The alpha 1/beta 1 and alpha 6/beta 1 integrin heterodimers mediate cell attachment to distinct sites on laminin.

This study was undertaken to determine the roles of individual alpha/beta 1 integrin heterodimers in promoting cellular interactions with the different attachment-promoting domains of laminin (LN). To do this, antibodies to the integrin beta 1 subunit or to specific integrin alpha subunits were tested for effects on cell attachment to LN, to elastase fragments E1-4 and E1, derived from the short arms and core of LN's cruciform structure, and to fragment E8 derived from the long arm of this structure. The human JAR choriocarcinoma cells used in this study attached to LN and to fragments E1 and E8. Attachment to E1-4 required a much higher substrate coating concentration, suggesting that it is a poor substrate for JAR cell attachment. The ability of cells to attach to different LN domains suggested the presence of more than one LN receptor. These multiple LN receptors were shown to be beta 1 integrin heterodimers because antibodies to the integrin beta 1 subunit inhibited attachment of JAR cells to LN and its three fragments. To identify the individual integrin alpha/beta 1 heterodimers that mediate interactions with these LN domains, mAbs specific for individual beta 1 heterodimers in human cells were used to study JAR cell interactions with LN and its fragments. An anti-alpha 6/beta 1-specific mAb, GoH3, virtually eliminated cell attachment to E8 and partially inhibited attachment to E1 and intact LN. Thus the major alpha 6/beta 1 attachment domain is present in fragment E8. An alpha 1/beta 1-specific mAb (S2G3) strongly inhibited cell attachment to collagen IV and partially inhibited JAR attachment to LN fragment E1. Thus, the alpha 1/beta 1 heterodimer is a dual receptor for collagen IV and LN, interacting with LN at a site in fragment E1. In combination, the anti-alpha 1- and anti-alpha 6-specific antibodies completely inhibited JAR cell attachment to LN and fragment E1. Thus, the alpha 1/beta 1 and alpha 6/beta 1 integrin heterodimers each function as LN receptors and act together to mediate the interactions of human JAR choriocarcinoma cells with LN

A differential identity for Green functions

If P is a differential operator with constant coefficients, an identity is derived to calculate the action of exp(P) on the product of two functions. In many-body theory, P describes the interaction Hamiltonian and the identity yields a hierarchy of Green functions. The identity is first derived for scalar fields and the standard hierarchy is recovered. Then the case of fermions is considered and the identity is used to calculate the generating function for the Green functions of an electron system in a time-dependent external potential.Comment: 14 page

Drain current multiplication in thin pillar vertical MOSFETs due to depletion isolation and charge coupling

Drain current multiplication in vertical MOSFETs due to body isolation by the drain depletion region and gate–gate charge coupling is investigated at pillar thicknesses in the range of 200–10 nm. For pillar thickness >120 nm depletion isolation does not occur and hence the body contact is found to be completely effective with no multiplication in drain current, whereas for pillar thicknesses <60 nm depletion isolation occurs for all drain biases and hence the body contact is ineffective. For intermediate pillar thicknesses of 60–120 nm, even though depletion isolation is apparent, the body contact is still effective in improving floating body effects and breakdown. At these intermediate pillar thicknesses, a kink is also observed in the output characteristics due to partial depletion isolation. The charging kink and the breakdown behavior are characterized as a function of pillar thickness, and a transition in the transistor behavior is seen at a pillar thickness of 60 nm. For pillar thickness greater than 60 nm, the voltage at which body charging occurs decreases (and the normalized breakdown current increases) with decreasing pillar thickness, whereas for pillar thickness less than 60 nm, the opposite trend is seen. The relative contributions to the drain current of depletion isolation and the inherent gate–gate charge coupling are quantified. For pillar thickness between 120 and 80 nm, the rise in the drain current is found to be mainly due to depletion isolation, whereas for pillar thicknesses <60 nm, the increase in the drain current is found to be governed by the inherent gate–gate charge coupling

Encounter complexes and dimensionality reduction in protein-protein association

An outstanding challenge has been to understand the mechanism whereby proteins associate. We report here the results of exhaustively sampling the conformational space in protein–protein association using a physics-based energy function. The agreement between experimental intermolecular paramagnetic relaxation enhancement (PRE) data and the PRE profiles calculated from the docked structures shows that the method captures both specific and non-specific encounter complexes. To explore the energy landscape in the vicinity of the native structure, the nonlinear manifold describing the relative orientation of two solid bodies is projected onto a Euclidean space in which the shape of low energy regions is studied by principal component analysis. Results show that the energy surface is canyon-like, with a smooth funnel within a two dimensional subspace capturing over 75% of the total motion. Thus, proteins tend to associate along preferred pathways, similar to sliding of a protein along DNA in the process of protein-DNA recognition

Multi-elemental composition of authigenic carbonates in benthic foraminifera from the eastern Bering Sea continental margin (International Ocean Discovery Program Site U1343)

This is the final version. Available from Elsevier via the DOI in this record. Bering Sea sediments represent exceptional archives, offering the potential to study past climates and biogeochemistry at a high resolution. However, abundant hydrocarbons of microbial origin, especially along the eastern Bering Sea continental margin, can hinder the applicability of palaeoceanographic proxies based on calcareous foraminifera, due to the formation of authigenic carbonates. Nonetheless, authigenic carbonates may also bear unique opportunities to reconstruct changes in the sedimentary redox environment. Here we use a suite of visual and geochemical evidence from single-specimens of the shallow infaunal benthic foraminiferal species Elphidium batialis Saidova (1961), recovered from International Ocean Discovery Program (IODP) Site U1343 in the eastern Bering Sea, to investigate the influence of authigenic carbonates on the foraminiferal trace metal composition. Our results demonstrate that foraminiferal calcite tests act as a nucleation template for secondary carbonate precipitation, altering their geochemistry where organoclastic sulphate reduction and anaerobic oxidation of methane cause the formation of low- and high-Mg calcite, respectively. The authigenic carbonates can occur as encrusting on the outside and/or inside of foraminiferal tests, in the form of recrystallization of the test wall, or as banding along natural laminations within the foraminiferal test walls. In addition to Mg, authigenic carbonates are enriched in U/Ca, Mn/Ca, Fe/Ca, and Sr/Ca, depending on the redox environment that they were formed in. Our results demonstrate that site-specific U/Ca thresholds are a promising tool to distinguish between diagenetically altered and pristine foraminiferal samples, important for palaeoceanographic reconstructions utilising the primary foraminiferal geochemistry. Consistent with previous studies, U/Mn ratios of foraminifera at IODP Site U1343 increase according to their degree of diagenetic alteration, suggesting a potential response of authigenic U/Mn to the microbial activity in turn linked to the sedimentary redox environment.BGS University Funding Initiative Ph.D. studentshi

On structural physical approximations and entanglement breaking maps

Very recently a conjecture saying that the so-called structural physical approximations (SPAa) to optimal positive maps (optimal entanglement witnesses) give entanglement breaking (EB) maps (separable states) has been posed [J. K. Korbicz {\it et al.}, Phys. Rev. A {\bf 78}, 062105 (2008)]. The main purpose of this contribution is to explore this subject. First, we extend the set of entanglement witnesses (EWs) supporting the conjecture. Then, we ask if SPAs constructed from other than the depolarizing channel maps also lead to EB maps and show that in general this is not the case. On the other hand, we prove an interesting fact that for any positive map $\Lambda$ there exists an EB channel $\Phi$ such that the SPA of $\Lambda$ constructed with the aid of $\Phi$ is again an EB channel. Finally, we ask similar questions in the case of continuous variable systems. We provide a simple way of construction of SPA and prove that in the case of the transposition map it gives EB channel.Comment: 22 pages, improved version, accepted by Journal of Physics

Not just fat: investigating the proteome of cetacean blubber tissue

Mammalian adipose tissue is increasingly being recognized as an endocrine organ involved in the regulation of a number of metabolic processes and pathways. It responds to signals from different hormone systems and the central nervous system, and expresses a variety of protein factors with important paracrine and endocrine functions. This study presents a first step towards the systematic analysis of the protein content of cetacean adipose tissue, the blubber, in order to investigate the kinds of proteins present and their relative abundance. Full depth blubber subsamples were collected from dead-stranded harbour porpoises (Phocoena phocoena) (n = 21). Three total protein extraction methods were trialled, and the highest total protein yields with the lowest extraction variability were achieved using a RIPA cell lysis and extraction buffer based protocol. Extracted proteins were separated using 1D Sodium Dodecyl Sulphate Polyacrylamide Gel Electrophoresis (SDS-PAGE), and identified using nanoflow Liquid Chromatography Electrospray Ionization in tandem with Mass Spectrometry (nLC-ESI–MS/MS). A range of proteins were identified (n = 295) and classed into eight functional groups, the most abundant of which were involved in cell function and metabolism (45%), immune response and inflammation (15%) and lipid metabolism (11%). These proteins likely originate both from the various cell types within the blubber tissue itself, and from the circulation. They therefore have the potential to capture information on the cellular and physiological stresses experienced by individuals at the time of sampling. The importance of this proteomic approach is two-fold: Firstly, it could help to assign novel functions to marine mammal blubber in keeping with current understanding of the multi-functional role of adipose tissue in other mammals. Secondly, it could lead to the development of a suite of biomarkers to better monitor the physiological state and health of live individuals though remote blubber biopsy sampling

A pragmatic randomised controlled trial of hydrotherapy and land exercises on overall well being and quality of life in rheumatoid arthritis

Background \ud Hydrotherapy is highly valued by people with rheumatoid arthritis yet few studies have compared the benefits of exercises in heated water against exercises on land. In particular, data on quality of life is rarely reported. This is especially important because patients treated with hydrotherapy often report an enhanced sense of well-being. We report a randomised controlled trial in which we compared the effects of hydrotherapy with exercises on land on overall response to treatment, physical function and quality of life in patients with rheumatoid arthritis. \ud \ud Methods \ud One hundred and fifteen patients with RA were randomised to receive a weekly 30-minute session of hydrotherapy or similar exercises on land for 6 weeks. Our primary outcome was a self-rated global impression of change – a measure of treatment effect on a 7-point scale ranging from 1(very much worse) to 7 (very much better) assessed immediately on completion of treatment. Secondary outcomes including EuroQol health related quality of life, EuroQol health status valuation, HAQ, 10 metre walk time and pain scores were collected at baseline, after treatment and 3 months later. Binary outcomes were analysed by Fisher's exact test and continuous variables by Wilcoxon or Mann-Whitney tests. \ud \ud Results \ud Baseline characteristics of the two groups were comparable. Significantly more patients treated with hydrotherapy (40/46, 87%) were much better or very much better than the patients treated with land exercise (19/40, 47.5%), p < 0.001 Fisher's exact test. Eleven patients allocated land exercise failed to complete treatment compared with 4 patients allocated hydrotherapy (p = 0.09). Sensitivity analyses confirmed an advantage for hydrotherapy if we assumed non-completers would all not have responded (response rates 70% versus 38%; p < 0.001) or if we assumed that non-completers would have had the same response as completers (response rates 82% versus 55% p = 0.002). Ten metre walk time improved after treatment in both cases (median pre-treatment time for both groups combined 10.9 seconds, post-treatment 9.1 s, and 3 months later 9.6 s). There was however no difference between treatment groups. Similarly there were no significant differences between groups in terms of changes to HAQ, EQ-5D utility score, EQ VAS and pain VAS. \ud \ud Conclusion \ud Patients with RA treated with hydrotherapy are more likely to report feeling much better or very much better than those treated with land exercises immediately on completion of the treatment programme. This perceived benefit was not reflected by differences between groups in 10-metre walk times, functional scores, quality of life measures and pain scores

Number of HIV-1 founder variants is determined by the recency of the source partner infection

During sexual transmission, the high genetic diversity of HIV-1 within an individual is frequently reduced to one founder variant that initiates infection. Understanding the drivers of this bottleneck is crucial to developing effective infection control strategies. Little is known about the importance of the source partner during this bottleneck. To test the hypothesis that the source partner affects the number of HIV founder variants, we developed a phylodynamic model calibrated using genetic and epidemiological data on all existing transmission pairs for whom the direction of transmission and the infection stage of the source partner are known. Our results suggest that acquiring infection from someone in the acute (early) stage of infection increases the risk of multiple-founder variant transmission compared with acquiring infection from someone in the chronic (later) stage of infection. This study provides the first direct test of source partner characteristics to explain the low frequency of multiple-founder strain infections