Animal models of Zika virus infection, pathogenesis, and immunity

Zika virus (ZIKV) is an emerging mosquito-transmitted flavivirus that now causes epidemics affecting millions of people on multiple continents. The virus has received global attention because of some of its unusual epidemiological and clinical features, including persistent infection in the male reproductive tract and sexual transmission, an ability to cross the placenta during pregnancy and infect the developing fetus to cause congenital malformations, and its association with Guillain-Barré syndrome in adults. This past year has witnessed an intensive effort by the global scientific community to understand the biology of ZIKV and to develop pathogenesis models for the rapid testing of possible countermeasures. Here, we review the recent advances in and utility and limitations of newly developed mouse and nonhuman primate models of ZIKV infection and pathogenesis

Mesons and Flavor on the Conifold

We explore the addition of fundamental matter to the Klebanov-Witten field theory. We add probe D7-branes to the ${\cal N}=1$ theory obtained from placing D3-branes at the tip of the conifold and compute the meson spectrum for the scalar mesons. In the UV limit of massless quarks we find the exact dimensions of the associated operators, which exhibit a simple scaling in the large-charge limit. For the case of massive quarks we compute the spectrum of scalar mesons numerically.Comment: 19 pages, 3 figures, v2: typos fixe

Foot Characteristics in Association With Inversion Ankle Injury

Objective: To review the literature that provides information to assist in analyzing the role of the foot in acute and chronic lateral ankle injury. Data Sources: We searched MEDLINE, CINAHL, Institute for Scientific Information's Web of Science, and SPORT Discus from 1965–2005 using the terms lateral, ankle, ligament, injury, risk factors, foot, subtalar joint, talocrural joint, gait analysis, and foot biomechanics. Data Synthesis: We found substantial information on the incidence and treatment of lateral ankle sprains in sport but very few articles that focused on risk factors associated with these injuries and even less information on the foot as it relates to this condition. Moreover, little information was available regarding the risk factors associated with the development of chronic instability after a lateral ankle sprain. We critically analyzed the foot articulations and the foot's role in the mechanism of injury to assist our clinical synopsis. Conclusions/Recommendations: An in-depth review of the foot complex in relation to lateral ankle sprains strongly suggested its importance when treating and preventing inversion ankle trauma. Throughout the literature, the only static foot measurements that show a significant correlation to this condition are an identified cavovarus deformity, increased foot width, and increased calcaneal eversion range of motion. Authors also provided dynamic measurements of the foot, which produced several significant findings that we discuss. Although our findings offer some insight into the relationship between foot characteristics and lateral ankle injuries, future research is needed to confirm the results of this review and expand this area of investigation

A multi-method approach to delineate and validate migratory corridors

Context: Managers are faced with numerous methods for delineating wildlife movement corridors, and often must make decisions with limited data. Delineated corridors should be robust to different data and models. Objectives: We present a multi-method approach for delineating and validating wildlife corridors using multiple data sources, which can be used conserve landscape connectivity. We used this approach to delineate and validate migration corridors for wildebeest (Connochaetes taurinus) in the Tarangire Ecosystem of northern Tanzania. Methods: We used two types of locational data (distance sampling detections and GPS collar locations), and three modeling methods (negative binomial regression, logistic regression, and Maxent), to generate resource selection functions (RSFs) and define resistance surfaces. We compared two corridor detection algorithms (cost-distance and circuit theory), to delineate corridors. We validated corridors by comparing random and wildebeest locations that fell within corridors, and cross-validated by data type. Results: Both data types produced similar RSFs. Wildebeest consistently selected migration habitat in flatter terrain farther from human settlements. Validation indicated three of the combinations of data type, modeling, and corridor detection algorithms (detection data with Maxent modeling, GPS collar data with logistic regression modeling, and GPS collar data with Maxent modeling, all using cost-distance) far outperformed the other seven. We merged the predictive corridors from these three data-method combinations to reveal habitat with highest probability of use. Conclusions: The use of multiple methods ensures that planning is able to prioritize conservation of migration corridors based on all available information

Cell-Type Specific Changes in Glial Morphology and Glucocorticoid Expression During Stress and Aging in the Medial Prefrontal Cortex.

Repeated exposure to stressors is known to produce large-scale remodeling of neurons within the prefrontal cortex (PFC). Recent work suggests stress-related forms of structural plasticity can interact with aging to drive distinct patterns of pyramidal cell morphological changes. However, little is known about how other cellular components within PFC might be affected by these challenges. Here, we examined the effects of stress exposure and aging on medial prefrontal cortical glial subpopulations. Interestingly, we found no changes in glial morphology with stress exposure but a profound morphological change with aging. Furthermore, we found an upregulation of non-nuclear glucocorticoid receptors (GR) with aging, while nuclear levels remained largely unaffected. Both changes are selective for microglia, with no stress or aging effect found in astrocytes. Lastly, we show that the changes found within microglia inversely correlated with the density of dendritic spines on layer III pyramidal cells. These findings suggest microglia play a selective role in synaptic health within the aging brain

Genetic Analysis Workshop 13: Simulated longitudinal data on families for a system of oligogenic traits

The Genetic Analysis Workshop 13 simulated data aimed to mimic the major features of the real Framingham Heart Study data that formed Problem 1, but under a known inheritance model and with 100 replicates, so as to allow evaluation of the statistical properties of various methods. The pedigrees used were the 330 real pedigree structures (comprising 4692 individuals) with some minor changes to protect confidentiality. Fifty trait genes and 399 microsatellite markers were simulated by gene dropping on 22 autosomal chromosomes. Assuming random ascertainment of families, a system of eight longitudinal quantitative traits (designed to be similar to those in the real data) was generated with a wide range of heritabilities, including some pleiotropic and interactive effects. Genes could affect either the baseline level or the rate of change of the phenotype. Hypertension diagnosis and treatment were simulated with treatment availability, compliance, and efficacy depending on calendar year. Nongenetic traits of smoking and alcohol were generated as covariates for other traits. Death was simulated as a hazard rate depending upon age, sex, smoking, cholesterol, and systolic blood pressure. After the complete data were simulated, missing data indicators were generated based on logistic models fitted to the real data, involving the subject's history of previous missing values, together with that of their spouses, parents, siblings, and offspring, as well as marital status, only-child indicators, current value at certain simulated traits, and the data collection pattern on the cohort into which each subject was ascertained

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