status and goals of the development of countermeasures against physiological problems associated with weightlessness.

Synthesis and characterization of a smart contrast agent sensitive to calcium.

PubMed

Dhingra, Kirti; Maier, Martin E; Beyerlein, Michael; Angelovski, Goran; Logothetis, Nikos K

2008-08-07

A novel first-generation Ca2+ sensitive contrast agent, Gd-DOPTRA has been synthesized and characterized. The agent shows approximately 100% relaxivity enhancement upon addition of Ca2+. The agent is selective and sensitive to Ca2+ also in the presence of Mg2+ and Zn2+. The relaxivity studies carried out in physiological fluids prove the prospects of the agent for in vivo measurements.

Genetic approaches in comparative and evolutionary physiology

PubMed Central

Bridgham, Jamie T.; Kelly, Scott A.; Garland, Theodore

2015-01-01

Whole animal physiological performance is highly polygenic and highly plastic, and the same is generally true for the many subordinate traits that underlie performance capacities. Quantitative genetics, therefore, provides an appropriate framework for the analysis of physiological phenotypes and can be used to infer the microevolutionary processes that have shaped patterns of trait variation within and among species. In cases where specific genes are known to contribute to variation in physiological traits, analyses of intraspecific polymorphism and interspecific divergence can reveal molecular mechanisms of functional evolution and can provide insights into the possible adaptive significance of observed sequence changes. In this review, we explain how the tools and theory of quantitative genetics, population genetics, and molecular evolution can inform our understanding of mechanism and process in physiological evolution. For example, lab-based studies of polygenic inheritance can be integrated with field-based studies of trait variation and survivorship to measure selection in the wild, thereby providing direct insights into the adaptive significance of physiological variation. Analyses of quantitative genetic variation in selection experiments can be used to probe interrelationships among traits and the genetic basis of physiological trade-offs and constraints. We review approaches for characterizing the genetic architecture of physiological traits, including linkage mapping and association mapping, and systems approaches for dissecting intermediary steps in the chain of causation between genotype and phenotype. We also discuss the promise and limitations of population genomic approaches for inferring adaptation at specific loci. We end by highlighting the role of organismal physiology in the functional synthesis of evolutionary biology. PMID:26041111

Chewing Over Physiology Integration

ERIC Educational Resources Information Center

Abdulkader, Fernando; Azevedo-Martins, Anna Karenina; de Arcisio Miranda, Manoel; Brunaldi, Kellen

2005-01-01

An important challenge for both students and teachers of physiology is to integrate the differentareas in which physiological knowledge is didactically divided. In developing countries, such an issue is even more demanding, because budget restrictions often affect the physiology program with laboratory classes being the first on the list when it…

DEVELOPMENT OF A PHYSIOLOGICALLY BASED PHARMACOKINETIC MODEL FOR DELTAMETHRIN IN DEVELOPING SPRAGUE-DAWLEY RATS

EPA Science Inventory

This work describes the development of a physiologically based pharmacokinetic (PBPK) model of deltamethrin, a type II pyrethroid, in the developing male Sprague-Dawley rat. Generalized Michaelis-Menten equations were used to calculate metabolic rate constants and organ weights ...

Peripubertal Vitamin D3 Deficiency Delays Puberty and Disrupts the Estrous Cycle in Adult Female Mice1

PubMed Central

Dicken, Cary L.; Israel, Davelene D.; Davis, Joe B.; Sun, Yan; Shu, Jun; Hardin, John; Neal-Perry, Genevieve

2012-01-01

ABSTRACT The mechanism(s) by which vitamin D3 regulates female reproduction is minimally understood. We tested the hypothesis that peripubertal vitamin D3 deficiency disrupts hypothalamic-pituitary-ovarian physiology. To test this hypothesis, we used wild-type mice and Cyp27b1 (the rate-limiting enzyme in the synthesis of 1,25-dihydroxyvitamin D3) null mice to study the effect of vitamin D3 deficiency on puberty and reproductive physiology. At the time of weaning, mice were randomized to a vitamin D3-replete or -deficient diet supplemented with calcium. We assessed the age of vaginal opening and first estrus (puberty markers), gonadotropin levels, ovarian histology, ovarian responsiveness to exogenous gonadotropins, and estrous cyclicity. Peripubertal vitamin D3 deficiency significantly delayed vaginal opening without affecting the number of GnRH-immunopositive neurons or estradiol-negative feedback on gonadotropin levels during diestrus. Young adult females maintained on a vitamin D3-deficient diet after puberty had arrested follicular development and prolonged estrous cycles characterized by extended periods of diestrus. Ovaries of vitamin D3-deficient Cyp27b1 null mice responded to exogenous gonadotropins and deposited significantly more oocytes into the oviducts than mice maintained on a vitamin D3-replete diet. Estrous cycles were restored when vitamin D3-deficient Cyp27b1 null young adult females were transferred to a vitamin D3-replete diet. This study is the first to demonstrate that peripubertal vitamin D3 sufficiency is important for an appropriately timed pubertal transition and maintenance of normal female reproductive physiology. These data suggest vitamin D3 is a key regulator of neuroendocrine and ovarian physiology. PMID:22572998

Different profiles of decision making and physiology under varying levels of stress in trained military personnel.

PubMed

Gamble, Katherine R; Vettel, Jean M; Patton, Debra J; Eddy, Marianna D; Caroline Davis, F; Garcia, Javier O; Spangler, Derek P; Thayer, Julian F; Brooks, Justin R

2018-03-23

Decision making is one of the most vital processes we use every day, ranging from mundane decisions about what to eat to life-threatening choices such as how to avoid a car collision. Thus, the context in which our decisions are made is critical, and our physiology enables adaptive responses that account for how environmental stress influences our performance. The relationship between stress and decision making can additionally be affected by one's expertise in making decisions in high-threat environments, where experts can develop an adaptive response that mitigates the negative impacts of stress. In the present study, 26 male military personnel made friend/foe discriminations in an environment where we manipulated the level of stress. In the high-stress condition, participants received a shock when they incorrectly shot a friend or missed shooting a foe; in the low-stress condition, participants received a vibration for an incorrect decision. We characterized performance using signal detection theory to investigate whether a participant changed their decision criterion to avoid making an error. Results showed that under high-stress, participants made more false alarms, mistaking friends as foes, and this co-occurred with increased high frequency heart rate variability. Finally, we examined the relationship between decision making and physiology, and found that participants exhibited adaptive behavioral and physiological profiles under different stress levels. We interpret this adaptive profile as a marker of an expert's ingrained training that does not require top down control, suggesting a way that expert training in high-stress environments helps to buffer negative impacts of stress on performance. Published by Elsevier B.V.

Computer tool to evaluate the cue reactivity of chemically dependent individuals.

PubMed

Silva, Meire Luci da; Frère, Annie France; Oliveira, Henrique Jesus Quintino de; Martucci Neto, Helio; Scardovelli, Terigi Augusto

2017-03-01

Anxiety is one of the major influences on the dropout of relapse and treatment of substance abuse treatment. Chemically dependent individuals need (CDI) to be aware of their emotional state in situations of risk during their treatment. Many patients do not agree with the diagnosis of the therapist when considering them vulnerable to environmental stimuli related to drugs. This research presents a cue reactivity detection tool based on a device acquiring physiological signals connected to personal computer. Depending on the variations of the emotional state of the drug addict, alteration of the physiological signals will be detected by the computer tool (CT) which will modify the displayed virtual sets without intervention of the therapist. Developed in 3ds Max® software, the CT is composed of scenarios and objects that are in the habit of marijuana and cocaine dependent individual's daily life. The interaction with the environment is accomplished using a Human-Computer Interface (HCI) that converts incoming physiological signals indicating anxiety state into commands that change the scenes. Anxiety was characterized by the average variability from cardiac and respiratory rate of 30 volunteers submitted stress environment situations. To evaluate the effectiveness of cue reactivity a total of 50 volunteers who were marijuana, cocaine or both dependent were accompanied. Prior to CT, the results demonstrated a poor correlation between the therapists' predictions and those of the chemically dependent individuals. After exposure to the CT, there was a significant increase of 73% in awareness of the risks of relapse. We confirmed the hypothesis that the CT, controlled only by physiological signals, increases the perception of vulnerability to risk situations of individuals with dependence on marijuana, cocaine or both. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

A simplified PBPK modeling approach for prediction of pharmacokinetics of four primarily renally excreted and CYP3A metabolized compounds during pregnancy.

PubMed

Xia, Binfeng; Heimbach, Tycho; Gollen, Rakesh; Nanavati, Charvi; He, Handan

2013-10-01

During pregnancy, a drug's pharmacokinetics may be altered and hence anticipation of potential systemic exposure changes is highly desirable. Physiologically based pharmacokinetics (PBPK) models have recently been used to influence clinical trial design or to facilitate regulatory interactions. Ideally, whole-body PBPK models can be used to predict a drug's systemic exposure in pregnant women based on major physiological changes which can impact drug clearance (i.e., in the kidney and liver) and distribution (i.e., adipose and fetoplacental unit). We described a simple and readily implementable multitissue/organ whole-body PBPK model with key pregnancy-related physiological parameters to characterize the PK of reference drugs (metformin, digoxin, midazolam, and emtricitabine) in pregnant women compared with the PK in nonpregnant or postpartum (PP) women. Physiological data related to changes in maternal body weight, tissue volume, cardiac output, renal function, blood flows, and cytochrome P450 activity were collected from the literature and incorporated into the structural PBPK model that describes HV or PP women PK data. Subsequently, the changes in exposure (area under the curve (AUC) and maximum concentration (C max)) in pregnant women were simulated. Model-simulated PK profiles were overall in agreement with observed data. The prediction fold error for C max and AUC ratio (pregnant vs. nonpregnant) was less than 1.3-fold, indicating that the pregnant PBPK model is useful. The utilization of this simplified model in drug development may aid in designing clinical studies to identify potential exposure changes in pregnant women a priori for compounds which are mainly eliminated renally or metabolized by CYP3A4.

Genome-Wide Screens Reveal New Gene Products That Influence Genetic Competence in Streptococcus mutans

PubMed Central

O'Brien, Greg; Maricic, Natalie; Kesterson, Alexandria; Grace, Megan

2017-01-01

ABSTRACT A network of genes and at least two peptide signaling molecules tightly control when Streptococcus mutans becomes competent to take up DNA from its environment. Widespread changes in the expression of genes occur when S. mutans is presented with competence signal peptides in vitro, including the increased production of the alternative sigma factor, ComX, which activates late competence genes. Still, the way that gene products that are regulated by competence peptides influence DNA uptake and cellular physiology are not well understood. Here, we developed and employed comprehensive transposon mutagenesis of the S. mutans genome, with a screen to identify mutants that aberrantly expressed comX, coupled with transposon sequencing (Tn-seq) to gain a more thorough understanding of the factors modulating comX expression and progression to the competent state. The screens effectively identified genes known to affect competence, e.g., comR, comS, comD, comE, cipB, clpX, rcrR, and ciaH, but disclosed an additional 20 genes that were not previously competence associated. The competence phenotypes of mutants were characterized, including by fluorescence microscopy to determine at which stage the mutants were impaired for comX activation. Among the novel genes studied were those implicated in cell division, the sensing of cell envelope stress, cell envelope biogenesis, and RNA stability. Our results provide a platform for determining the specific chemical and physical cues that are required for genetic competence in S. mutans, while highlighting the effectiveness of using Tn-seq in S. mutans to discover and study novel biological processes. IMPORTANCE Streptococcus mutans acquires DNA from its environment by becoming genetically competent, a physiologic state triggered by cell-cell communication using secreted peptides. Competence is important for acquiring novel genetic traits and has a strong influence on the expression of virulence-associated traits of S. mutans. Here, we used transposon mutagenesis and genomic technologies to identify novel genes involved in competence development. In addition to identifying genes previously known to be required for comX expression, 20 additional genes were identified and characterized. The findings create opportunities to diminish the pathogenic potential of S. mutans, while validating technologies that can rapidly advance our understanding of the physiology, biology, and genetics of S. mutans and related pathogens. PMID:29109185

Genome-wide screens reveal new gene products that influence genetic competence in Streptococcus mutans.

PubMed

Shields, Robert C; O'Brien, Greg; Maricic, Natalie; Kesterson, Alexandria; Grace, Megan; Hagen, Stephen J; Burne, Robert A

2017-11-06

A network of genes and at least two peptide signaling molecules tightly control when Streptococcus mutans becomes competent to take up DNA from its environment. Widespread changes in the expression of genes occur when S. mutans is presented with competence signal peptides in vitro , including increased production of the alternative sigma factor, ComX, which activates late competence genes. Still, the way that gene products that are regulated by competence peptides influence DNA uptake and cellular physiology are not well understood. Here, we developed and employed comprehensive transposon mutagenesis of the S. mutans genome with a screen to identify mutants that aberrantly expressed comX , coupled with transposon sequencing (Tn-seq) to gain a more thorough understanding of the factors modulating comX expression and progression to the competent state. The screens effectively identified genes known to affect competence, e.g. comR , comS , comD , comE , cipB , clpX , rcrR , ciaH , but disclosed an additional 20 genes that were not previously competence-associated. The competence phenotypes of mutants were characterized, including using fluorescence microscopy to determine at which stage the mutants were impaired for comX activation. Among the novel genes studied were those implicated in cell division, sensing of cell envelope stress, cell envelope biogenesis, and RNA stability. Our results provide a platform for determining the specific chemical and physical cues that are required for genetic competence in S. mutans , while highlighting the effectiveness of using Tn-seq in S. mutans to discover and study novel biological processes. IMPORTANCE Streptococcus mutans acquires DNA from its environment by becoming genetically competent, a physiologic state triggered by cell-cell communication using secreted peptides. Competence is important for acquiring novel genetic traits and has a strong influence on the expression of virulence-associated traits of S. mutans Here, we used transposon mutagenesis and genomic technologies to identify novel genes involved in competence development. In addition to identifying genes previously known to be required for comX expression, 20 additional genes were identified and characterized. The findings create opportunities to diminish the pathogenic potential of S. mutans , while validating technologies that can rapidly advance our understanding of the physiology, biology and genetics of S. mutans and related pathogens. Copyright © 2017 American Society for Microbiology.

Early sepsis does not stimulate reactive oxygen species production and does not reduce cardiac function despite an increased inflammation status.

PubMed

Léger, Thibault; Charrier, Alice; Moreau, Clarisse; Hininger-Favier, Isabelle; Mourmoura, Evangelia; Rigaudière, Jean-Paul; Pitois, Elodie; Bouvier, Damien; Sapin, Vincent; Pereira, Bruno; Azarnoush, Kasra; Demaison, Luc

2017-07-01

If it is sustained for several days, sepsis can trigger severe abnormalities of cardiac function which leads to death in 50% of cases. This probably occurs through activation of toll-like receptor-9 by bacterial lipopolysaccharides and overproduction of proinflammatory cytokines such as TNF- α and IL-1 β In contrast, early sepsis is characterized by the development of tachycardia. This study aimed at determining the early changes in the cardiac function during sepsis and at finding the mechanism responsible for the observed changes. Sixty male Wistar rats were randomly assigned to two groups, the first one being made septic by cecal ligation and puncture (sepsis group) and the second one being subjected to the same surgery without cecal ligation and puncture (sham-operated group). The cardiac function was assessed in vivo and ex vivo in standard conditions. Several parameters involved in the oxidative stress and inflammation were determined in the plasma and heart. As evidenced by the plasma level of TNF- α and gene expression of IL-1 β and TNF- α in the heart, inflammation was developed in the sepsis group. The cardiac function was also slightly stimulated by sepsis in the in vivo and ex vivo situations. This was associated with unchanged levels of oxidative stress, but several parameters indicated a lower cardiac production of reactive oxygen species in the septic group. In conclusion, despite the development of inflammation, early sepsis did not increase reactive oxygen species production and did not reduce myocardial function. The depressant effect of TNF- α and IL-1 β on the cardiac function is known to occur at very high concentrations. The influence of low- to moderate-grade inflammation on the myocardial mechanical behavior must thus be revisited. © 2017 French National Institute of Agronomical Research (INRA). Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

Zonal Articular Cartilage Possesses Complex Mechanical Behavior Spanning Multiple Length Scales: Dependence on Chemical Heterogeneity, Anisotropy, and Microstructure

NASA Astrophysics Data System (ADS)

Wahlquist, Joseph A.

This work focused on characterizing the mechanical behavior of biological material in physiologically relevant conditions and at sub millimeter length scales. Elucidating the time, length scale, and directionally dependent mechanical behavior of cartilage and other biological materials is critical to adequately recapitulate native mechanosensory cues for cells, create computational models that mimic native tissue behavior, and assess disease progression. This work focused on three broad aspects of characterizing the mechanical behavior of articular cartilage. First, we sought to reveal the causes of time-dependent deformation and variation of mechanical properties with distance from the articular surface. Second, we investigated size dependence of mechanical properties. Finally, we examined material anisotropy of both the calcified and uncalcified tissues of the osteochondral interface. This research provides insight into how articular cartilage serves to support physiologic loads and simultaneously sustain chondrocyte viability.

MicroRNAs and the metabolic hallmarks of aging.

PubMed

Victoria, Berta; Nunez Lopez, Yury O; Masternak, Michal M

2017-11-05

Aging, the natural process of growing older, is characterized by a progressive deterioration of physiological homeostasis at the cellular, tissue, and organismal level. Metabolically, the aging process is characterized by extensive changes in body composition, multi-tissue/multi-organ insulin resistance, and physiological declines in multiple signaling pathways including growth hormone, insulin/insulin-like growth factor 1, and sex steroids regulation. With this review, we intend to consolidate published information about microRNAs that regulate critical metabolic processes relevant to aging. In certain occasions we uncover relationships likely relevant to aging, which has not been directly described before, such as the miR-451/AMPK axis. We have also included a provocative section highlighting the potential role in aging of a new designation of miRNAs, namely fecal miRNAs, recently discovered to regulate intestinal microbiota in mammals. Copyright © 2016. Published by Elsevier B.V.

Characterization of interaction between doxycycline and human serum albumin by capillary electrophoresis-frontal analysis.

PubMed

Sun, Hanwen; He, Pan

2009-06-01

The binding of doxycycline to HSA under simulated physiological conditions (pH 7.4, 67 mM phosphate, I=0.17, drug concentration 100 microM, HSA concentration up to 475 microM, 36.5 degrees C) was studied by CE-frontal analysis. The number of primary binding sites, binding constant and physiological protein-binding percentage were 1.9, 1.51 x 10(3) M(-1) and 59.80%, respectively. In addition, the thermodynamic parameters including enthalpy change (DeltaH), entropy change (DeltaS) and free energy change (DeltaG) of the reaction were obtained in order to characterize the acting forces between doxycycline and HSA. Furthermore, to better understand the nature of doxycycline-HSA binding and to get information about potential interaction with other drugs, displacement experiments were performed. The results showed that doxycycline binds at site II of HSA.

A systems-theoretical framework for health and disease: inflammation and preconditioning from an abstract modeling point of view.

PubMed

Voit, Eberhard O

2009-01-01

Modern advances in molecular biology have produced enormous amounts of data characterizing physiological and disease states in cells and organisms. While bioinformatics has facilitated the organizing and mining of these data, it is the task of systems biology to merge the available information into dynamic, explanatory and predictive models. This article takes a step into this direction. It proposes a conceptual approach toward formalizing health and disease and illustrates it in the context of inflammation and preconditioning. Instead of defining health and disease states, the emphasis is on simplexes in a high-dimensional biomarker space. These simplexes are bounded by physiological constraints and permit the quantitative characterization of personalized health trajectories, health risk profiles that change with age, and the efficacy of different treatment options. The article mainly focuses on concepts but also briefly describes how the proposed concepts might be formulated rigorously within a mathematical framework.

Targeting PSMA by radioligands in non-prostate disease-current status and future perspectives.

PubMed

Backhaus, Philipp; Noto, Benjamin; Avramovic, Nemanja; Grubert, Lena Sophie; Huss, Sebastian; Bögemann, Martin; Stegger, Lars; Weckesser, Matthias; Schäfers, Michael; Rahbar, Kambiz

2018-05-01

Prostate-specific membrane antigen (PSMA) is the up-and-coming target for molecular imaging of prostate cancer. Despite its name, non-prostate-related PSMA expression in physiologic tissue as well as in benign and malignant disease has been reported in various publications. Unlike in prostate cancer, PSMA expression is only rarely observed in non-prostate tumor cells. Instead, expression occurs in endothelial cells of tumor-associated neovasculature, although no endothelial expression is observed under physiologic conditions. The resulting potential for tumor staging in non-prostate malignant tumors has been demonstrated in first patient studies. This review summarizes the first clinical studies and deduces future perspectives in staging, molecular characterization, and PSMA-targeted radionuclide therapy based on histopathologic examinations of PSMA expression. The non-exclusivity of PSMA in prostate cancer opens a window to utilize the spectrum of available radioactive PSMA ligands for imaging and molecular characterization and maybe even therapy of non-prostate disease.

Spectral and Temporal Laser Fluorescence Analysis Such as for Natural Aquatic Environments

NASA Technical Reports Server (NTRS)

Chekalyuk, Alexander (Inventor)

2015-01-01

An Advanced Laser Fluorometer (ALF) can combine spectrally and temporally resolved measurements of laser-stimulated emission (LSE) for characterization of dissolved and particulate matter, including fluorescence constituents, in liquids. Spectral deconvolution (SDC) analysis of LSE spectral measurements can accurately retrieve information about individual fluorescent bands, such as can be attributed to chlorophyll-a (Chl-a), phycobiliprotein (PBP) pigments, or chromophoric dissolved organic matter (CDOM), among others. Improved physiological assessments of photosynthesizing organisms can use SDC analysis and temporal LSE measurements to assess variable fluorescence corrected for SDC-retrieved background fluorescence. Fluorescence assessments of Chl-a concentration based on LSE spectral measurements can be improved using photo-physiological information from temporal measurements. Quantitative assessments of PBP pigments, CDOM, and other fluorescent constituents, as well as basic structural characterizations of photosynthesizing populations, can be performed using SDC analysis of LSE spectral measurements.

Proteome Regulation during Olea europaea Fruit Development

PubMed Central

Bianco, Linda; Alagna, Fiammetta; Baldoni, Luciana; Finnie, Christine; Svensson, Birte; Perrotta, Gaetano

2013-01-01

Background Widespread in the Mediterranean basin, Olea europaea trees are gaining worldwide popularity for the nutritional and cancer-protective properties of the oil, mechanically extracted from ripe fruits. Fruit development is a physiological process with remarkable impact on the modulation of the biosynthesis of compounds affecting the quality of the drupes as well as the final composition of the olive oil. Proteomics offers the possibility to dig deeper into the major changes during fruit development, including the important phase of ripening, and to classify temporal patterns of protein accumulation occurring during these complex physiological processes. Methodology/Principal Findings In this work, we started monitoring the proteome variations associated with olive fruit development by using comparative proteomics coupled to mass spectrometry. Proteins extracted from drupes at three different developmental stages were separated on 2-DE and subjected to image analysis. 247 protein spots were revealed as differentially accumulated. Proteins were identified from a total of 121 spots and discussed in relation to olive drupe metabolic changes occurring during fruit development. In order to evaluate if changes observed at the protein level were consistent with changes of mRNAs, proteomic data produced in the present work were compared with transcriptomic data elaborated during previous studies. Conclusions/Significance This study identifies a number of proteins responsible for quality traits of cv. Coratina, with particular regard to proteins associated to the metabolism of fatty acids, phenolic and aroma compounds. Proteins involved in fruit photosynthesis have been also identified and their pivotal contribution in oleogenesis has been discussed. To date, this study represents the first characterization of the olive fruit proteome during development, providing new insights into fruit metabolism and oil accumulation process. PMID:23349718

An agent-based modeling framework for evaluating hypotheses on risks for developing autism: effects of the gut microbial environment.

PubMed

Weston, Bronson; Fogal, Benjamin; Cook, Daniel; Dhurjati, Prasad

2015-04-01

The number of cases diagnosed with Autism Spectrum Disorders is rising at an alarming rate with the Centers for Disease Control estimating the 2014 incidence rate as 1 in 68. Recently, it has been hypothesized that gut bacteria may contribute to the development of autism. Specifically, the relative balances between the inflammatory microbes clostridia and desulfovibrio and the anti-inflammatory microbe bifidobacteria may become destabilized prior to autism development. The imbalance leads to a leaky gut, characterized by a more porous epithelial membrane resulting in microbial toxin release into the blood, which may contribute to brain inflammation and autism development. To test how changes in population dynamics of the gut microbiome may lead to the imbalanced microbial populations associated with autism patients, we constructed a novel agent-based model of clostridia, desulfovibrio, and bifidobacteria population interactions in the gut. The model demonstrates how changing physiological conditions in the gut can affect the population dynamics of the microbiome. Simulations using our agent-based model indicate that despite large perturbations to initial levels of bacteria, the populations robustly achieve a single steady-state given similar gut conditions. These simulation results suggests that disturbance such as a prebiotic or antibiotic treatment may only transiently affect the gut microbiome. However, sustained prebiotic treatments may correct low population counts of bifidobacteria. Furthermore, our simulations suggest that clostridia growth rate is a key determinant of risk of autism development. Treatment of high-risk infants with supra-physiological levels of lysozymes may suppress clostridia growth rate, resulting in a steep decrease in the clostridia population and therefore reduced risk of autism development. Copyright © 2015 Elsevier Ltd. All rights reserved.

A whole-body physiologically based pharmacokinetic (WB-PBPK) model of ciprofloxacin: a step towards predicting bacterial killing at sites of infection.

PubMed

Sadiq, Muhammad W; Nielsen, Elisabet I; Khachman, Dalia; Conil, Jean-Marie; Georges, Bernard; Houin, Georges; Laffont, Celine M; Karlsson, Mats O; Friberg, Lena E

2017-04-01

The purpose of this study was to develop a whole-body physiologically based pharmacokinetic (WB-PBPK) model for ciprofloxacin for ICU patients, based on only plasma concentration data. In a next step, tissue and organ concentration time profiles in patients were predicted using the developed model. The WB-PBPK model was built using a non-linear mixed effects approach based on data from 102 adult intensive care unit patients. Tissue to plasma distribution coefficients (Kp) were available from the literature and used as informative priors. The developed WB-PBPK model successfully characterized both the typical trends and variability of the available ciprofloxacin plasma concentration data. The WB-PBPK model was thereafter combined with a pharmacokinetic-pharmacodynamic (PKPD) model, developed based on in vitro time-kill data of ciprofloxacin and Escherichia coli to illustrate the potential of this type of approach to predict the time-course of bacterial killing at different sites of infection. The predicted unbound concentration-time profile in extracellular tissue was driving the bacterial killing in the PKPD model and the rate and extent of take-over of mutant bacteria in different tissues were explored. The bacterial killing was predicted to be most efficient in lung and kidney, which correspond well to ciprofloxacin's indications pneumonia and urinary tract infections. Furthermore, a function based on available information on bacterial killing by the immune system in vivo was incorporated. This work demonstrates the development and application of a WB-PBPK-PD model to compare killing of bacteria with different antibiotic susceptibility, of value for drug development and the optimal use of antibiotics .

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.

Super-resolved calibration-free flow cytometric characterization of platelets and cell-derived microparticles in platelet-rich plasma.

PubMed

Konokhova, Anastasiya I; Chernova, Darya N; Moskalensky, Alexander E; Strokotov, Dmitry I; Yurkin, Maxim A; Chernyshev, Andrei V; Maltsev, Valeri P

2016-02-01

Importance of microparticles (MPs), also regarded as extracellular vesicles, in many physiological processes and clinical conditions motivates one to use the most informative and precise methods for their characterization. Methods based on individual particle analysis provide statistically reliable distributions of MP population over characteristics. Although flow cytometry is one of the most powerful technologies of this type, the standard forward-versus-side-scattering plots of MPs and platelets (PLTs) overlap considerably because of similarity of their morphological characteristics. Moreover, ordinary flow cytometry is not capable of measurement of size and refractive index (RI) of MPs. In this study, we 1) employed the potential of the scanning flow cytometer (SFC) for identification and characterization of MPs from light scattering; 2) suggested the reference method to characterize MP morphology (size and RI) with high precision; and 3) determined the lowest size of a MP that can be characterized from light scattering with the SFC. We equipped the SFC with 405 and 488 nm lasers to measure the light-scattering profiles and side scattering from MPs, respectively. The developed two-stage method allowed accurate separation of PLTs and MPs in platelet-rich plasma. We used two optical models for MPs, a sphere and a bisphere, in the solution of the inverse light-scattering problem. This solution provides unprecedented precision in determination of size and RI of individual spherical MPs-median uncertainties (standard deviations) were 6 nm and 0.003, respectively. The developed method provides instrument-independent quantitative information on MPs, which can be used in studies of various factors affecting MP population. © 2015 International Society for Advancement of Cytometry.

Metabolomics applied to the pancreatic islet.

PubMed

Gooding, Jessica R; Jensen, Mette V; Newgard, Christopher B

2016-01-01

Metabolomics, the characterization of the set of small molecules in a biological system, is advancing research in multiple areas of islet biology. Measuring a breadth of metabolites simultaneously provides a broad perspective on metabolic changes as the islets respond dynamically to metabolic fuels, hormones, or environmental stressors. As a result, metabolomics has the potential to provide new mechanistic insights into islet physiology and pathophysiology. Here we summarize advances in our understanding of islet physiology and the etiologies of type-1 and type-2 diabetes gained from metabolomics studies. Copyright © 2015 Elsevier Inc. All rights reserved.

Coenzyme preference of Streptococcus pyogenes δ1-pyrroline-5-carboxylate reductase: evidence supporting NADPH as the physiological electron donor.

PubMed

Petrollino, Davide; Forlani, Giuseppe

2012-07-01

The streptococcal enzyme that catalyzes the last step in proline biosynthesis was heterologously expressed and the recombinant protein was purified to electrophoretic homogeneity and characterized thoroughly. As for δ1-pyrroline-5-carboxylate reductases from other sources, it was able to use either NADH or NADPH as the electron donor in vitro. However, with NADH the activity was markedly inhibited by physiological levels of NADP+. Results also strengthen the possibility that an unusual ordered substrate binding occurs, in which the dinucleotide binds last.

DEVELOPMENT OF A PHYSIOLOGICALLY BASED PHARMACOKINETIC MODEL FOR DELTAMETHRIN IN ADULT AND DEVELOPING SPRAGUE-DAWLEY RATS

EPA Science Inventory

This work describes the development of a physiologically based pharmacokinetic (PBPK) model of deltamethrin, a type II pyrethroid, in the developing male Sprague-Dawley rat. Generalized Michaelis-Menten equations were used to calculate metabolic rate constants and organ weights ...

Cardiovascular anatomy and physiology of the fetus, neonate, infant, child, and adolescent.

PubMed

Alyn, I B; Baker, L K

1992-04-01

Practicing cardiovascular nurses are aware that significant differences exist in the cardiac anatomy and physiology of children and adults. Generally, the younger the child the greater these differences are. The cellular anatomy and physiology are markedly different in the fetus, neonate, and infant. As development progresses, cardiac function begins to more closely approximate that of an adult. This article describes the anatomical and physiologic development of the fetus, neonate, infant, child, and adolescent. The developmental differences in preload, afterload, contractility, and heart rate are summarized.

The effectiveness of separating theory and practicum as a conduit to learning physiology.

PubMed

Schuijers, Johannes A; McDonald, Stuart J; Julien, Brianna L; Lexis, Louise A; Thomas, Colleen J; Chan, Siew; Samiric, T

2013-06-01

Many conventional science courses contain subjects embedded with laboratory-based activities. However, research on the benefits of positioning the practicals within the theory subject or developing them distinctly from the theory is largely absent. This report compared results in a physiology theory subject among three different cohorts of students: those taking the theory subject alone, those taking it concurrent with a physiology practicum subject, and those who previously took the subject when it had practicums embedded within the one subject. The path model shows that students taking both physiology theory and physiology practicum attained a significantly higher result in online tests compared with those who took the theory subject alone (P < 0.05) and that this translated to a significantly higher result in the end-of-semester examination. Similarly, students taking both physiology theory and the physiology practicum attained a significantly higher end-examination result compared with those who took the physiology subject in previous years when the practicums were embedded within the theory subject (P < 0.05). In both cases, this increase was largely attained in components that tested critical thinking and deep learning (short theory application questions and extended written questions). We conclude that students undertaking both physiology theory and the physiology practicum likely performed better in the theory subject due to better problem-solving skills and a more developed understanding of theoretical content. We suggest that consideration be given in all science curricula to the separation of theory and practicum by developing two subjects with clearly defined different learning outcomes.

Determinants of Physiological and Perceived Physiological Stress Reactivity in Children and Adolescents

PubMed Central

Evans, Brittany E.; Greaves-Lord, Kirstin; Euser, Anja S.; Tulen, Joke H. M.; Franken, Ingmar H. A.; Huizink, Anja C.

2013-01-01

Aims Abnormal physiological stress reactivity is increasingly investigated as a vulnerability marker for various physical and psychological health problems. However, studies are inconsistent in taking into account potential covariates that may influence the developing stress system. We systematically tested determinants (individual, developmental, environmental and substance use-related) of physiological and perceived physiological stress reactivity. We also examined the relation between physiological and perceived physiological stress reactivity. Method In a stratified sample of 363 children (7–12 years) and 344 adolescents (13–20 years) from the general population, we examined cortisol, heart rate, respiratory sinus arrhythmia and perceived physiological stress reactivity to a psychosocial stress procedure. Results Using multivariate linear regression models, we found that individual, developmental, environmental and substance use-related factors were related to each of the stress response indices. These determinant factors were different for each of the stress reactivity indices, and different in children versus adolescents. Perceived physiological stress reactivity predicted cortisol reactivity in adolescents only. All other relations between perceived physiological and physiological stress reactivity were not significant. Conclusions As physiological stress variables are often examined as vulnerability markers for the development of health problems, we maintain that it is essential that future studies take into consideration factors that may account for found relations. Our study provides an overview and indication of which variables should be considered in the investigation of the relation between physiological stress indices and illness. PMID:23620785

Developing a Physiologically-Based Pharmacokinetic Model Knowledgebase in Support of Provisional Model Construction

EPA Science Inventory

Developing physiologically-based pharmacokinetic (PBPK) models for chemicals can be resource-intensive, as neither chemical-specific parameters nor in vivo pharmacokinetic data are easily available for model construction. Previously developed, well-parameterized, and thoroughly-v...

PACAP receptor pharmacology and agonist bias: analysis in primary neurons and glia from the trigeminal ganglia and transfected cells

PubMed Central

Walker, C S; Sundrum, T; Hay, D L

2014-01-01

Background and Purpose A major challenge in the development of new medicines targeting GPCRs is the ability to quantify drug action in physiologically relevant models. Primary cell models that closely resemble the clinically relevant in vivo site of drug action are important translational tools in drug development. However, pharmacological studies in these models are generally very limited due to the methodology used. Experimental Approach We used a neuropeptide system to demonstrate the applicability of using highly sensitive signalling assays in primary cells. We quantified the action of pituitary adenylate cyclase-activating peptide (PACAP)-38, PACAP-27 and vasoactive intestinal polypeptide in primary cultures of neurons and glia derived from rat trigeminal ganglia (TG), comparing our observations to transfected cells. Key Results PACAP-responsive receptors in rat trigeminal neurons, glia and transfected PAC1n receptors were pharmacologically distinct. PACAP-38, but not PACAP-27, activated ERK in glia, while both forms stimulated cellular cAMP production. PACAP(6–38) also displayed cell-type-dependent, agonist-specific, antagonism. Conclusions and Implications The complexity of PACAP pharmacology in the TG may help to direct, more effectively, the development of disease treatments targeting the PACAP receptor. We suggest that these methodologies are broadly applicable to other primary cell types of human or animal origin, and that our approach may allow more thorough characterization of ligand properties in physiologically relevant cell types. PMID:24303997

Major component analysis of dynamic networks of physiologic organ interactions

NASA Astrophysics Data System (ADS)

Liu, Kang K. L.; Bartsch, Ronny P.; Ma, Qianli D. Y.; Ivanov, Plamen Ch

2015-09-01

The human organism is a complex network of interconnected organ systems, where the behavior of one system affects the dynamics of other systems. Identifying and quantifying dynamical networks of diverse physiologic systems under varied conditions is a challenge due to the complexity in the output dynamics of the individual systems and the transient and nonlinear characteristics of their coupling. We introduce a novel computational method based on the concept of time delay stability and major component analysis to investigate how organ systems interact as a network to coordinate their functions. We analyze a large database of continuously recorded multi-channel physiologic signals from healthy young subjects during night-time sleep. We identify a network of dynamic interactions between key physiologic systems in the human organism. Further, we find that each physiologic state is characterized by a distinct network structure with different relative contribution from individual organ systems to the global network dynamics. Specifically, we observe a gradual decrease in the strength of coupling of heart and respiration to the rest of the network with transition from wake to deep sleep, and in contrast, an increased relative contribution to network dynamics from chin and leg muscle tone and eye movement, demonstrating a robust association between network topology and physiologic function.

Interspecies physiological variation as a tool for cross-species assessments of global warming-induced endangerment: validation of an intrinsic determinant of macroecological and phylogeographic structure.

PubMed

Bernardo, Joseph; Ossola, Ryan J; Spotila, James; Crandall, Keith A

2007-12-22

Global warming is now recognized as the dominant threat to biodiversity because even protected populations and habitats are susceptible. Nonetheless, current criteria for evaluating species' relative endangerment remain purely ecological, and the accepted conservation strategies of habitat preservation and population management assume that species can mount ecological responses if afforded protection. The insidious threat from climate change is that it will attenuate or preclude ecological responses by species that are physiologically constrained; yet, quantitative, objective criteria for assessing relative susceptibility of diverse taxa to warming-induced stress are wanting. We explored the utility of using interspecies physiological variation for this purpose by relating species' physiological phenotypes to landscape patterns of ecological and genetic exchange. Using a salamander model system in which ecological, genetic and physiological diversity are well characterized, we found strong quantitative relationships of basal metabolic rates (BMRs) to both macroecological and phylogeographic patterns, with decreasing BMR leading to dispersal limitation (small contemporary ranges with marked phylogeographic structure). Measures of intrinsic physiological tolerance, which vary systematically with macroecological and phylogeographic patterns, afford objective criteria for assessing endangerment across a wide range of species and should be incorporated into conservation assessment criteria that currently rely exclusively upon ecological predictors.

Fatty acids identified in the Burmese python promote beneficial cardiac growth.

PubMed

Riquelme, Cecilia A; Magida, Jason A; Harrison, Brooke C; Wall, Christopher E; Marr, Thomas G; Secor, Stephen M; Leinwand, Leslie A

2011-10-28

Burmese pythons display a marked increase in heart mass after a large meal. We investigated the molecular mechanisms of this physiological heart growth with the goal of applying this knowledge to the mammalian heart. We found that heart growth in pythons is characterized by myocyte hypertrophy in the absence of cell proliferation and by activation of physiological signal transduction pathways. Despite high levels of circulating lipids, the postprandial python heart does not accumulate triglycerides or fatty acids. Instead, there is robust activation of pathways of fatty acid transport and oxidation combined with increased expression and activity of superoxide dismutase, a cardioprotective enzyme. We also identified a combination of fatty acids in python plasma that promotes physiological heart growth when injected into either pythons or mice.

The Esophagiome: concept, status, and future perspectives.

PubMed

Gregersen, Hans; Liao, Donghua; Brasseur, James G

2016-09-01

The term "Esophagiome" is meant to imply a holistic, multiscale treatment of esophageal function from cellular and muscle physiology to the mechanical responses that transport and mix fluid contents. The development and application of multiscale mathematical models of esophageal function are central to the Esophagiome concept. These model elements underlie the development of a "virtual esophagus" modeling framework to characterize and analyze function and disease by quantitatively contrasting normal and pathophysiological function. Functional models incorporate anatomical details with sensory-motor properties and functional responses, especially related to biomechanical functions, such as bolus transport and gastrointestinal fluid mixing. This brief review provides insight into Esophagiome research. Future advanced models can provide predictive evaluations of the therapeutic consequences of surgical and endoscopic treatments and will aim to facilitate clinical diagnostics and treatment. © 2016 New York Academy of Sciences.

Establishment of primary cell cultures from fish calcified tissues

PubMed Central

Marques, Cátia L.; Rafael, Marta S.; Cancela, M. Leonor

2007-01-01

Fishes have been recently recognized as a suitable model organism to study vertebrate physiological processes, in particular skeletal development and tissue mineralization. However, there is a lack of well characterized in vitro cell systems derived from fish calcified tissues. We describe here a protocol that was successfully used to develop the first calcified tissue-derived cell cultures of fish origin. Vertebra and branchial arches collected from young gilthead seabreams were fragmented then submitted to the combined action of collagenase and trypsin to efficiently release cells embedded in the collagenous extracellular matrix. Primary cultures were maintained under standard conditions and spontaneously transformed to form continuous cell lines suitable for studying mechanisms of tissue mineralization in seabream. This simple and inexpensive protocol is also applicable to other calcified tissues and species by adjusting parameters to each particular case. PMID:19002990

Prebiotics and probiotics – the importance of branding

PubMed Central

Crittenden, Ross

2012-01-01

The costs of developing a probiotic or prebiotic ingredient have always been substantial. Ingredient characterization, evaluation of technological and physiological properties, and demonstrations of safety and clinical efficacy require expensive research. The demanding regulatory requirements imposed by EFSA raise the bar even higher so that the costs of acquiring the necessary clinical evidence to support labeling of these food ingredients is approaching that of pharmaceuticals. In order to justify investment in such expensive clinical development, companies require certainty that they can gain a return on investment. Patenting can provide some protection but is not always possible to patent ingredients, and the period of protection is limited. All ingredients eventually face the prospect of commoditization once patents expire. Branding strategies offer one means of maintaining adequate product differentiation to protect market share and margins over the long term. PMID:23990815

Molecular interactions between chondroitin-dermatan sulfate and growth factors/receptors/matrix proteins.

PubMed

Mizumoto, Shuji; Yamada, Shuhei; Sugahara, Kazuyuki

2015-10-01

Recent functional studies on chondroitin sulfate-dermatan sulfate (CS-DS) demonstrated its indispensable roles in various biological events including brain development and cancer. CS-DS proteoglycans exert their physiological activity through interactions with specific proteins including growth factors, cell surface receptors, and matrix proteins. The characterization of these interactions is essential for regulating the biological functions of CS-DS proteoglycans. Although amino acid sequences on the bioactive proteins required for these interactions have already been elucidated, the specific saccharide sequences involved in the binding of CS-DS to target proteins have not yet been sufficiently identified. In this review, recent findings are described on the interaction between CS-DS and some proteins which are especially involved in the central nervous system and cancer development/metastasis. Copyright © 2015. Published by Elsevier Ltd.

Prebiotics and probiotics - the importance of branding.

PubMed

Crittenden, Ross

2012-01-01

The costs of developing a probiotic or prebiotic ingredient have always been substantial. Ingredient characterization, evaluation of technological and physiological properties, and demonstrations of safety and clinical efficacy require expensive research. The demanding regulatory requirements imposed by EFSA raise the bar even higher so that the costs of acquiring the necessary clinical evidence to support labeling of these food ingredients is approaching that of pharmaceuticals. In order to justify investment in such expensive clinical development, companies require certainty that they can gain a return on investment. Patenting can provide some protection but is not always possible to patent ingredients, and the period of protection is limited. All ingredients eventually face the prospect of commoditization once patents expire. Branding strategies offer one means of maintaining adequate product differentiation to protect market share and margins over the long term.

Erythrocytosis in children and adolescents-classification, characterization, and consensus recommendations for the diagnostic approach.

PubMed

Cario, Holger; McMullin, Mary Frances; Bento, Celeste; Pospisilova, Dagmar; Percy, Melanie J; Hussein, Kais; Schwarz, Jiri; Aström, Maria; Hermouet, Sylvie

2013-11-01

During recent years, the increasing knowledge of genetic and physiological changes in polycythemia vera (PV) and of different types of congenital erythrocytosis has led to fundamental changes in recommendations for the diagnostic approach to patients with erythrocytosis. Although widely accepted for adult patients this approach may not be appropriate with regard to children and adolescents affected by erythrocytosis. The "congenital erythrocytosis" working group established within the framework of the MPN&MPNr-EuroNet (COST action BM0902) addressed this question in a consensus finding process and developed a specific algorithm for the diagnosis of erythrocytosis in childhood and adolescence which is presented here. Copyright © 2013 Wiley Periodicals, Inc.

Proteoglycomics: Recent Progress and Future Challenges

PubMed Central

Ly, Mellisa; Laremore, Tatiana N.

2010-01-01

Abstract Proteoglycomics is a systematic study of structure, expression, and function of proteoglycans, a posttranslationally modified subset of a proteome. Although relying on the established technologies of proteomics and glycomics, proteoglycomics research requires unique approaches for elucidating structure–function relationships of both proteoglycan components, glycosaminoglycan chain, and core protein. This review discusses our current understanding of structure and function of proteoglycans, major players in the development, normal physiology, and disease. A brief outline of the proteoglycomic sample preparation and analysis is provided along with examples of several recent proteoglycomic studies. Unique challenges in the characterization of glycosaminoglycan component of proteoglycans are discussed, with emphasis on the many analytical tools used and the types of information they provide. PMID:20450439

Mesenchymal Stem/Stromal Cells: A New "Cells as Drugs" Paradigm. Efficacy and Critical Aspects in Cell Therapy

PubMed Central

de Girolamo, Laura; Lucarelli, Enrico; Alessandri, Giulio; Avanzini, Maria Antonietta; Bernardo, Maria Ester; Biagi, Ettore; Brini, Anna Teresa; D’Amico, Giovanna; Fagioli, Franca; Ferrero, Ivana; Locatelli, Franco; Maccario, Rita; Marazzi, Mario; Parolini, Ornella; Pessina, Augusto; Torre, Maria Luisa

2013-01-01

Mesenchymal stem cells (MSCs) were first isolated more than 50 years ago from the bone marrow. Currently MSCs may also be isolated from several alternative sources and they have been used in more than a hundred clinical trials worldwide to treat a wide variety of diseases. The MSCs mechanism of action is undefined and currently under investigation. For in vivo purposes MSCs must be produced in compliance with good manufacturing practices and this has stimulated research on MSCs characterization and safety. The objective of this review is to describe recent developments regarding MSCs properties, physiological effects, delivery, clinical applications and possible side effects. PMID:23278600

Aging and sarcopenia associate with specific interactions between gut microbes, serum biomarkers and host physiology in rats

PubMed Central

Karaz, Sonia; Morin-Rivron, Delphine; Masoodi, Mojgan; Feige, Jerome N.; Parkinson, Scott James

2017-01-01

The microbiome has been demonstrated to play an integral role in the maintenance of many aspects of health that are also associated with aging. In order to identify areas of potential exploration and intervention, we simultaneously characterized age-related alterations in gut microbiome, muscle physiology and serum proteomic and lipidomic profiles in aged rats to define an integrated signature of the aging phenotype. We demonstrate that aging skews the composition of the gut microbiome, in particular by altering the Sutterella to Barneseilla ratio, and alters the metabolic potential of intestinal bacteria. Age-related changes of the gut microbiome were associated with the physiological decline of musculoskeletal function, and with molecular markers of nutrient processing/availability, and inflammatory/immune status in aged versus adult rats. Altogether, our study highlights that aging leads to a complex interplay between the microbiome and host physiology, and provides candidate microbial species to target physical and metabolic decline during aging by modulating gut microbial ecology. PMID:28783713

Aging and sarcopenia associate with specific interactions between gut microbes, serum biomarkers and host physiology in rats.

PubMed

Siddharth, Jay; Chakrabarti, Anirikh; Pannérec, Alice; Karaz, Sonia; Morin-Rivron, Delphine; Masoodi, Mojgan; Feige, Jerome N; Parkinson, Scott James

2017-07-17

The microbiome has been demonstrated to play an integral role in the maintenance of many aspects of health that are also associated with aging. In order to identify areas of potential exploration and intervention, we simultaneously characterized age-related alterations in gut microbiome, muscle physiology and serum proteomic and lipidomic profiles in aged rats to define an integrated signature of the aging phenotype. We demonstrate that aging skews the composition of the gut microbiome, in particular by altering the Sutterella to Barneseilla ratio, and alters the metabolic potential of intestinal bacteria. Age-related changes of the gut microbiome were associated with the physiological decline of musculoskeletal function, and with molecular markers of nutrient processing/availability, and inflammatory/immune status in aged versus adult rats. Altogether, our study highlights that aging leads to a complex interplay between the microbiome and host physiology, and provides candidate microbial species to target physical and metabolic decline during aging by modulating gut microbial ecology.

Neuroticism and extraversion in relation to physiological stress reactivity during adolescence.

PubMed

Evans, Brittany E; Stam, Jacqueline; Huizink, Anja C; Willemen, Agnes M; Westenberg, P Michiel; Branje, Susan; Meeus, Wim; Koot, Hans M; van Lier, Pol A C

2016-05-01

The current study examined mean level and change in extraversion and neuroticism across adolescence in relation to physiological stress reactivity to social evaluation. Adolescents (n=327) from the Dutch general population reported on personality measures at five annual assessments. At age 17 years, adolescents participated in a psychosocial stress procedure characterized by social evaluation during which cortisol, heart rate, pre-ejection period (PEP) and heart rate variability were assessed. Dual latent growth curve models were fitted in which the intercepts (mean level) and slopes (change) of personality across adolescence predicted the intercepts (baseline) and slopes (reactivity) of the physiological stress measures. Most comparisons revealed no relation between personality and stress reactivity. Adolescents with higher mean level scores on extraversion did show lower cortisol reactivity. Adolescents with higher mean level neuroticism scores showed higher PEP reactivity. Our findings lend partial support for a relation between personality and physiological stress reactivity. Copyright © 2016 Elsevier B.V. All rights reserved.

Utilization of microgravity bioreactors for differentiation of mammalian skeletal tissue

NASA Technical Reports Server (NTRS)

Klement, B. J.; Spooner, B. S.

1993-01-01

Bioreactor cell and tissue culture vessels can be used to study bone development in a simulated microgravity environment. These vessels will also provide an advantageous, low maintenance culture system on space station Freedom. Although many types of cells and tissues can potentially utilize this system, our particular interest is in developing bone tissue. We have characterized an organ culture system utilizing embryonic mouse pre-metatarsal mesenchyme, documenting morphogenesis and differentiation as cartilage rods are formed, with subsequent terminal chondrocyte differentiation to hypertrophied cells. Further development to form bone tissue is achieved by supplementation of the culture medium. Research using pre-metatarsal tissue, combined with the bioreactor culture hardware, could give insight into the advantages and/or disadvantages of conditions experienced in microgravity. Studies such as these have the potential to enhance understanding of bone development and adult bone physiology, and may help define the processes of bone demineralization experienced in space and in pathological conditions here on earth.

SIGNALS AND REGULATORS THAT GOVERN STREPTOMYCES DEVELOPMENT

PubMed Central

McCormick, Joseph R.; Flärdh, Klas

2012-01-01

Streptomyces coelicolor is the genetically best characterized species of a populous genus belonging to the Gram-positive Actinobacteria. Streptomycetes are filamentous soil organisms, well known for the production of a plethora of biologically active secondary metabolic compounds. The Streptomyces developmental life cycle is uniquely complex, and involves coordinated multicellular development with both physiological and morphological differentiation of several cell types, culminating in production of secondary metabolites and dispersal of mature spores. This review presents a current appreciation of the signaling mechanisms used to orchestrate the decision to undergo morphological differentiation, and the regulators and regulatory networks that direct the intriguing development of multigenomic hyphae, first to form specialized aerial hyphae, and then to convert them into chains of dormant spores. This current view of S. coelicolor development is destined for rapid evolution as data from “-omics” studies shed light on gene regulatory networks, new genetic screens identify hitherto unknown players, and the resolution of our insights into the underlying cell biological processes steadily improve. PMID:22092088

A brief history of bacterial growth physiology.

PubMed

Schaechter, Moselio

2015-01-01

Arguably, microbial physiology started when Leeuwenhoek became fascinated by observing a Vorticella beating its cilia, my point being that almost any observation of microbes has a physiological component. With the advent of modern microbiology in the mid-19th century, the field became recognizably distinctive with such discoveries as anaerobiosis, fermentation as a biological phenomenon, and the nutritional requirements of microbes. Soon came the discoveries of Winogradsky and his followers of the chemical changes in the environment that result from microbial activities. Later, during the first half of the 20th century, microbial physiology became the basis for much of the elucidation of central metabolism. Bacterial physiology then became a handmaiden of molecular biology and was greatly influenced by the discovery of cellular regulatory mechanisms. Microbial growth, which had come of age with the early work of Hershey, Monod, and others, was later pursued by studies on a whole cell level by what became known as the "Copenhagen School." During this time, the exploration of physiological activities became coupled to modern inquiries into the structure of the bacterial cell. Recent years have seen the development of a further phase in microbial physiology, one seeking a deeper quantitative understanding of phenomena on a whole cell level. This pursuit is exemplified by the emergence of systems biology, which is made possible by the development of technologies that permit the gathering of information in huge amounts. As has been true through history, the research into microbial physiology continues to be guided by the development of new methods of analysis. Some of these developments may well afford the possibility of making stunning breakthroughs.