A new model of depression induced by psychogenenic stress

A new depression model has been obtained, based on use of stressors of the psychogenic nature. The laboratory rats in a special stress-camera turned out to be unable to induce the bilateral reaction of active avoidance, with subsequently led to formation of depression in the animals. Analysis of the tests sensitive to depression--a forceful swimming and a hanging by tail as well as of dynamics of the animals' body mass and of the behavior on the whole confirms development of their depression. This model has turned out to be sensitive to a selective inhibitor of the serotonin reuptake--fluoxetine; this also indicates our obtained model to be a model of depression.     

Maternal oxytocin response during mother-infant interaction: associations with adult temperament

Oxytocin is a neuropeptide associated with social affiliation and maternal caregiving. However, its effects appear to be moderated by various contextual factors and stable individual characteristics. The purpose of this study was to investigate the relationship of self-reported state and trait measures (such as temperament, mood and affect) with peripheral oxytocin response in mothers. Fifty-five first-time mothers participated in a semi-structured procedure, during which time repeated peripheral oxytocin levels were measured before, during and after an episode of mother-infant interaction. The maternal oxytocin response was then calculated, based on the difference in oxytocin concentration between initial baseline and interaction phase. Mothers also completed state measures of positive and negative affect and depression, and trait measures of temperament, personality disturbance and depression across time. Regression analyses determined which factors were independently associated with maternal oxytocin response. The trait measure of adult temperament emerged as a significant predictor of oxytocin response. Two out of four Adult Temperament Questionnaire factor scales were independently associated with oxytocin response: Effortful Control was negatively associated, whereas Orienting Sensitivity was positively associated. No state measure significantly predicted oxytocin response. The results indicate that mothers who show an increased oxytocin response when interacting with their infants are more sensitive of moods, emotions and physical sensations; and less compulsive, schedule driven and task oriented. These findings link differences in individual temperament in new mothers with the peripheral oxytocin response, which may have implications in the pharmacologic treatment of disorders such as maternal neglect, post-partum depression and maternal addiction. This article is part of a Special Issue entitled Oxytocin, Vasopressin, and Social Behavior.     

Majority Rules with Random Tie-Breaking in Boolean Gene Regulatory Networks

We consider threshold Boolean gene regulatory networks, where the update function of each gene is described as a majority rule evaluated among the regulators of that gene: it is turned ON when the sum of its regulator contributions is positive (activators contribute positively whereas repressors contribute negatively) and turned OFF when this sum is negative. In case of a tie (when contributions cancel each other out), it is often assumed that the gene keeps it current state. This framework has been successfully used to model cell cycle control in yeast. Moreover, several studies consider stochastic extensions to assess the robustness of such a model.Here, we introduce a novel, natural stochastic extension of the majority rule. It consists in randomly choosing the next value of a gene only in case of a tie. Hence, the resulting model includes deterministic and probabilistic updates. We present variants of the majority rule, including alternate treatments of the tie situation. Impact of these variants on the corresponding dynamical behaviours is discussed. After a thorough study of a class of two-node networks, we illustrate the interest of our stochastic extension using a published cell cycle model. In particular, we demonstrate that steady state analysis can be rigorously performed and can lead to effective predictions; these relate for example to the identification of interactions whose addition would ensure that a specific state is absorbing.     

The release of monovalent counterions by addition of divalent counterions in coulombic interaction system

The additivity rule of counterion activity or osmotic pressure in rodlike polyelectrolyte solutions has been discussed on the basis of the Fokker-Planck and Poisson equations in relation to the fluctuation of counterion distribution. This new theory has concluded that the additivity rule of counterion activity is less applicable than that of osmotic pressure due to the electric expansion force acting on the free-volume surface resulting from the fluctuation of counterion distribution. The theory has introduced an approximate relation between the counterion activities in the mixture solution of divalent and monovalent counterions, such that Deltaa+ = DeltaC++ - Deltaa++, in which Deltaa+ represents the increase of activity of monovalent counter-ions resulting from the addition of divalent counterionsDeltaC++, (in molar) to the solution, and Deltaa++ means the increase of the divalent counterion activity (in molar) in this process. This relation has been experimentally examined for Na-PSS solutions in the process of Cu2+ ion addition by the use of Na+ and Cu2+ sensitive electrodes, and it has been turned out that the relation is established in the low charge state of polyion.     

Hearing impairment and mental state in the elderly living at home.

Altogether 153 (60%) out of a sample of 253 people aged 70 years and over living in their own homes were found to have impaired hearing when tested by pure-tone audiometry. This is almost twice the prevalence found in all other studies, in which deafness was assessed clinically or by self-reporting. The prevalence of deafness increased with age. Evidence of organic brain syndrome (dementia), as determined by questionnaire, was present in 39 (16%) out of 245 respondents, and of depression in 82 (35%). Dementia and depression were both age related. An apparent association between deafness and dementia was shown to be due to age alone. A significant relation between deafness and depression was independent of age and socioeconomic state. The use of audiometric techniques of assessment established that an association exists between deafness and depression that is not simply a function of differential reporting reflecting the emotional state of the respondent.     

Short-term depression and transient memory in sensory cortex

Persistent neuronal activity is usually studied in the context of short-term memory localized in central cortical areas. Recent studies show that early sensory areas also can have persistent representations of stimuli which emerge quickly (over tens of milliseconds) and decay slowly (over seconds). Traditional positive feedback models cannot explain sensory persistence for at least two reasons: (i) They show attractor dynamics, with transient perturbations resulting in a quasi-permanent change of system state, whereas sensory systems return to the original state after a transient. (ii) As we show, those positive feedback models which decay to baseline lose their persistence when their recurrent connections are subject to short-term depression, a common property of excitatory connections in early sensory areas. Dual time constant network behavior has also been implemented by nonlinear afferents producing a large transient input followed by much smaller steady state input. We show that such networks require unphysiologically large onset transients to produce the rise and decay observed in sensory areas. Our study explores how memory and persistence can be implemented in another model class, derivative feedback networks. We show that these networks can operate with two vastly different time courses, changing their state quickly when new information is coming in but retaining it for a long time, and that these capabilities are robust to short-term depression. Specifically, derivative feedback networks with short-term depression that acts differentially on positive and negative feedback projections are capable of dynamically changing their time constant, thus allowing fast onset and slow decay of responses without requiring unrealistically large input transients.     

A Detailed Modular Analysis of Heat-Shock Protein Dynamics under Acute and Chronic Stress and Its Implication in Anxiety Disorders

Physiological and psychological stresses cause anxiety disorders such as depression and post-traumatic stress disorder (PTSD) and induce drastic changes at a molecular level in the brain. To counteract this stress, the heat-shock protein (HSP) network plays a vital role in restoring the homeostasis of the system. To study the stress-induced dynamics of heat-shock network, we analyzed three modules of the HSP90 network-namely trimerization reactions, phosphorylation-dephosphorylation reactions, and the conversion of HSP90 from an open to a closed conformation-and constructed a corresponding nonlinear differential equation model based on mass action kinetics laws. The kinetic parameters of the model were obtained through global optimization, and sensitivity analyses revealed that the most sensitive parameters are the kinase and phosphatase that drive the phosphorylation-dephosphorylation reactions. Bifurcation analysis carried out with the estimated kinetic parameters of the model with stress as bifurcation parameter revealed the occurrence of "mushroom", a type of complex dynamics in which S-shaped and Z-shaped hysteretic bistable forms are present together. We mapped the molecular events responsible for generating the mushroom dynamics under stress and interpreted the occurrence of the S-shaped hysteresis to a normal level of stress, and the Z-shaped hysteresis to the HSP90 variations under acute and chronic stress in the fear conditioned system, and further, we hypothesized that this can be extended to stress-related disorders such as depression and PTSD in humans. Finally, we studied the effect of parameter variations on the mushroom dynamics to get insight about the role of phosphorylation-dephosphorylation parameters in HSP90 network in bringing about complex dynamics such as isolas, where the stable steady states in a bistable system are isolated and separated from each other and not connected by an unstable steady state.     

Survival of Oocysts of Eimeria alabamensis on Pastures under Different Climatic Conditions in Sweden

The extent to which oocysts of the coccidian parasite Eimeria alabamensis can survive the winter and cause clinical coccidiosis in different parts of Sweden was investigated. Fecal samples were collected between May and July 1993 from calves on 59 farms where calves had grazed the same pasture for at least 5 consecutive years. The farms were situated in 9 regions of Sweden with different climatic conditions in the winter. On each farm, 5 samples of feces were collected from the floor of the calf-house before the calves were turned out in the spring, and again from the pasture on days 4 or 5, 8 or 9 and 10 or 11 after they were turned out. Overwintering of oocysts of E. alabamensis was considered to have occurred if an increase in the excretion rate of oocysts of this species could be demonstrated 8 to 11 days after calves had been turned out to pastures that had not been grazed since the previous autumn. Oocysts were shown to have overwintered on 27 farms, representing all 9 regions. Samples from 20 (34%) of the farms representing all the climatic regions contained more than 850000 oocysts per g of feces. This was comparable with the numbers found in animals with clinical coccidiosis due to E. alabamensis. Delaying turnout until the beginning of July did not affect the infection rate of the calves. However, calves which were turned out to pastures that had been grazed by older cattle or horses, either earlier in the spring or in previous years, excreted significantly fewer oocysts than calves which were turned out to pastures that had been grazed only by calves. A questionnaire answered by 321 dairy farmers revealed that of the 298 farmers who turned their first-season grazing cattle out to traditional pastures, 179 (60%) had used the same pasture for at least 5 years. These 179 farmers had experienced a significantly higher incidence of diarrhoea in their calves during the first 2 weeks at pasture than those farmers who had used different pastures.     

Modelling of different enzyme productions by solid-state fermentation on several agro-industrial residues

A simple kinetic model, with only three fitting parameters, for several enzyme productions in Petri dishes by solid-state fermentation is proposed in this paper, which may be a valuable tool for simulation of this type of processes. Basically, the model is able to predict temporal fungal enzyme production by solid-state fermentation on complex substrates, maximum enzyme activity expected and time at which these maxima are reached. In this work, several fermentations in solid state were performed in Petri dishes, using four filamentous fungi grown on different agro-industrial residues, measuring xylanase, exo-polygalacturonase, cellulose and laccase activities over time. Regression coefficients after fitting experimental data to the proposed model turned out to be quite high in all cases. In fact, these results are very interesting considering, on the one hand, the simplicity of the model and, on the other hand, that enzyme activities correspond to different enzymes, produced by different fungi on different substrates.     

A model for the dynamics of bipolar disorders

Bipolar disorders are characterized by recurrent, alternating episodes of mania and depression. To examine the dynamical bases of this cyclical illness we consider a minimal model for bipolar disorders based on the observation that the two poles of the disease are mutually exclusive. We assume that the propensities to mania and depression, which are correlated with the activity of two putative neural circuits that promote, respectively, the manic or the depressive state, inhibit each other. When mutual inhibition is sufficiently strong, the model predicts bistability: the bipolar system is then either in a depressive or in a manic state and can display abrupt switches between these stable states. We consider two simple mechanisms which, when added to mutual inhibition, allow the model to pass from bistability to oscillations. Self-sustained oscillations provide a mechanism for the spontaneous, recurrent switching between mania and depression. The model can generate oscillations with a variety of waveforms, including simple periodic oscillations with comparable or unequal durations of the manic and depressive episodes, or small-amplitude oscillations around one of the two states preceding large-amplitude periodic changes in the propensities to mania or depression. The model provides a theoretical framework that covers the bipolar spectrum, i.e., cycling between the two poles of the disease, or evolution to either mania or depression or to an intermediate state without alternating between the two poles of the disease. The model accounts for the clinical observation that antidepressants can trigger the transition to mania or increase the frequency of bipolar cycling.     

菌紫质D96N样品的光暗适应型及其转化机制

通过对菌紫质D96N基因突变形成的薄膜样品在光照下动态光谱的测定和分析,研究了此样品的光适应型、暗适应型特性及其之间的转化机制。实验证实,样品受光照激发后很快从暗适应型（D态）光适应型（B态）进入光循环,经过一系列的光化学中间体到边较稳定的M态。M态经过约1小时热驰豫完全回到光适应型B态,B态再经过24小时缓慢热驰豫完全回到暗适应型D态。B态受光则进入光循环,不受光则转化为D态,从而认为B态是菌紫质光循环路径中一个重要的分支节点。据此,提出了该样品在光照下B,D和M态之间转化的模型。     

Sensitive commercial NASBA assay for the detection of respiratory syncytial virus in clinical specimen

The aim of the study was to evaluate the usability of three diagnostic procedures for the detection of respiratory syncytial virus in clinical samples. Therefore, the FDA cleared CE marked NOW(R) RSV ELISA, the NucliSENS EasyQ RSV A+B NASBA, and a literature based inhouse RT-PCR protocol were compared for their relative sensitivities. Thereby, NASBA turned out to be the most sensitive method with a total number of 80 RSV positive samples out of a cohort of 251 nasopharyngeal washings from patients suffering from clinical symptoms, followed by the inhouse RT-PCR (62/251) and ELISA (52/251). Thus, NASBA may serve as a rapid and highly sensitive alternative for RSV diagnostics.     

Rumor Diffusion and Convergence during the 3.11 Earthquake: A Twitter Case Study

We focus on Internet rumors and present an empirical analysis and simulation results of their diffusion and convergence during emergencies. In particular, we study one rumor that appeared in the immediate aftermath of the Great East Japan Earthquake on March 11, 2011, which later turned out to be misinformation. By investigating whole Japanese tweets that were sent one week after the quake, we show that one correction tweet, which originated from a city hall account, diffused enormously. We also demonstrate a stochastic agent-based model, which is inspired by contagion model of epidemics SIR, can reproduce observed rumor dynamics. Our model can estimate the rumor infection rate as well as the number of people who still believe in the rumor that cannot be observed directly. For applications, rumor diffusion sizes can be estimated in various scenarios by combining our model with the real data.     

Adult Pacific Oyster (Crassostrea gigas) May Have Light Sensitivity

Light-sensitivity is an important aspect of mollusk survival as it plays a vital role in reproduction and predator avoidance. In the Pacific oyster Crassostrea gigas light sensitivity has been demonstrated in the larval stage but has not yet been conclusively demonstrated in adult oysters. In this paper we describe an experiment which was undertaken to determine if adult Pacific oysters were sensitive to light. One LED flashlight was used to shine light onto adult oysters while they were filtering seawater through their shell openings. We found that the degree of opening increased gradually during the light period but rapidly decreased when the flashlight was turned off in the treated group but not in the control group. These results suggest that adult Pacific oyster may be sensitive to light.     

Surface alterations in transformed epithelial and fibroblastic cells in culture: A disturbance of membrane degradation versus biosynthesis?

Fibroblasts which were transformed with oncogenic DNA or RNA viruses as well as by chemicals or spontaneously have, with very few exceptions, been shown to possess increased agglutinabilities with various plant agglutinins. This surface membrane alteration is now shown to hold true also for transformed epithelial cells and for tumors of epithelial origin as monitored by wheat germ agglutinin, Concanavalin A, phytohemagglutinin, Ricinus communis and Great Northern bean (GNB) agglutinin. An agglutinin from lentils did the opposite. It permitted the agglutination of normal liver cells but not that of hepatoma cells which led to the suggestion that some membrane glycoproteins or glycolipids may possibly be turned inside out while others are turned outside in (during the transformation process. Inhibition of protein synthesis in normal cells brought about the agglutinable membrane state in non-growing or resting cells but not in actively growing cells. Since this agglutinability could be inhibited by protease inhibitors and since proteolytic enzymes could bring about the agglutinable membrane state in growing normal cells, it was suggested that growing cells have as active a biosynthesis of membrane proteins as do non growing cells but that non-growing cells are actively catabolizing their membranes with proteases, much more so than non growing, stationary cells.     

Multi-step rhodopsin inactivation schemes can account for the size variability of single photon responses in Limulus ventral photoreceptors

Limulus ventral photoreceptors generate highly variable responses to the absorption of single photons. We have obtained data on the size distribution of these responses, derived the distribution predicted from simple transduction cascade models and compared the theory and data. In the simplest of models, the active state of the visual pigment (defined by its ability to activate G protein) is turned off in a single reaction. The output of such a cascade is predicted to be highly variable, largely because of stochastic variation in the number of G proteins activated. The exact distribution predicted is exponential, but we find that an exponential does not adequately account for the data. The data agree much better with the predictions of a cascade model in which the active state of the visual pigment is turned off by a multi-step process.     

A (13)C NMR study on [3-(13)C]-, [1-(13)C]Ala-, or [1-(13)C]Val-labeled transmembrane peptides of bacteriorhodopsin in lipid bilayers: insertion, rigid-body motions, and local conformational fluctuations at ambient temperature

We have recorded (13)C NMR spectra of selectively [3-(13)C]Ala-, [1-(13)C]Ala-, or [1-(13)C]Val-labeled synthetic transmembrane peptides of bacteriorhodopsin (bR) and enzymatically cleaved C-2 fragment in the solid and dimyristoylphosphatidylcholine bilayer. It turned out that these transmembrane peptides either in hexafluoroisopropanol or cast from it take an ordinary alpha-helix (alpha(I)-helix) irrespective of their amino acid sequences with reference to the conformation-dependent (13)C chemical shifts of (Ala)(n) taking the alpha-helix form. These transmembrane peptides are not always static in the lipid bilayer as in the solid state but undergo rigid-body motions with various frequencies as estimated from suppressed peaks either by fast isotropic or large-amplitude motions (>10(8) Hz) or intermediate frequencies (10(5) or 10(3) Hz). Further, (13)C chemical shifts of the [3-(13)C]Ala-labeled peptides in the bilayer were displaced downfield by 0.3-1.1 ppm depending upon amino acid sequence with respect to those in the solid state, which were explained in terms of local conformational fluctuation (10(2) Hz) deviated from the torsion angles (alpha(II)-helix) from those of standard alpha-helix, under anisotropic environment in lipid bilayer, in addition to the above-mentioned rigid-body motions. The carbonyl (13)C peaks, on the other hand, are not sensitively displaced by such local anisotropic fluctuations, because they are more sensitive to the manner of hydrogen-bond interactions. The amino acid sequences of these peptides inserted within the bilayer were not always the same as those of intact bR, causing disposition of the transmembrane alpha-helical segment from that of intact bR. Finally, we confirmed that the (13)C NMR peak positions of the random coil form are located at the boundary between the alpha-helix and a turned structure in loop regions.     

Cell-mediated fas-based lysis of dendritic cells which are apparently resistant to anti-Fas antibody

In this report, the controversy concerning the sensitivity of dendritic cells (DCs) to Fas-dependent induction of apoptosis was examined using murine DCs. Although DCs could not be lysed when exposed to an anti-Fas antibody, Jo2, the observed resistance turned out to reflect their lack of the expression of Fc(gamma)R necessary for crosslinking the antibody, rather than their intrinsic resistance. Thus, at least a fraction of DCs was sensitive to Jo2 in the presence of Fc(gamma)R-expressing by-standers. Consistently, a significant fraction of DCs was sensitive to Fas-dependent lysis mediated by T cells including the antigen-specific killing by CD4+ T cells. Both immature (class II MHClow) and mature (class II MHChigh) DCs were sensitive to the Fas-based induction of apoptosis.     

Quantitative Analysis of Endocytosis with Cytoplasmic pHluorin Chimeras

The pH‐sensitive green fluorescent protein (GFP) variant pHluorin is typically fused to the extracellular domain of transmembrane proteins to monitor endocytosis. Here, we have turned pHluorin inside‐out, and show that cytoplasmic fusions of pHluorin are effective quantitative reporters for endocytosis and multivesicular body (MVB) sorting. In yeast in particular, fusion of GFP and its variants on the extracellular side of transmembrane proteins can result in perturbed trafficking. In contrast, cytoplasmic fusions are well tolerated, allowing for the quantitative assessment of trafficking of virtually any transmembrane protein. Quenching of degradation‐resistant pHluorin in the acidic vacuole permits quantification of extravacuolar cargo proteins at steady‐state levels and is compatible with kinetic analysis of endocytosis in live cells.