Changes In Physiological State Research Articles

Dinucleotide-Sensing Proteins: Linking Signaling Networks and Regulating Transcription

Differential binding of dinucleotides to key regulatory proteins can modulate their interactions with other proteins and, in some cases, can signal fluctuations in the cellular redox state, to produce changes in transcription and physiological state. The dinucleotide-binding proteins human HSCARG and yeast transcription repressor Gal80p are examples that offer exciting glimpses into the potential for dinucleotide-sensing proteins to couple fluctuations in dinucleotide ratios to changes in transcription and to act as networking agents linking different classes of signaling molecules.

Physiological effects of the addition of n-dodecane as an oxygen vector during steady-state Bacillus licheniformis thermophillic fermentations perturbed by a starvation period or a glucose pulse

The effect of the presence of n-dodecane as a potential oxygen vector during oxygen-limited continuous cultures of a Bacillus strain was studied, under extreme nutrient supply conditions: glucose excess, limitation and starvation. The addition of n-dodecane to the aqueous phase of a mechanically agitated and aerated fermentation increased the k L a by up to 35%. The n-dodecane additions to Bacillus licheniformis cells during starvation (oxygen limitation with concomitant glucose starvation) caused a severe detrimental progressive change in cell physiological state with respect to cytoplasmic membrane polarisation and permeability which was mitigated against by alleviating either the oxygen limitation (by increasing the mean energy dissipation rate or by the addition of n-dodecane as an oxygen vector) or by alleviating the carbon limitation (by resuming the carbon feed or by the addition of a glucose pulse). Further that during periods of excess glucose (glucose pulse) a much higher k L a was required to prevent the onset of anaerobic mixed acid fermentation than could be provided by the addition of n-dodecane alone. n-Dodecane can be used to increase the k L a when added in sufficient quantities to the aqueous phase of a mechanically agitated and aerated bioreactor but the magnitude of this increase is process and vessel geometry specific.

Simulation of sow herd dynamics with emphasis on performance and distribution of periodic task events

SUMMARYCurrently, the diversity of sow herd management strategies has been described but there are no tools that explore how it promotes sow herd performance nor how it or performance are linked to work organization problems. The goal of the current study was to build a herd dynamic, stochastic object-oriented model capable of representing the herd dynamics and performance, and to predict the number of events workers will have to deal with. Each sow is individually represented in the model and the model works as a discrete event simulator with a predefined time step of 1 h. At each time step of simulation, the model searches for an event to be processed. An event may imply change of sow physiological state (e.g. oestrus, farrowing and insemination) and/or request an action from a worker (e.g. oestrous detection and farrowing supervision). This action may result in the planning of a new event (e.g. farrowing after mating) and/or modification of sow state (e.g. from oestrus to pregnant). The occurrences of some technical activities such as weaning are defined in time and frequency according to the management strategy of the farmer. The model is stochastic as sow biology is represented by several normal univariate distributions according to parity or by a threshold (fertility, abortion and mortality rates). When sows return into oestrus after mating they can be moved to another batch or culled depending on batch management strategy and culling policy. Outputs of this model focus on productivity of sows and distribution of tasks over the week. Definitions of the duration of simulation and number of replications to obtain the steady state and the variability of results are presented. The model is able to simulate several batch farrowing systems (BFS) and results of 1-, 3- and 4-week BFS are presented. Several simulations with modified management (no oestrous detection during the weekend and change of the weaning day) or with modified sow biology (increased variability of the weaning-to-oestrus interval and lower fertility rate) are performed. Results indicate that these modifications have specific consequences on performance and task distribution according to the BFS. The model provides useful information concerning the effects of herd management strategies on productivity and distribution of events over time and their sensitivity to biological criteria.

Homeokinetics/Homeodynamics: A Physical Heuristic for Life and Complexity

This essay addresses the puzzlement, the missing piece, sensed when attempts are made to build a bridge from the synchronic, informational genotype to the diachronic, dynamic phenotype—a regular mapping that seems to be extraphysical. There is no formal, dynamic foundation for the bridge. Albert Einstein, Max Delbrück, and Erwin Schrödinger all expressed acute awareness of limitations of contemporary physics when considering biology because physics addresses much simpler sysems. As a proposed remedy, a new physical heuristic, homeokinetics, developed by Arthur Iberall and Harry Soodak (and later recast for biology by me as homeodynamics) is introduced here as a foundation for comprehending energy flows and transformations in complex systems, including those in metabolic networks of living systems. Their individual dynamic stability is flexible and marginal—it must allow for adaptations and changes in physiological and behavioral states to occur in an orderly fashion as external circumstances change. At the population level, stability must allow for evolvability of chemical networks that have energized terrestrial living systems for about 3.9 billion years. Homeokinetics/homeodynamics emphasizes that persistent, marginally stable metabolic networks, as open thermodynamic systems, necessarily organize energy processing as cyclic, physical action modes. Conceptually, that organization is under 2 kinds of biological time pressure—time as a cycle that daily closes the thermodynamic books and time as an arrow orthogonally pressing the cyles into the future, creating joint time as a helix. In most animals, after maturity, the helix is additionally shaped into a tapered ellipsoid by a senesence process that gains influence as dynamic degrees of freedom are frozen out by the constructions of development.

Murine CD5+, CD8+ Normal Fetal Liver Cells Enhance an Immune Response: Benzo(α) Pyrene-Exposed CD5+ Fetal Liver Cells are Inhibitors

The effects of 150 ug benzo(α)pyrene/gm body weight given intraperitoneally to the pregnant mouse at mid-gestation leads to long-lasting (> 18 months post-birth) immune deficiency in the progeny. Although the progeny are immunodeficient their T cell subsets induced marked enhancement and/or inhibition of cell proliferation in an immune response. Earlier we saw a striking increase (up to 7-fold) in CD8+ cells in the 18 day gestation liver of benzo(α)pyrene-exposed fetuses. We hypothesized that immune deficiency in carcinogen-exposed progeny could be attributed to an increase in classical CD8+ suppressor T-cells. Surprisingly, however, we found that CD8+ and CD5+ (Lyt 1+) cells of normal fetal liver enhance cell proliferation in an immune response. However, liver CD5+ cells from benzo(α)pyrene-exposed fetuses led to a dramatic reduction of the enhancing effect. Thus, as a novel finding, it appears that the profile of CD5+ cells, under the ontogenic influence of benzo(α)pyrene, transforms from cells that normally augment cell proliferation in an immune response to cells that are inhibitors. On the other hand the functional status of CD8+ cells is not affected. This change in physiological status of CD5+ cells may have important implications on T and B cell interactions, and the role of CD5+cells in T cell receptor signaling.

Semiquantitative RT-PCR measurement of gene expression in rat tissues including a correction for varying cell size and number

BackgroundCurrent methodology of gene expression analysis limits the possibilities of comparison between cells/tissues of organs in which cell size and/or number changes as a consequence of the study (e.g. starvation). A method relating the abundance of specific mRNA copies per cell may allow direct comparison or different organs and/or changing physiological conditions.MethodsWith a number of selected genes, we analysed the relationship of the number of bases and the fluorescence recorded at a present level using cDNA standards. A lineal relationship was found between the final number of bases and the length of the transcript. The constants of this equation and those of the relationship between fluorescence and number of bases in cDNA were determined and a general equation linking the length of the transcript and the initial number of copies of mRNA was deduced for a given pre-established fluorescence setting. This allowed the calculation of the concentration of the corresponding mRNAs per g of tissue. The inclusion of tissue RNA and the DNA content per cell, allowed the calculation of the mRNA copies per cell.ResultsThe application of this procedure to six genes: Arbp, cyclophilin, ChREBP, T4 deiodinase 2, acetyl-CoA carboxylase 1 and IRS-1, in liver and retroperitoneal adipose tissue of food-restricted rats allowed precise measures of their changes irrespective of the shrinking of the tissue, the loss of cells or changes in cell size, factors that deeply complicate the comparison between changing tissue conditions. The percentage results obtained with the present methods were essentially the same obtained with the delta-delta procedure and with individual cDNA standard curve quantitative RT-PCR estimation.ConclusionThe method presented allows the comparison (i.e. as copies of mRNA per cell) between different genes and tissues, establishing the degree of abundance of the different molecular species tested.

Mechanisms of physiological regulation of RNA synthesis in bacteria: new discoveries breaking old schemes

Although in bacterial cells all genes are transcribed by RNA polymerase, there are 2 additional enzymes capable of catalyzing RNA synthesis: poly(A) polymerase I, which adds poly(A) residues to transcripts, and primase, which produces primers for DNA replication. Mechanisms of actions of these 3 RNA-synthesizing enzymes were investigated for many years, and schemes of their regulations have been proposed and generally accepted. Nevertheless, recent discoveries indicated that apart from well-understood mechanisms, there are additional regulatory processes, beyond the established schemes, which allow bacterial cells to respond to changing environmental and physiological conditions. These newly discovered mechanisms, which are discussed in this review, include: (i) specific regulation of gene expression by RNA polyadenylation, (ii) control of DNA replication by interactions of the starvation alarmones, guanosine pentaphosphate and guanosine tetraphosphate, (p)ppGpp, with DnaG primase, (iii) a role for the DksA protein in ppGpp-mediated regulation of transcription, (iv) allosteric modulation of the RNA polymerase catalytic reaction by specific inhibitors of transcription, rifamycins, (v) stimulation of transcription initiation by proteins binding downstream of the promoter sequences, and (vi) promoter-dependent control of transcription antitermination efficiency.

Optimal annual routines: behaviour in the context of physiology and ecology.

Organisms in a seasonal environment often schedule activities in a regular way over the year. If we assume that such annual routines have been shaped by natural selection then life-history theory should provide a basis for explaining them. We argue that many life-history trade-offs are mediated by underlying physiological variables that act on various time scales. The dynamics of these variables often preclude considering one period of the year in isolation. In order to capture the essence of annual routines, and many life-history traits, a detailed model of changes in physiological state over the annual cycle is required. We outline a modelling approach based on suitable physiological and ecological state variables that can capture this underlying biology, and describe how models based on this approach can be used to generate a range of insights and predictions.

Interplay Between Network Structures, Regulatory Modes and Sensing Mechanisms of Transcription Factors in the Transcriptional Regulatory Network of E. coli

Though the bacterial transcription regulation apparatus is distinct in terms of several structural and functional features from its eukaryotic counterpart, the gross structure of the transcription regulatory network (TRN) is believed to be similar in both superkingdoms. Here, we explore the fine structure of the bacterial TRN and the underlying “co-regulatory network” (CRN) to show that despite the superficial similarities to the TRN of the eukaryotic model organism yeast, the bacterial networks display entirely different organizational principles. In particular unlike in eukaryotes, hubs of the bacterial networks are both global regulators and integrators of diverse disparate transcriptional responses. These and other organizational differences might correlate with the fundamental differences in gene and promoter organization in the two superkingdoms, especially the presence of operons and regulons in bacteria. Further we explored to find the interplay, if any, between network structures, mode of regulatory interactions and signal sensing of transcription factors (TFs) in shaping up the bacterial transcriptional regulatory responses. For this purpose, we first classified TFs according to their regulatory mode (activator, repressor or dual regulator) and sensory mechanism (one-component systems responding to internal or external signals, TFs from two-component systems and chromosomal structure modifying TFs) in the bacterial model organism Escherichia coli and then we studied the overall evolutionary optimization of network structures. The incorporation of TFs in different hierarchical elements of the TRN appears to involve on a multi-dimensional selection process depending on regulatory and sensory modes of TFs in motifs, co-regulatory associations between TFs of different functional classes and transcript half-lives. As a result it appears to have generated circuits that allow intricately regulated physiological state changes. We identified the biological significance of most of these optimizations, which can be further used as the basis to explore similar controls in other bacteria. We also show that, though on the larger evolutionary scale, unrelated TFs have evolved to become hubs, within lineages like γ-proteobacteria there is strong tendency to retain hubs, as well as certain higher-order network modules that have emerged through lineage specific paralog duplications.

New insights into the electrophysiology of brainstem circuits controlling blood pressure

The brainstem contains the necessary circuitry for the maintenance and regulation of arterial blood pressure. It has become increasingly clear in the past few years that the characteristics of the neurons that constitute these circuits are not static, but can be altered in the face of chronic changes in physiological state. Alterations in voltage-gated and ligand-gated ion channels have been reported in neurons located within the nucleus of the solitary tract and the nucleus ambiguus in response to hypertension and exposures to hypoxia and environmental pollutants (eg, ozone and cigarette smoke). A discussion of these neuronal adaptations, the mechanisms that might initiate and sustain the adaptations, and their potential significance is the focus of this brief review.

Comparison of the non linear energy operator and the Hilbert transform in the estimation of the instantaneous amplitude and frequency

The instantaneous amplitude (ai) and frequency (fi) parameters of a biomedical signal can be useful for identification of signal physiological states or state changes. In this article the features ai and fi of simulated and experimental (real EEG and ECG) signals, are estimated using three methods: one based on the Hilbert Transform (HT), a modified version of this that improves the fi estimation in experimental signals (HTM), and the energy separation algorithm (DESA1), based on Teager’s energy operator (TEO). The algorithm comparison is made using the average relative error obtained in the signals’ demodulation process, their noise sensitivity, and computational efficiency. The obtained results showed that the HTM method produces the least fi estimation errors in noisy signals, and depending on the kind of signal considered, DESA1 and HTM methods produce the least ai estimation errors.

The fate of nitrogen fixed by diazotrophs in the ocean

Abstract. While we now know that N2 fixation is a significant source of new nitrogen (N) in the marine environment, little is known about the fate of this N (and associated C), despite the importance of diazotrophs to global carbon and nutrient cycles. Specifically, does N fixed during N2 fixation fuel autotrophic or heterotrophic growth and thus facilitate carbon (C) export from the euphotic zone, or does it contribute primarily to bacterial productivity and respiration in the euphotic zone? For Trichodesmium, the diazotroph we know the most about, the transfer of recently fixed N2 (and C) appears to be primarily through dissolved pools. The release of N varies among and within populations and as a result of the changing physiological state of cells and populations. The net result of trophic transfers appears to depend on the co-occurring organisms and the complexity of the colonizing community. In order to understand the impact of diazotrophy on carbon flow and export in marine systems, we need a better understanding of the trophic flow of elements in Trichodesmium-dominated communities and other diazotrophic communities under various defined physiological states. Nitrogen and carbon fixation rates themselves vary by orders of magnitude within and among studies of Trichodesmium, highlighting the difficulty in extrapolating global rates of N2 fixation from direct measurements. Because the stoichiometry of N2 and C fixation does not appear to be in balance with that of particles, and the relationship between C and N2 fixation rates is also variable, it is equally difficult to derive global rates of one from the other. This paper seeks to synthesize what is known about the fate of diazotrophic production in the environment. A better understanding of the physiology and physiological ecology of Trichodesmium and other marine diazotrophs is necessary to quantify and predict the effects of increased or decreased diazotrophy in the context of the carbon cycle and global change.

Bio‐cartogramography a novel presentation of physiological data

Anatomical drawings are often used to present organ-specific physiological data, such as tissue water content or metabolic rate. While effectively representing organ size and relative position in the body, inadequate weighting is given to the magnitude of dynamic physiological processes or static measures. We have developed a novel presentation for such physiological data through adaptation of geographic information systems methodology (GIS). GIS-derived cartograms are maps which rescale land areas based on magnitude of the attribute of interest (AoI), such as population or cancer prevalence. Newer GIS algorithms facilitate rescaling, creating distorted maps with constituent areas scaled by AoI magnitude, while maintaining recognizable shapes and topology. Cartograms could be used in presentation of biomedical information if applied to anatomic and physiological rather than geographic models. Instead of maps as starting points, an organism, the rat, has been used. Organ water-content cartograms are presented with rescaling of organ areas such that wet organs appear enlarged and dry organs smaller. Visual enhancement of AoI weighting improves recognition of physiological status changes occurring when AoI is altered by disease or trauma. Redistribution of organ water content post-hemorrhage is presented in cartograms generated with Dorling-style as well as newer diffusion based algorithms.

Stochastic model for analysis of longitudinal data on aging and mortality

Aging-related changes in a human organism follow dynamic regularities, which contribute to the observed age patterns of incidence and mortality curves. An organism’s ‘optimal’ (normal) physiological state changes with age, affecting the values of risks of disease and death. The resistance to stresses, as well as adaptive capacity, declines with age. An exposure to improper environment results in persisting deviation of individuals’ physiological (and biological) indices from their normal state (due to allostatic adaptation), which, in turn, increases chances of disease and death. Despite numerous studies investigating these effects, there is no conceptual framework, which would allow for putting all these findings together, and analyze longitudinal data taking all these dynamic connections into account. In this paper we suggest such a framework, using a new version of stochastic process model of aging and mortality. Using this model, we elaborated a statistical method for analyses of longitudinal data on aging, health and longevity and tested it using different simulated data sets. The results show that the model may characterize complicated interplay among different components of aging-related changes in humans and that the model parameters are identifiable from the data.

Physiological constraints on contest behaviour

Summary Contests may involve injurious fighting, other types of direct physical aggression and communication. They occur over ownership access to mates and other resources that may increase an individual's attractiveness and its chance of survival. Traits that enhance resource holding potential may be the result of sexual selection, natural selection or a combination of both. Agonistic behaviours are expected to be demanding to perform and costly in terms of changes in physiological state. The ability to meet the physiological costs may determine contest outcomes and constrain the intensity of agonistic activities. The energetic costs have been investigated in a broad range of taxa using a variety of techniques. They include the mobilization of energy reserves, but a key cost in several taxa appears to be limited anaerobic capacity and subsequent accumulation of lactic acid. Androgens, stress hormones and neurohormones have also been shown to constrain fighting behaviour. However, due to key differences in the endocrine systems of vertebrates and invertebrates, the effects of hormones are far less consistent across taxa than in the case of metabolites. Physiological constraints on fighting may vary according to their importance relative to circumstantial costs, the time‐scale over which they exert their effects, their effects on different roles and their causal links with behaviour. Incorporating these factors into theoretical studies of contest behaviour may give further insights of how the costs of fighting influence agonistic behaviour.

Escherichia coli pfs Transcription: Regulation and Proposed Roles in Autoinducer-2 Synthesis and Purine Excretion

Pfs expression is required for several metabolic pathways and limits the production of autoinducer-2, a molecule proposed to play a central role in interspecies quorum sensing. The present study reveals physiological conditions and promoter DNA elements that regulate Escherichia coli pfs transcription. Pfs transcription is shown to rely on both sigma 70 and sigma 38 (rpoS), and the latter is subject to induction that increases pfs expression. Transcription is maximal as the cells approach stationary phase, and this level can be increased by salt stress through induction of sigma 38-dependent expression. The pfs promoter is shown to contain both positive and negative elements, which can be used by both forms of RNA polymerase. The negative element is contained within the overlapping dgt promoter, which is involved in purine metabolism. Consideration of the physiological roles of sigma 38 and dgt leads to a model for how autoinducer production is controlled under changing physiological conditions.

Activation of Glucosidase via Stress-Induced Polymerization Rapidly Increases Active Pools of Abscisic Acid

Abscisic acid (ABA) is a phytohormone critical for plant growth, development, and adaptation to various stress conditions. Plants have to adjust ABA levels constantly to respond to changing physiological and environmental conditions. To date, the mechanisms for fine-tuning ABA levels remain elusive. Here we report that AtBG1, a beta-glucosidase, hydrolyzes glucose-conjugated, biologically inactive ABA to produce active ABA. Loss of AtBG1 causes defective stomatal movement, early germination, abiotic stress-sensitive phenotypes, and lower ABA levels, whereas plants with ectopic AtBG1 accumulate higher ABA levels and display enhanced tolerance to abiotic stress. Dehydration rapidly induces polymerization of AtBG1, resulting in a 4-fold increase in enzymatic activity. Furthermore, diurnal increases in ABA levels are attributable to polymerization-mediated AtBG1 activation. We propose that the activation of inactive ABA pools by polymerized AtBG1 is a mechanism by which plants rapidly adjust ABA levels and respond to changing environmental cues.

A Quick Release Mechanism for Abscisic Acid

The hormone abscisic acid regulates development and survival of plants in response to environmental stresses. now demonstrate that in response to stress, abscisic acid can be made available via polymerization of a beta-glucosidase enzyme. This enzyme is reported to hydrolyze glucose-conjugated abscisic acid, thus increasing active abscisic acid concentrations.

Seasonal changes in chronic social interactions and physiological states in female rat-like hamsters ( Tscheskia triton)

We examined the behavioral characteristics and physiological states related to solitary lifestyle and dominant–subordinate relationships in female rat-like hamsters ( Tscheskia triton), formerly known as Cricetulus triton. Wild adult hamsters were captured and caged singly in the laboratory during the non-breeding and breeding seasons. The experimental hamsters were subjected to 5 min staged dyadic encounters every day for 28 consecutive days by pairing two unfamiliar and weight matched females in a neutral arena. Aggressive behavior, defense and flank marking were quantified everyday within the first week and once each week during the last 3 weeks. Animals were then autopsied and their physiological and reproductive state assessed. Our results suggested that dominant–subordinate relationships could be established especially in non-breeding conditions, where the dominant displayed higher aggression and flank marking, and lower defense than its opponent. The breeding females followed this pattern except there was no difference in aggressive behavior, between the partners. The repeated encounters did not appear to reduce aggression or lead to amiable behavior or bonding. At the end of the experiment breeding females exhibited higher levels of serum estradiol, progesterone and corticosterone than non-breeding females. Both dominant and subordinate females in non-breeding condition had atrophied ovaries and uteri, whereas both dominant and subordinate females in breeding condition had hypertrophied ovaries and uteri. Non-breeding females possessed heavier and thicker flank glands than breeding females did. Dominant females displayed longer or thicker flank glands than subordinate did. Thus, our data suggest that the behavioral traits observed in our experiment support the solitary lifestyle of adult female rat-like hamsters and physiological state show some differences between social ranks or in both seasons.

A comparison of high cell density fed‐batch fermentations involving both induced and non‐induced recombinant Escherichia coli under well‐mixed small‐scale and simulated poorly mixed large‐scale conditions

In this work, multi-parameter flow cytometric techniques, coupled with dual colour fluorescent staining, have been used to study the metabolic consequences of inclusion body formation in high cell density fed-batch cultures of the recombinant E. coli strain MSD3735, producing the IPTG inducible model mammalian protein, AP50. Further, we report on the development of the scale-down, two compartment (STR + PFR) experimental simulation model to study, for the first time, the effect of a changing microenvironment with respect to three of the major spatial heterogeneities that may be associated with large-scale bioprocessing (pH, glucose and dissolved oxygen concentration) on a recombinant bacterial system. Using various time points for induction and various scale-down configurations, it has been shown that inclusion body formation is followed immediately by a detrimental progressive change in individual cell physiological state with respect to both cytoplasmic membrane polarisation and permeability, resulting in a lower final biomass yield. However, the extent of this change was found to be dependent on whether the AP50 protein was induced or not, on the time of induction and on which combination of heterogeneities was being simulated. From this and previous work, it is clear that the scale-down two-compartment model can be used to study the impact of genetically modifying an organism to produce inclusion bodies and any range and combination of potential heterogeneities known to exist at the large scale.