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Pyramidal neurons exhibit a complex dendritic tree that is decorated by a huge number of spine synapses receiving excitatory input. Synaptic signals not only act locally but are also conveyed to the nucleus of the postsynaptic neuron to regulate gene expression. This raises the question of how the spatio-temporal integration of synaptic inputs is accomplished at the genomic level and which molecular mechanisms are involved. Protein transport from synapse to nucleus has been shown in several studies and has the potential to encode synaptic signals at the site of origin and decode them in the nucleus. In this review, we summarize the knowledge about the properties of the synapto-nuclear messenger protein Jacob with special emphasis on a putative role in hippocampal neuronal plasticity. We will elaborate on the interactome of Jacob, the signals that control synapto-nuclear trafficking, the mechanisms of transport, and the potential nuclear function. In addition, we will address the organization of the Jacob/ NSMF gene, its origin and we will summarize the evidence for the existence of splice isoforms and their expression pattern., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Grochowska, Bär, Gomes, Kreutz and Karpova.)

Background: The high prevalence of mental disorders related to posttraumatic stress among Syrian refugees is often in contrast with their low utilization of mental health care in the host countries. Mental health self-stigma, i.e., internalized stigma of having a mental disorder, could prevent individuals from seeking mental health care. Therefore, we aimed to provide evidence on different aspects of mental health self-stigmatization among adult Syrian refugees with posttraumatic stress symptoms residing in Germany. Moreover, we investigated associations with sociodemographic and psychopathological variables in order to identify those at higher risk of self-stigmatization. Material and Methods: Overall, 133 participants with mild to moderate posttraumatic stress symptoms were recruited in the metropolitan areas of Leipzig, Dresden and Halle, Germany, using a multimodal approach. Mental health self-stigma was assessed using the Self-Stigma of Mental Illness Scale - Short Form (SSMIS-SF), consisting of four subscales ( Stereotype awareness, Stereotype agreement, Application to self , Harm to self-esteem ), each scoring from 5 (low) to 45 (high) points. Linear regression analysis was used to test associations of sociodemographic and psychopathological variables with self-stigma subscales. Results: On average, self-stigma ratings ranged from 16.5 (SD = 6.6) points on Application to self to 28.3 (SD = 7.5) points on Stereotype awareness . Results showed higher scores on Application to self for individuals who were younger ( t = 2.65, p = 0.009) and single ( F = 5.70, p = 0.004). Regression analyses yielded statistically significant associations between having multiple comorbidities and a higher Application to self stigma (β = 0.18, p = 0.044), controlling for sociodemographic covariates. Discussion: Mental health self-stigma was increased among Syrian refugees in Germany. Correlates of increased self-stigma could inform efforts to improve access to mental health care among Syrian refugees with mental ill-health. Longitudinal studies following an intersectional approach by concurrently examining multiple forms of public and internalized stigma could provide helpful insights for developing tailored stigma reduction efforts in this context., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Bär, Pabst, Röhr, Luppa, Renner, Nagl, Dams, Grochtdreis, Kersting, König and Riedel-Heller.)

Staphylococcus aureus causes chronic and relapsing infections, which may be difficult to treat. So-called small colony variants (SCVs) have been associated with chronic infections and their occurrence has been shown to increase under antibiotic pressure, low pH and intracellular localization. In clinics, S. aureus isolated from invasive infections often show a dysfunction in the accessory gene regulator ( agr ), a major virulence regulatory system in S. aureus . To assess whether intracellular environment and agr function influence SCV formation, an infection model was established using lung epithelial cells and skin fibroblasts. This allowed analyzing intracellular survival and localization of a panel of S. aureus wild type strains and their isogenic agr knock out mutants as well as a natural dysfunctional agr strain by confocal laser scanning microscopy (CLSM). Furthermore, bacterial colonies were quantified after 1, 3, and 5 days of intracellular survival by time-lapse analysis to determine kinetics of colony appearance and SCV formation. Here, we show that S. aureus strains with an agr knock out predominantly resided in a neutral environment, whereas wild type strains and an agr complemented strain resided in an acidic environment. S. aureus agr mutants derived from an intracellular environment showed a higher percentage of SCVs as compared to their corresponding wild type strains. Neutralizing acidic phagolysosomes with chloroquine resulted in a significant reduction of SCVs in S. aureus wild type strain 6850, but not in its agr mutant indicating a pH dependent formation of SCVs in the wild type strain. The in-depth understanding of the interplay between intracellular persistence, agr function and pH should help to identify new therapeutic options facilitating the treatment of chronic S. aureus infections in the future., (Copyright © 2020 Häffner, Bär, Dengler Haunreiter, Mairpady Shambat, Seidl, Crosby, Horswill and Zinkernagel.)

Inappropriate physical inactivity is a global health problem increasing the risk of cardiometabolic diseases. Wearable sensors show great potential to promote physical activity and thus a healthier lifestyle. While commercial activity trackers are available to estimate energy expenditure (EE) in non-disabled individuals, they are not designed for reliable assessments in individuals with an incomplete spinal cord injury (iSCI). Furthermore, activity recommendations for this population are currently rather vague and not tailored to their individual needs, and activity guidelines provided for the non-disabled population may not be easily translated for this population. However, especially in iSCI individuals with impaired abilities to stand and walk, the assessment of physical activities and appropriate recommendations for a healthy lifestyle are challenging. Therefore, the study aimed at developing an EE estimation model for iSCI individuals able to walk based on wearable sensor data. Additionally, the data collected within this study was used to translate common activity recommendations for the non-disabled population to easily understandable activity goals for ambulatory individuals with an iSCI. In total, 30 ambulatory individuals with an iSCI were equipped with wearable sensors while performing 12 different physical activities. EE was measured continuously and demographic and anthropometric variables, clinical assessment scores as well as wearable-sensor-derived features were used to develop different EE estimation models. The best EE estimation model comprised the estimation of resting EE using the updated Harris-Benedict equation, classifying activities using a k-nearest neighbor algorithm, and applying a multiple linear regression-based EE estimation model for each activity class. The mean absolute estimation error of this model was 15.2 ± 6.3% and the corresponding mean signed error was -3.4 ± 8.9%. Translating activity recommendations of global health institutions, we suggest a minimum of 2,000-3,000 steps per day for ambulatory individuals with an iSCI. If ambulatory individuals with an iSCI targeted the popular 10,000 steps a day recommendation for the non-disabled population, their equivalent would be around 8,000 steps a day. The combination of the presented dedicated EE estimation model for ambulatory individuals with an iSCI and the translated activity recommendations is an important step toward promoting an active lifestyle in this population., (Copyright © 2019 Popp, Schneider, Bär, Bösch, Spengler, Gassert and Curt.)

Actin is a versatile and ubiquitous cytoskeletal protein that plays a major role in both the establishment and the maintenance of neuronal polarity. For a long time, the most prominent roles that were attributed to actin in neurons were the movement of growth cones, polarized cargo sorting at the axon initial segment, and the dynamic plasticity of dendritic spines, since those compartments contain large accumulations of actin filaments (F-actin) that can be readily visualized using electron- and fluorescence microscopy. With the development of super-resolution microscopy in the past few years, previously unknown structures of the actin cytoskeleton have been uncovered: a periodic lattice consisting of actin and spectrin seems to pervade not only the whole axon, but also dendrites and even the necks of dendritic spines. Apart from that striking feature, patches of F-actin and deep actin filament bundles have been described along the lengths of neurites. So far, research has been focused on the specific roles of actin in the axon, while it is becoming more and more apparent that in the dendrite, actin is not only confined to dendritic spines, but serves many additional and important functions. In this review, we focus on recent developments regarding the role of actin in dendrite morphology, the regulation of actin dynamics by internal and external factors, and the role of F-actin in dendritic protein trafficking.