The interferon-stimulated gene IFITM3 restricts West Nile virus infection and pathogenesis

The interferon-induced transmembrane protein (IFITM) family of proteins inhibit infection of several different enveloped viruses in cell culture by virtue of their ability to restrict entry and fusion from late endosomes. As few studies have evaluated the importance of Ifitm3 in vivo in restricting viral pathogenesis, we investigated its significance as an antiviral gene against West Nile virus (WNV), an encephalitic flavivirus, in cells and mice. Ifitm3(−/−) mice were more vulnerable to lethal WNV infection, and this was associated with greater virus accumulation in peripheral organs and central nervous system tissues. As no difference in viral burden in the brain or spinal cord was observed after direct intracranial inoculation, Ifitm3 likely functions as an antiviral protein in nonneuronal cells. Consistent with this, Ifitm3(−/−) fibroblasts but not dendritic cells resulted in higher yields of WNV in multistep growth analyses. Moreover, transcomplementation experiments showed that Ifitm3 inhibited WNV infection independently of Ifitm1, Ifitm2, Ifitm5, and Ifitm6. Beyond a direct effect on viral infection in cells, analysis of the immune response in WNV-infected Ifitm3(−/−) mice showed decreases in the total number of B cells, CD4(+) T cells, and antigen-specific CD8(+) T cells. Finally, bone marrow chimera experiments demonstrated that Ifitm3 functioned in both radioresistant and radiosensitive cells, as higher levels of WNV were observed in the brain only when Ifitm3 was absent from both compartments. Our analyses suggest that Ifitm3 restricts WNV pathogenesis likely through multiple mechanisms, including the direct control of infection in subsets of cells. IMPORTANCE As part of the mammalian host response to viral infections, hundreds of interferon-stimulated genes (ISGs) are induced. The inhibitory activity of individual ISGs varies depending on the specific cell type and viral pathogen. Among ISGs, the genes encoding interferon-induced transmembrane protein (IFITM) have been reported to inhibit multiple families of viruses in cell culture. However, few reports have evaluated the impact of IFITM genes on viral pathogenesis in vivo. In this study, we characterized the antiviral activity of Ifitm3 against West Nile virus (WNV), an encephalitic flavivirus, using mice with a targeted gene deletion of Ifitm3. Based on extensive virological and immunological analyses, we determined that Ifitm3 protects mice from WNV-induced mortality by restricting virus accumulation in peripheral organs and, subsequently, in central nervous system tissues. Our data suggest that Ifitm3 restricts WNV pathogenesis by multiple mechanisms and functions in part by controlling infection in different cell types

QUASI-FERMI-LEVELS IN QUANTUM-WELL PHOTOLUMINESCENCE

The nonequilibrium quasi-Fermi-levels of electrons and holes in quantum wells are calculated during photoluminescence. It is assumed the electrons and holes are created by continuous laser excitation. Various recombination processes are included: electron radiative recombination with holes bound at neutral acceptors, electron radiative recombination with free holes, hole trapping at ionized acceptors, and Auger decay. A numerical example is presented for acceptors in GaAs/Ga(1-x)Al(x)As quantum wells.4473150315

EXCITATION OF THE 3 P-1,3 STATES OF MG BY ELECTRON-IMPACT

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Specifications of Standards in Systems and Synthetic Biology: Status and Developments in 2016

Standards are essential to the advancement of science and technology. In systems and synthetic biology, numerous standards and associated tools have been developed over the last 16 years. This special issue of the Journal of Integrative Bioinformatics aims to support the exchange, distribution and archiving of these standards, as well as to provide centralised and easily citable access to them

Influence de la fertilisation minérale sur la qualité physico-chimique et organoleptique du jus d’ananas transformé de Cayenne lisse au Bénin

L’objectif de l’étude est d’analyser l’influence de la fertilisation N, P et K sur les caractéristiques physico-chimique et organoleptique du jus Cayenne lisse produit au Bénin. Un essai en plan factoriel NPK complet a été installé à Soyo, un village de la commune d’Allada du Département de l’Atlantique en République du Bénin. Les traitements NPK appliqués en unités fertilisantes exprimées en g/plant et randomisés dans quatre blocs ont été les suivants : T1: 6,7-1,6-9,3 ; T2 : 2,7-2,7-2,7 ; T3: 10,7- 0,5-2,7 ;T5: 10,7- 2,7-16 ; T6: 2,7- 2,7-16 ; T7: 2,7- 2,7-16 ; T8: 10,7-2,7-2,7 ; T9:2,7-0,5-2,7 ;T10: 10,7- 0,5-16. Le degré Brix du jus a été déterminé au réfractomètre et le pH au pH-mètre. Une évaluation des caractéristiques sensorielles telles que le goût sucré, le goût acide et l’arôme du jus d’ananas fabriqué a été effectuée par un panel de dégustateurs sélectionnés et entraînés. Une analyse en composantes principales, suivie d’une classification numérique a été réalisée sur les caractéristiques sensorielles et physico-chimiques des fruits. Les traitements T1, T3, T5 et T6 ont permis d’obtenir des jus de qualité organoleptique appréciable.Mots clés : Intensification, Rendement, Jus, Evaluation sensorielle, Fumure, Allada

Clinical and genetic characterisation of dystrophin-deficient muscular dystrophy in a family of Miniature Poodle dogs

Four full-sibling intact male Miniature Poodles were evaluated at 4–19 months of age. One was clinically normal and three were affected. All affected dogs were reluctant to exercise and had generalised muscle atrophy, a stiff gait and a markedly elevated serum creatine kinase activity. Two affected dogs also showed poor development, learning difficulties and episodes of abnormal behaviour. In these two dogs, investigations into forebrain structural and metabolic diseases were unremarkable; electromyography demonstrated fibrillation potentials and complex repetitive discharges in the infraspinatus, supraspinatus and epaxial muscles. Histopathological, immunohistochemical and immunoblotting analyses of muscle biopsies were consistent with dystrophin-deficient muscular dystrophy. DNA samples were obtained from all four full-sibling male Poodles, a healthy female littermate and the dam, which was clinically normal. Whole genome sequencing of one affected dog revealed a >5 Mb deletion on the X chromosome, encompassing the entire DMD gene. The exact deletion breakpoints could not be experimentally ascertained, but we confirmed that this region was deleted in all affected males, but not in the unaffected dogs. Quantitative polymerase chain reaction confirmed all three affected males were hemizygous for the mutant X chromosome, while the wildtype chromosome was observed in the unaffected male littermate. The female littermate and the dam were both heterozygous for the mutant chromosome. Forty-four Miniature Poodles from the general population were screened for the mutation and were homozygous for the wildtype chromosome. The finding represents a naturally-occurring mutation causing dystrophin-deficient muscular dystrophy in the dog

Engaging with assessment: increasing student engagement through continuous assessment

Student engagement is intrinsically linked to two important metrics in learning: student satisfaction and the quality of the student experience. One of the ways that engagement can be influenced is through careful curriculum design. Using the knowledge that many students are ‘assessment-driven’ a low stakes continuous weekly summative e-assessment was introduced to a module. The impact this had on student engagement was measured by studying student activity within the module virtual learning environment (VLE). It was found that introduction of the e-assessments led to a significant increase in VLE activity compared to the VLE activity in that module the previous year, and also compared to the VLE activity of two other modules studied by the same student cohort. As many institutions move towards greater blended or online deliveries it will become more important to ensure that VLEs encourage high levels of student engagement in order to maintain or enhance the student experience. Keywords : continuous assessment, learning analytics, student engagement, virtual learning environment

Ferritins: furnishing proteins with iron

Ferritins are a superfamily of iron oxidation, storage and mineralization proteins found throughout the animal, plant, and microbial kingdoms. The majority of ferritins consist of 24 subunits that individually fold into 4-α-helix bundles and assemble in a highly symmetric manner to form an approximately spherical protein coat around a central cavity into which an iron-containing mineral can be formed. Channels through the coat at inter-subunit contact points facilitate passage of iron ions to and from the central cavity, and intrasubunit catalytic sites, called ferroxidase centers, drive Fe2+ oxidation and O2 reduction. Though the different members of the superfamily share a common structure, there is often little amino acid sequence identity between them. Even where there is a high degree of sequence identity between two ferritins there can be major differences in how the proteins handle iron. In this review we describe some of the important structural features of ferritins and their mineralized iron cores and examine in detail how three selected ferritins oxidise Fe2+ in order to explore the mechanistic variations that exist amongst ferritins. We suggest that the mechanistic differences reflect differing evolutionary pressures on amino acid sequences, and that these differing pressures are a consequence of different primary functions for different ferritins

Neutrino Mass, Sneutrino Dark Matter and Signals of Lepton Flavor Violation in the MRSSM

We study the phenomenology of mixed-sneutrino dark matter in the Minimal R-Symmetric Supersymmetric Standard Model (MRSSM). Mixed sneutrinos fit naturally within the MRSSM, as the smallness (or absence) of neutrino Yukawa couplings singles out sneutrino A-terms as the only ones not automatically forbidden by R-symmetry. We perform a study of randomly generated sneutrino mass matrices and find that (i) the measured value of $\Omega_{DM}$ is well within the range of typical values obtained for the relic abundance of the lightest sneutrino, (ii) with small lepton-number-violating mass terms $m_{nn}^{2} {\tilde n} {\tilde n}$ for the right-handed sneutrinos, random matrices satisfying the $\Omega_{DM}$ constraint have a decent probability of satisfying direct detection constraints, and much of the remaining parameter space will be probed by upcoming experiments, (iii) the $m_{nn}^{2} {\tilde n} {\tilde n}$ terms radiatively generate appropriately small Majorana neutrino masses, with neutrino oscillation data favoring a mostly sterile lightest sneutrino with a dominantly mu/tau-flavored active component, and (iv) a sneutrino LSP with a significant mu component can lead to striking signals of e-mu flavor violation in dilepton invariant-mass distributions at the LHC.Comment: Revised collider analysis in Sec. 5 after fixing error in particle spectrum, References adde