Retinoic acid inhibits dendritic cell differentiation driven by interleukin-4

All-trans-retinoic acid (atRA) appears to affect Th1-Th2 differentiation and its effects on immune responses might also be mediated by dendritic cell (DC). Nonetheless, studies have been showing contradictory results since was observed either induction or inhibition of DC differentiation. Our aim was to investigate atRA action on human monocyte derived DC differentiation. For this purpose we tested pharmacological and physiological doses of atRA with or without cytokines. Cell phenotypes were analyzed by flow cytometry and function was investigated by phagocytosis and respiratory burst. DC, positive control group, was differentiated with GM-CSF and IL-4 and maturated with TNF-alpha. We demonstrated that atRA effects depend on the dose used as pharmacological doses inhibited expression of all phenotypic markers tested while a physiological dose caused cell differentiation. However, atRA combined or not with cytokines did not promote DC differentiation. In fact, atRA was detrimental on IL-4 property as a DC inductor. (C) 2009 Elsevier Inc. All rights reserved.

High frequency of immature dendritic cells and altered in situ production of interleukin-4 and tumor necrosis factor-alpha in lung cancer

Introduction Antigen-presenting cells, like dendritic cells (DCs) and macrophages, play a significant role in the induction of an immune response and an imbalance in the proportion of macrophages, immature and mature DCs within the tumor could affect significantly the immune response to cancer. DCs and macrophages can differentiate from monocytes, depending on the milieu, where cytokines, like interleukin (IL)-4 and granulocyte-macrophage colony-stimulating factor (GM-CSF) induce DC differentiation and tumor necrosis factor (TNF)-alpha induce DC maturation. Thus, the aim of this work was to analyze by immunohistochemistry the presence of DCs (S100+ or CD1a+), macrophages (CD68+), IL-4 and TNF-alpha within the microenvironment of primary lung carcinomas. Results Higher frequencies of both immature DCs and macrophages were detected in the tumor-affected lung, when compared to the non-affected lung. Also, TNF-alpha-positive cells were more frequent, while IL-4-positive cells were less frequent in neoplastic tissues. This decreased frequency of mature DCs within the tumor was further confirmed by the lower frequency of CD14-CD80+ cells in cell suspensions obtained from the same lung tissues analyzed by flow cytometry. Conclusion These data are discussed and interpreted as the result of an environment that does not oppose monocyte differentiation into DCs, but that could impair DC maturation, thus affecting the induction of effective immune responses against the tumor.

Involvement of Eukaryotic Translation Initiation Factor 5A (eIF5A) in Skeletal Muscle Stem Cell Differentiation

The eukaryotic translation initiation factor 5A (eIF5A) contains a special amino acid residue named hypusine that is required for its activity, being produced by a post-translational modification using spermidine as substrate. Stem cells from rat skeletal muscles (satellite cells) were submitted to differentiation and an increase of eIF5A gene expression was observed. Higher content of eIF5A protein was found in satellite cells on differentiation in comparison to non-differentiated satellite cells and skeletal muscle. The treatment with NI-guanyl- 1,7-diaminoheptane (GC7), a hypusination inhibitor, reversibly abolished the differentiation process. In association with the differentiation blockage, an increase of glucose consumption and lactate production and a decrease of glucose and palmitic acid oxidation were observed. A reduction in cell proliferation and protein synthesis was also observed. L-Arginine, a spermidine precursor and partial suppressor of muscle dystrophic phenotype, partially abolished the GC7 inhibitory effect on satellite cell differentiation. These results reveal a new physiological role for eIF5A and contribute to elucidate the molecular mechanisms involved in muscle regeneration.

Petrogenesis of Early Cretaceous silicic volcanism in SE Uruguay: The role of mantle and crustal sources

Early Cretaceous (similar to 129 Ma) silicic rocks crop out in SE Uruguay between the Laguna Merin and Santa Lucia basins in the Lascano, Sierra Sao Miguel. Salamanca and Minas areas They are mostly rhyolites with minor quartz-trachytes and are nearly contemporaneous with the Parana-Etendeka igneous province and with the first stages of South Atlantic Ocean opening A strong geochemical variability (particularly evident from Rb/Nb, Nb/Y trace element ratios) and a wide range of Sr-Nd isotopic ratios ((143)Nd/(144)Nd((129)) = 0.51178-0.51209, (87)Sr/(86)Sr((129)) = 0.70840-0.72417) characterize these rocks Geochemistry allows to distiniguish two compositional groups, corresponding to the north-eastern (Lascano and Sierra Sao Miguel, emplaced on the Neo-Proterozoic southern sector of the Dom Feliciano mobile belt) and south-eastern localities (Salamanca, Minas, emplace on the much older (Archean) Nico Perez teriane or on the boundary between the Dom Feliciano and Nico Perez termites) These compositional differences between the two groups are explained by variable mantle source and crust contributions. The origin of the silicic magmas is best explained by complex processes involving assimilation and fractional crystallization and mixing of a basaltic magma with upper crustal lithologies, for Lascano and Sierra Sao Miguel rhyolites. In the Salamanea and Minas rocks genesis, a stronger contribution from lower crust is indicated.

Integration eller illusion : et deviance-perspektiv

Integration or illusion – a deviance perspective Denmark experienced one of its most successful periods of economic growth in 2004– 2008 with a tremendous reduction of unemployment, which in June 2008 was around. 1.5 percent, far below the expected level of structural unemployment. In the wake of this development the lack of utilization of migrants’ educations and skills became, once again, a core concern. The political, societal and academic debate followed to a great extent the traditional top-down approach to the problem and revolved around two axes: 1. How effective the labour market was/is to make use of migrants’ skills. 2. Whether there were patterns of over-education as expression of institutional and societal discrimination. The focus of the present study is, however, quite different: We examine the pattern of deviance in relation to labour market participation (not integration), and instead of searching for explanations for the lack of integration, we attempt to identify and explain the deviance pattern as a product of institutionally inherent possibilities and barriers on the one hand and articulating immigrants as rational actors (not victims) on the other. We argue that deviance is not only a more fruitful theoretical and analytical framework than integration and discrimination. Taking departure in empirical evidence on immigrants’ preferences and behaviour as bounded rational actors, and how they actually articulate their everyday life practical experiences, including adjustment of what they want and what they can, the deviance perspective, we believe, also reduces the theoretical and normative biases, that characterises the discrimination and integration framework, and provide more reliable explanations. 

City Of Toronto’S Approach On Implementing The New Federal Wastewater Effluent Regulations Using A GIS-Based Hydrologic And Hydraulic Model

Canada releases over 150 billion litres of untreated and undertreated wastewater into the water environment every year1. To clean up urban wastewater, new Federal Wastewater Systems Effluent Regulations (WSER) on establishing national baseline effluent quality standards that are achievable through secondary wastewater treatment were enacted on July 18, 2012. With respect to the wastewater from the combined sewer overflows (CSO), the Regulations require the municipalities to report the annual quantity and frequency of effluent discharges. The City of Toronto currently has about 300 CSO locations within an area of approximately 16,550 hectares. The total sewer length of the CSO area is about 3,450 km and the number of sewer manholes is about 51,100. A system-wide monitoring of all CSO locations has never been undertaken due to the cost and practicality. Instead, the City has relied on estimation methods and modelling approaches in the past to allow funds that would otherwise be used for monitoring to be applied to the reduction of the impacts of the CSOs. To fulfill the WSER requirements, the City is now undertaking a study in which GIS-based hydrologic and hydraulic modelling is the approach. Results show the usefulness of this for 1) determining the flows contributing to the combined sewer system in the local and trunk sewers for dry weather flow, wet weather flow, and snowmelt conditions; 2) assessing hydraulic grade line and surface water depth in all the local and trunk sewers under heavy rain events; 3) analysis of local and trunk sewer capacities for future growth; and 4) reporting of the annual quantity and frequency of CSOs as per the requirements in the new Regulations. This modelling approach has also allowed funds to be applied toward reducing and ultimately eliminating the adverse impacts of CSOs rather than expending resources on unnecessary and costly monitoring.

RWater – A Cyber Enabled Tool For Hydrologic Modeling And Analysis

Existing distributed hydrologic models are complex and computationally demanding for using as a rapid-forecasting policy-decision tool, or even as a class-room educational tool. In addition, platform dependence, specific input/output data structures and non-dynamic data-interaction with pluggable software components inside the existing proprietary frameworks make these models restrictive only to the specialized user groups. RWater is a web-based hydrologic analysis and modeling framework that utilizes the commonly used R software within the HUBzero cyber infrastructure of Purdue University. RWater is designed as an integrated framework for distributed hydrologic simulation, along with subsequent parameter optimization and visualization schemes. RWater provides platform independent web-based interface, flexible data integration capacity, grid-based simulations, and user-extensibility. RWater uses RStudio to simulate hydrologic processes on raster based data obtained through conventional GIS pre-processing. The program integrates Shuffled Complex Evolution (SCE) algorithm for parameter optimization. Moreover, RWater enables users to produce different descriptive statistics and visualization of the outputs at different temporal resolutions. The applicability of RWater will be demonstrated by application on two watersheds in Indiana for multiple rainfall events.

A new perspective on the PPP hypothesis

This paper the stastistical properties of the real exchange rates of G-5 countries for the Bretton-Woods peiod, and draw implications on the purchasing power parity (PPP) hypothesis. In contrast to most previous studies that consider only unit root and stationary process to describe the real exchange tae, this paper also considers two in-between processes, the locally persistent process ans the fractionally integrated process, to complement past studies. Seeking to be consistent with tha ample evidence of near unit in the real exchange rate movements very well. This finding implies that: 1) the real exchange movement is more persistent than the stationary case but less persistent than the unit root case; 2) the real exchange rate is non-stationary but the PPP reversion occurs and the PPP holds in the long run; 3) the real exchange rate does not exhibit the secular dependence of the fractional integration; 4) the real exchange rate evolves over time in a way that there is persistence over a range of time, but the effect of shocks will eventually disappear over time horizon longer than order O (nd), that is, at finite time horizon; 5) shocks dissipation is fasters than predicted by the fractional integracion, and the total sum of the effects of a unit innovation is finite, implying that a full PPP reversion occurs at finite horizons. These results may explain why pasrt empirical estudies could not provide a clear- conclusion on the real exchange rate processes and the PPP hypothesis.

Voice over IP 2.0: an analysis of limits and potential of IP2IP telecommunication

Internet Telephony (VoIP) is changing the telecommunication industry. Oftentimes free, VoIP is becoming more and more popular amongst users. Large software companies have entered the market and heavily invest into it. In 2011, for instance, Microsoft bought Skype for 8.5bn USD. This trend increasingly impacts the incumbent telecommunication operators. They see their main source of revenue – classic telephony – under siege and disappear. The thesis at hand develops a most-likely scenario in order to determine how VoIP is evolving further and it predicts, based on a ten-year forecast, the impact it will have on the players in the telecommunication industry.The paper presents a model combining Rogers’ diffusion and Christensen’s innovation research. The model has the goal of explaining the past evolution of VoIP and to isolate the factors that determine the further diffusion of the innovation. Interviews with industry experts serve to assess how the identified factors are evolving.Two propositions are offered. First, VoIP operators are becoming more important in international, corporate, and mobile telephony. End-to-end VoIP (IP2IP) will exhibit strong growth rates and increasingly cannibalize the telephony revenues of the classic operators. Second, fix-net telephony in SMEs and at home will continue to be dominated by the incumbents. Yet, as prices for telephony fall towards zero also they will implement IP2IP in order to save costs. By 2022, up to 90% of the calls will be IP2IP. The author recommends the incumbents and VoIP operators to proactively face the change, to rethink their business strategies, and to even be open for cooperation.

Global law in pieces fragmentation, regimes and pluralism

The idea that life undergoes a process of functional differentiation, and that, as a consequence, law becomes increasingly specialized – and maybe even transforms in its very nature – is now widespread. The specialized clusters of law or regulation are very often called regimes, in the international arena, international or transnational regimes. This paper deals, first, with three strong representations of international regimes and discusses some of their problems. It argues that, in order to make a good use of the category, it is necessary to keep in mind the differentiation between law and non-law in the wider context of governance. It then turns, firstly, to the notion of regimes as fragments of a unified and coherent public international law order and, secondly, as meeting points of regulations emerging from different legal orders as well as from other non-legal sources. Within public international law, regimes are seen as related to what is called the double fragmentation of that legal order. As clusters of regulation within a wider global regulatory order, regimes are put in relation to two types of legal or regulatory pluralism.

Essays on household taxation and competition between heterogeneous firms

Essa tese é constituída por três artigos: "Tax Filing Choices for the Household", "Optimal Tax for the Household: Collective and Unitary Approaches" e "Vertical Differentiation and Heterogeneous Firms".

Sonic hedgehog signaling regulates mode of cell division of early cerebral cortex progenitors and increases

The morphogen Sonic Hedgehog (SHH) plays a critical role in the development of different tissues. In the central nervous system, SHH is well known to contribute to the patterning of the spinal cord and separation of the brain hemispheres. In addition, it has recently been shown that SHH signaling also contributes to the patterning of the telencephalon and establishment of adult neurogenic niches. In this work, we investigated whether SHH signaling influences the behavior of neural progenitors isolated from the dorsal telencephalon, which generate excitatory neurons and macroglial cells in vitro. We observed that SHH increases proliferation of cortical progenitors and generation of astrocytes, whereas blocking SHH signaling with cyclopamine has opposite effects. In both cases, generation of neurons did not seem to be affected. However, cell survival was broadly affected by blockade of SHH signaling. SHH effects were related to three different cell phenomena: mode of cell division, cell cycle length and cell growth. Together, our data in vitro demonstrate that SHH signaling controls cell behaviors that are important for proliferation of cerebral cortex progenitors, as well as differentiation and survival of neurons and astroglial cells.

Análise da estabilidade genética de células-tronco mesenquimais humanas

Human multipotent mesenchymal stromal cells (MSCs), also known as mesenchymal stem cells, have become an important and attractive therapeutic tool since they are easily isolated and cultured, have in vitro expansion potential, substantial plasticity and secrete bioactive molecules that exert trophic effects. The human umbilical cord as a cell source for cell therapy will help to avoid several ethical, political, religious and technical issues. One of the main issues with SC lines from different sources, mainly those of embryonic origin, is the possibility of chromosomal alterations and genomic instability during in vitro expansion. Cells isolated from one umbilical cord exhibited a rare balanced paracentric inversion, likely a cytogenetic constitutional alteration, karyotype: 46,XY,inv(3)(p13p25~26). Important genes related to cancer predisposition and others involved in DNA repair are located in 3p25~26. Titanium is an excellent biomaterial for bone-implant integration; however, the use can result in the generation of particulate debris that can accumulate in the tissues adjacent to the prosthesis, in the local bone marrow, in the lymph nodes, liver and spleen. Subsequently may elicit important biological responses that aren´t well studied. In this work, we have studied the genetic stability of MSC isolated from the umbilical cord vein during in vitro expansion, after the cryopreservation, and under different concentrations and time of exposition to titanium microparticles. Cells were isolated, in vitro expanded, demonstrated capacity for osteogenic, adipogenic and chondrogenic differentiation and were evaluated using flow cytometry, so they met the minimum requirements for characterization as MSCs. The cells were expanded under different concentrations and time of exposition to titanium microparticles. The genetic stability of MSCs was assessed by cytogenetic analysis, fluorescence in situ hybridization (FISH) and analysis of micronucleus and other nuclear alterations (CBMN). The cells were able to internalize the titanium microparticles, but MSCs preserve their morphology, differentiation capacity and surface marker expression profiles. Furthermore, there was an increase in the genomic instability after long time of in vitro expansion, and this instability was greater when cells were exposed to high doses of titanium microparticles that induced oxidative stress. It is necessary always assess the risks/ benefits of using titanium in tissue therapy involving MSCs, considering the biosafety of the use of bone regeneration using titanium and MSCs. Even without using titanium, it is important that the therapeutic use of such cells is based on analyzes that ensure quality, security and cellular stability, with the standardization of quality control programs appropriate. In conclusion, it is suggested that cytogenetic analysis, FISH analysis and the micronucleus and other nuclear alterations are carried out in CTMH before implanting in a patient

Cryptic lineages and Pleistocene population expansion in a Brazilian Cerrado frog

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Leaf application of silicic acid to white oat and wheat

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)