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Results for “Physiology”

Search indexed bioRxiv preprints in genomics, neuroscience, cell biology and bioinformatics. Read source abstracts and check manuscript versions; preprints are not peer reviewed.

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At least 55 records · Page 3Linked to original sources

bioRxiv2018

A computational model to understand mouse iron physiology and diseases

It is well known that iron is an essential element for life but is toxic when in excess or in certain forms. Accordingly there are many diseases that result directly from either lack or excess of iron. Iron has also been associated with a wide range of other diseases and may have an important role in aging. Yet many molecular and physiological aspects of iron regulation have only been discovered recently and others are still awaiting elucidation. In the last 18 years, after the discovery of the hormone hepcidin, many details of iron regulation have become better understood and a clearer picture is starting to emerge, at least in qualitative terms. However there is still no good quantitative and dynamic description of iron absorption, distribution, storage and mobilization that agrees with the wide array of phenotypes presented in several iron-related diseases. The present work addresses this issue by developing a mathematical model of iron distribution in mice that was calibrated with existing ferrokinetic data and subsequently validated against data from a series of iron disorders, such as hemochromatosis, {beta}-thalassemia, atransferrinemia and anemia of inflammation. To adequately fit the ferrokinetic data required including the following mechanisms: a) the role of transferrin in deliving iron to tissues, b) the induction of hepcidin by high levels of transferrin-bound iron, c) the ferroportin-dependent hepcidin-regulated iron export from tissues, d) the erythropoietin regulation of erythropoiesis, and e) direct NTBI uptake by the liver. The utility of such a model to simulate disease interventions was demonstrated by using it to investigate the outcome of different schedules of transferrin treatment in {beta}-thalassemia. The present model is a successful step towards a comprehensive mathematical model of iron physiology incorporating cellular and organ level details.

systems biology↗

bioRxiv2018

Biophysical underpinning of astroglial physiology probed with realistic cell models

Electrically non-excitable astroglia take up neurotransmitters, buffer extracellular K+ and generate Ca2+ signals that release molecular regulators of neural circuitry. The underlying machinery remains enigmatic, mainly because the nanoscopic, sponge-like astrocyte morphology has been difficult to access experimentally or explore theoretically. Here, we have systematically evaluated the multi-scale morphology of protoplasmic astroglia to construct a realistic multi-compartmental cell model that can be biophysically interrogated in NEURON computational environment. This approach has been implemented as an astrocyte-model builder ASTRO. As a proof of concept, we explored a hippocampal astrocyte reconstructed in silico against a battery of physiological and imaging experiments. This exploration has unveiled some basic features of astroglial physiology inaccessible empirically, such as the characteristic length of membrane voltage propagation, membrane effects of local glutamate transport, spatiotemporal dynamics of intracellular K+ redistribution, key Ca2+ buffering properties, and some basic relationships between free Ca2+ dynamics and experimental readout of fluorescent Ca2+ indicators.

neuroscience↗

bioRxiv2018

Functional phenomics: An emerging field integrating high-throughput phenotyping, physiology, and bioinformatics

HighlightFunctional phenomics is an emerging field in plant biology that relies on high-throughput phenotyping, big data analytics, controlled manipulative experiments, and simulation modelling to increase understanding of plant physiology.\n\nAbstractThe emergence of functional phenomics signifies the rebirth of physiology as a 21st century science through the use of advanced sensing technologies and big data analytics. Functional phenomics highlights the importance of phenotyping beyond only identifying genetic regions because a significant knowledge gap remains in understanding which plant properties will influence ecosystem services beneficial to human welfare. Here, a general approach for the theory and practice of functional phenomics is outlined including exploring the phene concept as a unit of phenotype. The functional phenomics pipeline is proposed as a general method for conceptualizing, measuring, and validating utility of plant phenes. The functional phenomics pipeline begins with ideotype development. Second, a phenotyping platform is developed to maximize the throughput of phene measurements. A mapping population is screened measuring target phenes and indicators of plant performance such as yield and nutrient composition. Traditional forward genetics allows genetic mapping, while functional phenomics links phenes to plant performance. Based on these data, genotypes with contrasting phenotypes can be selected for smaller yet more intensive experiments to understand phene-environment interactions in depth. Simulation modeling can be used to understand the phenotypes and all stages of the pipeline feed back to ideotype and phenotyping platform development.

plant biology↗

bioRxiv2018

Evolutionarily conserved anatomical and physiological properties of olfactory pathway till fourth order neurons in a species of grasshopper (Hieroglyphus banian)

Olfactory systems of different species show variations in structure and physiology despite some conserved characteristics. We characterized the olfactory circuit of the grasshopper Hieroglyphus banian of family Acrididae (subfamily: Hemiacridinae) and compared it to a well-studied species of locust, Schistocerca americana (subfamily: Cyrtacanthacridinae), also belonging to family Acrididae. We used in vivo electrophysiological, immunohistochemical and anatomical (bulk tract tracing) methods to elucidate the olfactory pathway from the second order neurons in antennal lobe to the fourth order neurons in {beta}-lobe of H. banian.\n\nWe observe highly conserved anatomical and physiological characteristics till the fourth order neurons in the olfactory circuit of H. banian and S. americana, though they are evolutionarily divergent (~57 million years ago). However, we found one major difference between the two species-there are four antennal lobe tracts in H. banian while only one is reported in S. americana. Besides, we are reporting for the first time, a new class of bilateral neurons which respond weakly to olfactory stimuli even though they innervate densely downstream of Kenyon cells.

neuroscience↗

bioRxiv2015

Hyper-variability in Circulating Insulin Levels and Physiological Outcomes to High Fat Feeding in Male Ins1-/-:Ins2+/- Mice in a Specific Pathogen-free Facility

Insulin is an essential hormone with key roles in energy homeostasis and body composition. Mice and rats, unlike other mammals, have two insulin genes: the rodent-specific Ins1 gene and the ancestral Ins2 gene. The relationships between insulin gene dosage and obesity has previously been explored in male and female Ins2-/- mice with full or reduced Ins1 dosage, as well as in female Ins1-/- mice with full or partial Ins2 dosage. We report herein unexpected hyper-variability in circulating insulin and physiological responses to high fat feeding in male Ins1-/-:Ins2+/- mice. Two large cohorts of Ins1-/-:Ins2+/- mice and their Ins1-/-:Ins2+/+ littermates were fed chow diet or high fat diet (HFD) from weaning and housed in specific pathogen-free (SPF) conditions. Cohort A and cohort B were studied one year apart. Contrary to female mice from the same litters, inactivating one Ins2 allele on the complete Ins1-null background did not cause a consistent reduction of circulating insulin in male mice. In cohort A, HFD-fed males showed an equivalent degree of insulin hypersecretion and weight gain, regardless of Ins2 dosage. In cohort B, Ins1-/-:Ins2+/- males showed decreased insulin levels and body mass, compared to Ins1-/-:Ins2+/+ littermates. While experimental conditions were held consistent between cohorts, we found that HFD-fed Ins1-/-:Ins2+/- mice with lower insulin levels had increased corticosterone. Collectively, these observations highlight the hyper-variability and range of phenotypic characteristics modulated by Ins2 gene dosage, specifically in male mice.

Physiology↗

bioRxiv2017

Role Of Chymotrypsin-Like Elastase 1 In Lung Physiology And in α1-Antitrypsin Deficiency

1-antitrypsin (AAT) deficiency-related emphysema is the fourth leading indication for lung transplantation. We previously demonstrated that AAT covalently neutralizes chymotrypsin-like elastase 1 (Cela1) in vitro, that Cela1 is expressed during the alveolar stage of lung development in association with regions of lung elastin remodeling, and that lung stretch increases Cela1 expression and binding to lung elastin. Here we show that Cela1 is exclusively responsible for stretch-inducible lung elastase activity, reduces postnatal lung elastance, and is required for emphysema in an antisense oligo model of AAT deficiency. Cela1 mRNA is present in the human lung, and in the placental mammal lineage, Cela1 is more conserved than Cela2 or Cela3 with unique promoter and protein elements indicating a unique role for Cela1 in this lineage. These data demonstrate an adaptive role for Cela1 in placental mammal lung biology with physiologic relevance to AAT-deficient lung disease in humans.

physiology↗

bioRxiv2018

A model for physiological transmembrane transport derived from thermodynamical principles

A generic formulation for both passive and active transmembrane transport is derived from basic thermodynamical principles. The derivation takes into account the energy required for the motion of molecules across membranes, and includes the possibility of modeling asymmetric flow. Transmembrane currents can then be described by the generic model in the case of electrogenic flow. As it is desirable in new models, it is possible to derive other well known expressions for transmembrane currents as particular cases of the generic formulation. For instance, the conductance-based formulation for current turns out to be a linear approximation of the generic current. Also, under suitable assumptions, other formulas for current based on electrodiffusion, like the constant field approximation by Goldman, can also be recovered from the generic formulation. The applicability of the generic formulations is illustrated first with fits to existing data, and after, with models of transmembrane potential dynamics for pacemaking cardiocytes and neurons. The generic formulations presented here provide a common ground for the biophysical study of physiological phenomena that depend on transmembrane transport.

physiology↗

bioRxiv2014

A high resolution 7-Tesla resting-state fMRI test-retest dataset with cognitive and physiological measures

Here we present a test-retest dataset of functional magnetic resonance imaging (fMRI) data acquired at rest. 22 participants were scanned during two sessions spaced one week apart. Each session includes two 1.5 mm isotropic whole-brain scans and one 0.75 mm isotropic scan of the prefrontal cortex, giving a total of six timepoints. Additionally, the dataset includes measures of mood, sustained attention, blood pressure, respiration, pulse, and the content of self-generated thoughts (mind wandering). This data enables the investigation of sources of both intra- and inter-session variability not only limited to physiological changes, but also including alterations in cognitive and affective states, at high spatial resolution. The dataset is accompanied by a detailed experimental protocol and source code of all stimuli used.

Neuroscience↗

bioRxiv2015

Pollen contaminated with field-relevant levels of cyhalothrin affects honey bee survival, nutritional physiology, and pollen consumption behavior

Honey bees are exposed to a variety of environmental stressors that impact their health, including nutritional stress, pathogens, and chemicals in the environment. In particular, there has been increasing evidence that sublethal exposure to pesticides can cause subtle, yet important effects on honey bee health and behavior. Here, we add to this body of knowledge by presenting data on bee-collected pollen containing sublethal levels of cyhalothrin, a pyrethroid insecticide, which, when fed to young honey bees, results in significant changes in lifespan, nutritional physiology, and behavior. For the first time, we show that when young, nest-aged bees are presented with pollen containing field-relevant levels of cyhalothrin, they reduce their consumption of contaminated pollen. This indicates that, at least for some chemicals, young bees are able to detect contamination in pollen and change their behavioral response, even if the contamination levels do not prevent foraging honey bees from collecting the contaminated pollen.

Animal Behavior and Cognition↗

bioRxiv2016

Conformational dynamics of Tau in the cell quantified by an intramolecular FRET biosensor in physiological and pathological context

Impaired interactions of Tau protein with microtubules (MT) and Tau misfolding play a key role in Alzheimer disease (AD) and other neurodegenerative diseases collectively named Tauopathies. However, little is known about the molecular conformational changes that underlie Tau misfolding and aggregation in pathological conditions, due to the difficulty of studying structural aspects of this intrinsically unfolded protein, particularly in the context of living cells.\n\nHere we developed a new Conformational-Sensitive Tau sensor (CST), based on human Tau full length protein, to investigate the changes in 3D conformation and aggregation state of Tau upon modulation of its interactions with MTs in living cells, in physiological and pathological conditions. After showing that the CST fully preserves functional Tau activities in living cells, we demonstrated that MT-bound Tau displays a loop-like conformation, while soluble Tau assumes a relaxed conformation.\n\nThe imaging readout based on CST allowed to discover new conformational properties of full length Tau in living cells, when challenged with Alzheimer-relevant seeds from different sources, and to learn about different ways to induce the self-aggregation of full length Tau in cells. Furthermore, it allowed to investigate the contribution to the pathology of point mutations known to alter Tau/MTs interaction.\n\nSIGNIFICANCEThe microtubule-associated protein Tau regulates the stability of microtubules (MT) and its alteration and misfolding plays an important role in Alzheimer disease (AD) and in several other neurodegenerative diseases collectively named Tauopathies. However, little is known about the molecular mechanism that modulate the conformational changes of Tau in pathological conditions. Here, we developed a conformational sensitive Tau biosensor providing insights into the 3D conformation of Tau in living cells. This new tool showed that MT-bound Tau displays a loop-like conformation, while soluble Tau assume a relaxed conformation, which might be more prone to aggregation. Furthermore the CST was used to develop an assay to screen molecules and mutations involved in Tau self-aggregation in living cells. Remarkably, the imaging tool developed allowed to demonstrate that A{beta} oligomers induced Tau aggregation in living cells.

Neuroscience↗

bioRxiv2016

Physiological and biochemical changes associated with experimental dehydration in the desert adapted cactus mouse, Peromyscus eremicus

Characterizing traits critical for adaptation to a given environment is an important first step in understanding how phenotypes evolve. How animals adapt to the extreme heat and aridity commonplace to deserts represents is an exceptionally interesting example of these processes, and has been the focus of study for decades. In contrast to those studies, where experiments are conducted on either wild animals or captive animals held in non-desert conditions, the study described here leverages a unique environmental chamber that replicates desert conditions for captive Peromyscus eremicus (cactus mouse). Here we establish baseline values for daily water intake and for serum electrolytes, as well as the response of these variables to experimental dehydration. In brief, P. eremicus daily water intake is very low. Its serum electrolytes are distinct from many previously studied animals, and its response to acute dehydration is profound, though not suggestive of renal impairment, which is atypical of mammals.\n\nSummary statementThe establishment of baseline values for serum electrolytes and water intake, as well as their response to acute dehydration is critical for characterizing the physiology necessary for desert survival.\n\nConflict of Interest StatementThe authors declare no conflict of interest.

Zoology↗

bioRxiv2016

Behavioural effects of temperature on ectothermic animals: unifying thermal physiology and behavioural plasticity

Temperature imposes significant constraints on ectothermic animals, and these organisms have evolved numerous adaptations to respond to these constraints. While the impacts of temperature on the physiology of ectotherms have been extensively studied, there are currently no frameworks available that outline the multiple and often simultaneous pathways by which temperature can affect behaviour. Drawing from the literature on insects, we propose a unified framework that should apply to all ectothermic animals, generalizing temperature's behavioural effects into (1) Kinetic effects, resulting from temperature's bottom-up constraining influence on metabolism and neurophysiology over a range of timescales (from short-to long-term), and (2) Integrated effects, where the top-down integration of thermal information intentionally initiates or modifies a behaviour (behavioural thermoregulation, thermal orientation, thermosensory behavioural adjustments). We discuss the difficulty in distinguishing adaptive behavioural changes due to temperature from behavioural changes that are the products of constraints, and propose two complementary approaches to help make this distinction and class behaviours according to our framework: (i) behavioural kinetic null modeling and (ii) behavioural ecology experiments using temperature-insensitive mutants. Our framework should help to guide future research on the complex relationship between temperature and behaviour in ectothermic animals.

Ecology↗

bioRxiv2016

Gene expression analysis provides insight into the physiology of the important staple food crop cassava

O_LICassava (Manihot esculenta) feeds approximately 800 million people worldwide. Although this crop displays high productivity under drought and poor soil conditions, it is susceptible to disease, postharvest deterioration and the roots contain low nutritional content.\nC_LIO_LIHere, we provide molecular identities for eleven cassava tissue types through RNA-sequencing and develop an open access, web-based interface for further interrogation of the data.\nC_LIO_LIThrough this dataset, we report novel insight into the physiology of cassava and identify promoters able to drive specified tissue expression profiles. Specifically, we focus on identification of the transcriptional signatures that define the massive, underground storage roots used as a food source and the favored target tissue for transgene integration and genome editing, friable embryogenic callus (FEC).\nC_LIO_LIThe information gained from this study is of value for both conventional and biotechnological improvement programs.\nC_LI

Plant Biology↗

bioRxiv2016

Stomatal and physiological response of contrasting Z. mauritiana (Lamk.) clones to water stress.

Water stress is one of the major limitations to fruit production worldwide. Identifying suitable indicators, screening techniques and quantifiable traits would facilitate the genetic improvement process for water stress tolerance. In the present study, we evaluated the ability of physiological parameters (Transpiration, E; Fv/Fm; leaf water potential, {psi}leaf; leaf temperature, LT; and, leaf relative water content, RWC) to distinguish between contrasting Z. mauritiana clones subjected to a 30-d drought cycle. Four field-grown clones Seb and Gola (tetraploid) and Q 29 and B 5/4 (diploid) were studied. By 30 d after the onset of water stress treatment, the E, Fv/Fm, {psi}leaf and RWC of drought-stressed plants had declined significantly in all genotypes compared to values of well-watered treatments. However, the reductions were more severe in leaves of diploid clones. Under drought stress, the Seb and Gola, maintained higher E (31.5%), Fv/Fm (6.28%), {psi}leaf; (11.2%), and RWC (9.3 %) than Q 29 and B 5/4 clones. In general, LT of drought-stressed plants was higher (~4{degrees}C) than that of well-watered plants but the relative increase was greater among later than former ones. Under maximum drought stress, LT of Seb and Gola clones was on average 3.0{degrees}C lower than that of Q 29 and B 5/4. Former clones yielded 20% more than later ones, mainly reason being (14.8%) less fruit drop as an effect of water stress. The results indicate that presented parameters can be reliable in screening for water stress tolerance ability, with Fv/Fm, {psi}leaf, RWC and LT having the added advantage of being easily and quickly assessed.

Plant Biology↗

bioRxiv2016

An Electrochemistry Study of Cryoelectrolysis in Frozen Physiological Saline

This is the first quantitative study on the fundamental physical and electrochemical processes that occur during cryoelectrolysis. Cryoelectrolysis is a new minimally invasive tissue ablation surgical technique that combines the processes of electrolysis and solid/liquid phase transformation (freezing). We measured the pH front propagation and the changes in resistance in a tissue simulant made of physiological saline gel with a pH dye as a function of the sample temperature in the high subzero range above the eutectic. Results demonstrate that effective electrolysis can occur in a high subzero freezing milieu and that the propagation of the pH front is only weakly dependent on temperature. These observations are consistent with a mechanism involving ionic movement through the concentrated saline solution channels between ice crystals at subfreezing temperatures above the eutectic. The Joule heating in these microchannel may cause local microscopic melting, the observed weak dependence of pH front propagation on temperature, and the large changes in resistance with time. In addition, we observed that the pH front propagation from the anode is more rapid than from the cathode. The explanation is the electro-osmotic flow from the cathode to the anode. The findings in this paper may be of fundamental value for designing future cryoelectrolytic ablation surgery protocols.

Bioengineering↗

bioRxiv2016

A Saposin deficiency model in Drosophila: lysosomal storage, progressive neurodegeneration, sensory physiological decline and defective calcium homeostasis

Saposin deficiency is a childhood neurodegenerative lysosomal storage disorder (LSD) that can cause premature death within three months of life. Saposins are activator proteins that promote the function of lysosomal hydrolases in the degradation of sphingolipids. There are four saposin proteins in humans, which are encoded by the prosaposin gene. Mutations causing an absence of individual saposins or the whole prosaposin gene lead to distinct LSDs due to the storage of different classes of sphingolipids. The pathological events leading to neuronal dysfunction induced by lysosomal storage of sphingolipids are as yet poorly defined. We have generated and characterised a Drosophila model of saposin deficiency that shows striking similarities to the human diseases. Drosophila saposin-related (dSap-r) mutants show a reduced longevity, progressive neurodegeneration, lysosomal storage, dramatic swelling of neuronal soma, perturbations in sphingolipid catabolism, and sensory physiological deterioration. We have also revealed a genetic interaction with a calcium exchanger (CalX), suggesting that calcium homeostasis may be altered in saposin deficiency. Together these findings support the use of dSap-r mutants in advancing our understanding of the cellular pathology implicated in saposin deficiency and related LSDs.

Neuroscience↗

bioRxiv2017

In vitro assembly of the Rous Sarcoma Virus capsid protein into hexamer tubes under physiological conditions.

During a proteolytically-driven maturation process, the ortho-retroviral capsid protein (CA) assembles to form the convex shell that surrounds the viral genome. In some orthoretroviruses, including Rous Sarcoma Virus (RSV), CA carries a short and hydrophobic spacer peptide (SP) at its C-terminus early in the maturation process, which is progressively removed as maturation proceeds. In this work, we show that RSV CA assembles in vitro at physiological temperatures, forming hexamer tubes that effectively model the mature capsid surface. Tube assembly is strongly influenced by electrostatic effects, and is a nucleated process that remains thermodynamically favored at lower temperatures, but is effectively arrested by the large Gibbs energy barrier associated with nucleation. RSV CA tubes are multi-layered, being formed by nested and concentric tubes of capsid hexamers. However the spacer peptide acts as a layering determinant during tube assembly. If only a minor fraction of CA-SP is present, multi-layered tube formation is blocked, and single-layered tubes predominate. This likely prevents formation of biologically aberrant multi-layered capsids in the virion. The generation of single-layered hexamer tubes facilitated 3D helical image reconstruction from cryo-electron microscopy data, revealing the basic tube architecture.

biochemistry↗

bioRxiv2017

How to get the most bang for your buck: the evolution and physiology of nutrition-dependent resource allocation strategies

All organisms utilize resources to grow, survive, and reproduce. The supply of these resources varies widely across landscapes and time, imposing ultimate constraints on the maximal trait values for allocation-related traits. In this review, we address three key questions fundamental to our understanding of the evolution of allocation strategies and their underlying mechanisms. First, we ask: how diverse are flexible resource allocation strategies among different organisms? We find there are many, varied, examples of flexible strategies that depend on nutrition. However, this diversity is often ignored in some of the best-known cases of resource allocation shifts, such as the commonly observed pattern of lifespan extension under nutrient limitation. A greater appreciation of the wide variety of flexible allocation strategies leads directly to our second major question: what conditions select for different plastic allocation strategies? Here, we highlight the need for additional models that explicitly consider the evolution of phenotypically plastic allocation strategies and empirical tests of the predictions of those models in natural populations. Finally, we consider the question: what are the underlying mechanisms determining resource allocation strategies? Although evolutionary biologists assume differential allocation of resources is a major factor limiting trait evolution, few proximate mechanisms are known that specifically support the model. We argue that an integrated framework can reconcile evolutionary models with proximate mechanisms that appear at first glance to be in conflict with these models. Overall, we encourage future studies to 1) mimic ecological conditions in which those patterns evolve, and 2) take advantage of the omic opportunities to produce multi-level data and analytical models that effectively integrate across physiological and evolutionary theory.

evolutionary biology↗