Molecular insight into heart development and congenital heart disease: An update review from the Arab countries.

Congenital heart defect (CHD) has a major influence on affected individuals as well as on the supportive and associated environment such as the immediate family. Unfortunately, CHD is common worldwide with an incidence of approximately 1% and consequently is a major health concern. The Arab population has a high rate of consanguinity, fertility, birth, and annual population growth, in addition to a high incidence of diabetes mellitus and obesity. All these factors may lead to a higher incidence and prevalence of CHD within the Arab population than in the rest of the world, making CHD of even greater concern. Sadly, most Arab countries lack appropriate public health measures directed toward the control and prevention of congenital malformations and so the importance of CHD within the population remains unknown but is thought to be high. In approximately 85% of CHD patients, the multifactorial theory is considered as the pathologic basis. The genetic risk factors for CHD can be attributed to large chromosomal aberrations, copy number variations (CNV) of particular regions in the chromosome, and gene mutations in specific nuclear transcription pathways and in the genes that are involved in cardiac structure and development. The application of modern molecular biology techniques such as high-throughput nucleotide sequencing and chromosomal array and methylation array all have the potential to reveal more genetic defects linked to CHD. Exploring the genetic defects in CHD pathology will improve our knowledge and understanding about the diverse pathways involved and also about the progression of this disease. Ultimately, this will link to more efficient genetic diagnosis and development of novel preventive therapeutic strategies, as well as gene-targeted clinical management. This review summarizes our current understanding of the molecular basis of normal heart development and the pathophysiology of a wide range of CHD. The risk factors that might account for the high prevalence of CHD within the Arab population and the measures required to be undertaken for conducting research into CHD in Arab countries will also be discussed.

Biogeographic origin and radiation of the Old World crocidurine shrews (Mammalia: Soricidae) inferred from mitochondrial and nuclear genes.

The crocidurine shrews include the most speciose genus of mammals, Crocidura. The origin and evolution of their radiation is, however, poorly understood because of very scant fossil records and a rather conservative external morphology between species. Here, we use an alignment of 3560 base pairs of mitochondrial and nuclear DNA to generate a phylogenetic hypothesis for the evolution of Old World shrews of the subfamily Crocidurinae. These molecular data confirm the monophyly of the speciose African and Eurasian Crocidura, which also includes the fossorial, monotypic genus Diplomesodon. The phylogenetic reconstructions give further credit to a paraphyletic position of Suncus shrews, which are placed into at least two independent clades (one in Africa and sister to Sylvisorex and one in Eurasia), at the base of the Crocidura radiation. Therefore, we recommend restricting the genus Suncus to the Palaearctic and Oriental taxa, and to consider all the African Suncus as Sylvisorex. Using molecular dating and biogeographic reconstruction analyses, we suggest a Palaearctic-Oriental origin for Crocidura dating back to the Upper Miocene (6.8 million years ago) and several subsequent colonisations of the Afrotropical region by independent lineages of Crocidura.

Muco-cutaneous leishmaniasis in the New World: The ultimate subversion.

Infection by the human protozoan parasite Leishmania can lead, depending primarily on the parasite species, to either cutaneous or mucocutaneous lesions, or fatal generalized visceral infection. In the New World, Leishmania (Viannia) species can cause mucocutaneous leishmaniasis (MCL). Clinical MCL involves a strong hyper-inflammatory response and parasitic dissemination (metastasis) from a primary lesion to distant sites, leading to destructive metastatic secondary lesions especially in the nasopharyngal areas. Recently, we reported that metastasizing, but not non-metastatic strains of Leishmania (Viannia) guyanensis, have high burden of a non-segmented dsRNA virus, Leishmania RNA Virus (LRV). Viral dsRNA is sensed by the host Toll-like Receptor 3 (TLR3) thereby inducing a pro-inflammatory response and exacerbating the disease. The presence of LRV in Leishmania opens new perspectives not only in basic understanding of the intimate relation between the parasite and LRV, but also in understanding the importance of the inflammatory response in MCL patients.

The Swiss Willensnation at Risk: Teachers in the Cultural Gap during the First World War

As a neutral and multilingual country, Switzerland struggled with major domestic political conflicts during the First World War due to the two cultures of the French-speaking and German-speaking parts of the country. The divided cultural loyalties ('fossé moral', 'Röstigraben'), consisting of Swiss-Germans supporting Germany and Swiss-French supporting France, were discussed intensively in both of the main teachers' journals in Switzerland. Teachers felt the need to react and to promote unity from the beginning of the war. Despite the fact that the cantons are responsible for public education and, therefore, for the education of their students, teachers considered themselves called to educate their students to be national citizens rather than to be members of a language group. This threefold citizenship - communal, cantonal and national - was not scrutinised, but national unity became crucial due to the critical political circumstances. How did teachers promote and constitute citizenship for themselves and for their students in a nation united by free will during the First World War, a time of severe internal political conflicts?

The role of proteolytic processing and the stable signal peptide in expression of the Old World arenavirus envelope glycoprotein ectodomain.

Maturation of the arenavirus GP precursor (GPC) involves proteolytic processing by cellular signal peptidase and the proprotein convertase subtilisin kexin isozyme 1 (SKI-1)/site 1 protease (S1P), yielding a tripartite complex comprised of a stable signal peptide (SSP), the receptor-binding GP1, and the fusion-active transmembrane GP2. Here we investigated the roles of SKI-1/S1P processing and SSP in the biosynthesis of the recombinant GP ectodomains of lymphocytic choriomeningitis virus (LCMV) and Lassa virus (LASV). When expressed in mammalian cells, the LCMV and LASV GP ectodomains underwent processing by SKI-1/S1P, followed by dissociation of GP1 from GP2. The GP2 ectodomain spontaneously formed trimers as revealed by chemical cross-linking. The endogenous SSP, known to be crucial for maturation and transport of full-length arenavirus GPC was dispensable for processing and secretion of the soluble GP ectodomain, suggesting a specific role of SSP in the stable prefusion conformation and transport of full-length GPC.

Temporal and spatial origin of Gesneriaceae in the New World inferred from plastid DNA sequences

Gesneriaceae are represented in the New World (NW) by a major clade (c. 1000 species) currently recognized as subfamily Gesnerioideae. Radiation of this group occurred in all biomes of tropical America and was accompanied by extensive phenotypic and ecological diversification. Here we performed phylogenetic analyses using DNA sequences from three plastid loci to reconstruct the evolutionary history of Gesnerioideae and to investigate its relationship with other lineages of Gesneriaceae and Lamiales. Our molecular data confirm the inclusion of the South Pacific Coronanthereae and the Old World (OW) monotypic genus Titanotrichum in Gesnerioideae and the sister-group relationship of this subfamily to the rest of the OW Gesneriaceae. Calceolariaceae and the NW genera Peltanthera and Sanango appeared successively sister to Gesneriaceae, whereas Cubitanthus, which has been previously assigned to Gesneriaceae, is shown to be related to Linderniaceae. Based on molecular dating and biogeographical reconstruction analyses, we suggest that ancestors of Gesneriaceae originated in South America during the Late Cretaceous. Distribution of Gesneriaceae in the Palaeotropics and Australasia was inferred as resulting from two independent long-distance dispersals during the Eocene and Oligocene, respectively. In a short time span starting at 34 Mya, ancestors of Gesnerioideae colonized several Neotropical regions including the tropical Andes, Brazilian Atlantic forest, cerrado, Central America and the West Indies. Subsequent diversification within these areas occurred largely in situ and was particularly extensive in the mountainous systems of the Andes, Central America and the Brazilian Atlantic forest. Only two radiations account for 90% of the diversity of Gesneriaceae in the Brazilian Atlantic forest, whereas half of the species richness in the northern Andes and Central America originated during the last 10 Myr from a single radiation.