PLCε1 suppresses tumor growth by regulating murine T cell mobilization

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/154282/1/cei13409.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/154282/2/cei13409_am.pd

The tyrosine phosphatase SHP-1 promotes T cell adhesion by activating the adaptor protein CrkII in the immunological synapse

The adaptor protein CrkII is a key regulator of T cell adhesion through the recruitment of the Rap1-guanine exchange factor, C3G. Subsequently, Rap1 activates the integrin LFA-1 leading to T cell adhesion and interaction with antigen presenting cells (APC). The interphase between T cell and APC is known as the immunological synapse (IS). It is characterized by specific organization of proteins that can be divided into central supramolecular activation clusters (c- SMAC) and peripheral supramolecular activation clusters (p-SMAC). Using TIRF microscopy and support lipid bilayers we determined that activated Rap1 was recruited to the IS. Within the IS, Rap1 was localized to the p-SMAC. C3G and the active (dephosphorylated) form of CrkII were also localized to the same compartment. In contrast, inactive (phosphorylated) CrkII was limited to the c-SMAC. We then showed that activation of CrkII and subsequent trafficking from the c-SMAC to the p-SMAC were regulated by the phosphatase SHP-1 downstream of the antigen receptor. In the p-SMAC, CrkII recruited C3G, leading to Rap1 activation and LFA-1 mediated adhesion. Functionally, SHP-1 was necessary for both adhesion and migration of T cells. Thus, we uncovered a new signaling pathway where SHP-1 acts through CrkII to reshape the pattern of Rap1 activation in the IS

Expressão gênica em resposta a deficiência nutricional em folhas resistentes e suscetíveis ao bicho-mineiro.

A resposta de defesa de cafeeiros infestados pelo bicho-mineiro (Leucoptera coffeela) é influenciado por aspectos fisiológicos entre os quais está a disponibilidade de nutrientes. Plantas resistentes podem exibir lesões foliares correspondentes ao desenvolvimento do inseto quando a lavoura tem deficiência de adubação. O conhecimento sobre a interação entre mecanismos de transporte de nutrientes e resposta de defesa ao bicho-mineiro podem contribuir na elucidação da resistência ao inseto em cafeeiros. Este estudo avaliou a expressão relativa de genes associados ao metabolismo de potássio e nitrogênio, ao estresse oxidativo e a mecanismos de defesa em mudas de cafés submetidas a condições nutricionais limitantes. Mudas de progênies resistentes e suscetíveis ao bicho-mineiro foram mantidas em soluções contendo concentrações variáveis de macronutrientes (N+K+, N+K-, N-K+, N-K-). Após o tratamento, as folhas foram coletadas para extração do RNA e posterior caracterização da expressão de genes por qRT -PCR. Genes do metabolismo de potássio apresentaram expressão diferencial entre plantas resistentes e suscetíveis. O perfil de expressão dos genes do metabolismo de Nitrogênio não apresentou diferenças entre as progênies. Além disso, genes diretamente relacionados com a defesa ao bicho-mineiro e ao estresse oxidativo apresentaram expressões diferenciais significativas entre plantas resistentes e suscetíveis. Estas análises preliminares sugerem que a regulação da absorção e/ou transporte de nutrientes não são atividades iniciais na resposta de cafeeiros, e que a ativação de mecanismos de defesa em geral é a resposta inicial à deficiência nutricional

CD3e expression in HTLV-1-infected individuals is associated with proviral load and Tax expression

Financial support: FUNDHERP, CTC, INCTC, FAPESP, CNPq and CAPES

Desenvolvimento de marcadores associados à resistência do bicho-mineiro: seleção e validação de SNPs.

O objetivo deste estudo é o desenvolvimento de marcadores do tipo SNPs associados com a resistência ao bicho-mineiro em café. A estratégia principal utilizou as análises genômicas de microarranjo, para caracterização de expressão diferencial de genes-candidatos em plantas resistentes infestadas com o bicho-mineiro. Inicialmente, análises in silico de 2137 destes genes identificaram aqueles potencialmente relacionados com a especificidade da resposta de defesa da planta. Uma vez selecionados, o perfil de expressão de 22 genes foi confirmado por qRT-PCR em experimentos utilizando plantas resistentes e suscetíveis, infectadas pelo bicho-mineiro. Para busca de polimorfismos do tipo SNPs, que poderão ser utilizados como marcadores para seleção-assistida, selecionamos 4 genes, cujas regiões genômicas foram clonadas e sequenciadas em genótipos parentais da população em estudo. Após análises in silico de sequências genômicas, os polimorfismos do tipo SNPs identificados serviram de base para construção de sondas alelo-específicas, utilizadas na genotipagem de plantas parentais e progênies em seleção. A análise de segregação de SNPs identificados indicou que nenhum dos polimorfismos avaliados apresenta correlação com a característica de resistência ao bicho-mineiro. Estes polimorfismos estão associados com alguma outra característica agronômica não avaliada neste estudo. A genotipagem de outros SNPs identificados está em andamento.Título em inglês: Development of molecular markers associated with leaf-miner resistance: selection and validation of SNPs

Mechanical shear stress and leukocyte phenotype and function: Implications for ventricular assist device development and use

Heart failure (HF) remains a disease of ever increasing prevalence in the modern world. Patients with end-stage HF are being referred increasingly for mechanical circulatory support (MCS). MCS can assist patients who are ineligible for transplant and stabilise eligible patients prior to transplantation. It is also used during cardiopulmonary bypass (CPB) surgery to maintain circulation whilst operating on the heart. Whilst MCS can stabilise HF and improve quality of life, complications such as infection and thrombosis remain a common risk. Leukocytes can contribute to both of these complications. Contact with foreign surfaces and the introduction of artificial mechanical shear stress can lead to activation of leukocytes, reduced functionality, and the release of pro-inflammatory and pro-thrombogenic microparticles. Assessing the impact of mechanical trauma to leukocytes is largely overlooked in comparison to red blood cells and platelets. This review provides an overview of the available literature on the effects of in vitro to clinical MCS systems on leukocyte phenotype and function. One purpose of this review is to emphasise the importance of studying mechanical trauma to leukocytes to better understand the occurrence of adverse events during MCS

HIV prevalence among female sex workers, drug users and men who have sex with men in Brazil: A Systematic Review and Meta-analysis

<p>Abstract</p> <p>Background</p> <p>The Brazilian response towards AIDS epidemic is well known, but the absence of a systematic review of vulnerable populations ─ men who have sex with men (MSM), female sex workers (FSW), and drug users (DU) remains a main gap in the available literature. Our goal was to conduct a systematic review and meta-analysis of studies assessing HIV prevalence among MSM, FSW and DU, calculating a combined pooled prevalence and summarizing factors associated the pooled prevalence for each group.</p> <p>Methods</p> <p>Nine electronic databases (MEDLINE via PubMed, EMBASE, Cochrane CENTRAL, AIDSLINE, AMED, CINAHL, TOXNET, SciELO, and ISI-Web of Science) were searched for peer-reviewed papers published in English, French, Spanish or Portuguese, from 1999 to 2009. To be included in the review, studies had to measure HIV prevalence and/or incidence as the primary outcome among at least one specific population under analysis.</p> <p>Results</p> <p>The studies targeting the three populations analyzed mostly young participants aged 30 years or less. Among FSW, eight studies were selected (3,625 participants), consistently identifying higher condom use with sexual clients than with occasional and stable partners. The combined HIV prevalence for FSW was 6.2 (95% CI: 4.4-8.3). Ten studies targeting MSM were identified (6,475 participants). Unprotected anal intercourse was commonly reported on those studies, but with great variability according to the nature of the relationship - stable vs. occasional sex partners - and sexual practice - receptive vs. insertive anal sex. Pooled HIV prevalence for MSM was 13.6 (95% CI: 8.2-20.2). Twenty nine studies targeting DU were identified (13,063 participants). Those studies consistently identified injection drug use and syringe/needle sharing as key predictors of HIV-infection, as well as engagement in sex work and male-to-male sex. The combined HIV prevalence across studies targeting DU was 23.1 (95% CI: 16.7-30.2).</p> <p>Conclusions</p> <p>FSW, MSM and DU from Brazil have a much risk of acquiring HIV infection compared to the general population, among which HIV prevalence has been relatively low (~0.6%). Those vulnerable populations should be targeted by focused prevention strategies that provide accurate information, counseling and testing, as well as concrete means to foster behavior change (e.g. access to condoms, drug abuse treatment, and clean syringes in the case of active injecting drug users), tailored to gender and culture-specific needs. Programs that provide these services need to be implemented on public health services throughout the country, in order to decrease the vulnerability of those populations to HIV infection.</p