Free energies of membrane stalk formation from a lipidomics perspective

Many biological membranes are asymmetric and exhibit complex lipid composition, comprising hundreds of distinct chemical species. Identifying the biological function and advantage of this complexity is a central goal of membrane biology. Here, we study how membrane complexity controls the energetics of the first steps of membrane fusions, that is, the formation of a stalk. We first present a computationally efficient method for simulating thermodynamically reversible pathways of stalk formation at coarse-grained resolution. The method reveals that the inner leaflet of a typical plasma membrane is far more fusogenic than the outer leaflet, which is likely an adaptation to evolutionary pressure. To rationalize these findings by the distinct lipid compositions, we computed ~200 free energies of stalk formation in membranes with different lipid head groups, tail lengths, tail unsaturations, and sterol content. In summary, the simulations reveal a drastic influence of the lipid composition on stalk formation and a comprehensive fusogenicity map of many biologically relevant lipid classes

Politische vs. persönliche Kritik: die Darstellung von Politikern in der Nachrichtensatire 'heute-show'

Politische Nachrichtensatire bewegt sich in einem Spannungsfeld zwischen Information und Unterhaltung. Dies resultiert in hybriden Anforderungen an die Selektion und Darstellung politischer Akteure, speziell vor dem Hintergrund der Diskussion um Personalisierung und Privatisierung der medialen Politikvermittlung. Anhand einer Inhaltsanalyse untersucht die Studie daher die Politikerdarstellung in der ‚heute-show‘. Die Ergebnisse zeigen, dass sich die Nachrichtensatire auf nationale, einflussreiche Politiker fokussiert. Persönlich-private Eigenschaften werden dabei fast ebenso häufig attackiert wie politische Aspekte. Der hohe Anteil an Privatisierung bestätigt, dass die politische Nachrichtensatire nicht zwangsläufig politisch sein muss. Durch die bessere Visualisierbarkeit und den geringeren Schwierigkeitsgrad werden Witze über rollenferne Merkmale, speziell Äußerlichkeiten, möglicherweise bevorzugt.Political news satire can be characterized as a hybrid format between information and entertainment. This results in hybrid demands regarding the selection and depiction of political protagonists, especially against the background of the discussion about privatization. Conducting a content analysis of the heute-show, our study investigates the representation of politicians in a German news satire. Our findings show that the heute-show focuses on national, powerful politicians. Private and personal attributes are criticized almost as often as political characteristics. The high amount of privatization acknowledges that political news satire does not necessarily have to be political. Instead, jokes about not role-related attributes, especially about appearance, might be preferred, as they do rely less on background knowledge und are better visualizable

The Lantibiotic Nisin Induces Lipid II Aggregation, Causing Membrane Instability and Vesicle Budding

AbstractThe antimicrobial peptide nisin exerts its activity by a unique dual mechanism. It permeates the cell membranes of Gram-positive bacteria by binding to the cell wall precursor Lipid II and inhibits cell wall synthesis. Binding of nisin to Lipid II induces the formation of large nisin-Lipid II aggregates in the membrane of bacteria as well as in Lipid II-doped model membranes. Mechanistic details of the aggregation process and its impact on membrane permeation are still unresolved. In our experiments, we found that fluorescently labeled nisin bound very inhomogeneously to bacterial membranes as a consequence of the strong aggregation due to Lipid II binding. A correlation between cell membrane damage and nisin aggregation was observed in vivo. To further investigate the aggregation process of Lipid II and nisin, we assessed its dynamics by single-molecule microscopy of fluorescently labeled Lipid II molecules in giant unilamellar vesicles using light-sheet illumination. We observed a continuous reduction of Lipid II mobility due to a steady growth of nisin-Lipid II aggregates as a function of time and nisin concentration. From the measured diffusion constants of Lipid II, we estimated that the largest aggregates contained tens of thousands of Lipid II molecules. Furthermore, we observed that the formation of large nisin-Lipid II aggregates induced vesicle budding in giant unilamellar vesicles. Thus, we propose a membrane permeation mechanism that is dependent on the continuous growth of nisin-Lipid II aggregation and probably involves curvature effects on the membrane

Validation of the Apraxia Screen TULIA (AST) in Schizophrenia.

INTRODUCTION Deficits in social interaction and community functioning, including impaired use, performance, and perception of hand gestures, are key features in schizophrenia. A well-established tool to assess gesture deficits is the test of upper limb apraxia (TULIA). However, given its time-consuming application based on video analyses, research has proposed the bedside apraxia screen of TULIA (AST). This study aims to test the validity and reliability of the AST to detect gesture abnormalities at bedside in a sample of 27 patients diagnosed with schizophrenia, schizotypal disorder, acute and transient psychotic disorders, or schizoaffective disorder. METHODS Patients completed the 48-item TULIA and the 12-item AST. Two different raters assessed the AST: one at bedside (online) and the other based on the video recordings. RESULTS The total AST scores demonstrated a high parallel reliability, moderate inter-rater reliability on a single-item level, and good construct validities. CONCLUSIONS The psychometric properties of the AST suggest it can well be used for the clinical assessment of gesture deficits in schizophrenia. However, when detailed information is required, the AST rated from video or conducting the full TULIA is recommended. The findings call for refining the selection of the TULIA items for a psychosis-AST bedside test to increase specificity

Potential of digitalization within physiotherapy: a comparative survey

BACKGROUND Due to the global digitalization, implementation of digital elements into daily work can support physiotherapists' work but may also pose some challenges. Only little is known about physiotherapists' attitude towards digitalization. This study primarily aimed to analyze physiotherapists' attitude towards digitalization and to what extend digital tools have been implemented into their daily work. In second analysis, participants' characteristics such as age, working place, gender and mode of survey participation were assessed. METHODS A 12-main-item survey amongst voluntary course participants of one physiotherapeutic training center was conducted via paper-based as well as online questionnaires between July 2018 and June 2019 including questions on participants' general as well as particular attitude towards digitalization, the use of (mobile) applications and possible advantages and disadvantages of the ongoing digital transformation. Sub-analysis was performed for age (≤40 years versus > 40 years), gender, mode of participation (paper vs. online) and working place (practice vs. hospital). RESULTS Overall, 488 physiotherapists participated in the survey. In comparison of the age groups, younger participants had more concerns about data security (p = 0.042) and insufficient financial remuneration (p < 0.001). Younger participants stated higher satisfaction with data literacy than their counterparts (p = 0.0001). Physiotherapists working in the outpatient sector, rather than in hospitals, expected digitalization to increase more in relevance (p < 0.001). The online respondents (OG) indicated that they had more knowledge about key aspects of the current legal situation regarding digitalization than participants completing the paper-based survey (p = 0.002). 50.4% of the considered digitalization as useful for their job. CONCLUSIONS The majority of participants saw high potential for digitalization in the physiotherapy sector. Younger physiotherapists seem to be more concerned about data security and insufficient financial remuneration. Physiotherapists in the outpatient sector seem to see more potential in digital transformations. General concerns like missing reimbursement, lack of data security or knowledge on legal frameworks should be addressed in the future. Further studies should focus on identifying specific digital tools which can support physiotherapists

Flat-Field Super-Resolution Localization Microscopy with a Low-Cost Refractive Beam-Shaping Element.

Super-resolution single-molecule localization microscopy, often referred to as PALM/STORM, works by ensuring that fewer than one fluorophore in a diffraction-limited volume is emitting at any one time, allowing the observer to infer that the emitter is located at the center of the point-spread function. This requires careful control over the incident light intensity in order to control the rate at which fluorophores are switched on; if too many fluorophores are activated, their point-spread functions overlap, which impedes efficient localization. If too few are activated, the imaging time is impractically long. There is therefore considerable recent interest in constructing so-called 'top-hat' illumination profiles that provide a uniform illumination over the whole field of view. We present the use of a single commercially-available low-cost refractive beamshaping element that can be retrofitted to almost any existing microscope; the illumination profile created by this element demonstrates a marked improvement in the power efficiency of dSTORM microscopy, as well as a significant reduction in the propensity for reconstruction artifacts, compared to conventional Gaussian illumination

The Patient Typology about deprescribing and medication-related decisions: A quantitative exploration.

This study aimed to test the adequacy of a quantitative measure of our qualitatively-developed Patient Typology - categories of older adults' attitudes towards medicines and medicine decision-making - and identify characteristics associated with each Typology. We conducted secondary data analyses of a subset of survey item measures of adults (≥65 years) who were members of online survey panels in Australia, the UK, the US, and the Netherlands (n=4,688). Multinomial logistic regression analyses assessed associations between demographic, psychosocial, and medication-related measures. Mean age was 71.5 (5) and 47.5% of participants were female. Factors associated with an increased likelihood of identifying with Typology 1 'Attached to medicines' over Typology 2 'Open to deprescribing' were higher positive attitude towards polypharmacy (RRR=1.12, p =<.001) and higher need for certainty (RRR=1.11, p=.039). Factors associated with an increased likelihood of identifying with Typology 3 'Defers (medication decision-making) to others' over Typology 2 were older age (RRR=1.47 per 10-year age increase, p=<.001) and a decreased likelihood of prior deprescribing experience (RRR=0.73, p=.033). This study provides validation of the Typology with large samples from four countries, with the quantitatively-measured typologies generally aligning with the qualitatively-derived categories. Our Patient Typology measure provides a succinct way researchers can assess attitudes towards deprescribing

Three-Dimensional Observation of Atmospheric Processes in Cities

To cope with weather and climate-induced impacts as well as with air pollution in cities, the German research programme “Urban Climate Under Change” ([UC]2) aims at developing, testing and validating a new urban climate model, which is able to cover the full range of temporal and spatial scales of urban atmospheric processes. The project “Three-dimensional Observation of Atmospheric Processes in Cities” (3DO), which forms the module B of the [UC]2 research programme, aims at acquisition of comprehensive, accurate three-dimensional observational data sets on weather, climate and air quality in the German cities of Berlin, Hamburg and Stuttgart. Data sets from long-term observations and intense observation periods allow for evaluation of the performance of a new urban climate model called PALM‑4U that is developed by the project “Model-based city planning and application in climate change” (MOSAIK), which forms the module A of the [UC]2 research programme. This article focuses on collaborative activities for compilation of existing and acquisition of new observational data within the 3DO project

A fluorescent reporter system enables spatiotemporal analysis of host cell modification during herpes simplex virus-1 replication.

Herpesviruses are large and complex viruses that have a long history of coevolution with their host species. One important factor in the virus-host interaction is the alteration of intracellular morphology during viral replication with critical implications for viral assembly. However, the details of this remodeling event are not well understood, in part because insufficient tools are available to deconstruct this highly heterogeneous process. To provide an accurate and reliable method of investigating the spatiotemporal dynamics of virus-induced changes to cellular architecture, we constructed a dual-fluorescent reporter virus that enabled us to classify four distinct stages in the infection cycle of herpes simplex virus-1 at the single cell level. This timestamping method can accurately track the infection cycle across a wide range of multiplicities of infection. We used high-resolution fluorescence microscopy analysis of cellular structures in live and fixed cells in concert with our reporter virus to generate a detailed and chronological overview of the spatial and temporal reorganization during viral replication. The highly orchestrated and striking relocation of many organelles around the compartments of secondary envelopment during transition from early to late gene expression suggests that the reshaping of these compartments is essential for virus assembly. We furthermore find that accumulation of HSV-1 capsids in the cytoplasm is accompanied by fragmentation of the Golgi apparatus with potential impact on the late steps of viral assembly. We anticipate that in the future similar tools can be systematically applied for the systems-level analysis of intracellular morphology during replication of other viruses