AVALIAÇÃO DO PAPEL DE RECEPTORES TIPO TOLL 2 e 4 NA RESPOSTA IMUNE DE INDIVÍDUOS, SADIOS REATIVOS OU NÃO AO TESTE TUBERCULÍNICO, FRENTE AO DESAFIO in vitro COM Mycobacterium tuberculosis.

Acredita-se que indivíduos PPD+ representam um dos maiores reservatórios de transmissão da tuberculose, pois podem sofrer uma reativação da tuberculose latente e transmitir silenciosamente o bacilo Mycobacterium tuberculosis (Mtb) para seus contactantes. Em relação aos casos de tuberculose ativa existentes, sabe-se que a maioria é devido à reativação da infecção latente. Portanto a latência ainda é um grande obstáculo para alcançar o controle da tuberculose. A capacidade de controlar a infecção pelo Mtb está correlacionada com as funções imunológicas do hospedeiro. Os receptores Tipo Toll, principalmente TLR2 e TLR4, podem exercer participação direta a respeito dessa função imune, visto que possuem capacidade de iniciarem e direcionarem tanto a resposta inata quanto a adaptativa. Dessa forma, o objetivo deste estudo foi avaliar o papel de receptores do tipo Toll 2 e 4 na resposta imune de indivíduos sadios reativos ou não ao teste tuberculínico (PPD+ e PPD-) frente ao desafio in vitro com Mycobacterium tuberculosis. Para isso, foram arrolados 13 indivíduos PPD+ e 11 indivíduos PPD-, nos quais avaliamos: 1) a frequência de células T reguladoras, 2) a atividade microbicida, e o 3) perfil de citocinas e óxido nítrico, após a infecção com o Mtb com ou sem o bloqueio dos receptores TLR2 e TLR4. Observamos que indivíduos PPD+ apresentaram maior frequência de células T reguladoras e carga bacilar que o grupo PPD- e que os receptores TLR2 e TLR4 possuem papel distinto na ativação da resposta imune. O bloqueio do receptor TLR2 reduziu a frequência de células T reguladoras e a capacidade microbicida do grupo PPD+. Por outro lado o bloqueio do receptor TLR4 aumentou a capacidade microbicida dos grupos PPD+ e PPD-, o que pode estar associado à redução na produção da citocina IL10. Dessa forma, nossos dados sugerem que a pré-exposição ao Mtb e/ou micobactérias ambientais, apesar de levar a uma memória imunológica nos indivíduos PPD+, não influencia na capacidade de eliminação do patógeno por esse grupo. Diversos mecanismos podem estar associados a essa dificuldade na eliminação do Mtb sendo a imunorregulação provocada pelo aumento de células T reguladoras um desses mecanismos. Além disso, observamos que os receptores TLR 2 e TLR4 possuem capacidade de modular a resposta imune contra o Mtb e podem ser futuros alvos para tratamentos anti-TB e quimioprofilaxia da TB latente. Palavras-chave: Mycobacterium tuberculosis, tuberculose latente, Purified Protein Derivative, PPD, células T reguladoras, receptores tipo Toll

Avaliação da ação anti-oxidante de coberturas a base da proteína Z19 do milho BR451 em noz Macadâmia.

bitstream/CNPDIA-2009-09/11887/1/CiT45_2008.pd

Highly indistinguishable single photons from incoherently and coherently excited GaAs quantum dots

Semiconductor quantum dots are converging towards the demanding requirements of photonic quantum technologies. Among different systems, quantum dots with dimensions exceeding the free-exciton Bohr radius are appealing because of their high oscillator strengths. While this property has received much attention in the context of cavity quantum electrodynamics, little is known about the degree of indistinguishability of single photons consecutively emitted by such dots and on the proper excitation schemes to achieve high indistinguishability. A prominent example is represented by GaAs quantum dots obtained by local droplet etching, which recently outperformed other systems as triggered sources of entangled photon pairs. On these dots, we compare different single-photon excitation mechanisms, and we find (i) a "phonon bottleneck" and poor indistinguishability for conventional excitation via excited states and (ii) photon indistinguishablilities above 90% for both strictly resonant and for incoherent acoustic- and optical-phonon-assisted excitation. Among the excitation schemes, optical phonon-assisted excitation enables straightforward laser rejection without a compromise on the source brightness together with a high photon indistinguishability

Normas foliares para café conilon em pré-florada no sul da Bahia.

Objetivou-se estabelecer faixas de suficiências e normas DRIS para lavouras de cafeeiro Conilon em pré-florada, para região sul da Bahia (Atlântico)

Whole genome methylation profiles as independent markers of survival in stage IIIc melanoma patients

Background: The clinical course of cutaneous melanoma (CM) can differ significantly for patients with identical stages of disease, defined clinico-pathologically, and no molecular markers differentiate patients with such a diverse prognosis. This study aimed to define the prognostic value of whole genome DNA methylation profiles in stage III CM.Methods: Genome-wide methylation profiles were evaluated by the Illumina Human Methylation 27 BeadChip assay in short-term neoplastic cell cultures from 45 stage IIIC CM patients. Unsupervised K-means partitioning clustering was exploited to sort patients into 2 groups based on their methylation profiles. Methylation patterns related to the discovered groups were determined using the nearest shrunken centroid classification algorithm. The impact of genome-wide methylation patterns on overall survival (OS) was assessed using Cox regression and Kaplan-Meier analyses.Results: Unsupervised K-means partitioning by whole genome methylation profiles identified classes with significantly different OS in stage IIIC CM patients. Patients with a " favorable" methylation profile had increased OS (P = 0.001, log-rank = 10.2) by Kaplan-Meier analysis. Median OS of stage IIIC patients with a " favorable" vs. " unfavorable" methylation profile were 31.5 and 10.4 months, respectively. The 5 year OS for stage IIIC patients with a " favorable" methylation profile was 41.2% as compared to 0% for patients with an " unfavorable" methylation profile. Among the variables examined by multivariate Cox regression analysis, classification defined by methylation profile was the only predictor of OS (Hazard Ratio = 2.41, for " unfavorable" methylation profile; 95% Confidence Interval: 1.02-5.70; P = 0.045). A 17 gene methylation signature able to correctly assign prognosis (overall error rate = 0) in stage IIIC patients on the basis of distinct methylation-defined groups was also identified.Conclusions: A discrete whole-genome methylation signature has been identified as molecular marker of prognosis for stage IIIC CM patients. Its use in daily practice is foreseeable, and promises to refine the comprehensive clinical management of stage III CM patients. © 2012 Sigalotti et al.; licensee BioMed Central Ltd

Immunotherapy of brain metastases: breaking a "dogma"

Until very few years ago, the oncology community dogmatically excluded any clinical potential for immunotherapy in controlling brain metastases. Therefore, despite the significant therapeutic efficacy of monoclonal antibodies to immune check-point(s) across a wide range of tumor types, patients with brain disease were invariably excluded from clinical trials with these agents. Recent insights on the immune landscape of the central nervous system, as well as of the brain tumor microenvironment, are shedding light on the immune-biology of brain metastases. Interestingly, retrospective analyses, case series, and initial prospective clinical trials have recently investigated the role of different immune check-point inhibitors in brain metastases, reporting a significant clinical activity also in this subset of patients. These findings, and their swift translation in the daily practice, are driving fundamental changes in the clinical management of patients with brain metastases, and raise important neuroradiologic challenges. Along this line, neuro-oncology undoubtedly represents an additional area of active investigation and of growing interest to support medical oncologists in the evaluation of clinical responses of brain metastases to ICI treatment, and in the management of neurologic immune-related adverse events. Aim of this review is to summarize the most recent findings on brain metastases immunobiology, on the evolving scenario of clinical efficacy of ICI therapy in patients with brain metastases, as well as on the increasing relevance of neuroradiology in this therapeutic setting

Highly indistinguishable single photons from droplet-etched GaAs quantum dots integrated in single-mode waveguides and beamsplitters

The integration of on-demand quantum emitters into photonic integrated circuits (PICs) has drawn much of attention in recent years, as it promises a scalable implementation of quantum information schemes. A central property for several applications is the indistinguishability of the emitted photons. In this regard, GaAs quantum dots (QDs) obtained by droplet etching epitaxy show excellent performances with visibilities close to one for both individual and remote emitters. Therefore, the realization of these QDs into PICs is highly appealing. Here, we show the first implementation in this direction, realizing the key passive elements needed in PICs, i.e. single-mode waveguides (WGs) with integrated GaAs-QDs, which can be coherently controlled, as well as beamsplitters. We study both the statistical distribution of wavelength, linewidth and decay times of the excitonic line of multiple QDs, as well as the quantum optical properties of individual emitters under resonant excitation. Here, we achieve single-photon purities as high as $1-\text{g}^{(2)}(0)=0.929\pm0.009$ as well as two-photon interference visibilities of up to V$_{\text{TPI}}=0.939\pm0.004$ for two consecutively emitted photons