Characterization of a second open reading frame in genome segment 10 of bluetongue virus

Viruses have often evolved overlapping reading frames in order to maximise their coding capacity. Until recently, the segmented double-stranded (ds) RNA genome of viruses of the Orbivirus genus was thought to be monocistronic but the identification of the bluetongue virus (BTV) NS4 protein changed this assumption. A small open reading frame (ORF) in segment 10, overlapping the NS3 ORF in the +1 position that is maintained in more than 300 strains of the 26 different BTV serotypes and in more of 200 strains of the phylogenetically related African horse sickness (AHSV). In BTV, this ORF (named S10-ORF2 in this study) encodes a putative protein of 50-59 amino acid residues in length and appears to be under a strong positive selection. HA- or GFP-tagged versions of S10-ORF2 expressed from transfected plasmids localised within the nucleoli of transfected cells unless a putative nucleolar localisation signal was mutated S10-ORF2 inhibited gene expression, but not RNA translation, in transient transfection reporter assays. In both mammalian and insect cells, BTV S10-ORF2 deletion mutants (BTV8ΔS10-ORF2) displayed similar replication kinetics to wild type virus. In vivo, S10-ORF2 deletion mutants were pathogenic in mouse models of disease. Although further evidence is required for S10-ORF2 expression during infection, the data presented provide an initial characterisation of this open reading frame

Co-liquefaction of wastes and coal mixtures to produce added value liquid compounds

ABSTRACT: Nowadays there is an increasing need to find alternative fuels to reduce the dependency on imported ones and to decrease the negative environmental impact of wastes accumulation. Plastics are an important components of urban biowaste, thus their conversion into liquid fuels, in mixtures with other solid fuels still remains an important research goal. After the large experience obtained from coal gasification, it was found that co-liquefaction of coal and wastes may be a good solution to produce liquid fuels and raw materials for several industries. Co-liquefaction of coal blended with biomass gave unfavourable results, but co-liquefaction of coal mixed with PE (polyethylene) wastes led to encouraging results. The results obtained showed that the rise of PE content in coal blends led to an increase in liquid yield. As the main objective was the formation of liquid products, the mixture of coal with 50 wt% of PE was selected, as substantial total liquid yields were obtained, while using significant coal content. This blend was used to study the effect of initial hydrogen pressure, reaction temperature and time on products yields, using Response Surface Methodology (RSM) approach. Liquid yields were most affected by reaction temperature and pressure. The rise of temperature decreased liquid yields, while pressure had a positive effect, but the interaction between these two parameters showed a negative influence. Theoretical equations were used to calculate total and direct liquids yield (%daf). Total liquids are the sum of the liquids directly recovered from the autoclave (direct liquids) and the liquids extracted from the solid product. Both the theoretical model and the experimental results showed that the highest total liquids yields were obtained at 380 ºC, 1.4 MPa and 90 minutes.info:eu-repo/semantics/publishedVersio

The timing and magnitude of the type I interferon response are correlated with disease tolerance in arbovirus infection

This study was funded by an Investigator Award from the Wellcome Trust (206369/Z/17/Z). Additional funding was provided by the MRC (MC_UU_12014/10; MC_UU_12014/12).Infected hosts possess two alternative strategies to protect themselves against the negative impact of virus infections: resistance, used to abrogate virus replication, and disease tolerance, used to avoid tissue damage without controlling viral burden. The principles governing pathogen resistance are well understood, while less is known about those involved in disease tolerance. Here, we studied bluetongue virus (BTV), the cause of bluetongue disease of ruminants, as a model system to investigate the mechanisms of virus-host interactions correlating with disease tolerance. BTV induces clinical disease mainly in sheep, while cattle are considered reservoirs of infection, rarely exhibiting clinical symptoms despite sustained viremia. Using primary cells from multiple donors, we show that BTV consistently reaches higher titers in ovine cells than cells from cattle. The variable replication kinetics of BTV in sheep and cow cells were mostly abolished by abrogating the cell type I interferon (IFN) response. We identified restriction factors blocking BTV replication, but both the sheep and cow orthologues of these antiviral genes possess anti-BTV properties. Importantly, we demonstrate that BTV induces a faster host cell protein synthesis shutoff in primary sheep cells than cow cells, which results in an earlier downregulation of antiviral proteins. Moreover, by using RNA sequencing (RNA-seq), we also show a more pronounced expression of interferon-stimulated genes (ISGs) in BTV-infected cow cells than sheep cells. Our data provide a new perspective on how the type I IFN response in reservoir species can have overall positive effects on both virus and host evolution.Publisher PDFPeer reviewe

BII-Implementation: The causes and consequences of plant biodiversity across scales in a rapidly changing world

The proposed Biology Integration Institute will bring together two major research institutions in the Upper Midwest—the University of Minnesota (UMN) and University of Wisconsin-Madison (UW)—to investigate the causes and consequences of plant biodiversity across scales in a rapidly changing world—from genes and molecules within cells and tissues to communities, ecosystems, landscapes and the biosphere. The Institute focuses on plant biodiversity, defined broadly to encompass the heterogeneity within life that occurs from the smallest to the largest biological scales. A premise of the Institute is that life is envisioned as occurring at different scales nested within several contrasting conceptions of biological hierarchies, defined by the separate but related fields of physiology, evolutionary biology and ecology. The Institute will emphasize the use of ‘spectral biology’—detection of biological properties based on the interaction of light energy with matter—and process-oriented predictive models to investigate the processes by which biological components at one scale give rise to emergent properties at higher scales. Through an iterative process that harnesses cutting edge technologies to observe a suite of carefully designed empirical systems—including the National Ecological Observatory Network (NEON) and some of the world’s longest running and state-of-the-art global change experiments—the Institute will advance biological understanding and theory of the causes and consequences of changes in biodiversity and at the interface of plant physiology, ecology and evolution. INTELLECTUAL MERIT The Institute brings together a diverse, gender-balanced and highly productive team with significant leadership experience that spans biological disciplines and career stages and is poised to integrate biology in new ways. Together, the team will harness the potential of spectral biology, experiments, observations and synthetic modeling in a manner never before possible to transform understanding of how variation within and among biological scales drives plant and ecosystem responses to global change over diurnal, seasonal and millennial time scales. In doing so, it will use and advance state-of-the-art theory. The institute team posits that the designed projects will unearth transformative understanding and biological rules at each of the various scales that will enable an unprecedented capacity to discern the linkages between physiological, ecological and evolutionary processes in relation to the multi-dimensional nature of biodiversity in this time of massive planetary change. A strength of the proposed Institute is that it leverages prior federal investments in research and formalizes partnerships with foreign institutions heavily invested in related biodiversity research. Most of the planned projects leverage existing research initiatives, infrastructure, working groups, experiments, training programs, and public outreach infrastructure, all of which are already highly synergistic and collaborative, and will bring together members of the overall research and training team. BROADER IMPACTS A central goal of the proposed Institute is to train the next generation of diverse integrative biologists. Post-doctoral, graduate student and undergraduate trainees, recruited from non-traditional and underrepresented groups, including through formal engagement with Native American communities, will receive a range of mentoring and training opportunities. Annual summer training workshops will be offered at UMN and UW as well as training experiences with the Global Change and Biodiversity Research Priority Program (URPP-GCB) at the University of Zurich (UZH) and through the Canadian Airborne Biodiversity Observatory (CABO). The Institute will engage diverse K-12 audiences, the general public and Native American communities through Market Science modules, Minute Earth videos, a museum exhibit and public engagement and educational activities through the Bell Museum of Natural History, the Cedar Creek Ecosystem Science Reserve (CCESR) and the Wisconsin Tribal Conservation Association

Reducing the energy demand of corn based fuel ethanol through salt extractive distillation enabled by electrodialysis

The thermal energy demand for producing fuel ethanol from the fermentation broth of a contemporary corn-to-fuel ethanol plant in the U.S. is largely satisfied by combustion of fossil fuels, which impacts the possible economical and environmental advantages of bio-ethanol over fossil fuels. To reduce the thermal energy demand for producing fuel ethanol, a process integrating salt extractive distillation – enabled by a new scheme of electrodialysis and spray drying for salt recovery – in the water-ethanol separation train of a contemporary corn-to-fuel ethanol plant is investigated. Process simulation using Aspen Plus® 2006.5, with the ENRTL-RK property method to model the vapor liquid equilibrium of the water-ethanol-salt system, was carried out. The integrated salt extractive distillation process may provide a thermal energy savings of about 30%, when compared with the contemporary process for separating fuel ethanol from the beer column distillate

Avaliação da Vergonha em Adolescentes: ‘The Other as Shamer Scale’

Shame, as a self-conscious, multidimensional and socially focused emotion, plays a central role in the mental health of individuals. In adolescents, shame is also a frequent experience and its assessment is important for research and clinical practice. This study aims to validate a brief measure of external shame (Other as Shamer Scale – brief version for adolescents: (OASB-A). The participants were 834 adolescents with a mean age of 15 years. The final model of the OASB-A (8 items), obtained through CFA, presents a good fit to the data. The OASB-A shows a good internal consistency and an adequate temporal reliability. The OASB-A also reveals significant correlations with traumatic shame experiences (IES-R) and psychopathological symptoms (DASS-21). The OASB-A is an economic and reliable measure to assess external shame in adolescents

Targeting the substrate preference of a type I nitroreductase to develop antitrypanosomal quinone-based prodrugs.

Nitroheterocyclic prodrugs are used to treat infections caused by Trypanosoma cruzi and Trypanosoma brucei. A key component in selectivity involves a specific activation step mediated by a protein homologous with type I nitroreductases, enzymes found predominantly in prokaryotes. Using data from determinations based on flavin cofactor, oxygen-insensitive activity, substrate range, and inhibition profiles, we demonstrate that NTRs from T. cruzi and T. brucei display many characteristics of their bacterial counterparts. Intriguingly, both enzymes preferentially use NADH and quinones as the electron donor and acceptor, respectively, suggesting that they may function as NADH:ubiquinone oxidoreductases in the parasite mitochondrion. We exploited this preference to determine the trypanocidal activity of a library of aziridinyl benzoquinones against bloodstream-form T. brucei. Biochemical screens using recombinant NTR demonstrated that several quinones were effective substrates for the parasite enzyme, having K(cat)/K(m) values 2 orders of magnitude greater than those of nifurtimox and benznidazole. In tests against T. brucei, antiparasitic activity mirrored the biochemical data, with the most potent compounds generally being preferred enzyme substrates. Trypanocidal activity was shown to be NTR dependent, as parasites with elevated levels of this enzyme were hypersensitive to the aziridinyl agent. By unraveling the biochemical characteristics exhibited by the trypanosomal NTRs, we have shown that quinone-based compounds represent a class of trypanocidal compound

Specialist nursing and community support for the carers of people with dementia living at home: an evidence synthesis.

Specialist nurses are one way of providing support for family carers of people with dementia, but relatively little is known about what these roles achieve, or if they are more effective than roles that do not require a clinical qualification. The aim of this review was to synthesise the literature on the scope and effectiveness of specialist nurses, known as Admiral Nurses, and set this evidence in the context of other community-based initiatives to support family carers of people with dementia. We undertook a systematic review of the literature relating to the scope and effectiveness of Admiral Nurses and a review of reviews of interventions to support the family carers of people with dementia. To identify studies, we searched electronic databases, undertook lateral searches and contacted experts. Searches were undertaken in November 2012. Results are reported narratively with key themes relating to Admiral Nurses identified using thematic synthesis. We included 33 items relating to Admiral Nurses (10 classified as research) and 11 reviews evaluating community-based support for carers of people with dementia. There has been little work to evaluate specific interventions provided by Admiral Nurses, but three overarching thematic categories were identified: (i) relational support, (ii) co-ordinating and personalising support and (iii) challenges and threats to the provision of services by Admiral Nurses. There was an absence of clearly articulated goals and service delivery was subject to needs of the host organisation and the local area. The reviews of community-based support for carers of people with dementia included 155 studies but, in general, evidence that interventions reduced caregiver depression or burden was weak, although psychosocial and educational interventions may reduce depression in carers. Community support for carers of people with dementia, such as that provided by Admiral Nurses, is valued by family carers, but the impact of such initiatives is not clearly established

The pancreas anatomy conditions the origin and properties of resident macrophages

We examine the features, origin, turnover, and gene expression of pancreatic macrophages under steady state. The data distinguish macrophages within distinct intrapancreatic microenvironments and suggest how macrophage phenotype is imprinted by the local milieu. Macrophages in islets of Langerhans and in the interacinar stroma are distinct in origin and phenotypic properties. In islets, macrophages are the only myeloid cells: they derive from definitive hematopoiesis, exchange to a minimum with blood cells, have a low level of self-replication, and depend on CSF-1. They express Il1b and Tnfa transcripts, indicating classical activation, M1, under steady state. The interacinar stroma contains two macrophage subsets. One is derived from primitive hematopoiesis, with no interchange by blood cells and alternative, M2, activation profile, whereas the second is derived from definitive hematopoiesis and exchanges with circulating myeloid cells but also shows an alternative activation profile. Complete replacement of islet and stromal macrophages by donor stem cells occurred after lethal irradiation with identical profiles as observed under steady state. The extraordinary plasticity of macrophages within the pancreatic organ and the distinct features imprinted by their anatomical localization sets the base for examining these cells in pathological conditions