Noninfectious retrovirus particles drive the APOBEC3/Rfv3 dependent neutralizing antibody response.

Members of the APOBEC3 family of deoxycytidine deaminases counteract a broad range of retroviruses in vitro through an indirect mechanism that requires virion incorporation and inhibition of reverse transcription and/or hypermutation of minus strand transcripts in the next target cell. The selective advantage to the host of this indirect restriction mechanism remains unclear, but valuable insights may be gained by studying APOBEC3 function in vivo. Apobec3 was previously shown to encode Rfv3, a classical resistance gene that controls the recovery of mice from pathogenic Friend retrovirus (FV) infection by promoting a more potent neutralizing antibody (NAb) response. The underlying mechanism does not involve a direct effect of Apobec3 on B cell function. Here we show that while Apobec3 decreased titers of infectious virus during acute FV infection, plasma viral RNA loads were maintained, indicating substantial release of noninfectious particles in vivo. The lack of plasma virion infectivity was associated with a significant post-entry block during early reverse transcription rather than G-to-A hypermutation. The Apobec3-dependent NAb response correlated with IgG binding titers against native, but not detergent-lysed virions. These findings indicate that innate Apobec3 restriction promotes NAb responses by maintaining high concentrations of virions with native B cell epitopes, but in the context of low virion infectivity. Finally, Apobec3 restriction was found to be saturable in vivo, since increasing FV inoculum doses resulted in decreased Apobec3 inhibition. By analogy, maximizing the release of noninfectious particles by modulating APOBEC3 expression may improve humoral immunity against pathogenic human retroviral infections

Evidence for cervical muscle morphometric changes on magnetic resonance images after whiplash: A systematic review and meta-analysis

INTRODUCTION Morphometric changes to cervical musculature in whiplash associated disorder have been reported in several studies with varying results. However, the evidence is not clear because only a limited number of cohorts have been studied and one cohort has been reported in multiple publications. The aim of this study was to assess the evidence for cervical muscle morphometric changes on magnetic resonance (MR) images after whiplash using a systematic review with meta-analysis. MATERIALS AND METHODS PubMed, MEDLINE and Cochrane Library were searched without language restriction using combinations of the MeSH terms "muscles", "whiplash injuries", and "magnetic resonance imaging". Studies of acute and chronic whiplash were included if they compared whiplash and control cervical spine muscle morphometry measurements from MR images. The search identified 380 studies. After screening, eight studies describing five cohorts (one acute, three chronic, one both acute and chronic) met the inclusion criteria. Participant characteristics and outcome measures were extracted using a standard extraction format. Quality of eligible studies was assessed using the Newcastle-Ottawa Scale. Muscle cross-sectional area (CSA) and fat infiltrate (MFI) for acute and chronic whiplash cohorts were compared using mean difference and 95% confidence intervals. Meta-analysis models were created when data from more than two eligible cohorts was available, using inverse-variance random-effects models (RevMan5 version 5.3.5). RESULTS Quality assessment was uniformly good but only two studies blinded the assessor. Analysis of the acute cohorts revealed no consensus with respect to CSA. MFI was not measured in the acute cohorts. Analysis of the chronic cohorts revealed CSA is probably increased in some muscles after whiplash but there is insufficient evidence to confirm whether MFI is also increased. Because the available data were limited, meta-analyses of only multifidus were performed. In chronic whiplash multifidus CSA was significantly increased at C5 (Z = 3.51, p < 0.01) and C6 (Z = 2.66, p < 0.01); and MFI was significantly increased at C7 only (Z = 2.52, p < 0.01) but the heterogeneity was unacceptably high (I2 = 83%). CONCLUSIONS The strength of the evidence for cervical muscle morphometric changes on MR images after whiplash is inconsistent for CSA and MFI. Future study designs should be standardised with quantification of three-dimensional muscle morphometry

A Single Nucleotide Polymorphism in Tetherin Promotes Retrovirus Restriction In Vivo

Tetherin is a membrane protein of unusual topology expressed from rodents to humans that accumulates enveloped virus particles on the surface of infected cells. However, whether this ‘tethering’ activity promotes or restricts retroviral spread during acute retrovirus infection in vivo is controversial. We report here the identification of a single nucleotide polymorphism in the Tetherin gene of NZW/LacJ (NZW) mice that mutated the canonical ATG start site to GTG. Translation of NZW Tetherin from downstream ATGs deleted a conserved dual-tyrosine endosomal sorting motif, resulting in higher cell surface expression and more potent inhibition of Friend retrovirus release compared to C57BL/6 (B6) Tetherin in vitro. Analysis of (B6×NZW)F1 hybrid mice revealed that increased Tetherin cell surface expression in NZW mice is a recessive trait in vivo. Using a classical genetic backcrossing approach, NZW Tetherin expression strongly correlated with decreased Friend retrovirus replication and pathogenesis. However, the protective effect of NZW Tetherin was not observed in the context of B6 Apobec3/Rfv3 resistance. These findings identify the first functional Tetherin polymorphism within a mammalian host, demonstrate that Tetherin cell surface expression is a key parameter for retroviral restriction, and suggest the existence of a restriction factor hierarchy to counteract pathogenic retrovirus infections in vivo

Movement of walleye in an impounded reach of the Au Sable River, Michigan, USA

We estimated long-range spawning and foraging movements of walleye and observed their use of river and reservoir habitats between two large hydroelectric dams on the Au Sable River, Michigan. We used radiotelemetry to monitor seasonal and daily movements of 11 large walleye. Walleye ranged throughout the entire reach between the two dams. Eight of the 11 fish used both river and reservoir locations. Walleye migrated upriver in April or May and presumably spawned near the dam tailwaters. After spawning, walleye remained in the river for up to 6 months, usually establishing local ranges. During this time, they occupied low-velocity refuges within the first 25 km of the upstream dam. They seldom occupied the downstream area, which has higher variation around the mean temperature. Food availability and water temperature may have affected the length of time that walleye remained in the river after spawning. All walleye overwintered in the reservoir. We designed this study to evaluate if walleye have a potential negative impact on brown trout, Salmo trutta . In summer, walleye were often present near sites where fingerling trout were stocked. We found the highest potential for interaction between the two species occurs within the first 25 km of the upstream dam during summer. The movement patterns of and habitats used by large walleye validate concerns that walleye could compete with adult brown trout for food and resting sites and prey on juvenile brown trout.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/42646/1/10641_2004_Article_2864.pd

Sticking under wet conditions: the remarkable attachment abilities of the torrent frog, staurois guttatus

Tree frogs climb smooth surfaces utilising capillary forces arising from an air-fluid interface around their toe pads, whereas torrent frogs are able to climb in wet environments near waterfalls where the integrity of the meniscus is at risk. This study compares the adhesive capabilities of a torrent frog to a tree frog, investigating possible adaptations for adhesion under wet conditions. We challenged both frog species to cling to a platform which could be tilted from the horizontal to an upside-down orientation, testing the frogs on different levels of roughness and water flow. On dry, smooth surfaces, both frog species stayed attached to overhanging slopes equally well. In contrast, under both low and high flow rate conditions, the torrent frogs performed significantly better, even adhering under conditions where their toe pads were submerged in water, abolishing the meniscus that underlies capillarity. Using a transparent platform where areas of contact are illuminated, we measured the contact area of frogs during platform rotation under dry conditions. Both frog species not only used the contact area of their pads to adhere, but also large parts of their belly and thigh skin. In the tree frogs, the belly and thighs often detached on steeper slopes, whereas the torrent frogs increased the use of these areas as the slope angle increased. Probing small areas of the different skin parts with a force transducer revealed that forces declined significantly in wet conditions, with only minor differences between the frog species. The superior abilities of the torrent frogs were thus due to the large contact area they used on steep, overhanging surfaces. SEM images revealed slightly elongated cells in the periphery of the toe pads in the torrent frogs, with straightened channels in between them which could facilitate drainage of excess fluid underneath the pad

VLT/NACO near-infrared imaging and spectroscopy of N88A in the SMC

We present near-infrared imaging and spectroscopic high spatial resolution observations of the SMC region N88 containing the bright, excited, extincted and compact H II region N88A of size ~ 1 pc. To investigate its stellar content and reddening, N88 was observed using spectroscopy and imagery in the JHKs- and L'-band at a spatial resolution of ~ 0.1-0.3", using the VLT UT4 equipped with the NAOS adaptive optics system. In order to attempt to establish if the origin of the infra-red (IR) excess is due to bright nebulosity, circumstellar material and/or local dust, we used Ks vs J-K colour-magnitude (CM) and JHK colour-colour (CC) diagrams, as well as L' imagery.Our IR-data reveal in the N88 area an IR-excess fraction of geq 30 per cent of the detected stars,as well as an unprecedently detailed morphology of N88A. It consists of an embedded cluster of ~3.5" (~ 1 pc) in diameter, of at least thirteen resolved stars superposed with an unusual bright continuum centered on a very bright star. The four brightest stars in this cluster lie red-ward of H-K geq 0.45 mag, and could be classified as young stellar object (YSO) candidates. Four other probable YSO candidates are also detected in N88 along a south-north bow-shaped thin H2 filament at ~ 7" east of the young central bright star. At 0.2" east of this star, a heavily embedded core is detected that could be a massive class I protostar candidate. The 2.12 mu H2 image of N88A resembles a shell of diameter ~ 3" ~ 0.9 pc) centered on the bright star. The line ratios of H2 2-1 S(1) and 1-0 S(0) relative to 1-0 S(1), as well as the presence of high v lines, are indicative of photodissociation regions, rather than shocks.Comment: 15 pages, 14 figures, accepted by Astronomy and Astrophysics, uses pdflatex, aa.cl

Impact of human CA8 on thermal antinociception in relation to morphine equivalence in mice

Recently, we showed that murine dorsal root ganglion (DRG) Car8 expression is a cis-regulated eQTL that determines analgesic responses. In this report, we show that transduction through sciatic nerve injection of DRG with human wild-type carbonic anhydrase-8 using adeno-associated virus viral particles (AAV8-V5-CA8WT) produces analgesia in naive male C57BL/6J mice and antihyperalgesia after carrageenan treatment. A peak mean increase of about 4 s in thermal hindpaw withdrawal latency equaled increases in thermal withdrawal latency produced by 10 mg/kg intraperitoneal morphine in these mice. Allometric conversion of this intraperitoneal morphine dose in mice equals an oral morphine dose of about 146 mg in a 60-kg adult. Our work quantifies for the first time analgesia and antihyperalgesia in an inflammatory pain model after DRG transduction by CA8 gene therapy

Is Height2.7 Appropriate for Indexation of Left Ventricular Mass in Healthy Adolescents?:The Importance of Sex Differences

BACKGROUND:Left ventricular mass (LVM) is an important predictor of cardiovascular risk. In adolescence, LVM is commonly indexed to height2.7, although some evidence suggests that this may not fully account for sex differences.METHODS:We investigated appropriate allometric scaling of LVM to height, total lean mass, and body surface area, in a UK birth cohort of 2039 healthy adolescents (17±1 years). Allometric relationships were determined by linear regression stratified by sex, following log transformation of x and y variables [log(y)=a+b×log(x)], b is the allometric exponent.RESULTS:Log (LVM) showed linear relationships with log(height) and log(lean mass). Biased estimates of slope resulted when the sexes were pooled. The exponents were lower than the conventional estimate of 2.7 for males (mean [95% CI]=1.66 [1.30–2.03]) and females (1.58 [1.27–1.90]). When LVM was indexed to lean mass, the exponent was 1.16 (1.05–1.26) for males and 1.07 (0.97–1.16) for females. When LVM was indexed to estimated body surface area, the exponent was 1.53 (1.40–1.66) for males and 1.34 (1.24–1.45) for females.CONCLUSIONS:Allometric exponents derived from pooled data, including men and women without adjustment for sex were biased, possibly due to sex differences in body composition. We suggest that when assessing LVM, clinicians should consider body size, body composition, sex, and age. Our observations may also have implications for the identification of young individuals with cardiac hypertrophy