An Early Reduction in Treg Cells Correlates with Enhanced Local Inflammation in Cutaneous Leishmaniasis in CCR6-Deficient Mice

Resistance to Leishmania major infection is dependent on the development of a cell-mediated Th1 immune response in resistant C57BL/6 mice whereas Th2-prone BALB/c mice develop non-healing lesions after infection. The chemokine receptor CCR6 is shared by anti-inflammatory regulatory T cells and pro-inflammatory Th17 cells. In a recent study we showed that C57BL/6 mice deficient in CCR6 exhibited enhanced footpad swelling and impaired T helper cell migration indicated by reduced recruitment of total T helper cells into the skin after infection and a reduced delayed type hypersensitivity reaction. Based on these findings we tested whether the lack of CCR6 alters Treg or Th17 cell responses during the course of Leishmania major infection. When we analyzed T cell subsets in the lymph nodes of CCR6-deficient mice, Th17 cell numbers were not different. However, reduced numbers of Treg cells paralleled with a stronger IFNγ response. Furthermore, the early increase in IFNγ-producing cells correlated with increased local tissue inflammation at later time points. Our data indicate an important role of CCR6 for Treg cells and a redundant role for Th17 cells in a Th1 cell-driven anti-parasitic immune response against Leishmania major parasites in resistant C57BL/6 mice

Defect tolerance in as-deposited selenium-alloyed cadmium telluride solar cells

The efficiency of cadmium telluride (CdTe) solar cells is limited primarily by voltage, which is known to depend on the carrier concentration and carrier lifetimes within the absorber layer of the cell. Here, cathodoluminescence measurements are made on an as-deposited CdSeTe/CdTe solar cell that show that selenium alloyed CdTe material luminesces much more strongly than non-alloyed CdTe. This reduction in non-radiative recombination in the CdSeTe suggests that the selenium gives it a certain defect tolerance. This has implications for carrier lifetimes and voltages in cadmium telluride solar cells

DNA-DNA kissing complexes as a new tool for the assembly of DNA nanostructures

Kissing-loop annealing of nucleic acids occurs in nature in several viruses and in prokaryotic replication, among other circumstances. Nucleobases of two nucleic acid strands (loops) interact with each other, although the two strands cannot wrap around each other completely because of the adjacent doublestranded regions (stems). In this study, we exploited DNA kissing-loop interaction for nanotechnological application. We functionalized the vertices of DNA tetrahedrons with DNA stem-loop sequences. The complementary loop sequence design allowed the hybridization of different tetrahedrons via kissingloop interaction, which might be further exploited for nanotechnology applications like cargo transport and logical elements. Importantly, we were able to manipulate the stability of those kissing-loop complexes based on the choice and concentration of cations, the temperature and the number of complementary loops per tetrahedron either at the same or at different vertices. Moreover, variations in loop sequences allowed the characterization of necessary sequences within the loop as well as additional stability control of the kissing complexes. Therefore, the properties of the presented nanostructures make them an important tool for DNA nanotechnology

Percepções e sentimentos sobre o bebê subsequente à perda gestacional

A perda gestacional (PG) pode repercutir na gestação subsequente e na maternidade. Neste estudo, objetivou-se identificar e compreender as percepções e os sentimentos maternos sobre a gestação e o bebê subsequente à PG. Trata-se de estudo qualitativo e transversal, com quatro mães com PG nos últimos cinco anos, cujos bebês subsequentes tinham de 6 a 21 meses. Foram aplicados o Questionário de Dado Sociodemográficos e Clínicos, o Questionário sobre Vivências dePerda, o Brief Symptom Inventory e a Entrevista sobre Vivência de Luto Materno e Experiência da Maternidade Atual. Os resultados mostraram repercussões da PG nos sentimentos maternos sobre a gestação, como: ambivalência, medo de nova PG e angústia frente ao parto e nascimento; e nas percepções e sentimentos sobre o bebê, como: idealização das características dele e da relação mãe-bebê, medo da morte do bebê e substituição do bebê falecido. Os achados apontam a importância de ações de prevenção de saúde mental do binômio mãe-bebê em casos de P

Condições higiênico-sanitárias de estabelecimentos de alimentação de um parque multitemático no Vale do Itajaí, Santa Catarina, Brasil

As doenças transmitidas por alimentos podem estar relacionadas com as inadequações no controle higiênicosanitário. A partir dessa consideração, o objetivo deste estudo foi avaliar o nível de conformidade do controle higiênico-sanitário dos pontos terceirizados que comercializam alimentos em um parque multitemático do Vale do Itajaí (SC), antes e após auditoria, de acordo com a Resolução da Diretoria Colegiada no 216/2004 da Agência Nacional de Vigilância Sanitária. Foram avaliados 41 estabelecimentos do setor de alimentação, por meio de um check-list higiênico-sanitário próprio do parque, adaptado para cada categoria de estabelecimento: restaurantes, lanchonetes e confeitaria, sorveterias, cafeterias, bombonieres (industrializados) e pipoqueira, sorveteria e cafeteria. Após análise dos dados, os estabelecimentos foram classificados pela pontuação alcançada. Estabeleceu-se um prazo para melhoria das não conformidades, sendo realizada uma segunda auditoria após o prazo determinado. A maioria dos estabelecimentos não atingiu o percentual preconizado pela empresa na primeira auditoria e, após o retorno, prevaleceram as classificações nas categorias “bom” e “muito bom”. Foi possível verificar a importância da auditoria, uma vez que os percentuais de conformidade aumentaram entre elas

Professionalization of student teachers for inclusive science teaching

Durch die Ratifizierung der UN-Behindertenrechtskonvention (United Nations 2006, Artikel 24) hat sich Deutschland verpflichtet »Bildung für alle« (UNESCO 2015) im deutschen Schulsystem möglich zu machen. In der Lehrer*innenbildung stellen sich zwei Herausforderungen für die Fachdidaktiken: Erstens ist der Schulunterricht in verschiedene Fächer aufgegliedert, die jeweils eigene Fachinhalte aufweisen. Diese Inhalte müssen entlang fachdidaktischer Prinzipien inklusiv aufbereitet werden. Zweitens steigt die Komplexität der Fachinhalte vom Übergang der Grundschule in die Sekundarstufe deutlich an, sodass es für Lehrkräfte immer schwieriger wird, auf heterogene Lernvoraussetzungen angemessen einzugehen (Musenberg und Riegert 2015, 5). Die Professionalisierung von Lehrkräften muss gezielt auf diese Herausforderungen reagieren und Lehramtsstudierende nachhaltig auf ihr Tätigkeitsfeld vorbereiten. Wie diese Professionalisierung von Lehramtsstudierenden in Forschung und Lehre umgesetzt werden kann, wird exemplarisch an einem Projektseminar zum inklusiven naturwissenschaftlichen Unterricht vorgestellt. Das BMBF Projekt »Nawi-In« vereint Forschung und Lehre, indem es die Kompetenzentwicklung Studierender im Projektseminar beforscht. Dies wird durch videobasierte Kompetenzforschung begleitet (Riegel 2013).Germany ratified the UN Convention on the Rights of Persons with Disabilities (United Nations 2006, Article 24), and is therefore bound by contract to make »Education for All« possible (UNESCO 2015) in the German school system. Now there are two challenges for science education: first, the school education is divided in different subjects with different subject contents. The contents have to be prepared inclusively and subject-related. Second, the complexity of the subject contents rises noticeably from primary to secondary school, so it gets more difficult to regard all needs of a heterogeneous group of students adequately (Musenberg and Riegert 2015, 5). Therefore, a professionalization of teacher students should target these challenges to prepare them effectively for their working field. How the implementation of teacher students’ professionalization can be orchestrated is shown exemplary by a project seminar designed for inclusive science teaching. Research and teaching is united through the »Nawi-In«-project – funded by the Federal Ministry of Education and Research – by investigating the students’ development of competencies. This development is monitored by video-based competency research (Riegel 2013)

Three-dimensional deuterium-carbon correlation experiments for high-resolution solid-state MAS NMR spectroscopy of large proteins

Well-resolved 2H-13C correlation spectra, reminiscent of 1H-13C correlations, are obtained for perdeuterated ubiquitin and for perdeuterated outer-membrane protein G (OmpG) from E. coli by exploiting the favorable lifetime of 2H double-quantum (DQ) states. Sufficient signal-to-noise was achieved due to the short deuterium T 1, allowing for high repetition rates and enabling 3D experiments with a 2H-13C transfer step in a reasonable time. Well-resolved 3D 2HDQ-13C-13C correlations of ubiquitin and OmpG were recorded within 3.5days each. An essentially complete assignment of 2HDQα shifts and of a substantial fraction of 2HDQβ shifts were obtained for ubiquitin. In the case of OmpG, 2HDQα and 2HDQβ chemical shifts of a considerable number of threonine, serine and leucine residues were assigned. This approach provides the basis for a general heteronuclear 3D MAS NMR assignment concept utilizing pulse sequences with 2HDQ-13C transfer steps and evolution of deuterium double-quantum chemical shift

A Novel Siglec-4 Derived Spacer Improves the Functionality of CAR T Cells Against Membrane-Proximal Epitopes

A domain that is often neglected in the assessment of chimeric antigen receptor (CAR) functionality is the extracellular spacer module. However, several studies have elucidated that membrane proximal epitopes are best targeted through CARs comprising long spacers, while short spacer CARs exhibit highest activity on distal epitopes. This finding can be explained by the requirement to have an optimal distance between the effector T cell and target cell. Commonly used long spacer domains are the CH2-CH3 domains of IgG molecules. However, CARs containing these spacers generally show inferior in vivo efficacy in mouse models compared to their observed in vitro activity, which is linked to unspecific Fcγ-Receptor binding and can be abolished by mutating the respective regions. Here, we first assessed a CAR therapy targeting membrane proximal CD20 using such a modified long IgG1 spacer. However, despite these mutations, this construct failed to unfold its observed in vitro cytotoxic potential in an in vivo model, while a shorter but less structured CD8α spacer CAR showed complete tumor clearance. Given the shortage of well-described long spacer domains with a favorable functionality profile, we designed a novel class of CAR spacers with similar attributes to IgG spacers but without unspecific off-target binding, derived from the Sialic acid-binding immunoglobulin-type lectins (Siglecs). Of five constructs tested, a Siglec-4 derived spacer showed highest cytotoxic potential and similar performance to a CD8α spacer in a CD20 specific CAR setting. In a pancreatic ductal adenocarcinoma model, a Siglec-4 spacer CAR targeting a membrane proximal (TSPAN8) epitope was efficiently engaged in vitro, while a membrane distal (CD66c) epitope did not activate the T cell. Transfer of the TSPAN8 specific Siglec-4 spacer CAR to an in vivo setting maintained the excellent tumor killing characteristics being indistinguishable from a TSPAN8 CD8α spacer CAR while outperforming an IgG4 long spacer CAR and, at the same time, showing an advantageous central memory CAR T cell phenotype with lower release of inflammatory cytokines. In summary, we developed a novel spacer that combines cytotoxic potential with an advantageous T cell and cytokine release phenotype, which make this an interesting candidate for future clinical applications

Resolving the contributions of the membrane-bound and periplasmic nitrate reductase systems to nitric oxide and nitrous oxide production in Salmonella enterica serovar Typhimurium

The production of cytotoxic nitric oxide (NO) and conversion into the neuropharmacological agent and potent greenhouse gas nitrous oxide (N2O) is linked with anoxic nitrate catabolism by Salmonella enterica serovar Typhimurium. Salmonella can synthesize two types of nitrate reductase: a membrane-bound form (Nar) and a periplasmic form (Nap). Nitrate catabolism was studied under nitrate-rich and nitrate-limited conditions in chemostat cultures following transition from oxic to anoxic conditions. Intracellular NO production was reported qualitatively by assessing transcription of the NO-regulated genes encoding flavohaemoglobin (Hmp), flavorubredoxin (NorV) and hybrid cluster protein (Hcp). A more quantitative analysis of the extent of NO formation was gained by measuring production of N2O, the end-product of anoxic NO-detoxification. Under nitrate-rich conditions, the nar, nap, hmp, norV and hcp genes were all induced following transition from the oxic to anoxic state, and 20% of nitrate consumed in steady-state was released as N2O when nitrite had accumulated to millimolar levels. The kinetics of nitrate consumption, nitrite accumulation and N2O production were similar to those of wild-type in nitrate-sufficient cultures of a nap mutant. In contrast, in a narG mutant, the steady-state rate of N2O production was ~30-fold lower than that of the wild-type. Under nitrate-limited conditions, nap, but not nar, was up-regulated following transition from oxic to anoxic metabolism and very little N2O production was observed. Thus a combination of nitrate-sufficiency, nitrite accumulation and an active Nar-type nitrate reductase leads to NO and thence N2O production, and this can account for up to 20% of the nitrate catabolized