Experimental growth law for bubbles in a "wet" 3D liquid foam

We used X-ray tomography to characterize the geometry of all bubbles in a liquid foam of average liquid fraction $\phi_l\approx 17$ and to follow their evolution, measuring the normalized growth rate $\mathcal{G}=V^{-{1/3}}\frac{dV} {dt}$ for 7000 bubbles. While $\mathcal{G}$ does not depend only on the number of faces of a bubble, its average over $f-$faced bubbles scales as $G_f\sim f-f_0$ for large $f$s at all times. We discuss the dispersion of $\mathcal{G}$ and the influence of $V$ on $\mathcal{G}$.Comment: 10 pages, submitted to PR

Expression of Eukaryotic Membrane Proteins in Pichia pastoris.

A key point when it comes to heterologous expression of eukaryotic membrane proteins (EMPs) is the choice of the best-suited expression platform. The yeast Pichia pastoris has proven to be a very versatile system showing promising results in a growing number of cases. Indeed, its particular methylotrophic characteristics combined to the very simple handling of a eukaryotic microorganism that possesses the majority of mammalian-like machineries make it a very competitive expression system for various complex proteins, in amounts compatible with functional and structural studies. This chapter describes a set of robust methodologies routinely used for the successful expression of a variety of EMPs, going from yeast transformation with the recombinant plasmid to the analysis of the quality and quantity of the proteins produced.journal article2016importe

Neurodegenerative phagocytes mediate synaptic stripping in Neuro-HIV.

Glial cell activation is a hallmark of several neurodegenerative and neuroinflammatory diseases. During HIV infection, neuroinflammation is associated with cognitive impairment, even during sustained long-term suppressive antiretroviral therapy. However, the cellular subsets contributing to neuronal damage in the CNS during HIV infection remain unclear. Using post-mortem brain samples from eight HIV patients and eight non-neurological disease controls, we identify a subset of CNS phagocytes highly enriched in LGALS3, CTSB, GPNMB and HLA-DR, a signature identified in the context of ageing and neurodegeneration. In HIV patients, the presence of this phagocyte phenotype was associated with synaptic stripping, suggesting an involvement in the pathogenesis of HIV-associated neurocognitive disorder. Taken together, our findings elucidate some of the molecular signatures adopted by CNS phagocytes in HIV-positive patients and contribute to the understanding of how HIV might pave the way to other forms of cognitive decline in ageing HIV patient populations

Increasing cell biomass in Saccharomyces cerevisiae increases recombinant protein yield: the use of a respiratory strain as a microbial cell factory

<p>Abstract</p> <p>Background</p> <p>Recombinant protein production is universally employed as a solution to obtain the milligram to gram quantities of a given protein required for applications as diverse as structural genomics and biopharmaceutical manufacture. Yeast is a well-established recombinant host cell for these purposes. In this study we wanted to investigate whether our respiratory <it>Saccharomyces cerevisiae </it>strain, TM6*, could be used to enhance the productivity of recombinant proteins over that obtained from corresponding wild type, respiro-fermentative strains when cultured under the same laboratory conditions.</p> <p>Results</p> <p>Here we demonstrate at least a doubling in productivity over wild-type strains for three recombinant membrane proteins and one recombinant soluble protein produced in TM6* cells. In all cases, this was attributed to the improved biomass properties of the strain. The yield profile across the growth curve was also more stable than in a wild-type strain, and was not further improved by lowering culture temperatures. This has the added benefit that improved yields can be attained rapidly at the yeast's optimal growth conditions. Importantly, improved productivity could not be reproduced in wild-type strains by culturing them under glucose fed-batch conditions: despite having achieved very similar biomass yields to those achieved by TM6* cultures, the total volumetric yields were not concomitantly increased. Furthermore, the productivity of TM6* was unaffected by growing cultures in the presence of ethanol. These findings support the unique properties of TM6* as a microbial cell factory.</p> <p>Conclusions</p> <p>The accumulation of biomass in yeast cell factories is not necessarily correlated with a proportional increase in the functional yield of the recombinant protein being produced. The respiratory <it>S. cerevisiae </it>strain reported here is therefore a useful addition to the matrix of production hosts currently available as its improved biomass properties do lead to increased volumetric yields without the need to resort to complex control or cultivation schemes. This is anticipated to be of particular value in the production of challenging targets such as membrane proteins.</p

Identification of a novel protein-protein interaction motif mediating interaction of GPCR-associated sorting proteins with G protein-coupled receptors

<div><p>GPCR desensitization and down-regulation are considered key molecular events underlying the development of tolerance <i>in vivo</i>. Among the many regulatory proteins that are involved in these complex processes, GASP-1 have been shown to participate to the sorting of several receptors toward the degradation pathway. This protein belongs to the recently identified GPCR-associated sorting proteins (GASPs) family that comprises ten members for which structural and functional details are poorly documented. We present here a detailed structure–function relationship analysis of the molecular interaction between GASPs and a panel of GPCRs. In a first step, GST-pull down experiments revealed that all the tested GASPs display significant interactions with a wide range of GPCRs. Importantly, the different GASP members exhibiting the strongest interaction properties were also characterized by the presence of a small, highly conserved and repeated “GASP motif” of 15 amino acids. We further showed using GST-pull down, surface plasmon resonance and co-immunoprecipitation experiments that the central domain of GASP-1, which contains 22 GASP motifs, is essential for the interaction with GPCRs. We then used site directed mutagenesis and competition experiments with synthetic peptides to demonstrate that the GASP motif, and particularly its highly conserved core sequence SWFW, is critically involved in the interaction with GPCRs. Overall, our data show that several members of the GASP family interact with GPCRs and highlight the presence within GASPs of a novel protein-protein interaction motif that might represent a new target to investigate the involvement of GASPs in the modulation of the activity of GPCRs.</p> </div

Characterizing Interdisciplinarity of Researchers and Research Topics Using Web Search Engines

Researchers' networks have been subject to active modeling and analysis. Earlier literature mostly focused on citation or co-authorship networks reconstructed from annotated scientific publication databases, which have several limitations. Recently, general-purpose web search engines have also been utilized to collect information about social networks. Here we reconstructed, using web search engines, a network representing the relatedness of researchers to their peers as well as to various research topics. Relatedness between researchers and research topics was characterized by visibility boost-increase of a researcher's visibility by focusing on a particular topic. It was observed that researchers who had high visibility boosts by the same research topic tended to be close to each other in their network. We calculated correlations between visibility boosts by research topics and researchers' interdisciplinarity at individual level (diversity of topics related to the researcher) and at social level (his/her centrality in the researchers' network). We found that visibility boosts by certain research topics were positively correlated with researchers' individual-level interdisciplinarity despite their negative correlations with the general popularity of researchers. It was also found that visibility boosts by network-related topics had positive correlations with researchers' social-level interdisciplinarity. Research topics' correlations with researchers' individual- and social-level interdisciplinarities were found to be nearly independent from each other. These findings suggest that the notion of "interdisciplinarity" of a researcher should be understood as a multi-dimensional concept that should be evaluated using multiple assessment means.Comment: 20 pages, 7 figures. Accepted for publication in PLoS On

Translation of evidence-based Assistive Technologies into stroke rehabilitation: Users' perceptions of the barriers and opportunities

Background: Assistive Technologies (ATs), defined as "electrical or mechanical devices designed to help people recover movement", demonstrate clinical benefits in upper limb stroke rehabilitation; however translation into clinical practice is poor. Uptake is dependent on a complex relationship between all stakeholders. Our aim was to understand patients', carers' (P&Cs) and healthcare professionals' (HCPs) experience and views of upper limb rehabilitation and ATs, to identify barriers and opportunities critical to the effective translation of ATs into clinical practice. This work was conducted in the UK, which has a state funded healthcare system, but the findings have relevance to all healthcare systems. Methods. Two structurally comparable questionnaires, one for P&Cs and one for HCPs, were designed, piloted and completed anonymously. Wide distribution of the questionnaires provided data from HCPs with experience of stroke rehabilitation and P&Cs who had experience of stroke. Questionnaires were designed based on themes identified from four focus groups held with HCPs and P&Cs and piloted with a sample of HCPs (N = 24) and P&Cs (N = 8). Eight of whom (four HCPs and four P&Cs) had been involved in the development. Results: 292 HCPs and 123 P&Cs questionnaires were analysed. 120 (41%) of HCP and 79 (64%) of P&C respondents had never used ATs. Most views were common to both groups, citing lack of information and access to ATs as the main reasons for not using them. Both HCPs (N = 53 [34%]) and P&C (N = 21 [47%]) cited Functional Electrical Stimulation (FES) as the most frequently used AT. Research evidence was rated by HCPs as the most important factor in the design of an ideal technology, yet ATs they used or prescribed were not supported by research evidence. P&Cs rated ease of set-up and comfort more highly. Conclusion: Key barriers to translation of ATs into clinical practice are lack of knowledge, education, awareness and access. Perceptions about arm rehabilitation post-stroke are similar between HCPs and P&Cs. Based on our findings, improvements in AT design, pragmatic clinical evaluation, better knowledge and awareness and improvement in provision of services will contribute to better and cost-effective upper limb stroke rehabilitation. © 2014 Hughes et al.; licensee BioMed Central Ltd

Detailed spectral and morphological analysis of the shell type SNR RCW 86

Aims: We aim for an understanding of the morphological and spectral properties of the supernova remnant RCW~86 and for insights into the production mechanism leading to the RCW~86 very high-energy gamma-ray emission. Methods: We analyzed High Energy Spectroscopic System data that had increased sensitivity compared to the observations presented in the RCW~86 H.E.S.S. discovery publication. Studies of the morphological correlation between the 0.5-1~keV X-ray band, the 2-5~keV X-ray band, radio, and gamma-ray emissions have been performed as well as broadband modeling of the spectral energy distribution with two different emission models. Results:We present the first conclusive evidence that the TeV gamma-ray emission region is shell-like based on our morphological studies. The comparison with 2-5~keV X-ray data reveals a correlation with the 0.4-50~TeV gamma-ray emission.The spectrum of RCW~86 is best described by a power law with an exponential cutoff at $E_{cut}=(3.5\pm 1.2_{stat})$ TeV and a spectral index of $\Gamma$~$1.6\pm 0.2$. A static leptonic one-zone model adequately describes the measured spectral energy distribution of RCW~86, with the resultant total kinetic energy of the electrons above 1 GeV being equivalent to $\sim$0.1\% of the initial kinetic energy of a Type I a supernova explosion. When using a hadronic model, a magnetic field of $B$~100$\mu$G is needed to represent the measured data. Although this is comparable to formerly published estimates, a standard E$^{-2}$ spectrum for the proton distribution cannot describe the gamma-ray data. Instead, a spectral index of $\Gamma_p$~1.7 would be required, which implies that ~$7\times 10^{49}/n_{cm^{-3}}$erg has been transferred into high-energy protons with the effective density $n_{cm^{-3}}=n/ 1$ cm^-3. This is about 10\% of the kinetic energy of a typical Type Ia supernova under the assumption of a density of 1~cm^-3.Comment: accepted for publication by A&

Characterizing the gamma-ray long-term variability of PKS 2155-304 with H.E.S.S. and Fermi-LAT

Studying the temporal variability of BL Lac objects at the highest energies provides unique insights into the extreme physical processes occurring in relativistic jets and in the vicinity of super-massive black holes. To this end, the long-term variability of the BL Lac object PKS 2155-304 is analyzed in the high (HE, 100 MeV 200 GeV) gamma-ray domain. Over the course of ~9 yr of H.E.S.S observations the VHE light curve in the quiescent state is consistent with a log-normal behavior. The VHE variability in this state is well described by flicker noise (power-spectral-density index {\ss}_VHE = 1.10 +0.10 -0.13) on time scales larger than one day. An analysis of 5.5 yr of HE Fermi LAT data gives consistent results ({\ss}_HE = 1.20 +0.21 -0.23, on time scales larger than 10 days) compatible with the VHE findings. The HE and VHE power spectral densities show a scale invariance across the probed time ranges. A direct linear correlation between the VHE and HE fluxes could neither be excluded nor firmly established. These long-term-variability properties are discussed and compared to the red noise behavior ({\ss} ~ 2) seen on shorter time scales during VHE-flaring states. The difference in power spectral noise behavior at VHE energies during quiescent and flaring states provides evidence that these states are influenced by different physical processes, while the compatibility of the HE and VHE long-term results is suggestive of a common physical link as it might be introduced by an underlying jet-disk connection.Comment: 11 pages, 16 figure