Viral MicroRNA Effects on Pathogenesis of Polyomavirus SV40 Infections in Syrian Golden Hamsters

Shaojie Zhang, Vojtech Sroller, Preeti Zanwar, Steven J. Halvorson, Nadim J. Ajami, Corey W. Hecksel, Jody L. Swain, Connie Wong, Janet S. Butel, Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas, United States of AmericaChun Jung Chen, Christopher S. Sullivan, Department of Molecular Biosciences, The University of Texas at Austin, Austin, Texas, United States of AmericaJody L. Swain, Center for Comparative Medicine, Baylor College of Medicine, Houston, Texas, United States of AmericaEffects of polyomavirus SV40 microRNA on pathogenesis of viral infections in vivo are not known. Syrian golden hamsters are the small animal model for studies of SV40. We report here effects of SV40 microRNA and influence of the structure of the regulatory region on dynamics of SV40 DNA levels in vivo. Outbred young adult hamsters were inoculated by the intracardiac route with 1×107 plaque-forming units of four different variants of SV40. Infected animals were sacrificed from 3 to 270 days postinfection and viral DNA loads in different tissues determined by quantitative real-time polymerase chain reaction assays. All SV40 strains displayed frequent establishment of persistent infections and slow viral clearance. SV40 had a broad tissue tropism, with infected tissues including liver, kidney, spleen, lung, and brain. Liver and kidney contained higher viral DNA loads than other tissues; kidneys were the preferred site for long-term persistent infection although detectable virus was also retained in livers. Expression of SV40 microRNA was demonstrated in wild-type SV40-infected tissues. MicroRNA-negative mutant viruses consistently produced higher viral DNA loads than wild-type SV40 in both liver and kidney. Viruses with complex regulatory regions displayed modestly higher viral DNA loads in the kidney than those with simple regulatory regions. Early viral transcripts were detected at higher levels than late transcripts in liver and kidney. Infectious virus was detected infrequently. There was limited evidence of increased clearance of microRNA-deficient viruses. Wild-type and microRNA-negative mutants of SV40 showed similar rates of transformation of mouse cells in vitro and tumor induction in weanling hamsters in vivo. This report identified broad tissue tropism for SV40 in vivo in hamsters and provides the first evidence of expression and function of SV40 microRNA in vivo. Viral microRNA dampened viral DNA levels in tissues infected by SV40 strains with simple or complex regulatory regions.This work was supported in part by research grants R01 CA134524 (JSB) and R01 AI077746 (CSS) from the National Institutes of Health. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Molecular BiosciencesEmail: [email protected]

Microguards and micromessengers of the genome

The regulation of gene expression is of fundamental importance to maintain organismal function and integrity and requires a multifaceted and highly ordered sequence of events. The cyclic nature of gene expression is known as ‘transcription dynamics’. Disruption or perturbation of these dynamics can result in significant fitness costs arising from genome instability, accelerated ageing and disease. We review recent research that supports the idea that an important new role for small RNAs, particularly microRNAs (miRNAs), is in protecting the genome against short-term transcriptional fluctuations, in a process we term ‘microguarding’. An additional emerging role for miRNAs is as ‘micromessengers’—through alteration of gene expression in target cells to which they are trafficked within microvesicles. We describe the scant but emerging evidence that miRNAs can be moved between different cells, individuals and even species, to exert biologically significant responses. With these two new roles, miRNAs have the potential to protect against deleterious gene expression variation from perturbation and to themselves perturb the expression of genes in target cells. These interactions between cells will frequently be subject to conflicts of interest when they occur between unrelated cells that lack a coincidence of fitness interests. Hence, there is the potential for miRNAs to represent both a means to resolve conflicts of interest, as well as instigate them. We conclude by exploring this conflict hypothesis, by describing some of the initial evidence consistent with it and proposing new ideas for future research into this exciting topic

Arthropod distribution in a tropical rainforest: tackling a four dimensional puzzle

Quantifying the spatio-temporal distribution of arthropods in tropical rainforests represents a first step towards scrutinizing the global distribution of biodiversity on Earth. To date moststudies have focused on narrow taxonomic groups or lack a design that allows partitioning of the components of diversity. Here, we consider an exceptionally large dataset (113,952 individuals representing 5,858 species), obtained from the San Lorenzo forest in Panama, where the phylogenetic breadth of arthropod taxa was surveyed using 14 protocols targeting the soil, litter, understory, lower and upper canopy habitats, replicated across seasons in 2003 and 2004. This dataset is used to explore the relative influence of horizontal, vertical and seasonal drivers of arthropod distribution in this forest. We considered arthropod abundance, observed and estimated species richness, additive decomposition of species richness, multiplicative partitioning of species diversity, variation in species composition, species turnover and guild structure as components of diversity. At the scale of our study (2km of distance, 40m in height and 400 days), the effects related to the vertical and seasonal dimensions were most important. Most adult arthropods were collected from the soil/ litter or the upper canopy and species richness was highest in the canopy. We compared the distribution of arthropods and trees within our study system. Effects related to the seasonal dimension were stronger for arthropods than for trees. We conclude that: (1) models of beta diversity developed for tropical trees are unlikely to be applicable to tropical arthropods; (2) it is imperative that estimates of global biodiversity derived from mass collecting of arthropods in tropical rainforests embrace the strong vertical and seasonal partitioning observed here; and (3) given the high species turnover observed between seasons, global climate change may have severe consequences for rainforest arthropods

Elevational species richness gradients in a hyperdiverse insect taxon: a global meta-study on geometrid moths

AIMS: We aim to document elevational richness patterns of geometrid moths in a globally replicated, multi-gradient setting, and to test general hypotheses on environmental and spatial effects (i.e. productivity, temperature, precipitation, area, mid-domain effect and human habitat disturbance) on these richness patterns. LOCATION: Twenty-six elevational gradients world-wide (latitudes 28° S to 51° N). METHODS: We compiled field datasets on elevational gradients for geometrid moths, a lepidopteran family, and documented richness patterns across each gradient while accounting for local undersampling of richness. Environmental and spatial predictor variables as well as habitat disturbance were used to test various hypotheses. Our analyses comprised two pathways: univariate correlations within gradients, and multivariate modelling on pooled data after correcting for overall variation in richness among different gradients. RESULTS: The majority of gradients showed midpeak patterns of richness, irrespective of climate and geographical location. The exclusion of human-affected sampling plots did not change these patterns. Support for univariate main drivers of richness was generally low, although there was idiosyncratic support for particular predictors on single gradients. Multivariate models, in agreement with univariate results, provided the strongest support for an effect of area-integrated productivity, or alternatively for an elevational area effect. Temperature and the mid-domain effect received support as weaker, modulating covariates, while precipitation-related variables had no explanatory potential. MAIN CONCLUSIONS: Despite the predicted decreasing diversity–temperature relationship in ectotherms, geometrid moths are similar to ants and salamanders as well as small mammals and ferns in having predominantly their highest diversity at mid-elevations. As in those comparative analyses, single or clear sets of drivers are elusive, but both productivity and area appear to be influential. More comparative elevational studies for various insect taxa are necessary for a more comprehensive understanding of elevational diversity and productivity

Abundance of the Quorum-Sensing Factor Ax21 in Four Strains of Stenotrophomonas maltophilia Correlates with Mortality Rate in a New Zebrafish Model of Infection

Stenotrophomonas maltophilia is a Gram-negative pathogen with emerging nosocomial incidence. Little is known about its pathogenesis and the genomic diversity exhibited by clinical isolates complicates the study of pathogenicity and virulence factors. Here, we present a strategy to identify such factors in new clinical isolates of S. maltophilia, incorporating an adult-zebrafish model of S. maltophilia infection to evaluate relative virulence coupled to 2D difference gel electrophoresis to explore underlying differences in protein expression. In this study we report upon three recent clinical isolates and use the collection strain ATCC13637 as a reference. The adult-zebrafish model shows discrimination capacity, i.e. from very low to very high mortality rates, with clinical symptoms very similar to those observed in natural S. maltophilia infections in fish. Strain virulence correlates with resistance to human serum, in agreement with previous studies in mouse and rat and therefore supporting zebrafish as a replacement model. Despite its clinical origin, the collection strain ATCC13637 showed obvious signs of attenuation in zebrafish, with null mortality. Multilocus-sequence-typing analysis revealed that the most virulent strains, UV74 and M30, exhibit the strongest genetic similitude. Differential proteomic analysis led to the identification of 38 proteins with significantly different abundance in the three clinical strains relative to the reference strain. Orthologs of several of these proteins have been already reported to have a role in pathogenesis, virulence or resistance mechanisms thus supporting our strategy. Proof of concept is further provided by protein Ax21, whose abundance is shown here to be directly proportional to mortality in the zebrafish infection model. Indeed, recent studies have demonstrated that this protein is a quorum-sensing-related virulence factor

Controlo químico de infestantes

Uma planta é considerada infestante quando nasce espontaneamente num local e momento indesejados, podendo interferir negativamente com a cultura instalada. As infestantes competem com as culturas para o espaço, a luz, água e nutrientes, podendo atrasar e prejudicar as operações de colheita, depreciar o produto final e assegurarem a reinfestação nas culturas seguintes. Dado o modo de propagação diferenciado das diversas espécies de infestantes, com as anuais a propagarem-se por semente e as perenes ou vivazes a assegurarem a sua propagação através de órgãos vegetativos (rizomas, bolbos, tubérculos, etc.), assim, também o seu controlo quer químico, quer mecânico terá que ser diferenciado, ou seja, para controlar infestantes anuais será suficiente destruir a sua parte aérea, enquanto para controlar infestantes perenes teremos que destruir os seus órgãos reprodutivos. O controlo de infestantes poderá ser químico, através da utilização de herbicidas, ou mecânico pela utilização de alfaias agrícolas, tais como a charrua de aivecas, a charrua de discos, a grade de discos, o escarificador e a fresa. Quando a técnica utilizada na instalação das culturas é a sementeira directa, o controlo das infestantes terá que ser obrigatoriamente químico, enquanto se o recurso à mobilização do solo for a técnica mais utilizada (sistema de mobilização tradicional ou sistema de mobilização reduzida), o controlo das infestantes tanto poderá ser químico como mecânico. Neste trabalho iremos abordar apenas, o controlo químico de infestantes

Ability-Based Methods for Personalized Keyboard Generation

This study introduces an ability-based method for personalized keyboard generation, wherein an individual's own movement and human-computer interaction data are used to automatically compute a personalized virtual keyboard layout. Our approach integrates a multidirectional point-select task to characterize cursor control over time, distance, and direction. The characterization is automatically employed to develop a computationally efficient keyboard layout that prioritizes each user's movement abilities through capturing directional constraints and preferences. We evaluated our approach in a study involving 16 participants using inertial sensing and facial electromyography as an access method, resulting in significantly increased communication rates using the personalized keyboard (52.0 bits/min) when compared to a generically optimized keyboard (47.9 bits/min). Our results demonstrate the ability to effectively characterize an individual's movement abilities to design a personalized keyboard for improved communication. This work underscores the importance of integrating a user's motor abilities when designing virtual interfaces.Comment: 20 pages, 7 figure

Propriedades de betão drenante em misturas com agregados reciclados

O presente trabalho estuda o desenvolvimento de betão drenante para aplicação em pavimentos rodoviários, através do estudo das suas características físicas e mecânicas, apoiado numa campanha de ensaios laboratoriais, de várias composições. Os materiais de pavimento rígido com betão drenante, após sua construção, sofrem um processo de degradação sob a ação do tráfego e das condições climáticas. Esse processo, que ocorre durante a vida útil do piso, pode ser mais lento se for bem construído e mantido. Assim, é fundamental que a caracterização mecânica do betão seja adequada para a sua aplicação. Assim, os ensaios de trabalhabilidade e densidade devem ser realizados em relação ao betão fresco. No caso do betão endurecido, são os ensaios de resistência à compressão e flexão, os ensaios de permeabilidade e os ensaios de resistência ao desgaste. O betão permeável pode ser uma solução de segurança bem-sucedida para chuvas fortes e inundações cada vez mais frequentes. Este estudo teve como foco a obtenção de um betão permeável otimizado, dentro do escopo das normas internacionais, por meio da análise do betão feitos com as mesmas relações A/C e tempos de vibração e os diferentes percentuais de agregado reciclado. Os resultados mostram a forte influência de ambos os parâmetros sobre a distribuição de porosidade e permeabilidade e a influência negativa de porosidades mais altas sobre a resistência. O betão com relação de 0,35 W/C e tempo de vibração de 40 segundos e 30% de agregado reciclado foi selecionado por seu desempenho mecânico superior.Este trabalho foi financiado pela Adenda nº 20 ao Protocolo de Cooperação Cultural, Científica, Pedagógica e Institucional entre a Universidade do Minho e a Universidade Nacional de Timor Lorosa'e

Arthropod Distribution In A Tropical Rainforest: Tackling A Four Dimensional Puzzle

Quantifying the spatio-temporal distribution of arthropods in tropical rainforests represents a first step towards scrutinizing the global distribution of biodiversity on Earth. To date most studies have focused on narrow taxonomic groups or lack a design that allows partitioning of the components of diversity. Here, we consider an exceptionally large dataset (113,952 individuals representing 5,858 species), obtained from the San Lorenzo forest in Panama, where the phylogenetic breadth of arthropod taxa was surveyed using 14 protocols targeting the soil, litter, understory, lower and upper canopy habitats, replicated across seasons in 2003 and 2004. This dataset is used to explore the relative influence of horizontal, vertical and seasonal drivers of arthropod distribution in this forest. We considered arthropod abundance, observed and estimated species richness, additive decomposition of species richness, multiplicative partitioning of species diversity, variation in species composition, species turnover and guild structure as components of diversity. At the scale of our study (2km of distance, 40m in height and 400 days), the effects related to the vertical and seasonal dimensions were most important. Most adult arthropods were collected from the soil/litter or the upper canopy and species richness was highest in the canopy. We compared the distribution of arthropods and trees within our study system. Effects related to the seasonal dimension were stronger for arthropods than for trees. We conclude that: (1) models of beta diversity developed for tropical trees are unlikely to be applicable to tropical arthropods; (2) it is imperative that estimates of global biodiversity derived from mass collecting of arthropods in tropical rainforests embrace the strong vertical and seasonal partitioning observed here; and (3) given the high species turnover observed between seasons, global climate change may have severe consequences for rainforest arthropods.1012SolVin-Solvay SASTRIUnited Nations Environment ProgrammeSmithsonian Institution (Walcott Fund)European Science FoundationGlobal Canopy ProgrammeCzech Science foundation GACR grant [14-36098G]European Social FundCzech Ministry of Education [CZ.1.07/2.3.00/20.0064]U.S. National Science Fundation [DEB-0841885]Australian Research Council [FT100100040]Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)"Investissement d'Avenir'' grant [ANR-10-LABX-25-01]Norwegian Research CouncilGrant Agency of the Czech Republic [14-36098G