The malaria parasite Plasmodium vivax exhibits greater genetic diversity than Plasmodium falciparum

We sequenced and annotated the genomes of four P. vivax strains collected from disparate geographic locations, tripling the number of genome sequences available for this understudied parasite and providing the first genome-wide perspective of global variability in this species. We observe approximately twice as much SNP diversity among these isolates as we do among a comparable collection of isolates of P. falciparum, a malaria-causing parasite that results in higher mortality. This indicates a distinct history of global colonization and/or a more stable demographic history for P. vivax relative to P. falciparum, which is thought to have undergone a recent population bottleneck. The SNP diversity, as well as additional microsatellite and gene family variability, suggests a capacity for greater functional variation in the global population of P. vivax. These findings warrant a deeper survey of variation in P. vivax to equip disease interventions targeting the distinctive biology of this neglected but major pathogen.     

ESR dates for the hominid burial site of Es Skhul in Israel

The Middle East has been critical to our understanding of recent human evolution ever since the recovery of Neanderthal and early anatomically modern fossils from the caves of Tabun and Skhul (Mount Carmel) over 50 years ago. It was generally believed, on archaeological and morphological grounds, that middle eastern Neanderthals (such as those from Tabun, Amud and Kebara) probably dated from more than 50,000 years ago, whereas the earliest anatomically modern specimens (from Skhul and Qafzeh) probably dated from about 40,000 years. Recent thermoluminescence and electron spin resonance (ESR) determinations, however, have supported biostratigraphy in dating the Qafzeh deposits to an earlier part of the late Pleistocene, probably more than 90,000 years ago. These dates have been questioned on unspecified technical grounds, and it has also been argued that they create explanatory problems by separating the morphologically similar Qafzeh and Skhul samples by some 50,000 years, thus implying a long-term coexistence of early modern humans and Neanderthals in the area. Here we report the first radiometric dating analysis for Skhul, using ESR on bovine teeth from the hominid burial levels. Early uptake and linear uptake ages average 81 +/- 15 and 101 +/- 12 kyr respectively. These analyses suggest that the Skhul and Qafzeh samples are of a similar age and therefore it is possible that the presence of early modern humans in the area was episodic, rather than long-term during the early late Pleistocene.     

Predictive models of molecular machines involved in Caenorhabditis elegans early embryogenesis

Although numerous fundamental aspects of development have been uncovered through the study of individual genes and proteins, system-level models are still missing for most developmental processes. The first two cell divisions of Caenorhabditis elegans embryogenesis constitute an ideal test bed for a system-level approach. Early embryogenesis, including processes such as cell division and establishment of cellular polarity, is readily amenable to large-scale functional analysis. A first step toward a system-level understanding is to provide 'first-draft' models both of the molecular assemblies involved and of the functional connections between them. Here we show that such models can be derived from an integrated gene/protein network generated from three different types of functional relationship: protein interaction, expression profiling similarity and phenotypic profiling similarity, as estimated from detailed early embryonic RNA interference phenotypes systematically recorded for hundreds of early embryogenesis genes. The topology of the integrated network suggests that C. elegans early embryogenesis is achieved through coordination of a limited set of molecular machines. We assessed the overall predictive value of such molecular machine models by dynamic localization of ten previously uncharacterized proteins within the living embryo.     

Mutant frizzled-4 disrupts retinal angiogenesis in familial exudative vitreoretinopathy

Familial exudative vitreoretinopathy (FEVR) is a hereditary ocular disorder characterized by a failure of peripheral retinal vascularization. Loci associated with FEVR map to 11q13-q23 (EVR1; OMIM 133780, ref. 1), Xp11.4 (EVR2; OMIM 305390, ref. 2) and 11p13-12 (EVR3; OMIM 605750, ref. 3). Here we have confirmed linkage to the 11q13-23 locus for autosomal dominant FEVR in one large multigenerational family and refined the disease locus to a genomic region spanning 1.55 Mb. Mutations in FZD4, encoding the putative Wnt receptor frizzled-4, segregated completely with affected individuals in the family and were detected in affected individuals from an additional unrelated family, but not in normal controls. FZD genes encode Wnt receptors, which are implicated in development and carcinogenesis. Injection of wildtype and mutated FZD4 into Xenopus laevis embryos revealed that wildtype, but not mutant, frizzled-4 activated calcium/calmodulin-dependent protein kinase II (CAMKII) and protein kinase C (PKC), components of the Wnt/Ca(2+) signaling pathway. In one of the mutants, altered subcellular trafficking led to defective signaling. These findings support a function for frizzled-4 in retinal angiogenesis and establish the first association between a Wnt receptor and human disease.     

First record of multiple paternity in the pygmy rabbit ( Brachylagus idahoensis ): evidence from analysis of 16 microsatellite loci

Although promiscuity is believed to be common among leporids, little is known about the mating system of free-ranging pygmy rabbits ( Brachylagus idahoensis ). We used 16 polymorphic microsatellite markers and DNA extracted from tissue samples of 10 rabbits from 2 litters collected in east central Idaho to evaluate paternity. We incorporated maternal genotypes for better resolution and employed an exclusion approach to detect multiple paternity. Our results demonstrated multiple paternity at 6 of the 16 loci tested for each litter. These findings support the expectation that pygmy rabbits have a promiscuous mating system. It has been proposed that multiple paternity could lead to higher effective population sizes and help small populations maintain diversity. Given that pygmy rabbits persist in small and fragmented populations, a promiscuous mating system might be important for maintaining genetic diversity in free-ranging populations and could be advantageous for the captive breeding program. Aunque se cree que la promiscuidad es común entre los lepóridos, se conoce poco sobre el sistema de apareamiento del conejo pigmeo ( Brachylagus idahoensis ) en condiciones silvestres. Utilizamos 16 marcadores de microsatélites polimórficos y ADN extraído de muestras de tejido de 10 conejos de 2 camadas colectadas en la parte este central de Idaho para evaluar su paternidad. Los genotipos maternos fueron incorporados para lograr una mayor resolución y empleamos un método de exclusión para detectar la paternidad múltiple. Nuestros resultados demuestran paternidad múltiple en 6 de los 16 loci examinados en cada camada. Estos resultados apoyan la suposición de que los conejos pigmeos tienen un sistema de apareamiento promiscuo. Se ha propuesto que la paternidad múltiple podría conducir a tamaños efectivos de la población más grandes y ayudar a que las poblaciones pequeñas mantengan la diversidad. En vista de que el conejo pigmeo persiste en poblaciones pequeñas y fragmentadas, un sistema de apareamiento promiscuo podría ser importante para mantener la diversidad genética en poblaciones silvestres y podría resultar provechoso para el programa de cría en cautiverio.     

Helminth parasites of seven anuran species from northwestern Mexico

One hundred eighty-three specimens representing 7 anuran species were examined for helminth parasites: Bufo kelloggi, B. mazatlanensis, Leptodactylus melanonotus, Pachymedusa dacnicolor, Rana forreri, R. magnaocularis, Smilisca baudini . The following species were found: 8 species of Trematoda, Cephalogonimus americanus, Clinostomum attenuatum (larva), Glypthelmins poncedeleoni, G. quieta, Gorgoderina attenuata, Haematoloechus complexus, H. longiplexus , and Megalodiscus temperatus ; 2 species of Cestoda, Cylindrotaenia americana and Nematotaenia dispar ; 13 species of Nematoda, Aplectana incerta, A. itzocanensis, Cosmocerca podicipinus, Cosmocercella haberi, Cosmocercoides variabilis, Foleyellides striatus, Oswaldocruzia pipiens, Rhabdias americanus, R. ranae, Subulascaris falcaustriformis, Physaloptera sp. (larva), Physocephalus sp. (larva), and Spiroxys sp. (larva); and 1 species of Acanthocephala (cystacanth). Helminth species richness was 6.4 ± 2.4 s. Thirty-five new host records are reported.     

The detection of superoxide anion from the reaction of oxyhemoglobin and phenylhydrazine using EPR spectroscopy.

The low temperature EPR spectrum of a quickly reacted mixture of oxyhemoglobin and phenylhydrazine was studied. With the use of a computer, the spectral contribution of methemoglobin in the region of g = 2 was subtracted. The remaining spectrum was that of an axial free radical (g perpendicular = 2.00, g parallel = 2.06) having the magnetic parameters of superoxide anion. In the presence of superoxide dismutase, this axial radical was not seen, confirming that superoxide anion is indeed generated by the reaction.