A single positively selected West Nile viral mutation confers increased virogenesis in American crows

West Nile virus (WNV), first recognized in North America in 1999, has been responsible for the largest arboviral epiornitic and epidemic of human encephalitis in recorded history. Despite the well-described epidemiological patterns of WNV in North America, the basis for the emergence of WNV-associated avian pathology, particularly in the American crow (AMCR) sentinel species, and the large scale of the North American epidemic and epiornitic is uncertain. We report here that the introduction of a T249P amino acid substitution in the NS3 helicase (found in North American WNV) in a low-virulence strain was sufficient to generate a phenotype highly virulent to AMCRs. Furthermore, comparative sequence analyses of full-length WNV genomes demonstrated that the same site (NS3-249) was subject to adaptive evolution. These phenotypic and evolutionary results provide compelling evidence for the positive selection of a mutation encoding increased viremia potential and virulence in the AMCR sentinel bird species.     

Receiving mixed signals: uncoupling oligodendrocyte differentiation and myelination

The development and maturation of an oligodendroglial cell is comprised of three intimately related processes that include proliferation, differentiation, and myelination. Here we review how proliferation and differentiation are controlled by distinct molecular mechanisms and discuss whether differentiation is merely a default of inhibited proliferation. We then address whether differentiation and myelination can be uncoupled in a similar manner. This task is particularly challenging because an oligodendrocyte cannot myelinate without first differentiating, and these processes are therefore not mutually exclusive. Is it solely the presence of the axon that distinguishes a differentiated oligodendrocyte from a myelinating one? Uncoupling these two processes requires identifying specific signals that regulate myelination without affecting the differentiation process. We will review current understanding of the relationship between differentiation and myelination and discuss whether these two processes can truly be uncoupled.     

The human genome and understanding of common disease: present and future technologies

The study of candidate genes over the past three decades has yielded notable successes in common-disease genetics. During this time, however, interpretation of genetic association studies has been hampered by the use of clinical cohorts of inadequate power and insufficient information on genetic variation in candidate genes. The unavailability of highthroughput and low-cost genotyping technologies has also limited the scope of complex-disease genetic studies. More recently, however, the sequencing and characterization of variation within the human genome has revolutionized genetic studies and enabled full genome-wide scans for genes associated with disease. The identification of disease-associated (causative) genes has illuminated disease mechanisms. The translation of this knowledge into direct clinical benefit in diagnosis, prognosis and therapy for an individual’s disease still remains a challenge. Received 11 September 2006; received after revision 17 December 2006; accepted 18 January 2007     

Podocalyxin enhances the adherence of cells to platelets

Podocalyxin (PODXL) is a mucin protein of the CD34 family expressed in kidney glomerular podocytes, vascular endothelium, progenitor bone marrow and tumor cells. It is assumed that PODXL plays an anti-adherent role in kidney podocytes. CHO cells stably expressing human PODXL (CHO-PODXL) or human tumor cells (Tera-1) inherently expressing PODXL showed increased adherence to platelets. The adherence of cells was inhibited (70%) by blockers of platelet P-selectin, prevented by the soluble ectodomain of human PODXL (PODXL-Δ) or by the arginine-glycine-aspartate (RGDS) peptide and partially impeded by inhibition of integrin αVβ3/αVβ5, suggesting a coordinated action of P-selectin and integrins. Colocalization of platelet P-selectin and PODXL expressed on CHO cells was demonstrated by confocal immunofluorescence. No adherence to platelets was observed when PODXL was expressed in glycomutant CHO cells deficient in sialic acid. Received 14 August 2007; received after revision 12 September 2007; accepted 13 September 2007     

Chronobiology of sleep in humans

Periodic circadian (24-h) cycles play an important role in daily hormonal and behavioural rhythms. Usually our sleep/wake cycle, temperature and melatonin rhythms are internally synchronized with a stable phase relationship. When there is a desynchrony between the sleep/wake cycle and circadian rhythm, sleep disorders such as advanced and delayed sleep phase syndrome can arise as well as transient chronobiologic disturbances, for example from jet lag and shift work. Appropriately timed bright light is effective in re-timing the circadian rhythm and sleep pattern to a more desired time, ameliorating these disturbances. Other less potent retiming effects may also be obtained from the judicious use of melatonin and exercise.     

From old organisms to new molecules: integrative biology and therapeutic targets in accelerated human ageing

Understanding the basic biology of human ageing is a key milestone in attempting to ameliorate the deleterious consequences of old age. This is an urgent research priority given the global demographic shift towards an ageing population. Although some molecular pathways that have been proposed to contribute to ageing have been discovered using classical biochemistry and genetics, the complex, polygenic and stochastic nature of ageing is such that the process as a whole is not immediately amenable to biochemical analysis. Thus, attempts have been made to elucidate the causes of monogenic progeroid disorders that recapitulate some, if not all, features of normal ageing in the hope that this may contribute to our understanding of normal human ageing. Two canonical progeroid disorders are Werner's syndrome and Hutchinson-Gilford progeroid syndrome (also known as progeria). Because such disorders are essentially phenocopies of ageing, rather than ageing itself, advances made in understanding their pathogenesis must always be contextualised within theories proposed to help explain how the normal process operates. One such possible ageing mechanism is described by the cell senescence hypothesis of ageing. Here, we discuss this hypothesis and demonstrate that it provides a plausible explanation for many of the ageing phenotypes seen in Werner's syndrome and Hutchinson-Gilford progeriod syndrome. The recent exciting advances made in potential therapies for these two syndromes are also reviewed.     

Telomeres and meiosis in health and disease

Beyond their role in replication and chromosome end capping, telomeres are also thought to function in meiotic chromosome pairing, meiotic and mitotic chromosome segregation as well as in nuclear organization. Observations in both somatic and meiotic cells suggest that the positioning of telomeres within the nucleus is highly specific and believed to be dependent mainly on telomere interactions with the nuclear envelope either directly or through chromatin interacting proteins. Although little is known about the mechanism of telomere clustering, some studies show that it is an active process. Recent data have suggested a regulatory role for telomere chromatin structure in telomere movement. This review will summarize recent studies on telomere interactions with the nuclear matrix, telomere chromatin structure and factors that modify telomere chromatin structure as related to regulation of telomere movement.     

New findings of Hexalona-branch representatives in Brazil,with a description of Prenda gen. nov. (Crustacea: Anomopoda: Aloninae)

Altogether, Coronatella and Hexalona-branches are considered the main lineages of Aloninae – a subfamily of common bottom-dwelling microcrustaceans in freshwater environments. Although the taxonomic features of Brazilian members of the Hexalona-branch have been summarised for species from the costata-group and affinis-group, a revision of other widely distributed species in the world is still lacking in this country. The aim of this paper was to study the morphology of Brazilian populations from the guttata-group and intermedia-group, and to describe a new genus from the Hexalona-branch. The parthenogenetic females of Alona cf. guttata from Brazil have similar morphology when compared to data from the literature, but the armature of the terminal claw of its males seems to be different from those of Alona guttata sensu stricto, Alona barbulata and Alona werestschagini. The intermedia-group is formed by Alona elisae sp. nov., which seems to be endemic to the Cerrado of Brazil Central, and Alona isabellae sp. nov., which is widely distributed in Brazil; this species has a labral keel armed with 2–4 setulae, and postabdomen with setulae of lateral fascicles longer than the level of marginal denticles, morphological traits that differentiate it from Alona elisae sp. nov. Another endemic species from the Hexalona-branch is Prenda arvensis gen. nov. and sp. nov., which has two main head pores, a reduced seta on endite 1 of the first limb, sixth limb is a wide lobe. The potential of biodiversity from the Hexalona-branch from Brazil is still underestimated, and a global revision of the guttata-group and intermedia-group is very important for the progress of Aloninae taxonomy and systematics.

http://zoobank.org/urn:lsid:zoobank.org:pub:0A2E4A30-0C9C-43E8-8E72-1DEDA6AFF3C3     

The carcinofauna found in stomach contents of the flying gurnard (Dactylopterus volitans) on the continental shelf of the Campos Basin,Brazil

A total of 3109 crustaceans belonging to 50 taxa distributed in 42 families were found in 117 analysed stomachs of flying gurnard (Dactylopterus volitans). Samples were obtained in April 2008 by the R/V Gyre using a bottom trawl towed in 12 stations at 14–100 m depth on the continental shelf of the Campos Basin, Brazil. The carcinofauna was analysed and the order Calanoida (Copepoda) found to be the most important item in terms of relative abundance and frequency of occurrence, followed by the order Amphipoda (Peracarida), the infraorder Brachyura (Decapoda), the order Stomatopoda and the subclass Myodocopa (Ostracoda). In the order Calanoida, the species Pontellopsis cf. villosa (Pontellidae) represented 98.04% of total crustacean abundance. The diet of Dactylopterus volitans varied according to fish size, with higher diversity of Crustacea at smaller size classes, decreasing in larger fishes. A similar pattern regarding depth was obtained, with greater diversity of taxa in gurnard stomachs caught at shallower depths. Flying gurnard is considered a generalized carnivore of invertebrates, eating mobile macrobenthic organisms, such as crustaceans, and its diet varies with its life stage, without any specific group as its main food source.