Impairment experiences, identity and attitudes towards genetic screening : the views of people with Spinal Muscular Atrophy

Developments in genetics are rapidly changing the capacity and scope of screening practices. However, people with genetic conditions have been under-represented in the literature exploring their implications. This mixed methods study explores the attitudes of people with Spinal Muscular Atrophy (SMA) towards three different population-level genetic screening programmes for SMA: pre-conception, prenatal and newborn. Drawing on qualitative interviews (n= 15) and a survey (n=82), this study demonstrates that more severely affected individuals with early-onset symptoms (Type II SMA), are less likely to support screening and more likely to view SMA positively than those with milder, later onset and/or fluctuating symptoms (Types III/ IV SMA). Indeed, this clinically milder group were more likely to support all forms of screening and view SMA negatively. This paper highlights that screening is a complex issue for people with genetic conditions, and the nature of impairment experiences plays a critical role in shaping attitudes

Superconducting spintronics

The interaction between superconducting and spin-polarized orders has recently emerged as a major research field following a series of fundamental breakthroughs in charge transport in superconductor-ferromagnet heterodevices which promise new device functionality. Traditional studies which combine spintronics and superconductivity have mainly focused on the injection of spin-polarized quasiparticles into superconducting materials. However, a complete synergy between superconducting and magnetic orders turns out to be possible through the creation of spin-triplet Cooper pairs which are generated at carefully engineered superconductor interfaces with ferromagnetic materials. Currently, there is intense activity focused on identifying materials combinations which merge superconductivity and spintronics in order to enhance device functionality and performance. The results look promising: it has been shown, for example, that superconducting order can greatly enhance central effects in spintronics such as spin injection and magnetoresistance. Here, we review the experimental and theoretical advances in this field and provide an outlook for upcoming challenges related to the new concept of superconducting spintronics.J.L. was supported by the Research Council of Norway, Grants No. 205591 and 216700. J.W.A.R. was supported by the UK Royal Society and the Leverhulme Trust through an International Network Grant (IN-2013-033).This is the accepted manuscript. The final version is available at http://www.nature.com/nphys/journal/v11/n4/full/nphys3242.html

Who Benefits Most from a University Degree?: A Cross-National Comparison of Selection and Wage Returns in the US, UK, and Germany

Recent research on economic returns to higher education in the United States suggests that those with the highest wage returns to a college degree are least likely to obtain one. We extend the study of heterogeneous returns to tertiary education across multiple institutional contexts, investigating how the relationship between wage returns and the propensity to complete a degree varies by the level of expansion, differentiation, and cost of higher education. Drawing on panel data and matching techniques, we compare findings from the US with selection into degree completion in Germany and the UK. Contrary to previous studies, we find little evidence for population level heterogeneity in economic returns to higher education

Competing Activities of Heterotrimeric G Proteins in Drosophila Wing Maturation

Drosophila genome encodes six alpha-subunits of heterotrimeric G proteins. The Gαs alpha-subunit is involved in the post-eclosion wing maturation, which consists of the epithelial-mesenchymal transition and cell death, accompanied by unfolding of the pupal wing into the firm adult flight organ. Here we show that another alpha-subunit Gαo can specifically antagonize the Gαs activities by competing for the Gβ13F/Gγ1 subunits of the heterotrimeric Gs protein complex. Loss of Gβ13F, Gγ1, or Gαs, but not any other G protein subunit, results in prevention of post-eclosion cell death and failure of the wing expansion. However, cell death prevention alone is not sufficient to induce the expansion defect, suggesting that the failure of epithelial-mesenchymal transition is key to the folded wing phenotypes. Overactivation of Gαs with cholera toxin mimics expression of constitutively activated Gαs and promotes wing blistering due to precocious cell death. In contrast, co-overexpression of Gβ13F and Gγ1 does not produce wing blistering, revealing the passive role of the Gβγ in the Gαs-mediated activation of apoptosis, but hinting at the possible function of Gβγ in the epithelial-mesenchymal transition. Our results provide a comprehensive functional analysis of the heterotrimeric G protein proteome in the late stages of Drosophila wing development

CX3CR1 Is Expressed by Human B Lymphocytes and Meditates CX3CL1 Driven Chemotaxis of Tonsil Centrocytes

Background: Fractalkine/CX(3)CL1, a surface chemokine, binds to CX(3)CR1 expressed by different lymphocyte subsets. Since CX(3)CL1 has been detected in the germinal centres of secondary lymphoid tissue, in this study we have investigated CX(3)CR1 expression and function in human naive, germinal centre and memory B cells isolated from tonsil or peripheral blood.Methodology/Principal Findings: We demonstrate unambiguously that highly purified human B cells from tonsil and peripheral blood expressed CX(3)CR1 at mRNA and protein levels as assessed by quantitative PCR, flow cytometry and competition binding assays. In particular, naive, germinal centre and memory B cells expressed CX(3)CR1 but only germinal centre B cells were attracted by soluble CX(3)CL1 in a transwell assay. CX(3)CL1 signalling in germinal centre B cells involved PI3K, Erk1/2, p38, and Src phosphorylation, as assessed by Western blot experiments. CX(3)CR1(+) germinal centre B cells were devoid of centroblasts and enriched for centrocytes that migrated to soluble CX(3)CL1. ELISA assay showed that soluble CX(3)CL1 was secreted constitutively by follicular dendritic cells and T follicular helper cells, two cell populations homing in the germinal centre light zone as centrocytes. At variance with that observed in humans, soluble CX(3)CL1 did not attract spleen B cells from wild type mice. OVA immunized CX(3)CR1-/- or CX(3)CL1-/- mice showed significantly decreased specific IgG production compared to wild type mice.Conclusion/Significance: We propose a model whereby human follicular dendritic cells and T follicular helper cells release in the light zone of germinal centre soluble CX(3)CL1 that attracts centrocytes. The functional implications of these results warrant further investigation

Ontogeny of Numerical Abilities in Fish

Background: It has been hypothesised that human adults, infants, and non-human primates share two non-verbal systems for enumerating objects, one for representing precisely small quantities (up to 3–4 items) and one for representing approximately larger quantities. Recent studies exploiting fish’s spontaneous tendency to join the larger group showed that their ability in numerical discrimination closely resembles that of primates but little is known as to whether these capacities are innate or acquired. Methodology/Principal Findings: We used the spontaneous tendency to join the larger shoal to study the limits of the quantity discrimination of newborn and juvenile guppies. One-day old fish chose the larger shoal when the choice was between numbers in the small quantity range, 2 vs. 3 fish, but not when they had to choose between large numbers, 4 vs. 8 or 4 vs. 12, although the numerical ratio was larger in the latter case. To investigate the relative role of maturation and experience in large number discrimination, fish were raised in pairs (with no numerical experience) or in large social groups and tested at three ages. Forty-day old guppies from both treatments were able to discriminate 4 vs. 8 fish while at 20 days this was only observed in fish grown in groups. Control experiments showed that these capacities were maintained after guppies were prevented from using non numerical perceptual variables that co-vary with numerosity. Conclusions/Significance: Overall, our results suggest the ability of guppies to discriminate small numbers is innate and i

Enhancement of Cell Membrane Invaginations, Vesiculation and Uptake of Macromolecules by Protonation of the Cell Surface

The different pathways of endocytosis share an initial step involving local inward curvature of the cell’s lipid bilayer. It has been shown that to generate membrane curvature, proteins or lipids enforce transversal asymmetry of the plasma membrane. Thus it emerges as a general phenomenon that transversal membrane asymmetry is the common required element for the formation of membrane curvature. The present study demonstrates that elevating proton concentration at the cell surface stimulates the formation of membrane invaginations and vesiculation accompanied by efficient uptake of macromolecules (Dextran-FITC, 70 kD), relative to the constitutive one. The insensitivity of proton induced uptake to inhibiting treatments and agents of the known endocytic pathways suggests the entry of macromolecules to proceeds via a yet undefined route. This is in line with the fact that neither ATP depletion, nor the lowering of temperature, abolishes the uptake process. In addition, fusion mechanism such as associated with low pH uptake of toxins and viral proteins can be disregarded by employing the polysaccharide dextran as the uptake molecule. The proton induced uptake increases linearly in the extracellular pH range of 6.5 to 4.5, and possesses a steep increase at the range of 4> pH>3, reaching a plateau at pH≤3. The kinetics of the uptake implies that the induced vesicles release their content to the cytosol and undergo rapid recycling to the plasma membrane. We suggest that protonation of the cell’s surface induces local charge asymmetries across the cell membrane bilayer, inducing inward curvature of the cell membrane and consequent vesiculation and uptake

Mitochondrial dysfunction and biogenesis: do ICU patients die from mitochondrial failure?

Mitochondrial functions include production of energy, activation of programmed cell death, and a number of cell specific tasks, e.g., cell signaling, control of Ca2+ metabolism, and synthesis of a number of important biomolecules. As proper mitochondrial function is critical for normal performance and survival of cells, mitochondrial dysfunction often leads to pathological conditions resulting in various human diseases. Recently mitochondrial dysfunction has been linked to multiple organ failure (MOF) often leading to the death of critical care patients. However, there are two main reasons why this insight did not generate an adequate resonance in clinical settings. First, most data regarding mitochondrial dysfunction in organs susceptible to failure in critical care diseases (liver, kidney, heart, lung, intestine, brain) were collected using animal models. Second, there is no clear therapeutic strategy how acquired mitochondrial dysfunction can be improved. Only the benefit of such therapies will confirm the critical role of mitochondrial dysfunction in clinical settings. Here we summarized data on mitochondrial dysfunction obtained in diverse experimental systems, which are related to conditions seen in intensive care unit (ICU) patients. Particular attention is given to mechanisms that cause cell death and organ dysfunction and to prospective therapeutic strategies, directed to recover mitochondrial function. Collectively the data discussed in this review suggest that appropriate diagnosis and specific treatment of mitochondrial dysfunction in ICU patients may significantly improve the clinical outcome

Measurement of the average time-integrated mixing probability of b-flavored hadrons produced at the Fermilab Tevatron

We have measured the number of like-sign (LS) and opposite-sign (OS) lepton pairs arising from double semileptonic decays of b and (b) over bar hadrons, pair produced at the Fermilab Tevatron collider. The data samples were collected with the Collider Detector at Fermilab during the 1992-1995 collider run by triggering on the existence of mumu or emu candidates in an event. The observed ratio of LS to OS dileptons leads to a measurement of the average time-integrated mixing probability of all produced b-flavored hadrons which decay weakly, (χ) over bar =0.152+/-0.007 (stat)+/-0.011 (syst), that is significantly larger than the world average (χ) over bar =0.118+/-0.005