Vesicular Tubular Clusters between the ER and Golgi Mediate Concentration of Soluble Secretory Proteins by Exclusion from COPI-Coated Vesicles

AbstractWe have determined the concentrations of the secretory proteins amylase and chymotrypsinogen and the membrane proteins KDELr and rBet1 in COPII- and COPI-coated pre-Golgi compartments of pancreatic cells by quantitative immunoelectron microscopy. COPII was confined to ER membrane buds and adjacent vesicles. COPI occurred on vesicular tubular clusters (VTCs), Golgi cisternae, the trans-Golgi network, and immature secretory granules. Both secretory proteins exhibited a first, significant concentration step in noncoated segments of VTC tubules and were excluded from COPI-coated tips. By contrast, KDELr and rBet1 showed a first, significant concentration in COPII-coated ER buds and vesicles and were prominently present in COPI-coated tips of VTC tubules. These data suggest an important role of VTCs in soluble cargo concentration by exclusion from COPI-coated domains

Time-dependent effects of psychosocial stress on the contextualization of neutral memories

Memories about stressful experiences need to be both specific and generalizable to adequately guide future behavior. Memory strength is influenced by emotional significance, and contextualization (i.e., encoding experiences with their contextual details) enables selective context-dependent retrieval and protects against overgeneralization. The current randomized-controlled study investigated how the early and late phase of the endogenous stress response affects the contextualization of neutral and negative information. One hundred healthy male participants were randomly divided into three experimental groups that performed encoding either 1) without stress (control), 2) immediately after acute stress (early) or 3) two hours after acute stress (late). Stress was induced via the Trier Social Stress Test and salivary alpha-amylase and cortisol levels were measured throughout the experiment. In the Memory Contextualization Task, neutral and angry faces (items) were depicted against unique context pictures during encoding. During testing 24 h later, context-dependent recognition memory of the items was assessed by presenting these in either congruent or incongruent contexts (relative to encoding). Multilevel analyses revealed that neutral information was more contextualized when encoding took place two hours after psychosocial stress, than immediately after the stressor. Results suggest that the late effects in the unique, time-dependent sequence of a healthy endogenous stress response, could complement reduced contextualization immediately after stress. The contextualization of negative information was not influenced by psychosocial stress, as opposed to earlier reported effects of exogenous hydrocortisone administration. An imbalance between the early and late effects of the endogenous stress response could increase vulnerability for stress-related psychopathology.</p

No Time-Dependent Effects of Psychosocial Stress on Fear Contextualization and Generalization:A Randomized-Controlled Study With Healthy Participants

The formation of context-dependent fear memories (fear contextualization) can aid the recognition of danger in new, similar, situations. Overgeneralization of fear is often seen as hallmark of anxiety and trauma-related disorders. In this randomized-controlled study, we investigated whether exposure to a psychosocial stressor influences retention of fear contextualization and generalization in a time-dependent manner. The Trier Social Stress Test was used to induce psychosocial stress. Healthy male participants (n = 117) were randomly divided into three experimental groups that were subjected to the acquisition phase of the Fear Generalization Task: (1) without stress, (2) immediately after acute stress, or (3) 2 h after acute stress. In this task, a male with neutral facial expression (conditioned stimuli) was depicted in two different contexts that modulated the conditioned stimuli–unconditioned stimuli (=shock) association (threat, safe). Salivary alpha-amylase and cortisol levels were measured throughout the experiment. After a 24-h delay, context-dependency of fear memory was investigated with an unannounced memory test consisting of the threat and safe contexts alternated with a novel context (the generalization context). Multilevel analyses revealed that participants showed increased fear-potentiated startle responses to the conditioned stimuli in the threat compared to the safe context, at the end of the acquisition phase, indicating adequate fear contextualization. Directly after acquisition, there were no time-dependent effects of psychosocial stress on fear contextualization. Context-dependency of fear memories was retained 24 h later, as fear-potentiated startle responding was modulated by context (threat > safe or novel). At that time, the context-dependency of fear memories was also not influenced by the early or late effects of the endogenous stress response during acquisition. These results with experimental stress deviate in some aspects from those earlier obtained with exogenous hydrocortisone administration, suggesting a distinct role for stress mediators other than cortisol

An examination of the influence of prenatal sex hormones on handedness:Literature review and amniotic fluid data

Competing theories have posited roles for foetal androgen exposure in the development of human handedness. However, due to practical and ethical considerations, few studies have used hormonal measures to examine this possibility. The current paper reviews this literature and reveals a generally inconsistent pattern of results. We also present data from a longitudinal study of prenatal sex hormone exposure and subsequent handedness. More specifically, we examine correlations between testosterone and estradiol measured from second trimester amniotic fluid and hand preference (Dutch language version of the Edinburgh Handedness Inventory) and hand skill asymmetry (pegboard task) measured at 15 years of age. Prenatal sex hormone exposure was not associated with the direction of hand preference in either males or females. However, in females, high levels of prenatal testosterone were associated with weaker lateralisation of hand skill, and high levels of prenatal estradiol were associated with weaker hand preference. In addition, high levels of prenatal testosterone were associated with increased task duration (i.e., slow hand speed) for the right and left hands of males. The pattern of results observed here is not entirely consistent with any of the main theories linking sex hormones with handedness, suggesting that an association between these variables may be more complex than initially thought

Effect of dual tasking on a dynamic balance task in children with and without DCD

The purpose of this study was to compare performance of children with Developmental Coordination Disorder (DCD) and typically developing (TD) children in a dual task paradigm with a dynamic balance task on the Wii Fit as primary task and a concurrent cognitive (counting) or a concurrent bimanual fine motor task as secondary tasks. Using a cross-sectional design, 25 children with DCD and 38 TD children were assessed with the Movement Assessment Battery for Children, 2nd edition (MABC-2) and Divided Attention (DA) task of the KiTAP. Next, the single- and dual-tasks were performed and the level of interference or facilitation of the dual tasks was calculated. Regression analysis determined the predictive value of the DA and MABC-2 component balance outcomes on the dual task performance. On the motor and attentional tasks, the group of children with DCD scored significantly below the level of the TD children. The dual task effect showed similar interference and facilitation of tasks in the different dual-task conditions in both groups. In the dual task-cognitive condition, the divided attention abilities and the MABC-2 balance score predicted 25% of the Wii Fit dynamic balance task performance, whereas in the dual task-motor condition this was higher (31.6%). In both conditions, DA was a stronger predictor than MABC balance score and appears to be an important factor to consider when developing motor task training for children with DCD.</p

Pattern classification based on the amygdala does not predict an individual's response to emotional stimuli

Functional magnetic resonance imaging (fMRI) studies have often recorded robust univariate group effects in the amygdala of subjects exposed to emotional stimuli. Yet it is unclear to what extent this effect also holds true when multi-voxel pattern analysis (MVPA) is applied at the level of the individual participant. Here we sought to answer this question. To this end, we combined fMRI data from two prior studies (N = 112). For each participant, a linear support vector machine was trained to decode the valence of emotional pictures (negative, neutral, positive) based on brain activity patterns in either the amygdala (primary region-of-interest analysis) or the whole-brain (secondary exploratory analysis). The accuracy score of the amygdala-based pattern classifications was statistically significant for only a handful of participants (4.5%) with a mean and standard deviation of 37% ± 5% across all subjects (range: 28–58%; chance-level: 33%). In contrast, the accuracy score of the whole-brain pattern classifications was statistically significant in roughly half of the participants (50.9%), and had an across-subjects mean and standard deviation of 49% ± 6% (range: 33–62%). The current results suggest that the information conveyed by the emotional pictures was encoded by spatially distributed parts of the brain, rather than by the amygdala alone, and may be of particular relevance to studies that seek to target the amygdala in the treatment of emotion regulation problems, for example via real-time fMRI neurofeedback training.publishedVersio

Brain lateralization and self-reported symptoms of ADHD in a population sample of adults:A dimensional approach

Many clinical studies reported a compromised brain lateralization in patients with Attention-Deficit/Hyperactivity Disorder (ADHD) without being conclusive about whether the deficit existed in the left or right hemisphere. It is well-recognized that studying ADHD dimensionally is more controlled for comorbid problems and medication effects, and provides more accurate assessment of the symptoms. Therefore, the present study applied the dimensional approach to test the relationship between brain lateralization and self-reported ADHD symptoms in a population sample. Eighty-five right-handed university students filled in the Conners’ Adult ADHD Rating Scales and performed a lateralization reaction time task. The task consists of two matching conditions: one condition requires nominal identification for letters tapping left hemisphere specialization (Letter Name-Identity condition) and the other one requires physical and visuospatial identification for shapes tapping right hemisphere specialization (Shape Physical-Identity condition). The letters or shapes to be matched are presented in left or right visual field of a fixation cross. For both task conditions, brain lateralization was indexed as the difference in mean reaction time between left and right visual field. Linear regression analyses, controlled for mood symptoms reported by a depression, anxiety and stress scale, showed no relationship between the variables. These findings from a population sample of adults do not support the dimensionality of lateralized information processing deficit in ADHD symptomatology. However, group comparison analyses showed that subjects with high level of inattention symptoms close to or above the clinical cut-off had a reduced right hemisphere processing in the Shape Physical-Identity condition

Peri-Golgi vesicles contain retrograde but not anterograde proteins consistent with the cisternal progression model of intra-Golgi transport

A cisternal progression mode of intra-Golgi transport requires that Golgi resident proteins recycle by peri-Golgi vesicles, whereas the alternative model of vesicular transport predicts anterograde cargo proteins to be present in such vesicles. We have used quantitative immuno-EM on NRK cells to distinguish peri-Golgi vesicles from other vesicles in the Golgi region. We found significant levels of the Golgi resident enzyme mannosidase II and the transport machinery proteins giantin, KDEL-receptor, and rBet1 in coatomer protein I–coated cisternal rims and peri-Golgi vesicles. By contrast, when cells expressed vesicular stomatitis virus protein G this anterograde marker was largely absent from the peri-Golgi vesicles. These data suggest a role of peri-Golgi vesicles in recycling of Golgi residents, rather than an important role in anterograde transport

Barriers and facilitators for treatment-seeking for mental health conditions and substance misuse:Multi-perspective focus group study within the military

Background Globally, millions are exposed to stressors at work that increase their vulnerability to develop mental health conditions and substance misuse (such as soldiers, policemen, doctors). However, these types of professionals especially are expected to be strong and healthy, and this contrast may worsen their treatment gap. Although the treatment gap in the military has been studied before, perspectives of different stakeholders involved have largely been ignored, even though they play an important role. Aims To study the barriers and facilitators for treatment-seeking in the military, from three different perspectives. Method In total, 46 people participated, divided into eight homogeneous focus groups, including three perspectives: soldiers with mental health conditions and substance misuse (n = 20), soldiers without mental health conditions and substance misuse (n = 10) and mental health professionals (n = 16). Sessions were audio-taped and transcribed verbatim. Content analysis was done by applying a general inductive approach using ATLAS.ti-8.4.4 software. Results Five barriers for treatment-seeking were identified: fear of negative career consequences, fear of social rejection, confidentiality concerns, the ‘strong worker’ workplace culture and practical barriers. Three facilitators were identified: social support, accessibility and knowledge, and healthcare within the military. The views of the different stakeholder groups were highly congruent. Conclusions Barriers for treatment-seeking were mostly stigma related (fear of career consequences, fear of social rejection and the ‘strong worker’ workplace culture) and this was widely recognised by all groups. Social support from family, peers, supervisors and professionals were identified as important facilitators. A decrease in the treatment gap for mental health conditions and substance misuse is needed and these findings provide direction for future research and destigmatising interventions