Interleukin-12p40 overexpression promotes interleukin-12p70 and interleukin-23 formation but does not affect bacille Calmette-Guérin and Mycobacterium tuberculosis clearance.

Interleukin (IL)-12p40, a subunit of IL-12p70 and IL-23, has previously been shown to inhibit IL-12p70 activity and interferon-gamma (IFN-gamma) production. However, recent evidence has suggested that the role of IL-12p40 is more complex. To study the contribution of IL-12p40 to immune responses against mycobacterial infections, we have used transgenic (tg) mice overexpressing IL-12p40 under the control of a major histocompatibility complex-II promoter. The IL-12p40 transgene was expressed during steady state at concentrations of 129 +/- 25 ng/ml of serum and 75 +/- 13 ng per spleen, while endogenous IL-12p40 was hardly detectable in control littermates. Bacille Calmette-Guérin (BCG) infection strongly induced the expression of IL-12p40 transgene in infected organs, and IL-12p40 monomeric and dimeric forms were identified in spleen of IL-12p40 tg mice. Excessive production of IL-12p40 resulted in a 14-fold increase in IL-12p70 serum levels in tg mice versus non-transgenic mice. IL-23 was also strongly elevated in the serum and spleens of IL-12p40 tg mice through BCG infection. While IFN-gamma and tumour necrosis factor protein levels were similar in IL-12p40 tg and non-transgenic mice, Th2 type immune responses were reduced in IL-12p40 tg mice. The number of BCG granulomas and macrophage expressing inducible nitric oxide synthase were similar in IL-12p40 tg and non-transgenic mice. IL-12p40 tg mice were as resistant as non-transgenic mice to BCG and Mycobacterium tuberculosis infections as they could efficiently control bacillary growth. These data show that high amounts of IL-12p40 promotes IL-12p70 and IL-23 formation, but that does not affect T helper 1 type immune responses and granuloma function, thus leading to normal mycobacterial clearance in infected organs.

Expression and presentation of endogenous mouse mammary tumor virus superantigens by thymic and splenic dendritic cells and B cells.

Tolerance against superantigens (SAgs) encoded by endogenous mouse mammary tumor virus (Mtv) loci involves the intrathymic deletion of SAg-reactive T cells expressing a particular TCR V beta-chain, presumably upon presentation of the SAg by specialized APC. However, although the role of dendritic cells (DC) in the induction of tolerance against conventional Ags has been demonstrated, little is known about the role played by DC in tolerance induction against Mtv SAgs. Moreover, there is conflicting evidence concerning the capacity of DC to express and present Mtv SAgs. In this report we have analyzed the expression of Mtv SAgs in highly purified thymic and splenic DC and B cells by reverse transcriptase-PCR, using primers amplifying Mtv SAg-specific spliced mRNAs. DC express Mtv SAgs at levels comparable to B cells, but display a differential expression pattern of the various Mtv loci compared with B cells. Furthermore, our results show that DC are able to induce the deletion of SAg-reactive thymocytes in an in vitro assay, indicating that Mtv SAgs are functionally expressed on the DC surface. Collectively, our data are consistent with the hypothesis that DC play a role in the induction of intrathymic tolerance to Mtv SAgs.

Caracterização micropedológica de alguns solos da Zona da Mata Mineira

Realizou-se o estudo micromorfológico de oito solos da Zona da Mata Mineira, incluindo um Latossolo Una, dois Podzólicos Vermelho-Escuros, dois Brunizéns Avermelhados, uma Terra Roxa Estruturada, um Vertissolo e um Podzólico Vermelho-Amarelo câmbico. Após coleta, impregnação, polimerização e preparo de seções finas, estas foram analisadas por microscopia óptica para estudo micropedológico, caracterizando a microestrutura, porosidade, esqueleto, organização do plasma e estruturas associadas, com destaque para a argila iluviada. Em adição, análises em microscópio eletrônico de varredura da superfície de agregados foram realizadas em agregados individualizados. O horizonte B do Latossolo estudado apresenta forte microestrutura com influência de atividade biológica, que tende a coalescer intensamente em profundidade e torna-se apédico no saprolito, separado por cascalheiro de quartzo. Nódulos de hematita em processo de degradação foram observados, indicando o processo atual de goethização dos solos, notadamente no Vertissolo e no Latossolo Una. O estudo micromorfológico evidenciou solos com Bt que apresentaram cerosidade forte em observação macroscópica e não a evidenciaram claramente em microscópio, sendo esse fato mais marcante nos solos mais vermelhos. Solos com Bt mais amarelados mostraram cerosidade fraca no campo, com correspondente detecção de cutãs iluviais em microscopia óptica. O Podzólico Vermelho-Amarelo câmbico, com cerosidade fraca e comum no campo, não teve sua presença confirmada em nível microscópico, evidenciando seu caráter câmbico. Esse solo evidencia nódulos de hematita circundados por gibbsita, o que poderia contribuir para explicar a manutenção dos altos teores de óxidos de ferro desses solos. A não-confirmação, ao microscópio, da cerosidade descrita em campo nos solos com Bt indica a necessidade da intensificação de estudos (descrição x micropedologia) na tentativa de melhor aferição e consistência de resultados.

Comparação de métodos de campo para determinação da velocidade de infiltração básica

Vários são os métodos utilizados para determinar a velocidade de infiltração básica (VIB) do solo. Todavia, para utilização dos resultados, é importante conhecer como cada método interage com os atributos do solo. Assim, o objetivo deste trabalho foi comparar quatro métodos de determinação da VIB, considerando o tipo de solo sob sistema plantio direto. Foram realizados três experimentos em solos do estado de São Paulo, em Campinas, Campos Novos Paulista e Pindorama, em Latossolo textura argilosa, Latossolo textura média e Argissolo textura arenosa/média, respectivamente. As determinações foram feitas de setembro a novembro de 2000. Utilizaram-se um infiltrômetro de aspersão, um permeâmetro, um infiltrômetro de tensão e um infiltrômetro de pressão para determinação da VIB. Verificou-se que os métodos comportaram-se diferentemente em relação ao tipo de solo, tendo sido os menores valores de VIB determinados com o infiltrômetro de aspersão. Verificou-se que, no infiltrômetro de pressão e no permeâmetro, o movimento de água foi governado pela estrutura do solo e, no infiltrômetro de aspersão, onde é considerado o impacto das gotas de chuva, o processo de infiltração foi regido principalmente pela taxa de cobertura do solo e pelas suas características granulométricas.

Efficient T cell activation requires an optimal dwell-time of interaction between the TCR and the pMHC complex.

Cytotoxic T cell (CTL) activation by antigen requires the specific detection of peptide-major histocompatibility class I (pMHC) molecules on the target-cell surface by the T cell receptor (TCR). We examined the effect of mutations in the antigen-binding site of a Kb-restricted TCR on T cell activation, antigen binding and dissociation from antigen.These parameters were also examined for variants derived from a Kd-restricted peptide that was recognized by a CTL clone. Using these two independent systems, we show that T cell activation can be impaired by mutations that either decrease or increase the binding half-life of the TCR-pMHC interaction. Our data indicate that efficient T cell activation occurs within an optimal dwell-time range of TCR-pMHC interaction. This restricted dwell-time range is consistent with the exclusion of either extremely low or high affinity T cells from the expanded population during immune responses.

Compartmentalized secretory leukocyte protease inhibitor expression and hormone responses along the reproductive tract of postmenopausal women

Immunity and hormonal responses in the reproductive tissues of postmenopausal women are poorly understood. Secretory leukocyte protease inhibitor (SLPI), a multifunctional antimicrobial protein expressed at mucosal surfaces, is thought to play a key role in infectious and inflammatory contexts. The aim of this study was to measure SLPI production along the female reproductive tract in postmenopausal women with and without hormonal treatment. We additionally quantified estrogen receptor alpha (ERα) and progesterone receptor A (PRA) in these tissues. Expression of SLPI was decreased in the vagina and ectocervix of women under hormonal treatment. Endocervical ERα mRNA expression was increased while this did not reach significance at the protein level. SLPI expression in the endometrium was not influenced by hormonal treatment. We observed attenuated ERα expression in the cervix and endometrium of hormonally treated women, whereas vaginal expression was increased. PRA expression was augmented in the cervix and endometrium and unchanged in the vagina. Taken together, our results indicate that hormonal responses and receptor expression are differentially regulated in vaginal tissue compared with the cervix and endometrium.

Alterações químicas em solo submetido a diferentes formas de manejo do cafeeiro

A difusão de pacotes tecnológicos que preconizam o uso de altas dosagens de adubos químicos e o controle de pragas e doenças, como métodos para manter o potencial produtivo das lavouras, obriga o produtor a utilizar aplicações sistemáticas de fertilizantes inorgânicos e pesticidas, o que vem afetando a sustentabilidade do agroecossistema cafeeiro, gerando uma total dependência de insumos industrializados. O objetivo deste estudo foi relacionar as mudanças nas características químicas, físicas e microbiológicas de um Latossolo Vermelho distrófico (LVd), da região de Santo Antônio do Amparo (MG), sob agroecossistemas de produção de "café orgânico", "em conversão" e "convencional", em relação a um fragmento de mata nativa. Em duas fazendas sob influência de condições similares de clima e relevo, apresentando o mesmo cultivar (Acaiá IAC474-19) e idade da lavoura (cinco anos), foi realizado um levantamento de dados por um período de um ano. O solo foi amostrado na profundidade de 0-20 cm, em duas épocas (julho/1999 e dezembro/1999). A análise de componentes principais permitiu uma visualização conjunta das características que mais influíram no comportamento do solo dos diferentes sistemas estudados. De modo geral, as formas de manejo para produção de café orgânico, em conversão e convencional, proporcionaram aumentos na fertilidade do solo, quando comparados com a condição do solo do fragmento de mata nativa. No agroecossistema de produção de café orgânico, foram obtidas maiores alterações das características químicas em relação ao convencional; houve incrementos no pH e nos valores de Ca, Mg, K, P, Zn, B, CTC do solo, soma de bases, saturação por bases e diminuição do Al trocável.

Anorectal malformations and pregnancy-related disorders: a registry-based case-control study in 17 European regions.

OBJECTIVE: To identify pregnancy-related risk factors for different manifestations of congenital anorectal malformations (ARMs). DESIGN: A population-based case-control study. SETTING: Seventeen EUROCAT (European Surveillance of Congenital Anomalies) registries, 1980-2008. POPULATION: The study population consisted of 1417 cases with ARM, including 648 cases of isolated ARM, 601 cases of ARM with additional congenital anomalies, and 168 cases of ARM-VACTERL (vertebral, anal, cardiac, tracheo-esophageal, renal, and limb defects), along with 13 371 controls with recognised syndromes or chromosomal abnormalities. METHODS: Multiple logistic regression analyses were used to calculate adjusted odds ratios (ORs) for potential risk factors for ARM, such as fertility treatment, multiple pregnancy, primiparity, maternal illnesses during pregnancy, and pregnancy-related complications. MAIN OUTCOME MEASURES: Adjusted ORs for pregnancy-related risk factors for ARM. RESULTS: The ARM cases were more likely to be firstborn than the controls (OR 1.6, 95% CI 1.4-1.8). Fertility treatment and being one of twins or triplets seemed to increase the risk of ARM in cases with additional congenital anomalies or VACTERL (ORs ranging from 1.6 to 2.5). Maternal fever during pregnancy and pre-eclampsia were only associated with ARM when additional congenital anomalies were present (OR 3.9, 95% CI 1.3-11.6; OR 3.4, 95% CI 1.6-7.1, respectively), whereas maternal epilepsy during pregnancy resulted in a five-fold elevated risk of all manifestations of ARM (OR 5.1, 95% CI 1.7-15.6). CONCLUSIONS: This large European study identified maternal epilepsy, fertility treatment, multiple pregnancy, primiparity, pre-eclampsia, and maternal fever during pregnancy as potential risk factors primarily for complex manifestations of ARM with additional congenital anomalies and VACTERL.

Equipes de psychiatrie mobiles pour les trois âges de la vie: l'expérience lausannoise [Psychiatric mobile teams for the three ages of live: the Lausanne experience]

Des équipes mobiles de psychiatrie ont été développées dans les trois âges pour répondre aux besoins de personnes qui devraient bénéficier d'une évaluation ou de soins spécialisés, lorsque ceux-ci doivent avoir lieu à domicile. Pour arriver à ce but, les équipes tissent de forts liens de partenariat dans le réseau, que ce soit avec les proches ou avec les professionnels impliqués. Les principes généraux d'intervention sont semblables entre les âges : une population cible définie, une intervention à domicile au bénéfice également des proches et des soins de proximité, des équipes pluridisciplinaires avec une charge de cas limitée pour garantir leur disponibilité. Les spécificités de chaque âge seront analysées. Mobile teams have been developed for the three ages to meet the needs of people who should receive--but do not access to--a psychiatric assessment or to specialized care. To achieve this goal, the teams built a strong partnership within the social network, both with relatives and professionals involved. The general principles of intervention are similar between the ages: a focused target population, assertive outreach which benefits also relatives and carers, multidisciplinary teams with a limited caseload to ensure availability. The specificities of each age will be analyzed

DNA mismatch repair gene MSH6 implicated in determining age at natural menopause.

The length of female reproductive lifespan is associated with multiple adverse outcomes, including breast cancer, cardiovascular disease and infertility. The biological processes that govern the timing of the beginning and end of reproductive life are not well understood. Genetic variants are known to contribute to ∼50% of the variation in both age at menarche and menopause, but to date the known genes explain <15% of the genetic component. We have used genome-wide association in a bivariate meta-analysis of both traits to identify genes involved in determining reproductive lifespan. We observed significant genetic correlation between the two traits using genome-wide complex trait analysis. However, we found no robust statistical evidence for individual variants with an effect on both traits. A novel association with age at menopause was detected for a variant rs1800932 in the mismatch repair gene MSH6 (P = 1.9 × 10(-9)), which was also associated with altered expression levels of MSH6 mRNA in multiple tissues. This study contributes to the growing evidence that DNA repair processes play a key role in ovarian ageing and could be an important therapeutic target for infertility.

Die Befragung von Menschen am Rande der Gesellschaft: Bericht über eine Feldstudie bei Alkohol- und Drogenkranken im öffentlichen Raum.

Im Jahr 2008 befragte eine Forschergruppe randständige Menschen, die sich im öffentlichen Raum treffen, und ihr Umfeld in fünf kleineren und grösseren Schweizer Städten. Die Forschenden wollten sich dabei nicht nur der Suchtproblematik widmen, sondern auch Angaben zum sozialen Netzwerk, der psychischen und physischen Gesundheit und der Motivation der Randständigen für ihren Aufenthalt in der Öffentlichkeit erhalten. Die Resultate der Studie wurden bereits früher publiziert. In diesem Artikel geht es um die Rahmenbedingungen, welche die Befragungen der Menschen am Rande der Gesellschaft möglich machten. Er zeigt, dass es zentral ist, eine vertrauensvolle Beziehung zwischen Befragenden und Randständigen aufzubauen, wenn Angaben in guter Qualität gewonnen werden sollen. Der Bericht zeigt, dass mit einer offenen und zuhörenden Haltung der Befragenden die Randständigenkeineswegs abgeneigt sind, diesen Auskunft auch über persönliche Themen zu geben. Für sie war es eine Gelegenheit, ihre Anliegen über die Grenzen ihrer Szene hinaus zu kommunizieren. [Autoren]

Matrix metalloproteinase 9 (MMP-9/gelatinase B) proteolytically cleaves ICAM-1 and participates in tumor cell resistance to natural killer cell-mediated cytotoxicity.

Shedding of intercellular adhesion molecule 1 (ICAM-1) is believed to play a role in tumor cell resistance to cell-mediated cytotoxicity. However, the mechanism whereby ICAM-1 is shed from the surface of tumor cells remains unclear. In this study, we have addressed the possibility that matrix metalloproteinases are implicated in ICAM-1 shedding. Our observations suggest a functional relationship between ICAM-1 and matrix metalloproteinase 9 (MMP-9) whereby ICAM-1 provides a cell surface docking mechanism for proMMP-9, which, upon activation, proteolytically cleaves the extracellular domain of ICAM-1 leading to its release from the cell surface. MMP-9-dependent shedding of ICAM-1 is found to augment tumor cell resistance to natural killer (NK) cell-mediated cytotoxicity. Taken together, our observations propose a mechanism for ICAM-1 shedding from the cell surface and provide support for MMP involvement in tumor cell evasion of immune surveillance.

B cell response after MMTV infection: extrafollicular plasmablasts represent the main infected population and can transmit viral infection.

The immune response to mouse mammary tumor virus (MMTV) relies on the presentation of an MMTV-encoded superantigen by infected B cells to superantigen-specific T cells. The initial extrafollicular B cell differentiation involved the generation of B cells expressing low levels of B220. These B220low B cells corresponded to plasmablasts that expressed high levels of CD43 and syndecan-1 and were CD62 ligand- and IgD-. Viral DNA was detected nearly exclusively in these B220low B cells by PCR, and retroviral type-A particles were observed in their cytoplasm by electron microscopy. An MMTV transmission to the offspring was also achieved after transfer of B220low CD62 ligand- CD43+ plasmablasts into noninfected females. These data suggest that B220low plasmablasts, representing the bulk of infected B cells, are capable of sustaining viral replication and may be involved in the transmission of MMTV.

Trinkerszenen im öffentlichen Raum: ein Städtevergleich.

Ein ethnographischer Vergleich von Trinkerszenen in fünf Schweizer Städten zeigt eine zunehmende Reglementierung und konsumorientierte Ökonomisierung des öffentlichen Raums und entsprechende Ausgrenzungsmechanismen gegenüber den sich dort aufhaltenden Gruppen. Die Politik der Städte weist jedoch auch erhebliche Unterschiede auf.