Ras signaling contributes to survival of human T-cell leukemia/lymphoma virus type 1 (HTLV-1) Tax-positive T-cells

Ras signaling pathways play an important role in cellular proliferation and survival, and inappropriate activation of Ras frequently results in cell transformation and cancer. Human T-cell leukemia/lymphoma virus type 1 (HTLV-1) is the etiological agent of the adult T-cell leukemia/lymphoma (ATLL), a severe malignancy that has a poor prognosis and exhibits resistance to conventional chemotherapy. Although the mechanisms involved in cell transformation by HTLV-1 have not been completely clarified, it is generally thought that Tax plays a pivotal role in the process. We have previously proposed that a functionally active Ras protein is needed for efficient anti-apoptotic activity of Tax. In this study we report data indicating that the apoptotic resistance of cells expressing Tax, constitutively or transiently, is linked to the intracellular levels of Ras-GTP. Indeed, we found that Tax-positive cells have a high content of active Ras, and that inhibition of Ras signaling, using the antagonist farnesyl thyosalicylic acid (FTS), increases their sensitivity to apoptosis. FTS treatment was also accompanied by a decrease in ERK, but not Akt, phosphorylation. Thus, all together our data suggest that the interaction between Tax and Ras could be important to ATLL pathogenesis, and indicate Ras as a possible target for therapeutic intervention in ATLL patients

Quantifying the timescale and strength of Southern Hemisphere intra-seasonal stratosphere-troposphere coupling

The Southern Hemisphere (SH) zonal circulation manifests a downward influence of the stratosphere on the troposphere from late spring to early summer. However, the strength and timescale of the connection, given the stratospheric state, has not been explicitly quantified. Here, SH zonal wind reanalysis time-series are analysed with a methodology designed to detect the minimal set of statistical predictors of multiple interacting variables via conditional independence tests. Our results confirm from data that the variability of the stratospheric polar vortex is a predictor of the tropospheric eddy-driven jet between September and January. The vortex variability explains about 40% of monthly mean jet variability at a lead time of one month, and can entirely account for the observed jet persistence. Our statistical model can quantitatively connect the multi-decadal trends observed in the vortex and jet during the satellite era. This shows how short-term variability can help understand statistical links in long-term changes

In vitro malignant progression of cells derived from Abelson murine leukaemia virus-induced thymic lymphomas.

Cell lines derived from A-MuLV induced thymic lymphomas in BALB/c and C57BL/6 mice were analysed for their in vivo and in vitro potential of growth. Despite their immunogenicity, cell lines of BALB/c origin readily grew in syngeneic recipients. On the contrary, all cell lines of C57BL/6 origin failed to grow in immunocompetent hosts even though they were able to form tumours in immunosuppressed syngeneic mice. Among C57BL/6 lymphoma cells progression toward a more malignant phenotype was observed in TB6-3 cells, and in their derived clones, after several in vitro passages. This event was accompanied by the in vitro loss of requirement for exogenous growth factor(s) when tumorigenic TB6-3 cells were plated at high density. Moreover, culture medium from fully malignant TB-3 cells was mitogenic for mature T-lymphoma cells suggesting the involvement of an autocrine mechanism in the control of cell proliferation. Apparently, the viral oncogene (v-abl) is not directly involved in malignant progression since no differences between nontumorigenic and tumorigenic cells could be detected in A-MuLV integration patterns, v-abl specific mRNA expression, and P160gag-abl production

Genetic Features of Metachronous Esophageal Cancer Developed in Hodgkin's Lymphoma or Breast Cancer Long-Term Survivors: An Exploratory Study.

Background Development of novel therapeutic drugs and regimens for cancer treatment has led to improvements in patient long-term survival. This success has, however, been accompanied by the increased occurrence of second primary cancers. Indeed, patients who received regional radiotherapy for Hodgkin's Lymphoma (HL) or breast cancer may develop, many years later, a solid metachronous tumor in the irradiated field. Despite extensive epidemiological studies, little information is available on the genetic changes involved in the pathogenesis of these solid therapy-related neoplasms. Methods Using microsatellite markers located in 7 chromosomal regions frequently deleted in sporadic esophageal cancer, we investigated loss of heterozygosity (LOH) and microsatellite instability (MSI) in 46 paired (normal and tumor) samples. Twenty samples were of esophageal carcinoma developed in HL or breast cancer long-term survivors: 14 squamous cell carcinomas (ESCC) and 6 adenocarcinomas (EADC), while 26 samples, used as control, were of sporadic esophageal cancer (15 ESCC and 11 EADC). Results We found that, though the overall LOH frequency at the studied chromosomal regions was similar among metachronous and sporadic tumors, the latter exhibited a statistically different higher LOH frequency at 17q21.31 (p = 0.018). By stratifying for tumor histotype we observed that LOH at 3p24.1, 5q11.2 and 9p21.3 were more frequent in ESCC than in EADC suggesting a different role of the genetic determinants located nearby these regions in the development of the two esophageal cancer histotypes. Conclusions Altogether, our results strengthen the genetic diversity among ESCC and EADC whether they occurred spontaneously or after therapeutic treatments. The presence of histotype-specific alterations in esophageal carcinoma arisen in HL or breast cancer long-term survivors suggests that their transformation process, though the putative different etiological origin, may retrace sporadic ESCC and EADC carcinogenesis

Microwave dielectric permittivity and photoluminescence of Eu 2O3 doped laser heated pedestal growth Ta 2O5 fibers

Partilhar documento na coleção da comunidade Laboratório Associado I3NWe report the microwave dielectric properties and photoluminescence of undoped and europium oxide doped Ta2O5 fibers, grown by laser heated pedestal growth technique. The effects of Eu2O3 doping 1–3 mol % on the structural, optical, and dielectric properties were investigated. At a frequency of 5 GHz, the undoped material exhibits a dielectric permittivity of 21 and for Eu2O3 doped Ta2O5 samples it increases, reaching up to 36 for the highest doping concentration. Nevertheless, the dielectric losses maintain a very low value. For this wide band gap oxide, Eu3+ optical activation was achieved and the emission is observed up to room temperature. Thus, the transparency and high permittivity make this material promising for electronic devices and microwave applications. © 2008 American Institute of Physics.FCT-PTDC/FIS/66262/06FCT-PTDC/CTM/66195/200

Mechanism of action of probiotics

The modern diet doesn't provide the required amount of beneficial bacteria. Maintenance of a proper microbial ecology in the host is the main criteria to be met for a healthy growth. Probiotics are one such alternative that are supplemented to the host where by and large species of Lactobacillus, Bifidobacterium and Saccharomyces are considered as main probiotics. The field of probiotics has made stupendous strides though there is no major break through in the identification of their mechanism of action. They exert their activity primarily by strengthening the intestinal barrier and immunomodulation. The main objective of the study was to provide a deep insight into the effect of probiotics against the diseases, their applications and proposed mechanism of action

Quantifying causal pathways of teleconnections

Teleconnections are sources of predictability for regional weather and climate but the relative contributions of different teleconnections to regional anomalies are usually not understood. While physical knowledge about the involved mechanisms is often available, how to quantify a particular causal pathway from data is usually unclear. Here we argue for adopting a causal inference-based framework in the statistical analysis of teleconnections to overcome this challenge. A causal approach requires explicitly including expert knowledge in the statistical analysis, which allows one to draw quantitative conclusions. We illustrate some of the key concepts of this theory with concrete examples of well-known atmospheric teleconnections. We further discuss the particular challenges and advantages these imply for climate science and argue that a systematic causal approach to statistical inference should become standard practice in the study of teleconnections

Structural and optical properties on thulium-doped LHPG-grown Ta2O5 fibres

Structural, spectroscopic and dielectric properties of thulium-doped laser-heated pedestal Ta2O5 as-grown fibres were studied. Undoped samples grow preferentially with a single crystalline monoclinic structure. The fibre with the lowest thulium content (0.1 at%) also shows predominantly a monoclinic phase and no intra-4f12 Tm3+ recombination was observed. For sample with the highest thulium amount (1.0 at%), the appearance of a dominant triclinic phase as well as intraionic optical activation was observed. The dependence of photoluminescence on excitation energy allows identification of different site locations of Tm3+ ions in the lattice. The absence of recombination between the first and the ground-state multiplets as well as the temperature dependence of the observed transitions was justified by an efficient energy transfer between the Tm3+ ions. Microwave dielectric properties were investigated using the small perturbation theory. At a frequency of 5 GHz, the undoped material exhibits a dielectric permittivity of 21 and for thulium-doped Ta2O5 samples it decreases to 18 for the highest doping concentration. Nevertheless, the dielectric losses maintain a very low value.FCT - PTDC/CTM/66195/2006FCT - PTDC/FIS/66262/2006FCT - PTDC/FIS/72843/200

Low CD4/CD8 T-Cell Ratio Associated with Inflammatory Arthropathy in Human T-Cell Leukemia Virus Type I Tax Transgenic Mice

Human T-cell leukemia virus type I (HTLV-1) can cause an aggressive malignancy known as adult T-cell leukemia/lymphoma (ATL) as well as inflammatory diseases such as HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). A transgenic mouse that expresses HTLV-1 Tax also develops T-cell leukemia/lymphoma and an inflammatory arthropathy that resembles rheumatoid arthritis. The aim of this study was to identify the primary T-cell subsets involved in the development of arthropathy in Tax transgenic mice. mRNA was strong in the spleen and joints of arthropathic mice, with a 40-fold increase compared with healthy transgenic mice.Our findings reveal that Tax transgenic mice develop rheumatoid-like arthritis with proliferating synovial cells in the joints; however, the proportion of different splenic T-cell subsets in these mice was completely different from other commonly used animal models of rheumatoid arthritis. The crucial T-cell subsets in arthropathic Tax transgenic mice appear to resemble those in HAM/TSP patients rather than those in rheumatoid arthritis patients