Like all other viruses, a successful egress of functional particles from infected cells is a prerequisite for foamy virus (FV) spread within the host. The budding process of FVs involves steps, which are shared by other retroviruses, such as interaction of the capsid protein with components of cellular vacuolar protein sorting (Vps) machinery via late domains identified in some FV capsid proteins. Additionally, there are features of the FV budding strategy quite unique to the spumaretroviruses. This includes secretion of non-infectious subviral particles and a strict dependence on capsid-glycoprotein interaction for release of infectious virions from the cells. Virus-like particle release is not possible since FV capsid proteins lack a membrane-targeting signal. It is noteworthy that in experimental systems, the important capsid-glycoprotein interaction could be bypassed by fusing heterologous membrane-targeting signals to the capsid protein, thus enabling glycoprotein-independent egress. Aside from that, other systems have been developed to enable envelopment of FV capsids by heterologous Env proteins. In this review article, we will summarize the current knowledge on FV budding, the viral components and their domains involved as well as alternative and artificial ways to promote budding of FV particle structures, a feature important for alteration of target tissue tropism of FV-based gene transfer systems.

Alerting signals often serve to reduce temporal uncertainty by predicting the time of stimulus onset. The resulting response time benefits have often been explained by facilitated translation of stimulus codes into response codes on the basis of established stimulus-response (S-R) links. In paradigms of masked S-R priming alerting signals also modulate response activation processes triggered by subliminally presented prime stimuli. In the present study we tested whether facilitation of visuo-motor translation processes due to alerting signals critically depends on established S-R links. Alerting signals resulted in significantly enhanced masked priming effects for masked prime stimuli that included and that did not include established S-R links (i.e., target vs. novel primes). Yet, the alerting-priming interaction was more pronounced for target than for novel primes. These results suggest that effects of alerting signals on masked priming are especially evident when S-R links between prime and target exist. At the same time, an alerting-priming interaction also for novel primes suggests that alerting signals also facilitate stimulus-response translation processes when masked prime stimuli provide action-trigger conditions in terms of programmed S-R links.

Background: Multimorbidity is defined as suffering from coexistent chronic conditions. Multimorbid patients demand highly complex patient-centered care which often includes polypharmacy, taking an average of six different drugs per day. Adverse drug reactions, adverse drug events and medication errors are all potential consequences of polypharmacy. Our study aims to detect the status quo of the health care situation in Saxony’s general practices for multimorbid patients receiving multiple medications. We will identify the most common clinical profiles as well as documented adverse drug events and reactions that occur during the treatment of patients receiving multiple medications. We will focus on exploring the motives of general practitioners for the prescription of selected drugs in individual cases where there is evidence of potential drug-drug-interactions and potentially inappropriate medications in elderly patients. Furthermore, the study will explore general practitioners’ opinions on delegation of skills to other health professions to support medical care and monitoring of patients receiving multiple medications. Methods/design: This is a retrospective cross sectional study using mixed methods. Socio-demographic data as well as diagnoses, medication regimens and clinically important events will be analyzed retrospectively using general practitioners documentation in patients’ records. Based on these data, short vignettes will be generated and discussed by general practitioners in qualitative telephone interviews. Discussion: To be able to improve outpatient health care management for patients receiving multiple medications, the current status quo of care, risk factors for deficient treatment and characteristics of concerned patients must be investigated. Furthermore, it is necessary to understand the physicians’ decision making process regarding treatment.

Meta-analytic data highlight the value of the Implicit Association Test (IAT) as an indirect measure of personality. Based on evidence suggesting that confounding factors such as cognitive abilities contribute to the IAT effect, this study provides a first investigation of whether basic personality traits explain unwanted variance in the IAT. In a gender-balanced sample of 204 volunteers, the Big-Five dimensions were assessed via self-report, peer-report, and IAT. By means of structural equation modeling (SEM), latent Big-Five personality factors (based on self- and peer-report) were estimated and their predictive value for unwanted variance in the IAT was examined. In a first analysis, unwanted variance was defined in the sense of method-specific variance which may result from differences in task demands between the two IAT block conditions and which can be mirrored by the absolute size of the IAT effects. In a second analysis, unwanted variance was examined in a broader sense defined as those systematic variance components in the raw IAT scores that are not explained by the latent implicit personality factors. In contrast to the absolute IAT scores, this also considers biases associated with the direction of IAT effects (i.e., whether they are positive or negative in sign), biases that might result, for example, from the IAT's stimulus or category features. None of the explicit Big-Five factors was predictive for method-specific variance in the IATs (first analysis). However, when considering unwanted variance that goes beyond pure method-specific variance (second analysis), a substantial effect of neuroticism occurred that may have been driven by the affective valence of IAT attribute categories and the facilitated processing of negative stimuli, typically associated with neuroticism. The findings thus point to the necessity of using attribute category labels and stimuli of similar affective valence in personality IATs to avoid confounding due to recoding.

Introduction: The quality of neonatal care is mainly determined by long-term neurodevelopmental outcome. The neurodevelopment of preterm infants is related to postnatal head growth and depends on medical interventions such as nutritional support. Head circumference (HC) is currently used as a two-dimensional measure of head growth. Since head deformities are frequently found in preterm infants, HC may not always adequately reflect head growth. Laser aided head shape digitizers offer semiautomatic acquisition of HC and cranial volume (CrV) and could thus be useful in describing head size more precisely. Aims: 1) To evaluate reproducibility of a 3D digital capture system in newborns. 2) To compare manual and digital HC measurements in a neonatal cohort. 3) To determine correlation of HC and CrV and predictive value of HC. Methods: Within a twelve-month period data of head scans with a laser shape digitizer were analysed. Repeated measures were used for method evaluation. Manually and digitally acquired HC was compared. Regression analysis of HC and CrV was performed. Results: Interobserver reliability was excellent for HC (bias-0.005%, 95% Limits of Agreement (LoA) −0.39–0.39%) and CrV (bias1.5%, 95%LoA-0.8–3.6%). Method comparison data was acquired from 282 infants. It revealed interchangeability of the methods (bias-0.45%; 95%LoA-4.55–3.65%) and no significant systematic or proportional differences. HC and CrV correlated (r2 = 0.859, p<0.001), performance of HC predicting CrV was poor (RSD ±24 ml). Correlation was worse in infants with lower postmenstrual age (r2 = 0.745) compared to older infants (r2 = 0.843). Discussion: The current practice of measuring HC for describing head growth in preterm infants could be misleading since it does not represent a 3D approach. CrV can vary substantially in infants of equal HC. The 3D laser scanner represents a new and promising method to provide reproducible data of CrV and HC. Since it does not provide data on cerebral structures, additional imaging is required.

In addition to classical adhesion structures like filopodia or focal adhesions, dendritic cells similar to macrophages and osteoclasts assemble highly dynamic F-actin structures called podosomes. They are involved in cellular processes such as extracellular matrix degradation, bone resorption by osteoclasts, and trans-cellular diapedesis of lymphocytes. Besides adhesion and migration, podosomes enable dendritic cells to degrade connective tissue by matrix metalloproteinases. SWAP-70 interacts with RhoGTPases and F-actin and regulates migration of dendritic cells. SWAP-70 deficient osteoclasts are impaired in F-actin-ring formation and bone resorption. In the present study, we demonstrate that SWAP-70 is not required for podosome formation and F-actin turnover in dendritic cells. Furthermore, we found that toll-like receptor 4 ligand induced podosome disassembly and podosome-mediated matrix degradation is not affected by SWAP-70 in dendritic cells. Thus, podosome formation and function in dendritic cells is independent of SWAP-70.

SMC1 and SMC3 form a high-affinity heterodimer, which provides an open backbone of the cohesin ring, to be closed by a kleisin protein. RNAi mediated knock-down of either one heterodimer partner, SMC1 or SMC3, is expected to cause very similar if not identical phenotypes. However, we observed highly distinct, protein-specific phenotypes. Upon knock-down of human SMC1, much of SMC3 remains stable, accumulates in the cytoplasm and does not associate with other cohesin proteins. Most of the excess nuclear SMC3 is highly mobile and not or only weakly chromosome-associated. In contrast, human SMC3 knock-down rendered SMC1 instable without cytoplasmic accumulation. As observed by differential protein extraction and in FRAP experiments the remaining SMC1 or SMC3 proteins in the respective SMC1 or SMC3 knock-down experiments constituted a cohesin pool, which is associated with chromatin with highest affinity, likely the least expendable. Expression of bovine EGFP-SMC1 or mouse EGFP-SMC3 in human cells under conditions of human SMC1 or SMC3 knock-down rescued the respective phenotypes, but in untreated cells over-expressed exogenous SMC proteins mis-localized. Paucity of either one of the SMC proteins causes RAD21 degradation. These results argue for great caution in interpreting SMC1 and SMC3 RNAi or over-expression experiments. Under challenged conditions these two proteins unexpectedly behave differently, which may have biological consequences for regulation of cohesin-associated functions and for human cohesin pathologies.

Perturbation experiments for example using RNA interference (RNAi) offer an attractive way to elucidate gene function in a high throughput fashion. The placement of hit genes in their functional context and the inference of underlying networks from such data, however, are challenging tasks. One of the problems in network inference is the exponential number of possible network topologies for a given number of genes. Here, we introduce a novel mathematical approach to address this question. We formulate network inference as a linear optimization problem, which can be solved efficiently even for large-scale systems. We use simulated data to evaluate our approach, and show improved performance in particular on larger networks over state-of-the art methods. We achieve increased sensitivity and specificity, as well as a significant reduction in computing time. Furthermore, we show superior performance on noisy data. We then apply our approach to study the intracellular signaling of human primary nave CD4+ T-cells, as well as ErbB signaling in trastuzumab resistant breast cancer cells. In both cases, our approach recovers known interactions and points to additional relevant processes. In ErbB signaling, our results predict an important role of negative and positive feedback in controlling the cell cycle progression.

It has been repeatedly shown that functional magnetic resonance imaging (fMRI) triggers distress and neuroendocrine response systems. Prior studies have revealed that sympathetic arousal increases, particularly at the beginning of the examination. Against this background it appears likely that those stress reactions during the scanning procedure may influence task performance and neural correlates. However, the question how sympathetic arousal elicited by the scanning procedure itself may act as a potential confounder of fMRI data remains unresolved today. Thirty-seven scanner naive healthy subjects performed a simple cued target detection task. Levels of salivary alpha amylase (sAA), as a biomarker for sympathetic activity, were assessed in samples obtained at several time points during the lab visit. SAA increased two times, immediately prior to scanning and at the end of the scanning procedure. Neural activation related to motor preparation and timing as well as task performance was positively correlated with the first increase. Furthermore, the first sAA increase was associated with task induced deactivation (TID) in frontal and parietal regions. However, these effects were restricted to the first part of the experiment. Consequently, this bias of scanner related sympathetic activation should be considered in future fMRI investigations. It is of particular importance for pharmacological investigations studying adrenergic agents and the comparison of groups with different stress vulnerabilities like patients and controls or adolescents and adults.

Disgust causes specific reaction patterns, observable in mimic responses and body reactions. Most research on disgust deals with visual stimuli. However, pictures may cause another disgust experience than sounds, odors, or tactile stimuli. Therefore, disgust experience evoked by four different sensory channels was compared. A total of 119 participants received 3 different disgusting and one control stimulus, each presented through the visual, auditory, tactile, and olfactory channel. Ratings of evoked disgust as well as responses of the autonomic nervous system (heart rate, skin conductance level, systolic blood pressure) were recorded and the effect of stimulus labeling and of repeated presentation was analyzed. Ratings suggested that disgust could be evoked through all senses; they were highest for visual stimuli. However, autonomic reaction toward disgusting stimuli differed according to the channel of presentation. In contrast to the other, olfactory disgust stimuli provoked a strong decrease of systolic blood pressure. Additionally, labeling enhanced disgust ratings and autonomic reaction for olfactory and tactile, but not for visual and auditory stimuli. Repeated presentation indicated that participant's disgust rating diminishes to all but olfactory disgust stimuli. Taken together we argue that the sensory channel through which a disgust reaction is evoked matters.