Genetic determination and linkage mapping of Plasmodium falciparum malaria related traits in Senegal

Plasmodium falciparum malaria episodes may vary considerably in their severity and clinical manifestations. There is good evidence that host genetic factors contribute to this variability. To date, most genetic studies aiming at the identification of these genes have used a case/control study design for severe malaria, exploring specific candidate genes. Here, we performed a family-based genetic study of falciparum malaria related phenotypes in two independent longitudinal survey cohorts, as a first step towards the identification of genes and mechanisms involved in the outcome of infection. We studied two Senegalese villages, Dielmo and Ndiop that differ in ethnicity, malaria transmission and endemicity. We performed genome-scan linkage analysis of several malaria-related phenotypes both during clinical attacks and asymptomatic infection. We show evidence for a strong genetic contribution to both the number of clinical falciparum malaria attacks and the asymptomatic parasite density. The asymptomatic parasite density showed linkage to chromosome 5q31 (LOD = 2.26, empirical p = 0.0014, Dielmo), confirming previous findings in other studies. Suggestive linkage values were also obtained at three additional chromosome regions: the number of clinical malaria attacks on chromosome 5p15 (LOD = 2.57, empirical p = 0.001, Dielmo) and 13q13 (LOD = 2.37, empirical p = 0.0014 Dielmo), and the maximum parasite density during asymptomatic infection on chromosome 12q21 (LOD = 3.1, empirical p<10(-4), Ndiop). While regions of linkage show little overlap with genes known to be involved in severe malaria, the four regions appear to overlap with regions linked to asthma or atopy related traits, suggesting that common immune related pathways may be involved.     

ATP hydrolysis and pristinamycin IIA inhibition of the Staphylococcus aureus Vga(A), a dual ABC protein involved in streptogramin A resistance

In Gram-positive bacteria, a large subfamily of dual ATP-binding cassette proteins confers acquired or intrinsic resistance to macrolide, lincosamide, and streptogramin antibiotics by a far from well understood mechanism. Here, we report the first biochemical characterization of one such protein, Vga(A), which is involved in streptogramin A (SgA) resistance among staphylococci. Vga(A) is composed of two nucleotide-binding domains (NBDs), separated by a charged linker, with a C-terminal extension and without identified transmembrane domains. Highly purified Vga(A) displays a strong ATPase activity (K(m) = 78 mum, V(m) = 6.8 min(-1)) that was hardly inhibited by orthovanadate. Using mutants of the conserved catalytic glutamate residues, the two NBDs of Vga(A) were shown to contribute unequally to the total ATPase activity, the mutation at NBD2 being more detrimental than the other. ATPase activity of both catalytic sites was essential for Vga(A) biological function because each single Glu mutant was unable to confer SgA resistance in the staphylococcal host. Of great interest, Vga(A) ATPase was specifically inhibited in a non-competitive manner by the SgA substrate, pristinamycin IIA (PIIA). A deletion of the last 18 amino acids of Vga(A) slightly affected the ATPase activity without modifying the PIIA inhibition values. In contrast, this deletion reduced 4-fold the levels of SgA resistance. Altogether, our results suggest a role for the C terminus in regulation of the SgA antibiotic resistance mechanism conferred by Vga(A) and demonstrate that this dual ATP-binding cassette protein interacts directly and specifically with PIIA, its cognate substrate.     

Gnotobiotic Mouse Immune Response Induced by Bifidobacterium sp. Strains Isolated from Infants

Bifidobacterium, which is a dominant genus in infants’ fecal flora and can be used as a probiotic, has shown beneficial effects in various pathologies, including allergic diseases, but its role in immunity has so far been little known. Numerous studies have shown the crucial role of the initial intestinal colonization in the development of the intestinal immune system, and bifidobacteria could play a major role in this process. For a better understanding of the effect of Bifidobacterium on the immune system, we aimed at determining the impact of Bifidobacterium on the T-helper 1 (T_H1)/T_H2 balance by using gnotobiotic mice. Germfree mice were inoculated with Bifidobacterium longum NCC2705, whose genome is sequenced, and with nine Bifidobacterium strains isolated from infants’ fecal flora. Five days after inoculation, mice were killed. Transforming growth factor β1 (TGF-β1), interleukin-4 (IL-4), IL-10, and gamma interferon (IFN-γ) gene expressions in the ileum and IFN-γ, tumor necrosis factor alpha (TNF-α), IL-10, IL-4, and IL-5 secretions by splenocytes cultivated for 48 h with concanavalin A were quantified. Two Bifidobacterium species had no effect (B. adolescentis) or little effect (B. breve) on the immune system. Bifidobacterium bifidum, Bifidobacterium dentium, and one B. longum strain induced T_H1 and T_H2 cytokines at the systemic and intestinal levels. One B. longum strain induced a T_H2 orientation with high levels of IL-4 and IL-10, both secreted by splenocytes, and of TGF-β gene expression in the ileum. The other two strains induced T_H1 orientations with high levels of IFN-γ and TNF-α splenocyte secretions. Bifidobacterium's capacity to stimulate immunity is species specific, but its influence on the orientation of the immune system is strain specific.     

Aggression and Reconciliation in Cebus capucinus

Most data relating to aggressive and conciliatory behaviors are from Old World primates. We recorded agonistic interactions and post-conflict behaviors in a group of 12 white-faced capuchins (Cebus capucinus). After a conflict, we followed the aggressee as the focal individual during a 10-min postconflict period. We also conducted matched-control observations on the same individual. Conflicts involving physical contact were significantly bidirectional, and conflicts without physical contact were preferably unidirectional. Reconciliation was not be demonstrated at the group level. However, reconciliation occurred in kin and non-kin male/female dyads: their conciliatory tendencies were 48.1% and 21.2%, respectively. White-faced capuchins reconciled mainly during the first minutes after the end of the conflict. In kin and non-kin male/female dyads, selective attraction occurred, and aggressors were more likely to initiate affiliative contacts than aggressees. Hold-bottom and mount while emitting loud vocalizations were the most characteristic behaviors of reconciliation. Possible links may exist between aggressive and conciliatory patterns and other social variables.     

Development of a selective and sensitive polymerase chain reaction assay for the detection of Mycoplasma pirum

Abstract A new assay using the polymerase chain reaction to amplify a 173-nucleotide DNA fragment within the 16S ribosomal RNA gene of Mycoplasma pirum has been developed. The assay selectively amplified DNA from all strains of M. pirum tested with a high level of sensitivity, even in a context of human DNA. DNA from other mollicute species, including those closely related to M. pirum , from bacteria phylogenetically close to mollicutes ( Clostridium innocuum, C. ramosum and Bacillus subtilis ), from Escherichia coli and from human peripheral blood mononuclear cells, did not produce the amplified DNA product specific for M. pirum .     

Suppression by Thimerosal of Ex-Vivo CD4+ T Cell Response to Influenza Vaccine and Induction of Apoptosis in Primary Memory T Cells

Thimerosal is a preservative used widely in vaccine formulations to prevent bacterial and fungal contamination in multidose vials of vaccine. Thimerosal was included in the multidose non-adjuvanted pandemic 2009 H1N1 vaccine Panenza. In the context of the analysis of the ex-vivo T cell responses directed against influenza vaccine, we discovered the in vitro toxicity Panenza, due to its content in thimerosal. Because thimerosal may skew the immune response to vaccines, we investigated in detail the ex-vivo effects of thimerosal on the fate and functions of T cells in response to TCR ligation. We report that ex-vivo exposure of quiescent or TCR-activated primary human T cells to thimerosal induced a dose-dependent apoptotic cell death associated with depolarization of mitochondrial membrane, generation of reactive oxygen species, cytochrome c release from the mitochondria and caspase-3 activation. Moreover, exposure to non-toxic concentrations of thimerosal induced cell cycle arrest in G0/G1 phase of TCR-activated T cells, and inhibition of the release of proinflammatory cytokines such as IFN gamma, IL-1 beta, TNF alpha, IL-2, as well as the chemokine MCP1. No shift towards Th2 or Th17 cells was detected. Overall these results underline the proapoptotic effect of thimerosal on primary human lymphocytes at concentrations 100 times less to those contained in the multidose vaccine, and they reveal the inhibitory effect of this preservative on T-cell proliferation and functions at nanomolar concentrations.     

A multi-criteria approach for the selection of efficient biocontrol agents against <Emphasis Type="Italic">Botrytis cinerea</Emphasis> on tomato in Algeria

In order to find biocontrol agents that are both efficient against Botrytis cinerea Pers. and adapted to tomato growing conditions in Algeria, 121 bacterial strains were collected from tomato plants and nearby soils in two Bejaia greenhouses. A total of 37 strains were selected based on their ability to grow on agar medium and on their different level of B. cinerea mycelial growth inhibition in dual-culture tests. These strains were identified at the species level and those that corresponded to potential pathogens for humans or mammals were discarded. Among the remaining 25 candidates, three strains were selected among the Pseudomonas genus for their significant protective efficacy against B. cinerea on tomato, their ability to grow at 15–25 °C and their inability to grow at 37 °C. These three strains significantly reduced the development of necrotic lesion and the sporulation of B. cinerea in a dose-dependent manner. This study constitutes a first step towards the biological control of B. cinerea in tomato greenhouses in Algeria.     

Global health inequalities and the need for solidarity: a view from the Global South

Although the world has experienced remarkable progress in health care since the last half of the 20th century, global health inequalities still persist. In some poor countries life expectancy is between 37‐40 years lower than in rich countries; furthermore, maternal and infant mortality is high and there is lack of access to basic preventive and life‐saving medicines, as well a high prevalence of neglected diseases, HIV/AIDS, tuberculosis, and malaria. Moreover, globalization has made the world more connected than before such that health challenges today are no longer limited within national or regional boundaries, making all persons equally vulnerable. Because of this, diseases in the most affluent countries are closely connected with diseases in the poorest countries. In this paper, we argue that, because of global health inequalities, in a situation of equal vulnerability, there is need for global solidarity not only as a means of reducing health inequalities, but also as a way of putting up a united force against global health challenges. We argue for an African approach to solidarity in which the humanity of a person is not determined by his/her being human or rational capacity, but by his/her capacity to live a virtuous life. According to this view of solidarity, because no one is self‐sufficient, no individual can survive alone. If we are to collectively flourish in a world where no individual, nation or region has all the health resources or protection needed for survival, we must engage in solidarity where we remain compassionate and available to one another at all times.