Mutations in the E2 glycoprotein and the 3\u27 untranslated region enhance chikungunya virus virulence in mice

Chikungunya virus (CHIKV) is a mosquito-transmitted alphavirus that causes debilitating musculoskeletal pain and inflammation and can persist for months to years after acute infection. Although studies of humans and experimentally infected animals suggest that CHIKV infection persists in musculoskeletal tissues, the mechanisms for this remain poorly understood. To evaluate this further, we isolated CHIKV from the serum of persistently infected Rag1 -/- mice at day 28. When inoculated into naive wild-type (WT) mice, this persistently circulating CHIKV strain displayed a capacity for earlier dissemination and greater pathogenicity than the parental virus. Sequence analysis revealed a nonsynonymous mutation in the E2 glycoprotein (E2 K200R) and a deletion within the 3' untranslated region (3'-UTR). The introduction of these changes into the parental virus conferred enhanced virulence in mice, although primary tropism for musculoskeletal tissues was maintained. The E2 K200R mutation was largely responsible for enhanced viral dissemination and pathogenicity, although these effects were augmented by the 3'- UTR deletion. Finally, studies with Irf3/Irf7 -/- and Ifnar1 -/- mice suggest that the E2 K200R mutation enhances viral dissemination from the site of inoculation independently of interferon regulatory factor 3 (IRF3)-, IRF7-, and IFNAR1-mediated responses. As our findings reveal viral determinants of CHIKV dissemination and pathogenicity, their further study should help to elucidate host-virus interactions that determine acute and chronic CHIKV infection

Hypertension in older patients, a retrospective cohort study

Background: It is unknown to what extent General Practitioners (GPs) manage hypertension (HT) differently in older patients, as compared to younger age groups. The purpose of our study was to compare HT management in older patients to younger age groups. Methods: We performed a retrospective cohort study of patients of 159 GP's practices in the Integrated Primary Care Information (IPCI) database. The study period lasted from September 2010 through December 2012. The study population consisted of all patients aged 60 years or older with at least one blood pressure (BP) measurement during the inclusion period, without pre-existent HT, diabetes mellitus (DM) or atherosclerotic cardiovascular disease at time of study start. Study outcomes were a diagnosis of HT within one month after cohort entry and the use of antihypertensive medication within 4 months after cohort entry in HT diagnosed patients. We compared the incidence of outcomes between the age groups, stratified by systolic blood pressure (SBP). Logistic regression analysis was used to assess the influence of age-adjusted SBP Z-scores, age and gender on the outcomes. Results: We included 19,500 patients from 159 GP's practices of whom 1,181 (6.1 %) were newly diagnosed with HT. Corrected for age-adjusted SBP, older patients were less likely to be diagnosed with HT (odds ratio per year age increase 0.98, p < 0.001). Corrected for age-adjusted SBP, no significant effect of age on the probability of treatment in newly diagnosed HT patients was observed (p = 0.82). Conclusions: This study showed that GPs are less inclined to diagnose HT with increasing patient age, but do not withhold treatment when they diagnose HT in older patients

Time Interval Between Cover Crop Termination and Planting Influences Corn Seedling Disease, Plant Growth, and Yield

Experiments were established in a controlled-growth chamber and in the field to evaluate the effect of the length of time intervals between winter rye cover crop termination and corn planting on corn seedling disease, corn growth, and grain yield in 2014 and 2015. Rye termination dates ranged from 25 days before planting (DBP) to 2 days after planting (DAP) corn in the field and from 21 DBP to 1 DAP in controlled studies. Results were similar in both environments. In general, shorter intervals increased seedling disease and reduced corn emergence, shoot growth, and grain yield of corn following winter rye compared with corn planted 10 or more days after rye termination or without rye. Incidence of Pythium spp. increased with shorter intervals (less than 8 DBP); incidence of Fusarium spp. was not consistent between runs and experiments. In 2014, in the 1-DAP treatment, number of ears and grain yield were reduced (P = 0.05 and 0.02, respectively). In 2015, all termination intervals reduced plant population, number of ears, and yield (P = 0.01), with the 2-DBP treatment causing the biggest decrease. A 10- to 14-day interval between rye termination and corn planting should be followed to improve corn yield following a rye cover crop

Congruence within the Parent-Teacher Relationship: Associations with Children’s Functioning

Meaningful interactions between families and schools benefit multiple facets of children’s functioning including their academic, social, and behavioral adjustment (Christenson & Sheridan, 2001). Positive relationships between parents and teachers predict children’s enhanced social-emotional functioning and academic adjustment across time (Izzo, Weissberg, Kasprow, & Fendrich, 1999). Studies of parent-teacher relationships often focus on the association of child outcomes with separate parent or teacher reports of their relationship quality. Little attention has focused on the congruence of perceptions within parent-teacher dyads. It may be the case that when parents and teachers view their relationship in a similar positive light, better connections or partnerships across the home and school environments result, thereby enhancing children’s functioning. Conversely, when parents and teachers hold discrepant views about their relationship, or both view it negatively, they may be less likely to communicate and share goals for children; this disconnect may impede children’s functioning. This study examined the degree to which congruity and incongruity in parent and teacher views of their relationship are related to children’s academic, social, and behavioral functioning. Congruity was examined using a categorical approach: o Positive congruence: parents and teachers share positive views about their relationship o Non-positive congruence: parents and teachers share non-positive views about their relationship o Incongruence: parents and teachers hold differing views about the quality of their relationship Research Question and Hypothesis Is congruence/incongruence between parents and teachers in their views of their relationship related to children’s academic, social, and behavioral functioning? It was hypothesized that congruent, positive views of the parent-teacher relationship would be associated with children’s enhanced academic, social, and behavioral functioning to a greater extent than non-positive congruent or incongruent views

Fluorescence of Naphthol AS-MX is Readily Detectable in Dioxane Mixtures

Numerous enzymes have been demonstrated to be active in non-aqueous solutions, yet the utility of phosphatases under such conditions has been difficult to determine. Here, we demonstrate the ability to fluorescently detect naphthol AS‑MX in high percentages 1,4-dioxane with a fluorescence differential compared with naphthol AS‑MX phosphate. While intensities and maximum fluorescence wavelengths changed depending on solvent conditions, these results demonstrate this system’s potential for testing phosphatase activity in high amounts of dioxane

Interferons Regulate the Phenotype of Wild-type and Mutant Herpes Simplex Viruses In Vivo

Mechanisms responsible for neuroattenuation of herpes simplex virus (HSV) have been defined previously by studies of mutant viruses in cultured cells. The hypothesis that null mutations in host genes can override the attenuated phenotype of null mutations in certain viral genes was tested. Mutants such as those in infected cell protein (ICP) 0, thymidine kinase, ribonucleotide reductase, virion host shutoff, and ICP34.5 are reduced in their capacity to replicate in nondividing cells in culture and in vivo. The replication of these viruses was examined in eyes and trigeminal ganglia for 1–7 d after corneal inoculation in mice with null mutations (−/−) in interferon receptors (IFNR) for type I IFNs (IFN-α/βR), type II IFN (IFN-γR), and both type I and type II IFNs (IFN-α/β/γR). Viral titers in eyes and ganglia of IFN-γR−/− mice were not significantly different from congenic controls. However, in IFN-α/βR−/− or IFN-α/β/γR−/− mice, growth of all mutants, including those with significantly impaired growth in cell culture, was enhanced by up to 1,000-fold in eyes and trigeminal ganglia. Blepharitis and clinical signs of infection were evident in IFN-α/βR−/− and IFN-α/β/γR−/− but not control mice for all viruses. Also, IFNs were shown to significantly reduce productive infection of, and spread from intact, but not scarified, corneas. Particularly striking was restoration of near-normal trigeminal ganglion replication and neurovirulence of an ICP34.5 mutant in IFN-α/βR−/− mice. These data show that IFNs play a major role in limiting mutant and wild-type HSV replication in the cornea and in the nervous system. In addition, the in vivo target of ICP34.5 may be host IFN responses. These experiments demonstrate an unsuspected role for host factors in defining the phenotypes of some HSV mutants in vivo. The phenotypes of mutant viruses therefore cannot be interpreted based solely upon studies in cell culture but must be considered carefully in the context of host factors that may define the in vivo phenotype

Компаративний аналіз привабливості стратегічних зон господарювання підприємства

Запропоновано методику компаративного аналізу привабливості стратегічних зон господарювання підприємства з використанням методів багатокритеріального оцінювання.Предложена методика компаративного анализа привлекательности стратегических зон хозяйствования предприятия с использованием методов многокритериального оценивания.The article proposed a method for comparative analysis of attractiveness of enterprise strategic bussines unit using methods of multi-criteria evaluation

Is Schr\"{o}dinger's Conjecture for the Hydrogen Atom Coherent States Attainable

We construct the most general SO(4,2) hydrogen atom coherent states which are the counterpart of Schr\"{o}dinger's harmonic oscillator coherent states. We show that these states cannot be localized and cannot follow the classical orbits. Thus, Schr\"{o}dinger's conjecture for the hydrogen atom coherent states is unattainable.Comment: 10 pages, report