Autosomal Dominant Hypercholesterolemia: Needs for Early Diagnosis and Cascade Screening in the Tunisian Population

Autosomal dominant hypercholesterolemia (ADH) is characterized by an isolated elevation of plasmatic low-density lipoprotein (LDL), which predisposes to premature coronary artery disease (CAD) and early death. ADH is largely due to mutations in the low-density lipoprotein receptor gene (LDLR), the apolipoprotein B-100 gene (APOB), or the proprotein convertase subtilisin/kexin type 9 (PCSK9). Early diagnosis and initiation of treatment can modify the disease progression and its outcomes. Therefore, cascade screening protocol with a combination of plasmatic lipid measurements and DNA testing is used to identify relatives of index cases with a clinical diagnosis of ADH. In Tunisia, an attenuated phenotypic expression of ADH was previously reported, indicating that the establishment of a special screening protocol is necessary for this population.     

Les Nématodes Trichostrongylina parasites d'Amphibiens et de Reptiles: problèmes taxonomiques, phylétiques et biogéographiques

Except for four species of the Mertensinematinae (Molineoidea) not considered in this work, the Trichostrongylina parasitic in amphibians and reptiles, comprising 15 genera and 105 species, are reviewed. The morphological characteristics of each species are analysed. The most important characteristics are provided by the disposition of the caudal bursal rays, the morphology of the synlophe (at the oesophago-intestinal junction and mid-body level) and by the anatomy of the spicules. The species are classified into seven groups:Group 1: relict species with six lips and well-developed buccal capsule (six genera and 16 species).Group 2: ancient species with one or two primitive characters (eight genera and 15 species).Seventy-four species, without primitive characters, comprise the genus Oswaldocruzia which is subdivided into five groups.Group 3: Oriento-Ethiopian species with non-idiomorphic spicules with two to three tips (10 species).Group 4: Neo-Ethiopian species with non-idiomorphic spicules with numerous tips (11 species).Group 5: Holarctic species with idiomorphic spicules with the spicular fork divided above the distal third of the spicule length (24 species).Group 6: Continental Neotropical species with idiomorphic spicules and spicular fork divided within the distal third of the spicule length (21 species).Group 7: Caribbean Neotropical species with modified idiomorphic spicules, the three main branches of which are each divided into numerous tips (eight species).The geographical distribution of the species appears to be of greater significance than the host spectrum and suggests the following biogeographical hypotheses: Group 1, entirely Gondwanan, diversified during the Cretaceous era prior to the separation of the southern continents. The expansion of Group 2, which is represented by Gondwanan and Oriental species mainly from India, Malaysia and Indochina, could have occurred throughout South-East Asia at the end of the Cretaceous era when India collided with Eurasia. Group 3 could be interpreted either as a migration from Asia to Africa during the upper Eocene, or more likely during the Miocene, or, by a dispersion due to the migrations of Bufo melanostictus. Group 4 may result from the expansion of the former group in the Ethiopian region. Group 5 could be interpreted as a colonisation of western Europe and the Nearctic from Asia during the Tertiary. Group 6 could have arisen after the migration of the Neartic species to the Neotropical region during the Pliocene period and Group 7 by the expansion of the former group in the Caribbean.Amongst the Trichostrongylina, the relict and ancient genera parasitic in amphibians and reptiles can only be compared with the genera parasitic in birds and mammals, probably dating from the Palaeocene period (mainly marsupials and primitive insectivores). On the other hand, the genus Oswaldocruzia can be compared with other members of the Molineoidea parasitic in fissipeds, Pholidota and Chiroptera dating from a later period (Eocene) (see Durette-Desset, 1971). Thus, the Trichostrongylina of amphibians and reptiles are distinguished by the persistence of very old species, the evolution and the geographical distribution of which was arrested for millions of years, and by the existence (in some regions) of groups undergoing full evolutionary expansion.The new taxa proposed in the paper are: Bakeria (Moravec & Sey, 1986) status emend. (= Bakeria Moravec & Sey sub. g.), Ragenema n. g., Ragenema robustum (Baker, 1982) n. comb. (= Oswaldocruzia robusta), Typhlopsia quentini (Durette-Desset, 1980) n. comb. (= Trichoskrjabinia quentini), T. secundus (Pinnell & Schmidt, 1977) n. comb. (= Trichoskrjabinia secundus), T. gansi (Crusz & Ching, 1975) n. comb. (= Oswaldocruzia gansi), T. limnodynastes (Johnston & Simpson, 1942) n. comb. (= Oswaldocruzia limnodynastes), T. legendrei (Chabaud & Brygoo, 1962) n. comb. (= Oswaldocruzia legendrei).

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Les Nématodes Trichostrongylina parasites d'Amphibiens et de Reptiles: problèmes taxonomiques, phylétiques et biogéographiques

     

Membrane domains and polarized trafficking of sphingolipids

The plasma membrane of polarized cells consists of distinct domains, the apical and basolateral membrane, that are characterized by a distinct lipid and protein content. Apical protein transport is largely mediated by (glyco)sphingolipid--cholesterol enriched membrane microdomains, so called rafts. In addition changes in the direction of polarized sphingolipid transport appear instrumental in cell polarity development. Knowledge is therefore required of the mechanisms that mediate sphingolipid sorting and the complexity of the trafficking pathways that are involved in polarized transport of both sphingolipids and proteins. Here we summarize specific biophysical properties that underly mechanisms relevant to sphingolipid sorting, cargo recruitment and polarized trafficking, and discuss the central role of a subapical compartment, SAC or common endosome (CE), as a major intracellular site involved in polarized sorting of sphingolipids, and in development and maintenance of membrane polarity.     

Production of two entomopathogenic Aspergillus species and insecticidal activity against the mosquito Culex quinquefasciatus compared to Metarhizium anisopliae

The spore productivity and insecticidal activity of two opportunistic insect pathogenic Aspergillus species (namely: Aspergillus clavatus Desmazieres and Aspergillus flavus Link (Ascomycota: Eurotiales, Trichocomaceae)) were compared to Metarhizium anisopliae sensu lato (Metchnikoff) Sorokin (Ascomycota: Hypocreales, Clavicipitaceae) for mosquito (Diptera: Culicidae) control. The production of aerial spores on wheat bran and white rice was investigated in solid-, semi-solid-, and liquid-state media supplemented with a nutritive solution. Wheat bran-based media increased the spore yield in solid-state from three to sevenfold: A. clavatus produced 48.4?±?5.2 and 15.7?±?1.6?×?10⁸ spores/g, A. flavus produced 22.3?±?4.1 and 3.1?±?2.5?×?10⁸ spores/g, and M. anisopliae produced 39.6?±?6.5 and 13.1?±?2.6?×?10⁸ spores/g of wheat bran or white rice, respectively. A. clavatus, A. flavus and M. anisopliae spores harvested from wheat bran-based solid-state media showed lethal concentrations (LC₅₀) of 1.1, 1.8, and 1.3?×?10⁸ spores/ml against Culex quinquefasciatus Say larvae in 72?h. Because A. clavatus and M. anisopliae displayed similar features when cultured under these conditions, our results suggest that insect pathogenic Aspergillus species may be as productive and virulent against mosquito larvae as a well-recognised entomopathogenic fungus.     

Molecular characterization of Echinococcus granulosus in Tunisia and Mauritania by mitochondrial rrnS gene sequencing

Cystic hydatid disease is a zoonotic parasitic disease caused by the cestode Echinococcus granulosus and represents a major public health problem in many countries around the world, including North Africa. E. granulosus exists as a series of genetic variants or strains which differ in a wide variety of criteria that impact on the epidemiology, pathology and control of cystic hydatid disease. Nucleotide sequencing of the mitochondrial rrnS gene was here used to characterize 38 E. granulosus isolates collected from different regions and hosts in Tunisia and Mauritania. The results obtained reveal a significant genetic differentiation between E. granulosus hydatid cysts identified as belonging to the G1 genotype and to the G6/G7 cluster using the rrnS gene as marker, and indicate the circulation of the common sheep strain (G1) in all host species from Tunisia and the camel/pig strain cluster (G6/G7) in camel from Mauritania. Other investigations, using this method, are necessary for further genetic analysis of a wider range of isolates from different host species in order to more fully understand the genetic structure of E. granulosus populations and their transmission dynamics in this and neighbouring African countries.     

Molecular evidence for the occurrence of Contracaecum rudolphii A (Nematoda: Anisakidae) in shag Phalacrocorax aristotelis (Linnaeus) (Aves: Phalacrocoracidae) from Sardinia (western Mediterranean Sea)

Specimens of Contracaecum rudolphii Hartwich, 1964 (Nematoda: Anisakidae) from Phalacrocorax aristotelis (Linnaeus) from the Archipelago of La Maddalena (Sardinia, western Mediterranean Sea) were characterised genetically and compared with C. rudolphii A sensu D’Amelio et al. 1990 and C. rudolphii B sensu D’Amelio et al. 1990 from Phalacrocorax carbo sinensis (Blumenbach) from north-eastern Italy, and with C. rudolphii C sensu D’Amelio et al. 2007 from Phalacrocorax auritus (Lesson) from west-central Florida, USA. The sequencing of the small subunit of the mitochondrial ribosomal RNA gene (rrnS) and by polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLP) analysis of the same gene and of the internal transcribed spacers (ITS) of nuclear ribosomal DNA (rDNA) allowed the identification of all specimens of C. rudolphii from P. aristotelis as C. rudolphii A. The results confirmed that the definition of genetic markers, following the analysis of nuclear ribosomal and mitochondrial DNA, provides quick and practical diagnostic tools for the detection of the 3 sibling species of C. rudolphii. The occurrence of C. rudolphii in P. aristotelis is reported for the first time from the Mediterranean area, improving the picture of the dispersal patterns of the populations of these piscivorous birds, and confirming the existence of different and isolated populations between the North and South European waters.     

HLA polymorphism in type 1 diabetes Tunisians

Several studies of the association between HLA and type 1 diabetes have been carried out revealing differences between ethnic groups. Our study, as part of the studies that should be performed about this association in the rest of the word, aims at elucidating the HLA DRB1, DQB1 polymorphism in Tunisian type 1 diabetes. This study includes 43 unrelated type 1 diabetes patients, and their mean age at onset is less than 15 years. Analysis of the frequency of alleles and haplotypes in these subjects, compared to a reference group (n = 101) led to the following results. 1) The Tunisian insulin-dependent diabetics present similarities as well as differences with other ethnic groups (Caucasians, North Africans). 2) The haplotype DRB1*04 DQ*0302 and DRB1*03 DQB1*0201 is positively associated to type 1 diabetes. 3) The heterozygotic genotype DRB1*04 DQB1*0302 / DRB1*03 DQB1*0201 is strongly associated to type 1 diabetes. 4) The haplotypes DRB1*01501 DQB1*0602 and DRB1*11 DQB1*0301 proved to be protective. In addition, the study of the subtypes DRB1*04 showed that alleles DRB1*0405 predispose to type 1 diabetes, whereas the allele DRB1*0403, which is in linkage disequilibrium with the DQB1*0402 in the Tunisian population, has a protective effect.     

Mechanisms of sorting and transport of proteins to tw membrane domains of epithelial cells

Polarity is a fundamental characteristic of most eukaryotic cells. The plasma membrane of such cells consists in two structurally and functionally different domains, i.e., the basolateral and the apical membrane, separated by tight junctions. The generation of the distinct molecular identity of both domains and its maintenance in spite of the dynamics of lipids and proteins at either surface requires sophisticated sorting and trafficking mechanisms. Recent progress in the field of polarized trafficking reveals that, for a detailed understanding of its mechanism and regulation, an integrated approach that includes the flow of both lipids and proteins is imperative. In this review, some recent progress in understanding mechanisms involved in protein sorting and trafficking is discussed. We focus on the role of lipid microdomains (Rafts) in trafficking of proteins to the apical surface of polarized cells.