Genetic Resistance to Malaria Is Associated With Greater Enhancement of Immunoglobulin (Ig)M Than IgG Responses to a Broad Array of Plasmodium falciparum Antigens

Background. People of the Fulani ethnic group are more resistant to malaria compared with genetically distinct ethnic groups, such as the Dogon people, in West Africa, and studies suggest that this resistance is mediated by enhanced antibody responses to Plasmodium falciparum antigens. However, prior studies measured antibody responses to <0.1% of P falciparum proteins, so whether the Fulani mount an enhanced and broadly reactive immunoglobulin (Ig)M and IgG response to P falciparum remains unknown. In general, little is known about the extent to which host genetics influence the overall antigen specificity of IgM and IgG responses to natural infections. Methods. In a cross-sectional study in Mali, we collected plasma from asymptomatic, age-matched Fulani (n = 24) and Dogon (n = 22) adults with or without concurrent P falciparum infection. We probed plasma against a protein microarray containing 1087 P falciparum antigens and compared IgM and IgG profiles by ethnicity. Results. We found that the breadth and magnitude of P falciparum-specific IgM and IgG responses were significantly higher in the malaria-resistant Fulani versus the malaria-susceptible Dogon, and, unexpectedly, P falciparum-specific IgM responses more strongly distinguished the 2 ethnic groups. Conclusions. These findings point to an underappreciated role for IgM in protection from malaria, and they suggest that host genetics may influence the antigen specificity of IgM and IgG responses to infection

Type-specific herpes simplex virus-1 and herpes simplex virus-2 seroprevalence in Romania: comparison of prevalence and risk factors in women and men

AbstractObjectiveTo determine herpes simplex virus (HSV)-2 and HSV-1 seroprevalence in women and men in Romania.MethodsA cross-sectional seroprevalence survey was conducted between 2004 and 2005 on a total of 1058 women and men representative of the population of Bucharest. All participants were aged 15–44 years and completed a structured questionnaire. A blood sample was collected to detect IgG anti-HSV-1 and HSV-2 serum antibodies using the HerpeSelect ELISA (Focus Diagnostics).ResultsA total of 761 women (median age 29 years) and 297 men (median age 29 years) were included. Overall, HSV-2 seroprevalence (15.2%) increased with age. Among women, HSV-2 seroprevalence increased from 11.0% in 15–19-year-olds to 38.3% in 40–44-year-olds. Among men, seroprevalence increased from 4.0% in 20–24-year-olds to 27.1% in 40–44-year-olds. HSV-2 seroprevalence was significantly higher among women than men (17.0% vs. 10.8%). HSV-1 seropositivity was high (87.2%) in all age groups, with no clear trend by age or by sex. In addition to older age and female sex, risk factors for HSV-2 included greater number of lifetime sexual partners, lower educational attainment, and history of genital vesicles. Lower educational level and rural residence were associated with a higher risk of HSV-1 seropositivity.ConclusionsIn Romania, HSV-2 seroprevalence was higher in women than men, and was within European limits and lower than that in Africa and the USA. In contrast, HSV-1 seroprevalence was generally higher than that previously recorded in similarly aged populations in Western Europe

Changes in the levels of cytokines, chemokines and malaria-specific antibodies in response to Plasmodium falciparum infection in children living in sympatry in Mali

<p>Abstract</p> <p>Background</p> <p>The Fulani are known to be less susceptible to <it>Plasmodium falciparum </it>malaria as reflected by lower parasitaemia and fewer clinical symptoms than other sympatric ethnic groups. So far most studies in these groups have been performed on adults, which is why little is known about these responses in children. This study was designed to provide more information on this gap.</p> <p>Methods</p> <p>Circulating inflammatory factors and antibody levels in children from the Fulani and Dogon ethnic groups were measured. The inflammatory cytokines; interleukin (IL)-1beta, IL-6, IL-8, IL-10, IL-12p70, tumor necrosis factor (TNF) and the chemokines; regulated on activation normal T cell expressed and secreted (RANTES), monokine-induced by IFN-gamma (MIG), monocyte chemotactic protein (MCP)-1 and IFN-gamma-inducible protein (IP)-10 were measured by cytometric bead arrays. The levels of interferon (IFN)-alpha, IFN-gamma and malaria-specific antibodies; immunoglobulin (Ig) G, IgM and IgG subclasses (IgG1-IgG4) were measured by ELISA.</p> <p>Results</p> <p>The results revealed that the Fulani children had higher levels of all tested cytokines compared to the Dogon, in particular IFN-gamma, a cytokine known to be involved in parasite clearance. Out of all the tested chemokines, only MCP-1 was increased in the Fulani compared to the Dogon. When dividing the children into infected and uninfected individuals, infected Dogon had significantly lower levels of RANTES compared to their uninfected peers, and significantly higher levels of MIG and IP-10 as well as MCP-1, although the latter did not reach statistical significance. In contrast, such patterns were not seen in the infected Fulani children and their chemokine levels remained unchanged upon infection compared to uninfected counterparts. Furthermore, the Fulani also had higher titres of malaria-specific IgG and IgM as well as IgG1-3 subclasses compared to the Dogon.</p> <p>Conclusions</p> <p>Taken together, this study demonstrates, in accordance with previous work, that Fulani children mount a stronger inflammatory and antibody response against <it>P. falciparum </it>parasites compared to the Dogon and that these differences are evident already at an early age. The inflammatory responses in the Fulani were not influenced by an active infection which could explain why less clinical symptoms are seen in this group.</p

Le partage de la ressource en eau sur la Durance en 2050 : vers une évolution du mode de gestion des grands ouvrages duranciens ?

Congrès SHF: Water Tensions in Europe and in the Mediterranean: water crisis by 2050?, Paris, FRA, 08-/10/2015 - 09/10/2015International audienceUne vision prospective de la gestion de l'eau du bassin de la Durance et des territoires alimentés par ses eaux à l'horizon 2050 a été élaborée, appuyée par une chaine de modèles incluant des représentations du climat, de la ressource naturelle, des demandes en eau et du fonctionnement des grands ouvrages hydrauliques (Serre-Ponçon, Castillon et Sainte-Croix), sous contraintes de respect des débits réservés, de cotes touristiques dans les retenues et de restitution d'eau stockée pour des usages en aval. Cet ensemble, validé en temps présent, a été alimenté par des projections climatiques et paramétré pour intégrer les évolutions du territoire décrites par des scénarios de développement socio-économique avec une hypothèse de conservation des règles de gestion actuelles. Les résultats suggèrent à l'horizon 2050 : une hausse de la température moyenne de l'air impactant l'hydrologie de montagne ; une évolution incertaine des précipitations ; une réduction des stocks de neige et une fonte avancée dans l'année qui induisent une réduction des débits au printemps ; une diminution de la ressource en eau en période estivale ; une diminution de la demande globale en eau à l'échelle du territoire, cette demande étant fortement conditionnée par les scénarios territoriaux élaborés ici ; la satisfaction des demandes en eau en aval des ouvrages considérées comme prioritaires, au détriment de la production d'énergie en hiver (flexibilité moindre en période de pointe) et du maintien de cotes touristiques en été ;une diminution de la production d'énergie due notamment à la réduction des apports en amont des ouvrages hydroélectriques

Mitochondrial fusion is regulated by Reaper to modulate Drosophila programmed cell death

In most multicellular organisms, the decision to undergo programmed cell death in response to cellular damage or developmental cues is typically transmitted through mitochondria. It has been suggested that an exception is the apoptotic pathway of Drosophila melanogaster, in which the role of mitochondria remains unclear. Although IAP antagonists in Drosophila such as Reaper, Hid and Grim may induce cell death without mitochondrial membrane permeabilization, it is surprising that all three localize to mitochondria. Moreover, induction of Reaper and Hid appears to result in mitochondrial fragmentation during Drosophila cell death. Most importantly, disruption of mitochondrial fission can inhibit Reaper and Hid-induced cell death, suggesting that alterations in mitochondrial dynamics can modulate cell death in fly cells. We report here that Drosophila Reaper can induce mitochondrial fragmentation by binding to and inhibiting the pro-fusion protein MFN2 and its Drosophila counterpart dMFN/Marf. Our in vitro and in vivo analyses reveal that dMFN overexpression can inhibit cell death induced by Reaper or γ-irradiation. In addition, knockdown of dMFN causes a striking loss of adult wing tissue and significant apoptosis in the developing wing discs. Our findings are consistent with a growing body of work describing a role for mitochondrial fission and fusion machinery in the decision of cells to die

Identifying Determinants of Cullin Binding Specificity Among the Three Functionally Different Drosophila melanogaster Roc Proteins via Domain Swapping

BACKGROUND: Cullin-dependent E3 ubiquitin ligases (CDL) are key regulators of protein destruction that participate in a wide range of cell biological processes. The Roc subunit of CDL contains an evolutionarily conserved RING domain that binds ubiquitin charged E2 and is essential for ubiquitylation. Drosophila melanogaster contains three highly related Roc proteins: Roc1a and Roc2, which are conserved in vertebrates, and Roc1b, which is specific to Drosophila. Our previous genetic data analyzing Roc1a and Roc1b mutants suggested that Roc proteins are functionally distinct, but the molecular basis for this distinction is not known. METHODOLOGY/PRINCIPAL FINDINGS: Using co-immunoprecipitation studies we show that Drosophila Roc proteins bind specific Cullins: Roc1a binds Cul1-4, Roc1b binds Cul3, and Roc2 binds Cul5. Through domain swapping experiments, we demonstrate that Cullin binding specificity is strongly influenced by the Roc NH(2)-terminal domain, which forms an inter-molecular beta sheet with the Cullin. Substitution of the Roc1a RING domain with that of Roc1b results in a protein with similar Cullin binding properties to Roc1a that is active as an E3 ligase but cannot complement Roc1a mutant lethality, indicating that the identity of the RING domain can be an important determinant of CDL function. In contrast, the converse chimeric protein with a substitution of the Roc1b RING domain with that of Roc1a can rescue the male sterility of Roc1b mutants, but only when expressed from the endogenous Roc1b promoter. We also identified mutations of Roc2 and Cul5 and show that they cause no overt developmental phenotype, consistent with our finding that Roc2 and Cul5 proteins are exclusive binding partners, which others have observed in human cells as well. CONCLUSIONS: The Drosophila Roc proteins are highly similar, but have diverged during evolution to bind a distinct set of Cullins and to utilize RING domains that have overlapping, but not identical, function in vivo