Deep sequencing reveals complex mechanisms of diapause preparation in the invasive mosquito, Aedes albopictus.

PubMed

Poelchau, Monica F; Reynolds, Julie A; Elsik, Christine G; Denlinger, David L; Armbruster, Peter A

2013-05-22

Seasonal environments present fundamental physiological challenges to a wide range of insects. Many temperate insects surmount the exigencies of winter by undergoing photoperiodic diapause, in which photoperiod provides a token cue that initiates an alternative developmental programme leading to dormancy. Pre-diapause is a crucial preparatory phase of this process, preceding developmental arrest. However, the regulatory and physiological mechanisms of diapause preparation are largely unknown. Using high-throughput gene expression profiling in the Asian tiger mosquito, Aedes albopictus, we reveal major shifts in endocrine signalling, cell proliferation, metabolism, energy production and cellular structure across pre-diapause development. While some hallmarks of diapause, such as insulin signalling and stress response, were not important at the transcriptional level, two genes, Pepck and PCNA, appear to show diapause-induced transcriptional changes across insect taxa. These processes demonstrate physiological commonalities between Ae. albopictus pre-diapause and diapause strategies across insects, and support the idea of a genetic 'toolkit' for diapause. Observations of gene expression trends from a comparative developmental perspective suggest that individual physiological processes are delayed against a background of a fixed morphological ontogeny. Our results demonstrate how deep sequencing can provide new insights into elusive molecular bases of complex ecological adaptations.

'Multimorbidity' as the manifestation of network disturbances.

PubMed

Sturmberg, Joachim P; Bennett, Jeanette M; Martin, Carmel M; Picard, Martin

2017-02-01

We argue that 'multimorbidity' is the manifestation of interconnected physiological network processes within an individual in his or her socio-cultural environment. Networks include genomic, metabolomic, proteomic, neuroendocrine, immune and mitochondrial bioenergetic elements, as well as social, environmental and health care networks. Stress systems and other physiological mechanisms create feedback loops that integrate and regulate internal networks within the individual. Minor (e.g. daily hassles) and major (e.g. trauma) stressful life experiences perturb internal and social networks resulting in physiological instability with changes ranging from improved resilience to unhealthy adaptation and 'clinical disease'. Understanding 'multimorbidity' as a complex adaptive systems response to biobehavioural and socio-environmental networks is essential. Thus, designing integrative care delivery approaches that more adequately address the underlying disease processes as the manifestation of a state of physiological dysregulation is essential. This framework can shape care delivery approaches to meet the individual's care needs in the context of his or her underlying illness experience. It recognizes 'multimorbidity' and its symptoms as the end product of complex physiological processes, namely, stress activation and mitochondrial energetics, and suggests new opportunities for treatment and prevention. The future of 'multimorbidity' management might become much more discerning by combining the balancing of physiological dysregulation with targeted personalized biotechnology interventions such as small molecule therapeutics targeting specific cellular components of the stress response, with community-embedded interventions that involve addressing psycho-socio-cultural impediments that would aim to strengthen personal/social resilience and enhance social capital. © 2016 John Wiley & Sons, Ltd.

Physical Activity, Aging, and Physiological Function.

PubMed

Harridge, Stephen D R; Lazarus, Norman R

2017-03-01

Human evolution suggests that the default position for health is to be physically active. Inactivity, by contrast, has serious negative effects on health across the lifespan. Therefore, only in physically active people can the inherent aging process proceed unaffected by disuse complications. In such individuals, although the relationship between age and physiological function remains complex, function is generally superior with health, well being, and the aging process optimized. ©2017 Int. Union Physiol. Sci./Am. Physiol. Soc.

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).

Performance in Physiology Evaluation: Possible Improvement by Active Learning Strategies

ERIC Educational Resources Information Center

Montrezor, Luís H.

2016-01-01

The evaluation process is complex and extremely important in the teaching/learning process. Evaluations are constantly employed in the classroom to assist students in the learning process and to help teachers improve the teaching process. The use of active methodologies encourages students to participate in the learning process, encourages…

Use of concept mapping in an undergraduate introductory exercise physiology course.

PubMed

Henige, Kim

2012-09-01

Physiology is often considered a challenging course for students. It is up to teachers to structure courses and create learning opportunities that will increase the chance of student success. In an undergraduate exercise physiology course, concept maps are assigned to help students actively process and organize information into manageable and meaningful chunks and to teach them to recognize the patterns and regularities of physiology. Students are first introduced to concept mapping with a commonly relatable nonphysiology concept and are then assigned a series of maps that become more and more complex. Students map the acute response to a drop in blood pressure, the causes of the acute increase in stroke volume during cardiorespiratory exercise, and the factors contributing to an increase in maximal O(2) consumption with cardiorespiratory endurance training. In the process, students draw the integrative nature of physiology, identify causal relationships, and learn about general models and core principles of physiology.

Modern Communication: Exploring Physiological Transmission through Tech-Savvy Analogies

ERIC Educational Resources Information Center

Hollabaugh, Christopher R.; Milanick, Mark A.

2014-01-01

Analogies are often helpful for students to grasp key physiological concepts; sometimes the technical jargon makes the concept seem more complex than it actually is. In this article the authors provide several analogies for information transfer processes that sometimes confuse students. For an analogy to be useful, of course, it needs to be…

Fractal mechanisms in the electrophysiology of the heart

NASA Technical Reports Server (NTRS)

Goldberger, A. L.

1992-01-01

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

Stream computing for biomedical signal processing: A QRS complex detection case-study.

PubMed

Murphy, B M; O'Driscoll, C; Boylan, G B; Lightbody, G; Marnane, W P

2015-01-01

Recent developments in "Big Data" have brought significant gains in the ability to process large amounts of data on commodity server hardware. Stream computing is a relatively new paradigm in this area, addressing the need to process data in real time with very low latency. While this approach has been developed for dealing with large scale data from the world of business, security and finance, there is a natural overlap with clinical needs for physiological signal processing. In this work we present a case study of streams processing applied to a typical physiological signal processing problem: QRS detection from ECG data.

Detection of a novel, integrative aging process suggests complex physiological integration.

PubMed

Cohen, Alan A; Milot, Emmanuel; Li, Qing; Bergeron, Patrick; Poirier, Roxane; Dusseault-Bélanger, Francis; Fülöp, Tamàs; Leroux, Maxime; Legault, Véronique; Metter, E Jeffrey; Fried, Linda P; Ferrucci, Luigi

2015-01-01

Many studies of aging examine biomarkers one at a time, but complex systems theory and network theory suggest that interpretations of individual markers may be context-dependent. Here, we attempted to detect underlying processes governing the levels of many biomarkers simultaneously by applying principal components analysis to 43 common clinical biomarkers measured longitudinally in 3694 humans from three longitudinal cohort studies on two continents (Women's Health and Aging I & II, InCHIANTI, and the Baltimore Longitudinal Study on Aging). The first axis was associated with anemia, inflammation, and low levels of calcium and albumin. The axis structure was precisely reproduced in all three populations and in all demographic sub-populations (by sex, race, etc.); we call the process represented by the axis "integrated albunemia." Integrated albunemia increases and accelerates with age in all populations, and predicts mortality and frailty--but not chronic disease--even after controlling for age. This suggests a role in the aging process, though causality is not yet clear. Integrated albunemia behaves more stably across populations than its component biomarkers, and thus appears to represent a higher-order physiological process emerging from the structure of underlying regulatory networks. If this is correct, detection of this process has substantial implications for physiological organization more generally.

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

PubMed

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

2014-09-15

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

Validation of an in vitro digestive system for studying macronutrient decomposition in humans.

PubMed

Kopf-Bolanz, Katrin A; Schwander, Flurina; Gijs, Martin; Vergères, Guy; Portmann, Reto; Egger, Lotti

2012-02-01

The digestive process transforms nutrients and bioactive compounds contained in food to physiologically active compounds. In vitro digestion systems have proven to be powerful tools for understanding and monitoring the complex transformation processes that take place during digestion. Moreover, the investigation of the physiological effects of certain nutrients demands an in vitro digestive process that is close to human physiology. In this study, human digestion was simulated with a 3-step in vitro process that was validated in depth by choosing pasteurized milk as an example of a complex food matrix. The evolution and decomposition of the macronutrients was followed over the entire digestive process to the level of intestinal enterocyte action, using protein and peptide analysis by SDS-PAGE, reversed-phase HPLC, size exclusion HPLC, and liquid chromatography-MS. The mean peptide size after in vitro digestion of pasteurized milk was 5-6 amino acids (AA). Interestingly, mostly essential AA (93.6%) were released during in vitro milk digestion, a significantly different relative distribution compared to the total essential AA concentration of bovine milk (44.5%). All TG were degraded to FFA and monoacylglycerols. Herein, we present a human in vitro digestion model validated for its ability to degrade the macronutrients of dairy products comparable to physiological ranges. It is suited to be used in combination with a human intestinal cell culture system, allowing ex vivo bioavailability measurements and assessment of the bioactive properties of food components.

Physiological mechanisms of thermoregulation in reptiles: a review.

PubMed

Seebacher, Frank; Franklin, Craig E

2005-11-01

The thermal dependence of biochemical reaction rates means that many animals regulate their body temperature so that fluctuations in body temperature are small compared to environmental temperature fluctuations. Thermoregulation is a complex process that involves sensing of the environment, and subsequent processing of the environmental information. We suggest that the physiological mechanisms that facilitate thermoregulation transcend phylogenetic boundaries. Reptiles are primarily used as model organisms for ecological and evolutionary research and, unlike in mammals, the physiological basis of many aspects in thermoregulation remains obscure. Here, we review recent research on regulation of body temperature, thermoreception, body temperature set-points, and cardiovascular control of heating and cooling in reptiles. The aim of this review is to place physiological thermoregulation of reptiles in a wider phylogenetic context. Future research on reptilian thermoregulation should focus on the pathways that connect peripheral sensing to central processing which will ultimately lead to the thermoregulatory response.

Evaluation of physiologic complexity in time series using generalized sample entropy and surrogate data analysis

NASA Astrophysics Data System (ADS)

Eduardo Virgilio Silva, Luiz; Otavio Murta, Luiz

2012-12-01

Complexity in time series is an intriguing feature of living dynamical systems, with potential use for identification of system state. Although various methods have been proposed for measuring physiologic complexity, uncorrelated time series are often assigned high values of complexity, errouneously classifying them as a complex physiological signals. Here, we propose and discuss a method for complex system analysis based on generalized statistical formalism and surrogate time series. Sample entropy (SampEn) was rewritten inspired in Tsallis generalized entropy, as function of q parameter (qSampEn). qSDiff curves were calculated, which consist of differences between original and surrogate series qSampEn. We evaluated qSDiff for 125 real heart rate variability (HRV) dynamics, divided into groups of 70 healthy, 44 congestive heart failure (CHF), and 11 atrial fibrillation (AF) subjects, and for simulated series of stochastic and chaotic process. The evaluations showed that, for nonperiodic signals, qSDiff curves have a maximum point (qSDiffmax) for q ≠1. Values of q where the maximum point occurs and where qSDiff is zero were also evaluated. Only qSDiffmax values were capable of distinguish HRV groups (p-values 5.10×10-3, 1.11×10-7, and 5.50×10-7 for healthy vs. CHF, healthy vs. AF, and CHF vs. AF, respectively), consistently with the concept of physiologic complexity, and suggests a potential use for chaotic system analysis.

Comparative Analysis of Stress Induced Gene Expression in Caenorhabditis elegans following Exposure to Environmental and Lab Reconstituted Complex Metal Mixture

PubMed Central

Kumar, Ranjeet; Pradhan, Ajay; Khan, Faisal Ahmad; Lindström, Pia; Ragnvaldsson, Daniel; Ivarsson, Per; Olsson, Per-Erik; Jass, Jana

2015-01-01

Metals are essential for many physiological processes and are ubiquitously present in the environment. However, high metal concentrations can be harmful to organisms and lead to physiological stress and diseases. The accumulation of transition metals in the environment due to either natural processes or anthropogenic activities such as mining results in the contamination of water and soil environments. The present study used Caenorhabditis elegans to evaluate gene expression as an indicator of physiological response, following exposure to water collected from three different locations downstream of a Swedish mining site and a lab reconstituted metal mixture. Our results indicated that the reconstituted metal mixture exerted a direct stress response in C. elegans whereas the environmental waters elicited either a diminished or abrogated response. This suggests that it is not sufficient to use the biological effects observed from laboratory mixtures to extrapolate the effects observed in complex aquatic environments and apply this to risk assessment and intervention. PMID:26168046

From genotype to phenotype: unraveling the complexities of cold adaptation in forest trees

Treesearch

Glenn T. Howe; Sally N. Aitken; David B. Neale; Kathleen D. Jermstad; Nicholas C. Wheeler; Tony H.H Chen

2003-01-01

Adaptation to winter cold in temperate and boreal trees involves complex genetic, physiological, and developmental processes. Genecological studies demonstrate the existence of steep genetic clines for cold adaptation traits in relation to environmental (mostly temperature related) gradients. Population differentiation is generally stronger for cold adaptation traits...

The Use of Novel Camtasia Videos to Improve Performance of At-Risk Students in Undergraduate Physiology Courses

ERIC Educational Resources Information Center

Miller, Cynthia J.

2014-01-01

Students in undergraduate physiology courses often have difficulty understanding complex, multi-step processes, and these concepts consume a large portion of class time. For this pilot study, it was hypothesized that online multimedia resources may improve student performance in a high-risk population and reduce the in-class workload. A narrated…

Physiology of Calcium, Phosphate, Magnesium and Vitamin D.

PubMed

Allgrove, Jeremy

2015-01-01

The physiology of calcium and the other minerals involved in its metabolism is complex and intimately linked to the physiology of bone. Five principal humoral factors are involved in maintaining plasma concentrations of calcium, magnesium and phosphate and in coordinating the balance between their content in bone. The transmembrane transport of these elements is dependent on a series of complex mechanisms that are partly controlled by these hormones. The plasma concentration of calcium is initially sensed by a calcium-sensing receptor, which then sets up a cascade of events that initially determines parathyroid hormone secretion and eventually results in a specific action within the target organs, mainly bone and kidney. This chapter describes the physiology of these humoral factors and relates them to the pathological processes that give rise to disorders of calcium, phosphate and magnesium metabolism as well as of bone metabolism. This chapter also details the stages in the calcium cascade, describes the effects of calcium on the various target organs, gives details of the processes by which phosphate and magnesium are controlled and summarises the metabolism of vitamin D. The pathology of disorders of bone and calcium metabolism is described in detail in the relevant chapters. © 2015 S. Karger AG, Basel.

Endocytosis and Endosomal Trafficking in Plants.

PubMed

Paez Valencia, Julio; Goodman, Kaija; Otegui, Marisa S

2016-04-29

Endocytosis and endosomal trafficking are essential processes in cells that control the dynamics and turnover of plasma membrane proteins, such as receptors, transporters, and cell wall biosynthetic enzymes. Plasma membrane proteins (cargo) are internalized by endocytosis through clathrin-dependent or clathrin-independent mechanism and delivered to early endosomes. From the endosomes, cargo proteins are recycled back to the plasma membrane via different pathways, which rely on small GTPases and the retromer complex. Proteins that are targeted for degradation through ubiquitination are sorted into endosomal vesicles by the ESCRT (endosomal sorting complex required for transport) machinery for degradation in the vacuole. Endocytic and endosomal trafficking regulates many cellular, developmental, and physiological processes, including cellular polarization, hormone transport, metal ion homeostasis, cytokinesis, pathogen responses, and development. In this review, we discuss the mechanisms that mediate the recognition and sorting of endocytic and endosomal cargos, the vesiculation processes that mediate their trafficking, and their connection to cellular and physiological responses in plants.

Sensory processing of deep tissue nociception in the rat spinal cord and thalamic ventrobasal complex.

PubMed

Sikandar, Shafaq; West, Steven J; McMahon, Stephen B; Bennett, David L; Dickenson, Anthony H

2017-07-01

Sensory processing of deep somatic tissue constitutes an important component of the nociceptive system, yet associated central processing pathways remain poorly understood. Here, we provide a novel electrophysiological characterization and immunohistochemical analysis of neural activation in the lateral spinal nucleus (LSN). These neurons show evoked activity to deep, but not cutaneous, stimulation. The evoked responses of neurons in the LSN can be sensitized to somatosensory stimulation following intramuscular hypertonic saline, an acute model of muscle pain, suggesting this is an important spinal relay site for the processing of deep tissue nociceptive inputs. Neurons of the thalamic ventrobasal complex (VBC) mediate both cutaneous and deep tissue sensory processing, but in contrast to the lateral spinal nucleus our electrophysiological studies do not suggest the existence of a subgroup of cells that selectively process deep tissue inputs. The sensitization of polymodal and thermospecific VBC neurons to mechanical somatosensory stimulation following acute muscle stimulation with hypertonic saline suggests differential roles of thalamic subpopulations in mediating cutaneous and deep tissue nociception in pathological states. Overall, our studies at both the spinal (lateral spinal nucleus) and supraspinal (thalamic ventrobasal complex) levels suggest a convergence of cutaneous and deep somatosensory inputs onto spinothalamic pathways, which are unmasked by activation of muscle nociceptive afferents to produce consequent phenotypic alterations in spinal and thalamic neural coding of somatosensory stimulation. A better understanding of the sensory pathways involved in deep tissue nociception, as well as the degree of labeled line and convergent pathways for cutaneous and deep somatosensory inputs, is fundamental to developing targeted analgesic therapies for deep pain syndromes. © 2017 University College London. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

Functions and Mechanisms of Sleep

PubMed Central

Zielinski, Mark R.; McKenna, James T.; McCarley, Robert W.

2017-01-01

Sleep is a complex physiological process that is regulated globally, regionally, and locally by both cellular and molecular mechanisms. It occurs to some extent in all animals, although sleep expression in lower animals may be co-extensive with rest. Sleep regulation plays an intrinsic part in many behavioral and physiological functions. Currently, all researchers agree there is no single physiological role sleep serves. Nevertheless, it is quite evident that sleep is essential for many vital functions including development, energy conservation, brain waste clearance, modulation of immune responses, cognition, performance, vigilance, disease, and psychological state. This review details the physiological processes involved in sleep regulation and the possible functions that sleep may serve. This description of the brain circuitry, cell types, and molecules involved in sleep regulation is intended to further the reader’s understanding of the functions of sleep. PMID:28413828

The Role of the Clathrin Adaptor AP-1: Polarized Sorting and Beyond

PubMed Central

Nakatsu, Fubito; Hase, Koji; Ohno, Hiroshi

2014-01-01

The selective transport of proteins or lipids by vesicular transport is a fundamental process supporting cellular physiology. The budding process involves cargo sorting and vesicle formation at the donor membrane and constitutes an important process in vesicular transport. This process is particularly important for the polarized sorting in epithelial cells, in which the cargo molecules need to be selectively sorted and transported to two distinct destinations, the apical or basolateral plasma membrane. Adaptor protein (AP)-1, a member of the AP complex family, which includes the ubiquitously expressed AP-1A and the epithelium-specific AP-1B, regulates polarized sorting at the trans-Golgi network and/or at the recycling endosomes. A growing body of evidence, especially from studies using model organisms and animals, demonstrates that the AP-1-mediated polarized sorting supports the development and physiology of multi-cellular units as functional organs and tissues (e.g., cell fate determination, inflammation and gut immune homeostasis). Furthermore, a possible involvement of AP-1B in the pathogenesis of human diseases, such as Crohn’s disease and cancer, is now becoming evident. These data highlight the significant contribution of AP-1 complexes to the physiology of multicellular organisms, as master regulators of polarized sorting in epithelial cells. PMID:25387275

A simple and fast representation space for classifying complex time series

NASA Astrophysics Data System (ADS)

Zunino, Luciano; Olivares, Felipe; Bariviera, Aurelio F.; Rosso, Osvaldo A.

2017-03-01

In the context of time series analysis considerable effort has been directed towards the implementation of efficient discriminating statistical quantifiers. Very recently, a simple and fast representation space has been introduced, namely the number of turning points versus the Abbe value. It is able to separate time series from stationary and non-stationary processes with long-range dependences. In this work we show that this bidimensional approach is useful for distinguishing complex time series: different sets of financial and physiological data are efficiently discriminated. Additionally, a multiscale generalization that takes into account the multiple time scales often involved in complex systems has been also proposed. This multiscale analysis is essential to reach a higher discriminative power between physiological time series in health and disease.

Engineering cells for cell culture bioprocessing--physiological fundamentals.

PubMed

Seth, Gargi; Hossler, Patrick; Yee, Joon Chong; Hu, Wei-Shou

2006-01-01

In the past decade, we have witnessed a tremendous increase in the number of mammalian cell-derived therapeutic proteins with clinical applications. The success of making these life-saving biologics available to the public is partly due to engineering efforts to enhance process efficiency. To further improve productivity, much effort has been devoted to developing metabolically engineered producing cells, which possess characteristics favorable for large-scale bioprocessing. In this article we discuss the fundamental physiological basis for cell engineering. Different facets of cellular mechanisms, including metabolism, protein processing, and the balancing pathways of cell growth and apoptosis, contribute to the complex traits of favorable growth and production characteristics. We present our assessment of the current state of the art by surveying efforts that have already been undertaken in engineering cells for a more robust process. The concept of physiological homeostasis as a key determinant and its implications on cell engineering is emphasized. Integrating the physiological perspective with cell culture engineering will facilitate attainment of dream cells with superlative characteristics.

Complex for monitoring visual acuity and its application for evaluation of human psycho-physiological state

NASA Astrophysics Data System (ADS)

Sorokoumov, P. S.; Khabibullin, T. R.; Tolstaya, A. M.

2017-01-01

The existing psychological theories associate the movement of a human eye with its reactions to external change: what we see, hear and feel. By analyzing the glance, we can compare the external human response (which shows the behavior of a person), and the natural reaction (that they actually feels). This article describes the complex for detection of visual activity and its application for evaluation of the psycho-physiological state of a person. The glasses with a camera capture all the movements of the human eye in real time. The data recorded by the camera are transmitted to the computer for processing implemented with the help of the software developed by the authors. The result is given in an informative and an understandable report, which can be used for further analysis. The complex shows a high efficiency and stable operation and can be used both, for the pedagogic personnel recruitment and for testing students during the educational process.

[Complicated Grief in DSM-5 era].

PubMed

Carmassi, Claudia; Conversano, Ciro; Pinori, Marialisa; Bertelloni, Carlo Antonio; Dalle Luche, Riccardo; Gesi, Camilla; Dell'Osso, Liliana

2016-01-01

An increasing number of data has been recently focused on recognizing pathological grief reactions and on the distinction from physiological processes. Particularly, several studies have supported Complicated Grief (CG) as an independent disorder, in order to define the failure of spontaneous physiological mourning resolution. Upon these studies, the latest edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) with the name of "Persistent Complex Bereavement Disorder". This article aims at retracing the history of clinical research about the physiological and psychopathological processes related to grief and aims at presenting the main scientific studies that have described the features of the CG defining it as a distinct disorder. Similarities and distinctions among CG and Depression, Posttraumatic Stress Disorder and Adjustment Disorder were also reported.

A systems biology approach to studying Tai Chi, physiological complexity and healthy aging: design and rationale of a pragmatic randomized controlled trial.

PubMed

Wayne, Peter M; Manor, Brad; Novak, Vera; Costa, Madelena D; Hausdorff, Jeffrey M; Goldberger, Ary L; Ahn, Andrew C; Yeh, Gloria Y; Peng, C-K; Lough, Matthew; Davis, Roger B; Quilty, Mary T; Lipsitz, Lewis A

2013-01-01

Aging is typically associated with progressive multi-system impairment that leads to decreased physical and cognitive function and reduced adaptability to stress. Due to its capacity to characterize complex dynamics within and between physiological systems, the emerging field of complex systems biology and its array of quantitative tools show great promise for improving our understanding of aging, monitoring senescence, and providing biomarkers for evaluating novel interventions, including promising mind-body exercises, that treat age-related disease and promote healthy aging. An ongoing, two-arm randomized clinical trial is evaluating the potential of Tai Chi mind-body exercise to attenuate age-related loss of complexity. A total of 60 Tai Chi-naïve healthy older adults (aged 50-79) are being randomized to either six months of Tai Chi training (n=30), or to a waitlist control receiving unaltered usual medical care (n=30). Our primary outcomes are complexity-based measures of heart rate, standing postural sway and gait stride interval dynamics assessed at 3 and 6months. Multiscale entropy and detrended fluctuation analysis are used as entropy- and fractal-based measures of complexity, respectively. Secondary outcomes include measures of physical and psychological function and tests of physiological adaptability also assessed at 3 and 6months. Results of this study may lead to novel biomarkers that help us monitor and understand the physiological processes of aging and explore the potential benefits of Tai Chi and related mind-body exercises for healthy aging. Copyright © 2012 Elsevier Inc. All rights reserved.

Come one, come all.

PubMed

Lee, Siu Sylvia

2004-05-05

Aging is a complex process that involves the gradual functional decline of many different tissues and cells. Gene expression microarray analysis provides a comprehensive view of the gene expression signature associated with age and is particularly valuable for understanding the molecular mechanisms that contribute to the aging process. However, because of the stochastic nature of the aging process, animals of the same chronological age often manifest great physiological differences. Therefore, profiling the gene expression pattern of a large population of aging animals risks either exaggerating or masking the changes in gene expression that correspond to physiological aging. In a recent paper, Golden and Melov surveyed the gene expression profiles of individual aging Caenorhabditis elegans, hoping to circumvent the problem of variability among worms of the same chronological age. This initial analysis of age-dependent gene expression in individual aging worms is an important step toward deciphering the molecular basis of physiological aging.

Feed-back between geriatric syndromes: general system theory in geriatrics.

PubMed

Musso, Carlos G; Núñez, Juan F Macías

2006-01-01

Geriatrics has described three entities: confusional syndrome, incontinente and gait disorders, calling them geriatric giants. Aging process also induces changes in renal physiology such as glomerular filtration rate reduction, and alteration in water and electrolytes handling. These ageing renal changes have been named as nephrogeriatric giants. These two groups of giants, geriatric and nephrogeriatric, can predispose and potentiate each other leading old people to fatal outcomes. These phenomenon of feed-back between these geriatric syndromes has its roots in the loss of complexity that the ageing process has. Complexity means that all the body systems work harmoniously. The process of senescence weakens this coordination among systems undermining complexity and making the old person frail.

Monitoring cognitive and emotional processes through pupil and cardiac response during dynamic versus logical task.

PubMed

Causse, Mickaël; Sénard, Jean-Michel; Démonet, Jean François; Pastor, Josette

2010-06-01

The paper deals with the links between physiological measurements and cognitive and emotional functioning. As long as the operator is a key agent in charge of complex systems, the definition of metrics able to predict his performance is a great challenge. The measurement of the physiological state is a very promising way but a very acute comprehension is required; in particular few studies compare autonomous nervous system reactivity according to specific cognitive processes during task performance and task related psychological stress is often ignored. We compared physiological parameters recorded on 24 healthy subjects facing two neuropsychological tasks: a dynamic task that require problem solving in a world that continually evolves over time and a logical task representative of cognitive processes performed by operators facing everyday problem solving. Results showed that the mean pupil diameter change was higher during the dynamic task; conversely, the heart rate was more elevated during the logical task. Finally, the systolic blood pressure seemed to be strongly sensitive to psychological stress. A better taking into account of the precise influence of a given cognitive activity and both workload and related task-induced psychological stress during task performance is a promising way to better monitor operators in complex working situations to detect mental overload or pejorative stress factor of error.

Optical imaging of localized chemical events using programmable diamond quantum nanosensors

NASA Astrophysics Data System (ADS)

Rendler, Torsten; Neburkova, Jitka; Zemek, Ondrej; Kotek, Jan; Zappe, Andrea; Chu, Zhiqin; Cigler, Petr; Wrachtrup, Jörg

2017-03-01

Development of multifunctional nanoscale sensors working under physiological conditions enables monitoring of intracellular processes that are important for various biological and medical applications. By attaching paramagnetic gadolinium complexes to nanodiamonds (NDs) with nitrogen-vacancy (NV) centres through surface engineering, we developed a hybrid nanoscale sensor that can be adjusted to directly monitor physiological species through a proposed sensing scheme based on NV spin relaxometry. We adopt a single-step method to measure spin relaxation rates enabling time-dependent measurements on changes in pH or redox potential at a submicrometre-length scale in a microfluidic channel that mimics cellular environments. Our experimental data are reproduced by numerical simulations of the NV spin interaction with gadolinium complexes covering the NDs. Considering the versatile engineering options provided by polymer chemistry, the underlying mechanism can be expanded to detect a variety of physiologically relevant species and variables.

Elements of a nitrogen budget for a stream collector. Appendix IX

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

Not Available

1979-01-01

A simple diagram of a preliminary nitrogen budget for a generalized collector-gatherer is presented. The internal anatomy of chironomus sp. indicates its potential for fairly complex physiological processes. 26 refs., 2 figs.

Identification of complex metabolic states in critically injured patients using bioinformatic cluster analysis.

PubMed

Cohen, Mitchell J; Grossman, Adam D; Morabito, Diane; Knudson, M Margaret; Butte, Atul J; Manley, Geoffrey T

2010-01-01

Advances in technology have made extensive monitoring of patient physiology the standard of care in intensive care units (ICUs). While many systems exist to compile these data, there has been no systematic multivariate analysis and categorization across patient physiological data. The sheer volume and complexity of these data make pattern recognition or identification of patient state difficult. Hierarchical cluster analysis allows visualization of high dimensional data and enables pattern recognition and identification of physiologic patient states. We hypothesized that processing of multivariate data using hierarchical clustering techniques would allow identification of otherwise hidden patient physiologic patterns that would be predictive of outcome. Multivariate physiologic and ventilator data were collected continuously using a multimodal bioinformatics system in the surgical ICU at San Francisco General Hospital. These data were incorporated with non-continuous data and stored on a server in the ICU. A hierarchical clustering algorithm grouped each minute of data into 1 of 10 clusters. Clusters were correlated with outcome measures including incidence of infection, multiple organ failure (MOF), and mortality. We identified 10 clusters, which we defined as distinct patient states. While patients transitioned between states, they spent significant amounts of time in each. Clusters were enriched for our outcome measures: 2 of the 10 states were enriched for infection, 6 of 10 were enriched for MOF, and 3 of 10 were enriched for death. Further analysis of correlations between pairs of variables within each cluster reveals significant differences in physiology between clusters. Here we show for the first time the feasibility of clustering physiological measurements to identify clinically relevant patient states after trauma. These results demonstrate that hierarchical clustering techniques can be useful for visualizing complex multivariate data and may provide new insights for the care of critically injured patients.

Fractal dynamics in physiology: Alterations with disease and aging

PubMed Central

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

2002-01-01

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

Synaptic physiology of the flow of information in the cat's visual cortex in vivo

PubMed Central

Hirsch, Judith A; Martinez, Luis M; Alonso, José-Manuel; Desai, Komal; Pillai, Cinthi; Pierre, Carhine

2002-01-01

Each stage of the striate cortical circuit extracts novel information about the visual environment. We asked if this analytic process reflected laminar variations in synaptic physiology by making whole-cell recording with dye-filled electrodes from the cat's visual cortex and thalamus; the stimuli were flashed spots. Thalamic afferents terminate in layer 4, which contains two types of cell, simple and complex, distinguished by the spatial structure of the receptive field. Previously, we had found that the postsynaptic and spike responses of simple cells reliably followed the time course of flash-evoked thalamic activity. Here we report that complex cells in layer 4 (or cells intermediate between simple and complex) similarly reprised thalamic activity (response/trial, 99 ± 1.9 %; response duration 159 ± 57 ms; latency 25 ± 4 ms; average ± standard deviation; n = 7). Thus, all cells in layer 4 share a common synaptic physiology that allows secure integration of thalamic input. By contrast, at the second cortical stage (layer 2+3), where layer 4 directs its output, postsynaptic responses did not track simple patterns of antecedent activity. Typical responses to the static stimulus were intermittent and brief (response/trial, 31 ± 40 %; response duration 72 ± 60 ms, latency 39 ± 7 ms; n = 11). Only richer stimuli like those including motion evoked reliable responses. All told, the second level of cortical processing differs markedly from the first. At that later stage, ascending information seems strongly gated by connections between cortical neurons. Inputs must be combined in newly specified patterns to influence intracortical stages of processing. PMID:11927691

Physiological mechanisms underlying animal social behaviour.

PubMed

Seebacher, Frank; Krause, Jens

2017-08-19

Many species of animal live in groups, and the group represents the organizational level within which ecological and evolutionary processes occur. Understanding these processes, therefore, relies on knowledge of the mechanisms that permit or constrain group formation. We suggest that physiological capacities and differences in physiology between individuals modify fission-fusion dynamics. Differences between individuals in locomotor capacity and metabolism may lead to fission of groups and sorting of individuals into groups with similar physiological phenotypes. Environmental impacts such as hypoxia can influence maximum group sizes and structure in fish schools by altering access to oxygenated water. The nutritional environment determines group cohesion, and the increase in information collected by the group means that individuals should rely more on social information and form more cohesive groups in uncertain environments. Changing environmental contexts require rapid responses by individuals to maintain group coordination, which are mediated by neuroendocrine signalling systems such as nonapeptides and steroid hormones. Brain processing capacity may constrain social complexity by limiting information processing. Failure to evaluate socially relevant information correctly limits social interactions, which is seen, for example, in autism. Hence, functioning of a group relies to a large extent on the perception and appropriate processing of signals from conspecifics. Many if not all physiological systems are mechanistically linked, and therefore have synergistic effects on social behaviour. A challenge for the future lies in understanding these interactive effects, which will improve understanding of group dynamics, particularly in changing environments.This article is part of the themed issue 'Physiological determinants of social behaviour in animals'. © 2017 The Author(s).

Physiological mechanisms underlying animal social behaviour

PubMed Central

2017-01-01

Many species of animal live in groups, and the group represents the organizational level within which ecological and evolutionary processes occur. Understanding these processes, therefore, relies on knowledge of the mechanisms that permit or constrain group formation. We suggest that physiological capacities and differences in physiology between individuals modify fission–fusion dynamics. Differences between individuals in locomotor capacity and metabolism may lead to fission of groups and sorting of individuals into groups with similar physiological phenotypes. Environmental impacts such as hypoxia can influence maximum group sizes and structure in fish schools by altering access to oxygenated water. The nutritional environment determines group cohesion, and the increase in information collected by the group means that individuals should rely more on social information and form more cohesive groups in uncertain environments. Changing environmental contexts require rapid responses by individuals to maintain group coordination, which are mediated by neuroendocrine signalling systems such as nonapeptides and steroid hormones. Brain processing capacity may constrain social complexity by limiting information processing. Failure to evaluate socially relevant information correctly limits social interactions, which is seen, for example, in autism. Hence, functioning of a group relies to a large extent on the perception and appropriate processing of signals from conspecifics. Many if not all physiological systems are mechanistically linked, and therefore have synergistic effects on social behaviour. A challenge for the future lies in understanding these interactive effects, which will improve understanding of group dynamics, particularly in changing environments. This article is part of the themed issue ‘Physiological determinants of social behaviour in animals’. PMID:28673909

The Caenorhabditis elegans Excretory System: A Model for Tubulogenesis, Cell Fate Specification, and Plasticity

PubMed Central

Sundaram, Meera V.; Buechner, Matthew

2016-01-01

The excretory system of the nematode Caenorhabditis elegans is a superb model of tubular organogenesis involving a minimum of cells. The system consists of just three unicellular tubes (canal, duct, and pore), a secretory gland, and two associated neurons. Just as in more complex organs, cells of the excretory system must first adopt specific identities and then coordinate diverse processes to form tubes of appropriate topology, shape, connectivity, and physiological function. The unicellular topology of excretory tubes, their varied and sometimes complex shapes, and the dynamic reprogramming of cell identity and remodeling of tube connectivity that occur during larval development are particularly fascinating features of this organ. The physiological roles of the excretory system in osmoregulation and other aspects of the animal’s life cycle are only beginning to be explored. The cellular mechanisms and molecular pathways used to build and shape excretory tubes appear similar to those used in both unicellular and multicellular tubes in more complex organs, such as the vertebrate vascular system and kidney, making this simple organ system a useful model for understanding disease processes. PMID:27183565

TRPP2 ion channels: Critical regulators of organ morphogenesis in health and disease.

PubMed

Busch, Tilman; Köttgen, Michael; Hofherr, Alexis

2017-09-01

Ion channels control the membrane potential and mediate transport of ions across membranes. Archetypical physiological functions of ion channels include processes such as regulation of neuronal excitability, muscle contraction, or transepithelial ion transport. In that regard, transient receptor potential ion channel polycystin 2 (TRPP2) is remarkable, because it controls complex morphogenetic processes such as the establishment of properly shaped epithelial tubules and left-right-asymmetry of organs. The fascinating question of how an ion channel regulates morphogenesis has since captivated the attention of scientists in different disciplines. Four loosely connected key insights on different levels of biological complexity ranging from protein to whole organism have framed our understanding of TRPP2 physiology: 1) TRPP2 is a non-selective cation channel; 2) TRPP2 is part of a receptor-ion channel complex; 3) TRPP2 localizes to primary cilia; and 4) TRPP2 is required for organ morphogenesis. In this review, we will discuss the current knowledge in these key areas and highlight some of the challenges ahead. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Explicit Pharmacokinetic Modeling: Tools for Documentation, Verification, and Portability

EPA Science Inventory

Quantitative estimates of tissue dosimetry of environmental chemicals due to multiple exposure pathways require the use of complex mathematical models, such as physiologically-based pharmacokinetic (PBPK) models. The process of translating the abstract mathematics of a PBPK mode...

[Daily practice and pulp diseases].

PubMed

Calmein, S; Claisse, A

1990-09-01

Constructive or destructive processes of pulp tissue depend on many factors: anatomic topography, particular physiology, or intensity and duration of infectious, mechanical and chemical aggression. Also irritation of the pulpo-dentinal complex induce histologic and physiologic changes. The positive diagnosis of hyperemia, acute or chronic pulpitis, pulpal necrosis and acute or chronic apical abscess is performed by clinical investigations which allow a differential diagnosis with other dental or extra-dental diseases. These multiple steps lead to an adapted and appropriate treatment.

Modulation of ionotropic glutamate receptor function by vertebrate galectins.

PubMed

Copits, Bryan A; Vernon, Claire G; Sakai, Ryuichi; Swanson, Geoffrey T

2014-05-15

AMPA and kainate receptors are glutamate-gated ion channels whose function is known to be altered by a variety of plant oligosaccharide-binding proteins, or lectins, but the physiological relevance of this activity has been uncertain because no lectins with analogous allosteric modulatory effects have been identified in animals. We report here that members of the prototype galectin family, which are β-galactoside-binding lectins, exhibit subunit-specific allosteric modulation of desensitization of recombinant homomeric and heteromeric AMPA and kainate receptors. Galectin modulation of GluK2 kainate receptors was dependent upon complex oligosaccharide processing of N-glycosylation sites in the amino-terminal domain and downstream linker region. The sensitivity of GluA4 AMPA receptors to human galectin-1 could be enhanced by supplementation of culture media with uridine and N-acetylglucosamine (GlcNAc), precursors for the hexosamine pathway that supplies UDP-GlcNAc for synthesis of complex oligosaccharides. Neuronal kainate receptors in dorsal root ganglia were sensitive to galectin modulation, whereas AMPA receptors in cultured hippocampal neurons were insensitive, which could be a reflection of differential N-glycan processing or receptor subunit selectivity. Because glycan content of integral proteins can be modified dynamically, we postulate that physiological or pathological conditions in the CNS could arise in which galectins alter excitatory neurotransmission or neuronal excitability through their actions on AMPA or kainate receptors. © 2014 The Authors. The Journal of Physiology © 2014 The Physiological Society.

Fully integrated wearable sensor arrays for multiplexed in situ perspiration analysis.

PubMed

Gao, Wei; Emaminejad, Sam; Nyein, Hnin Yin Yin; Challa, Samyuktha; Chen, Kevin; Peck, Austin; Fahad, Hossain M; Ota, Hiroki; Shiraki, Hiroshi; Kiriya, Daisuke; Lien, Der-Hsien; Brooks, George A; Davis, Ronald W; Javey, Ali

2016-01-28

Wearable sensor technologies are essential to the realization of personalized medicine through continuously monitoring an individual's state of health. Sampling human sweat, which is rich in physiological information, could enable non-invasive monitoring. Previously reported sweat-based and other non-invasive biosensors either can only monitor a single analyte at a time or lack on-site signal processing circuitry and sensor calibration mechanisms for accurate analysis of the physiological state. Given the complexity of sweat secretion, simultaneous and multiplexed screening of target biomarkers is critical and requires full system integration to ensure the accuracy of measurements. Here we present a mechanically flexible and fully integrated (that is, no external analysis is needed) sensor array for multiplexed in situ perspiration analysis, which simultaneously and selectively measures sweat metabolites (such as glucose and lactate) and electrolytes (such as sodium and potassium ions), as well as the skin temperature (to calibrate the response of the sensors). Our work bridges the technological gap between signal transduction, conditioning (amplification and filtering), processing and wireless transmission in wearable biosensors by merging plastic-based sensors that interface with the skin with silicon integrated circuits consolidated on a flexible circuit board for complex signal processing. This application could not have been realized using either of these technologies alone owing to their respective inherent limitations. The wearable system is used to measure the detailed sweat profile of human subjects engaged in prolonged indoor and outdoor physical activities, and to make a real-time assessment of the physiological state of the subjects. This platform enables a wide range of personalized diagnostic and physiological monitoring applications.

Fully integrated wearable sensor arrays for multiplexed in situ perspiration analysis

NASA Astrophysics Data System (ADS)

Gao, Wei; Emaminejad, Sam; Nyein, Hnin Yin Yin; Challa, Samyuktha; Chen, Kevin; Peck, Austin; Fahad, Hossain M.; Ota, Hiroki; Shiraki, Hiroshi; Kiriya, Daisuke; Lien, Der-Hsien; Brooks, George A.; Davis, Ronald W.; Javey, Ali

2016-01-01

Wearable sensor technologies are essential to the realization of personalized medicine through continuously monitoring an individual’s state of health. Sampling human sweat, which is rich in physiological information, could enable non-invasive monitoring. Previously reported sweat-based and other non-invasive biosensors either can only monitor a single analyte at a time or lack on-site signal processing circuitry and sensor calibration mechanisms for accurate analysis of the physiological state. Given the complexity of sweat secretion, simultaneous and multiplexed screening of target biomarkers is critical and requires full system integration to ensure the accuracy of measurements. Here we present a mechanically flexible and fully integrated (that is, no external analysis is needed) sensor array for multiplexed in situ perspiration analysis, which simultaneously and selectively measures sweat metabolites (such as glucose and lactate) and electrolytes (such as sodium and potassium ions), as well as the skin temperature (to calibrate the response of the sensors). Our work bridges the technological gap between signal transduction, conditioning (amplification and filtering), processing and wireless transmission in wearable biosensors by merging plastic-based sensors that interface with the skin with silicon integrated circuits consolidated on a flexible circuit board for complex signal processing. This application could not have been realized using either of these technologies alone owing to their respective inherent limitations. The wearable system is used to measure the detailed sweat profile of human subjects engaged in prolonged indoor and outdoor physical activities, and to make a real-time assessment of the physiological state of the subjects. This platform enables a wide range of personalized diagnostic and physiological monitoring applications.

Measuring Anxious Responses to Predictable and Unpredictable Threat in Children and Adolescents

ERIC Educational Resources Information Center

Schmitz, Anja; Merikangas, Kathleen; Swendsen, Haruka; Cui, Lihong; Heaton, Leann; Grillon, Christian

2011-01-01

Research has highlighted the need for new methods to assess emotions in children on multiple levels to gain better insight into the complex processes of emotional development. The startle reflex is a unique translational tool that has been used to study physiological processes during fear and anxiety in rodents and in human participants. However,…

Development and Application of Learning Materials to Help Students Understand Ten Statements Describing the Nature of Scientific Observation

ERIC Educational Resources Information Center

Kim, Sangsoo; Park, Jongwon

2018-01-01

Observing scientific events or objects is a complex process that occurs through the interaction between the observer's knowledge or expectations, the surrounding context, physiological features of the human senses, scientific inquiry processes, and the use of observational instruments. Scientific observation has various features specific to this…

Predicting embryo presence and viability

USDA-ARS?s Scientific Manuscript database

Pregnancy establishment, followed by birth of live offspring, is essential to all mammals. The biological processes leading up to pregnancy establishment, maintenance, and birth are complex and dependent on the coordinated timing of a series of events at the molecular, cellular, and physiological le...

Can modular psychological concepts like affect and emotion be assigned to a distinct subset of regional neural circuits?. Comment on "The quartet theory of human emotions: An integrative and neurofunctional model" by S. Koelsch et al.

NASA Astrophysics Data System (ADS)

Fehr, Thorsten; Herrmann, Manfred

2015-06-01

The proposed Quartet Theory of Human Emotions by Koelsch and co-workers [11] adumbrates evidence from various scientific sources to integrate and assign the psychological concepts of 'affect' and 'emotion' to four brain circuits or to four neuronal core systems for affect-processing in the brain. The authors differentiate between affect and emotion and assign several facultative, or to say modular, psychological domains and principles of information processing, such as learning and memory, antecedents of affective activity, emotion satiation, cognitive complexity, subjective quality feelings, degree of conscious appraisal, to different affect systems. Furthermore, they relate orbito-frontal brain structures to moral affects as uniquely human, and the hippocampus to attachment-related affects. An additional feature of the theory describes 'emotional effector-systems' for motor-related processes (e.g., emotion-related actions), physiological arousal, attention and memory that are assumed to be cross-linked with the four proposed affect systems. Thus, higher principles of emotional information processing, but also modular affect-related issues, such as moral and attachment related affects, are thought to be handled by these four different physiological sub-systems that are on the other side assumed to be highly interwoven at both physiological and functional levels. The authors also state that the proposed sub-systems have many features in common, such as the selection and modulation of biological processes related to behaviour, perception, attention and memory. The latter aspect challenges an ongoing discussion about the mind-body problem: To which degree do the proposed sub-systems 'sufficiently' cover the processing of complex modular or facultative emotional/affective and/or cognitive phenomena? There are current models and scientific positions that almost completely reject the idea that modular psychological phenomena are handled by a distinct selection of regional brain systems or neural modules, but rather suggest highly complex and cross-linked neural networks individually shaped by livelong learning and experience [e.g., 6,7,10,13]. This holds in particular true for complex emotional phenomena such as aggression or empathy in social interaction [8,13]. It thus remains questionable, whether - beyond primary sensory and motor-processing - a small number of modular sub-systems sufficiently cover the organisation of specific phenomenological and social features of perception and behaviour [7,10].

Let's 'play' with molecular pharmacology.

PubMed

Choudhury, Supriyo; Pradhan, Richeek; Sengupta, Gairik; Das, Manisha; Chatterjee, Manojit; Roy, Ranendra Kumar; Chatterjee, Suparna

2015-01-01

Understanding concepts of molecular mechanisms of drug action involves sequential visualization of physiological processes and drug effects, a task that can be difficult at an undergraduate level. Role-play is a teaching-learning methodology whereby active participation of students as well as clear visualization of the phenomenon is used to convey complex physiological concepts. However, its use in teaching drug action, a process that demands understanding of a second level of complexity over the physiological process, has not been investigated. We hypothesized that role-play can be an effective and well accepted method for teaching molecular pharmacology. In an observational study, students were guided to perform a role-play on a selected topic involving drug activity. Students' gain in knowledge was assessed comparing validated pre- and post-test questionnaires as well as class average normalized gain. The acceptance of role-play among undergraduate medical students was evaluated by Likert scale analysis and thematic analysis of their open-ended written responses. Significant improvement in knowledge (P < 0.001) was noted in the pre- to post-test knowledge scores, while a high gain in class average normalized score was evident. In Likert scale analysis, most students (93%) expressed that role-play was an acceptable way of teaching. In a thematic analysis, themes of both strengths and weaknesses of the session emerged. Role-play can be effectively utilized while teaching selected topics of molecular pharmacology in undergraduate medical curricula.

Local spatio-temporal analysis in vision systems

NASA Astrophysics Data System (ADS)

Geisler, Wilson S.; Bovik, Alan; Cormack, Lawrence; Ghosh, Joydeep; Gildeen, David

1994-07-01

The aims of this project are the following: (1) develop a physiologically and psychophysically based model of low-level human visual processing (a key component of which are local frequency coding mechanisms); (2) develop image models and image-processing methods based upon local frequency coding; (3) develop algorithms for performing certain complex visual tasks based upon local frequency representations, (4) develop models of human performance in certain complex tasks based upon our understanding of low-level processing; and (5) develop a computational testbed for implementing, evaluating and visualizing the proposed models and algorithms, using a massively parallel computer. Progress has been substantial on all aims. The highlights include the following: (1) completion of a number of psychophysical and physiological experiments revealing new, systematic and exciting properties of the primate (human and monkey) visual system; (2) further development of image models that can accurately represent the local frequency structure in complex images; (3) near completion in the construction of the Texas Active Vision Testbed; (4) development and testing of several new computer vision algorithms dealing with shape-from-texture, shape-from-stereo, and depth-from-focus; (5) implementation and evaluation of several new models of human visual performance; and (6) evaluation, purchase and installation of a MasPar parallel computer.

Heart rate complexity in sinoaortic-denervated mice.

PubMed

Silva, Luiz Eduardo V; Rodrigues, Fernanda Luciano; de Oliveira, Mauro; Salgado, Hélio Cesar; Fazan, Rubens

2015-02-01

What is the central question of this study? New measurements for cardiovascular complexity, such as detrended fluctuation analysis (DFA) and multiscale entropy (MSE), have been shown to predict cardiovascular outcomes. Given that cardiovascular diseases are accompanied by autonomic imbalance and decreased baroreflex sensitivity, the central question is: do baroreceptors contribute to cardiovascular complexity? What is the main finding and its importance? Sinoaortic denervation altered both DFA scaling exponents and MSE, indicating that both short- and long-term mechanisms of complexity are altered in sinoaortic denervated mice, resulting in a loss of physiological complexity. These results suggest that the baroreflex is a key element in the complex structures involved in heart rate variability regulation. Recently, heart rate (HR) oscillations have been recognized as complex behaviours derived from non-linear processes. Physiological complexity theory is based on the idea that healthy systems present high complexity, i.e. non-linear, fractal variability at multiple scales, with long-range correlations. The loss of complexity in heart rate variability (HRV) has been shown to predict adverse cardiovascular outcomes. Based on the idea that most cardiovascular diseases are accompanied by autonomic imbalance and a decrease in baroreflex sensitivity, we hypothesize that the baroreflex plays an important role in complex cardiovascular behaviour. Mice that had been subjected to sinoaortic denervation (SAD) were implanted with catheters in the femoral artery and jugular vein 5 days prior to the experiment. After recording the baseline arterial pressure (AP), pulse interval time series were generated from the intervals between consecutive values of diastolic pressure. The complexity of the HRV was determined using detrended fluctuation analysis and multiscale entropy. The detrended fluctuation analysis α1 scaling exponent (a short-term index) was remarkably decreased in the SAD mice (0.79 ± 0.06 versus 1.13 ± 0.04 for the control mice), whereas SAD slightly increased the α2 scaling exponent (a long-term index; 1.12 ± 0.03 versus 1.04 ± 0.02 for control mice). In the SAD mice, the total multiscale entropy was decreased (13.2 ± 1.3) compared with the control mice (18.9 ± 1.4). In conclusion, fractal and regularity structures of HRV are altered in SAD mice, affecting both short- and long-term mechanisms of complexity, suggesting that the baroreceptors play a considerable role in the complex structure of HRV. © 2014 The Authors. Experimental Physiology © 2014 The Physiological Society.

Searching and Mining Visually Observed Phenotypes of Maize Mutants

USDA-ARS?s Scientific Manuscript database

There are thousands of maize mutants, which are invaluable resources for plant research. Geneticists use them to study underlying mechanisms of biochemistry, cell biology, cell development, and cell physiology. To streamline the understanding of such complex processes, researchers need the most curr...

Controls of Isotopic Patterns in Saprotrophic and Ectomycorrhizal Fungi

EPA Science Inventory

Isotopes of nitrogen (δ15N) and carbon (δ13C) in ectomycorrhizal and saprotrophic fungi contain important information about ecological functioning, but the complexity of physiological and ecosystem processes contributing to fungal carbon and nitrogen dynamics has limited our abil...

Leadership Maintenance: Filling the Gap for Leadership Competences

ERIC Educational Resources Information Center

Rajbhandari, Mani Man Singh; Rajbhandari, Smriti

2015-01-01

In this study, leadership maintenance employs psychological, sociological and physiological paradigms in creating a conducive environment for both leaders' and followers' well-being in educational settings. Leadership maintenance is an ongoing process, which entails the understanding of leader's cognitive complexity, relational approaches towards…

Circadian clocks in symbiotic corals: the duet between Symbiodinium algae and their coral host.

PubMed

Sorek, Michal; Díaz-Almeyda, Erika M; Medina, Mónica; Levy, Oren

2014-04-01

To date, the association and synchronization between two organismal circadian clocks ticking in parallel as part of a meta-organism (termed a symbiotic association), have rarely been investigated. Reef-building corals exhibit complex rhythmic responses to diurnal, lunar, and annual changes. Understanding circadian, circatidal, and annual regulation in reef-building corals is complicated by the presence of photosynthetic endosymbionts, which have a profound physiochemical influence on the intracellular environment. How corals tune their animal-based clock machinery to respond to external cues while simultaneously responding to internal physiological changes imposed by the symbiont, is not clear. There is insufficient molecular or physiological evidence of the existence of a circadian pacemaker that controls the metabolism, photosynthesis, synchronized mass spawning, and calcification processes in symbiotic corals. In this review, we present current knowledge regarding the animal pacemaker and the symbiotic-algal pacemaker. We examine the evidence from behavioral, physiological, molecular, and evolutionary perspectives. We explain why symbiotic corals are an interesting model with which to study the complexities and evolution of the metazoan circadian clock. We also provide evidence of why the chronobiology of corals is fundamental and extremely important for explaining the biology, physiology, and metabolism of coral reefs. A deeper understanding of these complex issues can help explain coral mass spawning, one of the earth's greatest and most mysterious behavioral phenomena. Copyright © 2014 Elsevier B.V. All rights reserved.

A hip joint simulator study using simplified loading and motion cycles generating physiological wear paths and rates.

PubMed

Barbour, P S; Stone, M H; Fisher, J

1999-01-01

In some designs of hip joint simulator the cost of building a highly complex machine has been offset with the requirement for a large number of test stations. The application of the wear results generated by these machines depends on their ability to reproduce physiological wear rates and processes. In this study a hip joint simulator has been shown to reproduce physiological wear using only one load vector and two degrees of motion with simplified input cycles. The actual path of points on the femoral head relative to the acetabular cup were calculated and compared for physiological and simplified input cycles. The in vitro wear rates were found to be highly dependent on the shape of these paths and similarities could be drawn between the shape of the physiological paths and the simplified elliptical paths.

Complex coacervates as a foundation for synthetic underwater adhesives

PubMed Central

Stewart, Russell J.; Wang, Ching Shuen; Shao, Hui

2011-01-01

Complex coacervation was proposed to play a role in the formation of the underwater bioadhesive of the Sandcastle worm (Phragmatopoma californica) based on the polyacidic and polybasic nature of the glue proteins and the balance of opposite charges at physiological pH. Morphological studies of the secretory system suggested the natural process does not involve complex coacervation as commonly defined. The distinction may not be important because electrostatic interactions likely play an important role in formation of the sandcastle glue. Complex coacervation has also been invoked in the formation of adhesive underwater silk fibers of caddisfly larvae and the adhesive plaques of mussels. A process similar to complex coacervation, that is, condensation and dehydration of biopolyelectrolytes through electrostatic associations, seems plausible for the caddisfly silk. This much is clear, the sandcastle glue complex coacervation model provided a valuable blueprint for the synthesis of a biomimetic, waterborne, underwater adhesive with demonstrated potential for repair of wet tissue. PMID:21081223

Knowledge environments representing molecular entities for the virtual physiological human.

PubMed

Hofmann-Apitius, Martin; Fluck, Juliane; Furlong, Laura; Fornes, Oriol; Kolárik, Corinna; Hanser, Susanne; Boeker, Martin; Schulz, Stefan; Sanz, Ferran; Klinger, Roman; Mevissen, Theo; Gattermayer, Tobias; Oliva, Baldo; Friedrich, Christoph M

2008-09-13

In essence, the virtual physiological human (VPH) is a multiscale representation of human physiology spanning from the molecular level via cellular processes and multicellular organization of tissues to complex organ function. The different scales of the VPH deal with different entities, relationships and processes, and in consequence the models used to describe and simulate biological functions vary significantly. Here, we describe methods and strategies to generate knowledge environments representing molecular entities that can be used for modelling the molecular scale of the VPH. Our strategy to generate knowledge environments representing molecular entities is based on the combination of information extraction from scientific text and the integration of information from biomolecular databases. We introduce @neuLink, a first prototype of an automatically generated, disease-specific knowledge environment combining biomolecular, chemical, genetic and medical information. Finally, we provide a perspective for the future implementation and use of knowledge environments representing molecular entities for the VPH.

Circadian rhythm and menopause.

PubMed

Pines, A

2016-12-01

Circadian rhythm is an internal biological clock which initiates and monitors various physiological processes with a fixed time-related schedule. The master circadian pacemaker is located in the suprachiasmatic nucleus in the hypothalamus. The circadian clock undergoes significant changes throughout the life span, at both the physiological and molecular levels. This cyclical physiological process, which is very complex and multifactorial, may be associated with metabolic alterations, atherosclerosis, impaired cognition, mood disturbances and even development of cancer. Sex differences do exist, and the well-known sleep disturbances associated with menopause are a good example. Circadian rhythm was detected in the daily pattern of hot flushes, with a peak in the afternoons. Endogenous secretion of melatonin decreases with aging across genders, and, among women, menopause is associated with a significant reduction of melatonin levels, affecting sleep. Although it might seem that hot flushes and melatonin secretion are likely related, there are not enough data to support such a hypothesis.

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

Visual Screening: A Procedure.

ERIC Educational Resources Information Center

Williams, Robert T.

Vision is a complex process involving three phases: physical (acuity), physiological (integrative), and psychological (perceptual). Although these phases cannot be considered discrete, they provide the basis for the visual screening procedure used by the Reading Services of Colorado State University and described in this document. Ten tests are…

Modeling energy expenditure in children and adolescents using quantile regression

USDA-ARS?s Scientific Manuscript database

Advanced mathematical models have the potential to capture the complex metabolic and physiological processes that result in energy expenditure (EE). Study objective is to apply quantile regression (QR) to predict EE and determine quantile-dependent variation in covariate effects in nonobese and obes...

A network-based approach for semi-quantitative knowledge mining and its application to yield variability

NASA Astrophysics Data System (ADS)

Schauberger, Bernhard; Rolinski, Susanne; Müller, Christoph

2016-12-01

Variability of crop yields is detrimental for food security. Under climate change its amplitude is likely to increase, thus it is essential to understand the underlying causes and mechanisms. Crop models are the primary tool to project future changes in crop yields under climate change. A systematic overview of drivers and mechanisms of crop yield variability (YV) can thus inform crop model development and facilitate improved understanding of climate change impacts on crop yields. Yet there is a vast body of literature on crop physiology and YV, which makes a prioritization of mechanisms for implementation in models challenging. Therefore this paper takes on a novel approach to systematically mine and organize existing knowledge from the literature. The aim is to identify important mechanisms lacking in models, which can help to set priorities in model improvement. We structure knowledge from the literature in a semi-quantitative network. This network consists of complex interactions between growing conditions, plant physiology and crop yield. We utilize the resulting network structure to assign relative importance to causes of YV and related plant physiological processes. As expected, our findings confirm existing knowledge, in particular on the dominant role of temperature and precipitation, but also highlight other important drivers of YV. More importantly, our method allows for identifying the relevant physiological processes that transmit variability in growing conditions to variability in yield. We can identify explicit targets for the improvement of crop models. The network can additionally guide model development by outlining complex interactions between processes and by easily retrieving quantitative information for each of the 350 interactions. We show the validity of our network method as a structured, consistent and scalable dictionary of literature. The method can easily be applied to many other research fields.

Fully integrated wearable sensor arrays for multiplexed in situ perspiration analysis

PubMed Central

Nyein, Hnin Yin Yin; Challa, Samyuktha; Chen, Kevin; Peck, Austin; Fahad, Hossain M.; Ota, Hiroki; Shiraki, Hiroshi; Kiriya, Daisuke; Lien, Der-Hsien; Brooks, George A.; Davis, Ronald W.; Javey, Ali

2016-01-01

Wearable sensor technologies are essential to the realization of personalized medicine through continuously monitoring an individual's state of health1–12. Sampling human sweat, which is rich in physiological information13, could enable non-invasive monitoring. Previously reported sweat-based and other non-invasive biosensors either can only monitor a single analyte at a time or lack on-site signal processing circuitry and sensor calibration mechanisms for accurate analysis of the physiological state14–18. Given the complexity of sweat secretion, simultaneous and multiplexed screening of target biomarkers is critical and requires full system integration to ensure the accuracy of measurements. Here we present a mechanically flexible and fully integrated (that is, no external analysis is needed) sensor array for multiplexed in situ perspiration analysis, which simultaneously and selectively measures sweat metabolites (such as glucose and lactate) and electrolytes (such as sodium and potassium ions), as well as the skin temperature (to calibrate the response of the sensors). Our work bridges the technological gap between signal transduction, conditioning (amplification and filtering), processing and wireless transmission in wearable biosensors by merging plastic-based sensors that interface with the skin with silicon integrated circuits consolidated on a flexible circuit board for complex signal processing. This application could not have been realized using either of these technologies alone owing to their respective inherent limitations. The wearable system is used to measure the detailed sweat profile of human subjects engaged in prolonged indoor and outdoor physical activities, and to make a real-time assessment of the physiological state of the subjects. This platform enables a wide range of personalized diagnostic and physiological monitoring applications. PMID:26819044

Dual personality of Mad1: regulation of nuclear import by a spindle assembly checkpoint protein.

PubMed

Cairo, Lucas V; Ptak, Christopher; Wozniak, Richard W

2013-01-01

Nuclear transport is a dynamic process that can be modulated in response to changes in cellular physiology. We recently reported that the transport activity of yeast nuclear pore complexes (NPCs) is altered in response to kinetochore-microtubule (KT-MT) interaction defects. Specifically, KT detachment from MTs activates a signaling pathway that prevents the nuclear import of cargos by the nuclear transport factor Kap121p. This loss of Kap121p-mediated import is thought to influence the nuclear environment, including the phosphorylation state of nuclear proteins. A key regulator of this process is the spindle assembly checkpoint protein Mad1p. In response to unattached KTs, Mad1p dynamically cycles between NPCs and KTs. This cycling appears to induce NPC molecular rearrangements that prevent the nuclear import of Kap121p-cargo complexes. Here, we discuss the underlying mechanisms and the physiological relevance of Mad1p cycling and the inhibition of Kap121p-mediated nuclear import, focusing on outstanding questions within the pathway.

Complex Networks - A Key to Understanding Brain Function

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

Sporns, Olaf

2008-01-23

The brain is a complex network of neurons, engaging in spontaneous and evoked activity that is thought to be the main substrate of mental life.  How this complex system works together to process information and generate coherent cognitive states, even consciousness, is not yet well understood.  In my talk I will review recent studies that have revealed characteristic structural and functional attributes of brain networks, and discuss efforts to build computational models of the brain that are informed by our growing knowledge of brain anatomy and physiology.

Complex Networks - A Key to Understanding Brain Function

ScienceCinema

Sporns, Olaf

2017-12-22

The brain is a complex network of neurons, engaging in spontaneous and evoked activity that is thought to be the main substrate of mental life.  How this complex system works together to process information and generate coherent cognitive states, even consciousness, is not yet well understood.  In my talk I will review recent studies that have revealed characteristic structural and functional attributes of brain networks, and discuss efforts to build computational models of the brain that are informed by our growing knowledge of brain anatomy and physiology.

Teaching cardiovascular physiology with equivalent electronic circuits in a practically oriented teaching module.

PubMed

Ribaric, Samo; Kordas, Marjan

2011-06-01

Here, we report on a new tool for teaching cardiovascular physiology and pathophysiology that promotes qualitative as well as quantitative thinking about time-dependent physiological phenomena. Quantification of steady and presteady-state (transient) cardiovascular phenomena is traditionally done by differential equations, but this is time consuming and unsuitable for most undergraduate medical students. As a result, quantitative thinking about time-dependent physiological phenomena is often not extensively dealt with in an undergraduate physiological course. However, basic concepts of steady and presteady state can be explained with relative simplicity, without the introduction of differential equation, with equivalent electronic circuits (EECs). We introduced undergraduate medical students to the concept of simulating cardiovascular phenomena with EECs. EEC simulations facilitate the understanding of simple or complex time-dependent cardiovascular physiological phenomena by stressing the analogies between EECs and physiological processes. Student perceptions on using EEC to simulate, study, and understand cardiovascular phenomena were documented over a 9-yr period, and the impact of the course on the students' knowledge of selected basic facts and concepts in cardiovascular physiology was evaluated over a 3-yr period. We conclude that EECs are a valuable tool for teaching cardiovascular physiology concepts and that EECs promote active learning.

A Systems Approach to the Physiology of Weightlessness

NASA Technical Reports Server (NTRS)

White, Ronald J.; Leonard, Joel I.; Rummel, John A.; Leach, Carolyn S.

1991-01-01

A systems approach to the unraveling of the complex response pattern of the human subjected to weightlessness is presented. The major goal of this research is to obtain an understanding of the role that each of the major components of the human system plays following the transition to and from space. The cornerstone of this approach is the utilization of a variety of mathematical models in order to pose and test alternative hypotheses concerned with the adaptation process. An integrated hypothesis for the human physiological response to weightlessness is developed.

The role of metals in protein conformational disorders - The case of prion protein and Aβ -peptide

NASA Astrophysics Data System (ADS)

De Santis, E.; Minicozzi, V.; Morante, S.; Rossi, G. C.; Stellato, F.

2016-02-01

Protein conformational disorders are members of a vast class of pathologies in which endogenous proteins or peptides undergo a misfolding process by switching from the physiological soluble configuration to a pathological fibrillar insoluble state. An important, but not yet fully elucidated, role in the process appears to be played by transition metal ions, mainly copper and zinc. X-ray absorption spectroscopy is one of the most suitable techniques for the structural characterization of biological molecules in complex with metal. Owing to its chemical selectivity and sensitivity to the local atomic geometry around the absorber, it can be successfully used to study the environment of metal ions in complex with proteins and peptides in physiological conditions. In this paper we present X-ray absorption spectroscopy studies of the metal ions coordination modes in systems where metals are complexed with specific amyloidogenic proteins and peptides. In particular, we show results concerning the Amyloid β peptide, that is involved in Alzheimer's disease, and the Prion protein, that is responsible for the Transmissible Spongiform Encephalopathy. Our findings suggest that the copper and zinc ions may play a crucial role in the aggregation and fibril formation process of these two biomolecules. Elucidating this kind of interaction could be a key preliminary step before any viable therapy can be conceived or designed.

Is Relaxation Training Effective in the Treatment of Clinical Depression?

ERIC Educational Resources Information Center

Beaty, Lee A.

The process of relaxation is a complex triarchic phenomenon that incorporates behavioral, cognitive, and physiological components. Existing literature is surveyed in order to determine the efficacy of treating various forms of depression with cognitive-behavioral relaxation strategies. Relaxation training has been shown to be effective in treating…

Biochemistry of the Envenomation Response--A Generator Theme for Interdisciplinary Integration

ERIC Educational Resources Information Center

Montagna, Erik; Guerreiro, Juliano R.; Torres, Bayardo B.

2010-01-01

The understanding of complex physiological processes requires information from many different areas of knowledge. To meet this interdisciplinary scenario, the ability of integrating and articulating information is demanded. The difficulty of such approach arises because, more often than not, information is fragmented through under graduation…

Multimodal Therapy for Anorexia Nervosa: An Holistic Approach to Treatment.

ERIC Educational Resources Information Center

O'Keefe, Edward J.; Castaldo, Christine

1985-01-01

Anorexia nervosa has received considerable attention lately because of its increased incidence, potential danger, and resistance to treatment. A review of the literature on anorexia nervosa suggests that, although it is characterized by complex interrelated psychological and physiological processes, it is often conceptualized and treated in…

Filter-based multiscale entropy analysis of complex physiological time series.

PubMed

Xu, Yuesheng; Zhao, Liang

2013-08-01

Multiscale entropy (MSE) has been widely and successfully used in analyzing the complexity of physiological time series. We reinterpret the averaging process in MSE as filtering a time series by a filter of a piecewise constant type. From this viewpoint, we introduce filter-based multiscale entropy (FME), which filters a time series to generate multiple frequency components, and then we compute the blockwise entropy of the resulting components. By choosing filters adapted to the feature of a given time series, FME is able to better capture its multiscale information and to provide more flexibility for studying its complexity. Motivated by the heart rate turbulence theory, which suggests that the human heartbeat interval time series can be described in piecewise linear patterns, we propose piecewise linear filter multiscale entropy (PLFME) for the complexity analysis of the time series. Numerical results from PLFME are more robust to data of various lengths than those from MSE. The numerical performance of the adaptive piecewise constant filter multiscale entropy without prior information is comparable to that of PLFME, whose design takes prior information into account.

Pyruvate dehydrogenase complex (PDC) export from the mitochondrial matrix.

PubMed

Ng, Fanny; Tang, Bor Luen

2014-01-01

Studies on mitochondria protein import had revealed in detail molecular mechanisms of how peptides and proteins could be selectively targeted and translocated across membrane bound organelles. The opposite process of mitochondrial export, while known to occur in various aspects of cellular physiology and pathology, is less well understood. Two very recent reports have indicated that a large mitochondrial matrix protein complex, the pyruvate dehydrogenase complex (PDC) (or its component subunits), could be exported to the lysosomes and the nucleus, respectively. In the case of the latter, evidence was presented to suggest that the entire complex of 8-10 MDa could translocate in its entirety from the mitochondrial matrix to the nucleus upon mitogenic or stress stimuli. We discuss these findings in perspective to what is currently known about the processes of transport in and out of the mitochondrion.

Differential roles of NADPH oxidases in vascular physiology and pathophysiology

PubMed Central

Amanso, Angelica M.; Griendling, Kathy K.

2012-01-01

Reactive oxygen species (ROS) are produced by all vascular cells and regulate the major physiological functions of the vasculature. Production and removal of ROS are tightly controlled and occur in discrete subcellular locations, allowing for specific, compartmentalized signaling. Among the many sources of ROS in the vessel wall, NADPH oxidases are implicated in physiological functions such as control of vasomotor tone, regulation of extracellular matrix and phenotypic modulation of vascular smooth muscle cells. They are involved in the response to injury, whether as an oxygen sensor during hypoxia, as a regulator of protein processing, as an angiogenic stimulus, or as a mechanism of wound healing. These enzymes have also been linked to processes leading to disease development, including migration, proliferation, hypertrophy, apoptosis and autophagy. As a result, NADPH oxidases participate in atherogenesis, systemic and pulmonary hypertension and diabetic vascular disease. The role of ROS in each of these processes and diseases is complex, and a more full understanding of the sources, targets, cell-specific responses and counterbalancing mechanisms is critical for the rational development of future therapeutics. PMID:22202108

Dynamics between actin and the VE-cadherin/catenin complex

PubMed Central

Abu Taha, Abdallah; Schnittler, Hans-J

2014-01-01

Endothelial adherens junctions are critical for physiological and pathological processes such as differentiation, maintenance of entire monolayer integrity, and the remodeling. The endothelial-specific VE-cadherin/catenin complex provides the backbone of adherens junctions and acts in close interaction with actin filaments and actin/myosin-mediated contractility to fulfill the junction demands. The functional connection between the cadherin/catenin complex and actin filaments might be either directly through α-catenins, or indirectly e.g., via linker proteins such as vinculin, p120ctn, α-actinin, or EPLIN. However, both junction integrity and dynamic remodeling have to be contemporarily coordinated. The actin-related protein complex ARP2/3 and its activating molecules, such as N-WASP and WAVE, have been shown to regulate the lammellipodia-mediated formation of cell junctions in both epithelium and endothelium. Recent reports now demonstrate a novel aspect of the ARP2/3 complex and the nucleating-promoting factors in the maintenance of endothelial barrier function and junction remodeling of established endothelial cell junctions. Those mechanisms open novel possibilities; not only in fulfilling physiological demands but obtained information may be of critical importance in pathologies such as wound healing, angiogenesis, inflammation, and cell diapedesis. PMID:24621569

[Dinitrosyl iron complexes are endogenous signaling agents in animal and human cells and tissues (a hypothesis)].

PubMed

Vanin, A F

2004-01-01

The hypothesis was advanced that dinitrosyl iron complexes generated in animal and human cells and tissues producing nitric oxide can function as endogenous universal regulators of biochemical and physiological processes. This function is realized by the ability of dinitrosyl iron complexes to act as donors of free nitric oxide molecules interacting with the heme groups of proteins, nitrosonium ions, or Fe+(NO+)2 interacting with the thiol groups of proteins. The effect of dinitrosyl iron complexes on the activity of some enzymes and the expression of the genome at the translation and transcription levels was considered.

Beauty and the brain: culture, history and individual differences in aesthetic appreciation.

PubMed

Jacobsen, Thomas

2010-02-01

Human aesthetic processing entails the sensation-based evaluation of an entity with respect to concepts like beauty, harmony or well-formedness. Aesthetic appreciation has many determinants ranging from evolutionary, anatomical or physiological constraints to influences of culture, history and individual differences. There are a vast number of dynamically configured neural networks underlying these multifaceted processes of aesthetic appreciation. In the current challenge of successfully bridging art and science, aesthetics and neuroanatomy, the neuro-cognitive psychology of aesthetics can approach this complex topic using a framework that postulates several perspectives, which are not mutually exclusive. In this empirical approach, objective physiological data from event-related brain potentials and functional magnetic resonance imaging are combined with subjective, individual self-reports.

Beauty and the brain: culture, history and individual differences in aesthetic appreciation

PubMed Central

Jacobsen, Thomas

2010-01-01

Human aesthetic processing entails the sensation-based evaluation of an entity with respect to concepts like beauty, harmony or well-formedness. Aesthetic appreciation has many determinants ranging from evolutionary, anatomical or physiological constraints to influences of culture, history and individual differences. There are a vast number of dynamically configured neural networks underlying these multifaceted processes of aesthetic appreciation. In the current challenge of successfully bridging art and science, aesthetics and neuroanatomy, the neuro-cognitive psychology of aesthetics can approach this complex topic using a framework that postulates several perspectives, which are not mutually exclusive. In this empirical approach, objective physiological data from event-related brain potentials and functional magnetic resonance imaging are combined with subjective, individual self-reports. PMID:19929909

Multiscale entropy-based methods for heart rate variability complexity analysis

NASA Astrophysics Data System (ADS)

Silva, Luiz Eduardo Virgilio; Cabella, Brenno Caetano Troca; Neves, Ubiraci Pereira da Costa; Murta Junior, Luiz Otavio

2015-03-01

Physiologic complexity is an important concept to characterize time series from biological systems, which associated to multiscale analysis can contribute to comprehension of many complex phenomena. Although multiscale entropy has been applied to physiological time series, it measures irregularity as function of scale. In this study we purpose and evaluate a set of three complexity metrics as function of time scales. Complexity metrics are derived from nonadditive entropy supported by generation of surrogate data, i.e. SDiffqmax, qmax and qzero. In order to access accuracy of proposed complexity metrics, receiver operating characteristic (ROC) curves were built and area under the curves was computed for three physiological situations. Heart rate variability (HRV) time series in normal sinus rhythm, atrial fibrillation, and congestive heart failure data set were analyzed. Results show that proposed metric for complexity is accurate and robust when compared to classic entropic irregularity metrics. Furthermore, SDiffqmax is the most accurate for lower scales, whereas qmax and qzero are the most accurate when higher time scales are considered. Multiscale complexity analysis described here showed potential to assess complex physiological time series and deserves further investigation in wide context.

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.

A Potential Role for mu-Opioids in Mediating the Positive Effects of Gratitude

PubMed Central

Henning, Max; Fox, Glenn R.; Kaplan, Jonas; Damasio, Hanna; Damasio, Antonio

2017-01-01

Gratitude is a complex emotional feeling associated with universally desirable positive effects in personal, social, and physiological domains. Why or how gratitude achieves these functional outcomes is not clear. Toward the goal of identifying its' underlying physiological processes, we recently investigated the neural correlates of gratitude. In our study, participants were exposed to gratitude-inducing stimuli, and rated each according to how much gratitude it provoked. As expected, self-reported gratitude intensity correlated with brain activity in distinct regions of the medial pre-frontal cortex associated with social reward and moral cognition. Here we draw from our data and existing literature to offer a theoretical foundation for the physiological correlates of gratitude. We propose that mu-opioid signaling (1) accompanies the mental experience of gratitude, and (2) may account for the positive effects of gratitude on social relationships, subjective wellbeing, and physiological health. PMID:28680408

A Potential Role for mu-Opioids in Mediating the Positive Effects of Gratitude.

PubMed

Henning, Max; Fox, Glenn R; Kaplan, Jonas; Damasio, Hanna; Damasio, Antonio

2017-01-01

Gratitude is a complex emotional feeling associated with universally desirable positive effects in personal, social, and physiological domains. Why or how gratitude achieves these functional outcomes is not clear. Toward the goal of identifying its' underlying physiological processes, we recently investigated the neural correlates of gratitude. In our study, participants were exposed to gratitude-inducing stimuli, and rated each according to how much gratitude it provoked. As expected, self-reported gratitude intensity correlated with brain activity in distinct regions of the medial pre-frontal cortex associated with social reward and moral cognition. Here we draw from our data and existing literature to offer a theoretical foundation for the physiological correlates of gratitude. We propose that mu-opioid signaling (1) accompanies the mental experience of gratitude, and (2) may account for the positive effects of gratitude on social relationships, subjective wellbeing, and physiological health.

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

Digestive Physiology of Octopus maya and O. mimus: Temporality of Digestion and Assimilation Processes

PubMed Central

Gallardo, Pedro; Olivares, Alberto; Martínez-Yáñez, Rosario; Caamal-Monsreal, Claudia; Domingues, Pedro M.; Mascaró, Maite; Sánchez, Ariadna; Pascual, Cristina; Rosas, Carlos

2017-01-01

Digestive physiology is one of the bottlenecks of octopus aquaculture. Although, there are successful experimentally formulated feeds, knowledge of the digestive physiology of cephalopods is fragmented, and focused mainly on Octopus vulgaris. Considering that the digestive physiology could vary in tropical and sub-tropical species through temperature modulations of the digestive dynamics and nutritional requirements of different organisms, the present review was focused on the digestive physiology timing of Octopus maya and Octopus mimus, two promising aquaculture species living in tropical (22–30°C) and sub-tropical (15–24°C) ecosystems, respectively. We provide a detailed description of how soluble and complex nutrients are digested, absorbed, and assimilated in these species, describing the digestive process and providing insight into how the environment can modulate the digestion and final use of nutrients for these and presumably other octopus species. To date, research on these octopus species has demonstrated that soluble protein and other nutrients flow through the digestive tract to the digestive gland in a similar manner in both species. However, differences in the use of nutrients were noted: in O. mimus, lipids were mobilized faster than protein, while in O. maya, the inverse process was observed, suggesting that lipid mobilization in species that live in relatively colder environments occurs differently to those in tropical ecosystems. Those differences are related to the particular adaptations of animals to their habitat, and indicate that this knowledge is important when formulating feed for octopus species. PMID:28620313

Estimating psycho-physiological state of a human by speech analysis

NASA Astrophysics Data System (ADS)

Ronzhin, A. L.

2005-05-01

Adverse effects of intoxication, fatigue and boredom could degrade performance of highly trained operators of complex technical systems with potentially catastrophic consequences. Existing physiological fitness for duty tests are time consuming, costly, invasive, and highly unpopular. Known non-physiological tests constitute a secondary task and interfere with the busy workload of the tested operator. Various attempts to assess the current status of the operator by processing of "normal operational data" often lead to excessive amount of computations, poorly justified metrics, and ambiguity of results. At the same time, speech analysis presents a natural, non-invasive approach based upon well-established efficient data processing. In addition, it supports both behavioral and physiological biometric. This paper presents an approach facilitating robust speech analysis/understanding process in spite of natural speech variability and background noise. Automatic speech recognition is suggested as a technique for the detection of changes in the psycho-physiological state of a human that typically manifest themselves by changes of characteristics of voice tract and semantic-syntactic connectivity of conversation. Preliminary tests have confirmed that the statistically significant correlation between the error rate of automatic speech recognition and the extent of alcohol intoxication does exist. In addition, the obtained data allowed exploring some interesting correlations and establishing some quantitative models. It is proposed to utilize this approach as a part of fitness for duty test and compare its efficiency with analyses of iris, face geometry, thermography and other popular non-invasive biometric techniques.

Binding of small molecules at interface of protein-protein complex - A newer approach to rational drug design.

PubMed

Gurung, A B; Bhattacharjee, A; Ajmal Ali, M; Al-Hemaid, F; Lee, Joongku

2017-02-01

Protein-protein interaction is a vital process which drives many important physiological processes in the cell and has also been implicated in several diseases. Though the protein-protein interaction network is quite complex but understanding its interacting partners using both in silico as well as molecular biology techniques can provide better insights for targeting such interactions. Targeting protein-protein interaction with small molecules is a challenging task because of druggability issues. Nevertheless, several studies on the kinetics as well as thermodynamic properties of protein-protein interactions have immensely contributed toward better understanding of the affinity of these complexes. But, more recent studies on hot spots and interface residues have opened up new avenues in the drug discovery process. This approach has been used in the design of hot spot based modulators targeting protein-protein interaction with the objective of normalizing such interactions.

Coding principles of the canonical cortical microcircuit in the avian brain

PubMed Central

Calabrese, Ana; Woolley, Sarah M. N.

2015-01-01

Mammalian neocortex is characterized by a layered architecture and a common or “canonical” microcircuit governing information flow among layers. This microcircuit is thought to underlie the computations required for complex behavior. Despite the absence of a six-layered cortex, birds are capable of complex cognition and behavior. In addition, the avian auditory pallium is composed of adjacent information-processing regions with genetically identified neuron types and projections among regions comparable with those found in the neocortex. Here, we show that the avian auditory pallium exhibits the same information-processing principles that define the canonical cortical microcircuit, long thought to have evolved only in mammals. These results suggest that the canonical cortical microcircuit evolved in a common ancestor of mammals and birds and provide a physiological explanation for the evolution of neural processes that give rise to complex behavior in the absence of cortical lamination. PMID:25691736

Multifractality of cerebral blood flow

NASA Astrophysics Data System (ADS)

West, Bruce J.; Latka, Miroslaw; Glaubic-Latka, Marta; Latka, Dariusz

2003-02-01

Scale invariance, the property relating time series across multiple scales, has provided a new perspective of physiological phenomena and their underlying control systems. The traditional “signal plus noise” paradigm of the engineer was first replaced with a model in which biological time series have a fractal structure in time (Fractal Physiology, Oxford University Press, Oxford, 1994). This new paradigm was subsequently shown to be overly restrictive when certain physiological signals were found to be characterized by more than one scaling parameter and therefore to belong to a class of more complex processes known as multifractals (Fractals, Plenum Press, New York, 1988). Here we demonstrate that in addition to heart rate (Nature 399 (1999) 461) and human gait (Phys. Rev. E, submitted for publication), the nonlinear control system for cerebral blood flow (CBF) (Phys. Rev. Lett., submitted for publication; Phys. Rev. E 59 (1999) 3492) is multifractal. We also find that this multifractality is greatly reduced for subjects with “serious” migraine and we present a simple model for the underlying control process to describe this effect.

Developing a physiologically based approach for modeling plutonium decorporation therapy with DTPA.

PubMed

Kastl, Manuel; Giussani, Augusto; Blanchardon, Eric; Breustedt, Bastian; Fritsch, Paul; Hoeschen, Christoph; Lopez, Maria Antonia

2014-11-01

To develop a physiologically based compartmental approach for modeling plutonium decorporation therapy with the chelating agent Diethylenetriaminepentaacetic acid (Ca-DTPA/Zn-DTPA). Model calculations were performed using the software package SAAM II (©The Epsilon Group, Charlottesville, Virginia, USA). The Luciani/Polig compartmental model with age-dependent description of the bone recycling processes was used for the biokinetics of plutonium. The Luciani/Polig model was slightly modified in order to account for the speciation of plutonium in blood and for the different affinities for DTPA of the present chemical species. The introduction of two separate blood compartments, describing low-molecular-weight complexes of plutonium (Pu-LW) and transferrin-bound plutonium (Pu-Tf), respectively, and one additional compartment describing plutonium in the interstitial fluids was performed successfully. The next step of the work is the modeling of the chelation process, coupling the physiologically modified structure with the biokinetic model for DTPA. RESULTS of animal studies performed under controlled conditions will enable to better understand the principles of the involved mechanisms.

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

PubMed

Shimano, Hitoshi; Sato, Ryuichiro

2017-12-01

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

A mathematics for medicine: The Network Effect

PubMed Central

West, Bruce J.

2014-01-01

The theory of medicine and its complement systems biology are intended to explain the workings of the large number of mutually interdependent complex physiologic networks in the human body and to apply that understanding to maintaining the functions for which nature designed them. Therefore, when what had originally been made as a simplifying assumption or a working hypothesis becomes foundational to understanding the operation of physiologic networks it is in the best interests of science to replace or at least update that assumption. The replacement process requires, among other things, an evaluation of how the new hypothesis affects modern day understanding of medical science. This paper identifies linear dynamics and Normal statistics as being such arcane assumptions and explores some implications of their retirement. Specifically we explore replacing Normal with fractal statistics and examine how the latter are related to non-linear dynamics and chaos theory. The observed ubiquity of inverse power laws in physiology entails the need for a new calculus, one that describes the dynamics of fractional phenomena and captures the fractal properties of the statistics of physiological time series. We identify these properties as a necessary consequence of the complexity resulting from the network dynamics and refer to them collectively as The Network Effect. PMID:25538622

Genomic Methods for Clinical and Translational Pain Research

PubMed Central

Wang, Dan; Kim, Hyungsuk; Wang, Xiao-Min; Dionne, Raymond

2012-01-01

Pain is a complex sensory experience for which the molecular mechanisms are yet to be fully elucidated. Individual differences in pain sensitivity are mediated by a complex network of multiple gene polymorphisms, physiological and psychological processes, and environmental factors. Here, we present the methods for applying unbiased molecular-genetic approaches, genome-wide association study (GWAS), and global gene expression analysis, to help better understand the molecular basis of pain sensitivity in humans and variable responses to analgesic drugs. PMID:22351080

Effect of Enriched (Complex) Environment on Nerve Conduction Velocity: New Data and Review of Implications for the Speed of Information Processing.

ERIC Educational Resources Information Center

Reed, T. Edward

1993-01-01

Results with 54 mice confirm that increased stimulation or usage, as would be provided by environmental enrichment (EE), increases peripheral nerve conduction velocity. These results suggest a role at the physiological level for EE (or deprivation) in affecting measured intelligence. (SLD)

Infrasound from Wind Turbines Could Affect Humans

ERIC Educational Resources Information Center

Salt, Alec N.; Kaltenbach, James A.

2011-01-01

Wind turbines generate low-frequency sounds that affect the ear. The ear is superficially similar to a microphone, converting mechanical sound waves into electrical signals, but does this by complex physiologic processes. Serious misconceptions about low-frequency sound and the ear have resulted from a failure to consider in detail how the ear…

The Psychophysiological and Health Corollaries of Child Problem Behaviours in Caregivers of Children with Autism and ADHD

ERIC Educational Resources Information Center

Lovell, B.; Moss, M.; Wetherell, M. A.

2015-01-01

Background: The positive relationship between problem behaviours of children with additional complex needs and psychological distress in their caregivers has been widely evidenced. Fewer studies, however, have assessed the relationship between care recipients' problem behaviours and key physiological processes, relevant for the physical…

The physiological basis for regeneration response to variable retention harvest treatments in three pine species

Treesearch

Matthew D. Powers; Kurt S. Pregitzer; Brian J. Palik; Christopher R. Webster

2011-01-01

Variable retention harvesting (VRH) is promoted for enhancing biodiversity and ecosystem processes in managed forests, but regeneration responses to the complex stand structures that result from VRH are poorly understood. We analyzed foliar stable carbon isotope ratios (δ13C), oxygen isotope ratios (δ18O...

Teaching Glycosis Regulation to Undergraduates Using An Electrical Power Generation Analogy

ERIC Educational Resources Information Center

Stavrianeas, Stasinos

2005-01-01

Biology, physiology, and allied health biochemistry textbooks cover metabolic pathways such as glycolysis; however, most do not include much discussion of how these pathways are regulated within the cell. Because the details of these complex regulatory processes can be difficult for students to learn, we have developed a robust teaching…

[Should antiseptics be used for chronic wounds?].

PubMed

Barrois, B

2001-02-01

Using antiseptics is common, it is adequate on safe skin, but no scientific study allow their use on break skin. Then, cicatrisation is a complex process with a physiological bacteriocycle. Usual antiseptics are responsible of fibroblasts destruction and only a short effect on bacteries. So, it is logical not to use antiseptics on break skin.

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

PubMed

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

2016-01-01

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

Molecular and physiological manifestations and measurement of aging in humans.

PubMed

Khan, Sadiya S; Singer, Benjamin D; Vaughan, Douglas E

2017-08-01

Biological aging is associated with a reduction in the reparative and regenerative potential in tissues and organs. This reduction manifests as a decreased physiological reserve in response to stress (termed homeostenosis) and a time-dependent failure of complex molecular mechanisms that cumulatively create disorder. Aging inevitably occurs with time in all organisms and emerges on a molecular, cellular, organ, and organismal level with genetic, epigenetic, and environmental modulators. Individuals with the same chronological age exhibit differential trajectories of age-related decline, and it follows that we should assess biological age distinctly from chronological age. In this review, we outline mechanisms of aging with attention to well-described molecular and cellular hallmarks and discuss physiological changes of aging at the organ-system level. We suggest methods to measure aging with attention to both molecular biology (e.g., telomere length and epigenetic marks) and physiological function (e.g., lung function and echocardiographic measurements). Finally, we propose a framework to integrate these molecular and physiological data into a composite score that measures biological aging in humans. Understanding the molecular and physiological phenomena that drive the complex and multifactorial processes underlying the variable pace of biological aging in humans will inform how researchers assess and investigate health and disease over the life course. This composite biological age score could be of use to researchers seeking to characterize normal, accelerated, and exceptionally successful aging as well as to assess the effect of interventions aimed at modulating human aging. © 2017 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

The anatomy and physiology of normal and abnormal swallowing in oropharyngeal dysphagia.

PubMed

Sasegbon, A; Hamdy, S

2017-11-01

Eating and drinking are enjoyable activities that positively impact on an individual's quality of life. The ability to swallow food and fluid is integral to the process of eating. Swallowing occupies a dual role being both part of the enjoyment of eating and being a critically important utilitarian activity to enable adequate nutrition and hydration. Any impairment to the process of swallowing can negatively affect a person's perception of their quality of life. The process of swallowing is highly complex and involves muscles in the mouth, pharynx, larynx, and esophagus. The oropharynx is the anatomical region encompassing the oral cavity and the pharynx. Food must be masticated, formed into a bolus and transported to the pharynx by the tongue whereas fluids are usually held within the mouth before being transported ab-orally. The bolus must then be transported through the pharynx to the esophagus without any matter entering the larynx. The muscles needed for all these steps are coordinated by swallowing centers within the brainstem which are supplied with sensory information by afferent nerve fibers from several cranial nerves. The swallowing centers also receive modulatory input from higher centers within the brain. Hence, a swallow has both voluntary and involuntary physiologic components and the term dysphagia is given to difficult swallowing while oropharyngeal dysphagia is difficult swallowing due to pathology within the oropharynx. Problems affecting any point along the complex swallowing pathway can result in dysphagia. This review focuses on the anatomy and physiology behind normal and abnormal oropharyngeal swallowing. It also details the common diseases and pathology causing oropharyngeal dysphagia. © 2017 John Wiley & Sons Ltd.

Role of Proangiogenic Factors in Immunopathogenesis of Multiple Sclerosis.

PubMed

Hamid, Kabir Magaji; Mirshafiey, Abbas

2016-02-01

Angiogenesis is a complex and balanced process in which new blood vessels form from preexisting ones by sprouting, splitting, growth and remodeling. This phenomenon plays a vital role in many physiological and pathological processes. However, the disturbance in physiological process can play a role in pathogenesis of some chronic inflammatory diseases, including multiple sclerosis (MS) in human and its animal model. Although the relation between abnormal blood vessels and MS lesions was established in previous studies, but the role of pathological angiogenesis remains unclear. In this study, the link between proangiogenic factors and multiple sclerosis pathogenesis was examined by conducting a systemic review. Thus we searched the English medical literature via PubMed, ISI web of knowledge, Medline and virtual health library (VHL) databases. In this review, we describe direct and indirect roles of some proangiogenic factors in MS pathogenesis and report the association of these factors with pathological and inflammatory angiogenesis.

The unconscious regulation of emotion: nonconscious reappraisal goals modulate emotional reactivity.

PubMed

Williams, Lawrence E; Bargh, John A; Nocera, Christopher C; Gray, Jeremy R

2009-12-01

People often encounter difficulty when making conscious attempts to regulate their emotions. We propose that nonconscious self-regulatory processes may be of help in these difficult circumstances because nonconscious processes are not subject to the same set of limitations as are conscious processes. Two experiments examined the effects of nonconsciously operating goals on people's emotion regulatory success. In Experiment 1, participants engaged in an anxiety-eliciting task. Participants who had a reappraisal emotion control goal primed and operating nonconsciously achieved the same decrease in physiological reactivity as those explicitly instructed to reappraise. In Experiment 2, the effect of nonconscious reappraisal priming on physiological reactivity was shown to be most pronounced for those who do not habitually use reappraisal strategies. The findings highlight the potential importance of nonconscious goals for facilitating emotional control in complex real-world environments and have implications for contemporary models of emotion regulation.

Enzyme technology for precision functional food ingredient processes.

PubMed

Meyer, Anne S

2010-03-01

A number of naturally occurring dietary substances may exert physiological benefits. The production of enhanced levels or particularly tailored versions of such candidate functional compounds can be targeted by enzymatic catalysis. The recent literature contains examples of enhancing bioavailability of iron via enzyme-catalyzed degradation of phytate in wheat bran, increasing diacyl-glycerol and conjugated linoleic acid levels by lipase action, enhancing the absorption of the citrus flavonoid hesperetin via rhamnosidase treatment, and obtaining solubilized dietary fiber via enzymatic modification of potato starch processing residues. Such targeted enzyme-catalyzed reactions provide new invention opportunities for designing functional foods with significant health benefits. The provision of well-defined naturally structured compounds can, moreover, assist in obtaining the much-needed improved understanding of the physiological benefits of complex natural substances.

Inferring Nonlinear Neuronal Computation Based on Physiologically Plausible Inputs

PubMed Central

McFarland, James M.; Cui, Yuwei; Butts, Daniel A.

2013-01-01

The computation represented by a sensory neuron's response to stimuli is constructed from an array of physiological processes both belonging to that neuron and inherited from its inputs. Although many of these physiological processes are known to be nonlinear, linear approximations are commonly used to describe the stimulus selectivity of sensory neurons (i.e., linear receptive fields). Here we present an approach for modeling sensory processing, termed the Nonlinear Input Model (NIM), which is based on the hypothesis that the dominant nonlinearities imposed by physiological mechanisms arise from rectification of a neuron's inputs. Incorporating such ‘upstream nonlinearities’ within the standard linear-nonlinear (LN) cascade modeling structure implicitly allows for the identification of multiple stimulus features driving a neuron's response, which become directly interpretable as either excitatory or inhibitory. Because its form is analogous to an integrate-and-fire neuron receiving excitatory and inhibitory inputs, model fitting can be guided by prior knowledge about the inputs to a given neuron, and elements of the resulting model can often result in specific physiological predictions. Furthermore, by providing an explicit probabilistic model with a relatively simple nonlinear structure, its parameters can be efficiently optimized and appropriately regularized. Parameter estimation is robust and efficient even with large numbers of model components and in the context of high-dimensional stimuli with complex statistical structure (e.g. natural stimuli). We describe detailed methods for estimating the model parameters, and illustrate the advantages of the NIM using a range of example sensory neurons in the visual and auditory systems. We thus present a modeling framework that can capture a broad range of nonlinear response functions while providing physiologically interpretable descriptions of neural computation. PMID:23874185

Development and application of a ruthenium(II) complex-based photoluminescent and electrochemiluminescent dual-signaling probe for nitric oxide.

PubMed

Zhang, Wenzhu; Zhang, Jingmei; Zhang, Hailei; Cao, Liyan; Zhang, Run; Ye, Zhiqiang; Yuan, Jingli

2013-11-15

A ruthenium(II) complex, [Ru(bpy)2(DA-phen)](PF6)2 (bpy: 2,2'-bipyridine; DA-phen: 5,6-diamino-1,10-phenanthroline), has been developed as a photoluminescent (PL) and electrochemiluminescent (ECL) dual-signaling probe for the highly sensitive and selective detection of nitric oxide (NO) in aqueous and biological samples. Due to the presence of electron transfer process from diamino group to the excited-state of the Ru(II) complex, the PL and ECL intensities of the probe are very weak. After the probe was reacted with NO in physiological pH aqueous media under aerobic conditions to afford its triazole derivative, [Ru(bpy)2(TA-phen)](2+) (TA-phen: 5,6-triazole-1,10-phenanthroline), the electron transfer process was inhibited, so that the PL and ECL efficiency of the Ru(II) complex was remarkably increased. The PL and ECL responses of the probe to NO in physiological pH media are highly sensitive with the detection limits at low micromolar concentration level, and highly specific without the interferences of other reactive oxygen/nitrogen species (ROS/RNS) and metal ions. Moreover, the probe has good cell-membrane permeability, and can be rapidly transferred into living cells for trapping the intracellular NO molecules. These features enabled the probe to be successfully used for the monitoring of the endogenous NO production in living biological cell and tissue samples with PL and ECL dual-modes. Copyright © 2013 Elsevier B.V. All rights reserved.

Automatic detection of slight parameter changes associated to complex biomedical signals using multiresolution q-entropy1.

PubMed

Torres, M E; Añino, M M; Schlotthauer, G

2003-12-01

It is well known that, from a dynamical point of view, sudden variations in physiological parameters which govern certain diseases can cause qualitative changes in the dynamics of the corresponding physiological process. The purpose of this paper is to introduce a technique that allows the automated temporal localization of slight changes in a parameter of the law that governs the nonlinear dynamics of a given signal. This tool takes, from the multiresolution entropies, the ability to show these changes as statistical variations at each scale. These variations are held in the corresponding principal component. Appropriately combining these techniques with a statistical changes detector, a complexity change detection algorithm is obtained. The relevance of the approach, together with its robustness in the presence of moderate noise, is discussed in numerical simulations and the automatic detector is applied to real and simulated biological signals.

A new way of thinking about complications of prematurity.

PubMed

Moore, Tiffany A; Berger, Ann M; Wilson, Margaret E

2014-01-01

The morbidity and mortality of preterm infants are impacted by their ability to maintain physiologic homeostasis using metabolic, endocrine, and immunologic mechanisms independent of the mother's placenta. Exploring McEwen's allostatic load model in preterm infants provides a new way to understand the altered physiologic processes associated with frequently occurring complications of prematurity such as bronchopulmonary dysplasia, intraventricular hemorrhage, necrotizing enterocolitis, and retinopathy of prematurity. The purpose of this article is to present a new model to enhance understanding of the altered physiologic processes associated with complications of prematurity. The model of allostatic load and complications of prematurity was derived to explore the relationship between general stress of prematurity and complications of prematurity. The proposed model uses the concepts of general stress of prematurity, allostasis, physiologic response patterns (adaptive-maladaptive), allostatic load, and complications of prematurity. These concepts are defined and theoretical relationships in the proposed model are interpreted using the four maladaptive response patterns of repeated hits, lack of adaptation, prolonged response, and inadequate response. Empirical evidence for cortisol, inflammation, and oxidative stress responses are used to support the theoretical relationships. The proposed model provides a new way of thinking about physiologic dysregulation in preterm infants. The ability to describe and understand complex physiologic mechanisms involved in complications of prematurity is essential for research. Advancing the knowledge of complications of prematurity will advance clinical practice and research and lead to testing of interventions to reduce negative outcomes in preterm infants.

A Tale of Two Fishes or a Quick Fix for Fick's Law

ERIC Educational Resources Information Center

Robischon, Marcel A.

2014-01-01

Gas diffusion, as a basis for complex biological processes such as respiration, is a core principle for understanding fundamental physiology. Students, however, often find these concepts challenging, in particular when expressed formally as in Fick's law of gas diffusion. This introduction to Fick's law uses the representations of…

3-PG simulations of young ponderosa pine plantations under varied management intensity: why do they grow so differently?

Treesearch

Liang Wei; Marshall John; Jianwei Zhang; Hang Zhou; Robert Powers

2014-01-01

Models can be powerful tools for estimating forest productivity and guiding forest management, but their credibility and complexity are often an issue for forest managers. We parameterized a process-based forest growth model, 3-PG (Physiological Principles Predicting Growth), to simulate growth of ponderosa pine (Pinus ponderosa) plantations in...

Interacting effects of multiple stresses on growth and physiological processes in northern forest trees

Treesearch

Judson G. Isebrands; Richard E. Dickson; Joanne Rebbeck; David F. Karnosky

2000-01-01

Global climate chagnge is a complex and controversial subject, both technically and politically. Recently, the Intergovernmental Panel on Climate Change (IPCC) of the United Nations concluded that "the balance of evidence suggests a discernible human influence on global climate" and that "further accumulation of greenhouse gases will commit the earth...

Teaching Anatomy and Physiology Using Computer-Based, Stereoscopic Images

ERIC Educational Resources Information Center

Perry, Jamie; Kuehn, David; Langlois, Rick

2007-01-01

Learning real three-dimensional (3D) anatomy for the first time can be challenging. Two-dimensional drawings and plastic models tend to over-simplify the complexity of anatomy. The approach described uses stereoscopy to create 3D images of the process of cadaver dissection and to demonstrate the underlying anatomy related to the speech mechanisms.…

Nanotechnology use with cosmeceuticals.

PubMed

Golubovic-Liakopoulos, Nevenka; Simon, Sanford R; Shah, Bhavdeep

2011-09-01

The skin is a complex organ and its aging is a complex process. Cutaneous aging is influenced by factors such as sun exposure, genetics, stress and the environment. While skin laxity, rhytides, and dyschromia appear on the surface, these processes originate in deeper layers including the dermis and subcutaneous tissues. Until recently, most topical skin treatments were applied to, and consequently only affected the skin surface. Skin care has evolved to be scientifically based, and as knowledge increases about the physiology of the skin, novel methods of maintaining its health and appearance are developed. New generation skin care products are targeting multiple aging mechanisms by utilizing functional active ingredients in combination with innovative delivery systems. Copyright © 2011 Elsevier Inc. All rights reserved.

Multi-enzyme logic network architectures for assessing injuries: digital processing of biomarkers.

PubMed

Halámek, Jan; Bocharova, Vera; Chinnapareddy, Soujanya; Windmiller, Joshua Ray; Strack, Guinevere; Chuang, Min-Chieh; Zhou, Jian; Santhosh, Padmanabhan; Ramirez, Gabriela V; Arugula, Mary A; Wang, Joseph; Katz, Evgeny

2010-12-01

A multi-enzyme biocatalytic cascade processing simultaneously five biomarkers characteristic of traumatic brain injury (TBI) and soft tissue injury (STI) was developed. The system operates as a digital biosensor based on concerted function of 8 Boolean AND logic gates, resulting in the decision about the physiological conditions based on the logic analysis of complex patterns of the biomarkers. The system represents the first example of a multi-step/multi-enzyme biosensor with the built-in logic for the analysis of complex combinations of biochemical inputs. The approach is based on recent advances in enzyme-based biocomputing systems and the present paper demonstrates the potential applicability of biocomputing for developing novel digital biosensor networks.

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

PubMed

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

2015-09-01

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

A new standard model for milk yield in dairy cows based on udder physiology at the milking-session level.

PubMed

Gasqui, Patrick; Trommenschlager, Jean-Marie

2017-08-21

Milk production in dairy cow udders is a complex and dynamic physiological process that has resisted explanatory modelling thus far. The current standard model, Wood's model, is empirical in nature, represents yield in daily terms, and was published in 1967. Here, we have developed a dynamic and integrated explanatory model that describes milk yield at the scale of the milking session. Our approach allowed us to formally represent and mathematically relate biological features of known relevance while accounting for stochasticity and conditional elements in the form of explicit hypotheses, which could then be tested and validated using real-life data. Using an explanatory mathematical and biological model to explore a physiological process and pinpoint potential problems (i.e., "problem finding"), it is possible to filter out unimportant variables that can be ignored, retaining only those essential to generating the most realistic model possible. Such modelling efforts are multidisciplinary by necessity. It is also helpful downstream because model results can be compared with observed data, via parameter estimation using maximum likelihood and statistical testing using model residuals. The process in its entirety yields a coherent, robust, and thus repeatable, model.

Fully integrated wearable sensor arrays for multiplexed in situ perspiration analysis

DOE PAGES

Gao, Wei; Emaminejad, Sam; Nyein, Hnin Yin Yin; ...

2016-01-27

We report that wearable sensor technologies are essential to the realization of personalized medicine through continuously monitoring an individual’s state of health. Sampling human sweat, which is rich in physiological information13, could enable non-invasive monitoring. Previously reported sweat-based and other noninvasive biosensors either can only monitor a single analyte at a time or lack on-site signal processing circuitry and sensor calibration mechanisms for accurate analysis of the physiological state14–18. Given the complexity of sweat secretion, simultaneous and multiplexed screening of target biomarkers is critical and requires full system integration to ensure the accuracy of measurements. Here we present a mechanicallymore » flexible and fully integrated (that is, no external analysis is needed) sensor array for multiplexed in situ perspiration analysis, which simultaneously and selectively measures sweat metabolites (such as glucose and lactate) and electrolytes (such as sodium and potassium ions), as well as the skin temperature (to calibrate the response of the sensors). Lastly, our work bridges the technological gap between signal transduction, conditioning (amplification and filtering), processing and wireless transmission in wearable biosensors by merging plasticbased sensors that interface with the skin with silicon integrated circuits consolidated on a flexible circuit board for complex signal processing.« less

Fully integrated wearable sensor arrays for multiplexed in situ perspiration analysis

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

Gao, Wei; Emaminejad, Sam; Nyein, Hnin Yin Yin

We report that wearable sensor technologies are essential to the realization of personalized medicine through continuously monitoring an individual’s state of health. Sampling human sweat, which is rich in physiological information13, could enable non-invasive monitoring. Previously reported sweat-based and other noninvasive biosensors either can only monitor a single analyte at a time or lack on-site signal processing circuitry and sensor calibration mechanisms for accurate analysis of the physiological state14–18. Given the complexity of sweat secretion, simultaneous and multiplexed screening of target biomarkers is critical and requires full system integration to ensure the accuracy of measurements. Here we present a mechanicallymore » flexible and fully integrated (that is, no external analysis is needed) sensor array for multiplexed in situ perspiration analysis, which simultaneously and selectively measures sweat metabolites (such as glucose and lactate) and electrolytes (such as sodium and potassium ions), as well as the skin temperature (to calibrate the response of the sensors). Lastly, our work bridges the technological gap between signal transduction, conditioning (amplification and filtering), processing and wireless transmission in wearable biosensors by merging plasticbased sensors that interface with the skin with silicon integrated circuits consolidated on a flexible circuit board for complex signal processing.« less

Using Synthetic Biology to Distinguish and Overcome Regulatory and Functional Barriers Related to Nitrogen Fixation

PubMed Central

Wang, Xia; Yang, Jian-Guo; Chen, Li; Wang, Ji-Long; Cheng, Qi; Dixon, Ray; Wang, Yi-Ping

2013-01-01

Biological nitrogen fixation is a complex process requiring multiple genes working in concert. To date, the Klebsiella pneumoniae nif gene cluster, divided into seven operons, is one of the most studied systems. Its nitrogen fixation capacity is subject to complex cascade regulation and physiological limitations. In this report, the entire K. pneumoniae nif gene cluster was reassembled as operon-based BioBrick parts in Escherichia coli. It provided ∼100% activity of native K. pneumoniae system. Based on the expression levels of these BioBrick parts, a T7 RNA polymerase–LacI expression system was used to replace the σ54-dependent promoters located upstream of nif operons. Expression patterns of nif operons were critical for the maximum activity of the recombinant system. By mimicking these expression levels with variable-strength T7-dependent promoters, ∼42% of the nitrogenase activity of the σ54-dependent nif system was achieved in E. coli. When the newly constructed T7-dependent nif system was challenged with different genetic and physiological conditions, it bypassed the original complex regulatory circuits, with minor physiological limitations. Therefore, we have successfully replaced the nif regulatory elements with a simple expression system that may provide the first step for further research of introducing nif genes into eukaryotic organelles, which has considerable potentials in agro-biotechnology. PMID:23935879

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

NASA Technical Reports Server (NTRS)

Foster, Tammy E.; Brooks, J. Renee

2004-01-01

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

Molecular cell biology and physiology of solute transport

PubMed Central

Caplan, Michael J.; Seo-Mayer, Patricia; Zhang, Li

2010-01-01

Purpose of review An enormous body of research has been focused on exploring the mechanisms through which epithelial cells establish their characteristic polarity. It is clear that under normal circumstances cell–cell contacts mediated by the calcium-dependent adhesion proteins of the intercellular adhesion junctions are required to initiate complete polarization. Furthermore, formation of the tight, or occluding, junctions that limit paracellular permeability has long been thought to help to establish polarity by preventing the diffusion of membrane proteins between the two plasmalemmal domains. This review will discuss several selected kinases and protein complexes and highlight their relevance to transporting epithelial cell polarization. Recent findings Recent work has shed new light on the roles of junctional complexes in establishing and maintaining epithelial cell polarity. In addition, work from several laboratories, suggests that the formation of these junctions is tied to processes that regulate cellular energy metabolism. Summary Junctional complexes and energy sensing kinases constitute a novel class of machinery whose capacity to generate and modulate epithelial cell polarity is likely to have wide ranging and important physiological ramifications. PMID:18695392

Molecular and Epigenetic Mechanisms for the Complex Effects of Stress on Synaptic Physiology and Cognitive Functions

PubMed Central

Yuen, Eunice Y.; Wei, Jing

2017-01-01

Abstract Evidence over the past decades has found that stress, particularly through the corticosterone stress hormones, produces complex changes in glutamatergic signaling in prefrontal cortex, which leads to the alteration of cognitive processes medicated by this brain region. Interestingly, the effects of stress on glutamatergic transmission appear to be “U-shaped,” depending upon the duration and severity of the stressor. These biphasic effects of acute vs chronic stress represent the adaptive vs maladaptive responses to stressful stimuli. Animal studies suggest that the stress-induced modulation of excitatory synaptic transmission involves changes in presynaptic glutamate release, postsynaptic glutamate receptor membrane trafficking and degradation, spine structure and cytoskeleton network, and epigenetic control of gene expression. This review will discuss current findings on the key molecules involved in the stress-induced regulation of prefrontal cortex synaptic physiology and prefrontal cortex-mediated functions. Understanding the molecular and epigenetic mechanisms that underlie the complex effects of stress will help to develop novel strategies to cope with stress-related mental disorders. PMID:29016816

Molecular and Epigenetic Mechanisms for the Complex Effects of Stress on Synaptic Physiology and Cognitive Functions.

PubMed

Yuen, Eunice Y; Wei, Jing; Yan, Zhen

2017-11-01

Evidence over the past decades has found that stress, particularly through the corticosterone stress hormones, produces complex changes in glutamatergic signaling in prefrontal cortex, which leads to the alteration of cognitive processes medicated by this brain region. Interestingly, the effects of stress on glutamatergic transmission appear to be "U-shaped," depending upon the duration and severity of the stressor. These biphasic effects of acute vs chronic stress represent the adaptive vs maladaptive responses to stressful stimuli. Animal studies suggest that the stress-induced modulation of excitatory synaptic transmission involves changes in presynaptic glutamate release, postsynaptic glutamate receptor membrane trafficking and degradation, spine structure and cytoskeleton network, and epigenetic control of gene expression. This review will discuss current findings on the key molecules involved in the stress-induced regulation of prefrontal cortex synaptic physiology and prefrontal cortex-mediated functions. Understanding the molecular and epigenetic mechanisms that underlie the complex effects of stress will help to develop novel strategies to cope with stress-related mental disorders. © The Author 2017. Published by Oxford University Press on behalf of CINP.

Neonatal pulmonary physiology.

PubMed

Davis, Ryan P; Mychaliska, George B

2013-11-01

Managing pulmonary issues faced by both term and preterm infants remains a challenge to the practicing pediatric surgeon. An understanding of normal fetal and neonatal pulmonary development and physiology is the cornerstone for understanding the pathophysiology and treatment of many congenital and acquired problems in the neonate. Progression through the phases of lung development and the transition to postnatal life requires a symphony of complex and overlapping events to work in concert for smooth and successful transition to occur. Pulmonary physiology and oxygen transport in the neonate are similar to older children; however, there are critical differences that are important to take into consideration when treating the youngest of patients. Our understanding of fetal and neonatal pulmonary physiology continues to evolve as the molecular and cellular events governing these processes are better understood. This deeper understanding has helped to facilitate groundbreaking research, leading to improved technology and treatment of term and preterm infants. As therapeutics and research continue to advance, a review of neonatal pulmonary physiology is essential to assist the clinician with his/her management of the wide variety of challenging congenital and acquired pulmonary disease. © 2013 Published by Elsevier Inc.

Lung evolution as a cipher for physiology

PubMed Central

Torday, J. S.; Rehan, V. K.

2009-01-01

In the postgenomic era, we need an algorithm to readily translate genes into physiologic principles. The failure to advance biomedicine is due to the false hope raised in the wake of the Human Genome Project (HGP) by the promise of systems biology as a ready means of reconstructing physiology from genes. like the atom in physics, the cell, not the gene, is the smallest completely functional unit of biology. Trying to reassemble gene regulatory networks without accounting for this fundamental feature of evolution will result in a genomic atlas, but not an algorithm for functional genomics. For example, the evolution of the lung can be “deconvoluted” by applying cell-cell communication mechanisms to all aspects of lung biology development, homeostasis, and regeneration/repair. Gene regulatory networks common to these processes predict ontogeny, phylogeny, and the disease-related consequences of failed signaling. This algorithm elucidates characteristics of vertebrate physiology as a cascade of emergent and contingent cellular adaptational responses. By reducing complex physiological traits to gene regulatory networks and arranging them hierarchically in a self-organizing map, like the periodic table of elements in physics, the first principles of physiology will emerge. PMID:19366785

Modeling plant growth and development.

PubMed

Prusinkiewicz, Przemyslaw

2004-02-01

Computational plant models or 'virtual plants' are increasingly seen as a useful tool for comprehending complex relationships between gene function, plant physiology, plant development, and the resulting plant form. The theory of L-systems, which was introduced by Lindemayer in 1968, has led to a well-established methodology for simulating the branching architecture of plants. Many current architectural models provide insights into the mechanisms of plant development by incorporating physiological processes, such as the transport and allocation of carbon. Other models aim at elucidating the geometry of plant organs, including flower petals and apical meristems, and are beginning to address the relationship between patterns of gene expression and the resulting plant form.

Health and disease phenotyping in old age using a cluster network analysis.

PubMed

Valenzuela, Jesus Felix; Monterola, Christopher; Tong, Victor Joo Chuan; Ng, Tze Pin; Larbi, Anis

2017-11-15

Human ageing is a complex trait that involves the synergistic action of numerous biological processes that interact to form a complex network. Here we performed a network analysis to examine the interrelationships between physiological and psychological functions, disease, disability, quality of life, lifestyle and behavioural risk factors for ageing in a cohort of 3,270 subjects aged ≥55 years. We considered associations between numerical and categorical descriptors using effect-size measures for each variable pair and identified clusters of variables from the resulting pairwise effect-size network and minimum spanning tree. We show, by way of a correspondence analysis between the two sets of clusters, that they correspond to coarse-grained and fine-grained structure of the network relationships. The clusters obtained from the minimum spanning tree mapped to various conceptual domains and corresponded to physiological and syndromic states. Hierarchical ordering of these clusters identified six common themes based on interactions with physiological systems and common underlying substrates of age-associated morbidity and disease chronicity, functional disability, and quality of life. These findings provide a starting point for indepth analyses of ageing that incorporate immunologic, metabolomic and proteomic biomarkers, and ultimately offer low-level-based typologies of healthy and unhealthy ageing.

Prohibitin( PHB) roles in granulosa cell physiology.

PubMed

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

2016-01-01

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

Prohibitin (PHB) roles in granulosa cell physiology

PubMed Central

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

2015-01-01

Ovarian granulosa cells (GC) play an important role in the growth and development of the follicle in the process known as folliculogenesis. In the present review, we focus on the recent developments in prohibitin (PHB) research in relation to GC physiological functions. PHB is a member of highly conserved eukaryotic protein family containing the repressor of estrogen activity (REA)/stomatin/prohibitin/flotillin/HflK/C (SPFH) domain [also known as the PHB domain] found in divergent species from prokaryotes to eukaryotes. PHB is ubiquitously expressed either in circulating free form or is present in multiple cellular compartments including mitochondria, nucleus and plasma membrane. In mitochondria, PHB is anchored to the mitochondrial inner membrane (IMM), and form complexes with the ATPases Associated with diverse cellular Activities (m-AAA) proteases. PHB continuously shuttles between the mitochondria, cytosol and nucleus. In the nucleus, PHB interacts with various transcription factors and modulate transcriptional activity directly or through interactions with chromatin remodeling proteins. Multiple functions have been attributed to the mitochondrial and nuclear prohibitin complexes such as cellular differentiation, anti-proliferation, morphogenesis and maintaining the functional integrity of the mitochondria. However, to date, the regulation of PHB expression patterns and GC physiological functions are not completely understood. PMID:26496733

The big and intricate dreams of little organelles: Embracing complexity in the study of membrane traffic.

PubMed

Liu, Allen P; Botelho, Roberto J; Antonescu, Costin N

2017-09-01

Compartmentalization of eukaryotic cells into dynamic organelles that exchange material through regulated membrane traffic governs virtually every aspect of cellular physiology including signal transduction, metabolism and transcription. Much has been revealed about the molecular mechanisms that control organelle dynamics and membrane traffic and how these processes are regulated by metabolic, physical and chemical cues. From this emerges the understanding of the integration of specific organellar phenomena within complex, multiscale and nonlinear regulatory networks. In this review, we discuss systematic approaches that revealed remarkable insight into the complexity of these phenomena, including the use of proximity-based proteomics, high-throughput imaging, transcriptomics and computational modeling. We discuss how these methods offer insights to further understand molecular versatility and organelle heterogeneity, phenomena that allow a single organelle population to serve a range of physiological functions. We also detail on how transcriptional circuits drive organelle adaptation, such that organelles may shift their function to better serve distinct differentiation and stress conditions. Thus, organelle dynamics and membrane traffic are functionally heterogeneous and adaptable processes that coordinate with higher-order system behavior to optimize cell function under a range of contexts. Obtaining a comprehensive understanding of organellar phenomena will increasingly require combined use of reductionist and system-based approaches. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

The Ins and Outs of Breath Holding: Simple Demonstrations of Complex Respiratory Physiology

ERIC Educational Resources Information Center

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

2015-01-01

The physiology of breath holding is complex, and voluntary breath-hold duration is affected by many factors, including practice, psychology, respiratory chemoreflexes, and lung stretch. In this activity, we outline a number of simple laboratory activities or classroom demonstrations that illustrate the complexity of the integrative physiology…

Climate Change, Nutrition, and Bottom-Up and Top-Down Food Web Processes.

PubMed

Rosenblatt, Adam E; Schmitz, Oswald J

2016-12-01

Climate change ecology has focused on climate effects on trophic interactions through the lenses of temperature effects on organismal physiology and phenological asynchronies. Trophic interactions are also affected by the nutrient content of resources, but this topic has received less attention. Using concepts from nutritional ecology, we propose a conceptual framework for understanding how climate affects food webs through top-down and bottom-up processes impacted by co-occurring environmental drivers. The framework integrates climate effects on consumer physiology and feeding behavior with effects on resource nutrient content. It illustrates how studying responses of simplified food webs to simplified climate change might produce erroneous predictions. We encourage greater integrative complexity of climate change research on trophic interactions to resolve patterns and enhance predictive capacities. Copyright © 2016 Elsevier Ltd. All rights reserved.

‘Integrative Physiology 2.0’: integration of systems biology into physiology and its application to cardiovascular homeostasis

PubMed Central

Kuster, Diederik W D; Merkus, Daphne; van der Velden, Jolanda; Verhoeven, Adrie J M; Duncker, Dirk J

2011-01-01

Since the completion of the Human Genome Project and the advent of the large scaled unbiased ‘-omics’ techniques, the field of systems biology has emerged. Systems biology aims to move away from the traditional reductionist molecular approach, which focused on understanding the role of single genes or proteins, towards a more holistic approach by studying networks and interactions between individual components of networks. From a conceptual standpoint, systems biology elicits a ‘back to the future’ experience for any integrative physiologist. However, many of the new techniques and modalities employed by systems biologists yield tremendous potential for integrative physiologists to expand their tool arsenal to (quantitatively) study complex biological processes, such as cardiac remodelling and heart failure, in a truly holistic fashion. We therefore advocate that systems biology should not become/stay a separate discipline with ‘-omics’ as its playing field, but should be integrated into physiology to create ‘Integrative Physiology 2.0’. PMID:21224228

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.

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

Electronic connection between the quinone and cytochrome C redox pools and its role in regulation of mitochondrial electron transport and redox signaling.

PubMed

Sarewicz, Marcin; Osyczka, Artur

2015-01-01

Mitochondrial respiration, an important bioenergetic process, relies on operation of four membranous enzymatic complexes linked functionally by mobile, freely diffusible elements: quinone molecules in the membrane and water-soluble cytochromes c in the intermembrane space. One of the mitochondrial complexes, complex III (cytochrome bc1 or ubiquinol:cytochrome c oxidoreductase), provides an electronic connection between these two diffusible redox pools linking in a fully reversible manner two-electron quinone oxidation/reduction with one-electron cytochrome c reduction/oxidation. Several features of this homodimeric enzyme implicate that in addition to its well-defined function of contributing to generation of proton-motive force, cytochrome bc1 may be a physiologically important point of regulation of electron flow acting as a sensor of the redox state of mitochondria that actively responds to changes in bioenergetic conditions. These features include the following: the opposing redox reactions at quinone catalytic sites located on the opposite sides of the membrane, the inter-monomer electronic connection that functionally links four quinone binding sites of a dimer into an H-shaped electron transfer system, as well as the potential to generate superoxide and release it to the intermembrane space where it can be engaged in redox signaling pathways. Here we highlight recent advances in understanding how cytochrome bc1 may accomplish this regulatory physiological function, what is known and remains unknown about catalytic and side reactions within the quinone binding sites and electron transfers through the cofactor chains connecting those sites with the substrate redox pools. We also discuss the developed molecular mechanisms in the context of physiology of mitochondria. Copyright © 2015 the American Physiological Society.

Study to Examine Psychological Processes in Suicidal Ideation and Behavior (STEPPS)

DTIC Science & Technology

2015-05-01

diagnoses to better understand suicide; suicide is the result of a complex interplay of psychological, social and biological factors . A more...encounter frequent physiological/psychological stressors, therefore identifying suicide risk and resilience factors in military personnel is vital; so...models have been developed to aid the identification of suicide-specific individual difference factors and patterns of thinking. This program of

Sleep in childhood and adolescence: age-specific sleep characteristics, common sleep disturbances and associated difficulties.

PubMed

Barclay, Nicola L; Gregory, Alice M

2014-01-01

Sleep changes throughout the lifespan, with particularly salient alterations occurring during the first few years of life, as well as during the transition from childhood to adolescence. Such changes are partly the result of brain maturation; complex changes in the organisation of the circadian system; as well as changes in daily routine, environmental demands and responsibilities. Despite the automaticity of sleep, given that it is governed by a host of complex mechanisms, there are times when sleep becomes disturbed. Sleep disturbances in childhood are common and may stem from behavioural difficulties or abnormalities in physiological processes-and, in some cases manifest into diagnosable sleep disorders. As well as occurring exclusively, childhood sleep disturbances often co-occur with other difficulties. The purpose of this chapter is to outline the neurobiology of typical sleep/wake processes, and describe changes in sleep physiology and architecture from birth to adulthood. Furthermore, common childhood sleep disorders are described as are their associations with other traits, including all of the syndromes presented in this handbook: ASDs, ADHD, schizophrenia and emotional/behavioural difficulties. Throughout, we attempt to explain possible mechanisms underlying these disorders and their associations.

Biochemical and physiological bases for the use of carbon and nitrogen isotopes in environmental and ecological studies

NASA Astrophysics Data System (ADS)

Ohkouchi, Naohiko; Ogawa, Nanako O.; Chikaraishi, Yoshito; Tanaka, Hiroyuki; Wada, Eitaro

2015-12-01

We review the biochemical and physiological bases of the use of carbon and nitrogen isotopic compositions as an approach for environmental and ecological studies. Biochemical processes commonly observed in the biosphere, including the decarboxylation and deamination of amino acids, are the key factors in this isotopic approach. The principles drawn from the isotopic distributions disentangle the complex dynamics of the biosphere and allow the interactions between the geosphere and biosphere to be analyzed in detail. We also summarize two recently examined topics with new datasets: the isotopic compositions of individual biosynthetic products (chlorophylls and amino acids) and those of animal organs for further pursuing the basis of the methodology. As a tool for investigating complex systems, compound-specific isotopic analysis compensates the intrinsic disadvantages of bulk isotopic signatures. Chlorophylls provide information about the particular processes of various photoautotrophs, whereas amino acids provide a precise measure of the trophic positions of heterotrophs. The isotopic distributions of carbon and nitrogen in a single organism as well as in the whole biosphere are strongly regulated, so that their major components such as amino acids are coordinated appropriately rather than controlled separately.

The role of hydroxo-bridged dinuclear species and the influence of "innocent" buffers in the reactivity of cis-[Co(III)(cyclen)(H₂O)₂]³⁺ and [Co(III)(tren)(H₂O)₂]³⁺ complexes with biologically relevant ligands at physiological pH.

PubMed

Basallote, Manuel G; Martínez, Manuel; Vázquez, Marta

2014-07-28

In view of the relevance of the reactivity of inert tetraamine Co(III) complexes having two substitutionally active cis positions capable of interact with biologically relevant ligands, the study of the reaction of cis-[Co(cyclen)(H2O)2](3+) and [Co(tren)(H2O)2](3+) with chlorides, inorganic phosphate and 5'-CMP (5'-cytidinemonophosphate) has been pursued at physiological pH. The results indicate that, in addition to the actuation of the expected labilising conjugate-base mechanism, the formation of mono and inert bis hydroxo-bridged species is relevant for understanding their speciation and reactivity. The reactivity pattern observed also indicates the key role played by the "innocent" buffers frequently used in most in vitro studies, which can make the results unreliable in many cases. The differences between the reactivity of inorganic and biologically relevant phosphates has also been found to be remarkable, with outer-sphere hydrogen bonding interactions being a dominant factor for the process. While for the inorganic phosphate substitution process the formation of μ-η(2)-OPO2O represents the termination of the reactivity monitored, for 5'-CMP only the formation of η(1)-OPO3 species is observed, which evolve with time to the final dead-end bis hydroxo-bridged complexes. The promoted hydrolysis of the 5'-CMP phosphate has not been observed in any of the processes studied.

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.

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

PubMed

Kimata-Ariga, Yoko; Hase, Toshiharu

2014-01-01

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

Cognitive flexibility and undergraduate physiology students: increasing advanced knowledge acquisition within an ill-structured domain.

PubMed

Rhodes, Ashley E; Rozell, Timothy G

2017-09-01

Cognitive flexibility is defined as the ability to assimilate previously learned information and concepts to generate novel solutions to new problems. This skill is crucial for success within ill-structured domains such as biology, physiology, and medicine, where many concepts are simultaneously required for understanding a complex problem, yet the problem consists of patterns or combinations of concepts that are not consistently used or needed across all examples. To succeed within ill-structured domains, a student must possess a certain level of cognitive flexibility: rigid thought processes and prepackaged informational retrieval schemes relying on rote memorization will not suffice. In this study, we assessed the cognitive flexibility of undergraduate physiology students using a validated instrument entitled Student's Approaches to Learning (SAL). The SAL evaluates how deeply and in what way information is processed, as well as the investment of time and mental energy that a student is willing to expend by measuring constructs such as elaboration and memorization. Our results indicate that students who rely primarily on memorization when learning new information have a smaller knowledge base about physiological concepts, as measured by a prior knowledge assessment and unit exams. However, students who rely primarily on elaboration when learning new information have a more well-developed knowledge base about physiological concepts, which is displayed by higher scores on a prior knowledge assessment and increased performance on unit exams. Thus students with increased elaboration skills possibly possess a higher level of cognitive flexibility and are more likely to succeed within ill-structured domains. Copyright © 2017 the American Physiological Society.

Origins of Aminergic Regulation of Behavior in Complex Insect Social Systems

PubMed Central

Kamhi, J. Frances; Arganda, Sara; Moreau, Corrie S.; Traniello, James F. A.

2017-01-01

Neuromodulators are conserved across insect taxa, but how biogenic amines and their receptors in ancestral solitary forms have been co-opted to control behaviors in derived socially complex species is largely unknown. Here we explore patterns associated with the functions of octopamine (OA), serotonin (5-HT) and dopamine (DA) in solitary ancestral insects and their derived functions in eusocial ants, bees, wasps and termites. Synthesizing current findings that reveal potential ancestral roles of monoamines in insects, we identify physiological processes and conserved behaviors under aminergic control, consider how biogenic amines may have evolved to modulate complex social behavior, and present focal research areas that warrant further study. PMID:29066958

The dynamic relationship between cerebellar Purkinje cell simple spikes and the spikelet number of complex spikes.

PubMed

Burroughs, Amelia; Wise, Andrew K; Xiao, Jianqiang; Houghton, Conor; Tang, Tianyu; Suh, Colleen Y; Lang, Eric J; Apps, Richard; Cerminara, Nadia L

2017-01-01

Purkinje cells are the sole output of the cerebellar cortex and fire two distinct types of action potential: simple spikes and complex spikes. Previous studies have mainly considered complex spikes as unitary events, even though the waveform is composed of varying numbers of spikelets. The extent to which differences in spikelet number affect simple spike activity (and vice versa) remains unclear. We found that complex spikes with greater numbers of spikelets are preceded by higher simple spike firing rates but, following the complex spike, simple spikes are reduced in a manner that is graded with spikelet number. This dynamic interaction has important implications for cerebellar information processing, and suggests that complex spike spikelet number may maintain Purkinje cells within their operational range. Purkinje cells are central to cerebellar function because they form the sole output of the cerebellar cortex. They exhibit two distinct types of action potential: simple spikes and complex spikes. It is widely accepted that interaction between these two types of impulse is central to cerebellar cortical information processing. Previous investigations of the interactions between simple spikes and complex spikes have mainly considered complex spikes as unitary events. However, complex spikes are composed of an initial large spike followed by a number of secondary components, termed spikelets. The number of spikelets within individual complex spikes is highly variable and the extent to which differences in complex spike spikelet number affects simple spike activity (and vice versa) remains poorly understood. In anaesthetized adult rats, we have found that Purkinje cells recorded from the posterior lobe vermis and hemisphere have high simple spike firing frequencies that precede complex spikes with greater numbers of spikelets. This finding was also evident in a small sample of Purkinje cells recorded from the posterior lobe hemisphere in awake cats. In addition, complex spikes with a greater number of spikelets were associated with a subsequent reduction in simple spike firing rate. We therefore suggest that one important function of spikelets is the modulation of Purkinje cell simple spike firing frequency, which has implications for controlling cerebellar cortical output and motor learning. © 2016 The Authors. The Journal of Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.

Refined generalized multiscale entropy analysis for physiological signals

NASA Astrophysics Data System (ADS)

Liu, Yunxiao; Lin, Youfang; Wang, Jing; Shang, Pengjian

2018-01-01

Multiscale entropy analysis has become a prevalent complexity measurement and been successfully applied in various fields. However, it only takes into account the information of mean values (first moment) in coarse-graining procedure. Then generalized multiscale entropy (MSEn) considering higher moments to coarse-grain a time series was proposed and MSEσ2 has been implemented. However, the MSEσ2 sometimes may yield an imprecise estimation of entropy or undefined entropy, and reduce statistical reliability of sample entropy estimation as scale factor increases. For this purpose, we developed the refined model, RMSEσ2, to improve MSEσ2. Simulations on both white noise and 1 / f noise show that RMSEσ2 provides higher entropy reliability and reduces the occurrence of undefined entropy, especially suitable for short time series. Besides, we discuss the effect on RMSEσ2 analysis from outliers, data loss and other concepts in signal processing. We apply the proposed model to evaluate the complexity of heartbeat interval time series derived from healthy young and elderly subjects, patients with congestive heart failure and patients with atrial fibrillation respectively, compared to several popular complexity metrics. The results demonstrate that RMSEσ2 measured complexity (a) decreases with aging and diseases, and (b) gives significant discrimination between different physiological/pathological states, which may facilitate clinical application.

Pharmacometric Models for Characterizing the Pharmacokinetics of Orally Inhaled Drugs.

PubMed

Borghardt, Jens Markus; Weber, Benjamin; Staab, Alexander; Kloft, Charlotte

2015-07-01

During the last decades, the importance of modeling and simulation in clinical drug development, with the goal to qualitatively and quantitatively assess and understand mechanisms of pharmacokinetic processes, has strongly increased. However, this increase could not equally be observed for orally inhaled drugs. The objectives of this review are to understand the reasons for this gap and to demonstrate the opportunities that mathematical modeling of pharmacokinetics of orally inhaled drugs offers. To achieve these objectives, this review (i) discusses pulmonary physiological processes and their impact on the pharmacokinetics after drug inhalation, (ii) provides a comprehensive overview of published pharmacokinetic models, (iii) categorizes these models into physiologically based pharmacokinetic (PBPK) and (clinical data-derived) empirical models, (iv) explores both their (mechanistic) plausibility, and (v) addresses critical aspects of different pharmacometric approaches pertinent for drug inhalation. In summary, pulmonary deposition, dissolution, and absorption are highly complex processes and may represent the major challenge for modeling and simulation of PK after oral drug inhalation. Challenges in relating systemic pharmacokinetics with pulmonary efficacy may be another factor contributing to the limited number of existing pharmacokinetic models for orally inhaled drugs. Investigations comprising in vitro experiments, clinical studies, and more sophisticated mathematical approaches are considered to be necessary for elucidating these highly complex pulmonary processes. With this additional knowledge, the PBPK approach might gain additional attractiveness. Currently, (semi-)mechanistic modeling offers an alternative to generate and investigate hypotheses and to more mechanistically understand the pulmonary and systemic pharmacokinetics after oral drug inhalation including the impact of pulmonary diseases.

Complexity analysis of human physiological signals based on case studies

NASA Astrophysics Data System (ADS)

Angelova, Maia; Holloway, Philip; Ellis, Jason

2015-04-01

This work focuses on methods for investigation of physiological time series based on complexity analysis. It is a part of a wider programme to determine non-invasive markers for healthy ageing. We consider two case studies investigated with actigraphy: (a) sleep and alternations with insomnia, and (b) ageing effects on mobility patterns. We illustrate, using these case studies, the application of fractal analysis to the investigation of regulation patterns and control, and change of physiological function. In the first case study, fractal analysis techniques were implemented to study the correlations present in sleep actigraphy for individuals suffering from acute insomnia in comparison with healthy controls. The aim was to investigate if complexity analysis can detect the onset of adverse health-related events. The subjects with acute insomnia displayed significantly higher levels of complexity, possibly a result of too much activity in the underlying regulatory systems. The second case study considered mobility patterns during night time and their variations with age. It showed that complexity metrics can identify change in physiological function with ageing. Both studies demonstrated that complexity analysis can be used to investigate markers of health, disease and healthy ageing.

iTRAQ-based analysis of changes in the cassava root proteome reveals pathways associated with post-harvest physiological deterioration.

PubMed

Owiti, Judith; Grossmann, Jonas; Gehrig, Peter; Dessimoz, Christophe; Laloi, Christophe; Hansen, Maria Benn; Gruissem, Wilhelm; Vanderschuren, Hervé

2011-07-01

The short storage life of harvested cassava roots is an important constraint that limits the full potential of cassava as a commercial food crop in developing countries. We investigated the molecular changes during physiological deterioration of cassava root after harvesting using isobaric tags for relative and absolute quantification (iTRAQ) of proteins in soluble and non-soluble fractions prepared during a 96 h post-harvest time course. Combining bioinformatic approaches to reduce information redundancy for unsequenced or partially sequenced plant species, we established a comprehensive proteome map of the cassava root and identified quantitatively regulated proteins. Up-regulation of several key proteins confirmed that physiological deterioration of cassava root after harvesting is an active process, with 67 and 170 proteins, respectively, being up-regulated early and later after harvesting. This included regulated proteins that had not previously been associated with physiological deterioration after harvesting, such as linamarase, glutamic acid-rich protein, hydroxycinnamoyl transferase, glycine-rich RNA binding protein, β-1,3-glucanase, pectin methylesterase, maturase K, dehydroascorbate reductase, allene oxide cyclase, and proteins involved in signal pathways. To confirm the regulation of these proteins, activity assays were performed for selected enzymes. Together, our results show that physiological deterioration after harvesting is a highly regulated complex process involving proteins that are potential candidates for biotechnology approaches to reduce such deterioration. © 2011 The Authors. The Plant Journal © 2011 Blackwell Publishing Ltd.

Regulation of feeding behavior in Drosophila through the interplay of gustation, physiology and neuromodulation.

PubMed

Bhumika; Singh, Arvind Kumar

2018-06-01

One of the most fundamental behaviors in all the organisms, in order to achieve a satiated state and internal energy homeostasis is feeding. The action of feeding in any being whether be it any vertebrate or an invertebrate involves the perception of the external environment along with the gamut of decision making processes to eat or to not eat. The feeding decision along with chemosensation through gustation and olfaction leads to intake of food with proper nutrient balance along with avoidance of bitter and toxic substances. The progressions in the understanding of the complexity of feeding behavior involving gustation, neuronal and physiological processes have been achieved through the use of unparalleled model organism Drosophila melanogaster . Here, in this review, we aim to discuss the studies about the taste perception of major macronutrients in Drosophila through gustatory receptors as well as how the involvement of neuropeptides and neuromodulators in feeding behavior modulate the plasticity in feeding decisions. This review also summarizes the involvement of insulin/insulin-like growth factor signaling pathway in nutrient sensing and how the interaction of Drosophila insulin-like peptides with neuromodulators regulate feeding decision process. The review provides an integrative approach towards a balanced metabolic state in Drosophila through the interplay of physiology, gustatory perception and neuromodulation.

Dunbar's number: group size and brain physiology in humans reexamined.

PubMed

de Ruiter, Jan; Weston, Gavin; Lyon, Stephen M

2011-01-01

Popular academic ideas linking physiological adaptations to social behaviors are spreading disconcertingly into wider societal contexts. In this article, we note our skepticism with one particularly popular—in our view, problematic—supposed causal correlation between neocortex size and social group size. The resulting Dunbar's Number, as it has come to be called, has been statistically tested against observed group size in different primate species. Although there may be reason to doubt the Dunbar's Number hypothesis among nonhuman primate species, we restrict ourselves here to the application of such an explanatory hypothesis to human, culture-manipulating populations. Human information process management, we argue, cannot be understood as a simple product of brain physiology. Cross-cultural comparison of not only group size but also relationship-reckoning systems like kinship terminologies suggests that although neocortices are undoubtedly crucial to human behavior, they cannot be given such primacy in explaining complex group composition, formation, or management.

Translational applications of evaluating physiologic variability in human endotoxemia

PubMed Central

Scheff, Jeremy D.; Mavroudis, Panteleimon D.; Calvano, Steve E.; Androulakis, Ioannis P.

2012-01-01

Dysregulation of the inflammatory response is a critical component of many clinically challenging disorders such as sepsis. Inflammation is a biological process designed to lead to healing and recovery, ultimately restoring homeostasis; however, the failure to fully achieve those beneficial results can leave a patient in a dangerous persistent inflammatory state. One of the primary challenges in developing novel therapies in this area is that inflammation is comprised of a complex network of interacting pathways. Here, we discuss our approaches towards addressing this problem through computational systems biology, with a particular focus on how the presence of biological rhythms and the disruption of these rhythms in inflammation may be applied in a translational context. By leveraging the information content embedded in physiologic variability, ranging in scale from oscillations in autonomic activity driving short-term heart rate variability (HRV) to circadian rhythms in immunomodulatory hormones, there is significant potential to gain insight into the underlying physiology. PMID:23203205

Impact of Leishmania Infection on Host Macrophage Nuclear Physiology and Nucleopore Complex Integrity

PubMed Central

Isnard, Amandine; Christian, Jan G.; Kodiha, Mohamed; Stochaj, Ursula; McMaster, W. Robert; Olivier, Martin

2015-01-01

The protease GP63 is an important virulence factor of Leishmania parasites. We previously showed that GP63 reaches the perinuclear area of host macrophages and that it directly modifies nuclear translocation of the transcription factors NF-κB and AP-1. Here we describe for the first time, using molecular biology and in-depth proteomic analyses, that GP63 alters the host macrophage nuclear envelope, and impacts on nuclear processes. Our results suggest that GP63 does not appear to use a classical nuclear localization signal common between Leishmania species for import, but degrades nucleoporins, and is responsible for nuclear transport alterations. In the nucleoplasm, GP63 activity accounts for the degradation and mislocalization of proteins involved amongst others in gene expression and in translation. Collectively, our data indicates that Leishmania infection strongly affects nuclear physiology, suggesting that targeting of nuclear physiology may be a strategy beneficial for virulent Leishmania parasites. PMID:25826301

Female perception of male body odor.

PubMed

Sergeant, Mark J T

2010-01-01

Olfaction is one of the most crucial forms of communication among nonhuman animals. Historically, olfaction has been perceived as being of limited importance for humans, but recent research has documented that not only do humans have sensitive olfactory abilities, but also odors have the potential to influence our physiology and behavior. This chapter reviews research on olfactory communication among humans, focusing on the effects of male bodily odors on female physiology and behavior. The process of body odor production and the detection of olfactory signals are reviewed, focusing on potential sex differences in these abilities. The effects of male body odors on female physiological and behavioral effects of body odors are considered. Finally, with specific regard to female mate choice, evidence regarding the influence of the major histocompatibility complex and fluctuating asymmetry on male olfactory cues is reviewed. Copyright © 2010 Elsevier Inc. All rights reserved.

Social aggravation: Understanding the complex role of social relationships on stress and health-relevant physiology.

PubMed

Birmingham, Wendy C; Holt-Lunstad, Julianne

2018-04-05

There is a rich literature on social support and physical health, but research has focused primarily on the protective effects of social relationship. The stress buffering model asserts that relationships may be protective by being a source of support when coping with stress, thereby blunting health relevant physiological responses. Research also indicates relationships can be a source of stress, also influencing health. In other words, the social buffering influence may have a counterpart, a social aggravating influence that has an opposite or opposing effect. Drawing upon existing conceptual models, we expand these to delineate how social relationships may influence stress processes and ultimately health. This review summarizes the existing literature that points to the potential deleterious physiological effects of our relationships when they are sources of stress or exacerbate stress. Copyright © 2018 Elsevier B.V. All rights reserved.

Understanding the Logics of Pheromone Processing in the Honeybee Brain: From Labeled-Lines to Across-Fiber Patterns

PubMed Central

Sandoz, Jean-Christophe; Deisig, Nina; de Brito Sanchez, Maria Gabriela; Giurfa, Martin

2007-01-01

Honeybees employ a very rich repertoire of pheromones to ensure intraspecific communication in a wide range of behavioral contexts. This communication can be complex, since the same compounds can have a variety of physiological and behavioral effects depending on the receiver. Honeybees constitute an ideal model to study the neurobiological basis of pheromonal processing, as they are already one of the most influential animal models for the study of general odor processing and learning at behavioral, cellular and molecular levels. Accordingly, the anatomy of the bee brain is well characterized and electro- and opto-physiological recording techniques at different stages of the olfactory circuit are possible in the laboratory. Here we review pheromone communication in honeybees and analyze the different stages of olfactory processing in the honeybee brain, focusing on available data on pheromone detection, processing and representation at these different stages. In particular, we argue that the traditional distinction between labeled-line and across-fiber pattern processing, attributed to pheromone and general odors respectively, may not be so clear in the case of honeybees, especially for social-pheromones. We propose new research avenues for stimulating future work in this area. PMID:18958187

USSR and Eastern Europe Scientific Abstracts, Biomedical and Behavioral Sciences, Number 67.

DTIC Science & Technology

1977-03-30

and Ecological Problems 14 Molecular Biology 23 Pharmacology. 25 Physiology. 27 Public Health 46 Radiobiology 48 Therapy . 49 BEHAVIORAL...normalizing metabolic processes be included in the complex therapy . USSR UDC 612.3 616.3 DIGESTIBILITY OF VEGETARIAN FISH MEAT PROTEINS BY PROTEOLYTIC...inactivation of one hemisphere, arising after unilateral electroconvulsive seizure, a study was made of the intelli- gibility of phonemes (vowels and

Insights into the selective binding and toxic mechanism of microcystin to catalase

NASA Astrophysics Data System (ADS)

Hu, Yuandong; Da, Liangjun

2014-03-01

Microcystin is a sort of cyclic nonribosomal peptides produced by cyanobacteria. It is cyanotoxin, which can be very toxic for plants and animals including humans. The present study evaluated the interaction of microcystin and catalase, under physiological conditions by means of fluorescence, three-dimensional (3D) fluorescence, circular dichroism (CD), Fourier Transform infrared (FT-IR) spectroscopy, and enzymatic reactionkinetic techniques. The fluorescence data showed that microcystin could bind to catalase to form a complex. The binding process was a spontaneous molecular interaction procedure, in which electrostatic interactions played a major role. Energy transfer and fluorescence studies proved the existence of a static binding process. Additionally, as shown by the three-dimensional fluorescence, CD and FT-IR results, microcystin could lead to conformational and microenvironmental changes of the protein, which may affect the physiological functions of catalase. The work provides important insights into the toxicity mechanism of microcystin in vivo.

Vitamin A Metabolism: An Update

PubMed Central

D’Ambrosio, Diana N.; Clugston, Robin D.; Blaner, William S.

2011-01-01

Retinoids are required for maintaining many essential physiological processes in the body, including normal growth and development, normal vision, a healthy immune system, normal reproduction, and healthy skin and barrier functions. In excess of 500 genes are thought to be regulated by retinoic acid. 11-cis-retinal serves as the visual chromophore in vision. The body must acquire retinoid from the diet in order to maintain these essential physiological processes. Retinoid metabolism is complex and involves many different retinoid forms, including retinyl esters, retinol, retinal, retinoic acid and oxidized and conjugated metabolites of both retinol and retinoic acid. In addition, retinoid metabolism involves many carrier proteins and enzymes that are specific to retinoid metabolism, as well as other proteins which may be involved in mediating also triglyceride and/or cholesterol metabolism. This review will focus on recent advances for understanding retinoid metabolism that have taken place in the last ten to fifteen years. PMID:21350678

Quo vadis plant hormone analysis?

PubMed

Tarkowská, Danuše; Novák, Ondřej; Floková, Kristýna; Tarkowski, Petr; Turečková, Veronika; Grúz, Jiří; Rolčík, Jakub; Strnad, Miroslav

2014-07-01

Plant hormones act as chemical messengers in the regulation of myriads of physiological processes that occur in plants. To date, nine groups of plant hormones have been identified and more will probably be discovered. Furthermore, members of each group may participate in the regulation of physiological responses in planta both alone and in concert with members of either the same group or other groups. The ideal way to study biochemical processes involving these signalling molecules is 'hormone profiling', i.e. quantification of not only the hormones themselves, but also their biosynthetic precursors and metabolites in plant tissues. However, this is highly challenging since trace amounts of all of these substances are present in highly complex plant matrices. Here, we review advances, current trends and future perspectives in the analysis of all currently known plant hormones and the associated problems of extracting them from plant tissues and separating them from the numerous potentially interfering compounds.

Tetrahydrocannabinol and endocannabinoids in feeding and appetite.

PubMed

Berry, Elliot M; Mechoulam, Raphael

2002-08-01

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

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

PubMed

Ivanov, K P

2014-01-01

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

Direct Deposition of Gas Phase Generated Aerosol Gold Nanoparticles into Biological Fluids - Corona Formation and Particle Size Shifts

PubMed Central

Svensson, Christian R.; Messing, Maria E.; Lundqvist, Martin; Schollin, Alexander; Deppert, Knut; Pagels, Joakim H.; Rissler, Jenny; Cedervall, Tommy

2013-01-01

An ongoing discussion whether traditional toxicological methods are sufficient to evaluate the risks associated with nanoparticle inhalation has led to the emergence of Air-Liquid interface toxicology. As a step in this process, this study explores the evolution of particle characteristics as they move from the airborne state into physiological solution. Airborne gold nanoparticles (AuNP) are generated using an evaporation-condensation technique. Spherical and agglomerate AuNPs are deposited into physiological solutions of increasing biological complexity. The AuNP size is characterized in air as mobility diameter and in liquid as hydrodynamic diameter. AuNP:Protein aggregation in physiological solutions is determined using dynamic light scattering, particle tracking analysis, and UV absorption spectroscopy. AuNPs deposited into homocysteine buffer form large gold-aggregates. Spherical AuNPs deposited in solutions of albumin were trapped at the Air-Liquid interface but was readily suspended in the solutions with a size close to that of the airborne particles, indicating that AuNP:Protein complex formation is promoted. Deposition into serum and lung fluid resulted in larger complexes, reflecting the formation of a more complex protein corona. UV absorption spectroscopy indicated no further aggregation of the AuNPs after deposition in solution. The corona of the deposited AuNPs shows differences compared to AuNPs generated in suspension. Deposition of AuNPs from the aerosol phase into biological fluids offers a method to study the protein corona formed, upon inhalation and deposition in the lungs in a more realistic way compared to particle liquid suspensions. This is important since the protein corona together with key particle properties (e.g. size, shape and surface reactivity) to a large extent may determine the nanoparticle effects and possible translocation to other organs. PMID:24086363

Mammalian HspB1 (Hsp27) is a molecular sensor linked to the physiology and environment of the cell.

PubMed

Arrigo, André-Patrick

2017-07-01

Constitutively expressed small heat shock protein HspB1 regulates many fundamental cellular processes and plays major roles in many human pathological diseases. In that regard, this chaperone has a huge number of apparently unrelated functions that appear linked to its ability to recognize many client polypeptides that are subsequently modified in their activity and/or half-life. A major parameter to understand how HspB1 is dedicated to interact with particular clients in defined cellular conditions relates to its complex oligomerization and phosphorylation properties. Indeed, HspB1 structural organization displays dynamic and complex rearrangements in response to changes in the cellular environment or when the cell physiology is modified. These structural modifications probably reflect the formation of structural platforms aimed at recognizing specific client polypeptides. Here, I have reviewed data from the literature and re-analyzed my own studies to describe and discuss these fascinating changes in HspB1 structural organization.

Physiological Informatics: Collection and Analyses of Data from Wearable Sensors and Smartphone for Healthcare.

PubMed

Bai, Jinwei; Shen, Li; Sun, Huimin; Shen, Bairong

2017-01-01

Physiological data from wearable sensors and smartphone are accumulating rapidly, and this provides us the chance to collect dynamic and personalized information as phenotype to be integrated to genotype for the holistic understanding of complex diseases. This integration can be applied to early prediction and prevention of disease, therefore promoting the shifting of disease care tradition to the healthcare paradigm. In this chapter, we summarize the physiological signals which can be detected by wearable sensors, the sharing of the physiological big data, and the mining methods for the discovery of disease-associated patterns for personalized diagnosis and treatment. We discuss the challenges of physiological informatics about the storage, the standardization, the analyses, and the applications of the physiological data from the wearable sensors and smartphone. At last, we present our perspectives on the models for disentangling the complex relationship between early disease prediction and the mining of physiological phenotype data.

The physiological equivalent temperature - a universal index for the biometeorological assessment of the thermal environment

NASA Astrophysics Data System (ADS)

Höppe, P.

With considerably increased coverage of weather information in the news media in recent years in many countries, there is also more demand for data that are applicable and useful for everyday life. Both the perception of the thermal component of weather as well as the appropriate clothing for thermal comfort result from the integral effects of all meteorological parameters relevant for heat exchange between the body and its environment. Regulatory physiological processes can affect the relative importance of meteorological parameters, e.g. wind velocity becomes more important when the body is sweating. In order to take into account all these factors, it is necessary to use a heat-balance model of the human body. The physiological equivalent temperature (PET) is based on the Munich Energy-balance Model for Individuals (MEMI), which models the thermal conditions of the human body in a physiologically relevant way. PET is defined as the air temperature at which, in a typical indoor setting (without wind and solar radiation), the heat budget of the human body is balanced with the same core and skin temperature as under the complex outdoor conditions to be assessed. This way PET enables a layperson to compare the integral effects of complex thermal conditions outside with his or her own experience indoors. On hot summer days, for example, with direct solar irradiation the PET value may be more than 20 K higher than the air temperature, on a windy day in winter up to 15 K lower.

Modulation of 14-3-3/Phosphotarget Interaction by Physiological Concentrations of Phosphate and Glycerophosphates

PubMed Central

Sluchanko, Nikolai N.; Chebotareva, Natalia A.; Gusev, Nikolai B.

2013-01-01

Molecular mechanisms governing selective binding of a huge number of various phosphorylated protein partners to 14-3-3 remain obscure. Phosphate can bind to 14-3-3 and therefore being present at high intracellular concentration, which undergoes significant changes under physiological conditions, phosphate can theoretically regulate interaction of 14-3-3 with phosphorylated targets. In order to check this hypothesis we analyzed effect of phosphate and other natural abundant anions on interaction of 14-3-3 with phosphorylated human small heat shock protein HspB6 (Hsp20) participating in regulation of different intracellular processes. Inorganic phosphate, glycerol-1-phosphate and glycerol-2-phosphate at physiologically relevant concentrations (5-15 mM) significantly destabilized complexes formed by 14-3-3ζ and phosphorylated HspB6 (pHspB6), presumably, via direct interaction with the substrate-binding site of 14-3-3. Phosphate also destabilized complexes between pHspB6 and 14-3-3γ or the monomeric mutant form of 14-3-3ζ. Inorganic sulfate and pyrophosphate were less effective in modulation of 14-3-3 interaction with its target protein. The inhibitory effect of all anions on pHspB6/14-3-3 interaction was concentration-dependent. It is hypothesized that physiological changes in phosphate anions concentration can modulate affinity and specificity of interaction of 14-3-3 with its multiple targets and therefore the actual phosphointeractome of 14-3-3. PMID:23977325

Modulation of 14-3-3/phosphotarget interaction by physiological concentrations of phosphate and glycerophosphates.

PubMed

Sluchanko, Nikolai N; Chebotareva, Natalia A; Gusev, Nikolai B

2013-01-01

Molecular mechanisms governing selective binding of a huge number of various phosphorylated protein partners to 14-3-3 remain obscure. Phosphate can bind to 14-3-3 and therefore being present at high intracellular concentration, which undergoes significant changes under physiological conditions, phosphate can theoretically regulate interaction of 14-3-3 with phosphorylated targets. In order to check this hypothesis we analyzed effect of phosphate and other natural abundant anions on interaction of 14-3-3 with phosphorylated human small heat shock protein HspB6 (Hsp20) participating in regulation of different intracellular processes. Inorganic phosphate, glycerol-1-phosphate and glycerol-2-phosphate at physiologically relevant concentrations (5-15 mM) significantly destabilized complexes formed by 14-3-3ζ and phosphorylated HspB6 (pHspB6), presumably, via direct interaction with the substrate-binding site of 14-3-3. Phosphate also destabilized complexes between pHspB6 and 14-3-3γ or the monomeric mutant form of 14-3-3ζ. Inorganic sulfate and pyrophosphate were less effective in modulation of 14-3-3 interaction with its target protein. The inhibitory effect of all anions on pHspB6/14-3-3 interaction was concentration-dependent. It is hypothesized that physiological changes in phosphate anions concentration can modulate affinity and specificity of interaction of 14-3-3 with its multiple targets and therefore the actual phosphointeractome of 14-3-3.

Quantifying seasonal dynamics of canopy structure and function using inexpensive narrowband spectral radiometers

NASA Astrophysics Data System (ADS)

Vierling, L. A.; Garrity, S. R.; Campbell, G.; Coops, N. C.; Eitel, J.; Gamon, J. A.; Hilker, T.; Krofcheck, D. J.; Litvak, M. E.; Naupari, J. A.; Richardson, A. D.; Sonnentag, O.; van Leeuwen, M.

2011-12-01

Increasing the spatial and temporal density of automated environmental sensing networks is necessary to quantify shifts in plant structure (e.g., leaf area index) and function (e.g., photosynthesis). Improving detection sensitivity can facilitate a mechanistic understanding by better linking plant processes to environmental change. Spectral radiometer measurements can be highly useful for tracking plant structure and function from diurnal to seasonal time scales and calibrating and validating satellite- and aircraft-based spectral measurements. However, dense ground networks of such instruments are challenging to establish due to the cost and complexity of automated instrument deployment. We therefore developed simple to operate, lightweight and inexpensive narrowband (~10nm bandwidth) spectral instruments capable of continuously measuring four to six discrete bands that have proven capacity to describe key physiological processes and structural features of plant canopies. These bands are centered at 530, 570, 675, 800, 880, and 970 nm to enable calculation of the physiological reflectance index (PRI), normalized difference vegetation index (NDVI), green NDVI (gNDVI), and water band index (WBI) collected above and within vegetation canopies. To date, measurements have been collected above grassland, semi-arid shrub steppe, piñon-juniper woodland, dense conifer forest, mixed deciduous-conifer forest, and cropland canopies, with additional measurements collected along vertical transects through a temperate conifer rainforest. Findings from this work indicate not only that key shifts in plant phenology, physiology, and structure can be captured using such instruments, but that the temporally dense nature of the measurements can help to disentangle heretofore unreported complexities of simultaneous phenological and structural change on canopy reflectance.

Some effects of smoking withdrawal on complex performance and physiological responses.

DOT National Transportation Integrated Search

1983-01-01

The effects of smoking withdrawal on complex (time-shared) performance and physiological responses were studied at a simulated aircraft cabin altitude of 6,500 ft. Seventeen habitual smokers, nine women and eight men 23 to 59 years of age, served as ...

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

NASA Technical Reports Server (NTRS)

Foster, Tammy E.; Brooks, J. Renee; Quincy, Charles (Technical Monitor)

2002-01-01

The functional grouping hypothesis, which suggests that complexity in function can be simplified by grouping species with similar responses, was tested in the Florida scrub habitat. Functional groups were identified based on how species in fire maintained FL scrub function in terms of carbon, water and nitrogen dynamics. The suite of physiologic parameters measured to determine function included both instantaneous gas exchange measurements obtained from photosynthetic light response curves and integrated measures of function. Using cluster analysis, five distinct physiologically-based functional groups were identified. Using non-parametric multivariate analyses, it was determined that these five groupings were not altered by plot differences or by the three different management regimes; prescribed burn, mechanically treated and burn, and fire-suppressed. The physiological groupings also remained robust between the two years 1999 and 2000. In order for these groupings to be of use for scaling ecosystem processes, there needs to be an easy-to-measure morphological indicator of function. Life form classifications were able to depict the physiological groupings more adequately than either specific leaf area or leaf thickness. THe ability of life forms to depict the groupings was improved by separating the parasitic Ximenia americana from the shrub category.

Eliciting candidate anatomical routes for protein interactions: a scenario from endocrine physiology

PubMed Central

2013-01-01

Background In this paper, we use: i) formalised anatomical knowledge of connectivity between body structures and ii) a formal theory of physiological transport between fluid compartments in order to define and make explicit the routes followed by proteins to a site of interaction. The underlying processes are the objects of mathematical models of physiology and, therefore, the motivation for the approach can be understood as using knowledge representation and reasoning methods to propose concrete candidate routes corresponding to correlations between variables in mathematical models of physiology. In so doing, the approach projects physiology models onto a representation of the anatomical and physiological reality which underpins them. Results The paper presents a method based on knowledge representation and reasoning for eliciting physiological communication routes. In doing so, the paper presents the core knowledge representation and algorithms using it in the application of the method. These are illustrated through the description of a prototype implementation and the treatment of a simple endocrine scenario whereby a candidate route of communication between ANP and its receptors on the external membrane of smooth muscle cells in renal arterioles is elicited. The potential of further development of the approach is illustrated through the informal discussion of a more complex scenario. Conclusions The work presented in this paper supports research in intercellular communication by enabling knowledge‐based inference on physiologically‐related biomedical data and models. PMID:23590598

Focus on the emerging new fields of network physiology and network medicine

NASA Astrophysics Data System (ADS)

Ivanov, Plamen Ch; Liu, Kang K. L.; Bartsch, Ronny P.

2016-10-01

Despite the vast progress and achievements in systems biology and integrative physiology in the last decades, there is still a significant gap in understanding the mechanisms through which (i) genomic, proteomic and metabolic factors and signaling pathways impact vertical processes across cells, tissues and organs leading to the expression of different disease phenotypes and influence the functional and clinical associations between diseases, and (ii) how diverse physiological systems and organs coordinate their functions over a broad range of space and time scales and horizontally integrate to generate distinct physiologic states at the organism level. Two emerging fields, network medicine and network physiology, aim to address these fundamental questions. Novel concepts and approaches derived from recent advances in network theory, coupled dynamical systems, statistical and computational physics show promise to provide new insights into the complexity of physiological structure and function in health and disease, bridging the genetic and sub-cellular level with inter-cellular interactions and communications among integrated organ systems and sub-systems. These advances form first building blocks in the methodological formalism and theoretical framework necessary to address fundamental problems and challenges in physiology and medicine. This ‘focus on’ issue contains 26 articles representing state-of-the-art contributions covering diverse systems from the sub-cellular to the organism level where physicists have key role in laying the foundations of these new fields.

Coordinate Activation of Redox-Dependent ASK1/TGF-β Signaling by a Multiprotein Complex (MPK38, ASK1, SMADs, ZPR9, and TRX) Improves Glucose and Lipid Metabolism in Mice.

PubMed

Seong, Hyun-A; Manoharan, Ravi; Ha, Hyunjung

2016-03-10

To explore the molecular connections between redox-dependent apoptosis signal-regulating kinase 1 (ASK1) and transforming growth factor-β (TGF-β) signaling pathways and to examine the physiological processes in which coordinated regulation of these two signaling pathways plays a critical role. We provide evidence that the ASK1 and TGF-β signaling pathways are interconnected by a multiprotein complex harboring murine protein serine-threonine kinase 38 (MPK38), ASK1, Sma- and Mad-related proteins (SMADs), zinc-finger-like protein 9 (ZPR9), and thioredoxin (TRX) and demonstrate that the activation of either ASK1 or TGF-β activity is sufficient to activate both the redox-dependent ASK1 and TGF-β signaling pathways. Physiologically, the restoration of the downregulated activation levels of ASK1 and TGF-β signaling in genetically and diet-induced obese mice by adenoviral delivery of SMAD3 or ZPR9 results in the amelioration of adiposity, hyperglycemia, hyperlipidemia, and impaired ketogenesis. Our data suggest that the multiprotein complex linking ASK1 and TGF-β signaling pathways may be a potential target for redox-mediated metabolic complications.

Control of electron transport routes through redox-regulated redistribution of respiratory complexes

PubMed Central

Liu, Lu-Ning; Bryan, Samantha J.; Huang, Fang; Yu, Jianfeng; Nixon, Peter J.; Rich, Peter R.; Mullineaux, Conrad W.

2012-01-01

In cyanobacteria, respiratory electron transport takes place in close proximity to photosynthetic electron transport, because the complexes required for both processes are located within the thylakoid membranes. The balance of electron transport routes is crucial for cell physiology, yet the factors that control the predominance of particular pathways are poorly understood. Here we use a combination of tagging with green fluorescent protein and confocal fluorescence microscopy in live cells of the cyanobacterium Synechococcus elongatus PCC 7942 to investigate the distribution on submicron scales of two key respiratory electron donors, type-I NAD(P)H dehydrogenase (NDH-1) and succinate dehydrogenase (SDH). When cells are grown under low light, both complexes are concentrated in discrete patches in the thylakoid membranes, about 100–300 nm in diameter and containing tens to hundreds of complexes. Exposure to moderate light leads to redistribution of both NDH-1 and SDH such that they become evenly distributed within the thylakoid membranes. The effects of electron transport inhibitors indicate that redistribution of respiratory complexes is triggered by changes in the redox state of an electron carrier close to plastoquinone. Redistribution does not depend on de novo protein synthesis, and it is accompanied by a major increase in the probability that respiratory electrons are transferred to photosystem I rather than to a terminal oxidase. These results indicate that the distribution of complexes on the scale of 100–300 nm controls the partitioning of reducing power and that redistribution of electron transport complexes on these scales is a physiological mechanism to regulate the pathways of electron flow. PMID:22733774

Pharmacokinetic considerations and recommendations in palliative care, with focus on morphine, midazolam and haloperidol.

PubMed

Franken, L G; de Winter, B C M; van Esch, H J; van Zuylen, L; Baar, F P M; Tibboel, D; Mathôt, R A A; van Gelder, T; Koch, B C P

2016-06-01

A variety of medications are used for symptom control in palliative care, such as morphine, midazolam and haloperidol. The pharmacokinetics of these drugs may be altered in these patients as a result of physiological changes that occur at the end stage of life. This review gives an overview of how the pharmacokinetics in terminally ill patients may differ from the average population and discusses the effect of terminal illness on each of the four pharmacokinetic processes absorption, distribution, metabolism, and elimination. Specific considerations are also given for three commonly prescribed drugs in palliative care: morphine, midazolam and haloperidol). The pharmacokinetics of drugs in terminally ill patients can be complex and limited evidence exists on guided drug use in this population. To improve the quality of life of these patients, more knowledge and more pharmacokinetic/pharmacodynamics studies in terminally ill patients are needed to develop individualised dosing guidelines. Until then knowledge of pharmacokinetics and the physiological changes that occur in the final days of life can provide a base for dosing adjustments that will improve the quality of life of terminally ill patients. As the interaction of drugs with the physiology of dying is complex, pharmacological treatment is probably best assessed in a multi-disciplinary setting and the advice of a pharmacist, or clinical pharmacologist, is highly recommended.

Amyloid Precursor Protein Processing and Alzheimer’s Disease

PubMed Central

O’Brien, Richard J.; Wong, Philip C.

2011-01-01

Alzheimer’s disease (AD), the leading cause of dementia worldwide, is characterized by the accumulation of the β-amyloid peptide (Aβ) within the brain along with hyperphosphorylated and cleaved forms of the microtubule-associated protein tau. Genetic, biochemical, and behavioral research suggest that physiologic generation of the neurotoxic Aβ peptide from sequential amyloid precursor protein (APP) proteolysis is the crucial step in the development of AD. APP is a single-pass transmembrane protein expressed at high levels in the brain and metabolized in a rapid and highly complex fashion by a series of sequential proteases, including the intramembranous γ-secretase complex, which also process other key regulatory molecules. Why Aβ accumulates in the brains of elderly individuals is unclear but could relate to changes in APP metabolism or Aβ elimination. Lessons learned from biochemical and genetic studies of APP processing will be crucial to the development of therapeutic targets to treat AD. PMID:21456963

Functional Dynamics within the Human Ribosome Regulate the Rate of Active Protein Synthesis.

PubMed

Ferguson, Angelica; Wang, Leyi; Altman, Roger B; Terry, Daniel S; Juette, Manuel F; Burnett, Benjamin J; Alejo, Jose L; Dass, Randall A; Parks, Matthew M; Vincent, C Theresa; Blanchard, Scott C

2015-11-05

The regulation of protein synthesis contributes to gene expression in both normal physiology and disease, yet kinetic investigations of the human translation mechanism are currently lacking. Using single-molecule fluorescence imaging methods, we have quantified the nature and timing of structural processes in human ribosomes during single-turnover and processive translation reactions. These measurements reveal that functional complexes exhibit dynamic behaviors and thermodynamic stabilities distinct from those observed for bacterial systems. Structurally defined sub-states of pre- and post-translocation complexes were sensitive to specific inhibitors of the eukaryotic ribosome, demonstrating the utility of this platform to probe drug mechanism. The application of three-color single-molecule fluorescence resonance energy transfer (smFRET) methods further revealed a long-distance allosteric coupling between distal tRNA binding sites within ribosomes bearing three tRNAs, which contributed to the rate of processive translation. Copyright © 2015 Elsevier Inc. All rights reserved.

Characterizing scaling properties of complex signals with missed data segments using the multifractal analysis.

PubMed

Pavlov, A N; Pavlova, O N; Abdurashitov, A S; Sindeeva, O A; Semyachkina-Glushkovskaya, O V; Kurths, J

2018-01-01

The scaling properties of complex processes may be highly influenced by the presence of various artifacts in experimental recordings. Their removal produces changes in the singularity spectra and the Hölder exponents as compared with the original artifacts-free data, and these changes are significantly different for positively correlated and anti-correlated signals. While signals with power-law correlations are nearly insensitive to the loss of significant parts of data, the removal of fragments of anti-correlated signals is more crucial for further data analysis. In this work, we study the ability of characterizing scaling features of chaotic and stochastic processes with distinct correlation properties using a wavelet-based multifractal analysis, and discuss differences between the effect of missed data for synchronous and asynchronous oscillatory regimes. We show that even an extreme data loss allows characterizing physiological processes such as the cerebral blood flow dynamics.

Functional dynamics within the human ribosome regulate the rate of active protein synthesis

PubMed Central

Ferguson, Angelica; Wang, Leyi; Altman, Roger B.; Terry, Daniel S.; Juette, Manuel F.; Burnett, Benjamin J.; Alejo, Jose L.; Dass, Randall A.; Parks, Matthew M.; Vincent, Theresa C.; Blanchard, Scott C.

2015-01-01

SUMMARY The regulation of protein synthesis contributes to gene expression in both normal physiology and disease, yet kinetic investigations of the human translation mechanism are currently lacking. Using single-molecule fluorescence imaging methods, we have quantified the nature and timing of structural processes in human ribosomes during single-turnover and processive translation reactions. These measurements reveal that functional complexes exhibit dynamic behaviors and thermodynamic stabilities distinct from those observed for bacterial systems. Structurally defined sub-states of pre- and post-translocation complexes were sensitive to specific inhibitors of the eukaryotic ribosome demonstrating the utility of this platform to probe drug mechanism. The application of three-color single-molecule FRET methods further revealed a long-distance allosteric coupling between distal tRNA binding sites within ribosomes bearing three tRNAs, which contributed to the rate of processive translation. PMID:26593721

Characterizing scaling properties of complex signals with missed data segments using the multifractal analysis

NASA Astrophysics Data System (ADS)

Pavlov, A. N.; Pavlova, O. N.; Abdurashitov, A. S.; Sindeeva, O. A.; Semyachkina-Glushkovskaya, O. V.; Kurths, J.

2018-01-01

The scaling properties of complex processes may be highly influenced by the presence of various artifacts in experimental recordings. Their removal produces changes in the singularity spectra and the Hölder exponents as compared with the original artifacts-free data, and these changes are significantly different for positively correlated and anti-correlated signals. While signals with power-law correlations are nearly insensitive to the loss of significant parts of data, the removal of fragments of anti-correlated signals is more crucial for further data analysis. In this work, we study the ability of characterizing scaling features of chaotic and stochastic processes with distinct correlation properties using a wavelet-based multifractal analysis, and discuss differences between the effect of missed data for synchronous and asynchronous oscillatory regimes. We show that even an extreme data loss allows characterizing physiological processes such as the cerebral blood flow dynamics.

Linguistic Complexity, Speech Production, and Comprehension in Parkinson's Disease: Behavioral and Physiological Indices

ERIC Educational Resources Information Center

Walsh, Bridget; Smith, Anne

2011-01-01

Purpose: To investigate the effects of increased syntactic complexity and utterance length demands on speech production and comprehension in individuals with Parkinson's disease (PD) using behavioral and physiological measures. Method: Speech response latency, interarticulatory coordinative consistency, accuracy of speech production, and response…

Multiscale analysis of information dynamics for linear multivariate processes.

PubMed

Faes, Luca; Montalto, Alessandro; Stramaglia, Sebastiano; Nollo, Giandomenico; Marinazzo, Daniele

2016-08-01

In the study of complex physical and physiological systems represented by multivariate time series, an issue of great interest is the description of the system dynamics over a range of different temporal scales. While information-theoretic approaches to the multiscale analysis of complex dynamics are being increasingly used, the theoretical properties of the applied measures are poorly understood. This study introduces for the first time a framework for the analytical computation of information dynamics for linear multivariate stochastic processes explored at different time scales. After showing that the multiscale processing of a vector autoregressive (VAR) process introduces a moving average (MA) component, we describe how to represent the resulting VARMA process using statespace (SS) models and how to exploit the SS model parameters to compute analytical measures of information storage and information transfer for the original and rescaled processes. The framework is then used to quantify multiscale information dynamics for simulated unidirectionally and bidirectionally coupled VAR processes, showing that rescaling may lead to insightful patterns of information storage and transfer but also to potentially misleading behaviors.

What develops during emotional development? A component process approach to identifying sources of psychopathology risk in adolescence.

PubMed

McLaughlin, Katie A; Garrad, Megan C; Somerville, Leah H

2015-12-01

Adolescence is a phase of the lifespan associated with widespread changes in emotional behavior thought to reflect both changing environments and stressors, and psychological and neurobiological development. However, emotions themselves are complex phenomena that are composed of multiple subprocesses. In this paper, we argue that examining emotional development from a process-level perspective facilitates important insights into the mechanisms that underlie adolescents' shifting emotions and intensified risk for psychopathology. Contrasting the developmental progressions for the antecedents to emotion, physiological reactivity to emotion, emotional regulation capacity, and motivation to experience particular affective states reveals complex trajectories that intersect in a unique way during adolescence. We consider the implications of these intersecting trajectories for negative outcomes such as psychopathology, as well as positive outcomes for adolescent social bonds.

Mitochondrial Physiology in the Major Arbovirus Vector Aedes aegypti: Substrate Preferences and Sexual Differences Define Respiratory Capacity and Superoxide Production

PubMed Central

Soares, Juliana B. R. Correa; Gaviraghi, Alessandro; Oliveira, Marcus F.

2015-01-01

Adult females of Aedes aegypti are facultative blood sucking insects and vectors of Dengue and yellow fever viruses. Insect dispersal plays a central role in disease transmission and the extremely high energy demand posed by flight is accomplished by a very efficient oxidative phosphorylation process, which take place within flight muscle mitochondria. These organelles play a central role in energy metabolism, interconnecting nutrient oxidation to ATP synthesis, but also represent an important site of cellular superoxide production. Given the importance of mitochondria to cell physiology, and the potential contributions of this organelle for A. aegypti biology and vectorial capacity, here, we conducted a systematic assessment of mitochondrial physiology in flight muscle of young adult A. aegypti fed exclusively with sugar. This was carried out by determining the activities of mitochondrial enzymes, the substrate preferences to sustain respiration, the mitochondrial bioenergetic efficiency and capacity, in both mitochondria-enriched preparations and mechanically permeabilized flight muscle in both sexes. We also determined the substrates preferences to promote mitochondrial superoxide generation and the main sites where it is produced within this organelle. We observed that respiration in A. aegypti mitochondria was essentially driven by complex I and glycerol 3 phosphate dehydrogenase substrates, which promoted distinct mitochondrial bioenergetic capacities, but with preserved efficiencies. Respiration mediated by proline oxidation in female mitochondria was strikingly higher than in males. Mitochondrial superoxide production was essentially mediated through proline and glycerol 3 phosphate oxidation, which took place at sites other than complex I. Finally, differences in mitochondrial superoxide production among sexes were only observed in male oxidizing glycerol 3 phosphate, exhibiting higher rates than in female. Together, these data represent a significant step towards the understanding of fundamental mitochondrial processes in A. aegypti, with potential implications for its physiology and vectorial capacity. PMID:25803027

Hydrogen Sulfide in Renal Physiology and Disease.

PubMed

Feliers, Denis; Lee, Hak Joo; Kasinath, Balakuntalam S

2016-11-01

Hydrogen sulfide (H2S) has only recently gained recognition for its physiological effects. It is synthesized widely in the mammalian tissues and regulates several biologic processes ranging from development, angiogenesis, neurotransmission to protein synthesis. Recent Advances: The aim of this review is to critically evaluate the evidence for a role for H2S in kidney function and disease. H2S regulates fundamental kidney physiologic processes such as glomerular filtration and sodium reabsorption. In kidney disease states H2S appears to play a complex role in a context-dependent manner. In some disease states such as ischemia-reperfusion and diabetic kidney disease it can serve as an agent that ameliorates kidney injury. In other diseases such as cis-platinum-induced kidney disease it may mediate kidney injury although more investigation is needed. Recent studies have revealed that the actions of nitric oxide and H2S may be integrated in kidney cells. Further studies are needed to understand the full impact of H2S on kidney physiology. As it is endowed with the properties of regulating blood flow, oxidative stress, and inflammation, H2S should be investigated for its role in inflammatory and toxic diseases of the kidney. Such in-depth exploration may identify specific kidney diseases in which H2S may constitute a unique target for therapeutic intervention. Antioxid. Redox Signal. 25, 720-731.

No Evidence for Emotional Empathy in Chickens Observing Familiar Adult Conspecifics

PubMed Central

Edgar, Joanne L.; Paul, Elizabeth S.; Harris, Lauren; Penturn, Sarah; Nicol, Christine J.

2012-01-01

The capacity of animals to empathise is of high potential relevance to the welfare of group-housed domestic animals. Emotional empathy is a multifaceted and multilayered phenomenon which ranges from relatively simple processes such as emotional matching behaviour to more complex processes involving interaction between emotional and cognitive perspective taking systems. Our previous research has demonstrated that hens show clear behavioural and physiological responses to the mild distress of their chicks. To investigate whether this capacity exists outside the mother/offspring bond, we conducted a similar experiment in which domestic hens were exposed to the mild distress of unrelated, but familiar adult conspecifics. Each observer hen was exposed to two replicates of four conditions, in counterbalanced order; control (C); control with noise of air puff (CN); air puff to conspecific hen (APC); air puff to observer hen (APH). During each test, the observer hens' behaviour and physiology were measured throughout a 10 min pre-treatment and a 10 min treatment period. Despite showing signs of distress in response to an aversive stimulus directed at themselves (APH), and using methodology sufficiently sensitive to detect empathy-like responses previously, observer hens showed no behavioural or physiological responses to the mild distress of a familiar adult conspecific. The lack of behavioural and physiological response indicates that hens show no basis for emotional empathy in this context. PMID:22348100

The psychophysiology of parenting: Individual differences in autonomic reactivity to positive and negative mood inductions and observed parental affect during dyadic interactions with children.

PubMed

Connell, Arin M; Dawson, Glen C; Danzo, Sarah; McKillop, Hannah N

2017-02-01

Parenting is a complex activity driven, in part, by parental emotional and physiological responses. However, work examining the physiological underpinnings of parenting behavior is still in its infancy, and very few studies have examined such processes beyond early childhood. The current study examines associations between Autonomic Nervous System (ANS) indices of parents' physiological reactivity to positive and negative mood states and observed parental affect during a series of discussion tasks with their adolescent child. Respiratory Sinus Arrhythmia (RSA) was measured as an index of parasympathetic nervous system (PNS) activation while viewing film clips designed to induce neutral, sad, and amused mood states. Parental positive affect, anger, and distress were observed during a series of parent-child discussion tasks, which included an ambiguous discussion regarding adolescent growth, a conflict discussion, and a fun-activity planning discussion. Results supported the association between aspects of parental physiological reactivity and observed affect during dyadic interactions. Further, RSA interacted with maternal depression to predict observed positive affect, anger, and distress, although differences across tasks and specific emotions were found regarding the nature of the interaction effects. Overall, results suggest that such neurobiological processes may be particularly important predictors of parental behavior, particularly in at-risk populations. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

A BK (Slo1) channel journey from molecule to physiology

PubMed Central

Contreras, Gustavo F; Castillo, Karen; Enrique, Nicolás; Carrasquel-Ursulaez, Willy; Castillo, Juan Pablo; Milesi, Verónica; Neely, Alan; Alvarez, Osvaldo; Ferreira, Gonzalo; González, Carlos; Latorre, Ramón

2013-01-01

Calcium and voltage-activated potassium (BK) channels are key actors in cell physiology, both in neuronal and non-neuronal cells and tissues. Through negative feedback between intracellular Ca2+ and membrane voltage, BK channels provide a damping mechanism for excitatory signals. Molecular modulation of these channels by alternative splicing, auxiliary subunits and post-translational modifications showed that these channels are subjected to many mechanisms that add diversity to the BK channel α subunit gene. This complexity of interactions modulates BK channel gating, modifying the energetic barrier of voltage sensor domain activation and channel opening. Regions for voltage as well as Ca2+ sensitivity have been identified, and the crystal structure generated by the 2 RCK domains contained in the C-terminal of the channel has been described. The linkage of these channels to many intracellular metabolites and pathways, as well as their modulation by extracellular natural agents, has been found to be relevant in many physiological processes. This review includes the hallmarks of BK channel biophysics and its physiological impact on specific cells and tissues, highlighting its relationship with auxiliary subunit expression. PMID:24025517

Integrating Multimedia Instructional Design Principles with Complex Physiological Concepts in Reproductive Science

ERIC Educational Resources Information Center

Oki, Angela Christine

2011-01-01

This dissertation examines the effect of digital multimedia presentations as a method to teach complex concepts in reproductive physiology. The digital presentations developed for this research consisted of two-dimensional (2-D) and three-dimensional (3-D) animations, scriptmessaging and narration. The topics were "Mammalian Ovarian…

The cooperative economy of food: Implications for human life history and physiology.

PubMed

Kramer, Karen L

2018-04-06

The human diet has undergone substantial modifications since the emergence of modern humans and varies considerably in today's traditional societies. Despite these changes and cross-cultural differences, the human diet can be characterized by several common elements. These include diverse, high quality foods, technological complexity to acquire and process food, and the establishment of home bases for storage, processing and consumption. Together these aspects of the human diet challenge any one individual to independently meet all of his or her daily caloric needs. Humans solve this challenge through food sharing, labor exchange and the division of labor. The cooperative nature of the human diet is associated with many downstream effects on our life history and physiology. This paper overviews the constellation of traits that likely led to a cooperative economy of food, and draws on ethnographic examples to illustrate its effects on human life history and physiology. Two detailed examples using body composition, time allocation and food acquisition data show how cooperation among Savanna Pumé hunter-gatherers affects activity levels, sexual dimorphism in body fat, maturational pace and age at first birth. Copyright © 2018. Published by Elsevier Inc.

Nutritional Systems Biology Modeling: From Molecular Mechanisms to Physiology

PubMed Central

de Graaf, Albert A.; Freidig, Andreas P.; De Roos, Baukje; Jamshidi, Neema; Heinemann, Matthias; Rullmann, Johan A.C.; Hall, Kevin D.; Adiels, Martin; van Ommen, Ben

2009-01-01

The use of computational modeling and simulation has increased in many biological fields, but despite their potential these techniques are only marginally applied in nutritional sciences. Nevertheless, recent applications of modeling have been instrumental in answering important nutritional questions from the cellular up to the physiological levels. Capturing the complexity of today's important nutritional research questions poses a challenge for modeling to become truly integrative in the consideration and interpretation of experimental data at widely differing scales of space and time. In this review, we discuss a selection of available modeling approaches and applications relevant for nutrition. We then put these models into perspective by categorizing them according to their space and time domain. Through this categorization process, we identified a dearth of models that consider processes occurring between the microscopic and macroscopic scale. We propose a “middle-out” strategy to develop the required full-scale, multilevel computational models. Exhaustive and accurate phenotyping, the use of the virtual patient concept, and the development of biomarkers from “-omics” signatures are identified as key elements of a successful systems biology modeling approach in nutrition research—one that integrates physiological mechanisms and data at multiple space and time scales. PMID:19956660

Time-dependent regulation of morphological changes and cartilage differentiation markers in the mouse pubic symphysis during pregnancy and postpartum recovery.

PubMed

Castelucci, Bianca Gazieri; Consonni, Sílvio Roberto; Rosa, Viviane Souza; Sensiate, Lucimara Aparecida; Delatti, Paula Cristina Rugno; Alvares, Lúcia Elvira; Joazeiro, Paulo Pinto

2018-01-01

Animal models commonly serve as a bridge between in vitro experiments and clinical applications; however, few physiological processes in adult animals are sufficient to serve as proof-of-concept models for cartilage regeneration. Intriguingly, some rodents, such as young adult mice, undergo physiological connective tissue modifications to birth canal elements such as the pubic symphysis during pregnancy; therefore, we investigated whether the differential expression of cartilage differentiation markers is associated with cartilaginous tissue morphological modifications during these changes. Our results showed that osteochondral progenitor cells expressing Runx2, Sox9, Col2a1 and Dcx at the non-pregnant pubic symphysis proliferated and differentiated throughout pregnancy, giving rise to a complex osteoligamentous junction that attached the interpubic ligament to the pubic bones until labour occurred. After delivery, the recovery of pubic symphysis cartilaginous tissues was improved by the time-dependent expression of these chondrocytic lineage markers at the osteoligamentous junction. This process potentially recapitulates embryologic chondrocytic differentiation to successfully recover hyaline cartilaginous pads at 10 days postpartum. Therefore, we propose that this physiological phenomenon represents a proof-of-concept model for investigating the mechanisms involved in cartilage restoration in adult animals.

Novel type of red-shifted chlorophyll a antenna complex from Chromera velia. I. Physiological relevance and functional connection to photosystems.

PubMed

Kotabová, Eva; Jarešová, Jana; Kaňa, Radek; Sobotka, Roman; Bína, David; Prášil, Ondřej

2014-06-01

Chromera velia is an alveolate alga associated with scleractinian corals. Here we present detailed work on chromatic adaptation in C. velia cultured under either blue or red light. Growth of C. velia under red light induced the accumulation of a light harvesting antenna complex exhibiting unusual spectroscopic properties with red-shifted absorption and atypical 710nm fluorescence emission at room temperature. Due to these characteristic features the complex was designated "Red-shifted Chromera light harvesting complex" (Red-CLH complex). Its detailed biochemical survey is described in the accompanying paper (Bina et al. 2013, this issue). Here, we show that the accumulation of Red-CLH complex under red light represents a slow acclimation process (days) that is reversible with much faster kinetics (hours) under blue light. This chromatic adaptation allows C. velia to maintain all important parameters of photosynthesis constant under both light colors. We further demonstrated that the C. velia Red-CLH complex is assembled from a 17kDa antenna protein and is functionally connected to photosystem II as it shows variability of chlorophyll fluorescence. Red-CLH also serves as an additional locus for non-photochemical quenching. Although overall rates of oxygen evolution and carbon fixation were similar for both blue and red light conditions, the presence of Red-CLH in C. velia cells increases the light harvesting potential of photosystem II, which manifested as a doubled oxygen evolution rate at illumination above 695nm. This data demonstrates a remarkable long-term remodeling of C. velia light-harvesting system according to light quality and suggests physiological significance of 'red' antenna complexes. Copyright © 2014 Elsevier B.V. All rights reserved.

Experimental strategies to assess the biological ramifications of multiple drivers of global ocean change-A review.

PubMed

Boyd, Philip W; Collins, Sinead; Dupont, Sam; Fabricius, Katharina; Gattuso, Jean-Pierre; Havenhand, Jonathan; Hutchins, David A; Riebesell, Ulf; Rintoul, Max S; Vichi, Marcello; Biswas, Haimanti; Ciotti, Aurea; Gao, Kunshan; Gehlen, Marion; Hurd, Catriona L; Kurihara, Haruko; McGraw, Christina M; Navarro, Jorge M; Nilsson, Göran E; Passow, Uta; Pörtner, Hans-Otto

2018-06-01

Marine life is controlled by multiple physical and chemical drivers and by diverse ecological processes. Many of these oceanic properties are being altered by climate change and other anthropogenic pressures. Hence, identifying the influences of multifaceted ocean change, from local to global scales, is a complex task. To guide policy-making and make projections of the future of the marine biosphere, it is essential to understand biological responses at physiological, evolutionary and ecological levels. Here, we contrast and compare different approaches to multiple driver experiments that aim to elucidate biological responses to a complex matrix of ocean global change. We present the benefits and the challenges of each approach with a focus on marine research, and guidelines to navigate through these different categories to help identify strategies that might best address research questions in fundamental physiology, experimental evolutionary biology and community ecology. Our review reveals that the field of multiple driver research is being pulled in complementary directions: the need for reductionist approaches to obtain process-oriented, mechanistic understanding and a requirement to quantify responses to projected future scenarios of ocean change. We conclude the review with recommendations on how best to align different experimental approaches to contribute fundamental information needed for science-based policy formulation. © 2018 John Wiley & Sons Ltd.

Caudal autotomy and regeneration in lizards.

PubMed

Clause, Amanda R; Capaldi, Elizabeth A

2006-12-01

Caudal autotomy, or the voluntary self-amputation of the tail, is an anti-predation strategy in lizards that depends on a complex array of environmental, individual, and species-specific characteristics. These factors affect both when and how often caudal autotomy is employed, as well as its overall rate of success. The potential costs of autotomy must be weighed against the benefits of this strategy. Many species have evolved specialized behavioral and physiological adaptations to minimize or compensate for any negative consequences. One of the most important steps following a successful autotomous escape involves regeneration of the lost limb. In some species, regeneration occurs rapidly; such swift regeneration illustrates the importance of an intact, functional tail in everyday experience. In lizards and other vertebrates, regeneration is a highly ordered process utilizing initial developmental programs as well as regeneration-specific mechanisms to produce the correct types and pattern of cells required to sufficiently restore the structure and function of the sacrificed tail. In this review, we discuss the behavioral and physiological features of self-amputation, with particular reference to the costs and benefits of autotomy and the basic mechanisms of regeneration. In the process, we identify how these behaviors could be used to explore the neural regulation of complex behavioral responses within a functional context. Copyright 2006 Wiley-Liss, Inc.

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

Variations in cell morphology in the canine cruciate ligament complex.

PubMed

Smith, K D; Vaughan-Thomas, A; Spiller, D G; Clegg, P D; Innes, J F; Comerford, E J

2012-08-01

Cell morphology may reflect the mechanical environment of tissues and influence tissue physiology and response to injury. Normal cruciate ligaments (CLs) from disease-free stifle joints were harvested from dog breeds with a high (Labrador retriever) and low (Greyhound) risk of cranial cruciate ligament (CCL) rupture. Antibodies against the cytoskeletal components vimentin and alpha tubulin were used to analyse cell morphology; nuclei were stained with 4',6-diamidino-2-phenylindole, and images were collected using conventional and confocal microscopy. Both cranial and caudal CLs contained cells of heterogenous morphologies. Cells were arranged between collagen bundles and frequently had cytoplasmic processes. Some of these processes were long (type A cells), others were shorter, thicker and more branched (type B cells), and some had no processes (type C cells). Processes were frequently shown to contact other cells, extending longitudinally and transversely through the CLs. Cells with longer processes had fusiform nuclei, and those with no processes had rounded nuclei and were more frequent in the mid-substance of both CLs. Cells with long processes were more commonly noted in the CLs of the Greyhound. As contact between cells may facilitate direct communication, variances in cell morphology between breeds at a differing risk of CCL rupture may reflect differences in CL physiology. Copyright © 2012 Elsevier Ltd. All rights reserved.

Decreased cerebellar-cerebral connectivity contributes to complex task performance

PubMed Central

Knops, André

2016-01-01

The cerebellum's role in nonmotor processes is now well accepted, but cerebellar interaction with cerebral targets is not well understood. Complex cognitive tasks activate cerebellar, parietal, and frontal regions, but the effective connectivity between these regions has never been tested. To this end, we used psycho-physiological interactions (PPI) analysis to test connectivity changes of cerebellar and parietal seed regions in complex (2-digit by 1-digit multiplication, e.g., 12 × 3) vs. simple (1-digit by 1-digit multiplication, e.g., 4 × 3) task conditions (“complex − simple”). For cerebellar seed regions (lobule VI, hemisphere and vermis), we found significantly decreased cerebellar-parietal, cerebellar-cingulate, and cerebellar-frontal connectivity in complex multiplication. For parietal seed regions (PFcm, PFop, PFm) we found significantly increased parietal-parietal and parietal-frontal connectivity in complex multiplication. These results suggest that decreased cerebellar-cerebral connectivity contributes to complex task performance. Interestingly, BOLD activity contrasts revealed partially overlapping parietal areas of increased BOLD activity but decreased cerebellar-parietal PPI connectivity. PMID:27334957

Second Generation Crop Yield Models Review

NASA Technical Reports Server (NTRS)

Hodges, T. (Principal Investigator)

1982-01-01

Second generation yield models, including crop growth simulation models and plant process models, may be suitable for large area crop yield forecasting in the yield model development project. Subjective and objective criteria for model selection are defined and models which might be selected are reviewed. Models may be selected to provide submodels as input to other models; for further development and testing; or for immediate testing as forecasting tools. A plant process model may range in complexity from several dozen submodels simulating (1) energy, carbohydrates, and minerals; (2) change in biomass of various organs; and (3) initiation and development of plant organs, to a few submodels simulating key physiological processes. The most complex models cannot be used directly in large area forecasting but may provide submodels which can be simplified for inclusion into simpler plant process models. Both published and unpublished models which may be used for development or testing are reviewed. Several other models, currently under development, may become available at a later date.

Towards understanding the complexity of cardiovascular oscillations: Insights from information theory.

PubMed

Javorka, Michal; Krohova, Jana; Czippelova, Barbora; Turianikova, Zuzana; Lazarova, Zuzana; Wiszt, Radovan; Faes, Luca

2018-07-01

Cardiovascular complexity is a feature of healthy physiological regulation, which stems from the simultaneous activity of several cardiovascular reflexes and other non-reflex physiological mechanisms. It is manifested in the rich dynamics characterizing the spontaneous heart rate and blood pressure variability (HRV and BPV). The present study faces the challenge of disclosing the origin of short-term HRV and BPV from the statistical perspective offered by information theory. To dissect the physiological mechanisms giving rise to cardiovascular complexity in different conditions, measures of predictive information, information storage, information transfer and information modification were applied to the beat-to-beat variability of heart period (HP), systolic arterial pressure (SAP) and respiratory volume signal recorded non-invasively in 61 healthy young subjects at supine rest and during head-up tilt (HUT) and mental arithmetics (MA). Information decomposition enabled to assess simultaneously several expected and newly inferred physiological phenomena, including: (i) the decreased complexity of HP during HUT and the increased complexity of SAP during MA; (ii) the suppressed cardiorespiratory information transfer, related to weakened respiratory sinus arrhythmia, under both challenges; (iii) the altered balance of the information transferred along the two arms of the cardiovascular loop during HUT, with larger baroreflex involvement and smaller feedforward mechanical effects; and (iv) an increased importance of direct respiratory effects on SAP during HUT, and on both HP and SAP during MA. We demonstrate that a decomposition of the information contained in cardiovascular oscillations can reveal subtle changes in system dynamics and improve our understanding of the complexity changes during physiological challenges. Copyright © 2018. Published by Elsevier Ltd.

Functional analysis of neuronal microRNAs in Caenorhabditis elegans dauer formation by combinational genetics and Neuronal miRISC immunoprecipitation.

PubMed

Than, Minh T; Kudlow, Brian A; Han, Min

2013-06-01

Identifying the physiological functions of microRNAs (miRNAs) is often challenging because miRNAs commonly impact gene expression under specific physiological conditions through complex miRNA::mRNA interaction networks and in coordination with other means of gene regulation, such as transcriptional regulation and protein degradation. Such complexity creates difficulties in dissecting miRNA functions through traditional genetic methods using individual miRNA mutations. To investigate the physiological functions of miRNAs in neurons, we combined a genetic "enhancer" approach complemented by biochemical analysis of neuronal miRNA-induced silencing complexes (miRISCs) in C. elegans. Total miRNA function can be compromised by mutating one of the two GW182 proteins (AIN-1), an important component of miRISC. We found that combining an ain-1 mutation with a mutation in unc-3, a neuronal transcription factor, resulted in an inappropriate entrance into the stress-induced, alternative larval stage known as dauer, indicating a role of miRNAs in preventing aberrant dauer formation. Analysis of this genetic interaction suggests that neuronal miRNAs perform such a role partly by regulating endogenous cyclic guanosine monophosphate (cGMP) signaling, potentially influencing two other dauer-regulating pathways. Through tissue-specific immunoprecipitations of miRISC, we identified miRNAs and their likely target mRNAs within neuronal tissue. We verified the biological relevance of several of these miRNAs and found that many miRNAs likely regulate dauer formation through multiple dauer-related targets. Further analysis of target mRNAs suggests potential miRNA involvement in various neuronal processes, but the importance of these miRNA::mRNA interactions remains unclear. Finally, we found that neuronal genes may be more highly regulated by miRNAs than intestinal genes. Overall, our study identifies miRNAs and their targets, and a physiological function of these miRNAs in neurons. It also suggests that compromising other aspects of gene expression, along with miRISC, can be an effective approach to reveal miRNA functions in specific tissues under specific physiological conditions.

Dynamics of Marine Microbial Metabolism and Physiology at Station ALOHA

NASA Astrophysics Data System (ADS)

Casey, John R.

Marine microbial communities influence global biogeochemical cycles by coupling the transduction of free energy to the transformation of Earth's essential bio-elements: H, C, N, O, P, and S. The web of interactions between these processes is extraordinarily complex, though fundamental physical and thermodynamic principles should describe its dynamics. In this collection of 5 studies, aspects of the complexity of marine microbial metabolism and physiology were investigated as they interact with biogeochemical cycles and direct the flow of energy within the Station ALOHA surface layer microbial community. In Chapter 1, and at the broadest level of complexity discussed, a method to relate cell size to metabolic activity was developed to evaluate allometric power laws at fine scales within picoplankton populations. Although size was predictive of metabolic rates, within-population power laws deviated from the broader size spectrum, suggesting metabolic diversity as a key determinant of microbial activity. In Chapter 2, a set of guidelines was proposed by which organic substrates are selected and utilized by the heterotrophic community based on their nitrogen content, carbon content, and energy content. A hierarchical experimental design suggested that the heterotrophic microbial community prefers high nitrogen content but low energy density substrates, while carbon content was not important. In Chapter 3, a closer look at the light-dependent dynamics of growth on a single organic substrate, glycolate, suggested that growth yields were improved by photoheterotrophy. The remaining chapters were based on the development of a genome-scale metabolic network reconstruction of the cyanobacterium Prochlorococcus to probe its metabolic capabilities and quantify metabolic fluxes. Findings described in Chapter 4 pointed to evolution of the Prochlorococcus metabolic network to optimize growth at low phosphate concentrations. Finally, in Chapter 5 and at the finest scale of complexity, a method was developed to predict hourly changes in both physiology and metabolic fluxes in Prochlorococcus by incorporating gene expression time-series data within the metabolic network model. Growth rates predicted by this method more closely matched experimental data, and diel changes in elemental composition and the energy content of biomass were predicted. Collectively, these studies identify and quantify the potential impact of variations in metabolic and physiological traits on the melee of microbial community interactions.

Light and Cognition: Roles for Circadian Rhythms, Sleep, and Arousal

PubMed Central

Fisk, Angus S.; Tam, Shu K. E.; Brown, Laurence A.; Vyazovskiy, Vladyslav V.; Bannerman, David M.; Peirson, Stuart N.

2018-01-01

Light exerts a wide range of effects on mammalian physiology and behavior. As well as synchronizing circadian rhythms to the external environment, light has been shown to modulate autonomic and neuroendocrine responses as well as regulating sleep and influencing cognitive processes such as attention, arousal, and performance. The last two decades have seen major advances in our understanding of the retinal photoreceptors that mediate these non-image forming responses to light, as well as the neural pathways and molecular mechanisms by which circadian rhythms are generated and entrained to the external light/dark (LD) cycle. By contrast, our understanding of the mechanisms by which lighting influences cognitive processes is more equivocal. The effects of light on different cognitive processes are complex. As well as the direct effects of light on alertness, indirect effects may also occur due to disrupted circadian entrainment. Despite the widespread use of disrupted LD cycles to study the role circadian rhythms on cognition, the different experimental protocols used have subtly different effects on circadian function which are not always comparable. Moreover, these protocols will also disrupt sleep and alter physiological arousal, both of which are known to modulate cognition. Studies have used different assays that are dependent on different cognitive and sensory processes, which may also contribute to their variable findings. Here, we propose that studies addressing the effects of different lighting conditions on cognitive processes must also account for their effects on circadian rhythms, sleep, and arousal if we are to fully understand the physiological basis of these responses. PMID:29479335

An instructional design process based on expert knowledge for teaching students how mechanisms are explained.

PubMed

Trujillo, Caleb M; Anderson, Trevor R; Pelaez, Nancy J

2016-06-01

In biology and physiology courses, students face many difficulties when learning to explain mechanisms, a topic that is demanding due to the immense complexity and abstract nature of molecular and cellular mechanisms. To overcome these difficulties, we asked the following question: how does an instructor transform their understanding of biological mechanisms and other difficult-to-learn topics so that students can comprehend them? To address this question, we first reviewed a model of the components used by biologists to explain molecular and cellular mechanisms: the MACH model, with the components of methods (M), analogies (A), context (C), and how (H). Next, instructional materials were developed and the teaching activities were piloted with a physical MACH model. Students who used the MACH model to guide their explanations of mechanisms exhibited both improvements and some new difficulties. Third, a series of design-based research cycles was applied to bring the activities with an improved physical MACH model into biology and biochemistry courses. Finally, a useful rubric was developed to address prevalent student difficulties. Here, we present, for physiology and biology instructors, the knowledge and resources for explaining molecular and cellular mechanisms in undergraduate courses with an instructional design process aimed at realizing pedagogical content knowledge for teaching. Our four-stage process could be adapted to advance instruction with a range of models in the life sciences. Copyright © 2016 The American Physiological Society.

Hemispheric asymmetry in new neurons in adulthood is associated with vocal learning and auditory memory.

PubMed

Tsoi, Shuk C; Aiya, Utsav V; Wasner, Kobi D; Phan, Mimi L; Pytte, Carolyn L; Vicario, David S

2014-01-01

Many brain regions exhibit lateral differences in structure and function, and also incorporate new neurons in adulthood, thought to function in learning and in the formation of new memories. However, the contribution of new neurons to hemispheric differences in processing is unknown. The present study combines cellular, behavioral, and physiological methods to address whether 1) new neuron incorporation differs between the brain hemispheres, and 2) the degree to which hemispheric lateralization of new neurons correlates with behavioral and physiological measures of learning and memory. The songbird provides a model system for assessing the contribution of new neurons to hemispheric specialization because songbird brain areas for vocal processing are functionally lateralized and receive a continuous influx of new neurons in adulthood. In adult male zebra finches, we quantified new neurons in the caudomedial nidopallium (NCM), a forebrain area involved in discrimination and memory for the complex vocalizations of individual conspecifics. We assessed song learning and recorded neural responses to song in NCM. We found significantly more new neurons labeled in left than in right NCM; moreover, the degree of asymmetry in new neuron numbers was correlated with the quality of song learning and strength of neuronal memory for recently heard songs. In birds with experimentally impaired song quality, the hemispheric difference in new neurons was diminished. These results suggest that new neurons may contribute to an allocation of function between the hemispheres that underlies the learning and processing of complex signals.

Hemispheric Asymmetry in New Neurons in Adulthood Is Associated with Vocal Learning and Auditory Memory

PubMed Central

Wasner, Kobi D.; Phan, Mimi L.; Pytte, Carolyn L.; Vicario, David S.

2014-01-01

Many brain regions exhibit lateral differences in structure and function, and also incorporate new neurons in adulthood, thought to function in learning and in the formation of new memories. However, the contribution of new neurons to hemispheric differences in processing is unknown. The present study combines cellular, behavioral, and physiological methods to address whether 1) new neuron incorporation differs between the brain hemispheres, and 2) the degree to which hemispheric lateralization of new neurons correlates with behavioral and physiological measures of learning and memory. The songbird provides a model system for assessing the contribution of new neurons to hemispheric specialization because songbird brain areas for vocal processing are functionally lateralized and receive a continuous influx of new neurons in adulthood. In adult male zebra finches, we quantified new neurons in the caudomedial nidopallium (NCM), a forebrain area involved in discrimination and memory for the complex vocalizations of individual conspecifics. We assessed song learning and recorded neural responses to song in NCM. We found significantly more new neurons labeled in left than in right NCM; moreover, the degree of asymmetry in new neuron numbers was correlated with the quality of song learning and strength of neuronal memory for recently heard songs. In birds with experimentally impaired song quality, the hemispheric difference in new neurons was diminished. These results suggest that new neurons may contribute to an allocation of function between the hemispheres that underlies the learning and processing of complex signals. PMID:25251077

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

PubMed

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

2012-08-03

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

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

PubMed Central

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

2012-01-01

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

Implications of the stability behavior of zinc oxide nanoparticles for toxicological studies

NASA Astrophysics Data System (ADS)

Meißner, Tobias; Oelschlägel, Kathrin; Potthoff, Annegret

2014-08-01

The increasing use of zinc oxide (ZnO) nanoparticles in sunscreens and other cosmetic products demands a risk assessment that has to be done in toxicological studies. Such investigations require profound knowledge of the behavior of ZnO in cell culture media. The current study was performed to get well-dispersed suspensions of a hydrophilic (ZnO-hydro) and a lipophilic coated (ZnO-lipo) ZnO nanomaterial for use in in vitro tests. Therefore, systematic tests were carried out with common dispersants (phosphate, lecithin, proteins) to elucidate chemical and physical changes of ZnO nanoparticles in water and physiological solutions (PBS, DMEM). Non-physiological stock suspensions were prepared using ultrasonication. Time-dependent changes of pH, conductivity, zeta potential, particle size and dissolution were recorded. Secondly, the stock suspensions were added to physiological media with or without albumin (BSA) or serum (FBS), to examine characteristics such as agglomeration and dissolution. Stable stock suspensions were obtained using phosphate as natural and physiological electrostatic stabilizing agent. Lecithin proved to be an effective wetting agent for ZnO-lipo. Although the particle size remained constant, the suspension changed over time. The pH increased as a result of ZnO dissolution and formation of zinc phosphate complexes. The behavior of ZnO in physiological media was found to depend strongly on the additives used. Applying only phosphate as additive, ZnO-hydro agglomerated within minutes. In the presence of lecithin or BSA/serum, agglomeration was inhibited. ZnO dissolution was higher under physiological conditions than in the stock suspension. Serum especially promoted this process. Using body-related dispersants (phosphate, lecithin) non-agglomerating stock suspensions of hydrophilic and lipophilic ZnO were prepared as a prerequisite to perform meaningful toxicological investigation. Both nanomaterials showed a non-negligible dissolution behavior that strongly depended on the surrounding conditions. Agglomeration of ZnO particles in physiological media is a complex function of particle coating, used dispersants and serum proteins if supplemented. The present study gives a clear guideline how to prepare and handle suspensions with ZnO for in vitro testing and allows the correlation between the chemical-physical particles behavior with findings from toxicological tests.

Glutathione-complexed [2Fe-2S] clusters function in Fe-S cluster storage and trafficking.

PubMed

Fidai, Insiya; Wachnowsky, Christine; Cowan, J A

2016-10-01

Glutathione-coordinated [2Fe-2S] complex is a non-protein-bound [2Fe-2S] cluster that is capable of reconstituting the human iron-sulfur cluster scaffold protein IscU. This complex demonstrates physiologically relevant solution chemistry and is a viable substrate for iron-sulfur cluster transport by Atm1p exporter protein. Herein, we report on some of the possible functional and physiological roles for this novel [2Fe-2S](GS4) complex in iron-sulfur cluster biosynthesis and quantitatively characterize its role in the broader network of Fe-S cluster transfer reactions. UV-vis and circular dichroism spectroscopy have been used in kinetic studies to determine second-order rate constants for [2Fe-2S] cluster transfer from [2Fe-2S](GS4) complex to acceptor proteins, such as human IscU, Schizosaccharomyces pombe Isa1, human and yeast glutaredoxins (human Grx2 and Saccharomyces cerevisiae Grx3), and human ferredoxins. Second-order rate constants for cluster extraction from these holo proteins were also determined by varying the concentration of glutathione, and a likely common mechanism for cluster uptake was determined by kinetic analysis. The results indicate that the [2Fe-2S](GS4) complex is stable under physiological conditions, and demonstrates reversible cluster exchange with a wide range of Fe-S cluster proteins, thereby supporting a possible physiological role for such centers.

The Systemic Control of Growth

PubMed Central

Boulan, Laura; Milán, Marco; Léopold, Pierre

2015-01-01

Growth is a complex process that is intimately linked to the developmental program to form adults with proper size and proportions. Genetics is an important determinant of growth, as exemplified by the role of local diffusible molecules setting up organ proportions. In addition, organisms use adaptive responses allowing modulating the size of individuals according to environmental cues, for example, nutrition. Here, we describe some of the physiological principles participating in the determination of final individual size. PMID:26261282

What develops during emotional development? A component process approach to identifying sources of psychopathology risk in adolescence

PubMed Central

McLaughlin, Katie A.; Garrad, Megan C.; Somerville, Leah H.

2015-01-01

Adolescence is a phase of the lifespan associated with widespread changes in emotional behavior thought to reflect both changing environments and stressors, and psychological and neurobiological development. However, emotions themselves are complex phenomena that are composed of multiple subprocesses. In this paper, we argue that examining emotional development from a process-level perspective facilitates important insights into the mechanisms that underlie adolescents' shifting emotions and intensified risk for psychopathology. Contrasting the developmental progressions for the antecedents to emotion, physiological reactivity to emotion, emotional regulation capacity, and motivation to experience particular affective states reveals complex trajectories that intersect in a unique way during adolescence. We consider the implications of these intersecting trajectories for negative outcomes such as psychopathology, as well as positive outcomes for adolescent social bonds. PMID:26869841

Complex and differential glial responses in Alzheimer's disease and ageing.

PubMed

Rodríguez, José J; Butt, Arthur M; Gardenal, Emanuela; Parpura, Vladimir; Verkhratsky, Alexei

2016-01-01

Glial cells and their association with neurones are fundamental for brain function. The emergence of complex neurone-glial networks assures rapid information transfer, creating a sophisticated circuitry where both types of neural cells work in concert, serving different activities. All glial cells, represented by astrocytes, oligodendrocytes, microglia and NG2-glia, are essential for brain homeostasis and defence. Thus, glia are key not only for normal central nervous system (CNS) function, but also to its dysfunction, being directly associated with all forms of neuropathological processes. Therefore, the progression and outcome of neurological and neurodegenerative diseases depend on glial reactions. In this review, we provide a concise account of recent data obtained from both human material and animal models demonstrating the pathological involvement of glia in neurodegenerative processes, including Alzheimer's disease (AD), as well as physiological ageing.

Measures of complexity in signal analysis

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

Kurths, J.; Schwarz, U.; Witt, A.

Observational data of natural systems, as measured in astrophysical, geophysical or physiological experiments are typically quite different from those obtained in laboratories. Due to the peculiarities with these data, well-known characteristics processes, such as periodicities or fractal dimension, often do not provide a suitable description. To study such data, we present here the use of measures of complexity, which are mainly basing on symbolic dynamics. We distinguish two types of such quantities: traditional measures (e.g. algorithmic complexity) which are measures of randomness and alternative measures (e.g. {epsilon}-complexity) which relate highest complexity to some critical points. It is important to notemore » that there is no optimum measure of complexity. Its choice should depend on the context. Mostly, a combination of some such quantities is appropriate. Applying this concept to three examples in astrophysics, cardiology and cognitive psychology, we show that it can be helpful also in cases where other tools of data analysis fail. {copyright} {ital 1996 American Institute of Physics.}« less

Effect of shoulder model complexity in upper-body kinematics analysis of the golf swing.

PubMed

Bourgain, M; Hybois, S; Thoreux, P; Rouillon, O; Rouch, P; Sauret, C

2018-06-25

The golf swing is a complex full body movement during which the spine and shoulders are highly involved. In order to determine shoulder kinematics during this movement, multibody kinematics optimization (MKO) can be recommended to limit the effect of the soft tissue artifact and to avoid joint dislocations or bone penetration in reconstructed kinematics. Classically, in golf biomechanics research, the shoulder is represented by a 3 degrees-of-freedom model representing the glenohumeral joint. More complex and physiological models are already provided in the scientific literature. Particularly, the model used in this study was a full body model and also described motions of clavicles and scapulae. This study aimed at quantifying the effect of utilizing a more complex and physiological shoulder model when studying the golf swing. Results obtained on 20 golfers showed that a more complex and physiologically-accurate model can more efficiently track experimental markers, which resulted in differences in joint kinematics. Hence, the model with 3 degrees-of-freedom between the humerus and the thorax may be inadequate when combined with MKO and a more physiological model would be beneficial. Finally, results would also be improved through a subject-specific approach for the determination of the segment lengths. Copyright © 2018 Elsevier Ltd. All rights reserved.

Outlier-resilient complexity analysis of heartbeat dynamics

NASA Astrophysics Data System (ADS)

Lo, Men-Tzung; Chang, Yi-Chung; Lin, Chen; Young, Hsu-Wen Vincent; Lin, Yen-Hung; Ho, Yi-Lwun; Peng, Chung-Kang; Hu, Kun

2015-03-01

Complexity in physiological outputs is believed to be a hallmark of healthy physiological control. How to accurately quantify the degree of complexity in physiological signals with outliers remains a major barrier for translating this novel concept of nonlinear dynamic theory to clinical practice. Here we propose a new approach to estimate the complexity in a signal by analyzing the irregularity of the sign time series of its coarse-grained time series at different time scales. Using surrogate data, we show that the method can reliably assess the complexity in noisy data while being highly resilient to outliers. We further apply this method to the analysis of human heartbeat recordings. Without removing any outliers due to ectopic beats, the method is able to detect a degradation of cardiac control in patients with congestive heart failure and a more degradation in critically ill patients whose life continuation relies on extracorporeal membrane oxygenator (ECMO). Moreover, the derived complexity measures can predict the mortality of ECMO patients. These results indicate that the proposed method may serve as a promising tool for monitoring cardiac function of patients in clinical settings.

Towards engineering of hormonal crosstalk in plant immunity.

PubMed

Shigenaga, Alexandra M; Berens, Matthias L; Tsuda, Kenichi; Argueso, Cristiana T

2017-08-01

Plant hormones regulate physiological responses in plants, including responses to pathogens and beneficial microbes. The last decades have provided a vast amount of evidence about the contribution of different plant hormones to plant immunity, and also of how they cooperate to orchestrate immunity activation, in a process known as hormone crosstalk. In this review we highlight the complexity of hormonal crosstalk in immunity and approaches currently being used to further understand this process, as well as perspectives to engineer hormone crosstalk for enhanced pathogen resistance and overall plant fitness. Copyright © 2017 Elsevier Ltd. All rights reserved.

Wireless sleep measurement: sensing sleep and breathing patterns using radio-frequency sensors.

PubMed

Heneghan, Conor

2014-01-01

Despite the fact that we spend nearly one third of our lives asleep, surprisingly little was known about sleep until the 20th century. Now, sleep medicine is firmly established as a significant branch of medical practice, taking its roots strongly from the work of Nathaniel Kleitman and colleagues at the University of Chicago in the 1950s. They were the first to show the existence of rapid eye movement (REM) sleep?commonly associated with ?dreaming?and began the process of opening our eyes to the complex physiological processes that occur during sleep.

On the analysis of complex biological supply chains: From Process Systems Engineering to Quantitative Systems Pharmacology.

PubMed

Rao, Rohit T; Scherholz, Megerle L; Hartmanshenn, Clara; Bae, Seul-A; Androulakis, Ioannis P

2017-12-05

The use of models in biology has become particularly relevant as it enables investigators to develop a mechanistic framework for understanding the operating principles of living systems as well as in quantitatively predicting their response to both pathological perturbations and pharmacological interventions. This application has resulted in a synergistic convergence of systems biology and pharmacokinetic-pharmacodynamic modeling techniques that has led to the emergence of quantitative systems pharmacology (QSP). In this review, we discuss how the foundational principles of chemical process systems engineering inform the progressive development of more physiologically-based systems biology models.

A systems approach to physiologic evolution: From micelles to consciousness.

PubMed

Torday, John S; Miller, William B

2018-01-01

A systems approach to evolutionary biology offers the promise of an improved understanding of the fundamental principles of life through the effective integration of many biologic disciplines. It is presented that any critical integrative approach to evolutionary development involves a paradigmatic shift in perspective, more than just the engagement of a large number of disciplines. Critical to this differing viewpoint is the recognition that all biological processes originate from the unicellular state and remain permanently anchored to that phase throughout evolutionary development despite their macroscopic appearances. Multicellular eukaryotic development can, therefore, be viewed as a series of connected responses to epiphenomena that proceeds from that base in continuous iterative maintenance of collective cellular homeostatic equipoise juxtaposed against an ever-changing and challenging environment. By following this trajectory of multicellular eukaryotic evolution from within unicellular First Principles of Physiology forward, the mechanistic nature of complex physiology can be identified through a step-wise analysis of a continuous arc of vertebrate evolution based upon serial exaptations. © 2017 Wiley Periodicals, Inc.

Direct spectrophotometric measurement of supra-physiological levels of ascorbate in plasma.

PubMed

Witmer, Jordan R; Wetherell, Bailey J; Wagner, Brett A; Du, Juan; Cullen, Joseph J; Buettner, Garry R

2016-08-01

Supra-physiological concentrations of ascorbate, vitamin C, in blood, greater than 1mM, achieved through intravenous administration (IV), are being tested in clinical trials to treat human disease, e.g. cancer. These trials need information on the high levels of ascorbate achieved in blood upon IV administration of pharmacological ascorbate so appropriate clinical decisions can be made. Here we demonstrate that in the complex matrix of human blood plasma supra-physiological levels of ascorbate can be quantified by direct UV spectroscopy with use of a microvolume UV-vis spectrophotometer. Direct quantitation of ascorbate in plasma in the range of 2.9mM, lower limit of detection, up to at least 35mM can be achieved without any sample processing, other than centrifugation. This approach is rapid, economical, and can be used to quantify supraphysiological blood levels of ascorbate associated with the use of IV administration of pharmacological ascorbate to treat disease. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

The role of TREX in gene expression and disease

PubMed Central

Heath, Catherine G.; Viphakone, Nicolas; Wilson, Stuart A.

2016-01-01

TRanscription and EXport (TREX) is a conserved multisubunit complex essential for embryogenesis, organogenesis and cellular differentiation throughout life. By linking transcription, mRNA processing and export together, it exerts a physiologically vital role in the gene expression pathway. In addition, this complex prevents DNA damage and regulates the cell cycle by ensuring optimal gene expression. As the extent of TREX activity in viral infections, amyotrophic lateral sclerosis and cancer emerges, the need for a greater understanding of TREX function becomes evident. A complete elucidation of the composition, function and interactions of the complex will provide the framework for understanding the molecular basis for a variety of diseases. This review details the known composition of TREX, how it is regulated and its cellular functions with an emphasis on mammalian systems. PMID:27679854

Physiology and biochemistry of honey bees

USDA-ARS?s Scientific Manuscript database

Despite their tremendous economic importance, honey bees are not a typical model system for studying general questions of insect physiology. This is primarily due to the fact that honey bees live in complex social settings which impact their physiological and biochemical characteristics. Not surpris...

Structural and dynamic determinants of ligand binding and regulation of cyclin-dependent kinase 5 by pathological activator p25 and inhibitory peptide CIP.

PubMed

Cardone, A; Hassan, S A; Albers, R W; Sriram, R D; Pant, H C

2010-08-20

The crystal structure of the cdk5/p25 complex has provided information on possible molecular mechanisms of the ligand binding, specificity, and regulation of the kinase. Comparative molecular dynamics simulations are reported here for physiological conditions. This study provides new insight on the mechanisms that modulate such processes, which may be exploited to control pathological activation by p25. The structural changes observed in the kinase are stabilized by a network of interactions involving highly conserved residues within the cyclin-dependent kinase (cdk) family. Collective motions of the proteins (cdk5, p25, and CIP) and their complexes are identified by principal component analysis, revealing two conformational states of the activation loop upon p25 complexation, which are absent in the uncomplexed kinase and not apparent from the crystal. Simulations of the uncomplexed inhibitor CIP show structural rearrangements and increased flexibility of the interfacial loop containing the critical residue E240, which becomes fully hydrated and available for interactions with one of several positively charged residues in the kinase. These changes provide a rationale for the observed high affinity and enhanced inhibitory action of CIP when compared to either p25 or the physiological activators of cdk5. Published by Elsevier Ltd.

Integrated Physiological, Proteomic, and Metabolomic Analysis of Ultra Violet (UV) Stress Responses and Adaptation Mechanisms in Pinus radiata*

PubMed Central

Pascual, Jesús; Cañal, María Jesús; Escandón, Mónica; Meijón, Mónica; Weckwerth, Wolfram

2017-01-01

Globally expected changes in environmental conditions, especially the increase of UV irradiation, necessitate extending our knowledge of the mechanisms mediating tree species adaptation to this stress. This is crucial for designing new strategies to maintain future forest productivity. Studies focused on environmentally realistic dosages of UV irradiation in forest species are scarce. Pinus spp. are commercially relevant trees and not much is known about their adaptation to UV. In this work, UV treatment and recovery of Pinus radiata plants with dosages mimicking future scenarios, based on current models of UV radiation, were performed in a time-dependent manner. The combined metabolome and proteome analysis were complemented with measurements of + physiological parameters and gene expression. Sparse PLS analysis revealed complex molecular interaction networks of molecular and physiological data. Early responses prevented phototoxicity by reducing photosystem activity and the electron transfer chain together with the accumulation of photoprotectors and photorespiration. Apart from the reduction in photosynthesis as consequence of the direct UV damage on the photosystems, the primary metabolism was rearranged to deal with the oxidative stress while minimizing ROS production. New protein kinases and proteases related to signaling, coordination, and regulation of UV stress responses were revealed. All these processes demonstrate a complex molecular interaction network extending the current knowledge on UV-stress adaptation in pine. PMID:28096192

A molecular signaling approach to linking intraspecific variation and macro-evolutionary patterns.

PubMed

Swanson, Eli M; Snell-Rood, Emilie C

2014-11-01

Macro-evolutionary comparisons are a valued tool in evolutionary biology. Nevertheless, our understanding of how systems involved in molecular signaling change in concert with phenotypic diversification has lagged. We argue that integrating our understanding of the evolution of molecular signaling systems with phylogenetic comparative methods is an important step toward understanding the processes linking variation among individuals with variation among species. Focusing mostly on the endocrine system, we discuss how the complexity and mechanistic nature of molecular signaling systems may influence the application and interpretation of macro-evolutionary comparisons. We also detail five hypotheses concerning the role that physiological mechanisms can play in shaping macro-evolutionary patterns, and discuss ways in which these hypotheses could influence phenotypic diversification. Finally, we review a series of tools able to analyze the complexity of physiological systems and the way they change in concert with the phenotypes for which they coordinate development. © The Author 2014. Published by Oxford University Press on behalf of the Society for Integrative and Comparative Biology. All rights reserved. For permissions please email: journals.permissions@oup.com.

Structural plasticity and dynamic selectivity of acid-sensing ion channel-spider toxin complexes

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

Baconguis, Isabelle; Gouaux, Eric

2012-07-29

Acid-sensing ion channels (ASICs) are voltage-independent, amiloride-sensitive channels involved in diverse physiological processes ranging from nociception to taste. Despite the importance of ASICs in physiology, we know little about the mechanism of channel activation. Here we show that psalmotoxin activates non-selective and Na +-selective currents in chicken ASIC1a at pH7.25 and 5.5, respectively. Crystal structures of ASIC1a–psalmotoxin complexes map the toxin binding site to the extracellular domain and show how toxin binding triggers an expansion of the extracellular vestibule and stabilization of the open channel pore. At pH7.25 the pore is approximately 10Å in diameter, whereas at pH5.5 the poremore » is largely hydrophobic and elliptical in cross-section with dimensions of approximately 5 by 7Å, consistent with a barrier mechanism for ion selectivity. These studies define mechanisms for activation of ASICs, illuminate the basis for dynamic ion selectivity and provide the blueprints for new therapeutic agents.« less

Understanding immunology via engineering design: the role of mathematical prototyping.

PubMed

Klinke, David J; Wang, Qing

2012-01-01

A major challenge in immunology is how to translate data into knowledge given the inherent complexity and dynamics of human physiology. Both the physiology and engineering communities have rich histories in applying computational approaches to translate data obtained from complex systems into knowledge of system behavior. However, there are some differences in how disciplines approach problems. By referring to mathematical models as mathematical prototypes, we aim to highlight aspects related to the process (i.e., prototyping) rather than the product (i.e., the model). The objective of this paper is to review how two related engineering concepts, specifically prototyping and "fitness for use," can be applied to overcome the pressing challenge in translating data into improved knowledge of basic immunology that can be used to improve therapies for disease. These concepts are illustrated using two immunology-related examples. The prototypes presented focus on the beta cell mass at the onset of type 1 diabetes and the dynamics of dendritic cells in the lung. This paper is intended to illustrate some of the nuances associated with applying mathematical modeling to improve understanding of the dynamics of disease progression in humans.

Notch Signaling in Vascular Smooth Muscle Cells

PubMed Central

Baeten, J.T.; Lilly, B.

2018-01-01

The Notch signaling pathway is a highly conserved pathway involved in cell fate determination in embryonic development and also functions in the regulation of physiological processes in several systems. It plays an especially important role in vascular development and physiology by influencing angiogenesis, vessel patterning, arterial/venous specification, and vascular smooth muscle biology. Aberrant or dysregulated Notch signaling is the cause of or a contributing factor to many vascular disorders, including inherited vascular diseases, such as cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, associated with degeneration of the smooth muscle layer in cerebral arteries. Like most signaling pathways, the Notch signaling axis is influenced by complex interactions with mediators of other signaling pathways. This complexity is also compounded by different members of the Notch family having both overlapping and unique functions. Thus, it is vital to fully understand the roles and interactions of each Notch family member in order to effectively and specifically target their exact contributions to vascular disease. In this chapter, we will review the Notch signaling pathway in vascular smooth muscle cells as it relates to vascular development and human disease. PMID:28212801

Gravity Plant Physiology Facility (GPPF) Team in the Spacelab Payload Operations Control Center (SL

NASA Technical Reports Server (NTRS)

1992-01-01

The primary payload for Space Shuttle Mission STS-42, launched January 22, 1992, was the International Microgravity Laboratory-1 (IML-1), a pressurized manned Spacelab module. The goal of IML-1 was to explore in depth the complex effects of weightlessness of living organisms and materials processing. Around-the-clock research was performed on the human nervous system's adaptation to low gravity and effects of microgravity on other life forms such as shrimp eggs, lentil seedlings, fruit fly eggs, and bacteria. Materials processing experiments were also conducted, including crystal growth from a variety of substances such as enzymes, mercury iodide, and a virus. The Huntsville Operations Support Center (HOSC) Spacelab Payload Operations Control Center (SL POCC) at the Marshall Space Flight Center (MSFC) was the air/ground communication channel used between the astronauts and ground control teams during the Spacelab missions. Featured is the Gravity Plant Physiology Facility (GPPF) team in the SL POCC during the IML-1 mission.

Modifications of pancreatic diffusion MRI by tissue characteristics: what are we weighting for?

PubMed

Nissan, Noam

2017-08-01

Diffusion-weighted imaging holds the potential to improve the diagnosis and biological characterization of pancreatic disease, and in particular pancreatic cancer, which exhibits decreased values of the apparent diffusion coefficient (ADC). Yet, variable and overlapping ADC values have been reported for the healthy and the pathological pancreas, including for cancer and other benign conditions. This controversy reflects the complexity of probing the water-diffusion process in the pancreas, which is dependent upon multiple biological factors within this organ's unique physiological environment. In recent years, extensive studies have investigated the correlation between tissue properties including cellularity, vascularity, fibrosis, secretion and microstructure and pancreatic diffusivity. Understanding how the various physiological and pathological features and the underlying functional processes affect the diffusion measurement may serve to optimize the method for improved diagnostic gain. Therefore, the aim of the present review article is to elucidate the relationship between pancreatic tissue characteristics and diffusion MRI measurement. Copyright © 2017 John Wiley & Sons, Ltd.

A novel Minimalist Cell-Free MHC Class II Antigen Processing System Identifies Immunodominant Epitopes

PubMed Central

Hartman, Isamu Z.; Kim, AeRyon; Cotter, Robert J.; Walter, Kimberly; Dalai, Sarat K.; Boronina, Tatiana; Griffith, Wendell; Schwenk, Robert; Lanar, David E.; Krzych, Urszula; Cole, Robert N.; Sadegh-Nasseri, Scheherazade

2010-01-01

Immunodominance is defined as restricted responsiveness of T cells to a few selected epitopes from complex antigens. Strategies currently used for elucidating CD4+ T cell epitopes are inadequate. To understand the mechanism of epitope selection for helper T cells, we established a cell-free antigen processing system composed of defined proteins: MHC class II, cathepsins, and HLA-DM. Our minimalist system successfully identified the physiologically selected immunodominant epitopes of model antigens, HA1 from influenza virus (A/Texas/1/77) and type II collagen. When applied for de novo epitope identification to a malaria antigen, or HA1 from H5N1 virus (Avian Flu), the system selected a single epitope from each protein that were confirmed to be immunodominant by their capacity to activate CD4+ T cells in HLA-DR1 positive human volunteers or transgenic mice immunized with the corresponding proteins. Thus, we provide a powerful new tool for the identification of physiologically relevant helper T cell epitopes from antigens. PMID:21037588

Proteomics as an approach to the understanding of the molecular physiology of fruit development and ripening.

PubMed

Palma, José M; Corpas, Francisco J; del Río, Luís A

2011-08-12

Fruit ripening is a developmental complex process which occurs in higher plants and involves a number of stages displayed from immature to mature fruits that depend on the plant species and the environmental conditions. Nowadays, the importance of fruit ripening comes mainly from the link between this physiological process in plants and the economic repercussions as a result of one of the human activities, the agricultural industry. In most cases, fruit ripening is accompanied by colour changes due to different pigment content and increases in sugar levels, among others. Major physiological modifications that affect colour, texture, flavour, and aroma are under the control of both external (light and temperature) and internal (developmental gene regulation and hormonal control) factors. Due to the huge amount of metabolic changes that take place during ripening in fruits from higher plants, the accomplishment of new throughput methods which can provide a global evaluation of this process would be desirable. Differential proteomics of immature and mature fruits would be a useful tool to gain information on the molecular changes which occur during ripening, but also the investigation of fruits at different ripening stages will provide a dynamic picture of the whole transformation of fruits. This subject is furthermore of great interest as many fruits are essential for human nutrition. Thus far different maturation profiles have been reported specific for each crop species. In this work, a thorough review of the proteomic database from fruit development and maturation of important crop species will be updated to understand the molecular physiology of fruits at ripening stages. Copyright © 2011 Elsevier B.V. All rights reserved.

A DYNAMIC PHYSIOLOGICALLY-BASED TOXICOKINETIC (DPBTK) MODEL FOR SIMULATION OF COMPLEX TOLUENE EXPOSURE SCENARIOS IN HUMANS

EPA Science Inventory

A GENERAL PHYSIOLOGICAL AND TOXICOKINETIC (GPAT) MODEL FOR SIMULATION OF COMPLEX TOLUENE EXPOSURE SCENARIOS IN HUMANS. E M Kenyon1, T Colemen2, C R Eklund1 and V A Benignus3. 1U.S. EPA, ORD, NHEERL, ETD, PKB, RTP, NC, USA; 2Biological Simulators, Inc., Jackson MS, USA, 3U.S. EP...

Scale dependency of forest functional diversity assessed using imaging spectroscopy and airborne laser scanning

NASA Astrophysics Data System (ADS)

Schneider, F. D.; Morsdorf, F.; Schmid, B.; Petchey, O. L.; Hueni, A.; Schimel, D.; Schaepman, M. E.

2016-12-01

Forest functional traits offer a mechanistic link between ecological processes and community structure and assembly rules. However, measuring functional traits of forests in a continuous and consistent way is particularly difficult due to the complexity of in-situ measurements and geo-referencing. New imaging spectroscopy measurements overcome these limitations allowing to map physiological traits on broad spatial scales. We mapped leaf chlorophyll, carotenoids and leaf water content over 900 ha of temperate mixed forest (Fig. 1a). The selected traits are functionally important because they are indicating the photosynthetic potential of trees, leaf longevity and protection, as well as tree water and drought stress. Spatially continuous measurements on the scale of individual tree crowns allowed to assess functional diversity patterns on a range of ecological extents. We used indexes of functional richness, divergence and evenness to map different aspects of diversity. Fig. 1b shows an example of physiological richness at an extent of 240 m radius. We compared physiological to morphological diversity patterns, derived based on plant area index, canopy height and foliage height diversity. Our results show that patterns of physiological and morphological diversity generally agree, independently measured by airborne imaging spectroscopy and airborne laser scanning, respectively. The occurrence of disturbance areas and mixtures of broadleaf and needle trees were the main drivers of the observed diversity patterns. Spatial patterns at varying extents and richness-area relationships indicated that environmental filtering is the predominant community assembly process. Our results demonstrate the potential for mapping physiological and morphological diversity in a temperate mixed forest between and within species on scales relevant to study community assembly and structure from space and test the corresponding measurement schemes.

Stress response physiology of thermophiles.

PubMed

Ranawat, Preeti; Rawat, Seema

2017-04-01

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

In vitro oral drug permeation models: the importance of taking physiological and physico-chemical factors into consideration.

PubMed

Joubert, Ruan; Steyn, Johan Dewald; Heystek, Hendrik Jacobus; Steenekamp, Jan Harm; Du Preez, Jan Lourens; Hamman, Josias Hendrik

2017-02-01

The assessment of intestinal membrane permeability properties of new chemical entities is a crucial step in the drug discovery and development process and a variety of in vitro models, methods and techniques are available to estimate the extent of oral drug absorption in humans. However, variations in certain physiological and physico-chemical factors are often not reflected in the results and the complex dynamic interplay between these factors is sometimes oversimplified with in vitro models. Areas covered: In vitro models to evaluate drug pharmacokinetics are briefly outlined, while both physiological and physico-chemical factors that may have an influence on these techniques are critically reviewed. The shortcomings identified for some of the in vitro techniques are discussed in conjunction with novel ways to improve and thereby overcome some challenges. Expert opinion: Although conventional in vitro methods and theories are used as basic guidelines to predict drug absorption, critical evaluations have identified some shortcomings. Advancements in technology have made it possible to investigate and understand the role of physiological and physico-chemical factors in drug delivery more clearly, which can be used to improve and refine the techniques to more closely mimic the in vivo environment.

Diagnosis and management of urinary incontinence and functional fecal incontinence (encopresis) in children.

PubMed

Nijman, Rien J M

2008-09-01

The ability to maintain normal continence for urine and stools is not achievable in all children by a certain age. Gaining control of urinary and fecal continence is a complex process, and not all steps and factors involved are fully understood. While normal development of anatomy and physiology are prerequisites to becoming fully continent, anatomic abnormalities, such as bladder exstrophy, epispadias, ectopic ureters, and neurogenic disturbances that can usually be recognized at birth and cause incontinence, will require specialist treatment, not only to restore continence but also to preserve renal function. Most forms of urinary incontinence are not caused by an anatomic or physiologic abnormality and, hence, are more difficult to diagnose and their management requires a sound knowledge of bladder and bowel function.

Toward Scalable Trustworthy Computing Using the Human-Physiology-Immunity Metaphor

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

Hively, Lee M; Sheldon, Frederick T

The cybersecurity landscape consists of an ad hoc patchwork of solutions. Optimal cybersecurity is difficult for various reasons: complexity, immense data and processing requirements, resource-agnostic cloud computing, practical time-space-energy constraints, inherent flaws in 'Maginot Line' defenses, and the growing number and sophistication of cyberattacks. This article defines the high-priority problems and examines the potential solution space. In that space, achieving scalable trustworthy computing and communications is possible through real-time knowledge-based decisions about cyber trust. This vision is based on the human-physiology-immunity metaphor and the human brain's ability to extract knowledge from data and information. The article outlines future steps towardmore » scalable trustworthy systems requiring a long-term commitment to solve the well-known challenges.« less

The importance of trace element speciation in biomedical science.

PubMed

Templeton, Douglas M

2003-04-01

According to IUPAC terminology, trace element speciation reflects differences in chemical composition at multiple levels from nuclear and electronic structure to macromolecular complexation. In the medical sciences, all levels of composition are important in various circumstances, and each can affect the bioavailability, distribution, physiological function, toxicity, diagnostic utility, and therapeutic potential of an element. Here we discuss, with specific examples, three biological principles in the intimate relation between speciation and biological behavior: i) the kinetics of interconversion of species determines distribution within the organism, ii) speciation governs transport across various biological barriers, and iii) speciation can limit potentially undesirable interactions between physiologically essential elements. We will also describe differences in the speciation of iron in states of iron overload, to illustrate how speciation analysis can provide insight into cellular processes in human disease.

Reconstruction method for data protection in telemedicine systems

NASA Astrophysics Data System (ADS)

Buldakova, T. I.; Suyatinov, S. I.

2015-03-01

In the report the approach to protection of transmitted data by creation of pair symmetric keys for the sensor and the receiver is offered. Since biosignals are unique for each person, their corresponding processing allows to receive necessary information for creation of cryptographic keys. Processing is based on reconstruction of the mathematical model generating time series that are diagnostically equivalent to initial biosignals. Information about the model is transmitted to the receiver, where the restoration of physiological time series is performed using the reconstructed model. Thus, information about structure and parameters of biosystem model received in the reconstruction process can be used not only for its diagnostics, but also for protection of transmitted data in telemedicine complexes.

A comparative study of the characterization of miR-155 in knockout mice

PubMed Central

Zhang, Dong; Cui, Yongchun; Li, Bin; Luo, Xiaokang; Li, Bo; Tang, Yue

2017-01-01

miR-155 is one of the most important miRNAs and plays a very important role in numerous biological processes. However, few studies have characterized this miRNA in mice under normal physiological conditions. We aimed to characterize miR-155 in vivo by using a comparative analysis. In our study, we compared miR-155 knockout (KO) mice with C57BL/6 wild type (WT) mice in order to characterize miR-155 in mice under normal physiological conditions using many evaluation methods, including a reproductive performance analysis, growth curve, ultrasonic estimation, haematological examination, and histopathological analysis. These analyses showed no significant differences between groups in the main evaluation indices. The growth and development were nearly normal for all mice and did not differ between the control and model groups. Using a comparative analysis and a summary of related studies published in recent years, we found that miR-155 was not essential for normal physiological processes in 8-week-old mice. miR-155 deficiency did not affect the development and growth of naturally ageing mice during the 42 days after birth. Thus, studying the complex biological functions of miR-155 requires the further use of KO mouse models. PMID:28278287

Obstructive sleep apnea.

PubMed

White, David P; Younes, Magdy K

2012-10-01

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

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.

Comprehensive Transcriptome Analysis of Sex-Biased Expressed Genes Reveals Discrete Biological and Physiological Features of Male and Female Schistosoma japonicum.

PubMed

Cai, Pengfei; Liu, Shuai; Piao, Xianyu; Hou, Nan; Gobert, Geoffrey N; McManus, Donald P; Chen, Qijun

2016-04-01

Schistosomiasis is a chronic and debilitating disease caused by blood flukes (digenetic trematodes) of the genus Schistosoma. Schistosomes are sexually dimorphic and exhibit dramatic morphological changes during a complex lifecycle which requires subtle gene regulatory mechanisms to fulfil these complex biological processes. In the current study, a 41,982 features custom DNA microarray, which represents the most comprehensive probe coverage for any schistosome transcriptome study, was designed based on public domain and local databases to explore differential gene expression in S. japonicum. We found that approximately 1/10 of the total annotated genes in the S. japonicum genome are differentially expressed between adult males and females. In general, genes associated with the cytoskeleton, and motor and neuronal activities were readily expressed in male adult worms, whereas genes involved in amino acid metabolism, nucleotide biosynthesis, gluconeogenesis, glycosylation, cell cycle processes, DNA synthesis and genome fidelity and stability were enriched in females. Further, miRNAs target sites within these gene sets were predicted, which provides a scenario whereby the miRNAs potentially regulate these sex-biased expressed genes. The study significantly expands the expressional and regulatory characteristics of gender-biased expressed genes in schistosomes with high accuracy. The data provide a better appreciation of the biological and physiological features of male and female schistosome parasites, which may lead to novel vaccine targets and the development of new therapeutic interventions.

Modulation of ionotropic glutamate receptor function by vertebrate galectins

PubMed Central

Copits, Bryan A; Vernon, Claire G; Sakai, Ryuichi; Swanson, Geoffrey T

2014-01-01

AMPA and kainate receptors are glutamate-gated ion channels whose function is known to be altered by a variety of plant oligosaccharide-binding proteins, or lectins, but the physiological relevance of this activity has been uncertain because no lectins with analogous allosteric modulatory effects have been identified in animals. We report here that members of the prototype galectin family, which are β-galactoside-binding lectins, exhibit subunit-specific allosteric modulation of desensitization of recombinant homomeric and heteromeric AMPA and kainate receptors. Galectin modulation of GluK2 kainate receptors was dependent upon complex oligosaccharide processing of N-glycosylation sites in the amino-terminal domain and downstream linker region. The sensitivity of GluA4 AMPA receptors to human galectin-1 could be enhanced by supplementation of culture media with uridine and N-acetylglucosamine (GlcNAc), precursors for the hexosamine pathway that supplies UDP-GlcNAc for synthesis of complex oligosaccharides. Neuronal kainate receptors in dorsal root ganglia were sensitive to galectin modulation, whereas AMPA receptors in cultured hippocampal neurons were insensitive, which could be a reflection of differential N-glycan processing or receptor subunit selectivity. Because glycan content of integral proteins can be modified dynamically, we postulate that physiological or pathological conditions in the CNS could arise in which galectins alter excitatory neurotransmission or neuronal excitability through their actions on AMPA or kainate receptors. PMID:24614744

Hepatic signaling by the mechanistic target of rapamycin complex 2 (mTORC2)

PubMed Central

Lamming, Dudley W.; Demirkan, Gokhan; Boylan, Joan M.; Mihaylova, Maria M.; Peng, Tao; Ferreira, Jonathan; Neretti, Nicola; Salomon, Arthur; Sabatini, David M.; Gruppuso, Philip A.

2014-01-01

The mechanistic target of rapamycin (mTOR) exists in two complexes that regulate diverse cellular processes. mTOR complex 1 (mTORC1), the canonical target of rapamycin, has been well studied, whereas the physiological role of mTORC2 remains relatively uncharacterized. In mice in which the mTORC2 component Rictor is deleted in liver [Rictor-knockout (RKO) mice], we used genomic and phosphoproteomic analyses to characterize the role of hepatic mTORC2 in vivo. Overnight food withdrawal followed by refeeding was used to activate mTOR signaling. Rapamycin was administered before refeeding to specify mTORC2-mediated events. Hepatic mTORC2 regulated a complex gene expression and post-translational network that affects intermediary metabolism, ribosomal biogenesis, and proteasomal biogenesis. Nearly all changes in genes related to intermediary metabolic regulation were replicated in cultured fetal hepatocytes, indicating a cell-autonomous effect of mTORC2 signaling. Phosphoproteomic profiling identified mTORC2-related signaling to 144 proteins, among which were metabolic enzymes and regulators. A reduction of p38 MAPK signaling in the RKO mice represents a link between our phosphoproteomic and gene expression results. We conclude that hepatic mTORC2 exerts a broad spectrum of biological effects under physiological conditions. Our findings provide a context for the development of targeted therapies to modulate mTORC2 signaling.—Lamming, D. W., Demirkan, G., Boylan, J. M., Mihaylova, M. M., Peng, T., Ferreira, J., Neretti, N., Salomon, A., Sabatini, D. M., Gruppuso, P. A. Hepatic signaling by the mechanistic target of rapamycin complex 2 (mTORC2). PMID:24072782

Endoplasmic reticulum-plasma membrane junctions: structure, function and dynamics.

PubMed

Okeke, Emmanuel; Dingsdale, Hayley; Parker, Tony; Voronina, Svetlana; Tepikin, Alexei V

2016-06-01

Endoplasmic reticulum (ER)-plasma membrane (PM) junctions are contact sites between the ER and the PM; the distance between the two organelles in the junctions is below 40 nm and the membranes are connected by protein tethers. A number of molecular tools and technical approaches have been recently developed to visualise, modify and characterise properties of ER-PM junctions. The junctions serve as the platforms for lipid exchange between the organelles and for cell signalling, notably Ca(2+) and cAMP signalling. Vice versa, signalling events regulate the development and properties of the junctions. Two Ca(2+) -dependent mechanisms of de novo formation of ER-PM junctions have been recently described and characterised. The junction-forming proteins and lipids are currently the focus of vigorous investigation. Junctions can be relatively short-lived and simple structures, forming and dissolving on the time scale of a few minutes. However, complex, sophisticated and multifunctional ER-PM junctions, capable of attracting numerous protein residents and other cellular organelles, have been described in some cell types. The road from simplicity to complexity, i.e. the transformation from simple 'nascent' ER-PM junctions to advanced stable multiorganellar complexes, is likely to become an attractive research avenue for current and future junctologists. Another area of considerable research interest is the downstream cellular processes that can be activated by specific local signalling events in the ER-PM junctions. Studies of the cell physiology and indeed pathophysiology of ER-PM junctions have already produced some surprising discoveries, likely to expand with advances in our understanding of these remarkable organellar contact sites. © 2016 The Authors. The Journal of Physiology © 2016 The Physiological Society.

Electronic Connection Between the Quinone and Cytochrome c Redox Pools and Its Role in Regulation of Mitochondrial Electron Transport and Redox Signaling

PubMed Central

Sarewicz, Marcin; Osyczka, Artur

2015-01-01

Mitochondrial respiration, an important bioenergetic process, relies on operation of four membranous enzymatic complexes linked functionally by mobile, freely diffusible elements: quinone molecules in the membrane and water-soluble cytochromes c in the intermembrane space. One of the mitochondrial complexes, complex III (cytochrome bc1 or ubiquinol:cytochrome c oxidoreductase), provides an electronic connection between these two diffusible redox pools linking in a fully reversible manner two-electron quinone oxidation/reduction with one-electron cytochrome c reduction/oxidation. Several features of this homodimeric enzyme implicate that in addition to its well-defined function of contributing to generation of proton-motive force, cytochrome bc1 may be a physiologically important point of regulation of electron flow acting as a sensor of the redox state of mitochondria that actively responds to changes in bioenergetic conditions. These features include the following: the opposing redox reactions at quinone catalytic sites located on the opposite sides of the membrane, the inter-monomer electronic connection that functionally links four quinone binding sites of a dimer into an H-shaped electron transfer system, as well as the potential to generate superoxide and release it to the intermembrane space where it can be engaged in redox signaling pathways. Here we highlight recent advances in understanding how cytochrome bc1 may accomplish this regulatory physiological function, what is known and remains unknown about catalytic and side reactions within the quinone binding sites and electron transfers through the cofactor chains connecting those sites with the substrate redox pools. We also discuss the developed molecular mechanisms in the context of physiology of mitochondria. PMID:25540143

Adapting High-Resolution Respirometry to Glucose-Limited Steady State Mycelium of the Filamentous Fungus Penicillium ochrochloron: Method Development and Standardisation

PubMed Central

Schinagl, Christoph W.; Vrabl, Pamela; Burgstaller, Wolfgang

2016-01-01

Fungal electron transport systems (ETS) are branched, involving alternative NADH dehydrogenases and an alternative terminal oxidase. These alternative respiratory enzymes were reported to play a role in pathogenesis, production of antibiotics and excretion of organic acids. The activity of these alternative respiratory enzymes strongly depends on environmental conditions. Functional analysis of fungal ETS under highly standardised conditions for cultivation, sample processing and respirometric assay are still lacking. We developed a highly standardised protocol to explore in vivo the ETS—and in particular the alternative oxidase—in Penicillium ochrochloron. This included cultivation in glucose-limited chemostat (to achieve a defined and reproducible physiological state), direct transfer without any manipulation of a broth sample to the respirometer (to maintain the physiological state in the respirometer as close as possible to that in the chemostat), and high-resolution respirometry (small sample volume and high measuring accuracy). This protocol was aimed at avoiding any changes in the physiological phenotype due to the high phenotypic plasticity of filamentous fungi. A stable oxygen consumption (< 5% change in 20 minutes) was only possible with glucose limited chemostat mycelium and a direct transfer of a broth sample into the respirometer. Steady state respiration was 29% below its maximum respiratory capacity. Additionally to a rotenone-sensitive complex I and most probably a functioning complex III, the ETS of P. ochrochloron also contained a cyanide-sensitive terminal oxidase (complex IV). Activity of alternative oxidase was present constitutively. The degree of inhibition strongly depended on the sequence of inhibitor addition. This suggested, as postulated for plants, that the alternative terminal oxidase was in dynamic equilibrium with complex IV—independent of the rate of electron flux. This means that the onset of activity does not depend on a complete saturation or inhibition of the cytochrome pathway. PMID:26771937

Effects of maturation and acidosis on the chaos-like complexity of the neural respiratory output in the isolated brainstem of the tadpole, Rana esculenta

PubMed Central

Samara, Ziyad; Fiamma, Marie-Noëlle; Bautin, Nathalie; Ranohavimparany, Anja; Le Coz, Patrick; Golmard, Jean-Louis; Darré, Pierre; Zelter, Marc; Poon, Chi-Sang; Similowski, Thomas

2011-01-01

Human ventilation at rest exhibits mathematical chaos-like complexity that can be described as long-term unpredictability mediated (in whole or in part) by some low-dimensional nonlinear deterministic process. Although various physiological and pathological situations can affect respiratory complexity, the underlying mechanisms remain incompletely elucidated. If such chaos-like complexity is an intrinsic property of central respiratory generators, it should appear or increase when these structures mature or are stimulated. To test this hypothesis, we employed the isolated tadpole brainstem model [Rana (Pelophylax) esculenta] and recorded the neural respiratory output (buccal and lung rhythms) of pre- (n = 8) and postmetamorphic tadpoles (n = 8), at physiologic (7.8) and acidic pH (7.4). We analyzed the root mean square of the cranial nerve V or VII neurograms. Development and acidosis had no effect on buccal period. Lung frequency increased with development (P < 0.0001). It also increased with acidosis, but in postmetamorphic tadpoles only (P < 0.05). The noise-titration technique evidenced low-dimensional nonlinearities in all the postmetamorphic brainstems, at both pH. Chaos-like complexity, assessed through the noise limit, increased from pH 7.8 to pH 7.4 (P < 0.01). In contrast, linear models best fitted the ventilatory rhythm in all but one of the premetamorphic preparations at pH 7.8 (P < 0.005 vs. postmetamorphic) and in four at pH 7.4 (not significant vs. postmetamorphic). Therefore, in a lower vertebrate model, the brainstem respiratory central rhythm generator accounts for ventilatory chaos-like complexity, especially in the postmetamorphic stage and at low pH. According to the ventilatory generators homology theory, this may also be the case in mammals. PMID:21325645

Effects of maturation and acidosis on the chaos-like complexity of the neural respiratory output in the isolated brainstem of the tadpole, Rana esculenta.

PubMed

Straus, Christian; Samara, Ziyad; Fiamma, Marie-Noëlle; Bautin, Nathalie; Ranohavimparany, Anja; Le Coz, Patrick; Golmard, Jean-Louis; Darré, Pierre; Zelter, Marc; Poon, Chi-Sang; Similowski, Thomas

2011-05-01

Human ventilation at rest exhibits mathematical chaos-like complexity that can be described as long-term unpredictability mediated (in whole or in part) by some low-dimensional nonlinear deterministic process. Although various physiological and pathological situations can affect respiratory complexity, the underlying mechanisms remain incompletely elucidated. If such chaos-like complexity is an intrinsic property of central respiratory generators, it should appear or increase when these structures mature or are stimulated. To test this hypothesis, we employed the isolated tadpole brainstem model [Rana (Pelophylax) esculenta] and recorded the neural respiratory output (buccal and lung rhythms) of pre- (n = 8) and postmetamorphic tadpoles (n = 8), at physiologic (7.8) and acidic pH (7.4). We analyzed the root mean square of the cranial nerve V or VII neurograms. Development and acidosis had no effect on buccal period. Lung frequency increased with development (P < 0.0001). It also increased with acidosis, but in postmetamorphic tadpoles only (P < 0.05). The noise-titration technique evidenced low-dimensional nonlinearities in all the postmetamorphic brainstems, at both pH. Chaos-like complexity, assessed through the noise limit, increased from pH 7.8 to pH 7.4 (P < 0.01). In contrast, linear models best fitted the ventilatory rhythm in all but one of the premetamorphic preparations at pH 7.8 (P < 0.005 vs. postmetamorphic) and in four at pH 7.4 (not significant vs. postmetamorphic). Therefore, in a lower vertebrate model, the brainstem respiratory central rhythm generator accounts for ventilatory chaos-like complexity, especially in the postmetamorphic stage and at low pH. According to the ventilatory generators homology theory, this may also be the case in mammals.

The micro and macro of nutrients across biological scales.

PubMed

Warne, Robin W

2014-11-01

During the past decade, we have gained new insights into the profound effects that essential micronutrients and macronutrients have on biological processes ranging from cellular function, to whole-organism performance, to dynamics in ecological communities, as well as to the structure and function of ecosystems. For example, disparities between intake and organismal requirements for specific nutrients are known to strongly affect animal physiological performance and impose trade-offs in the allocations of resources. However, recent findings have demonstrated that life-history allocation trade-offs and even microevolutionary dynamics may often be a result of molecular-level constraints on nutrient and metabolic processing, in which limiting reactants are routed among competing biochemical pathways. In addition, recent work has shown that complex ecological interactions between organismal physiological states such as exposure to environmental stressors and infectious pathogens can alter organismal requirements for, and, processing of, nutrients, and even alter subsequent nutrient cycling in ecosystems. Furthermore, new research is showing that such interactions, coupled with evolutionary and biogeographical constraints on the biosynthesis and availability of essential nutrients and micronutrients play an important, but still under-studied role in the structuring and functioning of ecosystems. The purpose of this introduction to the symposium "The Micro and Macro of Nutrient Effects in Animal Physiology and Ecology" is to briefly review and highlight recent research that has dramatically advanced our understanding of how nutrients in their varied forms profoundly affect and shape ecological and evolutionary processes. © The Author 2014. Published by Oxford University Press on behalf of the Society for Integrative and Comparative Biology. All rights reserved. For permissions please email: journals.permissions@oup.com.

The role of emotions on pacing strategies and performance in middle and long duration sport events.

PubMed

Baron, B; Moullan, F; Deruelle, F; Noakes, T D

2011-05-01

Thepacing strategy may be defined as the process in which the total energy expenditure during exercise is regulated on a moment-to-moment basis in order to ensure that the exercise bout can be completed in a minimum time and without a catastrophic biological failure. Experienced athletes develop a stable template of the power outputs they are able to sustain for different durations of exercise, but it is not known how they originally develop this template or how that template changes with training and experience. While it is understood that the athlete's physiological state makes an important contribution to this process, there has been much less interest in the contribution that the athlete's emotional status makes. The aim of this review is to evaluate the literature of physiological, neurophysiological and perceptual responses during exercise in order to propose a complex model interpretation of this process which may be a critical factor determining success in middle- and long-duration sporting competitions. We describe unconscious/physiological and conscious/emotional mechanisms of control, the focus of which are to ensure that exercise terminates before catastrophic failure occurs in any bodily system. We suggest that training sessions teach the athlete to select optimal pacing strategies by associating a level of emotion with the ability to maintain that pace for exercise of different durations. That pacing strategy is then adopted in future events. Finally, we propose novel perspectives to maximise performance and to avoid overtraining by paying attention also to the emotional state in training process.

Modeling tree growth and stable isotope ratios of white spruce in western Alaska.

NASA Astrophysics Data System (ADS)

Boucher, Etienne; Andreu-Hayles, Laia; Field, Robert; Oelkers, Rose; D'Arrigo, Rosanne

2017-04-01

Summer temperatures are assumed to exert a dominant control on physiological processes driving forest productivity in interior Alaska. However, despite the recent warming of the last few decades, numerous lines of evidence indicate that the enhancing effect of summer temperatures on high latitude forest populations has been weakening. First, satellite-derived indices of photosynthetic activity, such as the Normalized-Difference Vegetation Index (NDVI, 1982-2005), show overall declines in productivity in the interior boreal forests. Second, some white spruce tree ring series strongly diverge from summer temperatures during the second half of the 20th century, indicating a persistent loss of temperature sensitivity of tree ring proxies. Thus, the physiological response of treeline forests to ongoing climate change cannot be accurately predicted, especially from correlation analysis. Here, we make use of a process-based dendroecological model (MAIDENiso) to elucidate the complex linkages between global warming and increases in atmospheric CO2 concentration [CO2] with the response of treeline white spruce stands in interior Alaska (Seward). In order to fully capture the array of processes controlling tree growth in the area, multiple physiological indicators of white spruce productivity are used as target variables: NDVI images, ring widths (RW), maximum density (MXD) and newly measured carbon and oxygen stable isotope ratios from ring cellulose. Based on these data, we highlight the processes and mechanisms responsible for the apparent loss of sensitivity of white spruce trees to recent climate warming and [CO2] increase in order to elucidate the sensitivity and vulnerability of these trees to climate change.

Clinical metabolomics paves the way towards future healthcare strategies

PubMed Central

Collino, Sebastiano; Martin, François‐Pierre J.; Rezzi, Serge

2013-01-01

Metabolomics is recognized as a powerful top‐down system biological approach to understand genetic‐environment‐health paradigms paving new avenues to identify clinically relevant biomarkers. It is nowadays commonly used in clinical applications shedding new light on physiological regulatory processes of complex mammalian systems with regard to disease aetiology, diagnostic stratification and, potentially, mechanism of action of therapeutic solutions. A key feature of metabolomics lies in its ability to underpin the complex metabolic interactions of the host with its commensal microbial partners providing a new way to define individual and population phenotypes. This review aims at describing recent applications of metabolomics in clinical fields with insight into diseases, diagnostics/monitoring and improvement of homeostatic metabolic regulation. PMID:22348240

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

PubMed

Yamashita, Hiroshi; Ueda, Kazumitsu; Kioka, Noriyuki

2011-02-04

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

Proteomics-Based Analysis of Protein Complexes in Pluripotent Stem Cells and Cancer Biology.

PubMed

Sudhir, Putty-Reddy; Chen, Chung-Hsuan

2016-03-22

A protein complex consists of two or more proteins that are linked together through protein-protein interactions. The proteins show stable/transient and direct/indirect interactions within the protein complex or between the protein complexes. Protein complexes are involved in regulation of most of the cellular processes and molecular functions. The delineation of protein complexes is important to expand our knowledge on proteins functional roles in physiological and pathological conditions. The genetic yeast-2-hybrid method has been extensively used to characterize protein-protein interactions. Alternatively, a biochemical-based affinity purification coupled with mass spectrometry (AP-MS) approach has been widely used to characterize the protein complexes. In the AP-MS method, a protein complex of a target protein of interest is purified using a specific antibody or an affinity tag (e.g., DYKDDDDK peptide (FLAG) and polyhistidine (His)) and is subsequently analyzed by means of MS. Tandem affinity purification, a two-step purification system, coupled with MS has been widely used mainly to reduce the contaminants. We review here a general principle for AP-MS-based characterization of protein complexes and we explore several protein complexes identified in pluripotent stem cell biology and cancer biology as examples.

Proteomics-Based Analysis of Protein Complexes in Pluripotent Stem Cells and Cancer Biology

PubMed Central

Sudhir, Putty-Reddy; Chen, Chung-Hsuan

2016-01-01

A protein complex consists of two or more proteins that are linked together through protein–protein interactions. The proteins show stable/transient and direct/indirect interactions within the protein complex or between the protein complexes. Protein complexes are involved in regulation of most of the cellular processes and molecular functions. The delineation of protein complexes is important to expand our knowledge on proteins functional roles in physiological and pathological conditions. The genetic yeast-2-hybrid method has been extensively used to characterize protein-protein interactions. Alternatively, a biochemical-based affinity purification coupled with mass spectrometry (AP-MS) approach has been widely used to characterize the protein complexes. In the AP-MS method, a protein complex of a target protein of interest is purified using a specific antibody or an affinity tag (e.g., DYKDDDDK peptide (FLAG) and polyhistidine (His)) and is subsequently analyzed by means of MS. Tandem affinity purification, a two-step purification system, coupled with MS has been widely used mainly to reduce the contaminants. We review here a general principle for AP-MS-based characterization of protein complexes and we explore several protein complexes identified in pluripotent stem cell biology and cancer biology as examples. PMID:27011181

Integrated Central-Autonomic Multifractal Complexity in the Heart Rate Variability of Healthy Humans

PubMed Central

Lin, D. C.; Sharif, A.

2012-01-01

Purpose of Study: The aim of this study was to characterize the central-autonomic interaction underlying the multifractality in heart rate variability (HRV) of healthy humans. Materials and Methods: Eleven young healthy subjects participated in two separate ~40 min experimental sessions, one in supine (SUP) and one in, head-up-tilt (HUT), upright (UPR) body positions. Surface scalp electroencephalography (EEG) and electrocardiogram (ECG) were collected and fractal correlation of brain and heart rate data was analyzed based on the idea of relative multifractality. The fractal correlation was further examined with the EEG, HRV spectral measures using linear regression of two variables and principal component analysis (PCA) to find clues for the physiological processing underlying the central influence in fractal HRV. Results: We report evidence of a central-autonomic fractal correlation (CAFC) where the HRV multifractal complexity varies significantly with the fractal correlation between the heart rate and brain data (P = 0.003). The linear regression shows significant correlation between CAFC measure and EEG Beta band spectral component (P = 0.01 for SUP and P = 0.002 for UPR positions). There is significant correlation between CAFC measure and HRV LF component in the SUP position (P = 0.04), whereas the correlation with the HRV HF component approaches significance (P = 0.07). The correlation between CAFC measure and HRV spectral measures in the UPR position is weak. The PCA results confirm these findings and further imply multiple physiological processes underlying CAFC, highlighting the importance of the EEG Alpha, Beta band, and the HRV LF, HF spectral measures in the supine position. Discussion and Conclusion: The findings of this work can be summarized into three points: (i) Similar fractal characteristics exist in the brain and heart rate fluctuation and the change toward stronger fractal correlation implies the change toward more complex HRV multifractality. (ii) CAFC is likely contributed by multiple physiological mechanisms, with its central elements mainly derived from the EEG Alpha, Beta band dynamics. (iii) The CAFC in SUP and UPR positions is qualitatively different, with a more predominant central influence in the fractal HRV of the UPR position. PMID:22403548

Magnesium degradation as determined by artificial neural networks.

PubMed

Willumeit, Regine; Feyerabend, Frank; Huber, Norbert

2013-11-01

Magnesium degradation under physiological conditions is a highly complex process in which temperature, the use of cell culture growth medium and the presence of CO2, O2 and proteins can influence the corrosion rate and the composition of the resulting corrosion layer. Due to the complexity of this process it is almost impossible to predict the parameters that are most important and whether some parameters have a synergistic effect on the corrosion rate. Artificial neural networks are a mathematical tool that can be used to approximate and analyse non-linear problems with multiple inputs. In this work we present the first analysis of corrosion data obtained using this method, which reveals that CO2 and the composition of the buffer system play a crucial role in the corrosion of magnesium, whereas O2, proteins and temperature play a less prominent role. Copyright © 2013 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

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

Eccentric and concentric cardiac hypertrophy induced by exercise training: microRNAs and molecular determinants.

PubMed

Fernandes, T; Soci, U P R; Oliveira, E M

2011-09-01

Among the molecular, biochemical and cellular processes that orchestrate the development of the different phenotypes of cardiac hypertrophy in response to physiological stimuli or pathological insults, the specific contribution of exercise training has recently become appreciated. Physiological cardiac hypertrophy involves complex cardiac remodeling that occurs as an adaptive response to static or dynamic chronic exercise, but the stimuli and molecular mechanisms underlying transduction of the hemodynamic overload into myocardial growth are poorly understood. This review summarizes the physiological stimuli that induce concentric and eccentric physiological hypertrophy, and discusses the molecular mechanisms, sarcomeric organization, and signaling pathway involved, also showing that the cardiac markers of pathological hypertrophy (atrial natriuretic factor, β-myosin heavy chain and α-skeletal actin) are not increased. There is no fibrosis and no cardiac dysfunction in eccentric or concentric hypertrophy induced by exercise training. Therefore, the renin-angiotensin system has been implicated as one of the regulatory mechanisms for the control of cardiac function and structure. Here, we show that the angiotensin II type 1 (AT1) receptor is locally activated in pathological and physiological cardiac hypertrophy, although with exercise training it can be stimulated independently of the involvement of angiotensin II. Recently, microRNAs (miRs) have been investigated as a possible therapeutic approach since they regulate the translation of the target mRNAs involved in cardiac hypertrophy; however, miRs in relation to physiological hypertrophy have not been extensively investigated. We summarize here profiling studies that have examined miRs in pathological and physiological cardiac hypertrophy. An understanding of physiological cardiac remodeling may provide a strategy to improve ventricular function in cardiac dysfunction.

[Preliminary studies on physicochemical properties of Angelica sinensis polysaccharide-iron complex].

PubMed

Wang, Kai-ping; Zhang, Yu; Dai, Li-quan

2006-05-01

To study some physicochemical properties of Angelica sinensis polysaccharide-iron complex (APC). Based on the qualitatively identified reactions of iron (III), the qualitatively identified reactions of APC were found out by comparing hydroxide. The content of iron (III) in APC was determined with iodometry. The stability of APC under physiological pH conditions was judged by titrating APC with sodium hydroxide. The deoxidization of APC was tested with colorimetric analysis. APC showed the qualitatively identified reactions of iron (III). The content of iron (III) in APC ranged from 10% to 40%, and the water-solubility of APC was related to the content of iron (III). The complex was stable at physiological pH from 3 to 12, without precipitation and dissociation. At 37 degrees C, Fe (III) in the complex was completely reduced to Fe (III) by ascorbic acid in about 6 hours. APC can be qualitatively identified by using the qualitatively identified reactions of iron (III). When its iron (III) content is within 20%-25%, APC has a better ability to dissolve in water. And the complex is stable under physiological pH conditions.

Spectral convergence in tapping and physiological fluctuations: coupling and independence of 1/f noise in the central and autonomic nervous systems

PubMed Central

Rigoli, Lillian M.; Holman, Daniel; Spivey, Michael J.; Kello, Christopher T.

2014-01-01

When humans perform a response task or timing task repeatedly, fluctuations in measures of timing from one action to the next exhibit long-range correlations known as 1/f noise. The origins of 1/f noise in timing have been debated for over 20 years, with one common explanation serving as a default: humans are composed of physiological processes throughout the brain and body that operate over a wide range of timescales, and these processes combine to be expressed as a general source of 1/f noise. To test this explanation, the present study investigated the coupling vs. independence of 1/f noise in timing deviations, key-press durations, pupil dilations, and heartbeat intervals while tapping to an audiovisual metronome. All four dependent measures exhibited clear 1/f noise, regardless of whether tapping was synchronized or syncopated. 1/f spectra for timing deviations were found to match those for key-press durations on an individual basis, and 1/f spectra for pupil dilations matched those in heartbeat intervals. Results indicate a complex, multiscale relationship among 1/f noises arising from common sources, such as those arising from timing functions vs. those arising from autonomic nervous system (ANS) functions. Results also provide further evidence against the default hypothesis that 1/f noise in human timing is just the additive combination of processes throughout the brain and body. Our findings are better accommodated by theories of complexity matching that begin to formalize multiscale coordination as a foundation of human behavior. PMID:25309389

Two Parallel Olfactory Pathways for Processing General Odors in a Cockroach

PubMed Central

Watanabe, Hidehiro; Nishino, Hiroshi; Mizunami, Makoto; Yokohari, Fumio

2017-01-01

In animals, sensory processing via parallel pathways, including the olfactory system, is a common design. However, the mechanisms that parallel pathways use to encode highly complex and dynamic odor signals remain unclear. In the current study, we examined the anatomical and physiological features of parallel olfactory pathways in an evolutionally basal insect, the cockroach Periplaneta americana. In this insect, the entire system for processing general odors, from olfactory sensory neurons to higher brain centers, is anatomically segregated into two parallel pathways. Two separate populations of secondary olfactory neurons, type1 and type2 projection neurons (PNs), with dendrites in distinct glomerular groups relay olfactory signals to segregated areas of higher brain centers. We conducted intracellular recordings, revealing olfactory properties and temporal patterns of both types of PNs. Generally, type1 PNs exhibit higher odor-specificities to nine tested odorants than type2 PNs. Cluster analyses revealed that odor-evoked responses were temporally complex and varied in type1 PNs, while type2 PNs exhibited phasic on-responses with either early or late latencies to an effective odor. The late responses are 30–40 ms later than the early responses. Simultaneous intracellular recordings from two different PNs revealed that a given odor activated both types of PNs with different temporal patterns, and latencies of early and late responses in type2 PNs might be precisely controlled. Our results suggest that the cockroach is equipped with two anatomically and physiologically segregated parallel olfactory pathways, which might employ different neural strategies to encode odor information. PMID:28529476

Nuclear localization of matrix metalloproteinases.

PubMed

Mannello, Ferdinando; Medda, Virginia

2012-03-01

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

A photo-cross-linking approach to monitor folding and assembly of newly synthesized proteins in a living cell.

PubMed

Miyazaki, Ryoji; Myougo, Naomi; Mori, Hiroyuki; Akiyama, Yoshinori

2018-01-12

Many proteins form multimeric complexes that play crucial roles in various cellular processes. Studying how proteins are correctly folded and assembled into such complexes in a living cell is important for understanding the physiological roles and the qualitative and quantitative regulation of the complex. However, few methods are suitable for analyzing these rapidly occurring processes. Site-directed in vivo photo-cross-linking is an elegant technique that enables analysis of protein-protein interactions in living cells with high spatial resolution. However, the conventional site-directed in vivo photo-cross-linking method is unsuitable for analyzing dynamic processes. Here, by combining an improved site-directed in vivo photo-cross-linking technique with a pulse-chase approach, we developed a new method that can analyze the folding and assembly of a newly synthesized protein with high spatiotemporal resolution. We demonstrate that this method, named the pulse-chase and in vivo photo-cross-linking experiment (PiXie), enables the kinetic analysis of the formation of an Escherichia coli periplasmic (soluble) protein complex (PhoA). We also used our new technique to investigate assembly/folding processes of two membrane complexes (SecD-SecF in the inner membrane and LptD-LptE in the outer membrane), which provided new insights into the biogenesis of these complexes. Our PiXie method permits analysis of the dynamic behavior of various proteins and enables examination of protein-protein interactions at the level of individual amino acid residues. We anticipate that our new technique will have valuable utility for studies of protein dynamics in many organisms. © 2018 by The American Society for Biochemistry and Molecular Biology, Inc.

Inhomogeneous point-process entropy: An instantaneous measure of complexity in discrete systems

NASA Astrophysics Data System (ADS)

Valenza, Gaetano; Citi, Luca; Scilingo, Enzo Pasquale; Barbieri, Riccardo

2014-05-01

Measures of entropy have been widely used to characterize complexity, particularly in physiological dynamical systems modeled in discrete time. Current approaches associate these measures to finite single values within an observation window, thus not being able to characterize the system evolution at each moment in time. Here, we propose a new definition of approximate and sample entropy based on the inhomogeneous point-process theory. The discrete time series is modeled through probability density functions, which characterize and predict the time until the next event occurs as a function of the past history. Laguerre expansions of the Wiener-Volterra autoregressive terms account for the long-term nonlinear information. As the proposed measures of entropy are instantaneously defined through probability functions, the novel indices are able to provide instantaneous tracking of the system complexity. The new measures are tested on synthetic data, as well as on real data gathered from heartbeat dynamics of healthy subjects and patients with cardiac heart failure and gait recordings from short walks of young and elderly subjects. Results show that instantaneous complexity is able to effectively track the system dynamics and is not affected by statistical noise properties.

Multiple choice questions can be designed or revised to challenge learners' critical thinking.

PubMed

Tractenberg, Rochelle E; Gushta, Matthew M; Mulroney, Susan E; Weissinger, Peggy A

2013-12-01

Multiple choice (MC) questions from a graduate physiology course were evaluated by cognitive-psychology (but not physiology) experts, and analyzed statistically, in order to test the independence of content expertise and cognitive complexity ratings of MC items. Integration of higher order thinking into MC exams is important, but widely known to be challenging-perhaps especially when content experts must think like novices. Expertise in the domain (content) may actually impede the creation of higher-complexity items. Three cognitive psychology experts independently rated cognitive complexity for 252 multiple-choice physiology items using a six-level cognitive complexity matrix that was synthesized from the literature. Rasch modeling estimated item difficulties. The complexity ratings and difficulty estimates were then analyzed together to determine the relative contributions (and independence) of complexity and difficulty to the likelihood of correct answers on each item. Cognitive complexity was found to be statistically independent of difficulty estimates for 88 % of items. Using the complexity matrix, modifications were identified to increase some item complexities by one level, without affecting the item's difficulty. Cognitive complexity can effectively be rated by non-content experts. The six-level complexity matrix, if applied by faculty peer groups trained in cognitive complexity and without domain-specific expertise, could lead to improvements in the complexity targeted with item writing and revision. Targeting higher order thinking with MC questions can be achieved without changing item difficulties or other test characteristics, but this may be less likely if the content expert is left to assess items within their domain of expertise.

A meta-analysis to evaluate the cellular processes regulated by the interactome of endogenous and over-expressed estrogen receptor alpha.

PubMed

Simões, Joana; Amado, Francisco M; Vitorino, Rui; Helguero, Luisa A

2015-01-01

The nature of the proteins complexes that regulate ERα subcellular localization and activity is still an open question in breast cancer biology. Identification of such complexes will help understand development of endocrine resistance in ER+ breast cancer. Mass spectrometry (MS) has allowed comprehensive analysis of the ERα interactome. We have compared six published works analyzing the ERα interactome of MCF-7 and HeLa cells in order to identify a shared or different pathway-related fingerprint. Overall, 806 ERα interacting proteins were identified. The cellular processes were differentially represented according to the ERα purification methodology, indicating that the methodologies used are complementary. While in MCF-7 cells, the interactome of endogenous and over-expressed ERα essentially represents the same biological processes and cellular components, the proteins identified were not over-lapping; thus, suggesting that the biological response may differ as the regulatory/participating proteins in these complexes are different. Interestingly, biological processes uniquely associated to ERα over-expressed in HeLa cell line included L-serine biosynthetic process, cellular amino acid biosynthetic process and cell redox homeostasis. In summary, all the approaches analyzed in this meta-analysis are valid and complementary; in particular, for those cases where the processes occur at low frequency with normal ERα levels, and can be identified when the receptor is over-expressed. However special effort should be put into validating these findings in cells expressing physiological ERα levels.

Environmental and biological context modulates the physiological stress response of bats to human disturbance.

PubMed

Phelps, Kendra L; Kingston, Tigga

2018-06-01

Environmental and biological context play significant roles in modulating physiological stress responses of individuals in wildlife populations yet are often overlooked when evaluating consequences of human disturbance on individual health and fitness. Furthermore, most studies gauge individual stress responses based on a single physiological biomarker, typically circulating glucocorticoid concentrations, which limits interpretation of the complex, multifaceted responses of individuals to stressors. We selected four physiological biomarkers to capture short-term and prolonged stress responses in a widespread cave-roosting bat, Hipposideros diadema, across multiple gradients of human disturbance in and around caves in the Philippines. We used conditional inference trees and random forest analysis to determine the role of environmental quality (cave complexity, available roosting area), assemblage composition (intra- and interspecific associations and species richness), and intrinsic characteristics of individuals (sex and reproductive status) in modulating responses to disturbance. Direct cave disturbance (hunting pressure and human visitation) was the primary driver of neutrophil-to-lymphocyte ratios, with lower ratios associated with increased disturbance, while context-specific factors were more important in explaining total leukocyte count, body condition, and ectoparasite load. Moreover, conditional inference trees revealed complex interactions among human disturbance and modulating factors. Cave complexity often ameliorated individual responses to human disturbance, whereas conspecific abundance often compounded responses. Our study demonstrates the importance of an integrated approach that incorporates environmental and biological context when identifying drivers of physiological responses, and that assesses responses to gradients of direct and indirect disturbance using multiple complementary biomarkers.

A dual physiological character for sexual function: libido and sexual pheromones.

PubMed

Motofei, Ion G

2009-12-01

Human sexual response is a complex function involving many cerebral, spinal and peripheral aspects; the last are relatively known and benefit from good pharmacological control, as in the case of erectile dysfunction. Spinal cord sexual reflexes also have a good theoretical and experimental description. There is minimal understanding of the cerebral sexual processes (libido, sexual arousal, orgasm). The initial perspective was that the cerebral areas implied in sexuality exert descending stimulatory and inhibitory influences on spinal cord sexual centres/reflexes. This was a wrong supposition, which inhibited progress in this subject, with a considerable impact on a subject's individual and social life. A new approach to sexual function arises from the idea that simple neurological structures can support only simple functions, while a more complex function requires correspondingly complex anatomical structures. For this reason the spinal cord would not be able to realise the integration of multiple (spinal and psychosensorial) stimuli into a unique and coherent ejaculation response. Consequently, all mechanisms implied in human sexuality would be cerebral processes, ejaculation reflexes ascending in evolution to the cerebral level. This new evolutionary concept was developed after 2001 in five distinct articles on the cerebral duality of sexual arousal, sexual hormones, ejaculation and serotonergic receptors. During this period other published results suggested a possible cerebral duality for sexual pheromones and libido in humans. All these dual physiological aspects are integrated in this review into one neurophysiological model, thus trying to further develop the new concepts of sexual function and perhaps relational behaviour. In conclusion, ejaculation is a dual cerebral process with arousal sensation (hormonally modulated) and libido perception (pheromonally modulated) as the afferent part. Two neurophysiological axes could exist in both men and women. In this assumption the mechanisms for libido and sexual arousal are not the only ones invoked, their correlations and implications are also suggested, perhaps critical aspects for further developments in the field.

Entropy for the Complexity of Physiological Signal Dynamics.

PubMed

Zhang, Xiaohua Douglas

2017-01-01

Recently, the rapid development of large data storage technologies, mobile network technology, and portable medical devices makes it possible to measure, record, store, and track analysis of biological dynamics. Portable noninvasive medical devices are crucial to capture individual characteristics of biological dynamics. The wearable noninvasive medical devices and the analysis/management of related digital medical data will revolutionize the management and treatment of diseases, subsequently resulting in the establishment of a new healthcare system. One of the key features that can be extracted from the data obtained by wearable noninvasive medical device is the complexity of physiological signals, which can be represented by entropy of biological dynamics contained in the physiological signals measured by these continuous monitoring medical devices. Thus, in this chapter I present the major concepts of entropy that are commonly used to measure the complexity of biological dynamics. The concepts include Shannon entropy, Kolmogorov entropy, Renyi entropy, approximate entropy, sample entropy, and multiscale entropy. I also demonstrate an example of using entropy for the complexity of glucose dynamics.

Preserving privacy of online digital physiological signals using blind and reversible steganography.

PubMed

Shiu, Hung-Jr; Lin, Bor-Sing; Huang, Chien-Hung; Chiang, Pei-Ying; Lei, Chin-Laung

2017-11-01

Physiological signals such as electrocardiograms (ECG) and electromyograms (EMG) are widely used to diagnose diseases. Presently, the Internet offers numerous cloud storage services which enable digital physiological signals to be uploaded for convenient access and use. Numerous online databases of medical signals have been built. The data in them must be processed in a manner that preserves patients' confidentiality. A reversible error-correcting-coding strategy will be adopted to transform digital physiological signals into a new bit-stream that uses a matrix in which is embedded the Hamming code to pass secret messages or private information. The shared keys are the matrix and the version of the Hamming code. An online open database, the MIT-BIH arrhythmia database, was used to test the proposed algorithms. The time-complexity, capacity and robustness are evaluated. Comparisons of several evaluations subject to related work are also proposed. This work proposes a reversible, low-payload steganographic scheme for preserving the privacy of physiological signals. An (n,  m)-hamming code is used to insert (n - m) secret bits into n bits of a cover signal. The number of embedded bits per modification is higher than in comparable methods, and the computational power is efficient and the scheme is secure. Unlike other Hamming-code based schemes, the proposed scheme is both reversible and blind. Copyright © 2017 Elsevier B.V. All rights reserved.

Fluid flow in the osteocyte mechanical environment: a fluid-structure interaction approach.

PubMed

Verbruggen, Stefaan W; Vaughan, Ted J; McNamara, Laoise M

2014-01-01

Osteocytes are believed to be the primary sensor of mechanical stimuli in bone, which orchestrate osteoblasts and osteoclasts to adapt bone structure and composition to meet physiological loading demands. Experimental studies to quantify the mechanical environment surrounding bone cells are challenging, and as such, computational and theoretical approaches have modelled either the solid or fluid environment of osteocytes to predict how these cells are stimulated in vivo. Osteocytes are an elastic cellular structure that deforms in response to the external fluid flow imposed by mechanical loading. This represents a most challenging multi-physics problem in which fluid and solid domains interact, and as such, no previous study has accounted for this complex behaviour. The objective of this study is to employ fluid-structure interaction (FSI) modelling to investigate the complex mechanical environment of osteocytes in vivo. Fluorescent staining of osteocytes was performed in order to visualise their native environment and develop geometrically accurate models of the osteocyte in vivo. By simulating loading levels representative of vigorous physiological activity ([Formula: see text] compression and 300 Pa pressure gradient), we predict average interstitial fluid velocities [Formula: see text] and average maximum shear stresses [Formula: see text] surrounding osteocytes in vivo. Interestingly, these values occur in the canaliculi around the osteocyte cell processes and are within the range of stimuli known to stimulate osteogenic responses by osteoblastic cells in vitro. Significantly our results suggest that the greatest mechanical stimulation of the osteocyte occurs in the cell processes, which, cell culture studies have indicated, is the most mechanosensitive area of the cell. These are the first computational FSI models to simulate the complex multi-physics mechanical environment of osteocyte in vivo and provide a deeper understanding of bone mechanobiology.

Advances in heart rate variability signal analysis: joint position statement by the e-Cardiology ESC Working Group and the European Heart Rhythm Association co-endorsed by the Asia Pacific Heart Rhythm Society.

PubMed

Sassi, Roberto; Cerutti, Sergio; Lombardi, Federico; Malik, Marek; Huikuri, Heikki V; Peng, Chung-Kang; Schmidt, Georg; Yamamoto, Yoshiharu

2015-09-01

Following the publication of the Task Force document on heart rate variability (HRV) in 1996, a number of articles have been published to describe new HRV methodologies and their application in different physiological and clinical studies. This document presents a critical review of the new methods. A particular attention has been paid to methodologies that have not been reported in the 1996 standardization document but have been more recently tested in sufficiently sized populations. The following methods were considered: Long-range correlation and fractal analysis; Short-term complexity; Entropy and regularity; and Nonlinear dynamical systems and chaotic behaviour. For each of these methods, technical aspects, clinical achievements, and suggestions for clinical application were reviewed. While the novel approaches have contributed in the technical understanding of the signal character of HRV, their success in developing new clinical tools, such as those for the identification of high-risk patients, has been rather limited. Available results obtained in selected populations of patients by specialized laboratories are nevertheless of interest but new prospective studies are needed. The investigation of new parameters, descriptive of the complex regulation mechanisms of heart rate, has to be encouraged because not all information in the HRV signal is captured by traditional methods. The new technologies thus could provide after proper validation, additional physiological, and clinical meaning. Multidisciplinary dialogue and specialized courses in the combination of clinical cardiology and complex signal processing methods seem warranted for further advances in studies of cardiac oscillations and in the understanding normal and abnormal cardiac control processes. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.

Differential flank growth

NASA Astrophysics Data System (ADS)

Zieschang, H. E.; Sievers, A.

1994-08-01

With the mathematical basis for the precise analysis of developmental processes in plants, the patterns of growth in phototropic and gravitropic responses have become better understood. A detailed temporal and spatial quantification of a growth process is an important tool for evaluating hypotheses about the underlying physiological mechanisms. Studies of growth rates and curvature show that the original Cholodny-Went hypothesis cannot explain the complex growth patterns during tropic responses of shoots and roots. In addition, regulating factors other than the lateral redistribution of hormones must be taken into account. Electrophysiological studies on roots led to a modification of the Cholodny-Went hypothesis in that redistributions of bioelectrical activities are observed.

Neuroimmunology of disordered sleep in depression and alcoholism.

PubMed

Irwin, M

2001-11-01

The specific functions of sleep are not known, although sleep is commonly considered a restorative process that is important for the proper functioning of the immune system. Severity of disordered sleep in depressed and alcoholic subjects correlates with declines in natural and cellular immunity and is associated with alterations in the complex cytokine network. Despite evidence that sleep and sleep loss have effects on immune processes and nocturnal secretion of cytokines, the physiological significance of these immune changes is not known. Moreover, in view of basic evidence of a reciprocal interaction between sleep and cytokines, further research is needed to understand whether alterations in cytokines contribute to disordered sleep.

Arachidonic-acid-derived eicosanoids: roles in biology and immunopathology.

PubMed

Harizi, Hedi; Corcuff, Jean-Benoît; Gualde, Norbert

2008-10-01

Arachidonic acid (AA)-derived eicosanoids belong to a complex family of lipid mediators that regulate a wide variety of physiological responses and pathological processes. They are produced by various cell types through distinct enzymatic pathways and act on target cells via specific G-protein-coupled receptors. Although originally recognized for their capacity to elicit biological responses such as vascular homeostasis, protection of the gastric mucosa and platelet aggregation, eicosanoids are now understood to regulate immunopathological processes ranging from inflammatory responses to chronic tissue remodelling, cancer, asthma, rheumatoid arthritis and autoimmune disorders. Here, we review the major properties of eicosanoids and their expanding roles in biology and medicine.

Optimizing the management of elderly colorectal surgery patients.

PubMed

Tan, Kok-Yang; Konishi, Fumio; Tan, Lawrence; Chin, Wui-Kin; Ong, Hean-Yee; Tan, Phyllis

2010-11-01

With the ever increasing number of geriatric surgical patients, there is a need to develop efficient processes that address all of the potential issues faced by patients during the perioperative period. This article explores the physiological changes in elderly surgical patients and the outcomes achieved after major abdominal surgery. Perioperative management strategies for elderly surgical patients in line with the practices of the Geriatric Surgical Team of Alexandra Health, Singapore, are also presented. A coordinated transdisciplinary approach best tackles the complexities encountered in these patients.

Making useful gadgets with miniaturized G proteins

PubMed Central

Martemyanov, Kirill A.; Garcia-Marcos, Mikel

2018-01-01

G protein–coupled receptors (GPCRs) relay information from extracellular stimuli to intracellular responses in a wide range of physiological and pathological processes, but understanding their complex effects in live cells is a daunting task. In this issue of JBC, Wan et al. repurpose “mini G proteins”—previously used as affinity tools for structural studies—to develop a suite of probes to visualize GPCR activation in live cells. The approach is expected to revolutionize our understanding of the spatiotemporal control and mechanisms of GPCR signaling. PMID:29752421

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

Showercap Mindmap: A Spatial Activity for Learning Physiology Terminology and Location

ERIC Educational Resources Information Center

Vanags, Thea; Budimlic, Mira; Herbert, Elissa; Montgomery, Melena M.; Vickers, Tracy

2012-01-01

Students struggle with the volume and complexity of physiology terminology. We compared first-year undergraduate psychology students' learning of physiological terms using two teaching methods: one verbal (control group; n = 16) and one spatial and multisensory (experimental group; n = 19). The experimental group used clear plastic shower caps to…

Medicine and the call for a moral epistemology, part II: constructing a synthesis of values.

PubMed

Tauber, Alfred I

2008-01-01

The demands and needs of an individual patient require diverse value judgments to interpret and apply clinical data. Indeed, objective assessment takes on particular meaning in the context of the social and existential status of the patient, and thereby a complex calculus of values determines therapeutic goals. I have previously formulated how this moral thread of care becomes woven into the epistemological project as a "moral epistemology." Having argued its ethical justification elsewhere, I offer another perspective here: clinical choices employ diverse values directed at an array of goals, some of which are derived from a universal clinical science and others from the particular physiological, psychological, and social needs of the patient. Integrating these diverse elements that determine clinical care requires a complex synthesis of facts and judgments from several domains. This constructivist process relies on clinical facts, as well as on personal judgments and subjective assessments in an ongoing negotiation between patient and doctor. A philosophy of medicine must account for the conceptual basis of this process by identifying and addressing the judgments that govern the complex synthesis of these various elements.

Network Analysis of Postharvest Senescence Process in Citrus Fruits Revealed by Transcriptomic and Metabolomic Profiling1[OPEN

PubMed Central

Ding, Yuduan; Chang, Jiwei; Ma, Qiaoli; Chen, Lingling; Liu, Shuzhen; Jin, Shuai; Han, Jingwen; Xu, Rangwei; Zhu, Andan; Guo, Jing; Luo, Yi; Xu, Juan; Xu, Qiang; Zeng, YunLiu; Deng, Xiuxin

2015-01-01

Citrus (Citrus spp.), a nonclimacteric fruit, is one of the most important fruit crops in global fruit industry. However, the biological behavior of citrus fruit ripening and postharvest senescence remains unclear. To better understand the senescence process of citrus fruit, we analyzed data sets from commercial microarrays, gas chromatography-mass spectrometry, and liquid chromatography-mass spectrometry and validated physiological quality detection of four main varieties in the genus Citrus. Network-based approaches of data mining and modeling were used to investigate complex molecular processes in citrus. The Citrus Metabolic Pathway Network and correlation networks were constructed to explore the modules and relationships of the functional genes/metabolites. We found that the different flesh-rind transport of nutrients and water due to the anatomic structural differences among citrus varieties might be an important factor that influences fruit senescence behavior. We then modeled and verified the citrus senescence process. As fruit rind is exposed directly to the environment, which results in energy expenditure in response to biotic and abiotic stresses, nutrients are exported from flesh to rind to maintain the activity of the whole fruit. The depletion of internal substances causes abiotic stresses, which further induces phytohormone reactions, transcription factor regulation, and a series of physiological and biochemical reactions. PMID:25802366

Estimating the decomposition of predictive information in multivariate systems

NASA Astrophysics Data System (ADS)

Faes, Luca; Kugiumtzis, Dimitris; Nollo, Giandomenico; Jurysta, Fabrice; Marinazzo, Daniele

2015-03-01

In the study of complex systems from observed multivariate time series, insight into the evolution of one system may be under investigation, which can be explained by the information storage of the system and the information transfer from other interacting systems. We present a framework for the model-free estimation of information storage and information transfer computed as the terms composing the predictive information about the target of a multivariate dynamical process. The approach tackles the curse of dimensionality employing a nonuniform embedding scheme that selects progressively, among the past components of the multivariate process, only those that contribute most, in terms of conditional mutual information, to the present target process. Moreover, it computes all information-theoretic quantities using a nearest-neighbor technique designed to compensate the bias due to the different dimensionality of individual entropy terms. The resulting estimators of prediction entropy, storage entropy, transfer entropy, and partial transfer entropy are tested on simulations of coupled linear stochastic and nonlinear deterministic dynamic processes, demonstrating the superiority of the proposed approach over the traditional estimators based on uniform embedding. The framework is then applied to multivariate physiologic time series, resulting in physiologically well-interpretable information decompositions of cardiovascular and cardiorespiratory interactions during head-up tilt and of joint brain-heart dynamics during sleep.

Consensus statement understanding health and malnutrition through a systems approach: the ENOUGH program for early life.

PubMed

Kaput, Jim; van Ommen, Ben; Kremer, Bas; Priami, Corrado; Monteiro, Jacqueline Pontes; Morine, Melissa; Pepping, Fre; Diaz, Zoey; Fenech, Michael; He, Yiwu; Albers, Ruud; Drevon, Christian A; Evelo, Chris T; Hancock, Robert E W; Ijsselmuiden, Carel; Lumey, L H; Minihane, Anne-Marie; Muller, Michael; Murgia, Chiara; Radonjic, Marijana; Sobral, Bruno; West, Keith P

2014-01-01

Nutrition research, like most biomedical disciplines, adopted and often uses experimental approaches based on Beadle and Tatum's one gene-one polypeptide hypothesis, thereby reducing biological processes to single reactions or pathways. Systems thinking is needed to understand the complexity of health and disease processes requiring measurements of physiological processes, as well as environmental and social factors, which may alter the expression of genetic information. Analysis of physiological processes with omics technologies to assess systems' responses has only become available over the past decade and remains costly. Studies of environmental and social conditions known to alter health are often not connected to biomedical research. While these facts are widely accepted, developing and conducting comprehensive research programs for health are often beyond financial and human resources of single research groups. We propose a new research program on essential nutrients for optimal underpinning of growth and health (ENOUGH) that will use systems approaches with more comprehensive measurements and biostatistical analysis of the many biological and environmental factors that influence undernutrition. Creating a knowledge base for nutrition and health is a necessary first step toward developing solutions targeted to different populations in diverse social and physical environments for the two billion undernourished people in developed and developing economies.

RNA-sequencing elucidates the regulation of behavioural transitions associated with the mating process in honey bee queens.

PubMed

Manfredini, Fabio; Brown, Mark J F; Vergoz, Vanina; Oldroyd, Benjamin P

2015-07-31

Mating is a complex process, which is frequently associated with behavioural and physiological changes. However, understanding of the genetic underpinnings of these changes is limited. Honey bees are both a model system in behavioural genomics, and the dominant managed pollinator of human crops; consequently understanding the mating process has both pure and applied value. We used next-generation transcriptomics to probe changes in gene expression in the brains of honey bee queens, as they transition from virgin to mated reproductive status. In addition, we used CO2-narcosis, which induces oviposition without mating, to isolate the process of reproductive maturation. The mating process produced significant changes in the expression of vision, chemo-reception, metabolic, and immune-related genes. Differential expression of these genes maps clearly onto known behavioural and physiological changes that occur during the transition from being a virgin queen to a newly-mated queen. A subset of these changes in gene expression were also detected in CO2-treated queens, as predicted from previous physiological studies. In addition, we compared our results to previous studies that used microarray techniques across a range of experimental time-points. Changes in expression of immune- and vision-related genes were common to all studies, supporting an involvement of these groups of genes in the mating process. Our study is an important step in understanding the molecular mechanisms regulating post-mating behavioural transitions in a natural system. The weak overlap in patterns of gene expression with previous studies demonstrates the high sensitivity of genome-wide approaches. Thus, while we build on previous microarray studies that explored post-mating changes in honey bees, the broader experimental design, use of RNA-sequencing, and focus on Australian honey bees, which remain free from the devastating parasite Varroa destructor, in the current study, provide unique insights into the biology of the mating process in honey bees.

The therapeutic use of the relaxation response in stress-related diseases.

PubMed

Esch, Tobias; Fricchione, Gregory L; Stefano, George B

2003-02-01

The objective of this work was to investigate a possible (therapeutic) connection between the relaxation response (RR) and stress-related diseases. Further, common underlying molecular mechanisms and autoregulatory pathways were examined. For the question of (patho)physiology and significance of RR techniques in the treatment of stress-related diseases, we analyzed peer-reviewed references only. The RR has been shown to be an appropriate and relevant therapeutic tool to counteract several stress-related disease processes and certain health-restrictions, particularly in certain immunological, cardiovascular, and neurodegenerative diseases/mental disorders. Further, common underlying molecular mechanisms may exist that represent a connection between the stress response, pathophysiological findings in stress-related diseases, and physiological changes/autoregulatory pathways described in the RR. Here, constitutive or low-output nitric oxide (NO) production may be involved in a protective or ameliorating context, whereas inducible, high-output NO release may facilitate detrimental disease processes. In mild or early disease states, a high degree of biological and physiological flexibility may still be possible (dynamic balance). Here, the therapeutic use of RR techniques may be considered particularly relevant, and the observable (beneficial) effects may be exerted via activation of constitutive NO pathways. RR techniques, regularly part of professional stress management or mind/body medical settings, represent an important tool to be added to therapeutic strategies dealing with stress-related diseases. Moreover, as part of 'healthy' life-style modifications, they may serve primary (or secondary) prevention. Further studies are necessary to elucidate the complex physiology underlying the RR and its impact upon stress-related disease states.

Metabolomic Analysis in Brain Research: Opportunities and Challenges

PubMed Central

Vasilopoulou, Catherine G.; Margarity, Marigoula; Klapa, Maria I.

2016-01-01

Metabolism being a fundamental part of molecular physiology, elucidating the structure and regulation of metabolic pathways is crucial for obtaining a comprehensive perspective of cellular function and understanding the underlying mechanisms of its dysfunction(s). Therefore, quantifying an accurate metabolic network activity map under various physiological conditions is among the major objectives of systems biology in the context of many biological applications. Especially for CNS, metabolic network activity analysis can substantially enhance our knowledge about the complex structure of the mammalian brain and the mechanisms of neurological disorders, leading to the design of effective therapeutic treatments. Metabolomics has emerged as the high-throughput quantitative analysis of the concentration profile of small molecular weight metabolites, which act as reactants and products in metabolic reactions and as regulatory molecules of proteins participating in many biological processes. Thus, the metabolic profile provides a metabolic activity fingerprint, through the simultaneous analysis of tens to hundreds of molecules of pathophysiological and pharmacological interest. The application of metabolomics is at its standardization phase in general, and the challenges for paving a standardized procedure are even more pronounced in brain studies. In this review, we support the value of metabolomics in brain research. Moreover, we demonstrate the challenges of designing and setting up a reliable brain metabolomic study, which, among other parameters, has to take into consideration the sex differentiation and the complexity of brain physiology manifested in its regional variation. We finally propose ways to overcome these challenges and design a study that produces reproducible and consistent results. PMID:27252656

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.

Characterizing the Interaction between tartrazine and two serum albumins by a hybrid spectroscopic approach.

PubMed

Pan, Xingren; Qin, Pengfei; Liu, Rutao; Wang, Jing

2011-06-22

Tartrazine is an artificial azo dye commonly used in food products. The present study evaluated the interaction of tartrazine with two serum albumins (SAs), human serum albumin (HSA) and bovine serum albumin (BSA), under physiological conditions by means of fluorescence, three-dimensional fluorescence, UV-vis absorption, and circular dichroism (CD) techniques. The fluorescence data showed that tartrazine could bind to the two SAs to form a complex. The binding process was a spontaneous molecular interaction procedure, in which van der Waals and hydrogen bond interactions played a major role. Additionally, as shown by the UV-vis absorption, three-dimensional fluorescence, and CD results, tartrazine could lead to conformational and some microenvironmental changes of both SAs, which may affect the physiological functions of SAs. The work provides important insight into the mechanism of toxicity of tartrazine in vivo.

The physiological and pathological biophysics of phase separation and gelation of RNA binding proteins in amyotrophic lateral sclerosis and fronto-temporal lobar degeneration.

PubMed

St George-Hyslop, Peter; Lin, Julie Qiaojin; Miyashita, Akinori; Phillips, Emma C; Qamar, Seema; Randle, Suzanne J; Wang, GuoZhen

2018-04-30

Many RNA binding proteins, including FUS, contain moderately repetitive, low complexity, intrinsically disordered domains. These sequence motifs have recently been found to underpin reversible liquid: liquid phase separation and gelation of these proteins, permitting them to reversibly transition from a monodispersed state to liquid droplet- or hydrogel-like states. This function allows the proteins to serve as scaffolds for the formation of reversible membraneless intracellular organelles such as nucleoli, stress granules and neuronal transport granules. Using FUS as an example, this review examines the biophysics of this physiological process, and reports on how mutations and changes in post-translational state alter phase behaviour, and lead to neurodegenerative diseases such as amyotrophic lateral sclerosis and frontotemporal lobar degeneration. Copyright © 2018. Published by Elsevier B.V.

Experience Modulates the Reproductive Response to Heat Stress in C. elegans via Multiple Physiological Processes

PubMed Central

Gouvêa, Devin Y.; Aprison, Erin Z.; Ruvinsky, Ilya

2015-01-01

Natural environments are considerably more variable than laboratory settings and often involve transient exposure to stressful conditions. To fully understand how organisms have evolved to respond to any given stress, prior experience must therefore be considered. We investigated the effects of individual and ancestral experience on C. elegans reproduction. We documented ways in which cultivation at 15°C or 25°C affects developmental time, lifetime fecundity, and reproductive performance after severe heat stress that exceeds the fertile range of the organism but is compatible with survival and future fecundity. We found that experience modulates multiple aspects of reproductive physiology, including the male and female germ lines and the interaction between them. These responses vary in their environmental sensitivity, suggesting the existence of complex mechanisms for coping with unpredictable and stressful environments. PMID:26713620

Complexity Variability Assessment of Nonlinear Time-Varying Cardiovascular Control

NASA Astrophysics Data System (ADS)

Valenza, Gaetano; Citi, Luca; Garcia, Ronald G.; Taylor, Jessica Noggle; Toschi, Nicola; Barbieri, Riccardo

2017-02-01

The application of complex systems theory to physiology and medicine has provided meaningful information about the nonlinear aspects underlying the dynamics of a wide range of biological processes and their disease-related aberrations. However, no studies have investigated whether meaningful information can be extracted by quantifying second-order moments of time-varying cardiovascular complexity. To this extent, we introduce a novel mathematical framework termed complexity variability, in which the variance of instantaneous Lyapunov spectra estimated over time serves as a reference quantifier. We apply the proposed methodology to four exemplary studies involving disorders which stem from cardiology, neurology and psychiatry: Congestive Heart Failure (CHF), Major Depression Disorder (MDD), Parkinson’s Disease (PD), and Post-Traumatic Stress Disorder (PTSD) patients with insomnia under a yoga training regime. We show that complexity assessments derived from simple time-averaging are not able to discern pathology-related changes in autonomic control, and we demonstrate that between-group differences in measures of complexity variability are consistent across pathologies. Pathological states such as CHF, MDD, and PD are associated with an increased complexity variability when compared to healthy controls, whereas wellbeing derived from yoga in PTSD is associated with lower time-variance of complexity.

Rapid, Optimized Interactomic Screening

PubMed Central

Hakhverdyan, Zhanna; Domanski, Michal; Hough, Loren; Oroskar, Asha A.; Oroskar, Anil R.; Keegan, Sarah; Dilworth, David J.; Molloy, Kelly R.; Sherman, Vadim; Aitchison, John D.; Fenyö, David; Chait, Brian T.; Jensen, Torben Heick; Rout, Michael P.; LaCava, John

2015-01-01

We must reliably map the interactomes of cellular macromolecular complexes in order to fully explore and understand biological systems. However, there are no methods to accurately predict how to capture a given macromolecular complex with its physiological binding partners. Here, we present a screen that comprehensively explores the parameters affecting the stability of interactions in affinity-captured complexes, enabling the discovery of physiological binding partners and the elucidation of their functional interactions in unparalleled detail. We have implemented this screen on several macromolecular complexes from a variety of organisms, revealing novel profiles even for well-studied proteins. Our approach is robust, economical and automatable, providing an inroad to the rigorous, systematic dissection of cellular interactomes. PMID:25938370

Regulation of metabolism by the Mediator complex.

PubMed

Youn, Dou Yeon; Xiaoli, Alus M; Pessin, Jeffrey E; Yang, Fajun

2016-01-01

The Mediator complex was originally discovered in yeast, but it is conserved in all eukaryotes. Its best-known function is to regulate RNA polymerase II-dependent gene transcription. Although the mechanisms by which the Mediator complex regulates transcription are often complicated by the context-dependent regulation, this transcription cofactor complex plays a pivotal role in numerous biological pathways. Biochemical, molecular, and physiological studies using cancer cell lines or model organisms have established the current paradigm of the Mediator functions. However, the physiological roles of the mammalian Mediator complex remain poorly defined, but have attracted a great interest in recent years. In this short review, we will summarize some of the reported functions of selective Mediator subunits in the regulation of metabolism. These intriguing findings suggest that the Mediator complex may be an important player in nutrient sensing and energy balance in mammals.

Blood-brain barrier-on-a-chip: Microphysiological systems that capture the complexity of the blood-central nervous system interface.

PubMed

Phan, Duc Tt; Bender, R Hugh F; Andrejecsk, Jillian W; Sobrino, Agua; Hachey, Stephanie J; George, Steven C; Hughes, Christopher Cw

2017-11-01

The blood-brain barrier is a dynamic and highly organized structure that strictly regulates the molecules allowed to cross the brain vasculature into the central nervous system. The blood-brain barrier pathology has been associated with a number of central nervous system diseases, including vascular malformations, stroke/vascular dementia, Alzheimer's disease, multiple sclerosis, and various neurological tumors including glioblastoma multiforme. There is a compelling need for representative models of this critical interface. Current research relies heavily on animal models (mostly mice) or on two-dimensional (2D) in vitro models, neither of which fully capture the complexities of the human blood-brain barrier. Physiological differences between humans and mice make translation to the clinic problematic, while monolayer cultures cannot capture the inherently three-dimensional (3D) nature of the blood-brain barrier, which includes close association of the abluminal side of the endothelium with astrocyte foot-processes and pericytes. Here we discuss the central nervous system diseases associated with blood-brain barrier pathology, recent advances in the development of novel 3D blood-brain barrier -on-a-chip systems that better mimic the physiological complexity and structure of human blood-brain barrier, and provide an outlook on how these blood-brain barrier-on-a-chip systems can be used for central nervous system disease modeling. Impact statement The field of microphysiological systems is rapidly evolving as new technologies are introduced and our understanding of organ physiology develops. In this review, we focus on Blood-Brain Barrier (BBB) models, with a particular emphasis on how they relate to neurological disorders such as Alzheimer's disease, multiple sclerosis, stroke, cancer, and vascular malformations. We emphasize the importance of capturing the three-dimensional nature of the brain and the unique architecture of the BBB - something that until recently had not been well modeled by in vitro systems. Our hope is that this review will provide a launch pad for new ideas and methodologies that can provide us with truly physiological BBB models capable of yielding new insights into the function of this critical interface.

Simulating physiological interactions in a hybrid system of mathematical models.

PubMed

Kretschmer, Jörn; Haunsberger, Thomas; Drost, Erick; Koch, Edmund; Möller, Knut

2014-12-01

Mathematical models can be deployed to simulate physiological processes of the human organism. Exploiting these simulations, reactions of a patient to changes in the therapy regime can be predicted. Based on these predictions, medical decision support systems (MDSS) can help in optimizing medical therapy. An MDSS designed to support mechanical ventilation in critically ill patients should not only consider respiratory mechanics but should also consider other systems of the human organism such as gas exchange or blood circulation. A specially designed framework allows combining three model families (respiratory mechanics, cardiovascular dynamics and gas exchange) to predict the outcome of a therapy setting. Elements of the three model families are dynamically combined to form a complex model system with interacting submodels. Tests revealed that complex model combinations are not computationally feasible. In most patients, cardiovascular physiology could be simulated by simplified models decreasing computational costs. Thus, a simplified cardiovascular model that is able to reproduce basic physiological behavior is introduced. This model purely consists of difference equations and does not require special algorithms to be solved numerically. The model is based on a beat-to-beat model which has been extended to react to intrathoracic pressure levels that are present during mechanical ventilation. The introduced reaction to intrathoracic pressure levels as found during mechanical ventilation has been tuned to mimic the behavior of a complex 19-compartment model. Tests revealed that the model is able to represent general system behavior comparable to the 19-compartment model closely. Blood pressures were calculated with a maximum deviation of 1.8 % in systolic pressure and 3.5 % in diastolic pressure, leading to a simulation error of 0.3 % in cardiac output. The gas exchange submodel being reactive to changes in cardiac output showed a resulting deviation of less than 0.1 %. Therefore, the proposed model is usable in combinations where cardiovascular simulation does not have to be detailed. Computing costs have been decreased dramatically by a factor 186 compared to a model combination employing the 19-compartment model.

Applying systems biology methods to the study of human physiology in extreme environments

PubMed Central

2013-01-01

Systems biology is defined in this review as ‘an iterative process of computational model building and experimental model revision with the aim of understanding or simulating complex biological systems’. We propose that, in practice, systems biology rests on three pillars: computation, the omics disciplines and repeated experimental perturbation of the system of interest. The number of ethical and physiologically relevant perturbations that can be used in experiments on healthy humans is extremely limited and principally comprises exercise, nutrition, infusions (e.g. Intralipid), some drugs and altered environment. Thus, we argue that systems biology and environmental physiology are natural symbionts for those interested in a system-level understanding of human biology. However, despite excellent progress in high-altitude genetics and several proteomics studies, systems biology research into human adaptation to extreme environments is in its infancy. A brief description and overview of systems biology in its current guise is given, followed by a mini review of computational methods used for modelling biological systems. Special attention is given to high-altitude research, metabolic network reconstruction and constraint-based modelling. PMID:23849719

Novel delivery methods bypassing the blood-brain and blood-tumor barriers.

PubMed

Hendricks, Benjamin K; Cohen-Gadol, Aaron A; Miller, James C

2015-03-01

Glioblastoma (GBM) is the most common primary brain tumor and carries a grave prognosis. Despite years of research investigating potentially new therapies for GBM, the median survival rate of individuals with this disease has remained fairly stagnant. Delivery of drugs to the tumor site is hampered by various barriers posed by the GBM pathological process and by the complex physiology of the blood-brain and blood-cerebrospinal fluid barriers. These anatomical and physiological barriers serve as a natural protection for the brain and preserve brain homeostasis, but they also have significantly limited the reach of intraparenchymal treatments in patients with GBM. In this article, the authors review the functional capabilities of the physical and physiological barriers that impede chemotherapy for GBM, with a specific focus on the pathological alterations of the blood-brain barrier (BBB) in this disease. They also provide an overview of current and future methods for circumventing these barriers in therapeutic interventions. Although ongoing research has yielded some potential options for future GBM therapies, delivery of chemotherapy medications across the BBB remains elusive and has limited the efficacy of these medications.

Proline Precursors and Collagen Synthesis: Biochemical Challenges of Nutrient Supplementation and Wound Healing.

PubMed

Albaugh, Vance L; Mukherjee, Kaushik; Barbul, Adrian

2017-11-01

Wound healing is a complex process marked by highly coordinated immune fluxes into an area of tissue injury; these are required for re-establishment of normal tissue integrity. Along with this cascade of cellular players, wound healing also requires coordinated flux through a number of biochemical pathways, leading to synthesis of collagen and recycling or removal of damaged tissues. The availability of nutrients, especially amino acids, is critical for wound healing, and enteral supplementation has been intensely studied as a potential mechanism to augment wound healing-either by increasing tensile strength, decreasing healing time, or both. From a practical standpoint, although enteral nutrient supplementation may seem like a reasonable strategy to augment healing, a number of biochemical and physiologic barriers exist that limit this strategy. In this critical review, the physiology of enteral amino acid metabolism and supplementation and challenges therein are discussed in the context of splanchnic physiology and biochemistry. Additionally, a review of studies examining various methods of amino acid supplementation and the associated effects on wound outcomes are discussed. © 2017 American Society for Nutrition.

The perception of odor objects in everyday life: a review on the processing of odor mixtures

PubMed Central

Thomas-Danguin, Thierry; Sinding, Charlotte; Romagny, Sébastien; El Mountassir, Fouzia; Atanasova, Boriana; Le Berre, Elodie; Le Bon, Anne-Marie; Coureaud, Gérard

2014-01-01

Smelling monomolecular odors hardly ever occurs in everyday life, and the daily functioning of the sense of smell relies primarily on the processing of complex mixtures of volatiles that are present in the environment (e.g., emanating from food or conspecifics). Such processing allows for the instantaneous recognition and categorization of smells and also for the discrimination of odors among others to extract relevant information and to adapt efficiently in different contexts. The neurophysiological mechanisms underpinning this highly efficient analysis of complex mixtures of odorants is beginning to be unraveled and support the idea that olfaction, as vision and audition, relies on odor-objects encoding. This configural processing of odor mixtures, which is empirically subject to important applications in our societies (e.g., the art of perfumers, flavorists, and wine makers), has been scientifically studied only during the last decades. This processing depends on many individual factors, among which are the developmental stage, lifestyle, physiological and mood state, and cognitive skills; this processing also presents striking similarities between species. The present review gathers the recent findings, as observed in animals, healthy subjects, and/or individuals with affective disorders, supporting the perception of complex odor stimuli as odor objects. It also discusses peripheral to central processing, and cognitive and behavioral significance. Finally, this review highlights that the study of odor mixtures is an original window allowing for the investigation of daily olfaction and emphasizes the need for knowledge about the underlying biological processes, which appear to be crucial for our representation and adaptation to the chemical environment. PMID:24917831

Understanding Immunology via Engineering Design: The Role of Mathematical Prototyping

PubMed Central

Klinke, David J.; Wang, Qing

2012-01-01

A major challenge in immunology is how to translate data into knowledge given the inherent complexity and dynamics of human physiology. Both the physiology and engineering communities have rich histories in applying computational approaches to translate data obtained from complex systems into knowledge of system behavior. However, there are some differences in how disciplines approach problems. By referring to mathematical models as mathematical prototypes, we aim to highlight aspects related to the process (i.e., prototyping) rather than the product (i.e., the model). The objective of this paper is to review how two related engineering concepts, specifically prototyping and “fitness for use,” can be applied to overcome the pressing challenge in translating data into improved knowledge of basic immunology that can be used to improve therapies for disease. These concepts are illustrated using two immunology-related examples. The prototypes presented focus on the beta cell mass at the onset of type 1 diabetes and the dynamics of dendritic cells in the lung. This paper is intended to illustrate some of the nuances associated with applying mathematical modeling to improve understanding of the dynamics of disease progression in humans. PMID:22973412

The Role of Adenosine A2A Receptor, CYP450s, and PPARs in the Regulation of Vascular Tone

PubMed Central

Khayat, Maan T.

2017-01-01

Adenosine is an endogenous mediator involved in a myriad of physiologic functions, including vascular tone regulation. It is also implicated in some pathologic conditions. Four distinct receptor subtypes mediate the effects of adenosine, such as its role in the regulation of the vascular tone. Vascular tone regulation is a complex and continuous process which involves many mechanisms and mediators that are not fully disclosed. The vascular endothelium plays a pivotal role in regulating blood flow to and from all body organs. Also, the vascular endothelium is not merely a physical barrier; it is a complex tissue with numerous functions. Among adenosine receptors, A2A receptor subtype (A2AAR) stands out as the primary receptor responsible for the vasodilatory effects of adenosine. This review focuses on important effectors of the vascular endothelium, including adenosine, adenosine receptors, EETs (epoxyeicosatrienoic acids), HETEs (hydroxyeicosatetraenoic acids), PPARs (peroxisome proliferator-activated receptors), and KATP channels. Given the impact of vascular tone regulation in cardiovascular physiology and pathophysiology, better understanding of the mechanisms affecting it could have a significant potential for developing therapeutic agents for cardiovascular diseases. PMID:28884118

A Network-Based Algorithm for Clustering Multivariate Repeated Measures Data

NASA Technical Reports Server (NTRS)

Koslovsky, Matthew; Arellano, John; Schaefer, Caroline; Feiveson, Alan; Young, Millennia; Lee, Stuart

2017-01-01

The National Aeronautics and Space Administration (NASA) Astronaut Corps is a unique occupational cohort for which vast amounts of measures data have been collected repeatedly in research or operational studies pre-, in-, and post-flight, as well as during multiple clinical care visits. In exploratory analyses aimed at generating hypotheses regarding physiological changes associated with spaceflight exposure, such as impaired vision, it is of interest to identify anomalies and trends across these expansive datasets. Multivariate clustering algorithms for repeated measures data may help parse the data to identify homogeneous groups of astronauts that have higher risks for a particular physiological change. However, available clustering methods may not be able to accommodate the complex data structures found in NASA data, since the methods often rely on strict model assumptions, require equally-spaced and balanced assessment times, cannot accommodate missing data or differing time scales across variables, and cannot process continuous and discrete data simultaneously. To fill this gap, we propose a network-based, multivariate clustering algorithm for repeated measures data that can be tailored to fit various research settings. Using simulated data, we demonstrate how our method can be used to identify patterns in complex data structures found in practice.

AmapSim: a structural whole-plant simulator based on botanical knowledge and designed to host external functional models.

PubMed

Barczi, Jean-François; Rey, Hervé; Caraglio, Yves; de Reffye, Philippe; Barthélémy, Daniel; Dong, Qiao Xue; Fourcaud, Thierry

2008-05-01

AmapSim is a tool that implements a structural plant growth model based on a botanical theory and simulates plant morphogenesis to produce accurate, complex and detailed plant architectures. This software is the result of more than a decade of research and development devoted to plant architecture. New advances in the software development have yielded plug-in external functions that open up the simulator to functional processes. The simulation of plant topology is based on the growth of a set of virtual buds whose activity is modelled using stochastic processes. The geometry of the resulting axes is modelled by simple descriptive functions. The potential growth of each bud is represented by means of a numerical value called physiological age, which controls the value for each parameter in the model. The set of possible values for physiological ages is called the reference axis. In order to mimic morphological and architectural metamorphosis, the value allocated for the physiological age of buds evolves along this reference axis according to an oriented finite state automaton whose occupation and transition law follows a semi-Markovian function. Simulations were performed on tomato plants to demonstrate how the AmapSim simulator can interface external modules, e.g. a GREENLAB growth model and a radiosity model. The algorithmic ability provided by AmapSim, e.g. the reference axis, enables unified control to be exercised over plant development parameter values, depending on the biological process target: how to affect the local pertinent process, i.e. the pertinent parameter(s), while keeping the rest unchanged. This opening up to external functions also offers a broadened field of applications and thus allows feedback between plant growth and the physical environment.

AmapSim: A Structural Whole-plant Simulator Based on Botanical Knowledge and Designed to Host External Functional Models

PubMed Central

Barczi, Jean-François; Rey, Hervé; Caraglio, Yves; de Reffye, Philippe; Barthélémy, Daniel; Dong, Qiao Xue; Fourcaud, Thierry

2008-01-01

Background and Aims AmapSim is a tool that implements a structural plant growth model based on a botanical theory and simulates plant morphogenesis to produce accurate, complex and detailed plant architectures. This software is the result of more than a decade of research and development devoted to plant architecture. New advances in the software development have yielded plug-in external functions that open up the simulator to functional processes. Methods The simulation of plant topology is based on the growth of a set of virtual buds whose activity is modelled using stochastic processes. The geometry of the resulting axes is modelled by simple descriptive functions. The potential growth of each bud is represented by means of a numerical value called physiological age, which controls the value for each parameter in the model. The set of possible values for physiological ages is called the reference axis. In order to mimic morphological and architectural metamorphosis, the value allocated for the physiological age of buds evolves along this reference axis according to an oriented finite state automaton whose occupation and transition law follows a semi-Markovian function. Key Results Simulations were performed on tomato plants to demostrate how the AmapSim simulator can interface external modules, e.g. a GREENLAB growth model and a radiosity model. Conclusions The algorithmic ability provided by AmapSim, e.g. the reference axis, enables unified control to be exercised over plant development parameter values, depending on the biological process target: how to affect the local pertinent process, i.e. the pertinent parameter(s), while keeping the rest unchanged. This opening up to external functions also offers a broadened field of applications and thus allows feedback between plant growth and the physical environment. PMID:17766310

Advanced Physiological Estimation of Cognitive Status (APECS)

DTIC Science & Technology

2009-09-15

REPORT Advanced Physiological Estimation of Cognitive Status (APECS) Final Report 14. ABSTRACT 16. SECURITY CLASSIFICATION OF: EEG...fitness and transmit data to command and control systems. Some of the signals that the physiological sensors measure are readily interpreted, such as...electroencephalogram (EEG) and other signals requires a complex series of mathematical transformations or algorithms. Overall, research on algorithms

Identification of the TFII-I family target genes in the vertebrate genome.

PubMed

Chimge, Nyam-Osor; Makeyev, Aleksandr V; Ruddle, Frank H; Bayarsaihan, Dashzeveg

2008-07-01

GTF2I and GTF2IRD1 encode members of the TFII-I transcription factor family and are prime candidates in the Williams syndrome, a complex neurodevelopmental disorder. Our previous expression microarray studies implicated TFII-I proteins in the regulation of a number of genes critical in various aspects of cell physiology. Here, we combined bioinformatics and microarray results to identify TFII-I downstream targets in the vertebrate genome. These results were validated by chromatin immunoprecipitation and siRNA analysis. The collected evidence revealed the complexity of TFII-I-mediated processes that involve distinct regulatory networks. Altogether, these results lead to a better understanding of specific molecular events, some of which may be responsible for the Williams syndrome phenotype.

Regulation of Mammalian Physiology by Interconnected Circadian and Feeding Rhythms

PubMed Central

Atger, Florian; Mauvoisin, Daniel; Weger, Benjamin; Gobet, Cédric; Gachon, Frédéric

2017-01-01

Circadian clocks are endogenous timekeeping systems that adapt in an anticipatory fashion the physiology and behavior of most living organisms. In mammals, the master pacemaker resides in the suprachiasmatic nucleus and entrains peripheral clocks using a wide range of signals that differentially schedule physiology and gene expression in a tissue-specific manner. The peripheral clocks, such as those found in the liver, are particularly sensitive to rhythmic external cues like feeding behavior, which modulate the phase and amplitude of rhythmic gene expression. Consequently, the liver clock temporally tunes the expression of many genes involved in metabolism and physiology. However, the circadian modulation of cellular functions also relies on multiple layers of posttranscriptional and posttranslational regulation. Strikingly, these additional regulatory events may happen independently of any transcriptional oscillations, showing that complex regulatory networks ultimately drive circadian output functions. These rhythmic events also integrate feeding-related cues and adapt various metabolic processes to food availability schedules. The importance of such temporal regulation of metabolism is illustrated by metabolic dysfunctions and diseases resulting from circadian clock disruption or inappropriate feeding patterns. Therefore, the study of circadian clocks and rhythmic feeding behavior should be of interest to further advance our understanding of the prevention and therapy of metabolic diseases. PMID:28337174

Single-trial lie detection using a combined fNIRS-polygraph system

PubMed Central

Bhutta, M. Raheel; Hong, Melissa J.; Kim, Yun-Hee; Hong, Keum-Shik

2015-01-01

Deception is a human behavior that many people experience in daily life. It involves complex neuronal activities in addition to several physiological changes in the body. A polygraph, which can measure some of the physiological responses from the body, has been widely employed in lie-detection. Many researchers, however, believe that lie detection can become more precise if the neuronal changes that occur in the process of deception can be isolated and measured. In this study, we combine both measures (i.e., physiological and neuronal changes) for enhanced lie-detection. Specifically, to investigate the deception-related hemodynamic response, functional near-infrared spectroscopy (fNIRS) is applied at the prefrontal cortex besides a commercially available polygraph system. A mock crime scenario with a single-trial stimulus is set up as a deception protocol. The acquired data are classified into “true” and “lie” classes based on the fNIRS-based hemoglobin-concentration changes and polygraph-based physiological signal changes. Linear discriminant analysis is utilized as a classifier. The results indicate that the combined fNIRS-polygraph system delivers much higher classification accuracy than that of a singular system. This study demonstrates a plausible solution toward single-trial lie-detection by combining fNIRS and the polygraph. PMID:26082733

An integrated approach to develop, validate and operate thermo-physiological human simulator for the development of protective clothing.

PubMed

Psikuta, Agnes; Koelblen, Barbara; Mert, Emel; Fontana, Piero; Annaheim, Simon

2017-12-07

Following the growing interest in the further development of manikins to simulate human thermal behaviour more adequately, thermo-physiological human simulators have been developed by coupling a thermal sweating manikin with a thermo-physiology model. Despite their availability and obvious advantages, the number of studies involving these devices is only marginal, which plausibly results from the high complexity of the development and evaluation process and need of multi-disciplinary expertise. The aim of this paper is to present an integrated approach to develop, validate and operate such devices including technical challenges and limitations of thermo-physiological human simulators, their application and measurement protocol, strategy for setting test scenarios, and the comparison to standard methods and human studies including details which have not been published so far. A physical manikin controlled by a human thermoregulation model overcame the limitations of mathematical clothing models and provided a complementary method to investigate thermal interactions between the human body, protective clothing, and its environment. The opportunities of these devices include not only realistic assessment of protective clothing assemblies and equipment but also potential application in many research fields ranging from biometeorology, automotive industry, environmental engineering, and urban climate to clinical and safety applications.

An integrated approach to develop, validate and operate thermo-physiological human simulator for the development of protective clothing

PubMed Central

PSIKUTA, Agnes; KOELBLEN, Barbara; MERT, Emel; FONTANA, Piero; ANNAHEIM, Simon

2017-01-01

Following the growing interest in the further development of manikins to simulate human thermal behaviour more adequately, thermo-physiological human simulators have been developed by coupling a thermal sweating manikin with a thermo-physiology model. Despite their availability and obvious advantages, the number of studies involving these devices is only marginal, which plausibly results from the high complexity of the development and evaluation process and need of multi-disciplinary expertise. The aim of this paper is to present an integrated approach to develop, validate and operate such devices including technical challenges and limitations of thermo-physiological human simulators, their application and measurement protocol, strategy for setting test scenarios, and the comparison to standard methods and human studies including details which have not been published so far. A physical manikin controlled by a human thermoregulation model overcame the limitations of mathematical clothing models and provided a complementary method to investigate thermal interactions between the human body, protective clothing, and its environment. The opportunities of these devices include not only realistic assessment of protective clothing assemblies and equipment but also potential application in many research fields ranging from biometeorology, automotive industry, environmental engineering, and urban climate to clinical and safety applications. PMID:28966294

Beyond Fractals and 1/f Noise: Multifractal Analysis of Complex Physiological Time Series

NASA Astrophysics Data System (ADS)

Ivanov, Plamen Ch.; Amaral, Luis A. N.; Ashkenazy, Yosef; Stanley, H. Eugene; Goldberger, Ary L.; Hausdorff, Jeffrey M.; Yoneyama, Mitsuru; Arai, Kuniharu

2001-03-01

We investigate time series with 1/f-like spectra generated by two physiologic control systems --- the human heartbeat and human gait. We show that physiological fluctuations exhibit unexpected ``hidden'' structures often described by scaling laws. In particular, our studies indicate that when analyzed on different time scales the heartbeat fluctuations exhibit cascades of branching patterns with self-similar (fractal) properties, characterized by long-range power-law anticorrelations. We find that these scaling features change during sleep and wake phases, and with pathological perturbations. Further, by means of a new wavelet-based technique, we find evidence of multifractality in the healthy human heartbeat even under resting conditions, and show that the multifractal character and nonlinear properties of the healthy heart are encoded in the Fourier phases. We uncover a loss of multifractality for a life-threatening condition, congestive heart failure. In contrast to the heartbeat, we find that the interstride interval time series of healthy human gait, a voluntary process under neural regulation, is described by a single fractal dimension (such as classical 1/f noise) indicating monofractal behavior. Thus our approach can help distinguish physiological and physical signals with comparable frequency spectra and two-point correlations, and guide modeling of their control mechanisms.

Apoptosis in Alzheimer's disease: an understanding of the physiology, pathology and therapeutic avenues.

PubMed

Obulesu, M; Lakshmi, M Jhansi

2014-12-01

Alzheimer's disease (AD) is a devastative neurodegenerative disorder with complex etiology. Apoptosis, a biological process that plays an essential role in normal physiology to oust a few cells and contribute to the normal growth, when impaired or influenced by various factors such as Bcl2, Bax, caspases, amyloid beta, tumor necrosis factor-α, amyloid precursor protein intracellular C-terminal domain, reactive oxygen species, perturbation of enzymes leads to deleterious neurodegenerative disorders like AD. There are diverse pathways that provoke manifold events in mitochondria and endoplasmic reticulum (ER) to execute the process of cell death. This review summarizes the crucial apoptotic mechanisms occurring in both mitochondria and ER. It gives substantial summary of the diverse mechanisms studied in vivo and in vitro. A brief account on neuroprotection of several bioactive components, flavonoids and antioxidants of plants against apoptotic events of both mitochondria and ER in both in vitro and in vivo has been discussed. In light of this, the burgeoning need to develop animal models to study the efficacy of various therapeutic effects has been accentuated.

Salicylic acid beyond defence: its role in plant growth and development.

PubMed

Rivas-San Vicente, Mariana; Plasencia, Javier

2011-06-01

In recent years salicylic acid (SA) has been the focus of intensive research due to its function as an endogenous signal mediating local and systemic plant defence responses against pathogens. It has also been found that SA plays a role during the plant response to abiotic stresses such as drought, chilling, heavy metal toxicity, heat, and osmotic stress. In this sense, SA appears to be, just like in mammals, an 'effective therapeutic agent' for plants. Besides this function during biotic and abiotic stress, SA plays a crucial role in the regulation of physiological and biochemical processes during the entire lifespan of the plant. The discovery of its targets and the understanding of its molecular modes of action in physiological processes could help in the dissection of the complex SA signalling network, confirming its important role in both plant health and disease. Here, the evidence that supports the role of SA during plant growth and development is reviewed by comparing experiments performed by exogenous application of SA with analysis of genotypes affected by SA levels and/or perception.

Principles for integrating reactive species into in vivo biological processes: Examples from exercise physiology.

PubMed

Margaritelis, Nikos V; Cobley, James N; Paschalis, Vassilis; Veskoukis, Aristidis S; Theodorou, Anastasios A; Kyparos, Antonios; Nikolaidis, Michalis G

2016-04-01

The equivocal role of reactive species and redox signaling in exercise responses and adaptations is an example clearly showing the inadequacy of current redox biology research to shed light on fundamental biological processes in vivo. Part of the answer probably relies on the extreme complexity of the in vivo redox biology and the limitations of the currently applied methodological and experimental tools. We propose six fundamental principles that should be considered in future studies to mechanistically link reactive species production to exercise responses or adaptations: 1) identify and quantify the reactive species, 2) determine the potential signaling properties of the reactive species, 3) detect the sources of reactive species, 4) locate the domain modified and verify the (ir)reversibility of post-translational modifications, 5) establish causality between redox and physiological measurements, 6) use selective and targeted antioxidants. Fulfilling these principles requires an idealized human experimental setting, which is certainly a utopia. Thus, researchers should choose to satisfy those principles, which, based on scientific evidence, are most critical for their specific research question. Copyright © 2015 Elsevier Inc. All rights reserved.

Understanding brassinosteroid-regulated mechanisms to improve stress tolerance in plants: a critical review.

PubMed

Nawaz, Fahim; Naeem, Muhammad; Zulfiqar, Bilal; Akram, Asim; Ashraf, Muhammad Yasin; Raheel, Muhammad; Shabbir, Rana Nauman; Hussain, Rai Altaf; Anwar, Irfan; Aurangzaib, Muhammad

2017-07-01

Brassinosteroids (BRs) are steroidal plant hormones involved in regulation of physiological and molecular processes to ameliorate various biotic and abiotic stresses. Exogenous application of BRs to improve stress tolerance in plants has recently become a high research priority. Several studies have revealed the involvement of these steroidal hormones in upregulation of stress-related defense genes and their cross talk with other metabolic pathways. This is likely to stimulate research on many unanswered questions regarding their role in enhancing the ability of plants to tolerate adverse environmental conditions. Thus, this review appraises new insights on mechanisms mediating BR-regulated changes in plants, focused mainly on their involvement in regulation of physiological and molecular mechanisms under stress conditions. Herein, examples of BR-stimulated modulation of antioxidant defense system and upregulation of transcription factors in plants exposed to various biotic (bacterial, viral, and fungal attack) and abiotic stresses (drought, salinity, heat, low temperature, and heavy metal stress) are discussed. Based on these insights, future research in the current direction can be helpful to increase our understanding of BR-mediated complex and interrelated processes under stress conditions.

Classical Renin-Angiotensin System in Kidney Physiology

PubMed Central

Sparks, Matthew A.; Crowley, Steven D.; Gurley, Susan B.; Mirotsou, Maria; Coffman, Thomas M.

2014-01-01

The renin-angiotensin system has powerful effects in control of the blood pressure and sodium homeostasis. These actions are coordinated through integrated actions in the kidney, cardio-vascular system and the central nervous system. Along with its impact on blood pressure, the renin-angiotensin system also influences a range of processes from inflammation and immune responses to longevity. Here, we review the actions of the “classical” renin-angiotensin system, whereby the substrate protein angiotensinogen is processed in a two-step reaction by renin and angiotensin converting enzyme, resulting in the sequential generation of angiotensin I and angiotensin II, the major biologically active renin-angiotensin system peptide, which exerts its actions via type 1 and type 2 angiotensin receptors. In recent years, several new enzymes, peptides, and receptors related to the renin-angiotensin system have been identified, manifesting a complexity that was previously unappreciated. While the functions of these alternative pathways will be reviewed elsewhere in this journal, our focus here is on the physiological role of components of the “classical” renin-angiotensin system, with an emphasis on new developments and modern concepts. PMID:24944035

Mathematical modeling and experimental testing of three bioreactor configurations based on windkessel models

PubMed Central

Ruel, Jean; Lachance, Geneviève

2010-01-01

This paper presents an experimental study of three bioreactor configurations. The bioreactor is intended to be used for the development of tissue-engineered heart valve substitutes. Therefore it must be able to reproduce physiological flow and pressure waveforms accurately. A detailed analysis of three bioreactor arrangements is presented using mathematical models based on the windkessel (WK) approach. First, a review of the many applications of this approach in medical studies enhances its fundamental nature and its usefulness. Then the models are developed with reference to the actual components of the bioreactor. This study emphasizes different conflicting issues arising in the design process of a bioreactor for biomedical purposes, where an optimization process is essential to reach a compromise satisfying all conditions. Two important aspects are the need for a simple system providing ease of use and long-term sterility, opposed to the need for an advanced (thus more complex) architecture capable of a more accurate reproduction of the physiological environment. Three classic WK architectures are analyzed, and experimental results enhance the advantages and limitations of each one. PMID:21977286

Semi-automated Modular Program Constructor for physiological modeling: Building cell and organ models.

PubMed

Jardine, Bartholomew; Raymond, Gary M; Bassingthwaighte, James B

2015-01-01

The Modular Program Constructor (MPC) is an open-source Java based modeling utility, built upon JSim's Mathematical Modeling Language (MML) ( http://www.physiome.org/jsim/) that uses directives embedded in model code to construct larger, more complicated models quickly and with less error than manually combining models. A major obstacle in writing complex models for physiological processes is the large amount of time it takes to model the myriad processes taking place simultaneously in cells, tissues, and organs. MPC replaces this task with code-generating algorithms that take model code from several different existing models and produce model code for a new JSim model. This is particularly useful during multi-scale model development where many variants are to be configured and tested against data. MPC encodes and preserves information about how a model is built from its simpler model modules, allowing the researcher to quickly substitute or update modules for hypothesis testing. MPC is implemented in Java and requires JSim to use its output. MPC source code and documentation are available at http://www.physiome.org/software/MPC/.

Quantification of brain macrostates using dynamical nonstationarity of physiological time series.

PubMed

Latchoumane, Charles-Francois Vincent; Jeong, Jaeseung

2011-04-01

The brain shows complex, nonstationarity temporal dynamics, with abrupt micro- and macrostate transitions during its information processing. Detecting and characterizing these transitions in dynamical states of the brain is a critical issue in the field of neuroscience and psychiatry. In the current study, a novel method is proposed to quantify brain macrostates (e.g., sleep stages or cognitive states) from shifts of dynamical microstates or dynamical nonstationarity. A ``dynamical microstate'' is a temporal unit of the information processing in the brain with fixed dynamical parameters and specific spatial distribution. In this proposed approach, a phase-space-based dynamical dissimilarity map (DDM) is used to detect transitions between dynamically stationary microstates in the time series, and Tsallis time-dependent entropy is applied to quantify dynamical patterns of transitions in the DDM. We demonstrate that the DDM successfully detects transitions between microstates of different temporal dynamics in the simulated physiological time series against high levels of noise. Based on the assumption of nonlinear, deterministic brain dynamics, we also demonstrate that dynamical nonstationarity analysis is useful to quantify brain macrostates (sleep stages I, II, III, IV, and rapid eye movement (REM) sleep) from sleep EEGs with an overall accuracy of 77%. We suggest that dynamical nonstationarity is a useful tool to quantify macroscopic mental states (statistical integration) of the brain using dynamical transitions at the microscopic scale in physiological data.

Physiological changes in neurodegeneration - mechanistic insights and clinical utility.

PubMed

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

2018-05-01

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

Genomic and transcriptomic approaches to study immunology in cyprinids: What is next?

PubMed

Petit, Jules; David, Lior; Dirks, Ron; Wiegertjes, Geert F

2017-10-01

Accelerated by the introduction of Next-Generation Sequencing (NGS), a number of genomes of cyprinid fish species have been drafted, leading to a highly valuable collective resource of comparative genome information on cyprinids (Cyprinidae). In addition, NGS-based transcriptome analyses of different developmental stages, organs, or cell types, increasingly contribute to the understanding of complex physiological processes, including immune responses. Cyprinids are a highly interesting family because they comprise one of the most-diversified families of teleosts and because of their variation in ploidy level, with diploid, triploid, tetraploid, hexaploid and sometimes even octoploid species. The wealth of data obtained from NGS technologies provides both challenges and opportunities for immunological research, which will be discussed here. Correct interpretation of ploidy effects on immune responses requires knowledge of the degree of functional divergence between duplicated genes, which can differ even between closely-related cyprinid fish species. We summarize NGS-based progress in analysing immune responses and discuss the importance of respecting the presence of (multiple) duplicated gene sequences when performing transcriptome analyses for detailed understanding of complex physiological processes. Progressively, advances in NGS technology are providing workable methods to further elucidate the implications of gene duplication events and functional divergence of duplicates genes and proteins involved in immune responses in cyprinids. We conclude with discussing how future applications of NGS technologies and analysis methods could enhance immunological research and understanding. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Phenotyping of subjects for large scale studies on patients with IBS.

PubMed

Boeckxstaens, G E; Drug, V; Dumitrascu, D; Farmer, A D; Hammer, J; Hausken, T; Niesler, B; Pohl, D; Pojskic, L; Polster, A; Simren, M; Goebel-Stengel, M; Van Oudenhove, L; Vassallo, M; Wensaas, K-A; Aziz, Q; Houghton, L A

2016-08-01

Irritable bowel syndrome (IBS) is a complex condition with multiple factors contributing to its aetiology and pathophysiology. Aetiologically these include genetics, life-time events and environment, and physiologically, changes in motility, central processing, visceral sensitivity, immunity, epithelial permeability and gastrointestinal microflora. Such complexity means there is currently no specific reliable biomarker for IBS, and thus IBS continues to be diagnosed and classified according to symptom based criteria, the Rome Criteria. Carefully phenotyping and characterisation of a 'large' pool of IBS patients across Europe and even the world however, might help identify sub-populations with accuracy and consistency. This will not only aid future research but improve tailoring of treatment and health care of IBS patients. The aim of this position paper is to discuss the requirements necessary to standardize the process of selecting and phenotyping IBS patients and how to organise the collection and storage of patient information/samples in such a large multi-centre pan European/global study. We include information on general demographics, gastrointestinal symptom assessment, psychological factors, quality of life, physiological evaluation, genetic/epigenetic and microbiota analysis, biopsy/blood sampling, together with discussion on the organisational, ethical and language issues associated with implementing such a study. The proposed approach and documents selected to be used in such a study was the result of a thoughtful and thorough four-year dialogue amongst experts associated with the European COST action BM1106 GENIEUR (www.GENIEUR.eu). © 2016 John Wiley & Sons Ltd.

Rice Physiology

Treesearch

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

2002-01-01

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

Structures of Human Pumilio with Noncognate RNAs Reveal Molecular Mechanisms for Binding Promiscuity

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

Gupta,Y.; Nair, D.; Wharton, R.

2008-01-01

Pumilio is a founder member of the evolutionarily conserved Puf family of RNA-binding proteins that control a number of physiological processes in eukaryotes. A structure of human Pumilio (hPum) Puf domain bound to a Drosophila regulatory sequence showed that each Puf repeat recognizes a single nucleotide. Puf domains in general bind promiscuously to a large set of degenerate sequences, but the structural basis for this promiscuity has been unclear. Here, we describe the structures of hPum Puf domain complexed to two noncognate RNAs, CycBreverse and Puf5. In each complex, one of the nucleotides is ejected from the binding surface, inmore » effect, acting as a 'spacer.' The complexes also reveal the plasticity of several Puf repeats, which recognize noncanonical nucleotides. Together, these complexes provide a molecular basis for recognition of degenerate binding sites, which significantly increases the number of mRNAs targeted for regulation by Puf proteins in vivo.« less

Targeting mechanisms of high voltage-activated Ca2+ channels.

PubMed

Herlitze, Stefan; Xie, Mian; Han, Jing; Hümmer, Alexander; Melnik-Martinez, Katya V; Moreno, Rosa L; Mark, Melanie D

2003-12-01

Functional voltage-dependent Ca2+ channel complexes are assembled by three to four subunits: alpha1, beta, alpha2delta subunits (C. Leveque et al., 1994, J. Biol Chem. 269, 6306-6312; M. W. McEnery et al., 1991, Proc. Natl. Acad. Sci. U.S.A. 88, 11095-11099) and at least in muscle cells also y subunits (B. M. Curtis and W. A. Catterall, 1984, Biochemistry 23, 2113-2118). Ca2+ channels mediate the voltage-dependent Ca2+ influx in subcellular compartments, triggering such diverse processes as neurotransmitter release, dendritic action potentials, excitation-contraction, and excitation-transcription coupling. The targeting of biophysically defined Ca2+ channel complexes to the correct subcellular structures is, thus, critical to proper cell and physiological functioning. Despite their importance, surprisingly little is known about the targeting mechanisms by which Ca2+ channel complexes are transported to their site of function. Here we summarize what we know about the targeting of Ca2+ channel complexes through the cell to the plasma membrane and subcellular structures.

The BAF60 Subunit of the SWI/SNF Chromatin-Remodeling Complex Directly Controls the Formation of a Gene Loop at FLOWERING LOCUS C in Arabidopsis[W

PubMed Central

Jégu, Teddy; Latrasse, David; Delarue, Marianne; Hirt, Heribert; Domenichini, Séverine; Ariel, Federico; Crespi, Martin; Bergounioux, Catherine; Raynaud, Cécile; Benhamed, Moussa

2014-01-01

SWI/SNF complexes mediate ATP-dependent chromatin remodeling to regulate gene expression. Many components of these complexes are evolutionarily conserved, and several subunits of Arabidopsis thaliana SWI/SNF complexes are involved in the control of flowering, a process that depends on the floral repressor FLOWERING LOCUS C (FLC). BAF60 is a SWI/SNF subunit, and in this work, we show that BAF60, via a direct targeting of the floral repressor FLC, induces a change at the high-order chromatin level and represses the photoperiod flowering pathway in Arabidopsis. BAF60 accumulates in the nucleus and controls the formation of the FLC gene loop by modulation of histone density, composition, and posttranslational modification. Physiological analysis of BAF60 RNA interference mutant lines allowed us to propose that this chromatin-remodeling protein creates a repressive chromatin configuration at the FLC locus. PMID:24510722

Subcellular pigment distribution is altered under far-red light acclimation in cyanobacteria that contain chlorophyll f.

PubMed

Majumder, Erica L-W; Wolf, Benjamin M; Liu, Haijun; Berg, R Howard; Timlin, Jerilyn A; Chen, Min; Blankenship, Robert E

2017-11-01

Far-Red Light (FRL) acclimation is a process that has been observed in cyanobacteria and algae that can grow solely on light above 700 nm. The acclimation to FRL results in rearrangement and synthesis of new pigments and pigment-protein complexes. In this study, cyanobacteria containing chlorophyll f, Synechococcus sp. PCC 7335 and Halomicronema hongdechloris, were imaged as live cells with confocal microscopy. H. hongdechloris was further studied with hyperspectral confocal fluorescence microscopy (HCFM) and freeze-substituted thin-section transmission electron microscopy (TEM). Under FRL, phycocyanin-containing complexes and chlorophyll-containing complexes were determined to be physically separated and the synthesis of red-form phycobilisome and Chl f was increased. The timing of these responses was observed. The heterogeneity and eco-physiological response of the cells was noted. Additionally, a gliding motility for H. hongdechloris is reported.

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

Ren, Hao; Zhang, Yu; Guo, Sibei

The aggregation of amyloid beta (Aβ) peptides plays a crucial role in the pathology and etiology of Alzheimer's disease. Experimental evidence shows that copper ion is an aggregation-prone species with the ability to coordinately bind to Aβ and further induce the formation of neurotoxic Aβ oligomers. However, the detailed structures of Cu(II)–Aβ complexes have not been illustrated, and the kinetics and dynamics of the Cu(II) binding are not well understood. Two Cu(II)–Aβ complexes have been proposed to exist under physiological conditions, and another two might exist at higher pH values. By using ab initio simulations for the spontaneous resonance Ramanmore » and time domain stimulated resonance Raman spectroscopy signals, we obtained the characteristic Raman vibronic features of each complex. Finally, these signals contain rich structural information with high temporal resolution, enabling the characterization of transient states during the fast Cu–Aβ binding and interconversion processes.« less

Reactions of ferric hemoglobin and myoglobin with hydrogen sulfide under physiological conditions.

PubMed

Jensen, Birgitte; Fago, Angela

2018-05-01

Ferric hemoglobin (metHb) and myoglobin (metMb), present at low levels in vivo, have been recently found to oxidize hydrogen sulfide (H 2 S) in excess, thus potentially contributing to removal of toxic H 2 S in blood and heart, respectively. Here, we present a kinetic and thermodynamic study of the reaction of metHb and metMb with H 2 S under physiological conditions, i.e. at low H 2 S concentrations and with protein in excess of H 2 S. We show here that both proteins react with sub-stoichiometric H 2 S:heme ratios following two processes: a fast reversible binding of H 2 S to ferric heme that prevails at high H 2 S and a slow heme reduction to the ferrous state that prevails at low H 2 S. While these two processes are fast for metMb, H 2 S-induced heme reduction is slow for metHb and the metHb-H 2 S complex once formed is therefore relatively stable. We find that metHb binds H 2 S reversibly and cooperatively with a pH-dependent ligand affinity that is within the physiological range of H 2 S concentrations found in blood. Stopped-flow kinetics show identical association rate constants for H 2 S at varying pH, demonstrating that H 2 S and not HS - enters the ferric heme pocket. Dissociation rates of the metHb-H 2 S complex increase when decreasing pH, consistent with the pH-dependent affinity. Taken together, these data are consistent with a novel biological role of metHb as a H 2 S carrier in the blood, in parallel with the oxygen carrier function of the much more abundant ferrous Hb. In contrast, metMb in the heart could participate to redox-signaling involving H 2 S. Copyright © 2018 Elsevier Inc. All rights reserved.

Large Variability in the Diversity of Physiologically Complex Surgical Procedures Exists Nationwide Among All Hospitals Including Among Large Teaching Hospitals.

PubMed

Dexter, Franklin; Epstein, Richard H; Thenuwara, Kokila; Lubarsky, David A

2017-11-22

Multiple previous studies have shown that having a large diversity of procedures has a substantial impact on quality management of hospital surgical suites. At hospitals with substantial diversity, unless sophisticated statistical methods suitable for rare events are used, anesthesiologists working in surgical suites will have inaccurate predictions of surgical blood usage, case durations, cost accounting and price transparency, times remaining in late running cases, and use of intraoperative equipment. What is unknown is whether large diversity is a feature of only a few very unique set of hospitals nationwide (eg, the largest hospitals in each state or province). The 2013 United States Nationwide Readmissions Database was used to study heterogeneity among 1981 hospitals in their diversities of physiologically complex surgical procedures (ie, the procedure codes). The diversity of surgical procedures performed at each hospital was quantified using a summary measure, the number of different physiologically complex surgical procedures commonly performed at the hospital (ie, 1/Herfindahl). A total of 53.9% of all hospitals commonly performed <10 physiologically complex procedures (lower 99% confidence limit [CL], 51.3%). A total of 14.2% (lower 99% CL, 12.4%) of hospitals had >3-fold larger diversity (ie, >30 commonly performed physiologically complex procedures). Larger hospitals had greater diversity than the small- and medium-sized hospitals (P < .0001). Teaching hospitals had greater diversity than did the rural and urban nonteaching hospitals (P < .0001). A total of 80.0% of the 170 large teaching hospitals commonly performed >30 procedures (lower 99% CL, 71.9% of hospitals). However, there was considerable variability among the large teaching hospitals in their diversity (interquartile range of the numbers of commonly performed physiologically complex procedures = 19.3; lower 99% CL, 12.8 procedures). The diversity of procedures represents a substantive differentiator among hospitals. Thus, the usefulness of statistical methods for operating room management should be expected to be heterogeneous among hospitals. Our results also show that "large teaching hospital" alone is an insufficient description for accurate prediction of the extent to which a hospital sustains the operational and financial consequences of performing a wide diversity of surgical procedures. Future research can evaluate the extent to which hospitals with very large diversity are indispensable in their catchment area.

On the Evolution of the Mammalian Brain.

PubMed

Torday, John S; Miller, William B

2016-01-01

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

A novel encoding Lempel-Ziv complexity algorithm for quantifying the irregularity of physiological time series.

PubMed

Zhang, Yatao; Wei, Shoushui; Liu, Hai; Zhao, Lina; Liu, Chengyu

2016-09-01

The Lempel-Ziv (LZ) complexity and its variants have been extensively used to analyze the irregularity of physiological time series. To date, these measures cannot explicitly discern between the irregularity and the chaotic characteristics of physiological time series. Our study compared the performance of an encoding LZ (ELZ) complexity algorithm, a novel variant of the LZ complexity algorithm, with those of the classic LZ (CLZ) and multistate LZ (MLZ) complexity algorithms. Simulation experiments on Gaussian noise, logistic chaotic, and periodic time series showed that only the ELZ algorithm monotonically declined with the reduction in irregularity in time series, whereas the CLZ and MLZ approaches yielded overlapped values for chaotic time series and time series mixed with Gaussian noise, demonstrating the accuracy of the proposed ELZ algorithm in capturing the irregularity, rather than the complexity, of physiological time series. In addition, the effect of sequence length on the ELZ algorithm was more stable compared with those on CLZ and MLZ, especially when the sequence length was longer than 300. A sensitivity analysis for all three LZ algorithms revealed that both the MLZ and the ELZ algorithms could respond to the change in time sequences, whereas the CLZ approach could not. Cardiac interbeat (RR) interval time series from the MIT-BIH database were also evaluated, and the results showed that the ELZ algorithm could accurately measure the inherent irregularity of the RR interval time series, as indicated by lower LZ values yielded from a congestive heart failure group versus those yielded from a normal sinus rhythm group (p < 0.01). Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Complex network models reveal correlations among network metrics, exercise intensity and role of body changes in the fatigue process

PubMed Central

Pereira, Vanessa Helena; Gama, Maria Carolina Traina; Sousa, Filipe Antônio Barros; Lewis, Theodore Gyle; Gobatto, Claudio Alexandre; Manchado - Gobatto, Fúlvia Barros

2015-01-01

The aims of the present study were analyze the fatigue process at distinct intensity efforts and to investigate its occurrence as interactions at distinct body changes during exercise, using complex network models. For this, participants were submitted to four different running intensities until exhaustion, accomplished in a non-motorized treadmill using a tethered system. The intensities were selected according to critical power model. Mechanical (force, peak power, mean power, velocity and work) and physiological related parameters (heart rate, blood lactate, time until peak blood lactate concentration (lactate time), lean mass, anaerobic and aerobic capacities) and IPAQ score were obtained during exercises and it was used to construction of four complex network models. Such models have both, theoretical and mathematical value, and enables us to perceive new insights that go beyond conventional analysis. From these, we ranked the influences of each node at the fatigue process. Our results shows that nodes, links and network metrics are sensibility according to increase of efforts intensities, been the velocity a key factor to exercise maintenance at models/intensities 1 and 2 (higher time efforts) and force and power at models 3 and 4, highlighting mechanical variables in the exhaustion occurrence and even training prescription applications. PMID:25994386

Complex network models reveal correlations among network metrics, exercise intensity and role of body changes in the fatigue process

NASA Astrophysics Data System (ADS)

Pereira, Vanessa Helena; Gama, Maria Carolina Traina; Sousa, Filipe Antônio Barros; Lewis, Theodore Gyle; Gobatto, Claudio Alexandre; Manchado-Gobatto, Fúlvia Barros

2015-05-01

The aims of the present study were analyze the fatigue process at distinct intensity efforts and to investigate its occurrence as interactions at distinct body changes during exercise, using complex network models. For this, participants were submitted to four different running intensities until exhaustion, accomplished in a non-motorized treadmill using a tethered system. The intensities were selected according to critical power model. Mechanical (force, peak power, mean power, velocity and work) and physiological related parameters (heart rate, blood lactate, time until peak blood lactate concentration (lactate time), lean mass, anaerobic and aerobic capacities) and IPAQ score were obtained during exercises and it was used to construction of four complex network models. Such models have both, theoretical and mathematical value, and enables us to perceive new insights that go beyond conventional analysis. From these, we ranked the influences of each node at the fatigue process. Our results shows that nodes, links and network metrics are sensibility according to increase of efforts intensities, been the velocity a key factor to exercise maintenance at models/intensities 1 and 2 (higher time efforts) and force and power at models 3 and 4, highlighting mechanical variables in the exhaustion occurrence and even training prescription applications.

Metabolites involved in cellular communication among human cumulus-oocyte-complex and sperm during in vitro fertilization.

PubMed

Gómez-Torres, María José; García, Eva María; Guerrero, Jaime; Medina, Sonia; Izquierdo-Rico, María José; Gil-Izquierdo, Ángel; Orduna, Jesús; Savirón, María; González-Brusi, Leopoldo; Ten, Jorge; Bernabeu, Rafael; Avilés, Manuel

2015-11-09

Fertilization is a key physiological process for the preservation of the species. Consequently, different mechanisms affecting the sperm and the oocyte have been developed to ensure a successful fertilization. Thus, sperm acrosome reaction is necessary for the egg coat penetration and sperm-oolema fusion. Several molecules are able to induce the sperm acrosome reaction; however, this process should be produced coordinately in time and in the space to allow the success of fertilization between gametes. The goal of this study was to analyze the metabolites secreted by cumulus-oocyte-complex (COC) to find out new components that could contribute to the induction of the human sperm acrosome reaction and other physiological processes at the time of gamete interaction and fertilization. For the metabolomic analysis, eighteen aliquots of medium were used in each group, containing: a) only COC before insemination and after 3 h of incubation; b) COC and capacitated spermatozoa after insemination and incubated for 16-20 hours; c) only capacitated sperm after 16-20 h in culture and d) only fertilization medium as control. Six patients undergoing assisted reproduction whose male partners provided normozoospermic samples were included in the study. Seventy-two COC were inseminated. The metabolites identified were monoacylglycerol (MAG), lysophosphatidylcholine (LPC) and phytosphingosine (PHS). Analysis by PCR and in silico of the gene expression strongly suggests that the cumulus cells contribute to the formation of the PHS and LPC. LPC and PHS are secreted by cumulus cells during in vitro fertilization and they could be involved in the induction of human acrosome reaction (AR). The identification of new molecules with a paracrine effect on oocytes, cumulus cells and spermatozoa will provide a better understanding of gamete interaction.

The PREP pipeline: standardized preprocessing for large-scale EEG analysis.

PubMed

Bigdely-Shamlo, Nima; Mullen, Tim; Kothe, Christian; Su, Kyung-Min; Robbins, Kay A

2015-01-01

The technology to collect brain imaging and physiological measures has become portable and ubiquitous, opening the possibility of large-scale analysis of real-world human imaging. By its nature, such data is large and complex, making automated processing essential. This paper shows how lack of attention to the very early stages of an EEG preprocessing pipeline can reduce the signal-to-noise ratio and introduce unwanted artifacts into the data, particularly for computations done in single precision. We demonstrate that ordinary average referencing improves the signal-to-noise ratio, but that noisy channels can contaminate the results. We also show that identification of noisy channels depends on the reference and examine the complex interaction of filtering, noisy channel identification, and referencing. We introduce a multi-stage robust referencing scheme to deal with the noisy channel-reference interaction. We propose a standardized early-stage EEG processing pipeline (PREP) and discuss the application of the pipeline to more than 600 EEG datasets. The pipeline includes an automatically generated report for each dataset processed. Users can download the PREP pipeline as a freely available MATLAB library from http://eegstudy.org/prepcode.

Are We Listening to Music or Noise? Use of the Lyapunov Exponent for Comprehensive Assessment of Heart Rate Complexity During Hemorrhage in Sedated Conscious Miniature Swine

DTIC Science & Technology

2009-09-01

physiologic mechanisms underlying experimental observations: a practical example☆ Sven Zenker, Andreas Hoeft Department of Anaesthesiology and...to describe experi - mental data (goodness of fit) and its complexity (number of parameters). Their use in macroscopic physiologic investigations...BSP, and BRS could either be identical or vary across interventions, resulting in models with 4 to 12 parameters. After digitizing the experimental data

Interactions between rate processes with different timescales explain counterintuitive foraging patterns of arctic wintering eiders

PubMed Central

Heath, Joel P.; Gilchrist, H. Grant; Ydenberg, Ronald C.

2010-01-01

To maximize fitness, animals must respond to a variety of processes that operate at different rates or timescales. Appropriate decisions could therefore involve complex interactions among these processes. For example, eiders wintering in the arctic sea ice must consider locomotion and physiology of diving for benthic invertebrates, digestive processing rate and a nonlinear decrease in profitability of diving as currents increase over the tidal cycle. Using a multi-scale dynamic modelling approach and continuous field observations of individuals, we demonstrate that the strategy that maximizes long-term energy gain involves resting during the most profitable foraging period (slack currents). These counterintuitive foraging patterns are an adaptive trade-off between multiple overlapping rate processes and cannot be explained by classical rate-maximizing optimization theory, which only considers a single timescale and predicts a constant rate of foraging. By reducing foraging and instead digesting during slack currents, eiders structure their activity in order to maximize long-term energetic gain over an entire tide cycle. This study reveals how counterintuitive patterns and a complex functional response can result from a simple trade-off among several overlapping rate processes, emphasizing the necessity of a multi-scale approach for understanding adaptive routines in the wild and evaluating mechanisms in ecological time series. PMID:20504814

A Case Study of Infant Physiologic Response to Skin-to-Skin Contact After Surgery for Complex Congenital Heart Disease.

PubMed

Harrison, Tondi M; Ludington-Hoe, Susan

2015-01-01

Infants with complex congenital heart disease requiring surgical intervention within the first days or weeks of life may be the most seriously ill infants needing intensive nursing and medical care. Skin-to-skin contact (SSC) is well accepted and practiced as a positive therapeutic intervention in premature infants but is not routinely offered to infants in cardiac intensive care units. The physiologic effects of SSC in the congenital heart disease population must be examined before recommending incorporation of SSC into standard care routines. The purpose of this case study was to describe the physiologic response to a single session of SSC in an 18-day-old infant with hypoplastic left heart syndrome. Repeated measures of heart rate, respiratory rate, oxygen saturation, blood pressure, and temperature were recorded 30 minutes before SSC, during SSC (including interruptions for bottle and breast feedings), and 10 minutes after SSC was completed. All physiologic parameters were clinically acceptable throughout the 135-minute observation. This case study provides beginning evidence that SSC is safe in full-term infants after surgery for complex congenital heart disease. Further research with a larger sample is needed to examine the effects of SSC on infant physiology before surgery and earlier in the postoperative time period as well as on additional outcomes such as length of stay, maternal-infant interaction, and neurodevelopment.

Exploring the interactome: microfluidic isolation of proteins and interacting partners for quantitative analysis by electron microscopy.

PubMed

Giss, Dominic; Kemmerling, Simon; Dandey, Venkata; Stahlberg, Henning; Braun, Thomas

2014-05-20

Multimolecular protein complexes are important for many cellular processes. However, the stochastic nature of the cellular interactome makes the experimental detection of complex protein assemblies difficult and quantitative analysis at the single molecule level essential. Here, we present a fast and simple microfluidic method for (i) the quantitative isolation of endogenous levels of untagged protein complexes from minute volumes of cell lysates under close to physiological conditions and (ii) the labeling of specific components constituting these complexes. The method presented uses specific antibodies that are conjugated via a photocleavable linker to magnetic beads that are trapped in microcapillaries to immobilize the target proteins. Proteins are released by photocleavage, eluted, and subsequently analyzed by quantitative transmission electron microscopy at the single molecule level. Additionally, before photocleavage, immunogold can be employed to label proteins that interact with the primary target protein. Thus, the presented method provides a new way to study the interactome and, in combination with single molecule transmission electron microscopy, to structurally characterize the large, dynamic, heterogeneous multimolecular protein complexes formed.

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

PubMed Central

Yamashita, Hiroshi; Ueda, Kazumitsu; Kioka, Noriyuki

2011-01-01

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

Circadian clock: linking epigenetics to aging

PubMed Central

Orozco-Solis, Ricardo; Sassone-Corsi, Paolo

2015-01-01

Circadian rhythms are generated by an intrinsic cellular mechanism that controls a large array of physiological and metabolic processes. There is erosion in the robustness of circadian rhythms during aging, and disruption of the clock by genetic ablation of specific genes is associated with aging-related features. Importantly, environmental conditions are thought to modulate the aging process. For example, caloric restriction is a very strong environmental effector capable of delaying aging. Intracellular pathways implicating nutrient sensors, such as SIRTs and mTOR complexes, impinge on cellular and epigenetic mechanisms that control the aging process. Strikingly, accumulating evidences indicate that these pathways are involved in both the modulation of the aging process and the control of the clock. Hence, innovative therapeutic strategies focused at controlling the circadian clock and the nutrient sensing pathways might beneficially influence the negative effects of aging. PMID:25033025

Healing of the bone with anti-fracture drugs.

PubMed

Vannucci, Letizia; Brandi, Maria Luisa

2016-12-01

Fracture healing is a complex physiological process. As impaired fracture healing is more frequent in osteoporotic subjects, anti-osteoporotic drugs could have some impact on this process. Areas covered: We reviewed the current literature to evaluate the effects of these drugs on fracture healing and their potential role in supporting this process, especially when impaired. A PubMed/Medline search was undertaken combining the terms 'fracture healing', 'anti-resorptive drugs', 'anabolic agents', 'anti-osteoporotic drugs'. Expert opinion: As clinical evidence on the role of anti-osteoporotic drugs in the process of fracture healing consists mainly of case reports or studies with a relatively small number of patients, large randomized clinical trials are needed in order to extend to the human setting the promising results on these agents as inductors or co-adjuvants of bone healing derived from animal studies.

Mammalian follicular development and atresia: role of apoptosis.

PubMed

Asselin, E; Xiao, C W; Wang, Y F; Tsang, B K

2000-01-01

The regulation of follicular development and atresia is a complex process and involves interactions between endocrine factors (gonadotropins) and intraovarian regulators (sex steroids, growth factors and cytokines) in the control of follicular cell fate (i.e. proliferation, differentiation and programmed cell death). Granulosa and theca cells are key players in this fascinating process. As atresia is the fate of most follicles, understanding of how these physiological regulators participate in determining the destiny of the follicle (to degenerate or to ovulate) at cellular and subcellular levels is fundamental. This short review summarizes the role of intraovarian modulators of programmed cell death in the induction of atresia during follicular development. Copyright 2000 S. Karger AG, Basel

Neuro-immune modulation of the thymus microenvironment (review).

PubMed

Mignini, Fiorenzo; Sabbatini, Maurizio; Mattioli, Laura; Cosenza, Monica; Artico, Marco; Cavallotti, Carlo

2014-06-01

The thymus is the primary site for T-cell lympho-poiesis. Its function includes the maturation and selection of antigen specific T cells and selective release of these cells to the periphery. These highly complex processes require precise parenchymal organization and compartmentation where a plethora of signalling pathways occur, performing strict control on the maturation and selection processes of T lymphocytes. In this review, the main morphological characteristics of the thymus microenvironment, with particular emphasis on nerve fibers and neuropeptides were assessed, as both are responsible for neuro-immune‑modulation functions. Among several neurotransmitters that affect thymus function, we highlight the dopaminergic system as only recently has its importance on thymus function and lymphocyte physiology come to light.

Sleep and Cognition

PubMed Central

Deak, Maryann C.; Stickgold, Robert

2018-01-01

Sleep is a complex physiologic state, the importance of which has long been recognized. Lack of sleep is detrimental to humans and animals. Over the past decade, an important link between sleep and cognitive processing has been established. Sleep plays an important role in consolidation of different types of memory and contributes to insightful, inferential thinking. While the mechanism by which memories are processed in sleep remains unknown, several experimental models have been proposed. This article explores the link between sleep and cognition by reviewing (1) the effects of sleep deprivation on cognition, (2) the influence of sleep on consolidation of declarative and non-declarative memory, and 3) some proposed models of how sleep facilitates memory consolidation in sleep. PMID:26271496

Endocrine and other physiologic modulators of perinatal cardiomyocyte endowment

PubMed Central

Jonker, S S; Louey, S

2015-01-01

Immature contractile cardiomyocytes proliferate to rapidly increase cell number, establishing cardiomyocyte endowment in the perinatal period. Developmental changes in cellular maturation, size and attrition further contribute to cardiac anatomy. These physiological processes occur concomitant with a changing hormonal environment as the fetus prepares itself for the transition to extrauterine life. There are complex interactions between endocrine, hemodynamic and nutritional regulators of cardiac development. Birth has been long assumed to be the trigger for major differences between the fetal and postnatal cardiomyocyte growth patterns, but investigations in normally growing sheep and rodents suggest this may not be entirely true; in sheep, these differences are initiated before birth, while in rodents they occur after birth. The aim of this review is to draw together our understanding of the temporal regulation of these signals and cardiomyocyte responses relative to birth. Further, we consider how these dynamics are altered in stressed and suboptimal intrauterine environments. PMID:26432905

Dynamics of Lung Defense in Pneumonia: Resistance, Resilience, and Remodeling

PubMed Central

Quinton, Lee J.; Mizgerd, Joseph P.

2015-01-01

Pneumonia is initiated by microbes in the lung, but physiological processes integrating responses across diverse cell types and organ systems dictate the outcome of respiratory infection. Resistance, or actions of the host to eradicate living microbes, in the lungs involves a combination of innate and adaptive immune responses triggered by air-space infection. Resilience, or the ability of the host tissues to withstand the physiologically damaging effects of microbial and immune activities, is equally complex, precisely regulated, and determinative. Both immune resistance and tissue resilience are dynamic and change throughout the lifetime, but we are only beginning to understand such remodeling and how it contributes to the incidence of severe pneumonias, which diminishes as childhood progresses and then increases again among the elderly. Here, we review the concepts of resistance, resilience, and remodeling as they apply to pneumonia, highlighting recent advances and current significant knowledge gaps. PMID:25148693

Assay of Plasma Membrane H+-ATPase in Plant Tissues under Abiotic Stresses.

PubMed

Janicka, Małgorzata; Wdowikowska, Anna; Kłobus, Grażyna

2018-01-01

Plasma membrane (PM) H + -ATPase, which generates the proton gradient across the outer membrane of plant cells, plays a fundamental role in the regulation of many physiological processes fundamental for growth and development of plants. It is involved in the uptake of nutrients from external solutions, their loading into phloem and long-distance transport, stomata aperture and gas exchange, pH homeostasis in cytosol, cell wall loosening, and cell expansion. The crucial role of the enzyme in resistance of plants to abiotic and biotic stress factors has also been well documented. Such great diversity of physiological functions linked to the activity of one enzyme requires a suitable and complex regulation of H + -ATPase. This regulation comprises the transcriptional as well as post-transcriptional levels. Herein, we describe the techniques that can be useful for the analysis of the plasma membrane proton pump modifications at genetic and protein levels under environmental factors.

Fluctuation-driven mechanotransduction regulates mitochondrial-network structure and function

NASA Astrophysics Data System (ADS)

Bartolák-Suki, Erzsébet; Imsirovic, Jasmin; Parameswaran, Harikrishnan; Wellman, Tyler J.; Martinez, Nuria; Allen, Philip G.; Frey, Urs; Suki, Béla

2015-10-01

Cells can be exposed to irregular mechanical fluctuations, such as those arising from changes in blood pressure. Here, we report that ATP production, assessed through changes in mitochondrial membrane potential, is downregulated in vascular smooth muscle cells in culture exposed to monotonous stretch cycles when compared with cells exposed to a variable cyclic stretch that incorporates physiological levels of cycle-by-cycle variability in stretch amplitude. Variable stretch enhances ATP production by increasing the expression of ATP synthase’s catalytic domain, cytochrome c oxidase and its tyrosine phosphorylation, mitofusins and PGC-1α. Such a fluctuation-driven mechanotransduction mechanism is mediated by motor proteins and by the enhancement of microtubule-, actin- and mitochondrial-network complexity. We also show that, in aorta rings isolated from rats, monotonous stretch downregulates--whereas variable stretch maintains--physiological vessel-wall contractility through mitochondrial ATP production. Our results have implications for ATP-dependent and mechanosensitive intracellular processes.

Distinguishing cognitive state with multifractal complexity of hippocampal interspike interval sequences

PubMed Central

Fetterhoff, Dustin; Kraft, Robert A.; Sandler, Roman A.; Opris, Ioan; Sexton, Cheryl A.; Marmarelis, Vasilis Z.; Hampson, Robert E.; Deadwyler, Sam A.

2015-01-01

Fractality, represented as self-similar repeating patterns, is ubiquitous in nature and the brain. Dynamic patterns of hippocampal spike trains are known to exhibit multifractal properties during working memory processing; however, it is unclear whether the multifractal properties inherent to hippocampal spike trains reflect active cognitive processing. To examine this possibility, hippocampal neuronal ensembles were recorded from rats before, during and after a spatial working memory task following administration of tetrahydrocannabinol (THC), a memory-impairing component of cannabis. Multifractal detrended fluctuation analysis was performed on hippocampal interspike interval sequences to determine characteristics of monofractal long-range temporal correlations (LRTCs), quantified by the Hurst exponent, and the degree/magnitude of multifractal complexity, quantified by the width of the singularity spectrum. Our results demonstrate that multifractal firing patterns of hippocampal spike trains are a marker of functional memory processing, as they are more complex during the working memory task and significantly reduced following administration of memory impairing THC doses. Conversely, LRTCs are largest during resting state recordings, therefore reflecting different information compared to multifractality. In order to deepen conceptual understanding of multifractal complexity and LRTCs, these measures were compared to classical methods using hippocampal frequency content and firing variability measures. These results showed that LRTCs, multifractality, and theta rhythm represent independent processes, while delta rhythm correlated with multifractality. Taken together, these results provide a novel perspective on memory function by demonstrating that the multifractal nature of spike trains reflects hippocampal microcircuit activity that can be used to detect and quantify cognitive, physiological, and pathological states. PMID:26441562

Morphological Complexity as a Floral Signal: From Perception by Insect Pollinators to Co-Evolutionary Implications.

PubMed

Krishna, Shivani; Keasar, Tamar

2018-06-06

Morphologically complex flowers are characterized by bilateral symmetry, tube-like shapes, deep corolla tubes, fused petals, and/or poricidal anthers, all of which constrain the access of insect visitors to floral nectar and pollen rewards. Only a subset of potential pollinators, mainly large bees, learn to successfully forage on such flowers. Thus, complexity may comprise a morphological filter that restricts the range of visitors and thereby increases food intake for successful foragers. Such pollinator specialization, in turn, promotes flower constancy and reduces cross-species pollen transfer, providing fitness benefits to plants with complex flowers. Since visual signals associated with floral morphological complexity are generally honest (i.e., indicate food rewards), pollinators need to perceive and process them. Physiological studies show that bees detect distant flowers through long-wavelength sensitive photoreceptors. Bees effectively perceive complex shapes and learn the positions of contours based on their spatial frequencies. Complex flowers require long handling times by naive visitors, and become highly profitable only for experienced foragers. To explore possible pathways towards the evolution of floral complexity, we discuss cognitive mechanisms that potentially allow insects to persist on complex flowers despite low initial foraging gains, suggest experiments to test these mechanisms, and speculate on their adaptive value.

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).

The comparative osteology of the petrotympanic complex (ear region) of extant baleen whales (Cetacea: Mysticeti).

PubMed

Ekdale, Eric G; Berta, Annalisa; Deméré, Thomas A

2011-01-01

Anatomical comparisons of the ear region of baleen whales (Mysticeti) are provided through detailed osteological descriptions and high-resolution photographs of the petrotympanic complex (tympanic bulla and petrosal bone) of all extant species of mysticete cetaceans. Salient morphological features are illustrated and identified, including overall shape of the bulla, size of the conical process of the bulla, morphology of the promontorium, and the size and shape of the anterior process of the petrosal. We place our comparative osteological observations into a phylogenetic context in order to initiate an exploration into petrotympanic evolution within Mysticeti. The morphology of the petrotympanic complex is diagnostic for individual species of baleen whale (e.g., sigmoid and conical processes positioned at midline of bulla in Balaenoptera musculus; confluence of fenestra cochleae and perilymphatic foramen in Eschrichtius robustus), and several mysticete clades are united by derived characteristics. Balaenids and neobalaenids share derived features of the bulla, such as a rhomboid shape and a reduced anterior lobe (swelling) in ventral aspect, and eschrichtiids share derived morphologies of the petrosal with balaenopterids, including loss of a medial promontory groove and dorsomedial elongation of the promontorium. Monophyly of Balaenoidea (Balaenidae and Neobalaenidae) and Balaenopteroidea (Balaenopteridae and Eschrichtiidae) was recovered in phylogenetic analyses utilizing data exclusively from the petrotympanic complex. This study fills a major gap in our knowledge of the complex structures of the mysticete petrotympanic complex, which is an important anatomical region for the interpretation of the evolutionary history of mammals. In addition, we introduce a novel body of phylogenetically informative characters from the ear region of mysticetes. Our detailed anatomical descriptions, illustrations, and comparisons provide valuable data for current and future studies on the phylogenetic relationships, evolution, and auditory physiology of mysticetes and other cetaceans throughout Earth's history.

Phase transitions in the common brainstem and related systems investigated by nonstationary time series analysis.

PubMed

Lambertz, M; Vandenhouten, R; Grebe, R; Langhorst, P

2000-01-14

Neuronal activities of the reticular formation (RF) of the lower brainstem and the nucleus tractus solitarii (NTS, first relay station of baroreceptor afferents) were recorded together in the anesthized dog with related parameters of EEG, respiration and cardiovascular system. The RF neurons are part of the common brainstem system (CBS) which participates in regulation and coordination of cardiovascular, respiratory, somatomotor systems, and vigilance. Multiple time series of these physiological subsystems yield useful information about internal dynamic coordination of the organism. Essential problems are nonlinearity and instationarity of the signals, due to the dynamic complexity of the systems. Several time-resolving methods are presented to describe nonlinear dynamic couplings in the time course, particularly during phase transitions. The methods are applied to the recorded signals representing the complex couplings of the physiological subsystems. Phase transitions in these systems are detected by recurrence plots of the instationary signals. The pointwise transinformation and the pointwise conditional coupling divergence are measures of the mutual interaction of the subsystems in the state space. If the signals show marked rhythms, instantaneous frequencies and their shiftings are demonstrated by time frequency distributions, and instantaneous phase differences show couplings of oscillating subsystems. Transient signal components are reconstructed by wavelet packet time selective transient reconstruction. These methods are useful means for analyzing coupling characteristics of the complex physiological system, and detailed analyses of internal dynamic coordination of subsystems become possible. During phase transitions of the functional organization (a) the rhythms of the central neuronal activities and the peripheral systems are altered, (b) changes in the coupling between CBS neurons and cardiovascular signals, respiration and the EEG, and (c) between NTS neurons (influenced by baroreceptor afferents) and CBS neurons occur, and (d) the processing of baroreceptor input at the NTS neurons changes. The results of this complex analysis, which could not be done formerly in this manner, confirm and complete former investigations on the dynamic organization of the CBS with its changing relations to peripheral and other central nervous subsystems.

The approximate entropy concept extended to three dimensions for calibrated, single parameter structural complexity interrogation of volumetric images.

PubMed

Moore, Christopher; Marchant, Thomas

2017-07-12

Reconstructive volumetric imaging permeates medical practice because of its apparently clear depiction of anatomy. However, the tell tale signs of abnormality and its delineation for treatment demand experts work at the threshold of visibility for hints of structure. Hitherto, a suitable assistive metric that chimes with clinical experience has been absent. This paper develops the complexity measure approximate entropy (ApEn) from its 1D physiological origin into a three-dimensional (3D) algorithm to fill this gap. The first 3D algorithm for this is presented in detail. Validation results for known test arrays are followed by a comparison of fan-beam and cone-beam x-ray computed tomography image volumes used in image guided radiotherapy for cancer. Results show the structural detail down to individual voxel level, the strength of which is calibrated by the ApEn process itself. The potential for application in machine assisted manual interaction and automated image processing and interrogation, including radiomics associated with predictive outcome modeling, is discussed.

The approximate entropy concept extended to three dimensions for calibrated, single parameter structural complexity interrogation of volumetric images

NASA Astrophysics Data System (ADS)

Moore, Christopher; Marchant, Thomas

2017-08-01

Reconstructive volumetric imaging permeates medical practice because of its apparently clear depiction of anatomy. However, the tell tale signs of abnormality and its delineation for treatment demand experts work at the threshold of visibility for hints of structure. Hitherto, a suitable assistive metric that chimes with clinical experience has been absent. This paper develops the complexity measure approximate entropy (ApEn) from its 1D physiological origin into a three-dimensional (3D) algorithm to fill this gap. The first 3D algorithm for this is presented in detail. Validation results for known test arrays are followed by a comparison of fan-beam and cone-beam x-ray computed tomography image volumes used in image guided radiotherapy for cancer. Results show the structural detail down to individual voxel level, the strength of which is calibrated by the ApEn process itself. The potential for application in machine assisted manual interaction and automated image processing and interrogation, including radiomics associated with predictive outcome modeling, is discussed.

Synaptic dynamics contribute to long-term single neuron response fluctuations.

PubMed

Reinartz, Sebastian; Biro, Istvan; Gal, Asaf; Giugliano, Michele; Marom, Shimon

2014-01-01

Firing rate variability at the single neuron level is characterized by long-memory processes and complex statistics over a wide range of time scales (from milliseconds up to several hours). Here, we focus on the contribution of non-stationary efficacy of the ensemble of synapses-activated in response to a given stimulus-on single neuron response variability. We present and validate a method tailored for controlled and specific long-term activation of a single cortical neuron in vitro via synaptic or antidromic stimulation, enabling a clear separation between two determinants of neuronal response variability: membrane excitability dynamics vs. synaptic dynamics. Applying this method we show that, within the range of physiological activation frequencies, the synaptic ensemble of a given neuron is a key contributor to the neuronal response variability, long-memory processes and complex statistics observed over extended time scales. Synaptic transmission dynamics impact on response variability in stimulation rates that are substantially lower compared to stimulation rates that drive excitability resources to fluctuate. Implications to network embedded neurons are discussed.

Design Considerations for Developing Biodegradable Magnesium Implants

NASA Astrophysics Data System (ADS)

Brar, Harpreet S.; Keselowsky, Benjamin G.; Sarntinoranont, Malisa; Manuel, Michele V.

The integration of biodegradable and bioabsorbable magnesium implants into the human body is a complex undertaking that faces major challenges. The complexity arises from the fact that biomaterials must meet both engineering and physiological requirements to ensure the desired properties. Historically, efforts have been focused on the behavior of commercial magnesium alloys in biological environments and their resultant effect on cell-mediated processes. Developing causal relationships between alloy chemistry and micro structure, and its effect on cellular behavior can be a difficult and time intensive process. A systems design approach driven by thermodynamics has the power to provide significant contributions in developing the next generation of magnesium alloy implants with controlled degradability, biocompatibility, and optimized mechanical properties, at reduced time and cost. This approach couples experimental research with theory and mechanistic modeling for the accelerated development of materials. The aim of this article is to enumerate this strategy, design considerations and hurdles for developing new magnesium alloys for use as biodegradable implant materials [1].

Systems analysis of arrestin pathway functions.

PubMed

Maudsley, Stuart; Siddiqui, Sana; Martin, Bronwen

2013-01-01

To fully appreciate the diversity and specificity of complex cellular signaling events, such as arrestin-mediated signaling from G protein-coupled receptor activation, a complex systems-level investigation currently appears to be the best option. A rational combination of transcriptomics, proteomics, and interactomics, all coherently integrated with applied next-generation bioinformatics, is vital for the future understanding of the development, translation, and expression of GPCR-mediated arrestin signaling events in physiological contexts. Through a more nuanced, systems-level appreciation of arrestin-mediated signaling, the creation of arrestin-specific molecular response "signatures" should be made simple and ultimately amenable to drug discovery processes. Arrestin-based signaling paradigms possess important aspects, such as its specific temporal kinetics and ability to strongly affect transcriptional activity, that make it an ideal test bed for next-generation of drug discovery bioinformatic approaches such as multi-parallel dose-response analysis, data texturization, and latent semantic indexing-based natural language data processing and feature extraction. Copyright © 2013 Elsevier Inc. All rights reserved.

Perinuclear Arp2/3-driven actin polymerization enables nuclear deformation to facilitate cell migration through complex environments

PubMed Central

Thiam, Hawa-Racine; Vargas, Pablo; Carpi, Nicolas; Crespo, Carolina Lage; Raab, Matthew; Terriac, Emmanuel; King, Megan C.; Jacobelli, Jordan; Alberts, Arthur S.; Stradal, Theresia; Lennon-Dumenil, Ana-Maria; Piel, Matthieu

2016-01-01

Cell migration has two opposite faces: although necessary for physiological processes such as immune responses, it can also have detrimental effects by enabling metastatic cells to invade new organs. In vivo, migration occurs in complex environments and often requires a high cellular deformability, a property limited by the cell nucleus. Here we show that dendritic cells, the sentinels of the immune system, possess a mechanism to pass through micrometric constrictions. This mechanism is based on a rapid Arp2/3-dependent actin nucleation around the nucleus that disrupts the nuclear lamina, the main structure limiting nuclear deformability. The cells' requirement for Arp2/3 to pass through constrictions can be relieved when nuclear stiffness is decreased by suppressing lamin A/C expression. We propose a new role for Arp2/3 in three-dimensional cell migration, allowing fast-moving cells such as leukocytes to rapidly and efficiently migrate through narrow gaps, a process probably important for their function. PMID:26975831

Techniques and instrumental complex for research of influence of microwaves encoded by brain neural signals on biological objects’ psycho physiological state

NASA Astrophysics Data System (ADS)

Gurkovskiy, B. V.; Zhuravlev, B. V.; Onishchenko, E. M.; Simakov, A. B.; Trifonova, N. Yu; Voronov, Yu A.

2016-10-01

New instrumental technique for research of the psycho-physiological reactions of the bio-objects under the microwave electromagnetic radiation, modulated by interval patterns of neural activity in the brain registered under different biological motivations, are suggested. The preliminary results of these new tool tests in real psycho physiological experiments on rats are presented.

The physiology of rodent beta-cells in pancreas slices.

PubMed

Rupnik, M

2009-01-01

Beta-cells in pancreatic islets form complex syncytia. Sufficient cell-to-cell electrical coupling seems to ensure coordinated depolarization pattern and insulin release that can be further modulated by rich innervation. The complex structure and coordinated action develop after birth during fast proliferation of the endocrine tissue. These emergent properties can be lost due to various reasons later in life and can lead to glucose intolerance and diabetes mellitus. Pancreas slice is a novel method of choice to study the physiology of beta-cells still embedded in their normal cellulo-social context. I present major advantages, list drawbacks and provide an overview on recent advances in our understanding of the physiology of beta-cells using the pancreas slice approach.

Cancer as robust intrinsic state shaped by evolution: a key issues review

NASA Astrophysics Data System (ADS)

Yuan, Ruoshi; Zhu, Xiaomei; Wang, Gaowei; Li, Site; Ao, Ping

2017-04-01

Cancer is a complex disease: its pathology cannot be properly understood in terms of independent players—genes, proteins, molecular pathways, or their simple combinations. This is similar to many-body physics of a condensed phase that many important properties are not determined by a single atom or molecule. The rapidly accumulating large ‘omics’ data also require a new mechanistic and global underpinning to organize for rationalizing cancer complexity. A unifying and quantitative theory was proposed by some of the present authors that cancer is a robust state formed by the endogenous molecular-cellular network, which is evolutionarily built for the developmental processes and physiological functions. Cancer state is not optimized for the whole organism. The discovery of crucial players in cancer, together with their developmental and physiological roles, in turn, suggests the existence of a hierarchical structure within molecular biology systems. Such a structure enables a decision network to be constructed from experimental knowledge. By examining the nonlinear stochastic dynamics of the network, robust states corresponding to normal physiological and abnormal pathological phenotypes, including cancer, emerge naturally. The nonlinear dynamical model of the network leads to a more encompassing understanding than the prevailing linear-additive thinking in cancer research. So far, this theory has been applied to prostate, hepatocellular, gastric cancers and acute promyelocytic leukemia with initial success. It may offer an example of carrying physics inquiring spirit beyond its traditional domain: while quantitative approaches can address individual cases, however there must be general rules/laws to be discovered in biology and medicine.

Glycosylation Effects on FSH-FSHR Interaction Dynamics: A Case Study of Different FSH Glycoforms by Molecular Dynamics Simulations

PubMed Central

Meher, Biswa Ranjan; Dixit, Anshuman; Bousfield, George R.; Lushington, Gerald H.

2015-01-01

The gonadotropin known as follicle-stimulating hormone (FSH) plays a key role in regulating reproductive processes. Physiologically active FSH is a glycoprotein that can accommodate glycans on up to four asparagine residues, including two sites in the FSHα subunit that are critical for biochemical function, plus two sites in the β subunit, whose differential glycosylation states appear to correspond to physiologically distinct functions. Some degree of FSHβ hypo-glycosylation seems to confer advantages toward reproductive fertility of child-bearing females. In order to identify possible mechanistic underpinnings for this physiological difference we have pursued computationally intensive molecular dynamics simulations on complexes between the high affinity site of the gonadal FSH receptor (FSHR) and several FSH glycoforms including fully-glycosylated (FSH24), hypo-glycosylated (e.g., FSH15), and completely deglycosylated FSH (dgFSH). These simulations suggest that deviations in FSH/FSHR binding profile as a function of glycosylation state are modest when FSH is adorned with only small glycans, such as single N-acetylglucosamine residues. However, substantial qualitative differences emerge between FSH15 and FSH24 when FSH is decorated with a much larger, tetra-antennary glycan. Specifically, the FSHR complex with hypo-glycosylated FSH15 is observed to undergo a significant conformational shift after 5–10 ns of simulation, indicating that FSH15 has greater conformational flexibility than FSH24 which may explain the more favorable FSH15 kinetic profile. FSH15 also exhibits a stronger binding free energy, due in large part to formation of closer and more persistent salt-bridges with FSHR. PMID:26402790

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

Consciousness as a global property of brain dynamic activity

NASA Astrophysics Data System (ADS)

Mateos, D. M.; Wennberg, R.; Guevara, R.; Perez Velazquez, J. L.

2017-12-01

We seek general principles of the structure of the cellular collective activity associated with conscious awareness. Can we obtain evidence for features of the optimal brain organization that allows for adequate processing of stimuli and that may guide the emergence of cognition and consciousness? Analyzing brain recordings in conscious and unconscious states, we followed initially the classic approach in physics when it comes to understanding collective behaviours of systems composed of a myriad of units: the assessment of the number of possible configurations (microstates) that the system can adopt, for which we use a global entropic measure associated with the number of connected brain regions. Having found maximal entropy in conscious states, we then inspected the microscopic nature of the configurations of connections using an adequate complexity measure and found higher complexity in states characterized not only by conscious awareness but also by subconscious cognitive processing, such as sleep stages. Our observations indicate that conscious awareness is associated with maximal global (macroscopic) entropy and with the short time scale (microscopic) complexity of the configurations of connected brain networks in pathological unconscious states (seizures and coma), but the microscopic view captures the high complexity in physiological unconscious states (sleep) where there is information processing. As such, our results support the global nature of conscious awareness, as advocated by several theories of cognition. We thus hope that our studies represent preliminary steps to reveal aspects of the structure of cognition that leads to conscious awareness.

Uncertainty and variability in computational and mathematical models of cardiac physiology.

PubMed

Mirams, Gary R; Pathmanathan, Pras; Gray, Richard A; Challenor, Peter; Clayton, Richard H

2016-12-01

Mathematical and computational models of cardiac physiology have been an integral component of cardiac electrophysiology since its inception, and are collectively known as the Cardiac Physiome. We identify and classify the numerous sources of variability and uncertainty in model formulation, parameters and other inputs that arise from both natural variation in experimental data and lack of knowledge. The impact of uncertainty on the outputs of Cardiac Physiome models is not well understood, and this limits their utility as clinical tools. We argue that incorporating variability and uncertainty should be a high priority for the future of the Cardiac Physiome. We suggest investigating the adoption of approaches developed in other areas of science and engineering while recognising unique challenges for the Cardiac Physiome; it is likely that novel methods will be necessary that require engagement with the mathematics and statistics community. The Cardiac Physiome effort is one of the most mature and successful applications of mathematical and computational modelling for describing and advancing the understanding of physiology. After five decades of development, physiological cardiac models are poised to realise the promise of translational research via clinical applications such as drug development and patient-specific approaches as well as ablation, cardiac resynchronisation and contractility modulation therapies. For models to be included as a vital component of the decision process in safety-critical applications, rigorous assessment of model credibility will be required. This White Paper describes one aspect of this process by identifying and classifying sources of variability and uncertainty in models as well as their implications for the application and development of cardiac models. We stress the need to understand and quantify the sources of variability and uncertainty in model inputs, and the impact of model structure and complexity and their consequences for predictive model outputs. We propose that the future of the Cardiac Physiome should include a probabilistic approach to quantify the relationship of variability and uncertainty of model inputs and outputs. © 2016 The Authors. The Journal of Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.

The Brassinosteroid Signaling Pathway—New Key Players and Interconnections with Other Signaling Networks Crucial for Plant Development and Stress Tolerance

PubMed Central

Gruszka, Damian

2013-01-01

Brassinosteroids (BRs) are a class of steroid hormones regulating a wide range of physiological processes during the plant life cycle from seed development to the modulation of flowering and senescence. The last decades, and recent years in particular, have witnessed a significant advance in the elucidation of the molecular mechanisms of BR signaling from perception by the transmembrane receptor complex to the regulation of transcription factors influencing expression of the target genes. Application of the new approaches shed light on the molecular functions of the key players regulating the BR signaling cascade and allowed identification of new factors. Recent studies clearly indicated that some of the components of BR signaling pathway act as multifunctional proteins involved in other signaling networks regulating diverse physiological processes, such as photomorphogenesis, cell death control, stomatal development, flowering, plant immunity to pathogens and metabolic responses to stress conditions, including salinity. Regulation of some of these processes is mediated through a crosstalk between BR signalosome and the signaling cascades of other hormones, including auxin, abscisic acid, ethylene and salicylic acid. Unravelling the complicated mechanisms of BR signaling and its interconnections with other molecular networks may be of great importance for future practical applications in agriculture. PMID:23615468

Inflammation in aging part 1: physiology and immunological mechanisms.

PubMed

Hunt, Katherine J; Walsh, Bronagh M; Voegeli, David; Roberts, Helen C

2010-01-01

During the aging process, remodeling of several body systems occurs, and these changes can have a startling effect upon the immune system. The reduction in sex steroids and growth hormones and declines in vitamin D concentration that accompany the aging process are associated with increases in the baseline levels of inflammatory proteins. At the same time, inflammation arising from atherosclerosis and other chronic diseases further contributes to the inflammatory milieu and effects a state of chronic inflammation. This chronic inflammation, or ''inflammaging'' as it has been termed, seems to be associated with a host of adverse effects contributing to many of the health problems that increase morbidity and decrease both quality of life and the ability to maintain independence in old age. For nurses to be truly informed when caring for older people and to ensure that they have a detailed understanding of the complexities of older people's health needs, they must have a knowledge of the physiological and immunological changes with age. This is the first of a two-part article on inflammatory processes in aging. These age-related changes are presented here, including an examination of the impact of genetic and lifestyle factors. The effect of these changes on the health of the individual and implications for practice are described in Part 2.

Simulating the decentralized processes of the human immune system in a virtual anatomy model.

PubMed

Sarpe, Vladimir; Jacob, Christian

2013-01-01

Many physiological processes within the human body can be perceived and modeled as large systems of interacting particles or swarming agents. The complex processes of the human immune system prove to be challenging to capture and illustrate without proper reference to the spatial distribution of immune-related organs and systems. Our work focuses on physical aspects of immune system processes, which we implement through swarms of agents. This is our first prototype for integrating different immune processes into one comprehensive virtual physiology simulation. Using agent-based methodology and a 3-dimensional modeling and visualization environment (LINDSAY Composer), we present an agent-based simulation of the decentralized processes in the human immune system. The agents in our model - such as immune cells, viruses and cytokines - interact through simulated physics in two different, compartmentalized and decentralized 3-dimensional environments namely, (1) within the tissue and (2) inside a lymph node. While the two environments are separated and perform their computations asynchronously, an abstract form of communication is allowed in order to replicate the exchange, transportation and interaction of immune system agents between these sites. The distribution of simulated processes, that can communicate across multiple, local CPUs or through a network of machines, provides a starting point to build decentralized systems that replicate larger-scale processes within the human body, thus creating integrated simulations with other physiological systems, such as the circulatory, endocrine, or nervous system. Ultimately, this system integration across scales is our goal for the LINDSAY Virtual Human project. Our current immune system simulations extend our previous work on agent-based simulations by introducing advanced visualizations within the context of a virtual human anatomy model. We also demonstrate how to distribute a collection of connected simulations over a network of computers. As a future endeavour, we plan to use parameter tuning techniques on our model to further enhance its biological credibility. We consider these in silico experiments and their associated modeling and optimization techniques as essential components in further enhancing our capabilities of simulating a whole-body, decentralized immune system, to be used both for medical education and research as well as for virtual studies in immunoinformatics.

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

Zhang, Jiang; Malmirchegini, G. Reza; Clubb, Robert T.

Native mass spectrometry (MS) has become an invaluable tool for the characterization of proteins and non-covalent protein complexes under near physiological solution conditions. Here we report the structural characterization of human hemoglobin (Hb), a 64 kDa oxygen-transporting protein complex, by high resolution native top-down mass spectrometry using electrospray ionization (ESI) and a 15-Tesla Fourier transform ion cyclotron resonance (FTICR) mass spectrometer. Native MS preserves the non-covalent interactions between the globin subunits, and electron capture dissociation (ECD) produces fragments directly from the intact Hb complex without dissociating the subunits. Using activated ion ECD, we observe the gradual unfolding process of themore » Hb complex in the gas phase. Without protein ion activation, the native Hb shows very limited ECD fragmentation from the N-termini, suggesting a tightly packed structure of the native complex and therefore low fragmentation efficiency. Precursor ion activation allows steady increase of N-terminal fragment ions, while the C-terminal fragments remain limited (38 c ions and 4 z ions on the α chain; 36 c ions and 2 z ions on the β chain). This ECD fragmentation pattern suggests that upon activation, the Hb complex starts to unfold from the N-termini of both subunits, whereas the C-terminal regions and therefore the potential regions involved in the subunit binding interactions remain intact. ECD-MS of the Hb dimer show similar fragmentation patterns as the Hb tetramer, providing further evidence for the hypothesized unfolding process of the Hb complex in the gas phase. Native top-down ECD-MS allows efficient probing of the Hb complex structure and the subunit binding interactions in the gas phase. Finally, it may provide a fast and effective means to probe the structure of novel protein complexes that are intractable to traditional structural characterization tools.« less

Physiological models of the lateral superior olive

PubMed Central

2017-01-01

In computational biology, modeling is a fundamental tool for formulating, analyzing and predicting complex phenomena. Most neuron models, however, are designed to reproduce certain small sets of empirical data. Hence their outcome is usually not compatible or comparable with other models or datasets, making it unclear how widely applicable such models are. In this study, we investigate these aspects of modeling, namely credibility and generalizability, with a specific focus on auditory neurons involved in the localization of sound sources. The primary cues for binaural sound localization are comprised of interaural time and level differences (ITD/ILD), which are the timing and intensity differences of the sound waves arriving at the two ears. The lateral superior olive (LSO) in the auditory brainstem is one of the locations where such acoustic information is first computed. An LSO neuron receives temporally structured excitatory and inhibitory synaptic inputs that are driven by ipsi- and contralateral sound stimuli, respectively, and changes its spike rate according to binaural acoustic differences. Here we examine seven contemporary models of LSO neurons with different levels of biophysical complexity, from predominantly functional ones (‘shot-noise’ models) to those with more detailed physiological components (variations of integrate-and-fire and Hodgkin-Huxley-type). These models, calibrated to reproduce known monaural and binaural characteristics of LSO, generate largely similar results to each other in simulating ITD and ILD coding. Our comparisons of physiological detail, computational efficiency, predictive performances, and further expandability of the models demonstrate (1) that the simplistic, functional LSO models are suitable for applications where low computational costs and mathematical transparency are needed, (2) that more complex models with detailed membrane potential dynamics are necessary for simulation studies where sub-neuronal nonlinear processes play important roles, and (3) that, for general purposes, intermediate models might be a reasonable compromise between simplicity and biological plausibility. PMID:29281618

Spatial organization and correlation properties quantify structural changes on mesoscale of parenchymatous plant tissue

NASA Astrophysics Data System (ADS)

Valous, N. A.; Delgado, A.; Drakakis, K.; Sun, D.-W.

2014-02-01

The study of plant tissue parenchyma's intercellular air spaces contributes to the understanding of anatomy and physiology. This is challenging due to difficulty in making direct measurements of the pore space and the complex mosaic of parenchymatous tissue. The architectural complexity of pore space has shown that single geometrical measurements are not sufficient for characterization. The inhomogeneity of distribution depends not only on the percentage content of phase, but also on how the phase fills the space. The lacunarity morphometric, as multiscale measure, provides information about the distribution of gaps that correspond to degree of spatial organization in parenchyma. Additionally, modern theories have suggested strategies, where the focus has shifted from the study of averages and histograms to the study of patterns in data fluctuations. Detrended fluctuation analysis provides information on the correlation properties of the parenchyma at different spatial scales. The aim is to quantify (with the aid of the aforementioned metrics), the mesostructural changes—that occur from one cycle of freezing and thawing—in the void phase of pome fruit parenchymatous tissue, acquired with X-ray microcomputed tomography. Complex systems methods provide numerical indices and detailed insights regarding the freezing-induced modifications upon the arrangement of cells and voids. These structural changes have the potential to lead to physiological disorders. The work can further stimulate interest for the analysis of internal plant tissue structures coupled with other physico-chemical processes or phenomena.

Production of capsular polysaccharide from Escherichia coli K4 for biotechnological applications.

PubMed

Cimini, Donatella; Restaino, Odile Francesca; Catapano, Angela; De Rosa, Mario; Schiraldi, Chiara

2010-02-01

The production of industrially relevant microbial polysaccharides has recently gained much interest. The capsular polysaccharide of Escherichia coli K4 is almost identical to chondroitin, a commercially valuable biopolymer that is so far obtained from animal tissues entailing complex and expensive extraction procedures. In the present study, the production of capsular polysaccharide by E. coli K4 was investigated taking into consideration a potential industrial application. Strain physiology was first characterized in shake flask experiments to determine the optimal culture conditions for the growth of the microorganism and correlate it to polysaccharide production. Results show that the concentration of carbon source greatly affects polysaccharide production, while the complex nitrogen source is mainly responsible for the build up of biomass. Small-scale batch processes were performed to further evaluate the effect of the initial carbon source concentration and of growth temperatures on polysaccharide production, finally leading to the establishment of the medium to use in following fermentation experiments on a bigger scale. The fed-batch strategy next developed on a 2-L reactor resulted in a maximum cell density of 56 g(cww)/L and a titre of capsular polysaccharide equal to 1.4 g/L, approximately ten- and fivefold higher than results obtained in shake flask and 2-L batch experiments, respectively. The release kinetics of K4 polysaccharide into the medium were also explored to gain insight into the mechanisms underlying a complex aspect of the strain physiology.

Dissecting Arabidopsis Gβ Signal Transduction on the Protein Surface1[W][OA

PubMed Central

Jiang, Kun; Frick-Cheng, Arwen; Trusov, Yuri; Delgado-Cerezo, Magdalena; Rosenthal, David M.; Lorek, Justine; Panstruga, Ralph; Booker, Fitzgerald L.; Botella, José Ramón; Molina, Antonio; Ort, Donald R.; Jones, Alan M.

2012-01-01

The heterotrimeric G-protein complex provides signal amplification and target specificity. The Arabidopsis (Arabidopsis thaliana) Gβ-subunit of this complex (AGB1) interacts with and modulates the activity of target cytoplasmic proteins. This specificity resides in the structure of the interface between AGB1 and its targets. Important surface residues of AGB1, which were deduced from a comparative evolutionary approach, were mutated to dissect AGB1-dependent physiological functions. Analysis of the capacity of these mutants to complement well-established phenotypes of Gβ-null mutants revealed AGB1 residues critical for specific AGB1-mediated biological processes, including growth architecture, pathogen resistance, stomata-mediated leaf-air gas exchange, and possibly photosynthesis. These findings provide promising new avenues to direct the finely tuned engineering of crop yield and traits. PMID:22570469

Age-related variation in EEG complexity to photic stimulation: A multiscale entropy analysis

PubMed Central

Takahashi, Tetsuya; Cho, Raymond Y.; Murata, Tetsuhito; Mizuno, Tomoyuki; Kikuchi, Mitsuru; Mizukami, Kimiko; Kosaka, Hirotaka; Takahashi, Koichi; Wada, Yuji

2010-01-01

Objective This study was intended to examine variations in electroencephalographic (EEG) complexity in response to photic stimulation (PS) during aging to test the hypothesis that the aging process reduces physiologic complexity and functional responsiveness. Methods Multiscale entropy (MSE), an estimate of time-series signal complexity associated with long-range temporal correlation, is used as a recently proposed method for quantifying EEG complexity with multiple coarse-grained sequences. We recorded EEG in 13 healthy elderly subjects and 12 healthy young subjects during pre-PS and post-PS conditions and estimated their respective MSE values. Results For the pre-PS condition, no significant complexity difference was found between the groups. However, a significant MSE change (complexity increase) was found post-PS only in young subjects, thereby revealing a power-law scaling property, which means long-range temporal correlation. Conclusions Enhancement of long-range temporal correlation in young subjects after PS might reflect a cortical response to stimuli, which was absent in elderly subjects. These results are consistent with the general “loss of complexity/diminished functional response to stimuli” theory of aging. Significance Our findings demonstrate that application of MSE analysis to EEG is a powerful approach for studying age-related changes in brain function. PMID:19231279

PBPK models for the prediction of in vivo performance of oral dosage forms.

PubMed

Kostewicz, Edmund S; Aarons, Leon; Bergstrand, Martin; Bolger, Michael B; Galetin, Aleksandra; Hatley, Oliver; Jamei, Masoud; Lloyd, Richard; Pepin, Xavier; Rostami-Hodjegan, Amin; Sjögren, Erik; Tannergren, Christer; Turner, David B; Wagner, Christian; Weitschies, Werner; Dressman, Jennifer

2014-06-16

Drug absorption from the gastrointestinal (GI) tract is a highly complex process dependent upon numerous factors including the physicochemical properties of the drug, characteristics of the formulation and interplay with the underlying physiological properties of the GI tract. The ability to accurately predict oral drug absorption during drug product development is becoming more relevant given the current challenges facing the pharmaceutical industry. Physiologically-based pharmacokinetic (PBPK) modeling provides an approach that enables the plasma concentration-time profiles to be predicted from preclinical in vitro and in vivo data and can thus provide a valuable resource to support decisions at various stages of the drug development process. Whilst there have been quite a few successes with PBPK models identifying key issues in the development of new drugs in vivo, there are still many aspects that need to be addressed in order to maximize the utility of the PBPK models to predict drug absorption, including improving our understanding of conditions in the lower small intestine and colon, taking the influence of disease on GI physiology into account and further exploring the reasons behind population variability. Importantly, there is also a need to create more appropriate in vitro models for testing dosage form performance and to streamline data input from these into the PBPK models. As part of the Oral Biopharmaceutical Tools (OrBiTo) project, this review provides a summary of the current status of PBPK models available. The current challenges in PBPK set-ups for oral drug absorption including the composition of GI luminal contents, transit and hydrodynamics, permeability and intestinal wall metabolism are discussed in detail. Further, the challenges regarding the appropriate integration of results from in vitro models, such as consideration of appropriate integration/estimation of solubility and the complexity of the in vitro release and precipitation data, are also highlighted as important steps to advancing the application of PBPK models in drug development. It is expected that the "innovative" integration of in vitro data from more appropriate in vitro models and the enhancement of the GI physiology component of PBPK models, arising from the OrBiTo project, will lead to a significant enhancement in the ability of PBPK models to successfully predict oral drug absorption and advance their role in preclinical and clinical development, as well as for regulatory applications. Copyright © 2013 Elsevier B.V. All rights reserved.

Multi-complexity ensemble measures for gait time series analysis: application to diagnostics, monitoring and biometrics.

PubMed

Gavrishchaka, Valeriy; Senyukova, Olga; Davis, Kristina

2015-01-01

Previously, we have proposed to use complementary complexity measures discovered by boosting-like ensemble learning for the enhancement of quantitative indicators dealing with necessarily short physiological time series. We have confirmed robustness of such multi-complexity measures for heart rate variability analysis with the emphasis on detection of emerging and intermittent cardiac abnormalities. Recently, we presented preliminary results suggesting that such ensemble-based approach could be also effective in discovering universal meta-indicators for early detection and convenient monitoring of neurological abnormalities using gait time series. Here, we argue and demonstrate that these multi-complexity ensemble measures for gait time series analysis could have significantly wider application scope ranging from diagnostics and early detection of physiological regime change to gait-based biometrics applications.

Goodpasture Antigen-binding Protein/Ceramide Transporter Binds to Human Serum Amyloid P-Component and Is Present in Brain Amyloid Plaques*

PubMed Central

Mencarelli, Chiara; Bode, Gerard H.; Losen, Mario; Kulharia, Mahesh; Molenaar, Peter C.; Veerhuis, Robert; Steinbusch, Harry W. M.; De Baets, Marc H.; Nicolaes, Gerry A. F.; Martinez-Martinez, Pilar

2012-01-01

Serum amyloid P component (SAP) is a non-fibrillar glycoprotein belonging to the pentraxin family of the innate immune system. SAP is present in plasma, basement membranes, and amyloid deposits. This study demonstrates, for the first time, that the Goodpasture antigen-binding protein (GPBP) binds to human SAP. GPBP is a nonconventional Ser/Thr kinase for basement membrane type IV collagen. Also GPBP is found in plasma and in the extracellular matrix. In the present study, we demonstrate that GPBP specifically binds SAP in its physiological conformations, pentamers and decamers. The START domain in GPBP is important for this interaction. SAP and GPBP form complexes in blood and partly colocalize in amyloid plaques from Alzheimer disease patients. These data suggest the existence of complexes of SAP and GPBP under physiological and pathological conditions. These complexes are important for understanding basement membrane, blood physiology, and plaque formation in Alzheimer disease. PMID:22396542

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

PubMed

Kirilina, Evgeniya; Yu, Na; Jelzow, Alexander; Wabnitz, Heidrun; Jacobs, Arthur M; Tachtsidis, Ilias

2013-01-01

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

Speaking under pressure: Low linguistic complexity is linked to high physiological and emotional stress reactivity

PubMed Central

Saslow, Laura R.; McCoy, Shannon; van der Löwe, Ilmo; Cosley, Brandon; Vartan, Arbi; Oveis, Christopher; Keltner, Dacher; Moskowitz, Judith T.; Epel, Elissa S.

2014-01-01

What can a speech reveal about someone's state? We tested the idea that greater stress reactivity would relate to lower linguistic cognitive complexity while speaking. In Study 1, we tested whether heart rate and emotional stress reactivity to a stressful discussion would relate to lower linguistic complexity. In Studies 2 and 3 we tested whether a greater cortisol response to a standardized stressful task including a speech (Trier Social Stress Test) would be linked to speaking with less linguistic complexity during the task. We found evidence that measures of stress responsivity (emotional and physiological) and chronic stress are tied to variability in the cognitive complexity of speech. Taken together, these results provide evidence that our individual experiences of stress or ‘stress signatures’—how our body and mind react to stress both in the moment and over the longer term—are linked to how complexly we speak under stress. PMID:24354732

How to Do It. Plant Eco-Physiology: Experiments on Crassulacean Acid Metabolism, Using Minimal Equipment.

ERIC Educational Resources Information Center

Friend, Douglas J. C.

1990-01-01

Features of Crassulacean Acid Metabolism plants are presented. Investigations of a complex eco-physiological plant adaptation to the problems of growth in an arid environment are discussed. Materials and procedures for these investigations are described. (CW)

A Microbial Perspective on the Grand Challenges in Comparative Animal Physiology

PubMed Central

2018-01-01

ABSTRACT Interactions with microbial communities can have profound influences on animal physiology, thereby impacting animal performance and fitness. Therefore, it is important to understand the diversity and nature of host-microbe interactions in various animal groups (invertebrates, fish, amphibians, reptiles, birds, and mammals). In this perspective, I discuss how the field of host-microbe interactions can be used to address topics that have been identified as grand challenges in comparative animal physiology: (i) horizontal integration of physiological processes across organisms, (ii) vertical integration of physiological processes across organizational levels within organisms, and (iii) temporal integration of physiological processes during evolutionary change. Addressing these challenges will require the use of a variety of animal models and the development of systems approaches that can integrate large, multiomic data sets from both microbial communities and animal hosts. Integrating host-microbe interactions into the established field of comparative physiology represents an exciting frontier for both fields. PMID:29556549

A case study of infant physiologic response to skin-to-skin contact following surgery for complex congenital heart disease

PubMed Central

Harrison, Tondi M.; Ludington-Hoe, Susan

2014-01-01

Background Infants with complex congenital heart disease requiring surgical intervention within the first days or weeks of life may be the most seriously ill infants needing intensive nursing and medical care immediately after birth. Skin to skin contact (SSC) is well-accepted and practiced as a positive therapeutic intervention in premature infants, but is not routinely offered to infants in cardiac intensive care units. Physiologic effects of SSC in the congenital heart disease population must be examined before recommending incorporation of SSC into standard care routines. Objective The purpose of this case study was to describe the physiologic response to a single session of SSC in an 18-day-old infant with hypoplastic left heart syndrome. Methods Repeated measures of heart rate, respiratory rate, oxygen saturation, blood pressure, and temperature were recorded 30 minutes prior to SSC, during SSC (including interruptions for bottle and breast feedings), and 10 minutes after SSC was completed. Results All physiologic parameters were clinically acceptable throughout the 135-minute observation. Conclusion This case study provides beginning evidence that SSC is safe in full-term infants following surgery for complex congenital heart disease. Further research with a larger sample is needed to examine effects of SSC on infant physiology before surgery and earlier in the postoperative time period as well as on additional outcomes such as length of stay, maternal-infant interaction, and neurodevelopment. PMID:25325374

Role of Klotho in Osteoporosis and Renal Osteodystrophy

DTIC Science & Technology

2014-10-01

about the complex physiology of bone development and maintenance including the endocrine regulation of mineral homeostasis that is absolutely...percentage of bone. This should enhance the effects we have already seen in other lines and enable us to delve further into physiology of the phenotype...Klotho and FGFRs [11,12]. To dissect the role of parathyroid gland resident Klotho in physiology and in pathophysiological states such as CKD, we

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.

Carotenoid maintenance handicap and the physiology of carotenoid-based signalisation of health

NASA Astrophysics Data System (ADS)

Vinkler, Michal; Albrecht, Tomáš

2010-01-01

Despite a reasonable scientific interest in sexual selection, the general principles of health signalisation via ornamental traits remain still unresolved in many aspects. This is also true for the mechanism preserving honesty of carotenoid-based signals. Although it is widely accepted that this type of ornamentation reflects an allocation trade-off between the physiological utilisation of carotenoids (mainly in antioxidative processes) and their deposition in ornaments, some recent evidence suggests more complex interactions. Here, we further develop the models currently proposed to explain the honesty of carotenoid-based signalisation of heath status by adding the handicap principle concept regulated by testosterone. We propose that under certain circumstances carotenoids may be dangerous for the organism because they easily transform into toxic cleavage products. When reserves of other protective antioxidants are insufficient, physiological trade-offs may exist between maintenance of carotenoids for ornament expression and their removal from the body. Furthermore, we suggest that testosterone which enhances ornamentation by increasing carotenoid bioavailability may also promote oxidative stress and hence lower antioxidant reserves. The presence of high levels of carotenoids required for high-quality ornament expression may therefore represent a handicap and only individuals in prime health could afford to produce elaborate colourful ornaments. Although further testing is needed, this ‘carotenoid maintenance handicap’ hypothesis may offer a new insight into the physiological aspects of the relationship between carotenoid function, immunity and ornamentation.

Spatial Distribution, Structure, Biomass, and Physiology of Microbial Assemblages across the Southern Ocean Frontal Zones during the Late Austral Winter

PubMed Central

Hanson, Roger B.; Lowery, H. Kenneth

1985-01-01

We examined the spatial distributions of picoplankton, nanoplankton, and microplankton biomass and physiological state relative to the hydrography of the Southern Ocean along 90° W longitude and across the Drake Passage in the late austral winter. The eastern South Pacific Ocean showed some large-scale biogeographical differences and size class variability. Microbial ATP biomass was greatest in euphotic surface waters. The horizontal distributions of microbial biomass and physiological state (adenylate energy charge ratio) coincided with internal currents (fronts) of the Antarctic Circumpolar Current. In the Drake Passage, the biological scales in the euphotic and aphotic zones were complex, and ATP, total adenylate, and adenylate energy charge ratio isopleths were compressed due to the extension of the sea ice from Antarctica and constriction of the Circumpolar Current through the narrow passage. The physiological state of microbial assemblages and biomass were much higher in the Drake Passage than in the eastern South Pacific Ocean. The temperature of Antarctic waters, not dissolved organic carbon, was the major variable controlling picoplankton growth. Estimates of picoplankton production based on ATP increments with time suggest that production under reduced predation pressure was 1 to 10 μg of carbon per liter per day. Our results demonstrate the influence of large-scale hydrographic processes on the distribution and structure of microplankton, nanoplankton, and picoplankton across the Southern Ocean. PMID:16346777

Insulin transport into the brain.

PubMed

Gray, Sarah M; Barrett, Eugene J

2018-05-30

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

2D and 3D Matrices to Study Linear Invadosome Formation and Activity.

PubMed

Di Martino, Julie; Henriet, Elodie; Ezzoukhry, Zakaria; Mondal, Chandrani; Bravo-Cordero, Jose Javier; Moreau, Violaine; Saltel, Frederic

2017-06-02

Cell adhesion, migration, and invasion are involved in many physiological and pathological processes. For example, during metastasis formation, tumor cells have to cross anatomical barriers to invade and migrate through the surrounding tissue in order to reach blood or lymphatic vessels. This requires the interaction between cells and the extracellular matrix (ECM). At the cellular level, many cells, including the majority of cancer cells, are able to form invadosomes, which are F-actin-based structures capable of degrading ECM. Invadosomes are protrusive actin structures that recruit and activate matrix metalloproteinases (MMPs). The molecular composition, density, organization, and stiffness of the ECM are crucial in regulating invadosome formation and activation. In vitro, a gelatin assay is the standard assay used to observe and quantify invadosome degradation activity. However, gelatin, which is denatured collagen I, is not a physiological matrix element. A novel assay using type I collagen fibrils was developed and used to demonstrate that this physiological matrix is a potent inducer of invadosomes. Invadosomes that form along the collagen fibrils are known as linear invadosomes due to their linear organization on the fibers. Moreover, molecular analysis of linear invadosomes showed that the discoidin domain receptor 1 (DDR1) is the receptor involved in their formation. These data clearly demonstrate the importance of using a physiologically relevant matrix in order to understand the complex interactions between cells and the ECM.

Glucose-6-phosphate dehydrogenase, NADPH, and cell survival.

PubMed

Stanton, Robert C

2012-05-01

Glucose-6-phosphate dehydrogenase (G6PD) is the rate-limiting enzyme of the pentose phosphate pathway. Many scientists think that the roles and regulation of G6PD in physiology and pathophysiology have been well established as the enzyme was first identified 80 years ago. And that G6PD has been extensively studied especially with respect to G6PD deficiency and its association with hemolysis, and with respect to the role G6PD plays in lipid metabolism. But there has been a growing understanding of the central importance of G6PD to cellular physiology as it is a major source of NADPH that is required by many essential cellular systems including the antioxidant pathways, nitric oxide synthase, NADPH oxidase, cytochrome p450 system, and others. Indeed G6PD is essential for cell survival. It has also become evident that G6PD is highly regulated by many signals that affect transcription, post-translation, intracellular location, and interactions with other protein. Pathophysiologic roles for G6PD have also been identified in such disease processes as diabetes, aldosterone-induced endothelial dysfunction, cancer, and others. It is now clear that G6PD is under complex regulatory control and of central importance to many cellular processes. In this review the biochemistry, regulatory signals, physiologic roles, and pathophysiologic roles for G6PD that have been elucidated over the past 20 years are discussed. Copyright © 2012 Wiley Periodicals, Inc.

Building an experimental model of the human body with non-physiological parameters.

PubMed

Labuz, Joseph M; Moraes, Christopher; Mertz, David R; Leung, Brendan M; Takayama, Shuichi

2017-03-01

New advances in engineering and biomedical technology have enabled recent efforts to capture essential aspects of human physiology in microscale, in-vitro systems. The application of these advances to experimentally model complex processes in an integrated platform - commonly called a 'human-on-a-chip (HOC)' - requires that relevant compartments and parameters be sized correctly relative to each other and to the system as a whole. Empirical observation, theoretical treatments of resource distribution systems and natural experiments can all be used to inform rational design of such a system, but technical and fundamental challenges (e.g. small system blood volumes and context-dependent cell metabolism, respectively) pose substantial, unaddressed obstacles. Here, we put forth two fundamental principles for HOC design: inducing in-vivo -like cellular metabolic rates is necessary and may be accomplished in-vitro by limiting O 2 availability and that the effects of increased blood volumes on drug concentration can be mitigated through pharmacokinetics-based treatments of solute distribution. Combining these principles with natural observation and engineering workarounds, we derive a complete set of design criteria for a practically realizable, physiologically faithful, five-organ millionth-scale (× 10 -6 ) microfluidic model of the human body.

Examination of Duct Physiology in the Human Mammary Gland

PubMed Central

Mills, Dixie; Gomberawalla, Ameer; Gordon, Eva J.; Tondre, Julie; Nejad, Mitra; Nguyen, Tinh; Pogoda, Janice M.; Rao, Jianyu; Chatterton, Robert; Henning, Susanne; Love, Susan M.

2016-01-01

Background The human breast comprise several ductal systems, or lobes, which contain a small amount of fluid containing cells, hormones, proteins and metabolites. The complex physiology of these ducts is likely a contributing factor to the development of breast cancer, especially given that the vast majority of breast cancers begin in a single lobular unit. Methods We examined the levels of total protein, progesterone, estradiol, estrone sulfate, dehydroepiandrosterone sulfate, and macrophages in ductal fluid samples obtained from 3 ducts each in 78 women, sampled twice over a 6 month period. Samples were processed for both cytological and molecular analysis. Intraclass correlation coefficients and mixed models were utilized to identify significant data. Results We found that the levels of these ductal fluid components were generally uncorrelated among ducts within a single breast and over time, suggesting that each lobe within the breast has a distinct physiology. However, we also found that estradiol was more correlated in women who were nulliparous or produced nipple aspirate fluid. Conclusions Our results provide evidence that the microenvironment of any given lobular unit is unique to that individual unit, findings that may provide clues about the initiation and development of ductal carcinomas. PMID:27073976

Building an experimental model of the human body with non-physiological parameters

PubMed Central

Labuz, Joseph M.; Moraes, Christopher; Mertz, David R.; Leung, Brendan M.; Takayama, Shuichi

2017-01-01

New advances in engineering and biomedical technology have enabled recent efforts to capture essential aspects of human physiology in microscale, in-vitro systems. The application of these advances to experimentally model complex processes in an integrated platform — commonly called a ‘human-on-a-chip (HOC)’ — requires that relevant compartments and parameters be sized correctly relative to each other and to the system as a whole. Empirical observation, theoretical treatments of resource distribution systems and natural experiments can all be used to inform rational design of such a system, but technical and fundamental challenges (e.g. small system blood volumes and context-dependent cell metabolism, respectively) pose substantial, unaddressed obstacles. Here, we put forth two fundamental principles for HOC design: inducing in-vivo-like cellular metabolic rates is necessary and may be accomplished in-vitro by limiting O2 availability and that the effects of increased blood volumes on drug concentration can be mitigated through pharmacokinetics-based treatments of solute distribution. Combining these principles with natural observation and engineering workarounds, we derive a complete set of design criteria for a practically realizable, physiologically faithful, five-organ millionth-scale (× 10−6) microfluidic model of the human body. PMID:28713851

Maximizing information from space data resources: a case for expanding integration across research disciplines.

PubMed

Goswami, Nandu; Batzel, Jerry J; Clément, Gilles; Stein, T Peter; Hargens, Alan R; Sharp, M Keith; Blaber, Andrew P; Roma, Peter G; Hinghofer-Szalkay, Helmut G

2013-07-01

Regulatory systems are affected in space by exposure to weightlessness, high-energy radiation or other spaceflight-induced changes. The impact of spaceflight occurs across multiple scales and systems. Exploring such interactions and interdependencies via an integrative approach provides new opportunities for elucidating these complex responses. This paper argues the case for increased emphasis on integration, systematically archiving, and the coordination of past, present and future space and ground-based analogue experiments. We also discuss possible mechanisms for such integration across disciplines and missions. This article then introduces several discipline-specific reviews that show how such integration can be implemented. Areas explored include: adaptation of the central nervous system to space; cerebral autoregulation and weightlessness; modelling of the cardiovascular system in space exploration; human metabolic response to spaceflight; and exercise, artificial gravity, and physiologic countermeasures for spaceflight. In summary, spaceflight physiology research needs a conceptual framework that extends problem solving beyond disciplinary barriers. Administrative commitment and a high degree of cooperation among investigators are needed to further such a process. Well-designed interdisciplinary research can expand opportunities for broad interpretation of results across multiple physiological systems, which may have applications on Earth.

Manipulating neural activity in physiologically classified neurons: triumphs and challenges

PubMed Central

Gore, Felicity; Schwartz, Edmund C.; Salzman, C. Daniel

2015-01-01

Understanding brain function requires knowing both how neural activity encodes information and how this activity generates appropriate responses. Electrophysiological, imaging and immediate early gene immunostaining studies have been instrumental in identifying and characterizing neurons that respond to different sensory stimuli, events and motor actions. Here we highlight approaches that have manipulated the activity of physiologically classified neurons to determine their role in the generation of behavioural responses. Previous experiments have often exploited the functional architecture observed in many cortical areas, where clusters of neurons share response properties. However, many brain structures do not exhibit such functional architecture. Instead, neurons with different response properties are anatomically intermingled. Emerging genetic approaches have enabled the identification and manipulation of neurons that respond to specific stimuli despite the lack of discernable anatomical organization. These approaches have advanced understanding of the circuits mediating sensory perception, learning and memory, and the generation of behavioural responses by providing causal evidence linking neural response properties to appropriate behavioural output. However, significant challenges remain for understanding cognitive processes that are probably mediated by neurons with more complex physiological response properties. Currently available strategies may prove inadequate for determining how activity in these neurons is causally related to cognitive behaviour. PMID:26240431

The effects of incretins on energy homeostasis: physiology and implications for the treatment of type 2 diabetes mellitus and obesity.

PubMed

Karras, Spyridon; Goulis, Dimitrios G; Mintziori, Gesthimani; Katsiki, Niki; Tzotzas, Themistoklis

2012-11-01

Energy homeostasis in mammalians is a teleological process regulated by the interplay between caloric intake and energy expenditure. Incretins are a significant component of the complex homeostatic network regulating the metabolic state in humans. This narrative review will focus on the basic concepts regarding incretins physiology and their regulatory feedback mechanisms affecting energy homeostasis. In this context, glucagon-like peptide 1 (GLP-1) promotes satiety and weight loss through centrally and peripherally mediated pathways. On the other hand, gastric inhibitory peptide (GIP) is implicated in energy storage by its actions on adipose tissue. Understanding this biological model requires a holistic approach, since it is dually manifested by promoting weight reduction, in the case of GLP-1, or favoring lipid accumulation, in the case of GIP. The complete spectrum of incretin actions related to energy homeostasis is yet to be fully elucidated. Currently, new drugs based on incretin physiology are available for treatment of type 2 diabetes mellitus, whereas the implication of similar drugs in the treatment of obesity is under investigation. These agents exert several beneficial effects that minimize cardiovascular risk.

Metabolic Adaptation to Muscle Ischemia

NASA Technical Reports Server (NTRS)

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

2000-01-01

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

Hemispheric asymmetry in stress processing in rat prefrontal cortex and the role of mesocortical dopamine.

PubMed

Sullivan, R M

2004-06-01

The prefrontal cortex (PFC) is known to play an important role not only in the regulation of emotion, but in the integration of affective states with appropriate modulation of autonomic and neuroendocrine stress regulatory systems. The present review highlights findings in the rat which helps to elucidate the complex nature of prefrontal involvement in emotion and stress regulation. The medial PFC is particularly important in this regard and while dorsomedial regions appear to play a suppressive role in such regulation, the ventromedial (particularly infralimbic) region appears to activate behavioral, neuroendocrine and sympathetic autonomic systems in response to stressful situations. This may be especially true of spontaneous stress-related behavior or physiological responses to relatively acute stressors. The role of the medial PFC is somewhat more complex in conditions involving learned adjustments to stressful situations, such as the extinction of conditioned fear responses, but it is clear that the medial PFC is important in incorporating stressful experience for future adaptive behavior. It is also suggested that mesocortical dopamine plays an important adaptive role in this region by preventing excessive behavioral and physiological stress reactivity. The rat brain shows substantial hemispheric specialization in many respects, and while the right PFC is normally dominant in the activation of stress-related systems, the left may play a role in countering this activation through processes of interhemispheric inhibition. This proposed basic template for the lateralization of stress regulatory systems is suggested to be associated with efficient stress and emotional self-regulation, and also to be shaped by both early postnatal experience and gender differences.

Quite a few reasons for calling carnivores 'the most wonderful plants in the world'.

PubMed

Król, Elzbieta; Płachno, Bartosz J; Adamec, Lubomír; Stolarz, Maria; Dziubińska, Halina; Trebacz, Kazimierz

2012-01-01

A plant is considered carnivorous if it receives any noticeable benefit from catching small animals. The morphological and physiological adaptations to carnivorous existence is most complex in plants, thanks to which carnivorous plants have been cited by Darwin as 'the most wonderful plants in the world'. When considering the range of these adaptations, one realizes that the carnivory is a result of a multitude of different features. This review discusses a selection of relevant articles, culled from a wide array of research topics on plant carnivory, and focuses in particular on physiological processes associated with active trapping and digestion of prey. Carnivory offers the plants special advantages in habitats where nutrient supply is scarce. Counterbalancing costs are the investments in synthesis and the maintenance of trapping organs and hydrolysing enzymes. With the progress in genetic, molecular and microscopic techniques, we are well on the way to a full appreciation of various aspects of plant carnivory. Sufficiently complex to be of scientific interest and finite enough to allow conclusive appraisal, carnivorous plants can be viewed as unique models for the examination of rapid organ movements, plant excitability, enzyme secretion, nutrient absorption, food-web relationships, phylogenetic and intergeneric relationships or structural and mineral investment in carnivory.

Quite a few reasons for calling carnivores ‘the most wonderful plants in the world’

PubMed Central

Król, Elżbieta; Płachno, Bartosz J.; Adamec, Lubomír; Stolarz, Maria; Dziubińska, Halina; Trębacz, Kazimierz

2012-01-01

Background A plant is considered carnivorous if it receives any noticeable benefit from catching small animals. The morphological and physiological adaptations to carnivorous existence is most complex in plants, thanks to which carnivorous plants have been cited by Darwin as ‘the most wonderful plants in the world’. When considering the range of these adaptations, one realizes that the carnivory is a result of a multitude of different features. Scope This review discusses a selection of relevant articles, culled from a wide array of research topics on plant carnivory, and focuses in particular on physiological processes associated with active trapping and digestion of prey. Carnivory offers the plants special advantages in habitats where nutrient supply is scarce. Counterbalancing costs are the investments in synthesis and the maintenance of trapping organs and hydrolysing enzymes. With the progress in genetic, molecular and microscopic techniques, we are well on the way to a full appreciation of various aspects of plant carnivory. Conclusions Sufficiently complex to be of scientific interest and finite enough to allow conclusive appraisal, carnivorous plants can be viewed as unique models for the examination of rapid organ movements, plant excitability, enzyme secretion, nutrient absorption, food-web relationships, phylogenetic and intergeneric relationships or structural and mineral investment in carnivory. PMID:21937485

Movement Complexity and Neuromechanical Factors Affect the Entropic Half-Life of Myoelectric Signals

PubMed Central

Hodson-Tole, Emma F.; Wakeling, James M.

2017-01-01

Appropriate neuromuscular functioning is essential for survival and features underpinning motor control are present in myoelectric signals recorded from skeletal muscles. One approach to quantify control processes related to function is to assess signal variability using measures such as Sample Entropy. Here we developed a theoretical framework to simulate the effect of variability in burst duration, activation duty cycle, and intensity on the Entropic Half-Life (EnHL) in myoelectric signals. EnHLs were predicted to be <40 ms, and to vary with fluctuations in myoelectric signal amplitude and activation duty cycle. Comparison with myoelectic data from rats walking and running at a range of speeds and inclines confirmed the range of EnHLs, however, the direction of EnHL change in response to altered locomotor demand was not correctly predicted. The discrepancy reflected different associations between the ratio of the standard deviation and mean signal intensity (Ist:It¯) and duty factor in simulated and physiological data, likely reflecting additional information in the signals from the physiological data (e.g., quiescent phase content; variation in action potential shapes). EnHL could have significant value as a novel marker of neuromuscular responses to alterations in perceived locomotor task complexity and intensity. PMID:28974932

Potentiometric and spectroscopic study of the interaction of 3d transition metal ions with inositol hexakisphosphate

NASA Astrophysics Data System (ADS)

Veiga, Nicolás; Macho, Israel; Gómez, Kerman; González, Gabriel; Kremer, Carlos; Torres, Julia

2015-10-01

Among myo-inositol phosphates, the most abundant in nature is the myo-inositol hexakisphosphate, InsP6. Although it is known to be vital to cell functioning, the biochemical research into its metabolism needs chemical and structural analysis of all the protonation, complexation and precipitation processes that it undergoes in the biological media. In view of its high negative charge at physiological level, our group has been leading a thorough research into the InsP6 chemical and structural behavior in the presence of the alkali and alkaline earth metal ions essential for life. The aim of this article is to extend these studies, dealing with the chemical and structural features of the InsP6 interaction with biologically relevant 3d transition metal ions (Fe(II), Fe(III), Mn(II), Co(II), Ni(II), Cu(II) and Zn(II)), in a non-interacting medium and under simulated physiological conditions. The metal-complex stability constants were determined by potentiometry, showing under ligand-excess conditions the formation of mononuclear species in different protonation states. Under metal ion excess, polymetallic species were detected for Fe(II), Fe(III), Zn(II) and Cu(II). Additionally, the 31P NMR and UV-vis spectroscopic studies provided interesting structural aspects of the strong metal ion-InsP6 interaction.

Nuclear Factor Kappa-light-chain-enhancer of Activated B Cells (NF-κB) - a Friend, a Foe, or a Bystander - in the Neurodegenerative Cascade and Pathogenesis of Alzheimer's Disease.

PubMed

Marwarha, Gurdeep; Ghribi, Othman

2017-01-01

NF-κB is a ubiquitous transcription factor that was discovered three decades ago. Since its discovery, this protein complex has been implicated in numerous physiological and pathophysiological processes such as synaptic plasticity, learning and memory, inflammation, insulin resistance, and oxidative stress among other factors that are intricately involved and dysregulated in Alzheimer's disease (AD). We embarked on a methodical and an objective review of contemporary literature to integrate the indispensable physiological functions of NF-κB in neuronal phsyiology with the undesirable pathophysiological attributes of NF-κB in the etiopathogenesis of Alzheimer's disease. In our approach, we first introduced Alzheimer's disease and subsequently highlighted the multifaceted roles of NF-κB in the biological processes altered in the progression of Alzheimer's disease including synaptic transmission, synaptic plasticity, learning, and memory, neuronal survival and apoptosis, adult neurogenesis, regulation of neural processes and structural plasticity, inflammation, and Amyloid-β production and toxicity. Our comprehensive review highlights and dissects the physiological role of NF-κB from its pathological role in the brain and delineates both, its beneficial as well as deleterious, role in the etiopathogenesis of Alzheimer's disease. In light of our understanding of the duality of the role of NF-κB in the pathogenesis of Alzheimer's disease, further studies are warranted to dissect and understand the basis of the dichotomous effects of NF-κB, so that certain selective benevolent and benign attributes of NF-κB can be spared while targeting its deleterious attributes and facets that are integral in the pathogenesis of Alzheimer's disease. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Transferrin-functionalized nanographene oxide for delivery of platinum complexes to enhance cancer-cell selectivity and apoptosis-inducing efficacy.

PubMed

Zhu, Hai; Zhou, Binwei; Chan, Leung; Du, Yanxin; Chen, Tianfeng

2017-01-01

Rational design and construction of delivery nanosystems for anticancer metal complexes is a crucial strategy to improve solubility under physiological conditions and permeability and retention behavior in tumor cells. Therefore, in this study, we designed and synthesize a transferrin (Tf)-conjugated nanographene oxide (NGO) nanosystem as a cancer-targeted nanocarrier of Pt complexes (Tf-NGO@Pt). This nanodelivery system exhibited good solubility under physiological conditions. Moreover, Tf-NGO@Pt showed higher anticancer efficacy against MCF human breast cancer cells than the free Pt complex, and effectively inhibited cancer-cell migration and invasion, with involvement of reactive oxygen species overproduction. In addition, nanolization also enhanced the penetration ability and inhibitory effect of the Pt complex toward MCF7 breast cancer-cell tumor spheroids. The enhancement of anticancer efficacy was positively correlated with increased cellular uptake and cellular drug retention. This study provides a new strategy to facilitate the future application of metal complexes in cancer therapy.

Speaking under pressure: low linguistic complexity is linked to high physiological and emotional stress reactivity.

PubMed

Saslow, Laura R; McCoy, Shannon; van der Löwe, Ilmo; Cosley, Brandon; Vartan, Arbi; Oveis, Christopher; Keltner, Dacher; Moskowitz, Judith T; Epel, Elissa S

2014-03-01

What can a speech reveal about someone's state? We tested the idea that greater stress reactivity would relate to lower linguistic cognitive complexity while speaking. In Study 1, we tested whether heart rate and emotional stress reactivity to a stressful discussion would relate to lower linguistic complexity. In Studies 2 and 3, we tested whether a greater cortisol response to a standardized stressful task including a speech (Trier Social Stress Test) would be linked to speaking with less linguistic complexity during the task. We found evidence that measures of stress responsivity (emotional and physiological) and chronic stress are tied to variability in the cognitive complexity of speech. Taken together, these results provide evidence that our individual experiences of stress or "stress signatures"-how our body and mind react to stress both in the moment and over the longer term-are linked to how complex our speech under stress. Copyright © 2013 Society for Psychophysiological Research.

Distorted Immunodominance by Linker Sequences or other Epitopes from a Second Protein Antigen During Antigen-Processing

PubMed Central

Kim, AeRyon; Boronina, Tatiana N.; Cole, Robert N.; Darrah, Erika; Sadegh-Nasseri, Scheherazade

2017-01-01

The immune system focuses on and responds to very few representative immunodominant epitopes from pathogenic insults. However, due to the complexity of the antigen processing, understanding the parameters that lead to immunodominance has proved difficult. In an attempt to uncover the determinants of immunodominance among several dominant epitopes, we utilized a cell free antigen processing system and allowed the system to identify the hierarchies among potential determinants. We then tested the results in vivo; in mice and in human. We report here, that immunodominance of known sequences in a given protein can change if two or more proteins are being processed and presented simultaneously. Surprisingly, we find that new spacer/tag sequences commonly added to proteins for purification purposes can distort the capture of the physiological immunodominant epitopes. We warn against adding tags and spacers to candidate vaccines, or recommend cleaving it off before using for vaccination. PMID:28422163

Firmicutes dominate the bacterial taxa within sugar-cane processing plants

PubMed Central

Sharmin, Farhana; Wakelin, Steve; Huygens, Flavia; Hargreaves, Megan

2013-01-01

Sugar cane processing sites are characterised by high sugar/hemicellulose levels, available moisture and warm conditions, and are relatively unexplored unique microbial environments. The PhyloChip microarray was used to investigate bacterial diversity and community composition in three Australian sugar cane processing plants. These ecosystems were highly complex and dominated by four main Phyla, Firmicutes (the most dominant), followed by Proteobacteria, Bacteroidetes, and Chloroflexi. Significant variation (p < 0.05) in community structure occurred between samples collected from ‘floor dump sediment’, ‘cooling tower water’, and ‘bagasse leachate’. Many bacterial Classes contributed to these differences, however most were of low numerical abundance. Separation in community composition was also linked to Classes of Firmicutes, particularly Bacillales, Lactobacillales and Clostridiales, whose dominance is likely to be linked to their physiology as ‘lactic acid bacteria’, capable of fermenting the sugars present. This process may help displace other bacterial taxa, providing a competitive advantage for Firmicutes bacteria. PMID:24177592

Remodeling pathway control of mitochondrial respiratory capacity by temperature in mouse heart: electron flow through the Q-junction in permeabilized fibers.

PubMed

Lemieux, Hélène; Blier, Pierre U; Gnaiger, Erich

2017-06-06

Fuel substrate supply and oxidative phosphorylation are key determinants of muscle performance. Numerous studies of mammalian mitochondria are carried out (i) with substrate supply that limits electron flow, and (ii) far below physiological temperature. To analyze potentially implicated biases, we studied mitochondrial respiratory control in permeabilized mouse myocardial fibers using high-resolution respirometry. The capacity of oxidative phosphorylation at 37 °C was nearly two-fold higher when fueled by physiological substrate combinations reconstituting tricarboxylic acid cycle function, compared with electron flow measured separately through NADH to Complex I or succinate to Complex II. The relative contribution of the NADH pathway to physiological respiratory capacity increased with a decrease in temperature from 37 to 25 °C. The apparent excess capacity of cytochrome c oxidase above physiological pathway capacity increased sharply under hypothermia due to limitation by NADH-linked dehydrogenases. This mechanism of mitochondrial respiratory control in the hypothermic mammalian heart is comparable to the pattern in ectotherm species, pointing towards NADH-linked mt-matrix dehydrogenases and the phosphorylation system rather than electron transfer complexes as the primary drivers of thermal sensitivity at low temperature. Delineating the link between stress and remodeling of oxidative phosphorylation is important for understanding metabolic perturbations in disease evolution and cardiac protection.

Aquaporins and root water uptake

USDA-ARS?s Scientific Manuscript database

Water is one of the most critical resources limiting plant growth and crop productivity, and root water uptake is an important aspect of plant physiology governing plant water use and stress tolerance. Pathways of root water uptake are complex and are affected by root structure and physiological res...

Morphological and Physiological Alteration of Maize Root Architectures on Drought Stress.

USDA-ARS?s Scientific Manuscript database

Drought tolerance is a complex agronomic trait and root characteristics logically play an important role in determining the response of plants to drought stress. Research experiments were conducted to investigate genotypic variations in morphological and physiological responses of roots to drought s...

The Chemistry of Plant–Microbe Interactions in the Rhizosphere and the Potential for Metabolomics to Reveal Signaling Related to Defense Priming and Induced Systemic Resistance

PubMed Central

Mhlongo, Msizi I.; Piater, Lizelle A.; Madala, Ntakadzeni E.; Labuschagne, Nico; Dubery, Ian A.

2018-01-01

Plant roots communicate with microbes in a sophisticated manner through chemical communication within the rhizosphere, thereby leading to biofilm formation of beneficial microbes and, in the case of plant growth-promoting rhizomicrobes/-bacteria (PGPR), resulting in priming of defense, or induced resistance in the plant host. The knowledge of plant–plant and plant–microbe interactions have been greatly extended over recent years; however, the chemical communication leading to priming is far from being well understood. Furthermore, linkage between below- and above-ground plant physiological processes adds to the complexity. In metabolomics studies, the main aim is to profile and annotate all exo- and endo-metabolites in a biological system that drive and participate in physiological processes. Recent advances in this field has enabled researchers to analyze 100s of compounds in one sample over a short time period. Here, from a metabolomics viewpoint, we review the interactions within the rhizosphere and subsequent above-ground ‘signalomics’, and emphasize the contributions that mass spectrometric-based metabolomic approaches can bring to the study of plant-beneficial – and priming events. PMID:29479360

A physiology-based parametric imaging method for FDG-PET data

NASA Astrophysics Data System (ADS)

Scussolini, Mara; Garbarino, Sara; Sambuceti, Gianmario; Caviglia, Giacomo; Piana, Michele

2017-12-01

Parametric imaging is a compartmental approach that processes nuclear imaging data to estimate the spatial distribution of the kinetic parameters governing tracer flow. The present paper proposes a novel and efficient computational method for parametric imaging which is potentially applicable to several compartmental models of diverse complexity and which is effective in the determination of the parametric maps of all kinetic coefficients. We consider applications to [18 F]-fluorodeoxyglucose positron emission tomography (FDG-PET) data and analyze the two-compartment catenary model describing the standard FDG metabolization by an homogeneous tissue and the three-compartment non-catenary model representing the renal physiology. We show uniqueness theorems for both models. The proposed imaging method starts from the reconstructed FDG-PET images of tracer concentration and preliminarily applies image processing algorithms for noise reduction and image segmentation. The optimization procedure solves pixel-wise the non-linear inverse problem of determining the kinetic parameters from dynamic concentration data through a regularized Gauss-Newton iterative algorithm. The reliability of the method is validated against synthetic data, for the two-compartment system, and experimental real data of murine models, for the renal three-compartment system.

Complex physiological and molecular processes underlying root gravitropism

NASA Technical Reports Server (NTRS)

Chen, Rujin; Guan, Changhui; Boonsirichai, Kanokporn; Masson, Patrick H.

2002-01-01

Gravitropism allows plant organs to guide their growth in relation to the gravity vector. For most roots, this response to gravity allows downward growth into soil where water and nutrients are available for plant growth and development. The primary site for gravity sensing in roots includes the root cap and appears to involve the sedimentation of amyloplasts within the columella cells. This process triggers a signal transduction pathway that promotes both an acidification of the wall around the columella cells, an alkalinization of the columella cytoplasm, and the development of a lateral polarity across the root cap that allows for the establishment of a lateral auxin gradient. This gradient is then transmitted to the elongation zones where it triggers a differential cellular elongation on opposite flanks of the central elongation zone, responsible for part of the gravitropic curvature. Recent findings also suggest the involvement of a secondary site/mechanism of gravity sensing for gravitropism in roots, and the possibility that the early phases of graviresponse, which involve differential elongation on opposite flanks of the distal elongation zone, might be independent of this auxin gradient. This review discusses our current understanding of the molecular and physiological mechanisms underlying these various phases of the gravitropic response in roots.

Integrative Systems Biology for Data Driven Knowledge Discovery

PubMed Central

Greene, Casey S.; Troyanskaya, Olga G.

2015-01-01

Integrative systems biology is an approach that brings together diverse high throughput experiments and databases to gain new insights into biological processes or systems at molecular through physiological levels. These approaches rely on diverse high-throughput experimental techniques that generate heterogeneous data by assaying varying aspects of complex biological processes. Computational approaches are necessary to provide an integrative view of these experimental results and enable data-driven knowledge discovery. Hypotheses generated from these approaches can direct definitive molecular experiments in a cost effective manner. Using integrative systems biology approaches, we can leverage existing biological knowledge and large-scale data to improve our understanding of yet unknown components of a system of interest and how its malfunction leads to disease. PMID:21044756

An expanding universe of circadian networks in higher plants.

PubMed

Pruneda-Paz, Jose L; Kay, Steve A

2010-05-01

Extensive circadian clock networks regulate almost every biological process in plants. Clock-controlled physiological responses are coupled with daily oscillations in environmental conditions resulting in enhanced fitness and growth vigor. Identification of core clock components and their associated molecular interactions has established the basic network architecture of plant clocks, which consists of multiple interlocked feedback loops. A hierarchical structure of transcriptional feedback overlaid with regulated protein turnover sets the pace of the clock and ultimately drives all clock-controlled processes. Although originally described as linear entities, increasing evidence suggests that many signaling pathways can act as both inputs and outputs within the overall network. Future studies will determine the molecular mechanisms involved in these complex regulatory loops. 2010 Elsevier Ltd. All rights reserved.

Neuroscience and education.

PubMed

Goswami, Usha

2004-03-01

Neuroscience is a relatively new discipline encompassing neurology, psychology and biology. It has made great strides in the last 100 years, during which many aspects of the physiology, biochemistry, pharmacology and structure of the vertebrate brain have been understood. Understanding of some of the basic perceptual, cognitive, attentional, emotional and mnemonic functions is also making progress, particularly since the advent of the cognitive neurosciences, which focus specifically on understanding higher level processes of cognition via imaging technology. Neuroimaging has enabled scientists to study the human brain at work in vivo, deepening our understanding of the very complex processes underpinning speech and language, thinking and reasoning, reading and mathematics. It seems timely, therefore, to consider how we might implement our increased understanding of brain development and brain function to explore educational questions.

Scaling and universality in the human voice.

PubMed

Luque, Jordi; Luque, Bartolo; Lacasa, Lucas

2015-04-06

Speech is a distinctive complex feature of human capabilities. In order to understand the physics underlying speech production, in this work, we empirically analyse the statistics of large human speech datasets ranging several languages. We first show that during speech, the energy is unevenly released and power-law distributed, reporting a universal robust Gutenberg-Richter-like law in speech. We further show that such 'earthquakes in speech' show temporal correlations, as the interevent statistics are again power-law distributed. As this feature takes place in the intraphoneme range, we conjecture that the process responsible for this complex phenomenon is not cognitive, but it resides in the physiological (mechanical) mechanisms of speech production. Moreover, we show that these waiting time distributions are scale invariant under a renormalization group transformation, suggesting that the process of speech generation is indeed operating close to a critical point. These results are put in contrast with current paradigms in speech processing, which point towards low dimensional deterministic chaos as the origin of nonlinear traits in speech fluctuations. As these latter fluctuations are indeed the aspects that humanize synthetic speech, these findings may have an impact in future speech synthesis technologies. Results are robust and independent of the communication language or the number of speakers, pointing towards a universal pattern and yet another hint of complexity in human speech. © 2015 The Author(s) Published by the Royal Society. All rights reserved.

Integrated, systems metabolic picture of acetone-butanol-ethanol fermentation by Clostridium acetobutylicum.

PubMed

Liao, Chen; Seo, Seung-Oh; Celik, Venhar; Liu, Huaiwei; Kong, Wentao; Wang, Yi; Blaschek, Hans; Jin, Yong-Su; Lu, Ting

2015-07-07

Microbial metabolism involves complex, system-level processes implemented via the orchestration of metabolic reactions, gene regulation, and environmental cues. One canonical example of such processes is acetone-butanol-ethanol (ABE) fermentation by Clostridium acetobutylicum, during which cells convert carbon sources to organic acids that are later reassimilated to produce solvents as a strategy for cellular survival. The complexity and systems nature of the process have been largely underappreciated, rendering challenges in understanding and optimizing solvent production. Here, we present a system-level computational framework for ABE fermentation that combines metabolic reactions, gene regulation, and environmental cues. We developed the framework by decomposing the entire system into three modules, building each module separately, and then assembling them back into an integrated system. During the model construction, a bottom-up approach was used to link molecular events at the single-cell level into the events at the population level. The integrated model was able to successfully reproduce ABE fermentations of the WT C. acetobutylicum (ATCC 824), as well as its mutants, using data obtained from our own experiments and from literature. Furthermore, the model confers successful predictions of the fermentations with various network perturbations across metabolic, genetic, and environmental aspects. From foundation to applications, the framework advances our understanding of complex clostridial metabolism and physiology and also facilitates the development of systems engineering strategies for the production of advanced biofuels.

Integrated, systems metabolic picture of acetone-butanol-ethanol fermentation by Clostridium acetobutylicum

PubMed Central

Liao, Chen; Seo, Seung-Oh; Celik, Venhar; Liu, Huaiwei; Kong, Wentao; Wang, Yi; Blaschek, Hans; Jin, Yong-Su; Lu, Ting

2015-01-01

Microbial metabolism involves complex, system-level processes implemented via the orchestration of metabolic reactions, gene regulation, and environmental cues. One canonical example of such processes is acetone-butanol-ethanol (ABE) fermentation by Clostridium acetobutylicum, during which cells convert carbon sources to organic acids that are later reassimilated to produce solvents as a strategy for cellular survival. The complexity and systems nature of the process have been largely underappreciated, rendering challenges in understanding and optimizing solvent production. Here, we present a system-level computational framework for ABE fermentation that combines metabolic reactions, gene regulation, and environmental cues. We developed the framework by decomposing the entire system into three modules, building each module separately, and then assembling them back into an integrated system. During the model construction, a bottom-up approach was used to link molecular events at the single-cell level into the events at the population level. The integrated model was able to successfully reproduce ABE fermentations of the WT C. acetobutylicum (ATCC 824), as well as its mutants, using data obtained from our own experiments and from literature. Furthermore, the model confers successful predictions of the fermentations with various network perturbations across metabolic, genetic, and environmental aspects. From foundation to applications, the framework advances our understanding of complex clostridial metabolism and physiology and also facilitates the development of systems engineering strategies for the production of advanced biofuels. PMID:26100881

Experimental and density functional theory (DFT) studies on the interactions of Ru(II) polypyridyl complexes with the RAN triplex poly(U)˙poly(A)*poly(U).

PubMed

Zhang, Hong; Liu, Xuewen; He, Xiaojun; Liu, Ying; Tan, Lifeng

2014-11-01

There is renewed interest in investigating triple helices because these novel structures have been implicated as a possible means of controlling cellular processes by endogenous or exogenous mechanisms. Due to the Hoogsteen base pairing, triple helices are, however, thermodynamically less stable than the corresponding duplexes. The poor stability of triple helices limits their practical applications under physiological conditions. In contrast to DNA triple helices, small molecules stabilizing RNA triple helices at present are less well established. Furthermore, most of these studies are limited to organic compounds and, to a far lesser extent, to metal complexes. In this work, two Ru(II) complexes, [Ru(bpy)2(btip)](2+) (Ru1) and [Ru(phen)2(btip)](2+) (Ru2), have been synthesized and characterized. The binding properties of the two metal complexes with the triple RNA poly(U)˙poly(A)*poly(U) were studied by various biophysical and density functional theory methods. The main results obtained here suggest that the slight binding difference in Ru1 and Ru2 may be attributed to the planarity of the intercalative ligand and the LUMO level of Ru(II) complexes. This study further advances our knowledge on the triplex RNA-binding by metal complexes, particularly Ru(II) complexes.

Bone as an effect compartment : models for uptake and release of drugs.

PubMed

Stepensky, David; Kleinberg, Lilach; Hoffman, Amnon

2003-01-01

"Bone-seeking agents" are drugs characterised by high affinity for bone, and are disposed in bone for prolonged periods of time while maintaining remarkably low systemic concentrations. As a consequence, the bone becomes a reservoir for bone-seeking agents, and a site of both desirable and adverse effects, depending on the pharmacological activities of the specific agent. For some agents, significant systemic effects may also be produced following their prolonged release from bone, a process that is governed mostly by the rate of bone remodelling. This review covers the pharmacokinetic and pharmacodynamic features of bone-seeking agents with different pharmacological properties, including drugs (bisphosphonates, drug-bisphosphonate conjugates, radiopharmaceuticals and fluoride), bone markers (tetracycline, bone imaging agents) and toxins (lead, chromium, aluminium). In addition, drugs that do not possess bone-seeking properties but are used for therapy of bone diseases (such as antibacterials for treatment of osteomyelitis) are discussed, along with targeting of these drugs to the bone by conjugation to bone-seeking agents, local delivery systems, and other approaches. The pharmacokinetic and pharmacodynamic behaviour of bone-seeking agents is extremely complex due to heterogeneity in bone morphology and physiology. This complexity, accompanied by difficulties in human bone research caused by ethical and other limitations, gave rise to modelling approaches to study bone drug disposition. This review describes the pharmacokinetic models that have been proposed to describe the pharmacokinetic behaviour of bone-seeking agents and predict bone concentrations of these agents for different doses and patient populations. Models of different types (compartmental and physiologically based) and of different complexity have been applied, but their relevance to drug effects in the bone tissue is limited since they describe the behaviour of the "average" drug molecule. Understanding of the cellular and molecular processes responsible for the heterogeneity of bone tissue will provide better comprehension of the influence of microenvironment on drug bone disposition and the resulting pharmacological response.

Fractality of sensations and the brain health: the theory linking neurodegenerative disorder with distortion of spatial and temporal scale-invariance and fractal complexity of the visible world

PubMed Central

Zueva, Marina V.

2015-01-01

The theory that ties normal functioning and pathology of the brain and visual system with the spatial–temporal structure of the visual and other sensory stimuli is described for the first time in the present study. The deficit of fractal complexity of environmental influences can lead to the distortion of fractal complexity in the visual pathways of the brain and abnormalities of development or aging. The use of fractal light stimuli and fractal stimuli of other modalities can help to restore the functions of the brain, particularly in the elderly and in patients with neurodegenerative disorders or amblyopia. Non-linear dynamics of these physiological processes have a strong base of evidence, which is seen in the impaired fractal regulation of rhythmic activity in aged and diseased brains. From birth to old age, we live in a non-linear world, in which objects and processes with the properties of fractality and non-linearity surround us. Against this background, the evolution of man took place and all periods of life unfolded. Works of art created by man may also have fractal properties. The positive influence of music on cognitive functions is well-known. Insufficiency of sensory experience is believed to play a crucial role in the pathogenesis of amblyopia and age-dependent diseases. The brain is very plastic in its early development, and the plasticity decreases throughout life. However, several studies showed the possibility to reactivate the adult’s neuroplasticity in a variety of ways. We propose that a non-linear structure of sensory information on many spatial and temporal scales is crucial to the brain health and fractal regulation of physiological rhythms. Theoretical substantiation of the author’s theory is presented. Possible applications and the future research that can experimentally confirm or refute the theoretical concept are considered. PMID:26236232

Physiologic measures of sexual function in women: a review.

PubMed

Woodard, Terri L; Diamond, Michael P

2009-07-01

To review and describe physiologic measures of assessing sexual function in women. Literature review. Studies that use instruments designed to measure female sexual function. Women participating in studies of female sexual function. Various instruments that measure physiologic features of female sexual function. Appraisal of the various instruments, including their advantages and disadvantages. Many unique physiologic methods of evaluating female sexual function have been developed during the past four decades. Each method has its benefits and limitations. Many physiologic methods exist, but most are not well-validated. In addition there has been an inability to correlate most physiologic measures with subjective measures of sexual arousal. Furthermore, given the complex nature of the sexual response in women, physiologic measures should be considered in context of other data, including the history, physical examination, and validated questionnaires. Nonetheless, the existence of appropriate physiologic measures is vital to our understanding of female sexual function and dysfunction.

Integrated imaging of cardiac anatomy, physiology, and viability.

PubMed

Arrighi, James A

2009-03-01

Technologic developments in imaging will have a significant impact on cardiac imaging over the next decade. These advances will permit more detailed assessment of cardiac anatomy, complex assessment of cardiac physiology, and integration of anatomic and physiologic data. The distinction between anatomic and physiologic imaging is important. For assessing patients with known or suspected coronary artery disease, physiologic and anatomic imaging data are complementary. The strength of anatomic imaging rests in its ability to detect the presence of disease, whereas physiologic imaging techniques assess the impact of disease, such as whether a coronary atherosclerotic lesion limits myocardial blood flow. Research indicates that physiologic data are more prognostically important than anatomic data, but both may be important in patient management decisions. Integrated cardiac imaging is an evolving field, with many potential indications. These include assessment of coronary stenosis, myocardial viability, anatomic and physiologic characterization of atherosclerotic plaque, and advanced molecular imaging.

Cognitive Workload and Psychophysiological Parameters During Multitask Activity in Helicopter Pilots.

PubMed

Gaetan, Sophie; Dousset, Erick; Marqueste, Tanguy; Bringoux, Lionel; Bourdin, Christophe; Vercher, Jean-Louis; Besson, Patricia

2015-12-01

Helicopter pilots are involved in a complex multitask activity, implying overuse of cognitive resources, which may result in piloting task impairment or in decision-making failure. Studies usually investigate this phenomenon in well-controlled, poorly ecological situations by focusing on the correlation between physiological values and either cognitive workload or emotional state. This study aimed at jointly exploring workload induced by a realistic simulated helicopter flight mission and emotional state, as well as physiological markers. The experiment took place in the helicopter full flight dynamic simulator. Six participants had to fly on two missions. Workload level, skin conductance, RMS-EMG, and emotional state were assessed. Joint analysis of psychological and physiological parameters associated with workload estimation revealed particular dynamics in each of three profiles. 1) Expert pilots showed a slight increase of measured physiological parameters associated with the increase in difficulty level. Workload estimates never reached the highest level and the emotional state for this profile only referred to positive emotions with low emotional intensity. 2) Non-Expert pilots showed increasing physiological values as the perceived workload increased. However, their emotional state referred to either positive or negative emotions, with a greater variability in emotional intensity. 3) Intermediate pilots were similar to Expert pilots regarding emotional states and similar to Non-Expert pilots regarding physiological patterns. Overall, high interindividual variability of these results highlight the complex link between physiological and psychological parameters with workload, and question whether physiology alone could predict a pilot's inability to make the right decision at the right time.

Integrating multimedia instructional design principles with complex physiological concepts in reproductive science

NASA Astrophysics Data System (ADS)

Oki, Angela Christine

2011-12-01

This dissertation examines the effect of digital multimedia presentations as a method to teach complex concepts in reproductive physiology. The digital presentations developed for this research consisted of two-dimensional (2-D) and three-dimensional (3-D) animations, scriptmessaging and narration. The topics were "Mammalian Ovarian Follicular Dynamics", "The Physiology of the Menstrual Cycle", and "The Physiology of Parturition". In all four experiments, participants were randomly assigned to treatment groups and learning was measured with multiple-choice tests. Experiment 1 determined if type of animation impacted learning about the physiology of the menstrual cycle. The treatments were: 3-D and 2-D animation (n = 110), 2-D animation only (n = 109) and no animation (n = 108). All three presentations were 14 minutes. No treatment effects were found (p > 0.05), indicating that student performance was not influenced by animation type. In experiment 2, the influence of added narrative explanations about the physiology of parturition was determined. The delivery time for the two treatments was 14 minutes (n = 164) and 24 minutes (n = 157), respectively. There were no differences between treatment groups (p > 0.05), indicating that concise explanations were as effective as elaborate explanations. Experiment 3 determined the influence of a digital presentation on knowledge retention of follicular dynamics over the course of a semester. Treatments were: a digital presentation (n = 23) or a classroom lecture captured on video (n = 23). Students completed three tests during the semester. Students in the multimedia group outperformed students in the video lecture group on all three tests (p < 0.05). A fourth experiment determined if the multimedia modules could be effective for teaching physiological concepts to patients with varied educational backgrounds attending an Ob-Gyn clinic. Patients either read a booklet (n = 57) or viewed a multimedia presentation (n = 65) about parturition. Content was identical in each group. Patients in the multimedia group outperformed patients in the booklet group (p < 0.05). This set of four experiments indicates that digital multimedia presentations are effective for teaching complex concepts in reproductive physiology.

Technical Report: Serial collections of placentomes during parturition in cattle and subsequent reproductive performance

USDA-ARS?s Scientific Manuscript database

Placental separation is a complex physiological event in reproductive physiology and the underlying molecular mechanisms remain unclear. When comparing different experiments the timing of tissue collections is a significant consideration due to the variability in time between fetal expulsion and exp...

Cell–cell signaling drives the evolution of complex traits: introduction—lung evo-devo

PubMed Central

Torday, John S.; Rehan, V. K.

2009-01-01

Physiology integrates biology with the environment through cell–cell interactions at multiple levels. The evolution of the respiratory system has been “deconvoluted” (Torday and Rehan in Am J Respir Cell Mol Biol 31:8–12, 2004) through Gene Regulatory Networks (GRNs) applied to cell–cell communication for all aspects of lung biology development, homeostasis, regeneration, and aging. Using this approach, we have predicted the phenotypic consequences of failed signaling for lung development, homeostasis, and regeneration based on evolutionary principles. This cell–cell communication model predicts other aspects of vertebrate physiology as adaptational responses. For example, the oxygen-induced differentiation of alveolar myocytes into alveolar adipocytes was critical for the evolution of the lung in land dwelling animals adapting to fluctuating Phanarezoic oxygen levels over the past 500 million years. Adipocytes prevent lung injury due to oxygen radicals and facilitate the rise of endothermy. In addition, they produce the class I cytokine leptin, which augments pulmonary surfactant activity and alveolar surface area, increasing selection pressure for both respiratory oxygenation and metabolic demand initially constrained by high-systemic vascular pressure, but subsequently compensated by the evolution of the adrenomedullary beta-adrenergic receptor mechanism. Conserted positive selection for the lung and adrenals created further selection pressure for the heart, which becomes progressively more complex phylogenetically in tandem with the lung. Developmentally, increasing heart complexity and size impinges precociously on the gut mesoderm to induce the liver. That evolutionary-developmental interaction is significant because the liver provides regulated sources of glucose and glycogen to the evolving physiologic system, which is necessary for the evolution of the neocortex. Evolution of neocortical control furthers integration of physiologic systems. Such an evolutionary vertical integration of cell-to-tissue-to-organ-to-physiology of intrinsic cell–cell signaling and extrinsic factors is the reverse of the “top-down” conventional way in which physiologic systems are usually regarded. This novel mechanistic approach, incorporating a “middle-out” cell–cell signaling component, will lead to a readily available algorithm for integrating genes and phenotypes. This symposium surveyed the phylogenetic origins of such vertically integrated mechanisms for the evolution of cell–cell communication as the basis for complex physiologic traits, from sponges to man. PMID:20607136

Anatomy and physiology of genital organs - women.

PubMed

Graziottin, Alessandra; Gambini, Dania

2015-01-01

"Anatomy is destiny": Sigmund Freud viewed human anatomy as a necessary, although not a sufficient, condition for understanding the complexity of human sexual function with a solid biologic basis. The aim of the chapter is to describe women's genital anatomy and physiology, focusing on women's sexual function with a clinically oriented vision. Key points include: embryology, stressing that the "female" is the anatomic "default" program, differentiated into "male" only in the presence of androgens at physiologic levels for the gestational age; sex determination and sex differentiation, describing the interplay between anatomic and endocrine factors; the "clitoral-urethral-vaginal" complex, the most recent anatomy reading of the corpora cavernosa pattern in women; the controversial G spot; the role of the pelvic floor muscles in modulating vaginal receptivity and intercourse feelings, with hyperactivity leading to introital dyspareunia and contributing to provoked vestibulodynia and recurrent postcoital cystitis, whilst lesions during delivery reduce vaginal sensations, genital arousability, and orgasm; innervation, vessels, bones, ligaments; and the physiology of women's sexual response. Attention to physiologic aging focuses on "low-grade inflammation," genital and systemic, with its impact on women sexual function, especially after the menopause, if the woman does not or cannot use hormone replacement therapy. © 2015 Elsevier B.V. All rights reserved.

The Dendritic Cell Major Histocompatibility Complex II (MHC II) Peptidome Derives from a Variety of Processing Pathways and Includes Peptides with a Broad Spectrum of HLA-DM Sensitivity*

PubMed Central

Clement, Cristina C.; Becerra, Aniuska; Yin, Liusong; Zolla, Valerio; Huang, Liling; Merlin, Simone; Follenzi, Antonia; Shaffer, Scott A.; Stern, Lawrence J.; Santambrogio, Laura

2016-01-01

The repertoire of peptides displayed in vivo by MHC II molecules derives from a wide spectrum of proteins produced by different cell types. Although intracellular endosomal processing in dendritic cells and B cells has been characterized for a few antigens, the overall range of processing pathways responsible for generating the MHC II peptidome are currently unclear. To determine the contribution of non-endosomal processing pathways, we eluted and sequenced over 3000 HLA-DR1-bound peptides presented in vivo by dendritic cells. The processing enzymes were identified by reference to a database of experimentally determined cleavage sites and experimentally validated for four epitopes derived from complement 3, collagen II, thymosin β4, and gelsolin. We determined that self-antigens processed by tissue-specific proteases, including complement, matrix metalloproteases, caspases, and granzymes, and carried by lymph, contribute significantly to the MHC II self-peptidome presented by conventional dendritic cells in vivo. Additionally, the presented peptides exhibited a wide spectrum of binding affinity and HLA-DM susceptibility. The results indicate that the HLA-DR1-restricted self-peptidome presented under physiological conditions derives from a variety of processing pathways. Non-endosomal processing enzymes add to the number of epitopes cleaved by cathepsins, altogether generating a wider peptide repertoire. Taken together with HLA-DM-dependent and-independent loading pathways, this ensures that a broad self-peptidome is presented by dendritic cells. This work brings attention to the role of “self-recognition” as a dynamic interaction between dendritic cells and the metabolic/catabolic activities ongoing in every parenchymal organ as part of tissue growth, remodeling, and physiological apoptosis. PMID:26740625

An uracil-linked hydroxyflavone probe for the recognition of ATP

PubMed Central

Bojtár, Márton; Janzsó-Berend, Péter Zoltán; Mester, Dávid; Hessz, Dóra; Kállay, Mihály; Kubinyi, Miklós

2018-01-01

Background: Nucleotides are essential molecules in living systems due to their paramount importance in various physiological processes. In the past years, numerous attempts were made to selectively recognize and detect these analytes, especially ATP using small-molecule fluorescent chemosensors. Despite the various solutions, the selective detection of ATP is still challenging due to the structural similarity of various nucleotides. In this paper, we report the conjugation of a uracil nucleobase to the known 4’-dimethylamino-hydroxyflavone fluorophore. Results: The complexation of this scaffold with ATP is already known. The complex is held together by stacking and electrostatic interactions. To achieve multi-point recognition, we designed the uracil-appended version of this probe to include complementary base-pairing interactions. The theoretical calculations revealed the availability of multiple complex structures. The synthesis was performed using click chemistry and the nucleotide recognition properties of the probe were evaluated using fluorescence spectroscopy. Conclusions: The first, uracil-containing fluorescent ATP probe based on a hydroxyflavone fluorophore was synthesized and evaluated. A selective complexation with ATP was observed and a ratiometric response in the excitation spectrum. PMID:29719572

Production of reactive oxygen species in brain mitochondria: contribution by electron transport chain and non-electron transport chain sources.

PubMed

Adam-Vizi, Vera

2005-01-01

Overwhelming evidence has accumulated indicating that oxidative stress is a crucial factor in the pathogenesis of neurodegenerative diseases. The major site of production of superoxide, the primary reactive oxygen species (ROS), is considered to be the respiratory chain in the mitochondria, but the exact mechanism and the precise location of the physiologically relevant ROS generation within the respiratory chain have not been disclosed as yet. Studies performed with isolated mitochondria have located ROS generation on complex I and complex III, respectively, depending on the substrates or inhibitors used to fuel or inhibit respiration. A more "physiological" approach is to address ROS generation of in situ mitochondria, which are present in their normal cytosolic environment. Hydrogen peroxide formation in mitochondria in situ in isolated nerve terminals is enhanced when complex I, complex III, or complex IV is inhibited. However, to induce a significant increase in ROS production, complex III and complex IV have to be inhibited by >70%, which raises doubts as to the physiological importance of ROS generation by these complexes. In contrast, complex I inhibition to a small degree is sufficient to enhance ROS generation, indicating that inhibition of complex I by approximately 25-30% observed in postmortem samples of substantia nigra from patients suffering from Parkinson's disease could be important in inducing oxidative stress. Recently, it has been described that a key Krebs cycle enzyme, alpha-ketoglutarate dehydrogenase (alpha-KGDH), is also able to produce ROS. ROS formation by alpha-KGDH is regulated by the NADH/NAD+ ratio, suggesting that this enzyme could substantially contribute to generation of oxidative stress due to inhibition of complex I. As alpha-KGDH is not only a generator but also a target of ROS, it is proposed that alpha-KGDH is a key factor in a vicious cycle by which oxidative stress is induced and promoted in nerve terminals.

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

PubMed

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

2014-12-09

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

TAME5OX, abiotic siderophore analogue to enterobactin involving 8-hydroxyquinoline subunits: Thermodynamic and photophysical studies

NASA Astrophysics Data System (ADS)

Akbar, Rifat; Baral, Minati; Kanungo, B. K.

2015-05-01

The synthesis, thermodynamic and photophysical properties of trivalent metal complexes of biomimetic nonadentate analogue, 5,5‧-(2-(((8-hydroxyquinolin-5-yl)methylamino)methyl)-2-methylpropane-1,3-diyl)bis(azanediyl)bis(methylene)diquinolin-8-ol (TAME5OX), have been described. Combination of absorption and emission spectrophotometry, potentiometry, electrospray mass spectrometry, IR, and theoretical investigation were used to fully characterize metal (Fe+3, Al+3 and Cr+3) chelates of TAME5OX. In solution, TAME5OX forms protonated complexes [M(H3L)]3+ below pH 3.4, which consecutively deprotonates through one to three-proton processes with rise of pH. The formation constants (Log β11n) of neutral complexes formed at or above physiological pH, have been determined to be 30.18, 23.27 and 22.02 with pM values of 31.16, 18.07 and 18.12 for Fe+3, Al+3 and Cr+3 ions, respectively, calculated at pH 7.4, indicating TAME5OX is a powerful among synthetic metal chelator. The results clearly demonstrate that the ligand in a tripodal orchestration firmly binds these ions over wide pH range and forms distorted octahedral complexes. The binding and the coordination event could be monitored from absorption and fluorescence spectroscopy. The high thermodynamic stability in water at physiological pH of ferric complex of TAME5OX indicates that these complexes are resistant to hydrolysis and therefore are well suited for the development of device for applications as probes. The ligand displays high sensitive fluorescence enhancement to Al3+ at pH 7.4, in water. Moreover, TAME5OX can distinguish Al3+ from Fe3+ and Cr3+ via two different sensing mechanisms: photoinduced electron transfer (PET) for Al3+ and internal charge transfer (ICT) for Fe3+ and Cr3+. Density functional theory was employed for optimization and evaluation of vibrational modes, NBO analysis, excitation and emission properties of the different species of metal complexes observed by solution studies.

TAME5OX, abiotic siderophore analogue to enterobactin involving 8-hydroxyquinoline subunits: thermodynamic and photophysical studies.

PubMed

Akbar, Rifat; Baral, Minati; Kanungo, B K

2015-05-05

The synthesis, thermodynamic and photophysical properties of trivalent metal complexes of biomimetic nonadentate analogue, 5,5'-(2-(((8-hydroxyquinolin-5-yl)methylamino)methyl)-2-methylpropane-1,3-diyl)bis(azanediyl)bis(methylene)diquinolin-8-ol (TAME5OX), have been described. Combination of absorption and emission spectrophotometry, potentiometry, electrospray mass spectrometry, IR, and theoretical investigation were used to fully characterize metal (Fe(+3), Al(+3) and Cr(+3)) chelates of TAME5OX. In solution, TAME5OX forms protonated complexes [M(H3L)](3+) below pH 3.4, which consecutively deprotonates through one to three-proton processes with rise of pH. The formation constants (Logβ11n) of neutral complexes formed at or above physiological pH, have been determined to be 30.18, 23.27 and 22.02 with pM values of 31.16, 18.07 and 18.12 for Fe(+3), Al(+3) and Cr(+3) ions, respectively, calculated at pH 7.4, indicating TAME5OX is a powerful among synthetic metal chelator. The results clearly demonstrate that the ligand in a tripodal orchestration firmly binds these ions over wide pH range and forms distorted octahedral complexes. The binding and the coordination event could be monitored from absorption and fluorescence spectroscopy. The high thermodynamic stability in water at physiological pH of ferric complex of TAME5OX indicates that these complexes are resistant to hydrolysis and therefore are well suited for the development of device for applications as probes. The ligand displays high sensitive fluorescence enhancement to Al(3+) at pH 7.4, in water. Moreover, TAME5OX can distinguish Al(3+) from Fe(3+) and Cr(3+) via two different sensing mechanisms: photoinduced electron transfer (PET) for Al(3+) and internal charge transfer (ICT) for Fe(3+) and Cr(3+). Density functional theory was employed for optimization and evaluation of vibrational modes, NBO analysis, excitation and emission properties of the different species of metal complexes observed by solution studies. Copyright © 2015 Elsevier B.V. All rights reserved.

Inferring diffusion in single live cells at the single-molecule level

PubMed Central

Robson, Alex; Burrage, Kevin; Leake, Mark C.

2013-01-01

The movement of molecules inside living cells is a fundamental feature of biological processes. The ability to both observe and analyse the details of molecular diffusion in vivo at the single-molecule and single-cell level can add significant insight into understanding molecular architectures of diffusing molecules and the nanoscale environment in which the molecules diffuse. The tool of choice for monitoring dynamic molecular localization in live cells is fluorescence microscopy, especially so combining total internal reflection fluorescence with the use of fluorescent protein (FP) reporters in offering exceptional imaging contrast for dynamic processes in the cell membrane under relatively physiological conditions compared with competing single-molecule techniques. There exist several different complex modes of diffusion, and discriminating these from each other is challenging at the molecular level owing to underlying stochastic behaviour. Analysis is traditionally performed using mean square displacements of tracked particles; however, this generally requires more data points than is typical for single FP tracks owing to photophysical instability. Presented here is a novel approach allowing robust Bayesian ranking of diffusion processes to discriminate multiple complex modes probabilistically. It is a computational approach that biologists can use to understand single-molecule features in live cells. PMID:23267182

The PREP pipeline: standardized preprocessing for large-scale EEG analysis

PubMed Central

Bigdely-Shamlo, Nima; Mullen, Tim; Kothe, Christian; Su, Kyung-Min; Robbins, Kay A.

2015-01-01

The technology to collect brain imaging and physiological measures has become portable and ubiquitous, opening the possibility of large-scale analysis of real-world human imaging. By its nature, such data is large and complex, making automated processing essential. This paper shows how lack of attention to the very early stages of an EEG preprocessing pipeline can reduce the signal-to-noise ratio and introduce unwanted artifacts into the data, particularly for computations done in single precision. We demonstrate that ordinary average referencing improves the signal-to-noise ratio, but that noisy channels can contaminate the results. We also show that identification of noisy channels depends on the reference and examine the complex interaction of filtering, noisy channel identification, and referencing. We introduce a multi-stage robust referencing scheme to deal with the noisy channel-reference interaction. We propose a standardized early-stage EEG processing pipeline (PREP) and discuss the application of the pipeline to more than 600 EEG datasets. The pipeline includes an automatically generated report for each dataset processed. Users can download the PREP pipeline as a freely available MATLAB library from http://eegstudy.org/prepcode. PMID:26150785

Art and architecture as experience: an alternative approach to bridging art history and the neurosciences.

PubMed

Zschocke, Nina

2012-08-01

In 1972, Michael Baxandal characterizes the processes responsible for the cultural relativism of art experience as highly complex and unknown in their physiological detail. While art history still shows considerable interest in the brain sciences forty years later, most cross-disciplinary studies today are referring to the neurosciences in an attempt to seek scientific legitimization of variations of a generalized and largely deterministic model of perception, reducing interaction between a work of art and its observers to a set of biological automatisms. I will challenge such an approach and take up art theory's interest in the historico-cultural and situational dimensions of art experience. Looking at two examples of large-scale installation and sculptural post-war American art, I will explore instable perceptions of depth and changing experiences of space that indicate complex interactions between perceptual and higher cognitive processes. The argument will draw on recent theories describing neuronal processes underlying multistable phenomena, eye movement, visual attention and decision-making. As I will show a large number of neuroscientific studies provide theoretical models that help us analyse not the anthropological constants but the influence of cultural, individual and situational variables on aesthetic experience.

Proteomic Analysis of Mitotic RNA Polymerase II Reveals Novel Interactors and Association With Proteins Dysfunctional in Disease*

PubMed Central

Möller, André; Xie, Sheila Q.; Hosp, Fabian; Lang, Benjamin; Phatnani, Hemali P.; James, Sonya; Ramirez, Francisco; Collin, Gayle B.; Naggert, Jürgen K.; Babu, M. Madan; Greenleaf, Arno L.; Selbach, Matthias; Pombo, Ana

2012-01-01

RNA polymerase II (RNAPII) transcribes protein-coding genes in eukaryotes and interacts with factors involved in chromatin remodeling, transcriptional activation, elongation, and RNA processing. Here, we present the isolation of native RNAPII complexes using mild extraction conditions and immunoaffinity purification. RNAPII complexes were extracted from mitotic cells, where they exist dissociated from chromatin. The proteomic content of native complexes in total and size-fractionated extracts was determined using highly sensitive LC-MS/MS. Protein associations with RNAPII were validated by high-resolution immunolocalization experiments in both mitotic cells and in interphase nuclei. Functional assays of transcriptional activity were performed after siRNA-mediated knockdown. We identify >400 RNAPII associated proteins in mitosis, among these previously uncharacterized proteins for which we show roles in transcriptional elongation. We also identify, as novel functional RNAPII interactors, two proteins involved in human disease, ALMS1 and TFG, emphasizing the importance of gene regulation for normal development and physiology. PMID:22199231

Identifying Cu( ii )–amyloid peptide binding intermediates in the early stages of aggregation by resonance Raman spectroscopy: a simulation study

DOE PAGES

Ren, Hao; Zhang, Yu; Guo, Sibei; ...

2017-10-31

The aggregation of amyloid beta (Aβ) peptides plays a crucial role in the pathology and etiology of Alzheimer's disease. Experimental evidence shows that copper ion is an aggregation-prone species with the ability to coordinately bind to Aβ and further induce the formation of neurotoxic Aβ oligomers. However, the detailed structures of Cu(II)–Aβ complexes have not been illustrated, and the kinetics and dynamics of the Cu(II) binding are not well understood. Two Cu(II)–Aβ complexes have been proposed to exist under physiological conditions, and another two might exist at higher pH values. By using ab initio simulations for the spontaneous resonance Ramanmore » and time domain stimulated resonance Raman spectroscopy signals, we obtained the characteristic Raman vibronic features of each complex. Finally, these signals contain rich structural information with high temporal resolution, enabling the characterization of transient states during the fast Cu–Aβ binding and interconversion processes.« less

Cellular Cations Control Conformational Switching of Inositol Pyrophosphate Analogues

PubMed Central

Hager, Anastasia; Wu, Mingxuan; Wang, Huanchen; Brown, Nathaniel W.; Shears, Stephen B.

2016-01-01

The inositol pyrophosphate messengers (PP-InsPs) are emerging as an important class of cellular regulators. These molecules have been linked to numerous biological processes, including insulin secretion and cancer cell migration, but how they trigger such a wide range of cellular responses has remained unanswered in many cases. Here, we show that the PP-InsPs exhibit complex speciation behaviour and propose that a unique conformational switching mechanism could contribute to their multifunctional effects. We synthesised non-hydrolysable bisphosphonate analogues and crystallised the analogues in complex with mammalian PPIP5K2 kinase. Subsequently, the bisphosphonate analogues were used to investigate the protonation sequence, metal-coordination properties, and conformation in solution. Remarkably, the presence of potassium and magnesium ions enabled the analogues to adopt two different conformations near physiological pH. Understanding how the intrinsic chemical properties of the PP-InsPs can contribute to their complex signalling outputs will be essential to elucidate their regulatory functions. PMID:27460418

It's about time: Presentation in honor of Ira Hirsh

NASA Astrophysics Data System (ADS)

Grant, Ken

2002-05-01

Over his long and illustrious career, Ira Hirsh has returned time and time again to his interest in the temporal aspects of pattern perception. Although Hirsh has studied and published articles and books pertaining to many aspects of the auditory system, such as sound conduction in the ear, cochlear mechanics, masking, auditory localization, psychoacoustic behavior in animals, speech perception, medical and audiological applications, coupling between psychophysics and physiology, and ecological acoustics, it is his work on auditory timing of simple and complex rhythmic patterns, the backbone of speech and music, that are at the heart of his more recent work. Here, we will focus on several aspects of temporal processing of simple and complex signals, both within and across sensory systems. Data will be reviewed on temporal order judgments of simple tones, and simultaneity judgments and intelligibility of unimodal and bimodal complex stimuli where stimulus components are presented either synchronously or asynchronously. Differences in the symmetry and shape of ``temporal windows'' derived from these data sets will be highlighted.

Detection and characterization of gene-gene and gene-environment interactions in common human diseases and complex clinical endpoints

EPA Science Inventory

Biological organisms are complex systems that dynamically integrate inputs from a multitude of physiological and environmental factors. Therefore, in addressing questions concerning the etiology of complex health outcomes, it is essential that the systemic nature of biology be ta...

Forest, Trees, Dynamics: Results from a Novel Wisconsin Card Sorting Test Variant Protocol for Studying Global-Local Attention and Complex Cognitive Processes

PubMed Central

Cowley, Benjamin; Lukander, Kristian

2016-01-01

Background: Recognition of objects and their context relies heavily on the integrated functioning of global and local visual processing. In a realistic setting such as work, this processing becomes a sustained activity, implying a consequent interaction with executive functions. Motivation: There have been many studies of either global-local attention or executive functions; however it is relatively novel to combine these processes to study a more ecological form of attention. We aim to explore the phenomenon of global-local processing during a task requiring sustained attention and working memory. Methods: We develop and test a novel protocol for global-local dissociation, with task structure including phases of divided (“rule search”) and selective (“rule found”) attention, based on the Wisconsin Card Sorting Task (WCST). We test it in a laboratory study with 25 participants, and report on behavior measures (physiological data was also gathered, but not reported here). We develop novel stimuli with more naturalistic levels of information and noise, based primarily on face photographs, with consequently more ecological validity. Results: We report behavioral results indicating that sustained difficulty when participants test their hypotheses impacts matching-task performance, and diminishes the global precedence effect. Results also show a dissociation between subjectively experienced difficulty and objective dimension of performance, and establish the internal validity of the protocol. Contribution: We contribute an advance in the state of the art for testing global-local attention processes in concert with complex cognition. With three results we establish a connection between global-local dissociation and aspects of complex cognition. Our protocol also improves ecological validity and opens options for testing additional interactions in future work. PMID:26941689

Articulatory Complexity, Ambient Frequency, and Functional Load as Predictors of Consonant Development in Children

ERIC Educational Resources Information Center

Stokes, Stephanie F.; Surendran, Dinoj

2005-01-01

The notion of a universal pattern of phonological development, rooted in basic physiological constraints, is controversial, with some researchers arguing for a strong environmental (ambient language) influence on phonological development or an interaction of both physiological constraints and ambient language effects. This research examines the…

High-resolution Mass Spectrometry of Skin Mucus for Monitoring Physiological Impacts in Fish Exposed to Wastewater Effluent at a Great Lakes AOC

EPA Science Inventory

High-resolution mass spectrometry is advantageous for monitoring physiological impacts and contaminant biotransformation products in fish exposed to complex wastewater effluent. We evaluated this technique using skin mucus from male and female fathead minnows (Pimephales promela...

High‐resolution mass spectrometry of skin mucus for monitoring physiological impacts and contaminant biotransformation products in fathead minnows exposed to wastewater effluent

EPA Science Inventory

High‐resolution mass spectrometry is advantageous for monitoring physiological impacts and contaminant biotransformation products in fish exposed to complex wastewater effluent. We evaluated this technique using skin mucus from male and female fathead minnows (Pimephales pr...

Autonomic Physiological Response Patterns Related to Intelligence

ERIC Educational Resources Information Center

Melis, Cor; van Boxtel, Anton

2007-01-01

We examined autonomic physiological responses induced by six different cognitive ability tasks, varying in complexity, that were selected on the basis of on Guilford's Structure of Intellect model. In a group of 52 participants, task performance was measured together with nine different autonomic response measures and respiration rate. Weighted…

CARBON AND NITROGEN ALLOCATION MODEL FOR THE SUB-TROPICAL SEAGRASS THALASSIA TESTUDINUM AND THE TEMPERATE SEAGRASS ZOSTER MARINA

EPA Science Inventory

Our understanding of seagrass physiology is based on crude estimates of production and biomass. To better understand the complex physiological relationships between the plants and the environment we developed a model of carbon and nitrogen allocation in the sub-tropical seagrass ...

Colonic Fermentation: A Neglected Topic in Human Physiology Education

ERIC Educational Resources Information Center

Valeur, Jorgen; Berstad, Arnold

2010-01-01

Human physiology textbooks tend to limit their discussion of colonic functions to those of absorbing water and electrolytes and storing waste material. However, the colon is a highly active metabolic organ, containing an exceedingly complex society of microbes. By means of fermentation, gastrointestinal microbes break down nutrients that cannot be…

Bioorthogonal Chemistry: Fishing for Selectivity in a Sea of Functionality

PubMed Central

Sletten, Ellen M.

2010-01-01

The study of biomolecules in their native environments is a challenging task because of the vast complexity of cellular systems. Technologies developed in the last few years for the selective modification of biological species in living systems have yielded new insights into cellular processes. Key to these new techniques are bioorthogonal chemical reactions, whose components must react rapidly and selectively with each other under physiological conditions in the presence of the plethora of functionality necessary to sustain life. Herein we describe the bioorthogonal chemical reactions developed to date and how they can be used to study biomolecules. PMID:19714693

Bioorthogonal chemistry: fishing for selectivity in a sea of functionality.

PubMed

Sletten, Ellen M; Bertozzi, Carolyn R

2009-01-01

The study of biomolecules in their native environments is a challenging task because of the vast complexity of cellular systems. Technologies developed in the last few years for the selective modification of biological species in living systems have yielded new insights into cellular processes. Key to these new techniques are bioorthogonal chemical reactions, whose components must react rapidly and selectively with each other under physiological conditions in the presence of the plethora of functionality necessary to sustain life. Herein we describe the bioorthogonal chemical reactions developed to date and how they can be used to study biomolecules.

The Unicellular State as a Point Source in a Quantum Biological System

PubMed Central

Torday, John S.; Miller, William B.

2016-01-01

A point source is the central and most important point or place for any group of cohering phenomena. Evolutionary development presumes that biological processes are sequentially linked, but neither directed from, nor centralized within, any specific biologic structure or stage. However, such an epigenomic entity exists and its transforming effects can be understood through the obligatory recapitulation of all eukaryotic lifeforms through a zygotic unicellular phase. This requisite biological conjunction can now be properly assessed as the focal point of reconciliation between biology and quantum phenomena, illustrated by deconvoluting complex physiologic traits back to their unicellular origins. PMID:27240413

miRNA*: a passenger stranded in RNA-induced silencing complex?

PubMed

Mah, S M; Buske, C; Humphries, R K; Kuchenbauer, F

2010-01-01

Processing of the pre-microRNA (pre-miRNA) through Dicer1 generates a miRNA duplex, consisting of a miRNA and miRNA* strand (also termed guide strand and passenger strand, respectively). Despite the general consensus that miRNA*s have no regulatory activity, recent publications have provided evidence that the abundance, possible function, and physiological relevance of miRNA*s have been underestimated. This review provides an account of our current understanding of miRNA* origination and activity, mounting evidence for their unique functions and regulatory mechanisms, and examples of specific miRNA*s from the literature.

A review of concepts regarding the origin of respiratory muscle fatigue

NASA Astrophysics Data System (ADS)

Kuraszkiewicz, Bożena; Piotrkiewicz, Maria

2011-01-01

In this review, the classification of respiratory muscle fatigue from the perspective of its origin is presented. The fatigue is classified as central or peripheral, and the latter further subdivided into high- and low-frequency fatigue. However, muscle fatigue is a complex process and all three types of fatigue probably occur simultaneously in the overloaded respiratory muscles. The relative importance of each type depends on the duration of respiratory loading and other physiological variables. However, central and high-frequency fatigue resolve rapidly once muscle overload is removed, whereas low-frequency fatigue persists over long time.

Physiological studies of the brain: Implications for science teaching

NASA Astrophysics Data System (ADS)

Esler, William K.

Physiological changes resulting from repeated, long-term stimulation have been observed in the brains of both humans and laboratory animals. It may be speculated that these changes are related to short-term and long-term memory processes. A physiologically based model for memory processing (PBMMP) can serve to explain the interrelations of various areas of the brain as they process new stimuli and recall past events. The model can also serve to explain many current principles of learning theory and serve as a foundation for developing new theories of learning based upon the physiology of the brain.

Autophagy in C. elegans development.

PubMed

Palmisano, Nicholas J; Meléndez, Alicia

2018-04-27

Autophagy involves the sequestration of cytoplasmic contents in a double-membrane structure referred to as the autophagosome and the degradation of its contents upon delivery to lysosomes. Autophagy activity has a role in multiple biological processes during the development of the nematode Caenorhabditis elegans. Basal levels of autophagy are required to remove aggregate prone proteins, paternal mitochondria, and spermatid-specific membranous organelles. During larval development, autophagy is required for the remodeling that occurs during dauer development, and autophagy can selectively degrade components of the miRNA-induced silencing complex, and modulate miRNA-mediated silencing. Basal levels of autophagy are important in synapse formation and in the germ line, to promote the proliferation of proliferating stem cells. Autophagy activity is also required for the efficient removal of apoptotic cell corpses by promoting phagosome maturation. Finally, autophagy is also involved in lipid homeostasis and in the aging process. In this review, we first describe the molecular complexes involved in the process of autophagy, its regulation, and mechanisms for cargo recognition. In the second section, we discuss the developmental contexts where autophagy has been shown to be important. Studies in C. elegans provide valuable insights into the physiological relevance of this process during metazoan development. Copyright © 2018 Elsevier Inc. All rights reserved.

[Age factor in a complex evaluation of health of air staff].

PubMed

Ushakov, I B; Batishcheva, G A; Chernov, Iu N; Khomenko, M N; Soldatov, S K

2010-03-01

Was elaborated program of a complex of estimation of health condition of air staff with determination of capability of early diagnostic of functional tension of physiological systems. According to this system there were observed 73 airmen using a complex of tests (estimation of level of pectoral control, of personal and reactive anxiety, vegetal regulation etc.). Was detected, that length of service and sympato-adrenaline activeness with vicarious decrease of adrenoreactiveness are in direct proportion. Were marked the most informative indexes of estimation of functional tension of psycho-physiological functions, vegetative regulation and cardiovascular system. Was shown that the elaborated system of individual estimation of health of air staff permits diagnose prenosological conditions and determine indexes for rehabilitation treatment.

Cysteine-Zn2+ complexes: unique molecular switches for inducible nitric oxide synthase-derived NO.

PubMed

Kröncke, K D

2001-11-01

Nitric oxide (NO) in the low nanomolar range acts as a transcellular messenger molecule to initiate regulatory and physiological responses in nearby target cells via binding to the soluble guanylate cyclase heme moiety. Higher NO concentrations, as synthesized by the inducible NO synthase (iNOS) during inflammatory processes, show additional effects: NO may react with O2, yielding nitrogen oxides like N2O3 that are able to nitrosate thiols. A variety of proteins involved in very different functions of the cell contain cysteine-Zn2+ complexes. Effects of NO on different proteins containing cysteine-Zn2+ domains and playing essential roles during transcription, protein folding, and proteolysis are discussed. It is suggested that iNOS-derived NO acts as a signal molecule targeting cysteine-Zn2+ linkages, thus enabling cells to react toward nitrosative stress.

Neuroscience of water molecules: a salute to professor Linus Carl Pauling.

PubMed

Nakada, Tsutomu

2009-04-01

More than 35 years ago double Nobel laureate Linus Carl Pauling published a powerful model of the molecular mechanism of general anesthesia, generally referred to as the hydrate-microcrystal (aqueous-phase) theory. This hypothesis, based on the molecular behavior of water molecules, did not receive serious attention during Pauling's life time, when scientific tools for examining complex systems such as the brain were still in their infancy. The situation has since drastically changed, and, now, in the twenty first century, many scientific tools are available for examining different types of complex systems. The discovery of aquaporin-4, a subtype of water channel abundantly expressed in glial systems, further highlighted the concept that the dynamics of water molecules in the cerebral cortex play an important role in important physiological brain functions including consciousness and information processing.

THE RGM/DRAGON FAMILY OF BMP CO-RECEPTORS

PubMed Central

Corradini, Elena; Babitt, Jodie L.; Lin, Herbert Y.

2013-01-01

The BMP signaling pathway controls a number of cell processes during development and in adult tissues. At the cellular level, ligands of the BMP family act by binding a hetero-tetrameric signaling complex, composed of two type I and two type II receptors. BMP ligands make use of a limited number of receptors, which in turn activate a common signal transduction cascade at the intracellular level. A complex regulatory network is required in order to activate the signaling cascade at proper times and locations, and to generate specific downstream effects in the appropriate cellular context. One such regulatory mechanism is the repulsive guidance molecule (RGM) family of BMP co-receptors. This article reviews the current knowledge regarding the structure, regulation, and function of RGMs, focusing on known and potential roles of RGMs in physiology and pathophysiology. PMID:19897400

Use of Multiple GPUs to Speedup the Execution of a Three-Dimensional Computational Model of the Innate Immune System

NASA Astrophysics Data System (ADS)

Xavier, M. P.; do Nascimento, T. M.; dos Santos, R. W.; Lobosco, M.

2014-03-01

The development of computational systems that mimics the physiological response of organs or even the entire body is a complex task. One of the issues that makes this task extremely complex is the huge computational resources needed to execute the simulations. For this reason, the use of parallel computing is mandatory. In this work, we focus on the simulation of temporal and spatial behaviour of some human innate immune system cells and molecules in a small three-dimensional section of a tissue. To perform this simulation, we use multiple Graphics Processing Units (GPUs) in a shared-memory environment. Despite of high initialization and communication costs imposed by the use of GPUs, the techniques used to implement the HIS simulator have shown to be very effective to achieve this purpose.

An in vivo multiplexed small molecule screening platform

PubMed Central

Yang, Dian; Ogasawara, Daisuke; Dix, Melissa M.; Rogers, Zoë N.; Chuang, Chen-Hua; McFarland, Christopher D.; Chiou, Shin-Heng; Brown, J. Mark; Cravatt, Benjamin F.; Bogyo, Matthew; Winslow, Monte M.

2016-01-01

Phenotype-based small molecule screening is a powerful method to identify regulators of cellular function. However, such screens are generally performed in vitro using conditions that do not necessarily model complex physiological conditions or disease states. Here, we use molecular cell barcoding to enable direct in vivo phenotypic screening of libraries of small molecules. The multiplexed nature of this approach allows rapid in vivo analysis of hundreds to thousands of compounds. Using this platform, we screened >700 covalent inhibitors directed towards hydrolases for their effect on pancreatic cancer metastatic seeding. We identified multiple hits and confirmed the relevant target of one compound as the lipase ABHD6. Pharmacological and genetic studies confirmed the role of this enzyme as a regulator of metastatic fitness. Our results highlight the applicability of this multiplexed screening platform for investigating complex processes in vivo. PMID:27617390

Dual Role of Fas/FasL-Mediated Signal in Peripheral Immune Tolerance.

PubMed

Yamada, Akiko; Arakaki, Rieko; Saito, Masako; Kudo, Yasusei; Ishimaru, Naozumi

2017-01-01

Fas-mediated apoptosis contributes to physiological and pathological cellular processes, such as differentiation and survival. In particular, the roles of Fas in immune cells are complex and critical for the maintenance of immune tolerance. The precise pathways and unique functions associated with Fas/FasL-mediated signaling in the immune system are known. The dual character of Fas/FasL-mediated immune regulation that induces beneficial or harmful effects is associated with the onset or development of immune disorders. Studies on mutations in genes encoding Fas and FasL gene of humans and mice contributed to our understanding of the pathogenesis of autoimmune diseases. Here, we review the opposing functions of Fas/FasL-mediated signaling, bilateral effects of Fas/FasL on in immune cells, and complex pathogenesis of autoimmunity mediated by Fas/FasL.

Dual Role of Fas/FasL-Mediated Signal in Peripheral Immune Tolerance

PubMed Central

Yamada, Akiko; Arakaki, Rieko; Saito, Masako; Kudo, Yasusei; Ishimaru, Naozumi

2017-01-01

Fas-mediated apoptosis contributes to physiological and pathological cellular processes, such as differentiation and survival. In particular, the roles of Fas in immune cells are complex and critical for the maintenance of immune tolerance. The precise pathways and unique functions associated with Fas/FasL-mediated signaling in the immune system are known. The dual character of Fas/FasL-mediated immune regulation that induces beneficial or harmful effects is associated with the onset or development of immune disorders. Studies on mutations in genes encoding Fas and FasL gene of humans and mice contributed to our understanding of the pathogenesis of autoimmune diseases. Here, we review the opposing functions of Fas/FasL-mediated signaling, bilateral effects of Fas/FasL on in immune cells, and complex pathogenesis of autoimmunity mediated by Fas/FasL. PMID:28424702

Linguistic Analysis of the Human Heartbeat Using Frequency and Rank Order Statistics

NASA Astrophysics Data System (ADS)

Yang, Albert C.-C.; Hseu, Shu-Shya; Yien, Huey-Wen; Goldberger, Ary L.; Peng, C.-K.

2003-03-01

Complex physiologic signals may carry unique dynamical signatures that are related to their underlying mechanisms. We present a method based on rank order statistics of symbolic sequences to investigate the profile of different types of physiologic dynamics. We apply this method to heart rate fluctuations, the output of a central physiologic control system. The method robustly discriminates patterns generated from healthy and pathologic states, as well as aging. Furthermore, we observe increased randomness in the heartbeat time series with physiologic aging and pathologic states and also uncover nonrandom patterns in the ventricular response to atrial fibrillation.

Optimizing Complexity Measures for fMRI Data: Algorithm, Artifact, and Sensitivity

PubMed Central

Rubin, Denis; Fekete, Tomer; Mujica-Parodi, Lilianne R.

2013-01-01

Introduction Complexity in the brain has been well-documented at both neuronal and hemodynamic scales, with increasing evidence supporting its use in sensitively differentiating between mental states and disorders. However, application of complexity measures to fMRI time-series, which are short, sparse, and have low signal/noise, requires careful modality-specific optimization. Methods Here we use both simulated and real data to address two fundamental issues: choice of algorithm and degree/type of signal processing. Methods were evaluated with regard to resilience to acquisition artifacts common to fMRI as well as detection sensitivity. Detection sensitivity was quantified in terms of grey-white matter contrast and overlap with activation. We additionally investigated the variation of complexity with activation and emotional content, optimal task length, and the degree to which results scaled with scanner using the same paradigm with two 3T magnets made by different manufacturers. Methods for evaluating complexity were: power spectrum, structure function, wavelet decomposition, second derivative, rescaled range, Higuchi’s estimate of fractal dimension, aggregated variance, and detrended fluctuation analysis. To permit direct comparison across methods, all results were normalized to Hurst exponents. Results Power-spectrum, Higuchi’s fractal dimension, and generalized Hurst exponent based estimates were most successful by all criteria; the poorest-performing measures were wavelet, detrended fluctuation analysis, aggregated variance, and rescaled range. Conclusions Functional MRI data have artifacts that interact with complexity calculations in nontrivially distinct ways compared to other physiological data (such as EKG, EEG) for which these measures are typically used. Our results clearly demonstrate that decisions regarding choice of algorithm, signal processing, time-series length, and scanner have a significant impact on the reliability and sensitivity of complexity estimates. PMID:23700424

Physiological typing of Pseudallescheria and Scedosporium strains using Taxa Profile, a semi-automated, 384-well microtitre system.

PubMed

Horré, R; Schaal, K P; Marklein, G; de Hoog, G S; Reiffert, S-M

2011-10-01

During the last few decades, Pseudallescheria and Scedosporium infections in humans are noted with increasing frequency. Multi-drug resistance commonly occurring in this species complex interferes with adequate therapy. Rapid and correct identification of clinical isolates is of paramount significance for optimal treatment in the early stages of infection, while strain typing is necessary for epidemiological purposes. In view of the development of physiological diagnostic parameters, 570 physiological reactions were evaluated using the Taxa Profile Micronaut system, a semi-automatic, computer-assisted, 384-well microtitre platform. Thirty two strains of the Pseudallescheria and Scedosporium complex were analysed after molecular verification of correct species attribution. Of the compounds tested, 254 proved to be polymorphic. Cluster analysis was performed with the Micronaut profile software, which is linked to the ntsypc® program. The systemic opportunist S. prolificans was unambiguously separated from the remaining species. Within the P. boydii/P. apiosperma complex differentiation was noted at the level of individual strains, but no unambiguous parameters for species recognition were revealed. © 2011 Blackwell Verlag GmbH.