Atoh8, a bHLH Transcription Factor, Is Required for the Development of Retina and Skeletal Muscle in Zebrafish

Math6/atoh8, a bHLH transcription factor, is thought to be indispensable for early embryonic development and likely has important roles in vertebrate tissue-specific differentiation. However, the function of Atoh8 during early development is not clear because homozygous knockout causes embryonic lethality in mice. We have examined the effects of the atoh8 gene on the differentiation of retina and skeletal muscle during early development in zebrafish.We isolated a Math6 homologue in zebrafish, designated as zebrafish atoh8. Whole -mount in situ hybridization analysis showed that zebrafish atoh8 is dynamically expressed mainly in developing retina and skeletal muscle. Atoh8-MO knock-down resulted in reduced eye size with disorganization of retinal lamination. The reduction of atoh8 function also affected the arrangement of paraxial cells and differentiated muscle fibers during somite morphogenesis.Our results show that Atoh8 is an important regulator for the development of both the retina and skeletal muscles necessary for neural retinal cell and myogenic differentiation during zebrafish embryogenesis

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

Glycerol Monolaurate and Dodecylglycerol Effects on Staphylococcus aureus and Toxic Shock Syndrome Toxin-1 In Vitro and In Vivo

BACKGROUND:Glycerol monolaurate (GML), a 12 carbon fatty acid monoester, inhibits Staphylococcus aureus growth and exotoxin production, but is degraded by S. aureus lipase. Therefore, dodecylglycerol (DDG), a 12 carbon fatty acid monoether, was compared in vitro and in vivo to GML for its effects on S. aureus growth, exotoxin production, and stability. METHODOLOGY/PRINCIPAL FINDINGS:Antimicrobial effects of GML and DDG (0 to 500 microg/ml) on 54 clinical isolates of S. aureus, including pulsed-field gel electrophoresis (PFGE) types USA200, USA300, and USA400, were determined in vitro. A rabbit Wiffle ball infection model assessed GML and DDG (1 mg/ml instilled into the Wiffle ball every other day) effects on S. aureus (MN8) growth (inoculum 3x10(8) CFU/ml), toxic shock syndrome toxin-1 (TSST-1) production, tumor necrosis factor-alpha (TNF-alpha) concentrations and mortality over 7 days. DDG (50 and 100 microg/ml) inhibited S. aureus growth in vitro more effectively than GML (p<0.01) and was stable to lipase degradation. Unlike GML, DDG inhibition of TSST-1 was dependent on S. aureus growth. GML-treated (4 of 5; 80%) and DDG-treated rabbits (2 of 5; 40%) survived after 7 days. Control rabbits (5 of 5; 100%) succumbed by day 4. GML suppressed TNF-alpha at the infection site on day 7; however, DDG did not (<10 ng/ml versus 80 ng/ml, respectively). CONCLUSIONS/SIGNIFICANCE:These data suggest that DDG was stable to S. aureus lipase and inhibited S. aureus growth at lower concentrations than GML in vitro. However, in vivo GML was more effective than DDG by reducing mortality, and suppressing TNF-alpha, S. aureus growth and exotoxin production, which may reduce toxic shock syndrome. GML is proposed as a more effective anti-staphylococcal topical anti-infective candidate than DDG, despite its potential degradation by S. aureus lipase

Spatio-Temporal Tracking and Phylodynamics of an Urban Dengue 3 Outbreak in São Paulo, Brazil

The dengue virus has a single-stranded positive-sense RNA genome of ∼10.700 nucleotides with a single open reading frame that encodes three structural (C, prM, and E) and seven nonstructural (NS1, NS2A, NS2B, NS3, NS4A, NS4B, and NS5) proteins. It possesses four antigenically distinct serotypes (DENV 1–4). Many phylogenetic studies address particularities of the different serotypes using convenience samples that are not conducive to a spatio-temporal analysis in a single urban setting. We describe the pattern of spread of distinct lineages of DENV-3 circulating in São José do Rio Preto, Brazil, during 2006. Blood samples from patients presenting dengue-like symptoms were collected for DENV testing. We performed M-N-PCR using primers based on NS5 for virus detection and identification. The fragments were purified from PCR mixtures and sequenced. The positive dengue cases were geo-coded. To type the sequenced samples, 52 reference sequences were aligned. The dataset generated was used for iterative phylogenetic reconstruction with the maximum likelihood criterion. The best demographic model, the rate of growth, rate of evolutionary change, and Time to Most Recent Common Ancestor (TMRCA) were estimated. The basic reproductive rate during the epidemics was estimated. We obtained sequences from 82 patients among 174 blood samples. We were able to geo-code 46 sequences. The alignment generated a 399-nucleotide-long dataset with 134 taxa. The phylogenetic analysis indicated that all samples were of DENV-3 and related to strains circulating on the isle of Martinique in 2000–2001. Sixty DENV-3 from São José do Rio Preto formed a monophyletic group (lineage 1), closely related to the remaining 22 isolates (lineage 2). We assumed that these lineages appeared before 2006 in different occasions. By transforming the inferred exponential growth rates into the basic reproductive rate, we obtained values for lineage 1 of R0 = 1.53 and values for lineage 2 of R0 = 1.13. Under the exponential model, TMRCA of lineage 1 dated 1 year and lineage 2 dated 3.4 years before the last sampling. The possibility of inferring the spatio-temporal dynamics from genetic data has been generally little explored, and it may shed light on DENV circulation. The use of both geographic and temporally structured phylogenetic data provided a detailed view on the spread of at least two dengue viral strains in a populated urban area

"Nested" cryptic diversity in a widespread marine ecosystem engineer: a challenge for detecting biological invasions

<p>Abstract</p> <p>Background</p> <p>Ecosystem engineers facilitate habitat formation and enhance biodiversity, but when they become invasive, they present a critical threat to native communities because they can drastically alter the receiving habitat. Management of such species thus needs to be a priority, but the poorly resolved taxonomy of many ecosystem engineers represents a major obstacle to correctly identifying them as being either native or introduced. We address this dilemma by studying the sea squirt <it>Pyura stolonifera</it>, an important ecosystem engineer that dominates coastal communities particularly in the southern hemisphere. Using DNA sequence data from four independently evolving loci, we aimed to determine levels of cryptic diversity, the invasive or native status of each regional population, and the most appropriate sampling design for identifying the geographic ranges of each evolutionary unit.</p> <p>Results</p> <p>Extensive sampling in Africa, Australasia and South America revealed the existence of "nested" levels of cryptic diversity, in which at least five distinct species can be further subdivided into smaller-scale genetic lineages. The ranges of several evolutionary units are limited by well-documented biogeographic disjunctions. Evidence for both cryptic native diversity and the existence of invasive populations allows us to considerably refine our view of the native versus introduced status of the evolutionary units within <it>Pyura stolonifera </it>in the different coastal communities they dominate.</p> <p>Conclusions</p> <p>This study illustrates the degree of taxonomic complexity that can exist within widespread species for which there is little taxonomic expertise, and it highlights the challenges involved in distinguishing between indigenous and introduced populations. The fact that multiple genetic lineages can be native to a single geographic region indicates that it is imperative to obtain samples from as many different habitat types and biotic zones as possible when attempting to identify the source region of a putative invader. "Nested" cryptic diversity, and the difficulties in correctly identifying invasive species that arise from it, represent a major challenge for managing biodiversity.</p

Revealing the microscale spatial signature of dengue transmission and immunity in an urban population

It is well-known that the distribution of immunity in a population dictates the future incidence of infectious disease, but this process is generally understood at individual or macroscales. For example, herd immunity to multiple pathogens has been observed at national and city levels. However, the effects of population immunity have not previously been shown at scales smaller than the city (e.g., neighborhoods). In particular, no study has shownlong-termeffects of population immunity at scales consistent with the spatial scale of person-to-person transmission. Here, we use the location of dengue patients' homes in Bangkok with the serotype of the infecting pathogen to investigate the spatiotemporal distribution of disease risk at small spatial scales over a 5-y period. We find evidence for localized transmission at distances of under 1 km. We also observe patterns of spatiotemporal dependence consistent with the expected impacts of homotypic immunity, heterotypic immunity, and immune enhancement of disease at these distances. Our observations indicate that immunological memory of dengue serotypes occurs at the neighborhood level in this large urban setting. These methods have broad applications to studying the spatiotemporal structure of disease risk where pathogen serotype or genetic information is known

Atomic layer deposited alpha-Ga2O3 solar-blind photodetectors

Low temperature atomic layer deposition was used to deposit α-Ga2O3 films, which were subsequently annealed at various temperatures and atmospheres. The α-Ga2O3 phase is stable up to 400 °C, which is also the temperature that yields the most intense and sharpest reflection by x-ray diffraction. Upon annealing at 450 °C and above, the material gradually turns into the more thermodynamically stable ε or β phase. The suitability of the materials for solar-blind photodetector applications has been demonstrated with the best responsivity achieved being 1.2 A W−1 under 240 nm illumination and 10 V bias, for the sample annealed at 400 °C in argon. It is worth noting however that the device performance strongly depends on the annealing conditions, with the device annealed in forming gas behaving poorly. Given that the tested devices have similar microstructure, the discrepancies in device performance are attributed to hydrogen impurities