Stabilisation of Na,K-ATPase structure by the cardiotonic steroid ouabain

Cardiotonic steroids such as ouabain bind with high affinity to the membrane-bound cation-transporting P-type Na,K-ATPase, leading to complete inhibition of the enzyme. Using synchrotron radiation circular dichroism we show that the enzyme-ouabain complex is less susceptible to thermal denaturation (unfolding) than the ouabain-free enzyme, and this protection is observed with Na,K-ATPase purified from pig kidney as well as from shark rectal glands. It is also shown that detergent-solubilised preparations of Na,K-ATPase are stabilised by ouabain, which could account for the successful crystallisation of Na,K-ATPase in the ouabain-bound form. The secondary structure is not significantly affected by the binding of ouabain. Ouabain appears however, to induce a reorganization of the tertiary structure towards a more compact protein structure which is less prone to unfolding; recent crystal structures of the two enzymes are consistent with this interpretation. These circular dichroism spectroscopic studies in solution therefore provide complementary information to that provided by crystallography

Tunneling of polarized fermions in 3D double wells

We study the tunneling of a spin polarized Fermi gas in a three-dimensional double well potential, focusing on the time dynamics starting from an initial state in which there is an imbalance in the number of particles in the two wells. Although fermions in different doublets of the double well tunnel with different frequencies, we point out that (incoherent) oscillations of a large number of particles can arise, as a consequence of the presence of transverse degrees of freedom. Estimates of the doublet structure and of the occupation of transverse eigenstates for a realistic experimental setup are provided.Comment: 10 pages, Typos corrected and figures changed - published in Laser Physics, issue on the LPHYS'11 conference (Sarajevo, 2011

Spatial coherence of room-temperature monolayer WSe2_2 exciton-polaritons in a trap

The emergence of spatial and temporal coherence of light emitted from solid-state systems is a fundamental phenomenon, rooting in a plethora of microscopic processes. It is intrinsically aligned with the control of light-matter coupling, and canonical for laser oscillation. However, it also emerges in the superradiance of multiple, phase-locked emitters, and more recently, coherence and long-range order have been investigated in bosonic condensates of thermalized light, as well as in exciton-polaritons driven to a ground state via stimulated scattering. Here, we experimentally show that the interaction between photons in a Fabry-Perot microcavity and excitons in an atomically thin WSe$_2$ layer is sufficient such that the system enters the hybridized regime of strong light-matter coupling at ambient conditions. Via Michelson interferometry, we capture clear evidence of increased spatial and temporal coherence of the emitted light from the spatially confined system ground-state. The coherence build-up is accompanied by a threshold-like behaviour of the emitted light intensity, which is a fingerprint of a polariton laser effect. Valley-physics is manifested in the presence of an external magnetic field, which allows us to manipulate K and K' polaritons via the Valley-Zeeman-effect. Our findings are of high application relevance, as they confirm the possibility to use atomically thin crystals as simple and versatile components of coherent light-sources, and in valleytronic applications at room temperature.Comment: 13 pages, 4 figure

Electron spin resonance in membrane research: protein–lipid interactions from challenging beginnings to state of the art

Conventional electron paramagnetic resonance (EPR) spectra of lipids that are spin-labelled close to the terminal methyl end of the acyl chains are able to resolve the lipids directly contacting the protein from those in the fluid bilayer regions of the membrane. This allows determination of both the stoichiometry of lipid–protein interaction (i.e., number of lipid sites at the protein perimeter) and the selectivity of the protein for different lipid species (i.e., association constants relative to the background lipid). Spin-label EPR data are summarised for 20 or more different transmembrane peptides and proteins, and 7 distinct species of lipids. Lineshape simulations of the two-component conventional spin-label EPR spectra allow estimation of the rate at which protein-associated lipids exchange with those in the bulk fluid regions of the membrane. For lipids that do not display a selectivity for the protein, the intrinsic off-rates for exchange are in the region of 10 MHz: less than 10× slower than the rates of diffusive exchange in fluid lipid membranes. Lipids with an affinity for the protein, relative to the background lipid, have off-rates for leaving the protein that are correspondingly slower. Non-linear EPR, which depends on saturation of the spectrum at high radiation intensities, is optimally sensitive to dynamics on the timescale of spin-lattice relaxation, i.e., the microsecond regime. Both progressive saturation and saturation transfer EPR experiments provide definitive evidence that lipids at the protein interface are exchanging on this timescale. The sensitivity of non-linear EPR to low frequencies of spin exchange also allows the location of spin-labelled membrane protein residues relative to those of spin-labelled lipids, in double-labelling experiments

The words leader/líder and their resonances in an Italo-Latin American multinational corporation

© 2017, © The Author(s) 2017. The problems of ‘lost in translation’ are well known. Yet some terms of English managerial vocabulary, which are perfectly translatable in other languages, remain untranslated. One explanation of this phenomenon is what Linguistic anthropology call negative semantic resonances. Semantic resonances focused on the issue of which meanings can or cannot be expressed by a single word in different cultures. In this paper, based on an organisational ethnography of Latin American expatriates working for an Italo-Latin-American multinational corporation (Tubworld), we analyse the resonances of the word leader/líder and director, direttore, capo, guida, coordinador, caudillo among a group of expatriates; all Italian, Spanish or multilingual speakers who use English as a second language in their everyday interactions. The paper explains how the different uses contribute to create a meaning of what a leader should and should not be; someone who leads without leading, sometimes a manager. The authors, an Italian native speaker who learnt Spanish during childhood and use English as his everyday language and a Spanish native speaker, argue that Italian or Spanish speakers not only avoid the words duce and caudillo (the vernacular vocabulary for leader, not in use due to the political and cultural meaning) but also the word leader/líder itself, as it resonate to the other two (violent, authoritarian, autocratic, antidemocratic leadership) but furthermore because the word, a lexical loan from English, failed to encapsulate the complexity of leading multilingual organisations like Tubworld

Increased Prevalence of Metabolic Syndrome in Patients with Acne Inversa

BACKGROUND: Acne inversa (AI; also designated as Hidradenitis suppurativa) is a common chronic inflammatory skin disease, localized in the axillary, inguinal and perianal skin areas that causes painful, fistulating sinuses with malodorous purulence and scars. Several chronic inflammatory diseases are associated with the metabolic syndrome and its consequences including arteriosclerosis, coronary heart disease, myocardial infraction, and stroke. So far, the association of AI with systemic metabolic alterations is largely unexplored. METHODS AND FINDINGS: A hospital-based case-control study in 80 AI patients and 100 age- and sex-matched control participants was carried out. The prevalence of central obesity (odds ratio 5.88), hypertriglyceridemia (odds ratio 2.24), hypo-HDL-cholesterolemia (odds ratio 4.56), and hyperglycemia (odds ratio 4.09) in AI patients was significantly higher than in controls. Furthermore, the metabolic syndrome, previously defined as the presence of at least three of the five alterations listed above, was more common in those patients compared to controls (40.0% versus 13.0%; odds ratio 4.46, 95% confidence interval 2.02 to 9.96; P<0.001). AI patients with metabolic syndrome also had more pronounced metabolic alterations than controls with metabolic syndrome. Interestingly, there was no correlation between the severity or duration of the disease and the levels of respective parameters or the number of criteria defining the metabolic syndrome. Rather, the metabolic syndrome was observed in a disproportionately high percentage of young AI patients. CONCLUSIONS: This study shows for the first time that AI patients have a high prevalence of the metabolic syndrome and all of its criteria. It further suggests that the inflammation present in AI patients does not have a major impact on the development of metabolic alterations. Instead, evidence is given for a role of metabolic alterations in the development of AI. We recommend monitoring of AI patients in order to correct their modifiable cardiovascular risk factors

A method for detergent-free isolation of membrane proteins in their local lipid environment.

Despite the great importance of membrane proteins, structural and functional studies of these proteins present major challenges. A significant hurdle is the extraction of the functional protein from its natural lipid membrane. Traditionally achieved with detergents, purification procedures can be costly and time consuming. A critical flaw with detergent approaches is the removal of the protein from the native lipid environment required to maintain functionally stable protein. This protocol describes the preparation of styrene maleic acid (SMA) co-polymer to extract membrane proteins from prokaryotic and eukaryotic expression systems. Successful isolation of membrane proteins into SMA lipid particles (SMALPs) allows the proteins to remain with native lipid, surrounded by SMA. We detail procedures for obtaining 25 g of SMA (4 d); explain the preparation of protein-containing SMALPs using membranes isolated from Escherichia coli (2 d) and control protein-free SMALPS using E. coli polar lipid extract (1-2 h); investigate SMALP protein purity by SDS-PAGE analysis and estimate protein concentration (4 h); and detail biophysical methods such as circular dichroism (CD) spectroscopy and sedimentation velocity analytical ultracentrifugation (svAUC) to undertake initial structural studies to characterize SMALPs (∼2 d). Together, these methods provide a practical tool kit for those wanting to use SMALPs to study membrane proteins

The impact of diabetes on the pathogenesis of sepsis

Diabetes is associated with an increased susceptibility to infection and sepsis. Conflicting data exist on whether the mortality of patients with sepsis is influenced by the presence of diabetes, fuelling the ongoing debate on the benefit of tight glucose regulation in patients with sepsis. The main reason for which diabetes predisposes to infection appears to be abnormalities of the host response, particularly in neutrophil chemotaxis, adhesion and intracellular killing, defects that have been attributed to the effect of hyperglycaemia. There is also evidence for defects in humoral immunity, and this may play a larger role than previously recognised. We review the literature on the immune response in diabetes and its potential contribution to the pathogenesis of sepsis. In addition, the effect of diabetes treatment on the immune response is discussed, with specific reference to insulin, metformin, sulphonylureas and thiazolidinediones

The "Statinth" wonder of the world: a panacea for all illnesses or a bubble about to burst

After the introduction of statins in the market as effective lipid lowering agents, they were shown to have effects other than lipid lowering. These actions were collectively referred to as 'pleiotropic actions of statins.' Pleiotropism of statins formed the basis for evaluating statins for several indications other than lipid lowering. Evidence both in favour and against is available for several of these indications. The current review attempts to critically summarise the available data for each of these indications