Altered CD161bright CD8+ Mucosal Associated Invariant T (MAIT)-Like Cell Dynamics and Increased Differentiation States among Juvenile Type 1 Diabetics.

Type 1A diabetes (T1D) is believed to be caused by immune-mediated destruction of β-cells, but the immunological basis for T1D remains controversial. Microbial diversity promotes the maturation and activation of certain immune subsets, including CD161bright CD8+ mucosal associated invariant T (MAIT) cells, and alterations in gut mucosal responses have been reported in type 1 diabetics (T1Ds). We analyzed T cell populations in peripheral blood leukocytes from juvenile T1Ds and healthy controls. We found that proportion and absolute number of MAIT cells were similar between T1Ds and controls. Furthermore, while MAIT cell proportions increased with age among healthy controls, this trend was not observed among long-standing T1Ds. Additionally, the CD27- MAIT cell subset is significantly increased in T1Ds and positively correlated with HbA1c levels. However, after T1Ds are stratified by age, the younger group has significantly increased proportions of CD27- MAIT cells compared to age-matched controls, and this proportional increase appears to be independent of HbA1c levels. Finally, we analyzed function of the CD27- MAIT cells and observed that IL-17A production is increased in CD27- compared to CD27+ MAIT cells. Overall, our data reveal disparate MAIT cell dynamics between T1Ds and controls, as well as signs of increased MAIT cell activation in T1Ds. These changes may be linked to hyperglycemia and increased mucosal challenge among T1Ds

Cases, Regulations, and Statutes

<p><b>A</b>. Correlation of log(%MAIT cells of total leukocytes) versus age in years among controls and total type 1 diabetics (T1D). Controls values are represented by solid circles and a solid trend line. Values for T1D are represented by open circles and a dotted trend line. <b>B</b>. Correlation of log(%MAIT cells of total leukocytes) versus age in years among new-onset T1D (NT1D) and long-standing T1D (LT1D). Values for NT1D are represented by solid triangles and a solid trend line. Values for LT1D are represented by open squares and a dotted trend line. <b>C</b>. Results of Pearson’s r analysis and linear regression. * = p<0.05</p

No Detectable Fertility Benefit from a Single Additional Mating in Wild Stalk-Eyed Flies

Background: Multiple mating by female insects is widespread, and the explanation(s) for repeated mating by females has been the subject of much discussion. Females may profit from mating multiply through direct material benefits that increase their own reproductive output, or indirect genetic benefits that increase offspring fitness. One particular direct benefit that has attracted significant attention is that of fertility assurance, as females often need to mate multiply to achieve high fertility. This hypothesis has never been tested in a wild insect population.Methodology/Principal Findings: Female Malaysian stalk-eyed flies (Teleopsis dalmanni) mate repeatedly during their lifetime, and have been shown to be sperm limited under both laboratory and field conditions. Here we ask whether receiving an additional mating alleviates sperm limitation in wild females. In our experiment one group of females received a single additional mating, while a control group received an interrupted, and therefore unsuccessful, mating. Females that received an additional mating did not lay more fertilised eggs in total, nor did they lay proportionately more fertilised eggs. Female fertility declined significantly through time, demonstrating that females were sperm limited. However, receipt of an additional mating did not significantly alter the rate of this decline.Conclusions/Significance: Our data suggest that the fertility consequences of a single additional mating were small. We discuss this effect (or lack thereof), and suggest that it is likely to be attributed to small ejaculate size, a high proportion of failed copulations, and the presence of X-linked meiotic drive in this species

Livro didático público paranaense "lingua portuguesa e literatura" : o professor-autor e o gênero discursivo

Orientadora: Profa. Dra. Iara Bemquerer CostaAutor não autorizou a divulgação do arquivo digitalTese (doutorado) - Universidade Federal do Paraná, Setor de Ciências Humanas, Letras e Artes, Programa de Pós-Graduação em Letras. Defesa: Curitiba, 23/04/2012Bibliografia: fls. 163-178Área de concentração :Resumo: Esta pesquisa descritivo-explicativa tem como objetivo averiguar a relacao dialogica entre o Livro Didatico Publico Paranaense \Lingua Portuguesa e Literatura. (LDP-PR) e os livros representantes do genero discursivo Livro Didatico de Lingua Portuguesa (LD-LP). A partir de uma perspectiva socio-historico-discursiva e empregando fontes bibliografica e documental, desenvolvemos esta pesquisa em duas etapas. Na primeira, procuramos efetuar uma reflexao teorica sobre os Generos Discursivos (BAKHTIN) e sobre como a abordagem sociointeracionista se apropria desta concepcao bakhtiniana e discute a questao da didatizacao dos generos (SCHNEUWLY e DOLZ). Na segunda, aplicamos estes pressupostos ao LDP-PR com o intuito de averiguar o encaminhamento didatico dado aos textos de generos discursivos empregados neste material didatico. A partir desta averiguacao do conteudo tematico do LDP-PR, realizada pelo trabalho com as praticas de leitura, escrita e oralidade, buscamos sustentacao para a analise deste LD como um exemplar do genero LD-LP. Nossos resultados mostram que o LDP-PR inova na escolha do conteudo tematico, mas mantem o estilo (marcado pelo emprego de discursos injuntivos, explicativos e expositivos) e a construcao composicional (de textualidade multimodal) tipicos do genero LD-LP. Creditamos a autoria multipla (constituida por professores da rede escolar), marcada pela experiencia reduzida e a merce da Secretaria de Estado da Educacao do Parana (SEED-PR) este apego ao genero consolidado.Abstract: This descriptive-explanatory research aims to investigate the dialogic relationship between the Parana‘s Public Textbook "Portuguese and Literature" (LDP-PR) and the representative books of the discursive genre of Portuguese Textbook (LP-LD). From a socio-historic-discursive perspective and by the use of bibliographical and documentary sources, we developed this research in two stages. In the first one, we carried out a theoretical reflection about the Discursive Genres (BAKHTIN) and how the social interactionist approach appropriates this Bakhtinian concept and discusses the issue of making genre educational (SCHNEUWLY and DOLZ). In the second one, we applied these assumptions to the LDP-PR with the intent of investigating the educational directions given to the texts of discursive genres employed in such a teaching materials. From this investigation of the LDP-PR‘s thematic contents, performed through the work with reading, writing and speaking skills practices, we sought support for the analysis of this LD as an exemplar of the LD-LP genre. Our results reveal that the LDP-PR innovates the choice of the thematic content but retains the style (marked by the use of injunctive, explanatory and expository discourses) and compositional construction (multimodal textuality) that is typical of the LD-LP genre. We attribute to the multiple authorship (made up of teachers from the public educational system), marked by limited experience and at the mercy of the Parana‘s State Department of Education (SEED-PR), this attachment to the consolidated genre

Rare and low-frequency coding variants alter human adult height

Height is a highly heritable, classic polygenic trait with ~700 common associated variants identified so far through genome - wide association studies . Here , we report 83 height - associated coding variants with lower minor allele frequenc ies ( range of 0.1 - 4.8% ) and effects of up to 2 16 cm /allele ( e.g. in IHH , STC2 , AR and CRISPLD2 ) , >10 times the average effect of common variants . In functional follow - up studies, rare height - increasing alleles of STC2 (+1 - 2 cm/allele) compromise d proteolytic inhibition of PAPP - A and increased cleavage of IGFBP - 4 in vitro , resulting in higher bioavailability of insulin - like growth factors . The se 83 height - associated variants overlap genes mutated in monogenic growth disorders and highlight new biological candidates ( e.g. ADAMTS3, IL11RA, NOX4 ) and pathways ( e.g . proteoglycan/ glycosaminoglycan synthesis ) involved in growth . Our results demonstrate that sufficiently large sample sizes can uncover rare and low - frequency variants of moderate to large effect associated with polygenic human phenotypes , and that these variants implicate relevant genes and pathways

Fundamental Science Investigations to Develop a 6-MV Laser Triggered Gas Switch for ZR: First Annual Report.

In October 2005, an intensive three-year Laser Triggered Gas Switch (LTGS) development program was initiated to investigate and solve observed performance and reliability issues with the LTGS for ZR. The approach taken has been one of mission-focused research: to revisit and reassess the design, to establish a fundamental understanding of LTGS operation and failure modes, and to test evolving operational hypotheses. This effort is aimed toward deploying an initial switch for ZR in 2007, on supporting rolling upgrades to ZR as the technology can be developed, and to prepare with scientific understanding for the even higher voltage switches anticipated needed for future high-yield accelerators. The ZR LTGS was identified as a potential area of concern quite early, but since initial assessments performed on a simplified Switch Test Bed (STB) at 5 MV showed 300-shot lifetimes on multiple switch builds, this component was judged acceptable. When the Z{sub 20} engineering module was brought online in October 2003 frequent flashovers of the plastic switch envelope were observed at the increased stresses required to compensate for the programmatically increased ZR load inductance. As of October 2006, there have been 1423 Z{sub 20} shots assessing a variety of LTGS designs. Numerous incremental and fundamental switch design modifications have been investigated. As we continue to investigate the LTGS, the basic science of plastic surface tracking, laser triggering, cascade breakdown, and optics degradation remain high-priority mission-focused research topics. Significant progress has been made and, while the switch does not yet achieve design requirements, we are on the path to develop successively better switches for rolling upgrade improvements to ZR. This report summarizes the work performed in FY 2006 by the large team. A high-level summary is followed by detailed individual topical reports

Altered CD161^bright CD8⁺ Mucosal Associated Invariant T (MAIT)-Like Cell Dynamics and Increased Differentiation States among Juvenile Type 1 Diabetics

<div><p>Type 1A diabetes (T1D) is believed to be caused by immune-mediated destruction of β-cells, but the immunological basis for T1D remains controversial. Microbial diversity promotes the maturation and activation of certain immune subsets, including CD161^bright CD8⁺ mucosal associated invariant T (MAIT) cells, and alterations in gut mucosal responses have been reported in type 1 diabetics (T1Ds). We analyzed T cell populations in peripheral blood leukocytes from juvenile T1Ds and healthy controls. We found that proportion and absolute number of MAIT cells were similar between T1Ds and controls. Furthermore, while MAIT cell proportions increased with age among healthy controls, this trend was not observed among long-standing T1Ds. Additionally, the CD27- MAIT cell subset is significantly increased in T1Ds and positively correlated with HbA1c levels. However, after T1Ds are stratified by age, the younger group has significantly increased proportions of CD27- MAIT cells compared to age-matched controls, and this proportional increase appears to be independent of HbA1c levels. Finally, we analyzed function of the CD27- MAIT cells and observed that IL-17A production is increased in CD27- compared to CD27⁺ MAIT cells. Overall, our data reveal disparate MAIT cell dynamics between T1Ds and controls, as well as signs of increased MAIT cell activation in T1Ds. These changes may be linked to hyperglycemia and increased mucosal challenge among T1Ds.</p></div

Tips, tricks, and thoughts on the future of prehospital blood transfusions

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/173085/1/trf16955_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/173085/2/trf16955.pd

HbA1c levels are similar between age-stratified type 1 diabetic (T1D) populations, yet HbA1c is positively and significantly correlated with CD27^- proportions among older T1D (≥11 years old (y.o.)) and not with younger T1D (<11 years old (y.o.)).

<p><b>A</b>. Comparison of HbA1c levels between T1D<11 y.o. and T1D≥ 11 y.o. Significance was determined using the Mann-Whitney U Test. Bars represent median, NS = not significant. <b>B</b>. Correlation of log(%CD27^- of MAIT cells) versus HbA1c among T1D<11 y.o. and T1D≥ 11 y.o. Values for T1D<11 y.o. are represented by asterisks and a solid trend line, while T1D≥ 11 y.o. are represented by open diamonds and a dotted trend line. <b>C</b>. Results of Pearson’s r analysis and linear regression. * = p<0.05</p

Younger type 1 diabetics (T1D) possess increased proportions of CD27^- MAIT cells compared to age-matched controls.

<p><b>A</b>. T1D <11 years old (y.o.) have significantly increased proportions of CD27^- MAIT cells compared to age-matched controls (Control<11y.o.) and older controls (Control≥11y.o.), and approach a significant increase compared to T1D≥11 y.o. Significance was determined using the Mann-Whitney U Test. Bars represent median, * = p < 0.05, NS = not significant. <b>B</b>. Correlation of log(%CD27^- of MAIT cells) versus age in years splitting controls and type 1 diabetics at < 11 years of age and ≥ 11 years of age. <b>C</b>. Results of Pearson’s r analysis and linear regression. * = p<0.05</p