Peripheral Lymph Node Addressins are Expressed on Skin Endothelial Cells

The term “peripheral node addressins” describes a set of several endothelial adhesion molecules, which collectively bind to L-selectin and react with monoclonal antibody MECA-79. They regulate lymphocyte recirculation through peripheral nodes. Their expression is thought to be restricted to a specialized vascular segment within the node, called the high endothelial venule. In certain chronic skin diseases, however, postcapillary venules of the skin may also acquire a high endothelial venule-like morphology. Employing immunohistochemistry on cryostat sections, we found these skin endothelial cells – like peripheral node high endothelial venules – to be reactive with monoclonal antibody MECA-79. Tissue lysates from the same specimens were then analyzed by immunoprecipitation using recombinant human L-selectin Fc-chimeras followed by immunoblotting using monoclonal antibody MECA-79. In contrast to peripheral node endothelium, which mainly expressed peripheral node addressin moieties of molecular sizes 90–110 kDa and 160 kDa, endothelial cells in cutaneous T cell lymphoma skin lesions expressed an additional and not yet defined 220 kDa peripheral node addressin-like molecule. Most surprisingly, even in normal skin specimens, we found a distinct subset of endothelial cells located around hair follicles constitutively expressing 90–110 kDa peripheral node addressin-like moieties. It is intriguing to speculate that – in analogy to the role of peripheral node addressins in peripheral nodes – the induced expression of peripheral node addressins in chronic T cell mediated skin diseases is responsible for a sustained lymphocyte recruitment. The constitutive expression of peripheral node addressins on perifollicular endothelium may serve for a continuous lymphocyte recirculation through normal skin

Protein kinase CK1 interacts with and phosphorylates RanBPM in vitro

Members of the casein kinase 1 (CK1) family of serine/threonine kinases are highly conserved from yeast to mammals and are involved in the regulation of various cellular processes. Specifically, the CK1 isoforms δ and ε have been shown to be involved in the regulation of proliferative processes, differentiation, circadian rhythm, as well as in the regulation of nuclear transport. In this report we show that CK1δ and ε interact with murine RanBPM in the yeast two-hybrid system (YTH) and that the putative CK1δ-interacting domains of RanBPM are located between aa 155-386 and aa 515-653. Furthermore, in mammalian cells CK1δ partially co-localizes with RanBPM and can be co-immunoprecipitated with RanBPM. In addition, CK1δ strongly phosphorylates RanBPM within aa 436-514 in vitro. The identification of the interacting and scaffolding protein RanBPM as a new substrate of CK1δ points towards a possible function for CK1δ in modulating RanBPM specific functions

The Aesthetic Responsiveness Assessment (AReA): A screening tool to assess individual differences in responsiveness to art in English and German

People differ in how they respond to artworks. Measuring such individual differences is helpful for explaining response variability and selecting particularly responsive subsamples. On the basis of a sample of items indicating relevant behavior and experience, we exploratively constructed the Aesthetic Responsiveness Assessment (AReA), a screening tool for the assessment of individual differences in responsiveness to art in English and German. Exploratory and confirmatory factor analyses suggested three first-order factors labeled aesthetic appreciation, intense aesthetic experience, and creative behavior, and a second-order factor aesthetic responsiveness. Aesthetic responsiveness was assessed in N= 781 participants from the United States and Germany, and measurement invariance analysis demonstrated full metric and partial scalar invariance across language versions. AReA scale scores yielded good reliability estimates. Validation studies confirmed expected associations between AReA scale scores and measures of related constructs, as well as continuously and retrospectively recorded responses to music, visual art, and poetry. In summary, the AReA is a promising, psychometrically evaluated instrument to assess aesthetic responsiveness built on a mixture of exploratory and confirmatory construction strategies. It can be used as a screening tool both in English and German speaking samples

Altern nachfolgende Kohorten gesünder? Selbstberichtete Erkrankungen und funktionale Gesundheit im Kohortenvergleich

Trotz eines hohen Anteils von Personen mit Mehrfacherkrankungen berichten viele der 40- bis 85-Jährigen im Jahr 2014 von einer guten funktionalen Gesundheit. Bei der Gesundheit bestehen im Jahr 2014 große Bildungsunterschiede. Der Wandel hin zu weniger selbstberichteten Erkrankungen von 1996 zu 2008 setzt sich im Jahr 2014 nicht fort. Der Anteil an Personen mit guter funktionaler Gesundheit hat zwischen 2008 und 2014 zugenommen, allerdings nur bei den über 65-Jährigen

Inclusive Education in the diversifying environments of Finland, Iceland, and the Netherlands : A multilingual systematic review

This review investigates how the scholarly fields, themes and concepts of 'inclusive education' are applied in the research and educational contexts of Finland, Iceland and the Netherlands. It identifies and outlines which thematic areas of research and sub-fields of study are referenced in each country by applying a systematic, multilingual approach. We reviewed literature in the local languages of each of these countries over the past decade, from 2007 to 2018, paying particular attention to (a) micro-level, in-depth, classroom interactions; (b) social and political contexts; and (c) social categories. Results of this review emphasise that across all three countries (a) there are similar conceptualisations of inclusive education dominated by categories of disability and special needs, and (b) there is a similar lack of attention to modes of exclusion based on social class, gender, ethnicity and geography as well as to how these can be addressed by more advanced research on inclusive education in these local spheres.Peer reviewe

Driver Gene and Novel Mutations in Asbestos-Exposed Lung Adenocarcinoma and Malignant Mesothelioma Detected by Exome Sequencing

Background Asbestos is a carcinogen linked to malignant mesothelioma (MM) and lung cancer. Some gene aberrations related to asbestos exposure are recognized, but many associated mutations remain obscure. We performed exome sequencing to determine the association of previously known mutations (driver gene mutations) with asbestos and to identify novel mutations related to asbestos exposure in lung adenocarcinoma (LAC) and MM. MethodsExome sequencing was performed on DNA from 47 tumor tissues of MM (21) and LAC (26) patients, 27 of whom had been asbestos-exposed (18 MM, 9 LAC). In addition, 9 normal lung/blood samples of LAC were sequenced. Novel mutations identified from exome data were validated by amplicon-based deep sequencing. Driver gene mutations in BRAF, EGFR, ERBB2, HRAS, KRAS, MET, NRAS, PIK3CA, STK11, and ephrin receptor genes (EPHA1-8, 10 and EPHB1-4, 6) were studied for both LAC and MM, and in BAP1, CUL1, CDKN2A, and NF2 for MM. ResultsIn asbestos-exposed MM patients, previously non-described NF2 frameshift mutation (one) and BAP1 mutations (four) were detected. Exome data mining revealed some genes potentially associated with asbestos exposure, such as MRPL1 and SDK1. BAP1 and COPG1 mutations were seen exclusively in MM. Pathogenic KRAS mutations were common in LAC patients (42 %), both in non-exposed (n = 5) and exposed patients (n = 6). Pathogenic BRAF mutations were found in two LACs. ConclusionBAP1 mutations occurred in asbestos-exposed MM. MRPL1, SDK1, SEMA5B, and INPP4A could possibly serve as candidate genes for alterations associated with asbestos exposure. KRAS mutations in LAC were not associated with asbestos exposure.Peer reviewe

Risk factors for nosocomial SARS-CoV-2 infections in patients: results from a retrospective matched case–control study in a tertiary care university center

Background: Factors contributing to the spread of SARS-CoV-2 outside the acute care hospital setting have been described in detail. However, data concerning risk factors for nosocomial SARS-CoV-2 infections in hospitalized patients remain scarce. To close this research gap and inform targeted measures for the prevention of nosocomial SARS-CoV-2 infections, we analyzed nosocomial SARS-CoV-2 cases in our hospital during a defined time period. Methods: Data on nosocomial SARS-CoV-2 infections in hospitalized patients that occurred between May 2020 and January 2021 at Charite university hospital in Berlin, Germany, were retrospectively gathered. A SARS-CoV-2 infection was considered nosocomial if the patient was admitted with a negative SARS-CoV-2 reverse transcription polymerase chain reaction test and subsequently tested positive on day five or later. As the incubation period of SARS-CoV-2 can be longer than five days, we defined a subgroup of "definite" nosocomial SARS-CoV-2 cases, with a negative test on admission and a positive test after day 10, for which we conducted a matched case-control study with a one to one ratio of cases and controls. We employed a multivariable logistic regression model to identify factors significantly increasing the likelihood of nosocomial SARS-CoV-2 infections. Results: A total of 170 patients with a nosocomial SARS-CoV-2 infection were identified. The majority of nosocomial SARS-CoV-2 patients (n = 157, 92%) had been treated at wards that reported an outbreak of nosocomial SARS-CoV-2 cases during their stay or up to 14 days later. For 76 patients with definite nosocomial SARS-CoV-2 infections, controls for the case-control study were matched. For this subgroup, the multivariable logistic regression analysis revealed documented contact to SARS-CoV-2 cases (odds ratio: 23.4 (95% confidence interval: 4.6-117.7)) and presence at a ward that experienced a SARS-CoV-2 outbreak (odds ratio: 15.9 (95% confidence interval: 2.5-100.8)) to be the principal risk factors for nosocomial SARS-CoV-2 infection. Conclusions: With known contact to SARS-CoV-2 cases and outbreak association revealed as the primary risk factors, our findings confirm known causes of SARS-CoV-2 infections and demonstrate that these also apply to the acute care hospital setting. This underscores the importance of rapidly identifying exposed patients and taking adequate preventive measures

Emerging stability of forest productivity by mixing two species buffers temperature destabilizing effect

The increasing disturbances in monocultures around the world are testimony to their instability under global change. Many studies have claimed that temporal stability of productivity increases with species richness, although the ecological fundamentals have mainly been investigated through diversity experiments. To adequately manage forest ecosystems, it is necessary to have a comprehensive understanding of the effect of mixing species on the temporal stability of productivity and the way in which it is influenced by climate conditions across large geographical areas. Here, we used a unique dataset of 261 stands combining pure and two-species mixtures of four relevant tree species over a wide range of climate conditions in Europe to examine the effect of species mixing on the level and temporal stability of productivity. Structural equation modelling was employed to further explore the direct and indirect influence of climate, overyielding, species asynchrony and additive effect (i.e. temporal stability expected from the species growth in monospecific stands) on temporal stability in mixed forests. We showed that by adding only one tree species to monocultures, the level (overyielding: +6%) and stability (temporal stability: +12%) of stand growth increased significantly. We identified the key effect of temperature on destabilizing stand growth, which may be mitigated by mixing species. We further confirmed asynchrony as the main driver of temporal stability in mixed stands, through both the additive effect and species interactions, which modify between-species asynchrony in mixtures in comparison to monocultures. Synthesis and applications. This study highlights the emergent properties associated with mixing two species, which result in resource efficient and temporally stable production systems. We reveal the negative impact of mean temperature on temporal stability of forest productivity and how the stabilizing effect of mixing two species can counterbalance this impact. The overyielding and temporal stability of growth addressed in this paper are essential for ecosystem services closely linked with the level and rhythm of forest growth. Our results underline that mixing two species can be a realistic and effective nature-based climate solution, which could contribute towards meeting EU climate target policies.Emerging stability of forest productivity by mixing two species buffers temperature destabilizing effectpublishedVersio