GIMAP6 is required for T cell maintenance and efficient autophagy in mice

The GTPases of the immunity-associated proteins (GIMAP) GTPases are a family of proteins expressed strongly in the adaptive immune system. We have previously reported that in human cells one member of this family, GIMAP6, interacts with the ATG8 family member GABARAPL2, and is recruited to autophagosomes upon starvation, suggesting a role for GIMAP6 in the autophagic process. To study this possibility and the function of GIMAP6 in the immune system, we have established a mouse line in which the Gimap6 gene can be inactivated by Cre-mediated recombination. In mice bred to carry the CD2Cre transgene such that the Gimap6 gene was deleted within the T and B cell lineages there was a 50-70% reduction in peripheral CD4(+) and CD8(+) T cells. Analysis of splenocyte-derived proteins from these mice indicated increased levels of MAP1LC3B, particularly the lipidated LC3-II form, and S405-phosphorylation of SQSTM1. Electron microscopic measurements of Gimap6(-/-) CD4(+) T cells indicated an increased mitochondrial/cytoplasmic volume ratio and increased numbers of autophagosomes. These results are consistent with autophagic disruption in the cells. However, Gimap6(-/-) T cells were largely normal in character, could be effectively activated in vitro and supported T cell-dependent antibody production. Treatment in vitro of CD4(+) splenocytes from GIMAP6(fl/fl) ERT2Cre mice with 4-hydroxytamoxifen resulted in the disappearance of GIMAP6 within five days. In parallel, increased phosphorylation of SQSTM1 and TBK1 was observed. These results indicate a requirement for GIMAP6 in the maintenance of a normal peripheral adaptive immune system and a significant role for the protein in normal autophagic processes. Moreover, as GIMAP6 is expressed in a cell-selective manner, this indicates the potential existence of a cell-restricted mode of autophagic regulation.Peer reviewe

Orientation cues for high-flying nocturnal insect migrants: do turbulence-induced temperature and velocity fluctuations indicate the mean wind flow?

Migratory insects flying at high altitude at night often show a degree of common alignment, sometimes with quite small angular dispersions around the mean. The observed orientation directions are often close to the downwind direction and this would seemingly be adaptive in that large insects could add their self-propelled speed to the wind speed, thus maximising their displacement in a given time. There are increasing indications that high-altitude orientation may be maintained by some intrinsic property of the wind rather than by visual perception of relative ground movement. Therefore, we first examined whether migrating insects could deduce the mean wind direction from the turbulent fluctuations in temperature. Within the atmospheric boundary-layer, temperature records show characteristic ramp-cliff structures, and insects flying downwind would move through these ramps whilst those flying crosswind would not. However, analysis of vertical-looking radar data on the common orientations of nocturnally migrating insects in the UK produced no evidence that the migrants actually use temperature ramps as orientation cues. This suggests that insects rely on turbulent velocity and acceleration cues, and refocuses attention on how these can be detected, especially as small-scale turbulence is usually held to be directionally invariant (isotropic). In the second part of the paper we present a theoretical analysis and simulations showing that velocity fluctuations and accelerations felt by an insect are predicted to be anisotropic even when the small-scale turbulence (measured at a fixed point or along the trajectory of a fluid-particle) is isotropic. Our results thus provide further evidence that insects do indeed use turbulent velocity and acceleration cues as indicators of the mean wind direction

The variation of G in a negatively curved space-time

Scalar-tensor (ST) gravity theories provide an appropriate theoretical framework for the variation of Newton's fundamental constant, conveyed by the dynamics of a scalar-field non-minimally coupled to the space-time geometry. The experimental scrutiny of scalar-tensor gravity theories has led to a detailed analysis of their post-newtonian features, and is encapsulated into the so-called parametrised post-newtonian formalism (PPN). Of course this approach can only be applied whenever there is a newtonian limit, and the latter is related to the GR solution that is generalized by a given ST solution under consideration. This procedure thus assumes two hypothesis: On the one hand, that there should be a weak field limit of the GR solution; On the other hand that the latter corresponds to the limit case of given ST solution. In the present work we consider a ST solution with negative spatial curvature. It generalizes a general relativistic solution known as being of a degenerate class (A) for its unusual properties. In particular, the GR solution does not exhibit the usual weak field limit in the region where the gravitational field is static. The absence of a weak field limit for the hyperbolic GR solution means that such limit is also absent for comparison with the ST solution, and thus one cannot barely apply the PPN formalism. We therefore analyse the properties of the hyperbolic ST solution, and discuss the question o defining a generalised newtonian limit both for the GR solution and for the purpose of contrasting it with the ST solution. This contributes a basic framework to build up a parametrised pseudo-newtonian formalism adequate to test ST negatively curved space-times.Comment: 7 pages, 5 figures. Contribution to the Joint European and National Astronomy Meeting (JENAM) 2010; based on a talk given by JPM in the "From Varying Couplings to Fundamental Physics" Symposiu

Increasing condom use in heterosexual men: development of a theory-based interactive digital intervention

Increasing condom use to prevent sexually transmitted infections is a key public health goal. Interventions are more likely to be effective if they are theory- and evidence-based. The Behaviour Change Wheel (BCW) provides a framework for intervention development. To provide an example of how the BCW was used to develop an intervention to increase condom use in heterosexual men (the MenSS website), the steps of the BCW intervention development process were followed, incorporating evidence from the research literature and views of experts and the target population. Capability (e.g. knowledge) and motivation (e.g. beliefs about pleasure) were identified as important targets of the intervention. We devised ways to address each intervention target, including selecting interactive features and behaviour change techniques. The BCW provides a useful framework for integrating sources of evidence to inform intervention content and deciding which influences on behaviour to target

Evidence for a population of high-redshift submillimeter galaxies from interferometric imaging

We have used the Submillimeter Array to image a flux-limited sample of seven submillimeter galaxies, selected by the AzTEC camera on the JCMT at 1.1 mm, in the COSMOS field at 890 μ m with ~2\u27\u27 resolution. All of the sources—two radio-bright and five radio-dim—are detected as single point sources at high significance (\u3e6 σ), with positions accurate to ~0.2\u27\u27 that enable counterpart identification at other wavelengths observed with similarly high angular resolution. All seven have IRAC counterparts, but only two have secure counterparts in deep HST ACS imaging. As compared to the two radio-bright sources in the sample, and those in previous studies, the five radio-dim sources in the sample (1) have systematically higher submillimeter-to-radio flux ratios, (2) have lower IRAC 3.6-8.0 μ m fluxes, and (3) are not detected at 24 μ m . These properties, combined with size constraints at 890 μ m (θ 1.2\u27\u27), suggest that the radio-dim submillimeter galaxies represent a population of very dusty starbursts, with physical scales similar to local ultraluminous infrared galaxies, with an average redshift higher than radio-bright sources

Analysis of sexual phenotype and prezygotic fertility in natural populations of Fucus spiralis, F. vesiculosus (Fucaceae, Phaeophyceae) and their putative hybrids

In the genus Fucus, the character dioecy/hermaphroditism has undergone multiple state changes and hybridization is possible between taxa with contrasting mating systems, e.g. between the dioecious Fucus vesiculosus and the hermaphrodite F. spiralis. In the context of mating system evolution, we evaluated the potential consequences of hybridization by studying the variation in sexual phenotype and prezygotic fertility. Firstly, as a result of hybridization between the two sexual systems, gender variation may arise depending on the relative importance of genes with large versus small phenotypic effects. We thus qualitatively examined the extent of gender variation within and among individual hybrids in comparison with both parental species. Secondly, if hybridization breaks up co-adapted gene complexes, hybrid fertility may be reduced in comparison with both parental species. Therefore, we also quantified male and female prezygotic fertility in parental species and their hybrids in order to test for reduction in hybrid fitness. A total of 89 sexually mature individuals (20 F. spiralis, 40 F. vesiculosus, 10 hermaphrodite hybrids and 19 dioecious hybrids) were sampled in two geographically distant regions (France and Portugal) and six conceptacles per individual were observed. Within-individual variation was very restricted qualitatively – only one hybrid carried a conceptacle with a different sexual phenotype from the five others – as well as quantitatively. This suggests a simple genetic system for sex determination involving a few genes with major effects. In addition, analyses showed no significant decrease in hybrid fertility compared with parental species. Moreover, hybrids exhibited all sexual phenotypes, suggesting several generations of hybridization and backcrossing and, therefore, that hybrids are reproductively successful. Finally, the occurrence of sterile paraphyses in female and hermaphrodite individuals was interpreted as a relic of male function and suggests that, as in higher plants, evolution from hermaphroditism to dioecy may be the most parsimonious pathway

Reconfigurable superconducting vortex pinning potential for magnetic disks in hybrid structures

High resolution scanning Hall probe microscopy has been used to directly visualise the superconducting vortex behavior in hybrid structures consisting of a square array of micrometer-sized Py ferromagnetic disks covered by a superconducting Nb thin film. At remanence the disks exist in almost fully flux-closed magnetic vortex states, but the observed cloverleaf-like stray fields indicate the presence of weak in-plane anisotropy. Micromagnetic simulations suggest that the most likely origin is an unintentional shape anisotropy. We have studied the pinning of added free superconducting vortices as a function of the magnetisation state of the disks, and identified a range of different phenomena arising from competing energy contributions. We have also observed clear differences in the pinning landscape when the superconductor and the ferromagnet are electron ically coupled or insulated by a thin dielectric layer, with an indication of non-trivial vortex-vortex interactions. We demonstrate a complete reconfiguration of the vortex pinning potential when the magnetisation of the disks evolves from the vortex-like state to an onion-like one under an in-plane magnetic field. Our results are in good qualitative agreement with theoretical predictions and could form the basis of novel superconducting devices based on reconfigurable vortex pinning sites

Acute Achilles tendon rupture: minimally invasive surgery versus non operative treatment, with immediate full weight bearing. Design of a randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>We present the design of an open randomized multi-centre study on surgical versus conservative treatment of acute Achilles tendon ruptures. The study is designed to evaluate the effectiveness of conservative treatment in reducing complications when treating acute Achilles tendon rupture.</p> <p>Methods/Design</p> <p>At least 72 patients with acute Achilles tendon rupture will be randomized to minimally invasive surgical repair followed by functional rehabilitation using tape bandage or conservative treatment followed by functional rehabilitation with use of a functional bracing system. Both treatment arms use a 7 weeks post-rupture rehabilitation protocol. Four hospitals in the Netherlands will participate. Primary end-point will be reduction in complications other than re-rupture. Secondary end-point will be re-rupturing, time off work, sporting activity post rupture, functional outcome by Leppilahti score and patient satisfaction. Patient follow-up will be 12 month.</p> <p>Discussion</p> <p>By making this design study we wish to contribute to more profound research on AT rupture treatment and prevent publication bias for this open-labelled randomized trial.</p> <p>Trial registration</p> <p>ISRCTN50141196</p

Macrocheles species (Acari: Macrochelidae) associated with human corpses in Europe

The biology of macrochelid mites might offer new venues for the interpretation of the environmental conditions surrounding human death and decomposition. Three human corpses, one from Sweden and two from Spain, have been analysed for the occurrence of Macrochelidae species. Macrocheles muscaedomesticae females were associated with a corpse that was found in a popular beach area of southeast Spain. Their arrival coincides with the occurrence of one of their major carrier species, the filth fly Fannia scalaris, the activity of which peaks during mid-summer. M. glaber specimens were collected from a corpse in a shallow grave in a forest in Sweden at the end of summer, concurrent with the arrival of beetles attracted by odours from the corpse. M. perglaber adults were sampled from a corpse found indoors in the rural surroundings of Granada city, Spain. The phoretic behaviour of this species is similar to that of M. glaber, but being more specific to Scarabaeidae and Geotrupidae dung beetles, most of which favour human faeces. M. muscaedomesticae is known from urban and rural areas and poultry farms; M. glaber from outdoors, particularly the countryside; while M. perglaber from outdoor, rural, and remote, potentially mountainous locations. M. muscaedomesticae and M. perglaber are reported for the first time from the Iberian Peninsula. This is the first record of M. perglaber from human remains

Macrocheles species (Acari: Macrochelidae) associated with human corpses in Europe

The biology of macrochelid mites might offer new venues for the interpretation of the environmental conditions surrounding human death and decomposition. Three human corpses, one from Sweden and two from Spain, have been analysed for the occurrence of Macrochelidae species. Macrocheles muscaedomesticae females were associated with a corpse that was found in a popular beach area of southeast Spain. Their arrival coincides with the occurrence of one of their major carrier species, the filth fly Fannia scalaris, the activity of which peaks during mid-summer. M. glaber specimens were collected from a corpse in a shallow grave in a forest in Sweden at the end of summer, concurrent with the arrival of beetles attracted by odours from the corpse. M. perglaber adults were sampled from a corpse found indoors in the rural surroundings of Granada city, Spain. The phoretic behaviour of this species is similar to that of M. glaber, but being more specific to Scarabaeidae and Geotrupidae dung beetles, most of which favour human faeces. M. muscaedomesticae is known from urban and rural areas and poultry farms; M. glaber from outdoors, particularly the countryside; while M. perglaber from outdoor, rural, and remote, potentially mountainous locations. M. muscaedomesticae and M. perglaber are reported for the first time from the Iberian Peninsula. This is the first record of M. perglaber from human remains