Overlapping activator sequences determined for two oppositely oriented promoters in halophilic Archaea

Transcription of the genomic region involved in gas vesicle formation in Halobacterium salinarum (p-vac) and Haloferax mediterranei (mc-vac) is driven by two divergent promoters, PA and PD, separated by only 35 nt. Both promoters are activated by the transcription activator GvpE which in the case of PmcA requires a 20-nt sequence (UAS) consisting of two conserved 8-nt sequence portions located upstream of BRE. Here, we determined the two UAS elements in the promoter region of p-vac by scanning mutageneses using constructs containing PpD (without PpA) fused to the bgaH reporter gene encoding an enzyme with β-galactosidase activity, or the dual reporter construct pApD with PpD fused to bgaH and PpA to an altered version of gvpA. The two UAS elements found exhibited a similar extension and distance to BRE as previously determined for the UAS in PmcA. Their distal 8-nt portions almost completely overlapped in the centre of PpD–PpA, and mutations in this region negatively affected the GvpE-mediated activation of both promoters. Any alteration of the distance between BRE and UAS resulted in the loss of the GvpE activation, as did a complete substitution of the proximal 8-nt portion, underlining that a close location of UAS and BRE was very important

Medienpraktiken: situieren, erforschen, reflektieren; eine Einleitung

Mit dem Fokus auf Medienpraktiken bündelt dieses Heft aktuelle Positionen zur empirischen Erforschung von Medien. Die Beiträge gehen davon aus, dass Medien erst durch ihren Gebrauch zu Medien werden. Medienpraktiken zu erforschen, bedeutet jedoch nicht nur herauszufinden, was Menschen mit Medien tun, sondern auch was Medien mit Menschen machen. Diese für die Medienpraktikenforschung zentrale Einsicht lösen die interdisziplinären Beiträge des Bandes ein, indem sie aus den jeweiligen Positionen und Konstellationen verdeutlichen, wie Medien und Praktiken sich gegenseitig bedingen. Medienpraktikenforschung erfordert erstens, medienpraktische Phänomene in einem hohen Detailgrad zu fassen, um die Relation der beteiligten menschlichen und medialen Akteure zueinander in situ und in actu nachzuvollziehen. Erst durch die analytische Durchdringung dieser situativen Vollzugsmomente lässt sich zweitens der Status von Medien klären: was durch Praktiken zu einem Medium wird und wie die Praktiken unter Berücksichtigung der an ihnen konstitutiv beteiligten Medien beschaffen sind. Dadurch lassen sich ebenso übersituative Bezüge zur Praxis herstellen, durch die die Praktiken zur situativen Entfaltung kommen. Drittens muss dabei berücksichtigt werden, inwiefern die eigenen Medienpraktiken der Erforschung in ihren jeweiligen situativen Stadien die (Analyse der) Medienpraktik zurichten. Die Beiträge dieses Bandes lösen diese Forderungen in unterschiedlicher Gewichtung ein. Sie befassen sich aus medienethnologischer, kultursoziologischer, literaturwissenschaftlicher, historischer, soziologischer und medienwissenschaftlicher Perspektive damit, was jeweils als situierte Medienpraktik verstanden werden kann. Gemeinsam ist damit allen Beiträgen, dass sie erst aus ihren jeweiligen Untersuchungen und Perspektiven heraus bestimmen, was genau als Medienpraktik und Medien, die in ihnen zum Tragen kommen, gefasst werden kann

The local soft tissue status and the prediction of local complications following fractures of the ankle region

INTRODUCTION Well-known risk factors (RF) for soft tissue complications following surgical treatment of fracture of the ankle region include diabetes, smoking, and the local soft tissue status. A weighted analysis might provide a risk profile that guides the surgical treatment strategy. The aim of this meta-analysis was to provide a risk profile for soft tissue complications following closed fractures of the ankle region. METHODS This review provides a meta-analysis of studies that investigate potential risk factors for complications in fractures of the ankle region. INCLUSION CRITERIA Original articles that were published between 2000 and 2020 in English or German language that calculated odds ratios (OR) of RF for soft tissue complications. Further, this study only includes articles that investigated fractures of the ankle region including pilon fracture, calcaneal fractures, and fractures of the malleoli. This study excluded articles that provide exploratory analyses, narrative reviews, and case reports. RF were stratified as patient specific systemic RF (PSS), patient specific local RF (PSL), and non-patient specific RF (NPS). PSS RF includes comorbidities, American society of anaesthesiology (ASA), requirement of medication, additional injuries, and smoking or substance abuse. PSL RF includes soft tissue status, wounds, and associated complications. NPS RF includes duration of surgery, staged procedure, or time to definitive surgery. Random effect (RE) models were utilized to summarize the effect measure (OR) for each group or specific RF. RESULTS Out of 1352 unique articles, 34 were included for quantitative analyses. Out of 370 complications, the most commonly assessed RF were comorbidities (34.6%). Local soft tissue status accounted for 7.5% of all complications. The overall rate for complication was 10.9% (standard deviation, SD 8.7%). PSS RF had an OR of 1.04 (95%CI 1.01 to 1.06, p = 0.006), PSL an OR of 1.79 (95% 1.28 to 2.49, p = 0.0006), and NPS RF an OR of 1.01 (95%CI 0.97 to 1.05, p = 0.595). Additional injuries did not predict complications (OR 1.23, 95%CI 0.44 to 3.45, p = 0.516). The most predictive RF were open fracture (OR 3.47, 95%CI 1.64 to 7.34, p < 0.001), followed by local tissue damage (OR 3.05, 95%CI 1.23 to 40.92, p = 0.04), and diabetes (OR 2.3, 95%CI 1.1 to 4.79, p = 0.26). CONCLUSION Among all RFs for regional soft tissue complications, the most predictive is the local soft tissue status, while additional injuries or NPS RF were less predictive. The soft tissue damage can be quantified and outweighs the cofactors described in previous publications. The soft tissue status appears to have a more important role in the decision making of the treatment strategy when compared with comorbidities such as diabetes

Comparing Attitudes to Containment Measures of Patients, Health Care Professionals and Next of Kin

Background: In clinical psychiatric practice, health care professionals (HCP) must decide in exceptional circumstances after the weighing of interests, which, if any, containment measures including coercion are to be used. Here, the risk for patients, staff, and third parties, in addition to therapeutic considerations, factor into the decision. Patients' preference and the inclusion of relatives in these decisions are important; therefore, an understanding of how patients and next of kin (NOK) experience different coercive measures is crucial for clinical decision making. The aim of this study is to compare how patients, HCP, and NOK assess commonly used coercive measures.Methods: A sample of 435 patients, 372 HCP, and 230 NOK completed the Attitudes to Containment Measures Questionnaire (ACMQ). This standardized self-rating questionnaire assessed the degree of acceptance or rejection of 11 coercive measures.Results: In general, HCPs rated the coercive measures as more acceptable than did NOK and patients. The largest discrepancy in the ratings was found in regard to the application of coercive intramuscular injection of medication (effect size: 1.0 HCP vs. patients). However, the ratings by NOK were significantly closer to the patients' ratings compared to patients and HCP. The only exception was the acceptance of treatment in a closed acute psychiatric ward, which was deemed significantly more acceptable by NOK than by patients. Also, patients who had experienced coercive measures themselves more strongly refused other measures.Conclusion: Patients most firmly rejected intramuscular injections, and the authors agree that these should only be used with reservation considering a high threshold. This knowledge about the discrepancy of the ratings should therefore be incorporated into professional training of HCP

Development of a Framework for Scaling Up Community-Based Health Promotion: A Best Fit Framework Synthesis

Community-based health promotion with a focus on people with social disadvantages is essential to address persistently existing health inequities. However, achieving an impact on public health requires scaling up such approaches beyond manifold funded pilot projects. The aim of this qualitative review is to provide an overview of scaling-up frameworks in health promotion and to identify key components for scaling up community-based health promotion. First, we conducted a systematic search for scaling-up frameworks for health promotion in PubMed, CINAHL, Scopus, Web of Science, PsycInfo, and SportDiscus. Based on the included frameworks, we created an a priori framework. Second, we searched for primary research studies in the same databases that reported scaling-up processes of community-based health promotion. We coded the data using the a priori framework. From 80 articles, a total of 12 frameworks were eligible, and 5 were included for data extraction. The analysis yielded 10 a priori defined key components: “innovation characteristics”; “clarify and coordinate roles and responsibilities”; “build up skills, knowledge, and capacity”; “mobilize and sustain resources”; “initiate and maintain regular communication”; “plan, conduct, and apply assessment, monitoring, and evaluation”; “develop political commitment and advocacy”; “build and foster collaboration”; “encourage participation and ownership”; and “plan and follow strategic approaches”. We further identified 113 primary research studies; 10 were eligible. No new key components were found, but all a priori defined key components were supported by the studies. Ten key components for scaling up community-based health promotion represent the final framework. We further identified “encourage participation and ownership” as a crucial component regarding health equity

Short-term response of deep-water benthic megafauna to installation of a pipeline over a depth gradient on the Angolan Slope

Large structures are introduced into deep-water marine environments by several industrial activities, including hydrocarbon exploitation. Anthropogenic structures can alter ecosystem structure and functioning in many marine ecosystems but the responses on continental margins are poorly known. Here, we investigate the short-term response of benthic megafauna to the installation of a 56 km-long 30 cm diameter pipeline on the Angolan Margin (Block 31) from 700 to 1800 m water depth using remotely operated vehicle imagery. Clear depth-related patterns exist in the density, diversity and community structure of megafauna observed in 2013 prior to pipeline installation. These patterns are altered in a subsequent survey in 2014, three-months after pipeline installation. Significant increases in density, particularly in mid-slope regions are observed. Diversity is generally, but not consistently, enhanced, particularly in the shallower areas in 2014. Clear changes are noted in community structure between years. These changes are primarily caused by increases in the abundance of echinoderms, particularly the echinoid Phormosoma sp. indet. There was no evidence of colonisation of the pipeline in three months by visible fauna. The few large anemones observed attached to the pipe may be able to move as adults. The pipeline appeared to trap organic material and anthropogenic litter, and may enhance available food resources locally as well as providing hard substratum. These results indicate complex and ecosystem-dependent responses to structure installation and caution against simplistic approaches to environmental management

Population-based physical activity promotion with a focus on health equity: a review of reviews

Background The extent to which people are physically active is dependent upon social gradients. Numerous studies have shown that especially people with social disadvantages do not meet the physical activity (PA) recommendations. A promising strategy to alleviate this issue are approaches that promote PA in the general population. In addition, several researchers have raised concerns that population-based health interventions may increase health inequities. The aim of the current review of reviews was therefore to identify successful population-based PA promotion approaches with a particular focus on health equity. Methods Six electronic databases were examined for systematic reviews on population-based PA promotion for the period 2015 to 2021. A reference list and grey literature search were also conducted. Two independent reviewers used inclusion/exclusion criteria to screen titles and abstracts of the potentially relevant literature and conducted a quality assessment for each identified review. All included reviews of population-based approaches for PA promotion with a focus on disadvantaged populations and/or health equity were narratively summarized. Results Our search resulted in 4,411 hits. After a systematic review process, six reviews met the inclusion criteria and were included after they were all rated as high quality. We identified that mass-media campaigns, point-of-decision prompts, environmental approaches, policy approaches, and community-based multi-component approaches can promote PA in the general population. Across populations with social disadvantages mass-media campaigns, point-of-decision prompts and policy approaches are likely to be effective as long as they are tailored. Regarding environmental approaches, the results are inconsistent. None of the reviews on community-based multi-component approaches provided evidence on health equity. Conclusion There are several effective approaches to promote PA in the general population but evidence regarding health equity is still sparse. Future studies should therefore pay more attention to this missing focus. Furthermore, there is a lack of evidence regarding the type of tailoring and the long-term impact of population-based approaches to PA promotion. However, this requires appropriate funding programmes, complex study designs and evaluation methods.Hintergrund Das Ausmaß in dem Menschen körperlich aktiv sind hängt vom sozialen Gradienten ab. Zahlreiche Studien haben gezeigt, dass insbesondere Menschen mit sozialer Benachteiligung die Empfehlungen für Bewegung nicht umsetzen. Bevölkerungsbezogene Maßnahmen sind geeignet, um alle Menschen zu erreichen, gleichzeitig gibt es wissenschaftliche Hinweise dafür, dass dadurch gesundheitliche Ungleichheiten verstärkt werden können. Ziel dieses Umbrella Reviews war es daher, wirksame bevölkerungsbezogene Ansätze zur Förderung der körperlichen Aktivität mit besonderem Fokus auf gesundheitliche Chancengleichheit zu identifizieren. Methoden Mittels sechs elektronischen Wissenschaftsdatenbanken wurde für den Zeitraum von 2015 bis 2021 nach systematischen Reviews zur bevölkerungsbezogenen Bewegungsförderung gesucht. Darüber hinaus wurde auch eine Handsuche in den Referenzlisten gefundener Artikel sowie eine Suche nach grauer Literatur durchgeführt. Zwei unabhängige Gutachter:innen überprüften anhand von Ein- und Ausschlusskriterien die Titel und Abstracts der potenziell relevanten Literatur und führten für jedes eingeschlossene Review eine Qualitätsbewertung durch. Die Ergebnisse der identifizieren Übersichtsarbeiten zu bevölkerungsbezogenen Ansätzen zur Bewegungsförderung mit Fokus auf Menschen mit sozialer Benachteiligung und/oder gesundheitliche Chancengleichheit wurden narrativ zusammengefasst. Ergebnisse Insgesamt wurden 4.411 Reviews identifiziert. Nach einer systematischen Überprüfung, erfüllten sechs Reviews die Einschlusskriterien und wurden eingeschlossen, nachdem sie alle als qualitativ hochwertig eingestuft worden waren. Massenmediale Kampagnen, motivationale Entscheidungshilfen, umweltbezogene Ansätze, politikbezogene Ansätze und gemeindebasierte Mehrkomponentenansätze können das Bewegungsverhalten in der Allgemeinbevölkerung fördern. Für Bevölkerungsgruppen mit sozialer Benachteiligung liegt Evidenz vor, dass massenmediale Kampagnen, motivationale Entscheidungshilfen sowie politikbezogene Ansätze wirksam sind, sofern diese bedarfsgerecht (tailored) angepasst werden. Über umweltbezogene Ansätze wurden widersprüchliche Ergebnisse berichtet. Zu gemeindebasierten Mehrkomponentenansätzen fehlen bislang Ergebnisse hinsichtlich der Verbesserung von gesundheitlicher Chancengleichheit. Schlussfolgerung Es wurden mehrere wirksame Ansätze zur Bewegungsförderung der Allgemeinbevölkerung identifiziert, jedoch sind Erkenntnisse über den Einfluss auf die gesundheitliche Chancengleichheit gering. Künftige Studien sollten daher diesem fehlenden Fokus mehr Aufmerksamkeit widmen. Des Weiteren mangelt es an Wissen über die Art der bedarfsgerechten Anpassung (Tailoring) sowie die langfristigen Auswirkungen bevölkerungsbezogener Ansätze zur Bewegungsförderung. Dies erfordert geeignete Finanzierungsprogramme, komplexe Studiendesigns und Evalierungsmethoden

Inactivation of the tyrosine phosphatase SHP-2 drives vascular dysfunction in sepsis

Background: Sepsis, the most severe form of infection, involves endothelial dysfunction which contributes to organ failure. To improve therapeutic prospects, elucidation of molecular mechanisms underlying endothelial vascular failure is of essence. Methods: Polymicrobial contamination induced sepsis mouse model and primary endothelial cells incubated with sepsis serum were used to study SHP-2 in sepsis-induced endothelial inflammation. SHP-2 activity was assessed by dephosphorylation of pNPP, ROS production was measured by DCF oxidation and protein interactions were assessed by proximity ligation assay. Vascular inflammation was studied in the mouse cremaster model and in an in vitro flow assay. Findings: We identified ROS-dependent inactivation of the tyrosine phosphatase SHP-2 to be decisive for endothelial activation in sepsis. Using in vivo and in vitro sepsis models, we observed a significant reduction of endothelial SHP-2 activity, accompanied by enhanced adhesion molecule expression. The impaired SHP-2 activity was restored by ROS inhibitors and an IL-1 receptor antagonist. SHP-2 activity inversely correlated with the adhesive phenotype of endothelial cells exposed to IL-1β as well as sepsis serum via p38 MAPK and NF-κB. In vivo, SHP-2 inhibition accelerated IL-1β-induced leukocyte adhesion, extravasation and vascular permeability. Mechanistically, SHP-2 directly interacts with the IL-1R1 adaptor protein MyD88 via its tyrosine 257, resulting in reduced binding of p85/PI3-K to MyD88. Interpretation: Our data show that SHP-2 inactivation by ROS in sepsis releases a protective break, resulting in endothelial activation. Fund: German Research Foundation, LMU Mentoring excellence and FöFoLe Programme, Verein zur Förderung von Wissenschaft und Forschung, German Ministry of Education and Research. Keywords: Endothelial cells, IL-1β, MyD88, ROS, SHP-2, Sepsi

Genome-Wide DNA Methylation Maps in Follicular Lymphoma Cells Determined by Methylation-Enriched Bisulfite Sequencing

BACKGROUND: Follicular lymphoma (FL) is a form of non-Hodgkin's lymphoma (NHL) that arises from germinal center (GC) B-cells. Despite the significant advances in immunotherapy, FL is still not curable. Beyond transcriptional profiling and genomics datasets, there currently is no epigenome-scale dataset or integrative biology approach that can adequately model this disease and therefore identify novel mechanisms and targets for successful prevention and treatment of FL. METHODOLOGY/PRINCIPAL FINDINGS: We performed methylation-enriched genome-wide bisulfite sequencing of FL cells and normal CD19(+) B-cells using 454 sequencing technology. The methylated DNA fragments were enriched with methyl-binding proteins, treated with bisulfite, and sequenced using the Roche-454 GS FLX sequencer. The total number of bases covered in the human genome was 18.2 and 49.3 million including 726,003 and 1.3 million CpGs in FL and CD19(+) B-cells, respectively. 11,971 and 7,882 methylated regions of interest (MRIs) were identified respectively. The genome-wide distribution of these MRIs displayed significant differences between FL and normal B-cells. A reverse trend in the distribution of MRIs between the promoter and the gene body was observed in FL and CD19(+) B-cells. The MRIs identified in FL cells also correlated well with transcriptomic data and ChIP-on-Chip analyses of genome-wide histone modifications such as tri-methyl-H3K27, and tri-methyl-H3K4, indicating a concerted epigenetic alteration in FL cells. CONCLUSIONS/SIGNIFICANCE: This study is the first to provide a large scale and comprehensive analysis of the DNA methylation sequence composition and distribution in the FL epigenome. These integrated approaches have led to the discovery of novel and frequent targets of aberrant epigenetic alterations. The genome-wide bisulfite sequencing approach developed here can be a useful tool for profiling DNA methylation in clinical samples

Recommendations for the standardisation of open taxonomic nomenclature for image-based identifications

This paper recommends best practice for the use of open nomenclature (ON) signs applicable to image-based faunal analyses. It is one of numerous initiatives to improve biodiversity data input to improve the reliability of biological datasets and their utility in informing policy and management. Image-based faunal analyses are increasingly common but have limitations in the level of taxonomic precision that can be achieved, which varies among groups and imaging methods. This is particularly critical for deep-sea studies owing to the difficulties in reaching confident species-level identifications of unknown taxa. ON signs indicate a standard level of identification and improve clarity, precision and comparability of biodiversity data. Here we provide examples of recommended usage of these terms for input to online databases and preparation of morphospecies catalogues. Because the processes of identification differ when working with physical specimens and with images of the taxa, we build upon previously provided recommendations for specific use with image-based identifications