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

Pump less wearable microfluidic device for real time pH sweat monitoring

This paper presents the fabrication and the performance of a novel, wearable, robust, flexible and disposable microfluidic device which incorporates micro-Light Emitting Diodes (μ-LEDs) as a detection system, for monitoring in real time mode the pH of the sweat generated during an exercising period

The population of SNe/SNRs in the starburst galaxy Arp 220. A self-consistent analysis of 20 years of VLBI monitoring

The nearby ultra-luminous infrared galaxy (ULIRG) Arp 220 is an excellent laboratory for studies of extreme astrophysical environments. For 20 years, Very Long Baseline Interferometry (VLBI) has been used to monitor a population of compact sources thought to be supernovae (SNe), supernova remnants (SNRs) and possibly active galactic nuclei (AGNs). Using new and archival VLBI data spanning 20 years, we obtain 23 high-resolution radio images of Arp 220 at wavelengths from 18 cm to 2 cm. From model-fitting to the images we obtain estimates of flux densities and sizes of all detected sources. We detect radio continuum emission from 97 compact sources and present flux densities and sizes for all analysed observation epochs. We find evidence for a LD-relation within Arp 220, with larger sources being less luminous. We find a compact source LF $n(L)\propto L^\beta$ with $\beta=-2.19\pm0.15$, similar to SNRs in normal galaxies. Based on simulations we argue that there are many relatively large and weak sources below our detection threshold. The observations can be explained by a mixed population of SNe and SNRs, where the former expand in a dense circumstellar medium (CSM) and the latter interact with the surrounding interstellar medium (ISM). Nine sources are likely luminous, type IIn SNe. This number of luminous SNe correspond to few percent of the total number of SNe in Arp 220 which is consistent with a total SN-rate of 4 yr$^{-1}$ as inferred from the total radio emission given a normal stellar initial mass function (IMF). Based on the fitted luminosity function, we argue that emission from all compact sources, also below our detection threshold, make up at most 20\% of the total radio emission at GHz frequencies.Comment: Accepted for publication in Astronomy and Astrophysic

The opposites task: Using general rules to test cognitive flexibility in preschoolers

A brief narrative description of the journal article, document, or resource. Executive functions play an important role in cognitive development, and during the preschool years especially, children's performance is limited in tasks that demand flexibility in their behavior. We asked whether preschoolers would exhibit limitations when they are required to apply a general rule in the context of novel stimuli on every trial (the "opposites" task). Two types of inhibitory processing were measured: response interference (resistance to interference from a competing response) and proactive interference (resistance to interference from a previously relevant rule). Group data show 3-year-olds have difficulty inhibiting prepotent tendencies under these conditions, whereas 5-year-olds' accuracy is near ceiling in the task. (Contains 4 footnotes and 1 table.

SiO masers in TX Cam: Simultaneous VLBA observations of two 43 GHz masers at four epochs

We present the results of simultaneous high resolution observations of v=1 and v=2, J=1-0 SiO masers toward TX Cam at four epochs covering a stellar cycle. Near maser maximum (Epochs III and IV), the individual components of both masers are distributed in ring-like structures but the ring is severely disrupted near stellar maser minimum (Epochs I and II). In Epochs III and IV there is a large overlap between the radii at which the two maser transitions occur. However in both epochs the average radius of the v=2 maser ring is smaller than for the v=1 maser ring, the difference being larger for Epoch IV. The observed relative ring radii in the two transitions, and the trends on the ring thickness, are close to those predicted by the model of Humphreys et al. (\cite{humphreys02}). In many individual features there is an almost exact overlap in space and velocity of emission from the two transitions, arguing against pure radiative pumping. At both Epochs III and IV in many spectral features only 50% of the flux density is recovered in our images, implying significant smooth maser structure. For both transitions we find that red- and blue-shifted masers occur in all parts of the rings, with relatively few masers at the systemic velocity. Thus there is no evidence for rotation, although the blue-shifted masers are somewhat more prominent to the west. At all four epochs red-shifted components are generally brighter than blue-shifted ones. At Epochs III and IV, we see many filamentary or spoke-like features in both v=1 and v=2 masers, especially in the red-shifted gas. These spokes show systematic velocity gradients consistent with a decelerating outward flow with increasing radius. We outline a possible model to explain why, given the presence of these spokes, there is a deficit of maser features at the systemic velocity.Comment: 15 pages, 10 figs, accepted to A&A, Abstract is reduced (see the paper for full length

Neutrophil-bead collision assay: Pharmacologically induced changes in membrane mechanics regulate the PSGL-1/P-selectin adhesion lifetime

Visualization of flowing neutrophils colliding with adherent 1-µm-diameter beads presenting P-selectin allowed the simultaneous measurement of collision efficiency (ε), membrane tethering fraction (f), membrane tether growth dynamics, and PSGL-1/P-selectin binding lifetime. For 1391 collisions analyzed over venous wall shear rates from 25 to 200 s-1 ε decreased from 0.17 to 0.004, whereas f increased from 0.15 to 0.70, and the average projected membrane tether length, ∠mtether, increased from 0.35 µm to ⋍2.0 µm over this shear range. At all shear rates tested, adhesive collisions lacking membrane tethers had average bond lifetimes less than those observed for collisions with tethers. For adhesive collisions that failed to form membrane tethers, the regressed Bell parameters (consistent with single bond Monte Carlo simulation) were zero-stress offrate, Koff(0) = 0.56 s-1and reactive compliance, r = 0.10 nm, similar to published atomic force microscopy (AFM) measurements. For all adhesion events (± tethers), the bond lifetime distributions were more similar to those obtained by rolling assay and best simulated by Monte Carlo with the above Bell parameters and an average of 1.48 bonds (n = 1 bond (67%), n = 2 (22%), and n = 3–5 (11%)). For collisions at 100 s-1, pretreatment of neutrophils with actin depolymerizing agents, latrunculin or cytochalasin D, had no effect on ε, but increased ∠mtether by 1.74- or 2.65-fold and prolonged the average tether lifetime by 1.41- or 1.65-fold, respectively. Jasplakinolide, an actin polymerizing agent known to cause blebbing, yielded results similar to the depolymerizing agents. Conversely, cholesterol-depletion with methyl-ß-cyclodextrin or formaldehyde fixation had no effect on ε, but reduced ∠mtether by 66% or 97% and reduced the average tether lifetime by 30% or 42%, respectively. The neutrophilbead collision assay combines advantages of atomic force microscopy (small contact zone), aggregometry (discrete interactions), micropipette manipulation (tether visualization), and rolling assays (physiologic flow loading). Membrane tether growth can be enhanced or reduced pharmacologically with consequent effects on PSGL-1/P-selectin lifetimes

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

Reconnection in a Weakly Stochastic Field

We examine the effect of weak, small scale magnetic field structure on the rate of reconnection in a strongly magnetized plasma. This affects the rate of reconnection by reducing the transverse scale for reconnection flows, and by allowing many independent flux reconnection events to occur simultaneously. Allowing only for the first effect and using Goldreich and Sridhar's model of strong turbulence in a magnetized plasma with negligible intermittency, we find that the lower limit for the reconnection speed is the Alfven speed times the Lundquist number to the power (-3/16). The upper limit on the reconnection speed is typically a large fraction of Alfven speed. We argue that generic reconnection in turbulent plasmas will normally occur at close to this upper limit. The fraction of magnetic energy that goes directly into electron heating scales as Lundquist number to the power (-2/5) and the thickness of the current sheet scales as the Lundquist number to the power (-3/5). A significant fraction of the magnetic energy goes into high frequency Alfven waves. We claim that the qualitative sense of these conclusions, that reconnection is fast even though current sheets are narrow, is almost independent of the local physics of reconnection and the nature of the turbulent cascade. As the consequence of this the Galactic and Solar dynamos are generically fast, i.e. do not depend on the plasma resistivity.Comment: Extended version accepted to ApJ, 44pages, 2 figure