Human SP-A- genes, structure, function- and lung diseases

Surfactant associated protein-A (SP-A) is the most abundant pulmonary surfactant protein and belongs to the family of innate host defence proteins termed collectins. The aim of the study was to elucidate the role of SP-A in human lung disease. This study was designed to analyze the relation between genetics, structure and function of SP-A in a CF, chronic bronchitis and asthma and healthy control population ex vivo. Beginning with the analysis of SP-A oligomeric forms, there were no correlations between serum and BAL SP-A distribution forms. The forms showed only a significantly different distribution comparing serum samples from bronchitis patients and controls. In serum and BAL of CF patients the forms containing the first peak were correlated with a better lung function (Fev1 (% pred.)age20). Also higher relative SP-A amount in the first peak is associated with a milder lung disease and a better course of lung disease. Additionally, SP-A self-agglutination is dependent on the amount of particular SP-A oligomers present in a sample, i.e. the relative strength of SP-A molecular forms in a sample. All SP-A structures self-agglutinate in serum better than in BAL in samples of the patients groups while in control samples BAL and serum SP-A showed the same abilities. There was also a difference between the self-agglutination ability of BAL samples from CF, Bro and control derived SP-A, but none in serum. SP-A from control BAL agglutinated better than from bronchitis BAL and this better than from CF BAL. These results are also supported by the fact that a better agglutination ability of SP-A was significantly associated with lung function. Therefore the degree of the presence of active oligomeric forms within a BAL or serum sample seems to be important for a better lung function outcome. The SP-A oligomerization is associated with one SFTPA1 rs1136451 and one SFTPA2 SNP rs17881665 which are coupled, while the mutated allele seems to cause a lack of complex oligomers. The wildtype alleles of the SP-A2 SNPs rs1965708 and rs1975006 were associated with CF compared to the bronchitis and control group. There was a significant association between the mean ∆ Fev1 (%pred.) / year and V50L a SNP in the SFTPA1 gene (p = 0.0038) while the mutated allele was associated with a worse course of lung disease. The SP-A BAL level was significantly associated with the SP-A1 SNP rs1136451 (p = 0.002) and the SP-A2 SNP rs17881665r (p = 0.002). The SP-A serum level was significantly associated with SP-A1 N9T (p = 0.028). In addition in the CF study population there was a significant association between the SP-A level in BAL and the Fev1 (% pred.) estimated for age 20 (p = 0.009). The higher the SP-A levels were in BAL the bigger were the values of the Fev1 (% pred.) estimated for age 20. There was no correlation between the SP-A BAL or serum level and any other clinical characteristic such as BMI, age, gender, IgG or IgE in serum. In conclusion, these results indicate a very important role for SP-A in human lung immunity. Future areas for clinical research include disease specific SP-A expression pattern and their functional consequences, the differential roles of SP-A1 and SP-A2 in human lung diseases, and therapeutic approaches to correct altered SP-A levels

When the Queers Come Sweeping Down the Plain: An English Educators' Guide to Serving as LGBTQ Allies in American Schools

The purpose of this inquiry, located in Oklahoma, is to create a public document that can guide U.S. professional educators as designers and teachers of middle and high school English curricula that welcome queer identities unique to one another based on race, class, ideology, sexuality, and gender expression. This work is focused on lesbian, gay, bisexual, transgender, queer, and questioning youth both in and out of school, who are constantly navigating their identities in environments often indifferent or hostile to their very existence. This educators’ guide describes the devastating and harsh realities of their growing and living in a world that favors heterosexuality and cisgendered identity. It situates these problems in the connections among schools, homes, and their surrounding societies and communities. When discussing LGBTQ issues, especially in red states like Oklahoma, very real considerations have to be given to political and religious beliefs that constrain how curriculum is developed, and how students of vulnerable populations are educated. Finally, after grappling with concerns of faith and morality, and the overall importance of children’s general wellbeing and educational development, this work suggests how middle and high school English educators can rethink their curriculum to begin creating a space that includes LGBTQ identities, and allows straight and cisgendered students also to tackle their own assumptions on gender expression and sexual biases. Teachers, teacher educators, and other educational influences, such as librarians, play important parts as LGBTQ allies and as advocates for their students and their overall development as future members of a shared civic society. This work proposes that such teachers can become leaders within their schools, and begin to create environments that are welcome to a variety of personal identities both within their individual classrooms and also within the school community as a whole. Such teacher leaders must pursue individual research and personal learning to fulfill their roles as LGBTQ allies and advocates

Rente mit 67 - Folgen für den Arbeitsmarkt?

Welche Anforderungen an den Arbeitsmarkt sind mit der schrittweisen Anhebung der Regelaltersgrenze in der gesetzlichen Rentenversicherung auf 67 Jahre verbunden? Heinrich Tiemann, Bundesministerium für Arbeit und Soziales, unterstreicht, dass nicht nur die Bundesregierung und die Verantwortlichen in den Ländern und Kommunen, sondern auch die Sozialpartner auf betrieblicher und überbetrieblicher Ebene gefordert sind. Stefanie Wahl, Institut für Wirtschaft und Gesellschaft, Bonn, sieht die größte Anpassungslast bei den Unternehmen und Arbeitnehmern: "Erstere müssen künftig Innovationen und Produktivität, sprich: ihre internationale Wettbewerbsfähigkeit mit den vorhandenen älter werdenden Mitarbeitern erreichen. Letztere müssen alles daran setzen, dass sie die fachlichen und physisch-psychischen Anforderungen bis zum Erreichen der Altersgrenze erfüllen." Alexander Gunkel, Bundesvereinigung der Deutschen Arbeitgeberverbände, fordert ergänzend beschäftigungsfördernde Reformen, insbesondere im Bereich der Bildung. Und für Reinhold Schnabel, Universität Duisburg-Essen, ist es entscheidend, die Qualifikation der Erwerbstätigen zu sichern.Altersgrenze, Arbeitsmarkt, Gesetzliche Rentenversicherung, Ältere Arbeitskräfte, Beschäftigung, Deutschland

Transport and kinase activities of CbrA of Pseudomonas putida KT2440

The CbrA/CbrB system is a two-component signal transduction system known to participate in the regulation of the cellular carbon/nitrogen balance and to play a central role in carbon catabolite repression in Pseudomonas species. CbrA is composed of a domain with similarity to proteins of the solute/sodium symporter family (SLC5) and domains typically found in bacterial sensor kinases. Here, the functional properties of the sensor kinase CbrA and its domains are analyzed at the molecular level using the system of the soil bacterium P. putida KT2440 as a model. It is demonstrated that CbrA can bind and transport L-histidine. Transport is specific for L-histidine and probably driven by an electrochemical proton gradient. The kinase domain is not required for L-histidine uptake by the SLC5 domain of CbrA, and has no significant impact on transport kinetics. Furthermore, it is shown that the histidine kinase can autophosphorylate and transfer the phosphoryl group to the response regulator CbrB. The SLC5 domain is not essential for these activities but appears to modulate the autokinase activity. A phosphatase activity of CbrA is not detected. None of the activities is significantly affected by L-histidine. The results demonstrate that CbrA functions as a L-histidine transporter and sensor kinase

Kommunikations- und Notationsverhalten von Erstsemesterstudierenden beim Lernen mit Videotutorials

Im BMBF-geförderten Projekt mamdim soll der Einfluss digitaler Medien auf das Lernen von beschreibender Statistik bei Studierenden unterschiedlicher Fachrichtungen in der Studieneingangsphase an verschiedenen Hochschulen untersucht werden. Mithilfe der Erfassung des Fachwissens, der Motivation und der Selbstwirksamkeitsüberzeugungen der Studierenden vor und nach einer videographierten Interventionsphase mit verschiedenen instruktionalen Formaten (z.B. Lernvideos, kommentierte Präsentationen) zur beschreibenden Statistik werden Gemeinsamkeiten und Unterschiede im Kommunikations- und Notationsverhaltens in den Blick genommen. In diesem Beitrag werden die Analysen der Videoaufnahmen eines Standortes (Lehramtsstudierende der Universität Bielefeld) beim Lernen mit Videotutorials mit beziehungsweise ohne inhaltsbezogene Fragen dargestellt

Insulin gene polymorphisms in type I diabetes, Addison's disease and the polyglandular autoimmune syndrome type II

Background: Polymorphisms within the insulin gene can influence insulin expression in the pancreas and especially in the thymus, where self-antigens are processed, shaping the T cell repertoire into selftolerance, a process that protects from ß-cell autoimmunity. Methods: We investigated the role of the -2221Msp(C/T) and -23HphI(A/T) polymorphisms within the insulin gene in patients with a monoglandular autoimmune endocrine disease [patients with isolated type 1 diabetes (T1D, n = 317), Addison´s disease (AD, n = 107) or Hashimoto´s thyroiditis (HT, n = 61)], those with a polyglandular autoimmune syndrome type II (combination of T1D and/or AD with HT or GD, n = 62) as well as in healthy controls (HC, n = 275). Results: T1D patients carried significantly more often the homozygous genotype "CC" -2221Msp(C/T) and "AA" -23HphI(A/T) polymorphisms than the HC (78.5% vs. 66.2%, p = 0.0027 and 75.4% vs. 52.4%, p = 3.7 × 10-8, respectively). The distribution of insulin gene polymorphisms did not show significant differences between patients with AD, HT, or APS-II and HC. Conclusion: We demonstrate that the allele "C" of the -2221Msp(C/T) and "A" -23HphI(A/T) insulin gene polymorphisms confer susceptibility to T1D but not to isolated AD, HT or as a part of the APS-II

Food Intake, Diet Quality and Behavioral Problems in Children: Results from the GINI-plus/LISA-plus Studies

Background/Aims: To assess the association between food intake and diet quality and behavioral problems at the 10-year follow-up of the two population-based birth cohorts of the studies German Infant Nutritional Intervention and `Influences of lifestyle-related factors on the immune system and the development of allergies in childhood'. Methods: Cross-sectional data on food intake over the past year were collected by a parent-reported food frequency questionnaire. Diet quality was based on reference values of food amounts of the optimized mixed diet. Behavioral problems were assessed by a parent-reported Strengths and Difficulties Questionnaire. Relationships between food category intake, diet quality and behavior problems were examined using multivariable regression modeling adjusted for gender, sociodemographic characteristics, body mass index, physical exercise, television viewing/PC use and total energy intake. A total of 3,361 children with complete data were analyzed. Results: Children with increased intake of confectionery had increased odds of having emotional symptoms {[}adjusted odds ratio (ORadj) 1.19, 95% confidence interval (CI) 1.08-1.32] compared to children with low intake. A higher diet quality score was associated with lower likelihood of emotional symptoms (ORadj 0.89, 95% CI 0.80-0.98). The un-adjusted significant relationship between diet quality and hyperactivity/inattention was attenuated by adjusting for several confounders to an ORadj of 0.92 (95% CI 0.82-1.03). Conclusions: Increased consumption of high-sugar products and lower diet quality are associated with a higher likelihood of emotional symptoms in children. Copyright (C) 2012 S. Karger AG, Base

Forty Years after the Discovery of Its Nucleolytic Activity: [Cu(phen)(2)](2+) Shows Unattended DNA Cleavage Activity upon Fluorination

[Cu(phen)(2)](2+) (phen=1,10-phenanthroline) is the first and still one of the most efficient artificial nucleases. In general, when the phen ligand is modified, the nucleolytic activity of its Cu-II complex is significantly reduced. This is most likely due to higher steric bulk of such ligands and thus lower affinity to DNA. Cu-II complexes with phen ligands having fluorinated substituents (F, CF3, SF5, SCF3) surprisingly showed excellent DNA cleavage activity-in contrast to the unsubstituted [Cu(phen)(2)](2+)-in the absence of the otherwise required classical, bioabundant external reducing agents like thiols or ascorbate. This nucleolytic activity correlates well with the half-wave potentials E-1/2 of the complexes. Cancer cell studies show cytotoxic effects of all complexes with fluorinated ligands in the low mu m range, whereas they were less toxic towards healthy cells (fibroblasts)