Preferential expression of the transcription coactivator HTIF1alpha gene in acute myeloid leukemia and MDS-related AML

HTIF1α, a transcription coactivator which is able to mediate RARα activity and functionally interact with PML, is encoded by a gene on chromosome 7q32–34, which is a critical region in acute myeloid leukemias (AML). With the assumption that this gene may be related to AML, we investigated the HTIF1α DNA structure and RNA expression in leukemic cells from 36 M1–M5 AML patients (28 ‘de novo’ and eight ‘secondary’ to myelodysplastic syndrome (MDS)). Abnormal HTIF1α DNA fragments were never found, whereas loss of HTIF1α DNA was observed in the patients with chromosome 7q32 deletion and translocation, and in one case without detectable chromosome 7 abnormality. HTIF1α RNA was found in acute myelocytic leukemic blasts, and was almost undetectable in normal mononuclear cells. The expression varied among the patients: higher in M1 to M3 subtypes, with the highest values in M1; low levels were constantly observed in M4 and M5 AML. In addition, HTIF1α was significantly overexpressed in MDS-related AML (MDR-AML), but not in MDS. We also found that HTIF1α expression was high in myeloid cell lines. In myeloblastic HL60 and promyelocytic NB4 cells, induced to differentiate along the monocytic–macrophage pathway by TPA or vitamin D3, HTIF1α expression decreased, whereas it was maintained at high levels on induction to granulocytic differentiation by RA or DMSO. In K562 cells, HTIF1α RNA levels did not change after hemin-induced erythroid differentiation. These results suggest that HTIF1α could play a role in myeloid differentiation, being distinctly regulated in hematopoietic lineages

Extrafloral-nectar based partner manipulation in plant-ant relationship

Plant–ant interactions are generally considered as mutualisms, with both parties gaining benefits from the association. It has recently emerged that some of these mutualistic associations have, however, evolved towards other forms of relationships and, in particular, that plants may manipulate their partner ants to make reciprocation more beneficial, thereby stabilizing the mutualism. Focusing on plants bearing extrafloral nectaries, we review recent studies and address three key questions: (i) how can plants attract potential partners and maintain their services; (ii) are there compounds in extrafloral nectar that could mediate partner manipulation; and (iii) are ants susceptible to such compounds? After reviewing the current knowledge on plant–ant associations, we propose a possible scenario where plant-derived chemicals, such as secondary metabolites, known to have an impact on animal brain, could have evolved in plants to attract and manipulate ant behaviour. This new viewpoint would place plant–animal interaction in a different ecological context, opening new ecological and neurobiological perspectives of drug seeking and use

The Immune Response to Tumors as a Tool toward Immunotherapy

Until recently cancer medical therapy was limited to chemotherapy that could not differentiate cancer cells from normal cells. More recently with the remarkable mushroom of immunology, newer tools became available, resulting in the novel possibility to attack cancer with the specificity of the immune system. Herein we will review some of the recent achievement of immunotherapy in such aggressive cancers as melanoma, prostatic cancer, colorectal carcinoma, and hematologic malignancies. Immunotherapy of tumors has developed several techniques: immune cell transfer, vaccines, immunobiological molecules such as monoclonal antibodies that improve the immune responses to tumors. This can be achieved by blocking pathways limiting the immune response, such as CTLA-4 or Tregs. Immunotherapy may also use cytokines especially proinflammatory cytokines to enhance the activity of cytotoxic T cells (CTLs) derived from tumor infiltrating lymphocytes (TILs). The role of newly discovered cytokines remains to be investigated. Alternatively, an other mechanism consists in enhancing the expression of TAAs on tumor cells. Finally, monoclonal antibodies may be used to target oncogenes

Breeding Strategies for \u3cem\u3eBrachiaria\u3c/em\u3e spp. to Improve Productivity–An Ongoing Project

Two strategies have been used in the breeding of Brachiaria (syn. Urochloa) to produce new cultivars. The first involves exploring the natural variability existing in nature, which is the selection of ecotypes, mostly apomicts, from the diversity in germplasm banks. This strategy proved efficient originally and the cultivars in use in Brazil were derived in this way, but progress with this strategy is limited in the medium to long term

In vitro biosafety profile evaluation of multipotent mesenchymal stem cells derived from the bone marrow of sarcoma patients.

BACKGROUND: In osteosarcoma (OS) and most Ewing sarcoma (EWS) patients, the primary tumor originates in the bone. Although tumor resection surgery is commonly used to treat these diseases, it frequently leaves massive bone defects that are particularly difficult to be treated. Due to the therapeutic potential of mesenchymal stem cells (MSCs), OS and EWS patients could benefit from an autologous MSCs-based bone reconstruction. However, safety concerns regarding the in vitro expansion of bone marrow-derived MSCs have been raised. To investigate the possible oncogenic potential of MSCs from OS or EWS patients (MSC-SAR) after expansion, this study focused on a biosafety assessment of MSC-SAR obtained after short- and long-term cultivation compared with MSCs from healthy donors (MSC-CTRL). METHODS: We initially characterized the morphology, immunophenotype, and differentiation multipotency of isolated MSC-SAR. MSC-SAR and MSC-CTRL were subsequently expanded under identical culture conditions. Cells at the early (P3/P4) and late (P10) passages were collected for the in vitro analyses including: the sequencing of genes frequently mutated in OS and EWS, evaluation of telomerase activity, assessment of the gene expression profile and activity of major cancer pathways, cytogenetic analysis on synchronous MSC, and molecular karyotyping using a comparative genomic hybridization (CGH) array. RESULTS: MSC-SAR displayed comparable morphology, immunophenotype, proliferation rate, differentiation potential, and telomerase activity to MSC-CTRL. Both cell types displayed signs of senescence in the late stages of culture with no relevant changes in cancer gene expression. However, cytogenetic analysis detected chromosomal anomalies in the early and late stages of MSC-SAR and MSC-CTRL after culture. CONCLUSIONS: Our results demonstrated that the in vitro expansion of MSC does not influence or favor malignant transformation since MSC-SAR were not more prone than MSC-CTRL to deleterious changes during culture. However, the presence of chromosomal aberrations supports rigorous phenotypic, functional and genetic evaluation of the biosafety of MSCs, which is important for clinical applications

Transcriptoma supersage de feijão-caupi sob desidratação radicular.

O feijão-caupi é uma planta de ampla plasticidade fenotípica, podendo produzir mesmo em condições não satisfatória para outras culturas. Assim, identificar genes estresse responsivo nesta cultura é de vital importância, tanto para a espécie quanto para outras leguminosas. Estudos em transcriptômica, proporcionados pela técnica SuperSAGE, origina tags de 26 pb que podem ser quantificadas e estatisticamente analisadas, sendo classificadas em superexpressas ou reprimidas. Unitags (tags diferentes) de raízes de feijao-caupi submetidas a estresse de desidratação radicular (de até 150 min, após exposição ao ar) foram analisadas procurando-se identificar unitags diferencialmente expressas nas respostas dos genótipos analisados, considerados tolerante e sensível a seca. As anotações de gene/ função das unitags, associadas à regulação (induzida ou reprimida nas bibliotecas sob estresse em relação às bibliotecas controle) permitiram identificar alvos moleculares com potencial para desenvolvimento de marcadores moleculares e ou estudos de transgenia, visando uso futuro em programas de melhoramentos da espécie e de leguminosas relacionadas