Phylogeography of Recently Emerged DENV-2 in Southern Viet Nam

Revealing the dispersal of dengue viruses (DENV) in time and space is central to understanding their epidemiology. However, the processes that shape DENV transmission patterns at the scale of local populations are not well understood, particularly the impact of such factors as human population movement and urbanization. Herein, we investigated trends in the spatial dynamics of DENV-2 transmission in the highly endemic setting of southern Viet Nam. Through a phylogeographic analysis of 168 full-length DENV-2 genome sequences obtained from hospitalized dengue cases from 10 provinces in southern Viet Nam, we reveal substantial genetic diversity in both urban and rural areas, with multiple lineages identified in individual provinces within a single season, and indicative of frequent viral migration among communities. Focusing on the recently introduced Asian I genotype, we observed particularly high rates of viral exchange between adjacent geographic areas, and between Ho Chi Minh City, the primary urban center of this region, and populations across southern Viet Nam. Within Ho Chi Minh City, patterns of DENV movement appear consistent with a gravity model of virus dispersal, with viruses traveling across a gradient of population density. Overall, our analysis suggests that Ho Chi Minh City may act as a source population for the dispersal of DENV across southern Viet Nam, and provides further evidence that urban areas of Southeast Asia play a primary role in DENV transmission. However, these data also indicate that more rural areas are also capable of maintaining virus populations and hence fueling DENV evolution over multiple seasons

Persistence of DNA threads in human anaphase cells suggests late completion of sister chromatid decatenation

PICH (Plk1-interacting checkpoint helicase) was recently identified as an essential component of the spindle assembly checkpoint and shown to localize to kinetochores, inner centromeres, and thin threads connecting separating chromosomes even during anaphase. In this paper, we have used immuno-fiber fluorescence in situ hybridization and chromatin-immunoprecipitation to demonstrate that PICH associates with centromeric chromatin during anaphase. Furthermore, by careful analysis of PICH-positive anaphase threads through FISH as well as bromo-deoxyurdine and CREST labeling, we strengthen the evidence that these threads comprise mainly alphoid centromere deoxyribonucleic acid. Finally, by timing the addition of ICRF-193 (a specific inhibitor of topoisomerase-II alpha) to cells synchronized in anaphase, we demonstrate that topoisomerase activity is required specifically to resolve PICH-positive threads during anaphase (as opposed to being required to prevent the formation of such threads during earlier cell cycle stages). These data indicate that PICH associates with centromeres during anaphase and that most PICH-positive threads evolve from inner centromeres as these stretch in response to tension. Moreover, they show that topoisomerase activity is required during anaphase for the resolution of PICH-positive threads, implying that the complete separation of sister chromatids occurs later than previously assumed

FGF2 regulates melanocytes viability through the STAT3-transactivated PAX3 transcription

PAX3 (paired box 3) is known to have an important role in melanocyte development through modulation of microphthalmia-associated transcription factor transcription. Here we found that PAX3 transcriptional activity could be regulated through FGF2 (basic fibroblast growth factor)-STAT3 (signal transducer and activator of transcription 3) signaling in the pigment cells. To study its function in vivo, we have generated a transgenic mouse model expressing PAX3 driven by tyrosinase promoter in a tissue-specific fashion. These animals exhibit hyperpigmentation in the epidermis, evident in the skin color of their ears and tails. We showed that the darker skin color results from both increased melanocyte numbers and melanin synthesis. Together, our study delineated a novel pathway in the melanocyte lineage, linking FGF2-STAT3 signaling to increased PAX3 transcription. Moreover, our results suggest that this pathway might contribute to the regulation of melanocyte numbers and melanin levels, and thereby provide an alternative strategy to induce pigmentation

A Tradeoff Drives the Evolution of Reduced Metal Resistance in Natural Populations of Yeast

Various types of genetic modification and selective forces have been implicated in the process of adaptation to novel or adverse environments. However, the underlying molecular mechanisms are not well understood in most natural populations. Here we report that a set of yeast strains collected from Evolution Canyon (EC), Israel, exhibit an extremely high tolerance to the heavy metal cadmium. We found that cadmium resistance is primarily caused by an enhanced function of a metal efflux pump, PCA1. Molecular analyses demonstrate that this enhancement can be largely attributed to mutations in the promoter sequence, while mutations in the coding region have a minor effect. Reconstruction experiments show that three single nucleotide substitutions in the PCA1 promoter quantitatively increase its activity and thus enhance the cells' cadmium resistance. Comparison among different yeast species shows that the critical nucleotides found in EC strains are conserved and functionally important for cadmium resistance in other species, suggesting that they represent an ancestral type. However, these nucleotides had diverged in most Saccharomyces cerevisiae populations, which gave cells growth advantages under conditions where cadmium is low or absent. Our results provide a rare example of a selective sweep in yeast populations driven by a tradeoff in metal resistance

The Histone H3K79 Methyltransferase Dot1L Is Essential for Mammalian Development and Heterochromatin Structure

Dot1 is an evolutionarily conserved histone methyltransferase specific for lysine 79 of histone H3 (H3K79). In Saccharomyces cerevisiae, Dot1-mediated H3K79 methylation is associated with telomere silencing, meiotic checkpoint control, and DNA damage response. The biological function of H3K79 methylation in mammals, however, remains poorly understood. Using gene targeting, we generated mice deficient for Dot1L, the murine Dot1 homologue. Dot1L-deficient embryos show multiple developmental abnormalities, including growth impairment, angiogenesis defects in the yolk sac, and cardiac dilation, and die between 9.5 and 10.5 days post coitum. To gain insights into the cellular function of Dot1L, we derived embryonic stem (ES) cells from Dot1L mutant blastocysts. Dot1L-deficient ES cells show global loss of H3K79 methylation as well as reduced levels of heterochromatic marks (H3K9 di-methylation and H4K20 tri-methylation) at centromeres and telomeres. These changes are accompanied by aneuploidy, telomere elongation, and proliferation defects. Taken together, these results indicate that Dot1L and H3K79 methylation play important roles in heterochromatin formation and in embryonic development

Corpus Callosum Morphology in Capuchin Monkeys Is Influenced by Sex and Handedness

Sex differences have been reported in both overall corpus callosum area and its regional subdivisions in humans. Some have suggested this reflects a unique adaptation in humans, as similar sex differences in corpus callosum morphology have not been reported in any other species of primate examined to date. Furthermore, an association between various measurements of corpus callosum morphology and handedness has been found in humans and chimpanzees. In the current study, we report measurements of corpus callosum cross-sectional area from midsagittal MR images collected in vivo from 14 adult capuchin monkeys, 9 of which were also characterized for hand preference on a coordinated bimanual task. Adult females were found to have a significantly larger corpus callosum: brain volume ratio, rostral body, posterior midbody, isthmus, and splenium than adult males. Left-handed individuals had a larger relative overall corpus callosum area than did right-handed individuals. Additionally, a significant sex and handedness interaction was found for anterior midbody, with right-handed males having a significantly smaller area than right-handed females. These results suggest that sex and handedness influences on corpus callosum morphology are not restricted to Homo sapiens

Acoustic-Friction Networks and the Evolution of Precursory Rupture Fronts in Laboratory Earthquakes

We show that the mesoscopic and transport characteristics of networks follow the same trends for the same type of the shear ruptures in terms of rupture speed while also comparing the results of three different friction experiments.The classified fronts obtained from a saw cut Westerly granite fault regarding friction network parameters show a clear separation into two groups indicating two different rupture fronts. With respect to the scaling of local ruptures durations with the networks parameters we show that the gap is related to the possibility of a separation between slow and regular fronts

Diferenças de nichos entre duas espécies simpátricas de lagartos (Cnemidophorus abaetensis e C. ocellifer) em habitat de restinga no nordeste do Brasil

Differences among sympatric lizard species usually result from differences in the use of three resources: space, time and food or some combination of these three. However, differences in resource utilization among sympatric species may simply reflect their specific ecological needs rather than competitive pressures. In this study, we analyzed the temporal, spatial and food niche of two congeneric teiids (Cnemidophorus abaetensis and C. ocellifer) living sympatrically in the "restinga" habitat of Abaeté in the Salvador Municipality, Bahia State, Brazil to assess the degree of niche differentiation among them. The whiptail species overlapped considerably in an hourly activity (Ojk = 0.93), in microhabitat use (Ojk = 0.97) and in the prey items consumed (Ojk = 0.89). Differences in amount of vegetation in the microhabitats used by both lizard species may have contributed to differences in the activity period and in the distribution of the main prey eaten by these lizards which may, in turn, facilitate their coexistence in Abaeté. Although sympatric C. ocellifer and C. abaetensis in Abaeté differed only slightly in their use of microhabitats, period of activity and diet, the most important niche dimension segregating the two species seemed to be the food niche._____________________________________________________________________________________ RESUMO: As diferenças entre espécies simpátricas geralmente podem ser atribuídas às variações na utilização de três dimensões primárias de recurso: o período de atividade, o microhabitat e o alimento ou a alguma combinação das três. No entanto, tais diferenças na utilização de recursos entre espécies simpátricas têm sido sugeridas mais como um reflexo de suas necessidades ecológicas específicas do que resultado de pressão competitiva. Neste estudo, avaliou-se o nicho temporal, o espacial e o alimentar de dois teídeos cogenéricos (Cnemidophorus abaetensis e C. ocellifer) vivendo em simpatria na restinga de Abaeté em Salvador, Bahia. As duas espécies de lagartos sobrepõem-se consideravelmente no período de atividade (Ojk = 0,93), no uso dos microhabitats (Ojk = 0,97) e nos tipos de presas consumidas (Ojk = 0,89). As diferenças na quantidade de vegetação nos microhabitats utilizadas pelas duas espécies podem ter contribuído para as diferenças no período de atividade e na distribuição dos principais tipos de presas consumidas por estas duas espécies de lagartos, o que pode ter favorecido a coexistência entre elas na restinga do Abaeté. No entanto, as diferenças na dieta são as mais significativas para a segregação