Of tolerance in mice and men : studies in APECED and Aire

Autoimmune diseases affect 5 % of the population and come in many forms, such as diabetes, rheumatoid arthritis and MS. However, how and why autoimmune diseases arise are not yet fully resolved. In this thesis, the onset of autoimmunity was investigated using both patient samples and a mouse model of autoimmunity. Autoimmune diseases are usually complex, due to a number of different causative genes and environmental factors. However, a few monogenic autoimmune diseases have been described, which are caused by mutations in only one gene per disease. One of such disease is called APECED (autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy) and is enriched in the Finnish population. The causative gene behind APECED is named AIRE from AutoImmune REgulator. How malfunction of just one gene product can cause the multitude of disease components found in APECED is not yet resolved. This thesis sought out to find out more about the functions of AIRE, in order to reveal why APECED and other autoimmune diseases arise and what goes wrong? Usually, immune cells are taught to distinguish between self and non-self during their development. That way, immune cells can fight off bacteria and microbes while leaving the tissues and organs of the host organism itself unharmed. In APECED, the development of immune cells called αβ T cells is incomplete. The cells are not able to fully distinguish between self and non-self. This leads to autodestruction of self tissues and autoimmune disease. One of the achievements of this thesis was the finding that the development of another set of T cells called γδ T cells is not affected by AIRE in mice or in men. Instead, we found that another type of immune cell important in tolerance, called the dendritic cell is defective in APECED patients and is not able to respond to microbial stimulus in a normal fashion. Finally, we studied Aire-deficient mice and found that autoantibodies expressed in the mice were not targeted against the same molecules as those found in APECED patients. This indicates differences in the autoimmune pathology in mice and men. More work is still required before we understand the mechanisms of tolerance and autoimmunity well enough to be able to cure APECED, let alone the more complex autoimmune diseases. Yet altogether, the findings of this thesis work bring us one step closer to finding out why and how APECED and common autoimmune diseases arise.

Dyslipidaemia, glucose intolerance and cardiovascular disease mortality and morbidity in Europeans and Asians

Dyslipidaemia, a major risk factor of cardiovascular disease (CVD), is prevalent not only in diabetic patients but also in individuals with impaired glucose tolerance (IGT) or impaired fasting glucose (IFG). The aims of this study were: 1) to investigate lipid levels in relation to glucose in European (Study I) and Asian (Study II) populations without a prior history of diabetes; 2) to study the ethnic difference in lipid profiles controlling for glucose levels (Study III); 3) to estimate the relative risk for cardiovascular mortality (Study IV) and morbidity (Study V) associated with dyslipidaemia in individuals with different glucose tolerance status. Data of 15 European cohorts with 19 476 subjects (I and III) and 13 Asian cohorts with 19 763 individuals (II and III) from 21 countries aged 25-89 years, without a prior history of diabetes at enrollment, representing Asian Indian, Chinese, European, Japanese and Mauritian Indian, were compared. The lipid-CVD relationship was studied in 14 European cohorts of 17 763 men and women which provided with follow-up data on vital status, with 871 CVD deaths occurred during the average 10-year follow-up (IV). The impact of dyslipidaemia on incidence of coronary heart disease (CHD) in persons with different glucose categories (V) was further evaluated in 6 European studies, with 9087 individuals free of CHD at baseline and 457 developed CHD during follow-up. Z-scores of each lipid component were used in the data analysis (I, II, IV and V) to reduce the differences in methodology between studies. Analyses of cardiovascular mortality and morbidity were performed using Cox proportional hazards regression analysis adjusting for potential confounding factors. Within each glucose category, fasting plasma glucose (FPG) levels were correlated with increasing levels of triglycerides (TG), total cholesterol (TC), TC to high-density lipoprotein (HDL) ratio and non-HDL cholesterol (non-HDL-C) (p<0.05 in most of the ethnic groups) and inversely associated with HDL-C (p<0.05 in some, but not all, of the populations). The association of lipids with 2-h plasma glucose (2hPG) followed a similar pattern as that for the FPG, except the stronger association of HDL-C with 2hPG. Compared with Central & Northern (C & N) Europeans, multivariable adjusted odd ratios (95% CIs) for having low HDL-C were 4.74 (4.19-5.37), 5.05 (3.88-6.56), 3.07 (2.15-4.40) and 2.37 (1.67-3.35) in Asian Indian men but 0.12 (0.09-0.16), 0.07 (0.04-0.13), 0.11 (0.07-0.20) and 0.16 (0.08-0.32) in Chinese men who had normoglycaemia, prediabetes, undiagnosed and diagnosed diabetes, respectively. Similar results were obtained for women. The prevalence of low HDL-C remained higher in Asian Indians than in others even in individuals with LDL-C < 3 mmol/l. Dyslipidaemia was associated with increased CVD mortality or CHD incidence in individuals with isolated fasting hyperglycaemia or IFG, but not in those with isolated post-load hyperglycaemia or IGT. In conclusion, hyperglycaemia is associated with adverse lipid profiles in Europeans and Asians without a prior history of diabetes. There are distinct patterns of lipid profiles associated with ethnicity regardless of the glucose levels, suggesting that ethnic-specific strategies and guidelines on risk assessment and prevention of CVD are required. Dyslipidaemia predicts CVD in either diabetic or non-diabetic individuals defined based on the fasting glucose criteria, but not on the 2-hour criteria. The findings may imply considering different management strategies in people with fasting or post-load hyperglycaemia.

A Safe Vaccine (DV-STM-07) against Salmonella Infection Prevents Abortion and Confers Protective Immunity to the Pregnant and New Born Mice

Pregnancy is a transient immuno-compromised condition which has evolved to avoid the immune rejection of the fetus by the maternal immune system. The altered immune response of the pregnant female leads to increased susceptibility to invading pathogens, resulting in abortion and congenital defects of the fetus and a subnormal response to vaccination. Active vaccination during pregnancy may lead to abortion induced by heightened cell mediated immune response. In this study, we have administered the highly attenuated vaccine strain delta pmrG-HM-D (DV-STM-07) in female mice before the onset of pregnancy and followed the immune reaction against challenge with virulent S. Typhimurium in pregnant mice. Here we demonstrate that DV-STM-07 vaccine gives protection against Salmonella in pregnant mice and also prevents Salmonella induced abortion. This protection is conferred by directing the immune response towards Th2 activation and Th1 suppression. The low Th1 response prevents abortion. The use of live attenuated vaccine just before pregnancy carries the risk of transmission to the fetus. We have shown that this vaccine is safe as the vaccine strain is quickly eliminated from the mother and is not transmitted to the fetus. This vaccine also confers immunity to the new born mice of vaccinated mothers. Since there is no evidence of the vaccine candidate reaching the new born mice, we hypothesize that it may be due to trans-colostral transfer of protective anti-Salmonella antibodies. These results suggest that our vaccine DV-STM-07 can be very useful in preventing abortion in the pregnant individuals and confer immunity to the new born. Since there are no such vaccine candidates which can be given to the new born and to the pregnant women, this vaccine holds a very bright future to combat Salmonella induced pregnancy loss.

Photo induced optical changes in Sb/As2S3 multilayered film and (As2S3)(0.93)Sb-0.07 film of equal thickness

The increase in optical band gap (photo bleaching) due to light illumination was studied at room temperature as well as at low (4.2 K) temperature for Sb/As2S3 multilayered film of 640 nm thickness by Fourier Transform Infrared Technique. The interdiffusion of Sb into As2S3 matrix results the formation of Sb-As2S3 ternary solid solutions which is explained by the change in optical band gap (E-g), absorption coefficient (alpha), Tauc parameter (B-1/2), Urbach edge (E-e). At the same time, photo darkening phenomena was observed in (As2S3)(0.93)Sb-0.07 film of same thickness both at low and room temperatures. From our X-ray Photoelectron Spectroscopy measurements,we are able to show that some of the As-As, S-S and Sb-Sb bonds are converted into As-S and S-Sb bonds in case of multilayers. We found that the energetically favoured heteropolar bond formation take place by a phonon-assisted mechanism using the lone pair pi electrons of S-2(0). But in case of (As2S3)(0.93)Sb-0.02 film, the homopolar bonds are playing a major role. (C) 2010 Elsevier B.V. All rights reserved.

Synthesis dependent characteristics of Sr1-xMnxTiO3 (x=0.03, 0.05, 0.07 and 0.09)

Sr1-xMnxTiO3 (where x=0.03, 0.05, 0.07 and 0.09) was synthesized via different routes that include solid-state, oxalate precipitation and freeze drying. In oxalate precipitation technique, compositions corresponding to 3 and 5 mol% doping of Mn were monophasic whereas the higher compositions revealed the presence of the secondary phases such as MnO, Mn3O4 etc., as confirmed by high resolution X-ray diffraction (XRD) studies. The decomposition behavior of the precursors prepared using oxalate precipitation method corresponding to the above mentioned compositions was studied. Nanopowders of compositions pertaining to 5 to 9 mol% of Mn doping were obtained using freeze-drying technique. The average crystallite size of these nanopowders was found to be in the 35 to 65 nm range. The microstructural studies carried out on the sintered ceramics, fabricated using powders synthesized by different routes established the fine grained nature ( < 1 mu m) of the one obtained by freeze drying method. Raman scattering studies were carried out in order to complement the observations made from XRD regarding the phase purity. The dielectric properties of the ceramics obtained by different synthesis routes were studied in the 80-300 K temperature range at 100 kHz and the effect of grain size has been discussed. (C) 2012 Elsevier Inc. All rights reserved.

Memory effect in SrRu(1-x)O3 (0.01 < x < 0.07)

SrRuO3 is widely known to be an itinerant ferromagnet with a T-C similar to 160 K. It is well known that glassy materials exhibit time dependent phenomena such as memory effect due to their generic slow dynamics. However, for the first time, we have observed memory effect in SrRu(1-x)O3 (0.01

Identificación macroscópica de patologías hepáticas de mayor prevalencia en bovinos faenados en el matadero PROINCASA, período del 07 de julio del 2010 - enero del 2011

El presente estudio se llevó a cabo para determinar la prevalencia de las patologías macroscópicas en hígados decomisados (condenados) de bovinos faenados en el matadero PROINCASA, identificando las patologías hepáticas mediante la inspección, clasificando los tipos de enfermedades (primarias o secundarias) según las patologías identificadas y determinando las pérdidas económicas representadas por los hígados decomisados. Los datos recopilados se obtuvieron a través de la inspección post mortem de los órganos, en los que se realizó la debida observación, palpación, limpieza y laminado de los mismos. Se utilizó estadística descriptiva con distribuciones de frecuencias a partir de los datos recolectados, se estructuró la base de datos en hoja electrónica Microsoft Excel℗, se realizó un análisis de los datos mediante la prueba de Chi2 (X2), utilizando el programa estadístico SPSS℗, generando tablas de contingencia a una P <0.05. Las variables evaluadas fueron: prevalencia total de patologías, prevalencia de patologías específicas, y pérdidas económicas; con los datos recopilados, se encontró desde el punto de vista general, que el mes con mayor prevalencia de hígados afectados fue septiembre con un 16%, y el mes con menor prevalencia fue julio con 12%; haciendo un análisis individual por patología, el mes con mayor prevalencia de hígados afectados con abscesos fue julio con un 5%, telangiectasia en octubre con un 9%, Ictericia en agosto con un 5% y para adherencia fue octubre con un 8%, del total de hígados con diferentes patologías por mes se obtuvo la mayor prevalencia en octubre con un 56% para abscesos, telangiectasia en octubre con un 70%, ictericia en septiembre con un 26% y adherencia en octubre con un 27%. De un total de 11 286 hígados inspeccionados, 1 555 resultaron afectados, lo que equivale a un 13.78% de afección, a su vez estos representan económicamente la pérdida de C$ 466,500 Córdobas netos.

Prudentia Iuris, 1982, n° 07 (número completo)

Contenido: Editorial – Jorge Joaquín Llambías / Mario Amadeo – El aporte de Llambías en materia de efectos de la nulidad de los actos jurídicos / Roberto Martínez Ruíz – El matrimonio en la regulación propuesta por el anteproyecto de 1954 / Jorge A. Mazzinghi – La reparación del agravio moral / Guillermo R. Quintana Terán – Responsabilidad civil de las personas jurídicas y, en especial, del estado / Federico N. Videla Escalada – La mora en las obligaciones cuyo lugar de pago es el domicilio del deudor / Francisco Alberto Vocos – Algunas páginas de Llambías – Documentos – Notas bibliográficas

[Discurso do Deputado Áureo Melo : Sessão da Câmara dos Deputados de 07 de maio de 1964]

Aborda a campanha de certos jornais do Rio de Janeiro contra Brasília. Destaca o verdadeiro pensamento dos cariocas relativamente ao pretendido retorno da capital da República para a Guanabara.

[Discurso do Deputado Múcio Athayde : Sessão da Câmara dos Deputados de 07 de maio de 1985]

Aborda a necessidade de representação política, em todos os níveis, para o Distrito Federal e da implantação de Câmara de Vereadores em cada cidade satélite. Faz críticas à Comissão Interpartidária encarregada da efetivação das reformas políticas e eleitorais.

Audiências públicas como instrumento de democracia deliberativa: estudo de caso do PL nº 612/07, lei das sacolas

Monografia (especialização) – Curso de Política e Representação Parlamentar, Câmara dos Deputados, Centro de Formação, Treinamento e Aperfeiçoamento (Cefor), 2013.

Lei Maria da Penha : Lei nº 11.340, de 07 de agosto de 2006, que dispõe sobre mecanismos para coibir a violência doméstica e familiar contra a mulher

Analisa a lei que cria mecanismos para coibir a violência doméstica e familiar contra a mulher, nos termos do § 8º do art. 226 da Constituição Federal, da Convenção sobre a Eliminação de Todas as Formas de Discriminação contra as Mulheres e da Convenção Interamericana para Prevenir, Punir e Erradicar a Violência contra a Mulher; dispõe sobre a criação dos Juizados de Violência Doméstica e Familiar contra a Mulher; altera o Código de Processo Penal, o Código Penal e a Lei de Execução Penal; e dá outras providências.

Cruise Report: Spring 2007 Survey of ecological conditions along the continental shelf off Florida from Anclote Key to West Palm Beach NOAA Ship NANCY FOSTER NF-07-08-NCCOS (May 15 - May 28, 2007)

This cruise report is a summary of a field survey conducted in coastal-ocean waters off Florida from Anclote Key to West Palm Beach and from approximately 1 nautical mile (nm) offshore seaward to the shelf break (100 m). The survey was conducted May 15 - May 28, 2007 on NOAA Ship NANCY FOSTER Cruise NF-07-08-NCCOS. Multiple indicators of ecological condition were sampled synoptically at each of 50 stations throughout the region including 10 stations within the Florida Keys National Marine Sanctuary (FKNMS) using a random probabilistic sampling design. Samples were collected for the analysis of benthic community structure and composition; concentrations of chemical contaminants (metals, pesticides, PAHs, PCBs, PBDEs) in sediments and target demersal biota; nutrient and chlorophyll levels in the water column; and other basic habitat characteristics such as depth, salinity, temperature, dissolved oxygen, pH, sediment grain size, and organic carbon content. The overall purpose of the survey was to collect data to assess the status of ecological condition in coastal-ocean waters of the region, based on these various indicators, and to provide this information as a baseline for determining how environmental conditions may be changing with time. The results will be of value in helping to broaden our understanding of the status of ecological resources and their controlling factors, including impacts of potential ecosystem stressors, in such strategic coastal areas. (PDF contains 34 pages

Observations of deep coral and sponge assemblages in Olympic Coast National Marine Sanctuary, Washington. Cruise Report: NOAA Ship McArthur II Cruise AR06-07/07

From May 22 to June 4, 2006, NOAA scientists led a research cruise using the ROPOS Remotely Operated Vehicle (ROV) to conduct a series of dives at targeted sites in the Olympic Coast National Marine Sanctuary (OCNMS) with the goal of documenting deep coral and sponge communities. Dive sites were selected from areas for which OCNMS had side scan sonar data indicating the presence of hard or complex substrate. The team completed 11 dives in sanctuary waters ranging from six to 52 hours in length, at depths ranging from 100 to 650 meters. Transect surveys were completed at 15 pre-selected sites, with additional observations made at five other sites. The survey locations included sites both inside and outside the Essential Fish Habitat (EFH) Conservation Area, known as Olympic 2, established by the Pacific Fishery Management Council, enacted on June 12, 2006. Bottom trawling is prohibited in the Olympic 2 Conservation Area for nontribal fishermen. The Conservation Area covers 159.4 square nautical miles or about 15 percent of the sanctuary. Several species of corals and sponges were documented at 14 of the 15 sites surveyed, at sites both inside and outside the Conservation Area, including numerous gorgonians and the stony corals Lophelia pertusa and Desmophyllum dianthus, as well as small patches of the reef building sponge Farrea occa. The team also documented Lophelia sp. and Desmophyllum sp. coral rubble, dead gorgonians, lost fishing gear, and other anthropogenic debris, supporting concerns over potential risks of environmental disturbances to coral health. (PDF contains 60 pages.)