Commitment to natural killer cells requires the helix–loop–helix inhibitor Id2

We have previously described how T and natural killer (NK) lineage commitment proceeds from common T/NK progenitors (p-T/NK) in the murine fetal thymus (FT), with the use of a clonal assay system capable of discriminating p-T/NK from unipotent T or NK lineage-committed progenitors (p-T and p-NK, respectively). The molecular mechanisms controlling the commitment processes, however, are yet to be defined. In this study, we investigated the progenitor activity of FT cells from Id2−/− mice that exhibit defective NK cell development. In the Id2−/− FT, NK cells were greatly reduced, and a cell population that exclusively contains p-NK in the wild-type thymus was completely missing. Id2−/− FT progenitors were unable to differentiate into NK cells in IL-2-supplemented-FT organ culture. Single progenitor analysis demonstrated that all Id2−/− fetal thymic progenitors are destined for the T cell lineage, whereas progenitors for T/NK, T, and NK cell lineages were found in the control. Interestingly, the total progenitor number was similar between Id2−/− and Id2+/+ embryos analyzed. Expression of Id2 was correlated with p-NK activity. Our results suggest that Id2 is indispensable in thymic NK cell development, where it most probably restricts bipotent T/NK progenitors to the NK cell lineage.

一种鉴定正品藏茵陈川西獐牙菜的分子试剂盒及其鉴定方法

本发明涉及一种鉴定正品藏茵陈川西獐牙菜的分子试剂盒及其应用。该试剂盒反应液主要由DNA片段引物IDl：GGCTTGCCTCTCGACGCTC，ID2：GCAAGCGTCACGAAGACGCG，和DMSO试剂等组成。该试剂盒的应用包括以下步骤：1、对药材进行总DNA提取；2、利用引物对提取的DNA进行PCR扩增，若得到约500bp片段的扩增产物，则为川西獐牙菜；无此扩增片段，则是伪品种类。

Histone deacetylase 7 controls endothelial cell growth through modulation of beta-catenin

Rationale: Histone deacetylase (HDAC)7 is expressed in the early stages of embryonic development and may play a role in endothelial function.

Objective: This study aimed to investigate the role of HDAC7 in endothelial cell (EC) proliferation and growth and the underlying mechanism.

Methods and Results: Overexpression of HDAC7 by adenoviral gene transfer suppressed human umbilical vein endothelial cell (HUVEC) proliferation by preventing nuclear translocation of ß-catenin and downregulation of T-cell factor-1/Id2 (inhibitor of DNA binding 2) and cyclin D1, leading to G1 phase elongation. Further assays with the TOPFLASH reporter and quantitative RT-PCR for other ß-catenin target genes such as Axin2 confirmed that overexpression of HDAC7 decreased ß-catenin activity. Knockdown of HDAC7 by lentiviral short hairpin RNA transfer induced ß-catenin nuclear translocation but downregulated cyclin D1, cyclin E1 and E2F2, causing HUVEC hypertrophy. Immunoprecipitation assay and mass spectrometry analysis revealed that HDAC7 directly binds to ß-catenin and forms a complex with 14-3-3 e, ?, and ? proteins. Vascular endothelial growth factor treatment induced HDAC7 degradation via PLC?-IP3K (phospholipase C?–inositol-1,4,5-trisphosphate kinase) signal pathway and partially rescued HDAC7-mediated suppression of proliferation. Moreover, vascular endothelial growth factor stimulation suppressed the binding of HDAC7 with ß-catenin, disrupting the complex and releasing ß-catenin to translocate into the nucleus.

Conclusions: These findings demonstrate that HDAC7 interacts with ß-catenin keeping ECs in a low proliferation stage and provides a novel insight into the mechanism of HDAC7-mediated signal pathways leading to endothelial growth

Maximizing the Social Welfare of Virtual Power Players Operation in Case of Excessive Wind Power

The integration of growing amounts of distributed generation in power systems, namely at distribution networks level, has been fostered by energy policies in several countries around the world, including in Europe. This intensive integration of distributed, non-dispatchable, and natural sources based generation (including wind power) has caused several changes in the operation and planning of power systems and of electricity markets. Sometimes the available non-dispatchable generation is higher than the demand. This generation must be used; otherwise it is wasted if not stored or used to supply additional demand. New policies and market rules, as well as new players, are needed in order to competitively integrate all the resources. The methodology proposed in this paper aims at the maximization of the social welfare in a distribution network operated by a virtual power player that aggregates and manages the available energy resources. When facing a situation of excessive non-dispatchable generation, including wind power, real time pricing is applied in order to induce the increase of consumption so that wind curtailment is minimized. This method is especially useful when actual and day-ahead resources forecast differ significantly. The distribution network characteristics and concerns are addressed by including the network constraints in the optimization model. The proposed methodology has been implemented in GAMS optimization tool and its application is illustrated in this paper using a real 937-bus distribution network with 20.310 consumers and 548 distributed generators, some of them non-dispatchable and with must take contracts. The implemented scenario corresponds to a real day in Portuguese power system.

Transcriptional regulation of effector CD8+ T cell differentiation and molecular dysfunction during HIV-1 infection

Les cellules T CD8+ jouent un rôle primordial dans le contrôle des infections virales en limitant la dissémination des cellules infectées. Lors de l’infection chronique par le virus HIV, les cellules T CD8+ HIV-spécifiques ne se différencient pas en cellules effectrices fonctionnelles capables de tuer les cellules infectées par le virus ; ces cellules ne sont plus capables de proliférer ou de produire l’ IL-2. Ces cellules expriment PD-1 et l’engagement de PD-1, par son ligand, aboutit a plusieurs de ces déficits fonctionnels des cellules T . Le rôle de PD-1 dans la régulation d'évènements transcriptionnels contrôlant la différentiation et l'obtention des fonction effectrices des cellules T CD8+ reste à démontrer. Id2 joue un rôle central dans la différenciation des cellules T CD8+ effectrices. Nous avons émis l’hypothèse que le défaut de maturation observé chez les cellules T CD8+ PD-1 high HIV-spécifiques (CD8+PD-1hi) au cours de l’infection chronique par le virus HIV pouvait être lié à la diminution d’expression du régulateur Id2. Nous avons ainsi démontré que l'engagement de PD-1 contribuait à une diminution d'expression de Id2 et de ses cibles transcriptionnelles. La surexpression de Id2 de ces cellules a permis de restaurer l'expression de marqueurs tels que Granzyme B et Bcl-2 et diminuir l’expression du marqueur de maturation de CD27. La famille des cytokines à chaine gamma joue un rôle clef dans la survie et l’homéostasie des cellules T. Dans ce travail, nous avons démontré que l’IL-15 était unique grâce à ses capacités de stimulation de l’expression d’Id2 et ses propriétés favorisant la survie ainsi que la différenciation des cellules T CD8+ effectrices. l’IL-15 induit la prolifération de toutes les populations de cellules T mémoires provenant de donneurs sains. L’addition de cette cytokine aux sous-populations cellulaires Ttm et Tem a permis leur différenciation en cellules effectrices capables de produire Granzyme B alors que la stimulation par l’IL-15 des cellules Tcm ne favorise pas leur différenciation. Un test de cytotoxicitié par cytométrie en flux nous a permis de confirmer que la stimulation de cellules T CD8+ HIV spécifiques par l’IL-15 favorisait l’expression de Id2 et restaurait les fonctions cytotoxiques des cellules T CD8+ HIV spécifiques. En conclusion, nous avons pour la première fois dans cette thèse défini les mécanismes moléculaires impliqués dans la modulation de l’expression du régulateur transcriptionnel Id2 par l’IL-15. Nous avons également révélé comment l’engagement de PD-1 conduisait a une altération de l’expression et de la fonction d’Id2 et favorisait la diminution des fonctions effectrices des cellules T CD8-HIV spécifiques. Une perspective de traitement avec des agents tels que l’IL-15 ou le bloquage de PD-1, en combinaison avec les traitements conventionnels, pourrait contribuer à une meilleure stimulation des réponses immunes favorisant ainsi la réactivation des cellules T CD8+ et permettant la destruction de cellules T CD4+ infectées de manière latente.

Estudo das alterações funcionais respiratórias em pacientes submetidos à colecistectomia videolaparoscópica

Pós-graduação em Bases Gerais da Cirurgia - FMB

Retificador entrelaçado com elevado fator de potência para operação de um veículo trólebus alimentado por redes em CA Ou CC

This paper presents the development and the main results for an interleaved boost rectifier operating as a special input power stage for a trolleybus type vehicle, allowing its feeding by alternate current (AC) or direct current (DC) distribution power systems. When feeding with two wires (single phase) alternate current distribution system, the converter accomplish active power factor correction, providing a relatively sinusoidal current with low total harmonic distortion (THD) and fully complying with IEC 61000-3-4 standards. In addition, a management control system promotes the required automatic operation changes for the proposed rectifier when the vehicle is changing from the DC distribution power system to the AC distribution power system and vice-versa, keeping its original electrical DC system characteristics for the adjustable speed driver sub-system. The main experimental results for a prototype rated at 150kW are presented, considering its application for a trolleybus with DC adjustable speed driver, demonstrating the proposed converter benefits and the possibility of AC feeding system for trolleybus type vehicle.

Compensação ativa paralela baseada na teoria de potência conservativa

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Estratégia de controle multifuncional para sistemas fotovoltaicos de geração de energia elétrica

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Microinversor integrado ao módulo fotovoltaico para sistemas conectados à rede elétrica utilizando controlador ressonante

This paper shows the modeling and control of a single-phase full-bridge inverter with high-frequency transformer that may be used as part of a two-stage converter with transformerless DC-DC side or as a single-stage converter (simple DC-AC converter) for grid-connected PV applications. The inverter is modeled in order to obtain a small-signal transfer function used to design the P+Resonant current controller. A highfrequency step-up transformer results in reduced voltage switches and better efficiency compared with converters in which the transformer is used on the DC-DC side. Simulations and experimental results with a 200 W prototype are shown. 1

Proposta de metodologia para o gerenciamento automático de sistemas fotovoltaicos de geração distribuída

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Controle flexível para conversores monofásicos conectados a sistemas elétricos distorcidos de baixa tensão

This paper presents a technique to add flexibility in the control of power electronic converters. The power converter can function as an active power filter, as a local power source interface or perform both functions i. e. mitigate current disturbances and inject power into the grid simultaneously, configuring it as a multifunctional device. The main goal is to extract the full capability of the grid connected power electronic converter to achieve maximum benefits. To achieve this goal, the orthogonal current decomposition of the Conservative Power Theory is used. Each orthogonal current component is weighted by means of different compensation factors (k_i), which are set instantaneously and independently, in any percentage by means of the load performance factors (λ_i), providing an online flexibility in relation to compensation objectives. Finally, to validate the effectiveness and performance the proposed approach, simulations and experimental results are presented.

Unveiling novel genes upregulated by both rhBMP2 and rhBMP7 during early osteoblastic transdifferentiation of C2C12 cells

Abstract Findings We set out to analyse the gene expression profile of pre-osteoblastic C2C12 cells during osteodifferentiation induced by both rhBMP2 and rhBMP7 using DNA microarrays. Induced and repressed genes were intercepted, resulting in 1,318 induced genes and 704 repressed genes by both rhBMP2 and rhBMP7. We selected and validated, by RT-qPCR, 24 genes which were upregulated by rhBMP2 and rhBMP7; of these, 13 are related to transcription (Runx2, Dlx1, Dlx2, Dlx5, Id1, Id2, Id3, Fkhr1, Osx, Hoxc8, Glis1, Glis3 and Cfdp1), four are associated with cell signalling pathways (Lrp6, Dvl1, Ecsit and PKCδ) and seven are associated with the extracellular matrix (Ltbp2, Grn, Postn, Plod1, BMP1, Htra1 and IGFBP-rP10). The novel identified genes include: Hoxc8, Glis1, Glis3, Ecsit, PKCδ, LrP6, Dvl1, Grn, BMP1, Ltbp2, Plod1, Htra1 and IGFBP-rP10. Background BMPs (bone morphogenetic proteins) are members of the TGFβ (transforming growth factor-β) super-family of proteins, which regulate growth and differentiation of different cell types in various tissues, and play a critical role in the differentiation of mesenchymal cells into osteoblasts. In particular, rhBMP2 and rhBMP7 promote osteoinduction in vitro and in vivo, and both proteins are therapeutically applied in orthopaedics and dentistry. Conclusion Using DNA microarrays and RT-qPCR, we identified both previously known and novel genes which are upregulated by rhBMP2 and rhBMP7 during the onset of osteoblastic transdifferentiation of pre-myoblastic C2C12 cells. Subsequent studies of these genes in C2C12 and mesenchymal or pre-osteoblastic cells should reveal more details about their role during this type of cellular differentiation induced by BMP2 or BMP7. These studies are relevant to better understanding the molecular mechanisms underlying osteoblastic differentiation and bone repair.