Entwicklung eines Themenfeldes "Digitale Welt" für den Berliner Rahmenlehrplan Sachunterricht

Die Arbeit beschäftigt sich mit Unterrichtsentwicklung im Kontext der Digitalisierung. Es werden Möglichkeiten der Angliederung von digitalisierungsbezogenen Themen in den Sachunterricht gezeigt. Eine Angliederung von digitalisierungsbezogenen Themen, die sich durch künftige gesellschaftliche Transformationsprozesse ergeben, in die bereits bestehenden und vorgeschlagenen Themen im Perspektivrahmen Sachunterricht ist möglich und konnte in der Arbeit graphisch gestützt dargestellt werden. Es konnte zudem gezeigt werden, dass sich allein durch die Aufnahme eines Themas aus der digitalen Welt in den Sachunterricht nicht nur Sachunterrichtskompetenzen, sondern auch weitere digitale Kompetenzen erwerben lassen können und somit besonders das Fach Sachunterricht mit seiner mehrperspektivischen Ausrichtung einen Beitrag zur digitalen Bildung leisten kann. Bislang gibt es kein verbindliches thematisches Curriculum für die Grundschule zum Thema "Digiale Welt". Die Arbeit widmet sich einem innovativen Feld und kann als Vorlage für weitere Forschung und Bildungsplangestaltung dienen

Retrospektiver Vergleich zur Sicherheit und Ökonomie der Widerhakennaht V-Loc mit konventionellem Wundverschluss bei körperformenden Operationen

Hintergrund der Studie ist die Einführung von Widerhakennähten 2004 zur Anwen-dung beim Wundverschluss. Über die Anwendungssicherheit und den ökonomischen Einsatz von Widerhakennähten liegen gegensätzliche Ergebnisse vor. In der vorliegenden Studie sollte erstens überprüft werden, inwiefern Widerhakennähte einen medizinischen Nutzen aufweisen und inwiefern sie zweitens einen ökonomisch effizienten Einsatz ermöglichen. Dabei wurden Widerhakennähte mit glattwandigem Nahtmaterial beim Wundverschluss von körperformenden Eingriffen verglichen. Aus der Abteilung für plastische und ästhetische Chirurgie am Universitätsklinikum Bonn wurden retrospektiv alle Patienten erfasst, bei denen vom 01.01.2008 bis 16.3.2010 ein körperformender Eingriff stattfand. Insgesamt 146 Eingriffe wurden vom selben Operateur durchgeführt. Die primären Endpunkte waren folgende postoperative Wundkomplikationen: Wunddehiszenz, Fadenexposition, Nekrosen oder sekundäre Wundheilung und Narbenveränderungen. Des Weiteren wurde zur Betrachtung des ökonomischen Faktors die Schnitt-Naht-Zeit der Eingriffe verglichen. Die Ergebnisse der V-Loc Gruppe zeigten im Vergleich zur Non-V-Loc Gruppe ein vergleichbares Wundkomplikationsprofil hinsichtlich o.g. Wundkomplikationen. Im Zusammenhang mit aktuellen randomisiert kontrollierten Studien konnten wir aufzeigen, dass Widerhakennähte nicht zu mehr Wundkomplikationen führen. Dieses Ergebnis ist durch die Limitation der Fallzahl nicht signifikant, bestätigt jedoch auch den subjektiven Erfahrungswert des Operateurs. Der medizinische Nutzen von Widerhakennähten ist also nach den vorliegenden Ergebnissen im Vergleich zu glattwandigem Nahtmaterial als gleichwertig anzusehen. Die Analyse der Schnitt-Naht-Zeit ergab eine signifikante Zeitersparnis von 30,48 Minuten im Rahmen von Abdominoplastiken und eine Zeitersparnis von 19,77 Minuten bei Mammareduktionen. Parallel zu Studien höherer Evidenzlevel konnte auch in der vorliegenden Studie eine Zeitersparnis beim Einsatz V-Loc Faden herausgestellt werden. Vermutlich sind hier die der Wegfall von Knoten, der sofortige straffe Sitz im Gewebe und die Möglichkeit, alleine – ohne dritte Hand – nähen zu können, wesentliche Einflussfaktoren für die Zeitersparnis

Targeted inhibition of Gq signaling induces airway relaxation in mouse models of asthma

Obstructive lung diseases are common causes of disability and death worldwide. A hallmark feature is aberrant activation of Gq protein–dependent signaling cascades. Currently, drugs targeting single G protein (heterotrimeric guanine nucleotide–binding protein)–coupled receptors (GPCRs) are used to reduce airway tone. However, therapeutic efficacy is often limited, because various GPCRs contribute to bronchoconstriction, and chronic exposure to receptor-activating medications results in desensitization. We therefore hypothesized that pharmacological Gq inhibition could serve as a central mechanism to achieve efficient therapeutic bronchorelaxation. We found that the compound FR900359 (FR), a membrane-permeable inhibitor of Gq, was effective in silencing Gq signaling in murine and human airway smooth muscle cells. Moreover, FR both prevented bronchoconstrictor responses and triggered sustained airway relaxation in mouse, pig, and human airway tissue ex vivo. Inhalation of FR in healthy wild-type mice resulted in high local concentrations of the compound in the lungs and prevented airway constriction without acute effects on blood pressure and heart rate. FR administration also protected against airway hyperreactivity in murine models of allergen sensitization using ovalbumin and house dust mite as allergens. Our findings establish FR as a selective Gq inhibitor when applied locally to the airways of mice in vivo and suggest that pharmacological blockade of Gq proteins may be a useful therapeutic strategy to achieve bronchorelaxation in asthmatic lung disease

Natural Occurrence of 2′,5′-Linked Heteronucleotides in Marine Sponges

2′,5′-oligoadenylate synthetases (OAS) as a component of mammalian interferon-induced antiviral enzymatic system catalyze the oligomerization of cellular ATP into 2′,5′-linked oligoadenylates (2-5A). Though vertebrate OASs have been characterized as 2′-nucleotidyl transferases under in vitro conditions, the natural occurrence of 2′,5′-oligonucleotides other than 2-5A has never been demonstrated. Here we have demonstrated that OASs from the marine sponges Thenea muricata and Chondrilla nucula are able to catalyze in vivo synthesis of 2-5A as well as the synthesis of a series 2′,5′-linked heteronucleotides which accompanied high levels of 2′,5′-diadenylates. In dephosphorylated perchloric acid extracts of the sponges, these heteronucleotides were identified as A2′p5′G, A2′ p5′U, A2′p5′C, G2′p5′A and G2′ p5′U. The natural occurrence of 2′-adenylated NAD+ was also detected. In vitro assays demonstrated that besides ATP, GTP was a good substrate for the sponge OAS, especially for OAS from C. nucula. Pyrimidine nucleotides UTP and CTP were also used as substrates for oligomerization, giving 2′,5′-linked homo-oligomers. These data refer to the substrate specificity of sponge OASs that is remarkably different from that of vertebrate OASs. Further studies of OASs from sponges may help to elucidate evolutionary and functional aspects of OASs as proteins of the nucleotidyltransferase family

Aufbruch ins sozialistische Paradies – Propagandaplakate der frühen Volksrepublik China:

Die 1950er Jahre waren eine Zeit der Kampagnen zur Industrialisierung, Modernisierung und der Verwirklichung der sozialistischen Vision. Was Realität werden sollte, zeigen die Propagandaplakate. Die Studierenden des Seminars Plakatkunst und Propaganda in der frühen Volksrepublik China haben beispielhafte Exemplare der groß angelegten Kampagnen aus der Plakatsammlung des Amsterdamer International Institute of Social History ausgewählt. Diese haben sie im Hinblick auf ihren historischen Kontext untersucht und die Ergebnisse auf zusätzlichen Infoplakaten zusammengefasst. Der Katalog zeigt die Exponate und vermittelt die entsprechenden zeit- und kunsthistorischen Hintergründe

HLA-DPA1*02:01~B1*01:01 is a risk haplotype for primary sclerosing cholangitis mediating activation of NKp44+ NK cells

Objective Primary sclerosing cholangitis (PSC) is characterised by bile duct strictures and progressive liver disease, eventually requiring liver transplantation. Although the pathogenesis of PSC remains incompletely understood, strong associations with HLA-class II haplotypes have been described. As specific HLA-DP molecules can bind the activating NK-cell receptor NKp44, we investigated the role of HLA-DP/NKp44-interactions in PSC. Design Liver tissue, intrahepatic and peripheral blood lymphocytes of individuals with PSC and control individuals were characterised using flow cytometry, immunohistochemical and immunofluorescence analyses. HLA-DPA1 and HLA-DPB1 imputation and association analyses were performed in 3408 individuals with PSC and 34 213 controls. NK cell activation on NKp44/HLA-DP interactions was assessed in vitro using plate-bound HLA-DP molecules and HLA-DPB wildtype versus knock-out human cholangiocyte organoids. Results NKp44+NK cells were enriched in livers, and intrahepatic bile ducts of individuals with PSC showed higher expression of HLA-DP. HLA-DP haplotype analysis revealed a highly elevated PSC risk for HLA-DPA1*02:01~B1*01:01 (OR 1.99, p=6.7×10-50). Primary NKp44+NK cells exhibited significantly higher degranulation in response to plate-bound HLA-DPA1*02:01-DPB1*01:01 compared with control HLA-DP molecules, which were inhibited by anti-NKp44-blocking. Human cholangiocyte organoids expressing HLA-DPA1*02:01-DPB1*01:01 after IFN-γ-exposure demonstrated significantly increased binding to NKp44-Fc constructs compared with unstimulated controls. Importantly, HLA-DPA1*02:01-DPB1*01:01-expressing organoids increased degranulation of NKp44+NK cells compared with HLA-DPB1-KO organoids. Conclusion Our studies identify a novel PSC risk haplotype HLA-DP A1*02:01~DPB1*01:01 and provide clinical and functional data implicating NKp44+NK cells that recognise HLA-DPA1*02:01-DPB1*01:01 expressed on cholangiocytes in PSC pathogenesis

Parent-of-origin-specific allelic associations among 106 genomic loci for age at menarche.

Age at menarche is a marker of timing of puberty in females. It varies widely between individuals, is a heritable trait and is associated with risks for obesity, type 2 diabetes, cardiovascular disease, breast cancer and all-cause mortality. Studies of rare human disorders of puberty and animal models point to a complex hypothalamic-pituitary-hormonal regulation, but the mechanisms that determine pubertal timing and underlie its links to disease risk remain unclear. Here, using genome-wide and custom-genotyping arrays in up to 182,416 women of European descent from 57 studies, we found robust evidence (P < 5 × 10(-8)) for 123 signals at 106 genomic loci associated with age at menarche. Many loci were associated with other pubertal traits in both sexes, and there was substantial overlap with genes implicated in body mass index and various diseases, including rare disorders of puberty. Menarche signals were enriched in imprinted regions, with three loci (DLK1-WDR25, MKRN3-MAGEL2 and KCNK9) demonstrating parent-of-origin-specific associations concordant with known parental expression patterns. Pathway analyses implicated nuclear hormone receptors, particularly retinoic acid and γ-aminobutyric acid-B2 receptor signalling, among novel mechanisms that regulate pubertal timing in humans. Our findings suggest a genetic architecture involving at least hundreds of common variants in the coordinated timing of the pubertal transition

Hemolysis Is Associated with Low Reticulocyte Production Index and Predicts Blood Transfusion in Severe Malarial Anemia

Background: Falciparum Malaria, an infectious disease caused by the apicomplexan parasite Plasmodium falciparum, is among the leading causes of death and morbidity attributable to infectious diseases worldwide. In Gabon, Central Africa, one out of four inpatients have severe malarial anemia (SMA), a life-threatening complication if left untreated. Emerging drug resistant parasites might aggravate the situation. This case control study investigates biomarkers of enhanced hemolysis in hospitalized children with either SMA or mild malaria (MM). Methods and Findings: Ninety-one children were included, thereof 39 SMA patients. Strict inclusion criteria were chosen to exclude other causes of anemia. At diagnosis, erythrophagocytosis (a direct marker for extravascular hemolysis, EVH) was enhanced in SMA compared to MM patients (5.0 arbitrary units (AU) (interquartile range (IR): 2.2–9.6) vs. 2.1 AU (IR: 1.3–3.9), p<0.01). Furthermore, indirect markers for EVH, (i.e. serum neopterin levels, spleen size enlargement and monocyte pigment) were significantly increased in SMA patients. Markers for erythrocyte ageing, such as CD35 (complement receptor 1), CD55 (decay acceleration factor) and phosphatidylserine exposure (annexin-V-binding) were investigated by flow cytometry. In SMA patients, levels of CD35 and CD55 on the red blood cell surface were decreased and erythrocyte removal markers were increased when compared to MM or reconvalescent patients. Additionally, intravascular hemolysis (IVH) was quantified using several indirect markers (LDH, alpha-HBDH, haptoglobin and hemopexin), which all showed elevated IVH in SMA. The presence of both IVH and EVH predicted the need for blood transfusion during antimalarial treatment (odds ratio 61.5, 95% confidence interval (CI): 8.9–427). Interestingly, this subpopulation is characterized by a significantly lowered reticulocyte production index (RPI, p<0.05). Conclusions: Our results show the multifactorial pathophysiology of SMA, whereby EVH and IVH play a particularly important role. We propose a model where removal of infected and non-infected erythrocytes of all ages (including reticulocytes) by EVH and IVH is a main mechanism of SMA. Further studies are underway to investigate the mechanism and extent of reticulocyte removal to identify possible interventions to reduce the risk of SMA development