The spatial effect of protein deuteration on nitroxide spin-label relaxation:implications for EPR distance measurement

This work was supported by a Wellcome Trust Senior Fellowship (095062) to T.O.-H. The Authors would also like to acknowledge funding from The MRC – United Kingdom, Grant G1100021.Pulsed electron-electron double resonance (PELDOR) coupled with site-directed spin labeling is a powerful technique for the elucidation of protein or nucleic acid, macromolecular structure and interactions. The intrinsic high sensitivity of electron paramagnetic resonance enables measurement on small quantities of bio-macromolecules, however short relaxation times impose a limit on the sensitivity and size of distances that can be measured using this technique. The persistence of the electron spin-echo, in the PELDOR experiment, is one of the most crucial limitations to distance measurement. At a temperature of around 50 K one of the predominant factors affecting persistence of an echo, and as such, the sensitivity and measurable distance between spin labels, is the electron spin echo dephasing time (Tm). It has become normal practice to use deuterated solvents to extend Tm and recently it has been demonstrated that deuteration of the underlying protein significantly extends Tm. Here we examine the spatial effect of segmental deuteration of the underlying protein, and also explore the concentration and temperature dependence of highly deuterated systems.Publisher PDFPeer reviewe

Epithelial-mesenchymal transitions: the importance of changing cell state in development and disease

The events that convert adherent epithelial cells into individual migratory cells that can invade the extracellular matrix are known collectively as epithelial-mesenchymal transition (EMT). Throughout evolution, the capacity of cells to switch between these two cellular states has been fundamental in the generation of complex body patterns. Here, we review the EMT events that build the embryo and further discuss two prototypical processes governed by EMT in amniotes: gastrulation and neural crest formation. Cells undergo EMT to migrate and colonize distant territories. Not surprisingly, this is also the mechanism used by cancer cells to disperse throughout the body

Xanthan gum as an alternative to replace fat for coating and flavoring the extruded snacks

Food industries adapt their products and processes to the needs and desires of consumers. Extruded snacks include 10–20% fat sprinkled to fix flavors, seasonings, and salt. Considering the need to flavor snacks and simultaneously reduce the intake of calories, a polysaccharide is proposed in this study as a fat replacer. Impact of aqueous xanthan gum (Xg) solutions (0.25, 0.5, 1.0%) under two pH conditions (3.5 and 7.0) on structural and sensory characteristics of extruded snacks was analyzed. Rheological features of the coating solutions, as flow behaviour and viscoelastic profile (storage and loss moduli), were assessed. Texture analysis, to evaluate the snacks firmness and moisture content, water activity, retraction, and agglomeration index of the coated snacks, were also evaluated. Results for the aqueous Xg coatings were very encouraging showing good coating properties, not damaging the texture of the extrudates or causing agglomeration. Sensory analysis reflected a good overall acceptability of these snacks, as compared to oil-coated snacks. Therefore, xanthan gum should be used by the industry, to replace fat, on extruded snacks flavor coating solutionsinfo:eu-repo/semantics/publishedVersio

High prevalence of bronchiectasis is linked to HTLV-1-associated inflammatory disease.

BACKGROUND: Human T-lymphotropic virus type 1 (HTLV-1), a retrovirus, is the causative agent of HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and adult T-cell leukaemia/lymphoma (ATLL). The reported association with pulmonary disease such as bronchiectasis is less certain. METHODS: A retrospective case review of a HTLV-1 seropositive cohort attending a national referral centre. The cohort was categorised into HTLV-1 symptomatic patients (SPs) (ATLL, HAM/TSP, Strongyloidiasis and HTLV associated inflammatory disease (HAID)) and HTLV-1 asymptomatic carriers (ACs). The cohort was reviewed for diagnosis of bronchiectasis. RESULT: 34/246 ACs and 30/167 SPs had been investigated for respiratory symptoms by computer tomography (CT) with productive cough +/- recurrent chest infections the predominant indications. Bronchiectasis was diagnosed in one AC (1/246) and 13 SPs (2 HAID, 1 ATLL, 10 HAM/TSP) (13/167, RR 19.2 95 % CI 2.5-14.5, p = 0.004) with high resolution CT. In the multivariate analysis ethnicity (p = 0.02) and disease state (p < 0.001) were independent predictors for bronchiectasis. The relative risk of bronchiectasis in SPs was 19.2 (95 % CI 2.5-14.5, p = 0.004) and in HAM/TSP patients compared with all other categories 8.4 (95 % CI 2.7-26.1, p = 0.0002). Subjects not of African/Afro-Caribbean ethnicity had an increased prevalence of bronchiectasis (RR 3.45 95 % 1.2-9.7, p = 0.02). CONCLUSIONS: Bronchiectasis was common in the cohort (3.4 %). Risk factors were a prior diagnosis of HAM/TSP and ethnicity but not HTLV-1 viral load, age and gender. The spectrum of HTLV-associated disease should now include bronchiectasis and HTLV serology should be considered in patients with unexplained bronchiectasis

Stainless steel made to rust: a robust water-splitting catalyst with benchmark characteristics

The oxygen evolution reaction (OER) is known as the efficiency-limiting step for the electrochemical cleavage of water mainly due to the large overpotentials commonly used materials on the anode side cause. Since Ni–Fe oxides reduce overpotentials occurring in the OER dramatically they are regarded as anode materials of choice for the electrocatalytically driven water-splitting reaction. We herewith show that a straightforward surface modification carried out with AISI 304, a general purpose austenitic stainless steel, very likely, based upon a dissolution mechanism, to result in the formation of an ultra-thin layer consisting of Ni, Fe oxide with a purity >99%. The Ni enriched thin layer firmly attached to the steel substrate is responsible for the unusual highly efficient anodic conversion of water into oxygen as demonstrated by the low overpotential of 212 mV at 12 mA cm−2 current density in 1 M KOH, 269.2 mV at 10 mA cm−2 current density in 0.1 M KOH respectively. The Ni, Fe-oxide layer formed on the steel creates a stable outer sphere, and the surface oxidized steel samples proved to be inert against longer operating times (>150 ks) in alkaline medium. In addition Faradaic efficiency measurements performed through chronopotentiometry revealed a charge to oxygen conversion close to 100%, thus underpinning the conclusion that no “inner oxidation” based on further oxidation of the metal matrix below the oxide layer occurs. These key figures achieved with an almost unrivalled-inexpensive and unrivalled-accessible material, are among the best ever presented activity characteristics for the anodic water-splitting reaction at pH 13

Biopiracy <i>versus </i>one-world medicine – from colonial relicts to global collaborative concepts

Background: Practices of biopiracy to use genetic resources and indigenous knowledge by Western companies without benefit-sharing of those, who generated the traditional knowledge, can be understood as form of neocolonialism.Hypothesis: : The One-World Medicine concept attempts to merge the best of traditional medicine from developing countries and conventional Western medicine for the sake of patients around the globe.Study design: Based on literature searches in several databases, a concept paper has been written. Legislative initiatives of the United Nations culminated in the Nagoya protocol aim to protect traditional knowledge and regulate benefit-sharing with indigenous communities. The European community adopted the Nagoya protocol, and the corresponding regulations will be implemented into national legislation among the member states. Despite pleasing progress, infrastructural problems of the health care systems in developing countries still remain. Current approaches to secure primary health care offer only fragmentary solutions at best. Conventional medicine from industrialized countries cannot be afforded by the impoverished population in the Third World. Confronted with exploding costs, even health systems in Western countries are endangered to burst. Complementary and alternative medicine (CAM) is popular among the general public in industrialized countries, although the efficacy is not sufficiently proven according to the standards of evidence-based medicine. CAM is often available without prescription as over-the-counter products with non-calculated risks concerning erroneous self-medication and safety/toxicity issues. The concept of integrative medicine attempts to combine holistic CAM approaches with evidence-based principles of conventional medicine.Conclusion: To realize the concept of One-World Medicine, a number of standards have to be set to assure safety, efficacy and applicability of traditional medicine, e.g. sustainable production and quality control of herbal products, performance of placebo-controlled, double-blind, randomized clinical trials, phytovigilance, as well as education of health professionals and patients

Synaptic Accumulation of PSD-95 and Synaptic Function Regulated by Phosphorylation of Serine-295 of PSD-95

SummaryThe scaffold protein PSD-95 promotes the maturation and strengthening of excitatory synapses, functions that require proper localization of PSD-95 in the postsynaptic density (PSD). Here we report that phosphorylation of ser-295 enhances the synaptic accumulation of PSD-95 and the ability of PSD-95 to recruit surface AMPA receptors and potentiate excitatory postsynaptic currents. We present evidence that a Rac1-JNK1 signaling pathway mediates ser-295 phosphorylation and regulates synaptic content of PSD-95. Ser-295 phosphorylation is suppressed by chronic elevation, and increased by chronic silencing, of synaptic activity. Rapid dephosphorylation of ser-295 occurs in response to NMDA treatment that causes chemical long-term depression (LTD). Overexpression of a phosphomimicking mutant (S295D) of PSD-95 inhibited NMDA-induced AMPA receptor internalization and blocked the induction of LTD. The data suggest that synaptic strength can be regulated by phosphorylation-dephosphorylation of ser-295 of PSD-95 and that synaptic depression requires the dephosphorylation of ser-295

High field level crossing studies on spin dimers in the low dimensional quantum spin system Na2_2T2_2(C2_2O4_4)3_3(H2_2O)2_2 with T=Ni,Co,Fe,Mn

In this paper we demonstrate the application of high magnetic fields to study the magnetic properties of low dimensional spin systems. We present a case study on the series of 2-leg spin-ladder compounds Na$_2$T$_2$(C$_2$O$_4$)$_3$(H$_2$O)$_2$ with T = Ni, Co, Fe and Mn. In all compounds the transition metal is in the $T^{2+}$ high spin configuation. The localized spin varies from S=1 to 3/2, 2 and 5/2 within this series. The magnetic properties were examined experimentally by magnetic susceptibility, pulsed high field magnetization and specific heat measurements. The data are analysed using a spin hamiltonian description. Although the transition metal ions form structurally a 2-leg ladder, an isolated dimer model consistently describes the observations very well. This behaviour can be understood in terms of the different coordination and superexchange angles of the oxalate ligands along the rungs and legs of the 2-leg spin ladder. All compounds exhibit magnetic field driven ground state changes which at very low temperatures lead to a multistep behaviour in the magnetization curves. In the Co and Fe compounds a strong axial anisotropy induced by the orbital magnetism leads to a nearly degenerate ground state and a strongly reduced critical field. We find a monotonous decrease of the intradimer magnetic exchange if the spin quantum number is increased