Increased responses of the reward circuitry to positive task feedback following acute stress in healthy controls but not in siblings of schizophrenia patients.

Acute stress is known to affect the way we process rewards. For example, during, or directly after stress, activity within key brain areas of the reward circuitry is reduced when a reward is presented. Generally, the effects of stress on the brain are time-dependent, changing neural and cognitive processing in the aftermath of stress to aid recovery. Such a dynamic response to stress is important for resilience on the longer term. However, relatively little is known about reward processing during the recovery phase of stress and whether this is changed in individuals at increased risk for stress-related psychopathology. Healthy male individuals (N = 40) and unaffected siblings of schizophrenia patients (N = 40) were randomized to either an acute stress task (Trier Social Stress Test) or a no-stress task. Neural responses during reward anticipation and reward feedback (monetary gain or no gain) were examined 50 min later using an fMRI monetary incentive delay task. The ventral striatum and orbitofrontal cortex (OFC) were used as predefined hypothesis-driven regions of interest. Neural responses following stress differed between controls and siblings during reward feedback (group × stress interaction OFC p = 0.003, ventral striatum p = 0.031), showing increased ventral striatum and OFC responses following stress in healthy controls only. Exploratory analyses revealed that this effect was most pronounced during hit trials (compared to when a reward was omitted), and independent of monetary value. Stress did not affect subsequent reward processing in siblings of schizophrenia patients. We found no significant differences between controls and siblings in ventral striatum and OFC responses during reward anticipation following stress. This study shows that ventral striatum and OFC responses to positive task feedback are increased in the aftermath of stress in healthy male controls, regardless of monetary value. This indicates a dynamic shift from previously reported reduced responses in the striatum and OFC to reward feedback directly after stress to increased responses to both reward and non-reward feedback during the recovery phase of stress. These increased neural responses following stress were absent in siblings of schizophrenia patients. Together, these findings indicate that stress recovery is affected in this at-risk group, particularly in responses to positive feedback following stress.

Investigating two mobile just-in-time adaptive interventions to foster psychological resilience: research protocol of the DynaM-INT study.

BACKGROUND: Stress-related disorders such as anxiety and depression are highly prevalent and cause a tremendous burden for affected individuals and society. In order to improve prevention strategies, knowledge regarding resilience mechanisms and ways to boost them is highly needed. In the Dynamic Modelling of Resilience - interventional multicenter study (DynaM-INT), we will conduct a large-scale feasibility and preliminary efficacy test for two mobile- and wearable-based just-in-time adaptive interventions (JITAIs), designed to target putative resilience mechanisms. Deep participant phenotyping at baseline serves to identify individual predictors for intervention success in terms of target engagement and stress resilience. METHODS: DynaM-INT aims to recruit N = 250 healthy but vulnerable young adults in the transition phase between adolescence and adulthood (18-27 years) across five research sites (Berlin, Mainz, Nijmegen, Tel Aviv, and Warsaw). Participants are included if they report at least three negative burdensome past life events and show increased levels of internalizing symptoms while not being affected by any major mental disorder. Participants are characterized in a multimodal baseline phase, which includes neuropsychological tests, neuroimaging, bio-samples, sociodemographic and psychological questionnaires, a video-recorded interview, as well as ecological momentary assessments (EMA) and ecological physiological assessments (EPA). Subsequently, participants are randomly assigned to one of two ecological momentary interventions (EMIs), targeting either positive cognitive reappraisal or reward sensitivity. During the following intervention phase, participants' stress responses are tracked using EMA and EPA, and JITAIs are triggered if an individually calibrated stress threshold is crossed. In a three-month-long follow-up phase, parts of the baseline characterization phase are repeated. Throughout the entire study, stressor exposure and mental health are regularly monitored to calculate stressor reactivity as a proxy for outcome resilience. The online monitoring questionnaires and the repetition of the baseline questionnaires also serve to assess target engagement. DISCUSSION: The DynaM-INT study intends to advance the field of resilience research by feasibility-testing two new mechanistically targeted JITAIs that aim at increasing individual stress resilience and identifying predictors for successful intervention response. Determining these predictors is an important step toward future randomized controlled trials to establish the efficacy of these interventions.

Translocation of polymers in a lattice model.

Voltage-driven polymer translocation is studied by means of a stochastic lattice model. The model incorporates voltage drop over the membrane as a bias in the hopping rate through the pore and exhibits the two main ingredients of the translocation process: driven motion through the pore and diffusive supply of chain length towards the pore on the cis-side and the drift away from the pore on the trans-side. The translocation time is either bias limited or diffusion limited. In the bias-limited regime the translocation time is inversely proportional to the voltage drop over the membrane. In the diffusion-limited regime the translocation time is independent of the applied voltage, but it is rather sensitive to the motion rules of the model. We find that the whole regime is well described by a single curve determined by the initial slope and the saturation value. The dependence of these parameters on the length of the chain, the motion rules and the repton statistics are established. Repulsion of reptons as well as the increase of chain length decrease the throughput of the polymer through the pore. As for free polymers, the inclusion of a mechanism for hernia creations/annihilations leads to the cross-over from Rouse-like behaviour to reptation. For the experimentally most relevant case (Rouse dynamics) the bimodal power law dependence of the translocation time on the chain length is found.

Structural modes of a polymer in the repton model.

Using extensive computer simulations, the behavior of the structural modes-more precisely, the eigenmodes of a phantom Rouse polymer-are characterized for a polymer in the three-dimensional repton model and are used to study the polymer dynamics at time scales well before the tube renewal. Although these modes are not the eigenmodes for a polymer in the repton model, we show that numerically the modes maintain a high degree of statistical independence. The correlations in the mode amplitudes decay exponentially with (p∕N)(2)A(t), in which p is the mode number, N is the polymer length, and A(t) is a single function shared by all modes. In time, the quantity A(t) causes an exponential decay for the mode amplitude correlation functions for times <1; a stretched exponential with an exponent 1∕2 between times 1 and τ(R) ∼ N(2), the time-scale for diffusion of tagged reptons along the contour of the polymer; and again an exponential decay for times t > τ(R). Having assumed statistical independence and the validity of a single function A(t) for all modes, we compute the temporal behavior of three structural quantities: the vectorial distance between the positions of the middle monomer and the center-of-mass, the end-to-end vector, and the vector connecting two nearby reptons around the middle of the polymer. Furthermore, we study the mean-squared displacement of the center-of-mass and the middle repton, and their relation with the temporal behavior of the modes.

Dorsal attention network centrality increases during recovery from acute stress exposure.

Stress is a major risk factor for the development of almost all psychiatric disorders. In addition to the acute stress response, an efficient recovery in the aftermath of stress is important for optimal resilience. Increased stress vulnerability across psychiatric disorders may therefore be related to altered trajectories during the recovery phase following stress. Such recovery trajectories can be quantified by changes in functional brain networks. This study therefore evaluated longitudinal functional network changes related to stress in healthy individuals (N = 80), individuals at risk for psychiatric disorders (healthy siblings of schizophrenia patients) (N = 39), and euthymic bipolar I disorder (BD) patients (N = 36). Network changes were evaluated before and at 20 and 90 min after onset of an experimental acute stress task (Trier Social Stress Test) or a control condition. Whole-brain functional networks were analyzed using eigenvector centrality as a proxy for network importance, centrality change over time was related to the acute stress response and recovery for each group. In healthy individuals, centrality of the dorsal attention network (DAN; p = 0.007) changed over time in relation to stress. More specifically, DAN centrality increased during the recovery phase after acute stress exposure (p = 0.020), while no DAN centrality change was observed during the initial stress response (p = 0.626). Such increasing DAN centrality during stress recovery was also found in healthy siblings (p = 0.016), but not in BD patients (p = 0.554). This study highlights that temporally complex and precise changes in network configuration are vital to understand the response to and recovery from stress.

Statistics of fluctuating colloidal fluid-fluid interfaces.

Fluctuations of the interface between coexisting colloidal fluid phases have been measured with confocal microscopy. Due to a very low surface tension, the thermal motions of the interface are so slow that a record can be made of the positions of the interface. The theory of the interfacial height fluctuations is developed. For a host of correlation functions, the experimental data are compared with the theoretical expressions. The agreement between theory and experiment is remarkably good.

Crossover from reptation to Rouse dynamics in the extended Rubinstein-Duke model.

The competition between reptation and Rouse dynamics is incorporated in the Rubinstein-Duke model for polymer motion by extending it with sideways motions, which cross barriers and create or annihilate hernias. Using the density-matrix renormalization-group method as a solver of the master equation, the renewal time and the diffusion coefficient are calculated as functions of the length of the chain and the strength of the sideways motion. These types of moves have a strong and delicate influence on the asymptotic behavior of long polymers. The effects are analyzed as functions of the chain length in terms of effective exponents and crossover scaling functions.

At-risk individuals display altered brain activity following stress.

Stress is a major risk factor for almost all psychiatric disorders, however, the underlying neurobiological mechanisms remain largely elusive. In healthy individuals, a successful stress response involves an adequate neuronal adaptation to a changing environment. This adaptive response may be dysfunctional in vulnerable individuals, potentially contributing to the development of psychopathology. In the current study, we investigated brain responses to emotional stimuli following stress in healthy controls and at-risk individuals. An fMRI study was conducted in healthy male controls (N = 39) and unaffected healthy male siblings of schizophrenia patients (N = 39) who are at increased risk for the development of a broad range of psychiatric disorders. Brain responses to pictures from the International Affective Picture System (IAPS) were measured 33 min after exposure to stress induced by the validated trier social stress test (TSST) or a control condition. Stress-induced levels of cortisol, alpha-amylase, and subjective stress were comparable in both groups. Yet, stress differentially affected brain responses of schizophrenia siblings versus controls. Specifically, control subjects, but not schizophrenia siblings, showed reduced brain activity in key nodes of the default mode network (PCC/precuneus and mPFC) and salience network (anterior insula) as well as the STG, MTG, MCC, vlPFC, precentral gyrus, and cerebellar vermis in response to all pictures following stress. These results indicate that even in the absence of a psychiatric disorder, at-risk individuals display abnormal functional activation following stress, which in turn may increase their vulnerability and risk for adverse outcomes.

Efficient simulation of semiflexible polymers with stiff bonds.

We investigate the simulation of stiff (extensible) and rigid (inextensible) semiflexible polymers in solution. In particular, we focus on polymers represented as chains of beads, interconnected by bonds with a low to zero extensibility, and significant persistence in the bond orientations along the chain, whose dynamical behavior is described by the Langevin equation. We review the derivation of the pseudopotential needed for rigid bonds. The efficiency of a number of routines for such simulations is determined. We propose a routine for handling rigid bonds which is, for longer chains, substantially more efficient than the existing ones. We also show that for extensible polymers, the Rouse modes can be exploited to achieve highly efficient simulations. At realistic values for the extensibility, e.g., that of double-stranded DNA, the simulations are orders of magnitude faster than those for rigid bonds. With increasing stiffness, however, the allowable time step and hence the efficiency decreases, until a crossover point is reached below which the routines with rigid bonds are more efficient; we present a numerical estimate of this crossover point.

Exact solution for a one-dimensional model for reptation.

We discuss the exact solution for the properties of the recently introduced "necklace" model for reptation. The solution gives the drift velocity, diffusion constant, and renewal time for asymptotically long chains. Its properties are also related to a special case of the Rubinstein-Duke model in one dimension.

Crossover from reptation to Rouse dynamics in a one-dimensional model.

A simple one-dimensional model is constructed for polymer motion. It exhibits the crossover from reptation to Rouse dynamics through gradually allowing hernia creation and annihilation. The model is treated by the density matrix technique which permits an accurate finite-size-scaling analysis of the behavior of long polymers.

Crossover from reptation to Rouse dynamics in the cage model.

The two-dimensional cage model for polymer motion is discussed with an emphasis on the effect of sideways motions, which cross the barriers imposed by the lattice. Using the density matrix method as a solver of the master equation, the renewal time and the diffusion coefficient are calculated as a function of the strength of the barrier crossings. A strong crossover influence of the barrier crossings is found and it is analyzed in terms of effective exponents for a given chain length. The crossover scaling functions and the crossover scaling exponents are calculated.

Dynamics of a double-stranded DNA segment in a shear flow.

We study the dynamics of a double-stranded DNA (dsDNA) segment, as a semiflexible polymer, in a shear flow, the strength of which is customarily expressed in terms of the dimensionless Weissenberg number Wi. Polymer chains in shear flows are well known to undergo tumbling motion. When the chain lengths are much smaller than the persistence length, one expects a (semiflexible) chain to tumble as a rigid rod. At low Wi, a polymer segment shorter than the persistence length does indeed tumble as a rigid rod. However, for higher Wi the chain does not tumble as a rigid rod, even if the polymer segment is shorter than the persistence length. In particular, from time to time the polymer segment may assume a buckled form, a phenomenon commonly known as Euler buckling. Using a bead-spring Hamiltonian model for extensible dsDNA fragments, we first analyze Euler buckling in terms of the oriented deterministic state (ODS), which is obtained as the steady-state solution of the dynamical equations by turning off the stochastic (thermal) forces at a fixed orientation of the chain. The ODS exhibits symmetry breaking at a critical Weissenberg number Wi_{c}, analogous to a pitchfork bifurcation in dynamical systems. We then follow up the analysis with simulations and demonstrate symmetry breaking in computer experiments, characterized by a unimodal to bimodal transformation of the probability distribution of the second Rouse mode with increasing Wi. Our simulations reveal that shear can cause strong deformation for a chain that is shorter than its persistence length, similar to recent experimental observations.

Efficient simulation of semiflexible polymers.

Using a recently developed bead-spring model for semiflexible polymers that takes into account their natural extensibility, we report an efficient algorithm to simulate the dynamics for polymers like double-stranded DNA (dsDNA) in the absence of hydrodynamic interactions. The dsDNA is modeled with one bead-spring element per base pair, and the polymer dynamics is described by the Langevin equation. The key to efficiency is that we describe the equations of motion for the polymer in terms of the amplitudes of the polymer's fluctuation modes, as opposed to the use of the physical positions of the beads. We show that, within an accuracy tolerance level of 5% of several key observables, the model allows for single Langevin time steps of ≈1.6, 8, 16, and 16 ps for a dsDNA model chain consisting of 64, 128, 256, and 512 base pairs (i.e., chains of 0.55, 1.11, 2.24, and 4.48 persistence lengths), respectively. Correspondingly, in 1 h, a standard desktop computer can simulate 0.23, 0.56, 0.56, and 0.26 ms of these dsDNA chains, respectively. We compare our results to those obtained from other methods, in particular, the (inextensible discretized) wormlike chain (WLC) model. Importantly, we demonstrate that at the same level of discretization, i.e., when each discretization element is one base pair long, our algorithm gains about five to six orders of magnitude in the size of time steps over the inextensible WLC model. Further, we show that our model can be mapped one on one to a discretized version of the extensible WLC model, implying that the speed-up we achieve in our model must hold equally well for the latter. We also demonstrate the use of the method by simulating efficiently the tumbling behavior of a dsDNA segment in a shear flow.

Force correlations in the q model for general q distributions.

We study force correlations in the q model for granular media at infinite depth for general q distributions. We show that there are no two-point force correlations as long as q values at different sites are uncorrelated. However, higher-order correlations can persist, and if they do, they only decay with a power of the distance. Furthermore, we find the entire set of q distributions for which the force distribution factorizes. It includes distributions ranging from infinitely sharp to almost critical. Finally, we show that two-point force correlations do appear whenever there are correlations between q values at different sites in a layer; various cases are evaluated explicitly.

Crossover behavior for long reptating polymers.

The Rubinstein-Duke model for polymer reptation is analyzed by means of density matrix renormalization techniques. It is found that the crossover in the scaling behavior of polymer renewal time (or viscosity) arises from the competing effect of the contribution due to tube length fluctuations and higher-order corrections, which are of opposite sign. Experiments which ought to emphasize both contributions are suggested. The exponent describing the subleading scaling behavior of the diffusion coefficient is also investigated.

Pulling reptating polymers by one end: magnetophoresis in the Rubinstein-Duke model.

We consider the magnetophoresis problem within the Rubinstein-Duke model, i.e., a reptating polymer pulled by a constant field applied to a single end of a chain. Extensive density matrix renormalization calculations are presented of the drift velocity and the profile of the chain for various strengths of the driving field and chain lengths. We show that the velocities and the average densities of the stored length are well described by simple interpolating crossover formulas, derived under the assumption that the difference between the drift and curvilinear velocities vanishes for sufficiently long chains. The profiles, which describe the average shape of the reptating chain, also show such interesting features as some nonmonotonic behavior of the link densities for sufficiently strong pulling fields. We develop a description in which a distinction is made between links entering at the pulled head and at the unpulled tail. At weak fields the separation between the head zone and the tail zone meanders through the whole chain, while the probability of finding it close to the edges drops off. At strong fields the tail zone is confined to a small region close to the unpulled edge of the polymer.

Ensemble theory for force networks in hyperstatic granular matter.

An ensemble approach for force networks in static granular packings is developed. The framework is based on the separation of packing and force scales, together with an a priori flat measure in the force phase space under the constraints that the contact forces are repulsive and balance on every particle. In this paper we will give a general formulation of this force network ensemble, and derive the general expression for the force distribution P(f). For small regular packings these probability densities are obtained in closed form, while for larger packings we present a systematic numerical analysis. Since technically the problem can be written as a noninvertible matrix problem (where the matrix is determined by the contact geometry), we study what happens if we perturb the packing matrix or replace it by a random matrix. The resulting P(f) 's differ significantly from those of normal packings, which touches upon the deep question of how network statistics is related to the underlying network structure. Overall, the ensemble formulation opens up a different perspective on force networks that is analytically accessible, and which may find applications beyond granular matter.

Assessment of health risks of large semi-wild herbivores in urbanized areas.

The health risks for both domestic animals and humans caused by large herbivores in self-sustaining ecosystems are largely unknown. The aim of this article is to make an inventory of these risks, to explore ways to manage them in practice, and to make recommendations for the quantification of risks. Potential hazards from herbivores in and around Europe are listed using the data of the OIE (Office International des Epizooties). The desired health status and the implementation of control or surveillance measures are important factors when assessing the risks. Results indicate that a regular yearly system of health monitoring of herbivores is necessary. To get more insight into the importance of certain risks (Infectious Bovine Rhinotracheitis, biodegradation of carrion in the field) epidemiological investigations have to be carried out to assess the risk of transmission in different situations (with or without intervention). Analysing and managing risks enable decision-makers to formulate the conditions for the development of nature reserves. In Europe more has to be done to increase the quality of nature in terms of de-fragmentation and de-isolation, but regulations concerning the health of large herbivores also have to be improved.

[Trends in research related to the health of pigs]. / Ontwikkelingen in het onderzoek met betrekking tot de gezondheid van het varken.

The intensification of pig husbandry has important consequences for pig health care. More attention must not only be paid to clinical outbreaks of disease but also to subclinical problems and disturbances of production. More research must be done to improve the efficiency of disease control and beyond this to the optimalization of prevention. The roles of etiology, biotechnology, the research on pathogenesis, epidemiology and immunology in meeting these goals are roughly outlined and illustrated with concrete examples derived from the program of the C.V.I. (Central Veterinary Institute) in the Netherlands. How this research will affect research immediately connected with health care is explored at the end of this article.