Proteins Do Not Have Strong Spines After All

In this issue of Structure, Berkholz et al. show that the detailed backbone geometry of proteins depends on the local conformation and suggest how this information can be practically used in modeling and refining protein structures

Linking Self-Incompatibility, Dichogamy, and Flowering Synchrony in Two Euphorbia Species: Alternative Mechanisms for Avoiding Self-Fertilization?

Background: Plant species have several mechanisms to avoid selfing such as dichogamy or a self-incompatibility response. Dichogamy in a single flower may reduce autogamy but, to avoid geitonogamy, plants must show flowering synchronization among all their flowers (i.e. synchronous dichogamy). It is hypothesized that one species would not simultaneously show synchronous dichogamy and self-incompatibility because they are redundant mechanisms to reduce selfing; however, this has not been accurately assessed. Methodology/Principal Findings: This expectation was tested over two years in two natural populations of the closely related Mediterranean spurges Euphorbia boetica and E. nicaeensis, which completely avoid autogamy by protogyny at the cyathia level. Both spurges showed a high population synchrony (Z,79), and their inflorescences flower synchronously. In E. nicaeensis, there was no overlap among the cyathia in anthesis of successive inflorescence levels and the overlap between sexual phases of cyathia of the same inflorescence level was uncommon (4–16%). In contrast, E. boetica showed a high overlap among consecutive inflorescence levels (74–93%) and between sexual phases of cyathia of the same inflorescence level (48–80%). The flowering pattern of both spurges was consistent in the two populations and over the two successive years. A hand-pollination experiment demonstrated that E. nicaeensis was strictly self-compatible whereas E. boetica was partially self-incompatible. Conclusions/Significance: We propose that the complex pattern of synchronized protogyny in E. nicaeensis prevents geitonogamous crosses and, consequently, avoids selfing and inbreeding depression. In E. boetica, a high probability of geitonogamous crosses may occur but, alternatively, this plant escapes selfing through a self-incompatibility response. We posit that synchronous dichogamy and physiological self-incompatibility do not co-occur in the same species because each process is sufficiently effective in avoiding self-fertilization.España Ministerio de Ciencia y Tecnología PLO CGL2005-03731; CGL2008-02533-EEspaña Ministerio de Ciencia y Tecnología MA CGL2009-0825

Etude de l'apparition du répertoire immunitaire et des mécanismes de reconnaissance du soi et du non soi

Doctorat en Sciencesinfo:eu-repo/semantics/nonPublishe

Relationship between the synthesis of autoimmune antibodies and the formation of clusters of B, T and APC cells during the syngeneic mixed lymphocyte reaction in BALB/c and NZB mice: a technique for isolation of the spleen autoimmune compartment of non-immunized pathogen-free mice.

Cells from the spleens of non-immunized mice were cultured in horizontal tubes, rotating very slowly around their long axis. Under these conditions, the flux speed gradient of the cell suspension near the tube walls greatly increased the chances of cells coming into contact with one another. Mixed clusters of B, T and APC cells were soon found adhering firmly to the walls of the tube; cluster formation leveled off after about 3 h. The clustered cells were easily separated from those remaining in suspension and constituted a particular cell compartment comprising a maximum of 20-30% of the total. B cells from this compartment, cultured in complete medium for 48 h, almost exclusively produced IgM antibodies. Antibodies reacting with self antigens were so numerous in the culture medium that it is likely all IgM were self antibodies. That the clusters obtained under these conditions constituted a compartment of autoimmune cells is supported by previous work which showed that 20-30% of spleen cells secrete IgM antibodies almost exclusively. Cluster formation as a function of age was compared in NZB mice which are used as a model of lupus erythematosus, and in BALB/c mice which never manifest self-immune pathology. The number of cells found in clusters per whole spleen increased exponentially with age in NZB mice and linearly in BALB/c mice. The production of autoimmune antibodies as a function of age also increased exponentially for NZB mice and linearly in BALB/c mice, which provides further striking support for the hypothesis that the clusters formed constitute the autoimmune comportment.Journal ArticleSCOPUS: ar.jinfo:eu-repo/semantics/publishe

Interleukine 10: Facteur favorisant l'échappement d'une tumeur à la surveillance immunitaire ?Ou facteur favorisant son rejet ?

Tumors developed different ways of escaping immune recognition. The ability to release immunosuppressive factors directed against T lymphocytes may be one mechanism of such escape. Interleukin 10 (IL10) has been proposed to be one of these factors, because of its potent immunosuppressive properties on cell-mediated immune responses. Moreover, if the pattern of cytokine gene expression is analyzed within solid tumors, the IL10 gene is one of the most frequently expressed in many different tumor types. This suggests that the IL10 secretion in a tumor microenvironment may play a role in carcinogenesis by preventing an adequate antitumoral immune response. Contrarily to what was hypothesized, the transfer of the IL10 cDNA and its subsequent expression in mouse melanoma cells result in a loss of their tumorigenicity in syngeneic mice. Moreover, a single vaccination with IL10 producing melanoma cells is able to protect the mice against a subsequent challenge with parental cells. Thus, in this tumor model IL10 seems to be immunostimulatory rather than immunosuppressive, and has a surprising antitumoral activity. It remains to determine if this effect could be generalized to other tumor types and if IL10 is finally a factor favoring the escape of a tumor to the immune system or if it could increase the immunogenicity of a tumor and help its rejection.SCOPUS: sh.jinfo:eu-repo/semantics/publishe

Cancer escape from immune surveillance: How can it be overcome by gene transfer?

SCOPUS: re.jinfo:eu-repo/semantics/publishe

Cytokine gene transfer for the treatment of cancer

SCOPUS: cp.jinfo:eu-repo/semantics/publishe

Highly successful therapeutic vaccinations combining dendritic cells and tumor cells secreting granulocyte macrophage colony-stimulating factor.

In an attempt to induce potent immune antitumor activities, we investigated, within the rat 9L gliosarcoma model, distal therapeutic vaccinations associating three therapies: dendritic cell vaccination, intratumoral granulocyte macrophage colony-stimulating factor (GM-CSF) gene transfer, and tumor apoptosis induction. Vaccines of dendritic cells coinjected with processed GM-CSF secreting 9L cells induced systemic responses, resulting in the complete regression of distant preimplanted 9L tumor masses in, with the best strategy, 94% of male rats. All of the cured rats developed a long-term resistance to a rechallenge with parental cells. The curative responses were correlated with the detection of elevated specific cytotoxic activities and a CD4+, CD8+ T cell-, and natural killer (NK) cell-mediated IFN-gamma production. The survival rate of the rat seemed more directly linked to the amount of GM-CSF secreted by the transduced tumor cells, which in turn depended on the toxicity of the apoptosis-inducing treatment, than to the level of apoptosis induced. Unexpectedly, alive GM-CSF secreting 9L cells became apoptotic when injected in vivo. Thus we documented the positive role of apoptosis in the induction of therapeutic antitumor responses by comparing, at equal GM-CSF exogenous supply, the effects of dendritic cells coinjected with apoptotic or necrotic 9L cells. The data showed the superior therapeutic efficiency of combined vaccines containing apoptotic tumor cells. In conclusion, vaccinations with dendritic cells associated with apoptotic tumor cells secreting GM-CSF show a very high therapeutic potency that should show promise for the treatment of human cancer.Journal ArticleResearch Support, Non-U.S. Gov'tinfo:eu-repo/semantics/publishe

The two SH2-domain-containing inositol 5-phosphatases SHIP1 and SHIP2 are coexpressed in human T lymphocytes.

The activation of many hematopoietic cells via cytokine receptors, as well as B and T cell receptors, leads to the tyrosine phosphorylation of Shc and its association with both Grb2-Sos1 complexes and with a 145 kDa protein referred to as the SH2 containing inositol 5-phosphatase (SHIP1). In a search of putative 5-phosphatase isoenzymes, we have isolated a second SH2 domain containing inositol 5-phosphatase, referred to as (SHIP2). Both SHIP1 and SHIP2 are coexpressed in human T lymphocytes. This was shown at the protein level by Western blot analysis in transformed T cell lines and in peripheral blood T lymphocytes either unstimulated or after in vitro activation through TCR-CD3 complex. SHIP1 protein level was not modulated after activation of T lymphocytes, in contrast to SHIP2, which was increased after long-term stimulation. SHIP1 was tyrosine phosphorylated in resting naive T cells. This was not observed in the transformed T cell lines. T lymphocyte is therefore a model of coexpression of the two SH2-containing inositol 5-phosphatases SHIP1 and SHIP2.Journal ArticleResearch Support, Non-U.S. Gov'tinfo:eu-repo/semantics/publishe

expression of the adhesion molecules VCAM-1 and ICAM-1 in differents models of experimental autoimmune uveitis

info:eu-repo/semantics/nonPublishe