Etude entomologique de cinq foyers de leishmaniose cutanée dans la province de Sidi Kacem au nord du Maroc

Résumé. La leishmaniose cutanée est un important problème de santé publique dans la province de Sidi Kacem au nord-ouest du Maroc. L'incidence de cette affetion, due aussi bien à Leishmania tropica qu'à L. infantum est en augmentation progressive depuis 1997. La présente étude a été menée dans le but d'étudier l'écologie et la dynamique des populations des vecteurs de cette maladie dans les principaux foyers de cette province. Un total de 4504 spécimens appartenant à deux genres et six espèces a été capturé à l'aide de pièges adhésifs et lumineux, dans cinq foyers. Les espèces dominantes sont Phlebotomus sergenti représentant 42,6% du total des phlébotomes capturés et P. longicuspis avec 27,2% des captures. Ces deux espèces sont présentes de mai à novembre et évoluent en deux générations avec deux pics de densité, le premier en juin et le second en septembre. En considérant la grande spécificité vecteur-parasite connue en épidémiologie des leishmanioses ainsi que l'abondance des espèces capturées pendant la saison favorable à la transmission, P. sergenti et P. longicuspis seraient respectivement les vecteurs les plus probables des leishmanioses à L. tropica et à L. infantum dans la région étudiée. Le risque de transmission de la maladie serait plus grand durant le deuxième pic de densité en fin été- début automne.     

Making sense of ‘mixture’: states and the classification of ‘mixed’ people

Caribbean diaspora intellectuals have contributed significantly to African-American political struggles over the years, despite arguments by some African-American intellectuals about what they discern as West Indian negativism, extremism, and divisiveness in American political life. This essay examines the legacy of a representative sample of diasporic Caribbean intellectuals since the time of the Harlem Renaissance in the 1920s and culminating in the 1970s, notably, Garvey, members of the African Blood Brotherhood [ABB], C.L.R. James, and Walter Rodney, to demonstrate the phenomenal ideological vision, organizational capability, and political activism they have brought into fostering solidarity with African Americans in the struggle for fundamental change. The focus here is on their respective contributions to the debate on the relationship between class and race in America and the black diaspora generally, which has helped to shape the form, and orient the direction of African-American and Caribbean diasporic struggles for the better part of the twentieth century.     

Children's labour in ethnic family businesses: The case of Chinese take‐away businesses in Britain

Reliance upon unpaid and committed family labour is said to make many ethnic businesses competitive. However, most analysts' references to this labour have not taken into account the nature of family members' and, in particular, children's work roles or the ways in which their labour is elicited and maintained. Here, the nature of children's labour participation in ethnic businesses is investigated in the case of families running Chinese take‐away businesses in Britain. This article focuses on how children in these families understand their often double‐edged experiences of ‘helping out’, as part of a ‘family work contract’, and on the ways in which families negotiate children's labour over time. Given these families' experiences of migration and ethnic minority status, I argue that Chinese children's work in take‐away businesses must be examined in relation to the intersections of family obligations and relationships, livelihood strategies and pressures, and issues of cultural identity.     

Phenylimino-2H-chromen-3-carboxamide derivatives as novel small molecule inhibitors of β-secretase (BACE1)

The inhibition of β secretase (BACE1) is potentially important approach to treatment of Alzheimer disease (AD). A novel series of 4-bromophenyl piperazine derivatives coupled to the phenylimino-2H-chromen-3-carboxamide scaffold were investigated as BACE1 inhibitors in this study. Docking study suggested that the phenyl-imino group of the scaffold establishes favorable π–π stacking interaction with side chain of Phe108 of flap pocket. Some of the docking proposed derivatives were synthesized and evaluated for BACE1 inhibitory activity using a FRET-based assay. High BACE1 inhibitory activities were observed from derivatives containing fused heteroaromtic groups attached through the aliphatic linkage to the N4-piperazine moiety, which may be attributed to the engagement of effective interactions with S1–S′1 sub-pocket residues. Of the most potent compounds, 9e displayed an IC₅₀ value for BACE1 of 98 nM. Some of these derivatives demonstrated good inhibitory activity on Aβ production in N2a-APPswe cells at 5 and 10 μM. These compounds might be considered as promising BACE1 inhibitory agents that could lower Aβ production in AD.     

Modeling of human cytomegalovirus maternal-fetal transmission in a novel decidual organ culture

Human cytomegalovirus (HCMV) is the leading cause of congenital infection, associated with severe birth defects and intrauterine growth retardation. The mechanism of HCMV transmission via the maternal-fetal interface is largely unknown, and there are no animal models for HCMV. The initial stages of infection are believed to occur in the maternal decidua. Here we employed a novel decidual organ culture, using both clinically derived and laboratory-derived viral strains, for the ex vivo modeling of HCMV transmission in the maternal-fetal interface. Viral spread in the tissue was demonstrated by the progression of infected-cell foci, with a 1.3- to 2-log increase in HCMV DNA and RNA levels between days 2 and 9 postinfection, the expression of immediate-early and late proteins, the appearance of typical histopathological features of natural infection, and dose-dependent inhibition of infection by ganciclovir and acyclovir. HCMV infected a wide range of cells in the decidua, including invasive cytotrophoblasts, macrophages, and endothelial, decidual, and dendritic cells. Cell-to-cell viral spread was revealed by focal extension of infected-cell clusters, inability to recover infectious extracellular virus, and high relative proportions (88 to 93%) of cell-associated viral DNA. Intriguingly, neutralizing HCMV hyperimmune globulins exhibited inhibitory activity against viral spread in the decidua even when added at 24 h postinfection-providing a mechanistic basis for their clinical use in prenatal prevention. The ex vivo-infected decidual cultures offer unique insight into patterns of viral tropism and spread, defining initial stages of congenital HCMV transmission, and can facilitate evaluation of the effects of new antiviral interventions within the maternal-fetal interface milieu.     

Recognition and killing of human and murine pancreatic beta cells by the NK receptor NKp46

Type 1 diabetes is an incurable disease that is currently treated by insulin injections or in rare cases by islet transplantation. We have recently shown that NKp46, a major killer receptor expressed by NK cells, recognizes an unknown ligand expressed by β cells and that in the absence of NKp46, or when its activity is blocked, diabetes development is inhibited. In this study, we investigate whether NKp46 is involved in the killing of human β cells that are intended to be used for transplantation, and we also thoroughly characterize the interaction between NKp46 and its human and mouse β cell ligands. We show that human β cells express an unknown ligand for NKp46 and are killed in an NKp46-dependent manner. We further demonstrate that the expression of the NKp46 ligand is detected on human β cells already at the embryonic stage and that it appears on murine β cells only following birth. Because the NKp46 ligand is detected on healthy β cells, we wondered why type 1 diabetes does not develop in all individuals and show that NK cells are absent from the vicinity of islets of healthy mice and are detected in situ in proximity with β cells in NOD mice. We also investigate the molecular mechanisms controlling NKp46 interactions with its β cell ligand and demonstrate that the recognition is confined to the membrane proximal domain and stalk region of NKp46 and that two glycosylated residues of NKp46, Thr(125) and Asn(216), are critical for this recognition.     

Bio-diesel production directly from the microalgae biomass of Nannochloropsis by microwave and ultrasound radiation

This work offers an optimized method for the direct conversion of harvested Nannochloropsis algae into bio-diesel using two novel techniques. The first is a unique bio-technology-based environmental system utilizing flue gas from coal burning power stations for microalgae cultivation. This method reduces considerably the cost of algae production. The second technique is the direct transesterification (a one-stage method) of the Nannochloropsis biomass to bio-diesel production using microwave and ultrasound radiation with the aid of a SrO catalyst. These two techniques were tested and compared to identify the most effective bio-diesel production method. Based on our results, it is concluded that the microwave oven method appears to be the most simple and efficient method for the one-stage direct transesterification of the as-harvested Nannochloropsis algae.     

Anticancer and antimetastatic activity of Hypomyces chrysospermus,a cosmopolitan parasite in different human cancer cells

The importance of microbial natural compounds in drug research is increasing every year and they are used to prevent or treat a variety of diseases. Hypomyces chrysospermus is a cosmopolitan parasite of many Boletaceae members. Since not much work has been conducted to date, this study is undertaken to explore the anticancer effect, including the antiproliferative and antimetastatic activity of Hypomyces chrysospermus. The aim of this study is to determine the antiproliferative and antimetastatic activity of Hypomyces chrysospermus ethyl acetate extract, having antioxidant activity, against A549, Caco2, MCF-7 human cancer and CCD-19 Lu and CCD 841 CoN healthy human cell lines. Firstly, cytotoxic activity was determined by the WST-1 assay. After cell proliferations and anti-metastatic effects were investigated by a real-time cell analysis system (RTCA-DP) and IC₅₀ concentrations were calculated for each cell line. In addition, the expression levels of Apaf-1, TNF and NF-kB mRNA in cancer cells were investigated with RealTime-PCR. The ethyl acetate extract of Hypomyces chrysospermus presented anticancer activities including antiproliferative and antimetastatic effects. Hypomyces chrysospermus as a source of biologically active metabolites can be used as an important resource in the development of new anticancer effective agents.

     

Control of pancreatic β cell regeneration by glucose metabolism

Recent studies revealed a surprising regenerative capacity of insulin-producing β cells in mice, suggesting that regenerative therapy for human diabetes could in principle be achieved. Physiologic β cell regeneration under stressed conditions relies on accelerated proliferation of surviving β cells, but the factors that trigger and control this response remain unclear. Using islet transplantation experiments, we show that β cell mass is controlled systemically rather than by local factors such as tissue damage. Chronic changes in β cell glucose metabolism, rather than blood glucose levels per se, are the main positive regulator of basal and compensatory β cell proliferation in vivo. Intracellularly, genetic and pharmacologic manipulations reveal that glucose induces β cell replication via metabolism by glucokinase, the first step of glycolysis, followed by closure of K(ATP) channels and membrane depolarization. Our data provide a molecular mechanism for homeostatic control of β cell mass by metabolic demand.     

Aurora B kinase and protein phosphatase 1 have opposing roles in modulating kinetochore assembly

The outer kinetochore binds microtubules to control chromosome movement. Outer kinetochore assembly is restricted to mitosis, whereas the inner kinetochore remains tethered to centromeres throughout the cell cycle. The cues that regulate this transient assembly are unknown. We find that inhibition of Aurora B kinase significantly reduces outer kinetochore assembly in Xenopus laevis and human tissue culture cells, frog egg extracts, and budding yeast. In X. leavis M phase extracts, preassembled kinetochores disassemble after inhibiting Aurora B activity with either drugs or antibodies. Kinetochore disassembly, induced by Aurora B inhibition, is rescued by restraining protein phosphatase 1 (PP1) activity. PP1 is necessary for kinetochores to disassemble at the exit from M phase, and purified enzyme is sufficient to cause disassembly on isolated mitotic nuclei. These data demonstrate that Aurora B activity is required for kinetochore maintenance and that PP1 is necessary and sufficient to disassemble kinetochores. We suggest that Aurora B and PP1 coordinate cell cycle-dependent changes in kinetochore assembly though phosphorylation of kinetochore substrates.