bluuebunny/crossref_metadata_2025 huggingface dataset:
Mitogen-activated protein kinase-dependent and -independent routes control shedding of transmembrane growth factors through multiple secretases
Authors: MONTERO Juan Carlos , YUSTE Laura , DÍAZ-RODRÍGUEZ Elena , ESPARÍS-OGANDO Azucena , PANDIELLA Atanasio
Published: August 2015

Solubilization of a number of membrane proteins occurs by the action of cell-surface proteases, termed secretases. Recently, the activity of these secretases has been reported to be controlled by the extracellular signal-regulated kinases 1 and 2 (ERK1/ERK2) and the p38 mitogen-activated protein kinase (MAPK) routes. In the present paper, we show that shedding of membrane-anchored growth factors (MAGFs) may also occur through MAPK-independent routes. In Chinese-hamster ovary cells, cleavage induced by protein kinase C (PKC) stimulation was largely insensitive to inhibitors of the ERK1/ERK2 and p38 routes. Other reagents such as sorbitol or UV light stimulated MAGF cleavage independent of PKC. The action of sorbitol on cleavage was only partially prevented by the combined action of inhibitors of the p38 and ERK1/ERK2 routes, indicating that sorbitol can also stimulate shedding by MAPK-dependent and -independent routes. Studies in cells devoid of activity of the secretase tumour necrosis factor-α-converting enzyme (TACE) indicated that this protease had an essential role in PKC- and ERK1/ERK2-mediated shedding. However, secretases other than TACE may also cleave MAGFs since sorbitol could still induce shedding in these cells. These observations suggest that cleavage of MAGFs is a complex process in which multiple secretases, activated through different MAPK-dependent and -independent routes, are involved.
Endolysosomal proteolysis and its regulation
Authors: PILLAY Ché S. , ELLIOTT Edith , DENNISON Clive
Published: August 2015

The endolysosomal system comprises a unique environment for proteolysis, which is regulated in a manner that apparently does not involve protease inhibitors. The system comprises a series of membrane-bound intracellular compartments, within which endocytosed material and redundant cellular components are hydrolysed. Endocytosed material tends to flow vectorially through the system, proceeding through the early endosome, the endosome carrier vesicle, the late endosome and the lysosome. Phagocytosis and autophagy provide alternative entry points into the system. Late endosomes, lysosome/late endosome hybrid organelles, phagosomes and autophagosomes are the principal sites for proteolysis. In each case, hydrolytic competence is due to components of the endolysosomal system, i.e. proteases, lysosome-associated membrane proteins, H+-ATPases and possibly cysteine transporters. The view is emerging that lysosomes are organelles for the storage of hydrolases, perhaps in an inactivated form. Once a substrate has entered a proteolytically competent environment, the rate-limiting proteolytic steps are probably effected by cysteine endoproteinases. As these are affected by pH and possibly redox potential, they may be regulated by the organelle luminal environment. Regulation is probably also affected, among other factors, by organelle fusion reactions, whereby the meeting of enzyme and substrate may be controlled. Such systems would permit simultaneous regulation of a number of unrelated hydrolases.
Ferritin expression modulates cell cycle dynamics and cell responsiveness to H-ras-induced growth via expansion of the labile iron pool
Authors: KAKHLON Or , GRUENBAUM Yosef , CABANTCHIK Z. Ioav
Published: August 2015

Repression or overexpression of ferritin accelerated or retarded cell cycling respectively, via changes in the cellular labile iron pool (LIP). A rise in LIP is caused by ferritin repression enhanced growth, induced by H-ras, and reverted growth arrest is induced by dominant negative H-ras. The studies indicate that repression of ferritin expression provides a mechanism by which certain oncogenes lead to cell growth stimulation.
Mutational analysis of the two zinc-binding sites of the Bacillus cereus 569/H/9 metallo-β-lactamase
Authors: de SENY Dominique , PROSPERI-MEYS Christelle , BEBRONE Carine , ROSSOLINI Gian Maria , PAGE Michael I. , NOEL Philippe , FRÈRE Jean-Marie , GALLENI Moreno
Published: August 2015

The metallo-β-lactamase BcII from Bacillus cereus 569/H/9 possesses a binuclear zinc centre. The mono-zinc form of the enzyme displays an appreciably high activity, although full efficiency is observed for the di-zinc enzyme. In an attempt to assign the involvement of the different zinc ligands in the catalytic properties of BcII, individual substitutions of selected amino acids were generated. With the exception of His116→Ser (H116S), C221A and C221S, the mono- and di-zinc forms of all the other mutants were poorly active. The activity of H116S decreases by a factor of 10 when compared with the wild type. The catalytic efficiency of C221A and C221S was zinc-dependent. The mono-zinc forms of these mutants exhibited a low activity, whereas the catalytic efficiency of their respective di-zinc forms was comparable with that of the wild type. Surprisingly, the zinc contents of the mutants and the wild-type BcII were similar. These data suggest that the affinity of the β-lactamase for the metal was not affected by the substitution of the ligand. The pH-dependence of the H196S catalytic efficiency indicates that the zinc ions participate in the hydrolysis of the β-lactam ring by acting as a Lewis acid. The zinc ions activate the catalytic water molecule, but also polarize the carbonyl bond of the β-lactam ring and stabilize the development of a negative charge on the carbonyl oxygen of the tetrahedral reaction intermediate. Our studies also demonstrate that Asn233 is not directly involved in the interaction with the substrates.
Differential effect of the inhibition of Grb2–SH3 interactions in platelet activation induced by thrombin and by Fc receptor engagement
Authors: SACI Abdelhafid , LIU Wang-Qing , VIDAL Michel , GARBAY Christiane , RENDU Francine , BACHELOT-LOZA Christilla
Published: August 2015

The adaptor protein Grb2 (growth factor receptor-bound protein 2) is involved in cell proliferation via the Ras signalling pathway. In order to study the role of Grb2 in blood platelet responses, we used a peptide containing two proline-rich sequences derived from Sos (peptidimer), which binds to Grb2—Src homology 3 domain (SH3) with a high affinity, and hence inhibits Grb2—SH3-mediated protein interactions. Platelet aggregation and 5-hydroxytryptamine (serotonin) release measured in the presence of the peptidimer were: (i) significantly decreased when induced by thrombin; and (ii) potentiated when induced by the engagement of the Fc receptor. In thrombin-activated platelets, the Grb2—SH2 domain formed an association with the β3 subunit of the αIIb—β3 integrin (GPIIb—IIIa), Shc, Syk, Src and SHP1 (SH2-containing phosphotyrosine phosphatase 1), whereas these associations did not occur after the engagement of the receptor for the Fc domain of IgG (FcγRIIa) or in resting platelets. Grb2—SH3 domains formed an association with the proline-rich sequences of Sos and Cbl in both resting and activated platelets, since the peptidimer abolished these associations. Inhibition of both fibrinogen binding and platelet aggregation by the peptide RGDS (Arg-Gly-Asp-Ser) had no effect on thrombin-induced Grb2—SH2 domain association with the aforementioned signalling molecules, indicating that these associations occurred during thrombin-induced ‘inside-out’ signalling. Platelet aggregation induced by direct activation via αIIb—β3 ('outside-in’ signalling) was potentiated by the peptidimer. The results show that inhibition of Grb2—SH3 interactions with signal-transduction proteins down-regulates thrombin-induced platelet activation, but also potentiates Fc receptor- and αIIb—β3-mediated platelet activation.
Utilization of green fluorescent protein as a marker for studying the expression and turnover of the monocarboxylate permease Jen1p of Saccharomyces cerevisiae
Authors: PAIVA Sandra , KRUCKEBERG Arthur L. , CASAL Margarida
Published: August 2015

Green fluorescent protein (GFP) from Aequorea victoria was used as an in vivo reporter protein when fused to the C-terminus of the Jen1 lactate permease of Saccharomyces cerevisiae. The Jen1 protein tagged with GFP is a functional lactate transporter with a cellular abundance of 1670 molecules/cell, and a catalytic-centre activity of 123s−1. It is expressed and tagged to the plasma membrane under induction conditions. The factors involved in proper localization and turnover of Jen1p were revealed by expression of the Jen1p—GFP fusion protein in a set of strains bearing mutations in specific steps of the secretory and endocytic pathways. The chimaeric protein Jen1p—GFP is targeted to the plasma membrane via a Sec6-dependent process; upon treatment with glucose, it is endocytosed via END3 and targeted for degradation in the vacuole. Experiments performed in a Δdoa4 mutant strain showed that ubiquitination is associated with the turnover of the permease.
Stopped-flow kinetic analysis of long-chain fatty acid dissociation from bovine serum albumin
Authors: DEMANT Erland J.F. , RICHIERI Gary V. , KLEINFELD Alan M.
Published: August 2015

The kinetics of the interaction of long-chain fatty acids (referred to as fatty acids) with albumin is critical to understanding the role of albumin in fatty acid transport. In this study we have determined the kinetics of fatty acid dissociation from BSA and the BSA-related fatty acid probe BSA-HCA (BSA labelled with 7-hydroxycoumarin-4-acetic acid) by stopped-flow methods. Fatty acid—albumin complexes of a range of natural fatty acid types and albumin molecules (donors) were mixed with three fatty acid-binding acceptor proteins. Dissociation of fatty acids from the donor was monitored by either the time course of donor fluorescence/absorbance or the time course of acceptor fluorescence. The results of these measurements indicate that fatty acid dissociation from BSA as well as BSA-HCA is well described by a single exponential function over the entire range of fatty acid/albumin molar ratios used in these measurements, from 0.5:1 to 6:1. The observed rate constants (kobs) for the dissociation of each fatty acid type reveal little or no dependence on the initial fatty acid/albumin ratio. However, dissociation rates were dependent upon the type of fatty acid. In the case of native BSA with an initial fatty acid/BSA molar ratio of 3:1, the order of kobs values was stearic acid (1.5s−1)<oleic acid<palmitic acid≅linoleic acid<arachidonic acid (8s−1) at 37°C. The corresponding values for BSA-HCA were about half the values for BSA. The results of this study show that the rate of fatty acid dissociation from native BSA is more than 10-fold faster than reported previously and that the off-rate constants for the five primary fatty acid-binding sites differ by less than a factor of 2. We conclude that for reported rates of fatty acid transport across cell membranes, dissociation of fatty acids from the fatty acid—BSA complexes used in the transport studies should not be rate-limiting.
Characterization of a murine gene encoding a developmentally regulated cytoplasmic dual-specificity mitogen-activated protein kinase phosphatase
Authors: DICKINSON Robin J. , WILLIAMS David J. , SLACK David N. , WILLIAMSON Jill , SETERNES Ole-Morten , KEYSE Stephen M.
Published: August 2015

Mitogen-activated protein kinases (MAPKs) play a vital role in cellular growth control, but far less is known about these signalling pathways in the context of embryonic development. Duration and magnitude of MAPK activation are crucial factors in cell fate decisions, and reflect a balance between the activities of upstream activators and specific MAPK phosphatases (MKPs). Here, we report the isolation and characterization of the murine Pyst3 gene, which encodes a cytosolic dual-specificity MKP. This enzyme selectively interacts with, and is catalytically activated by, the ‘classical’ extracellular signal-regulated kinases (ERKs) 1 and 2 and, to a lesser extent, the stress-activated MAPK p38α. These properties define the ability of this enzyme to dephosphorylate and inactivate ERK1/2 and p38α, but not JNK (c-Jun N-terminal kinase) in vivo. When expressed in mammalian cells, the Pyst3 protein is predominantly cytoplasmic. Furthermore, leptomycin B causes a complete redistribution of the protein to the nucleus, implicating a CRM (chromosomal region maintenance)1/exportin 1-dependent nuclear export signal in determining the subcellular localization of this enzyme. Finally, whole-mount in situ hybridization studies in mouse embryos reveal that the Pyst3 gene is expressed specifically in the placenta, developing liver and in migratory muscle cells. Our results suggest that this enzyme may have a critical role in regulating the activity of MAPK signalling during early development and organogenesis.
Nitric oxide inhibits the shedding of the glycosylphosphatidylinositol-anchored dipeptidase from porcine renal proximal tubules
Authors: PARK Sung Wook , YOON Hyun Joong , LEE Hwanghee Blaise , HOOPER Nigel M. , PARK Haeng Soon
Published: August 2015

NO is related to the pathological condition acute renal failure, in which we previously observed that the level of soluble dipeptidase in urine was decreased. In this study the role of NO in the shedding of the glycosylphosphatidylinositol (GPI)-anchored form of renal dipeptidase (RDPase) was examined. The NO donors sodium nitroprusside (SNP) and S-nitroso-N-acetylpenicillamine rapidly inhibited the release of RDPase from porcine kidney proximal tubules. The substrate of NO synthase, l-Arg, also inhibited the release of RDPase, and this effect was reversed by the NO synthase inhibitor Nω-nitro-l-arginine methyl ester. Western-blot analyses using antibodies raised against porcine RDPase and the inositol-1,2-cyclic monophosphate moiety formed on phospholipase C cleavage of the GPI anchor demonstrated that SNP mediated its inhibitory effect on the release of RDPase via a GPI-specific phospholipase C (GPI-PLC). Peroxynitrite scavengers (deferoxamine and superoxide dismutase) or reducing agent (dithiothreitol) did not affect SNP's inhibition of the release of RDPase. Exposure to the G-protein activator AlF−4 mimicked the l-Arg effect in the presence of a low concentration of l-Arg, and the effect was completely reversed by U73122, an intracellular phosphatidylinositol-specific PLC (PI-PLC) inhibitor. These results suggest a signal-transduction pathway involving NO, which is produced by NO synthase(s) following activation of a G-protein-coupled PI-PLC, resulting in inhibition of the GPI-PLC that cleaves and releases RDPase. Therefore, this indicates a role for NO as an inhibitory regulator of the shedding of the GPI-anchored RDPase in acute renal failure.
Adenovirus-mediated overexpression of liver carnitine palmitoyltransferase I in INS1E cells: effects on cell metabolism and insulin secretion
Authors: RUBÍ Blanca , ANTINOZZI Peter A. , HERRERO Laura , ISHIHARA Hisamitsu , ASINS Guillermina , SERRA Dolors , WOLLHEIM Claes B. , MAECHLER Pierre , HEGARDT Fausto G.
Published: August 2015

Lipid metabolism in the β-cell is critical for the regulation of insulin secretion. Pancreatic β-cells chronically exposed to fatty acids show higher carnitine palmitoyltransferase I (CPT I) protein levels, higher palmitate oxidation rates and an altered insulin response to glucose. We examined the effect of increasing CPT I levels on insulin secretion in cultured β-cells. We prepared a recombinant adenovirus containing the cDNA for the rat liver isoform of CPT I. The overexpression of CPT I in INS1E cells caused a more than a 5-fold increase in the levels of CPT I protein (detected by Western blotting), a 6-fold increase in the CPT activity, and an increase in fatty acid oxidation at 2.5mM glucose (1.7-fold) and 15mM glucose (3.1-fold). Insulin secretion was stimulated in control cells by 15mM glucose or 30mM KCl. INS1E cells overexpressing CPT I showed lower insulin secretion on stimulation with 15mM glucose (−40%; P<0.05). This decrease depended on CPT I activity, since the presence of etomoxir, a specific inhibitor of CPT I, in the preincubation medium normalized the CPT I activity, the fatty-acid oxidation rate and the insulin secretion in response to glucose. Exogenous palmitate (0.25mM) rescued glucose-stimulated insulin secretion (GSIS) in CPT I-overexpressing cells, indicating that the mechanism of impaired GSIS was through the depletion of a critical lipid. Depolarizing the cells with KCl or intermediary glucose concentrations (7.5mM) elicited similar insulin secretion in control cells and cells overexpressing CPT I. Glucose-induced ATP increase, glucose metabolism and the triacylglycerol content remained unchanged. These results provide further evidence that CPT I activity regulates insulin secretion in the β-cell. They also indicate that up-regulation of CPT I contributes to the loss of response to high glucose in β-cells exposed to fatty acids.
Anatomy and pathology of HIV-1 peptidase
Authors: Dunn Ben M
Published: August 2015

The peptidase of the HIV type 1 (HIV PR) is required for the replication of and further infection by the virus. A concerted effort has taken place in the past 15 years to understand the properties of this enzyme, as it serves as an excellent drug target for control of the virus. Owing to drug pressure, many mutations arise during turnover of the virus and some of these lead to resistance to the effects of the inhibitors. Recent advances in the understanding of the changes these mutations cause to the enzyme and its interaction with substrates and inhibitors have been described. In addition, studies of closely related retroviral enzymes from simian immunodeficiency virus, feline immunodeficiency virus and HIV-2 have expanded the structure-function paradigm. The role of the flexibility of ligands and of the enzyme in active-site interactions is discussed.
Antioxidants in food packaging: a risk factor?
Authors: Scott Gerald
Published: August 2015

It is current practice to test all new additives for packaging polymers for toxicity before permitting them to be used in food contact applications. However, many antioxidants and stabilizers act sacrificially and are converted to oxidation products in the process of preventing polymer degradation. In most cases, little is known about the toxicity of antioxidant transformation products, and in some cases there is reason to suspect that they may be more toxic than the chemicals from which they are derived. Two possible solutions are presently showing promise. The first is to chemically react the antioxidant or stabilizer with the polymer, either at the polymer synthesis stage or preferably during processing, so that neither the antioxidant nor its transformation products can be leached into food. The second is to use a biological antioxidant (e.g. α-tocopherol) whose oxidation chemistry and toxicology are known.
Alzheimer's disease: inside, outside, upside down
Authors: Yan Shi Du , Schmidt Ann M. , Stern David
Published: August 2015

Neurotoxicity of ϐ-amyloid peptide (Aϐ) in Alzheimer's disease (AD) is usually thought to arise from the nonspecific effects of high concentrations of Aϐ on vulnerable neurons, resulting in membrane destabilization and increasing intracellular calcium concentration. This review advances the hypothesis that at early stages of AD, when Aϐ is present in lower amounts, its ability to perturb the function of cellular targets is mediated by specific cofactors present on the cell surface and intracellularly. Receptor for advanced glycation endproducts (RAGE) is a cell-surface receptor which binds Aϐ and amplifies its effects on cells in the nanomolar range. The intracellular enzyme Aϐ-binding alcohol dehydrogenase (ABAD) is likely to engage nascent Aϐ formed in the endoplasmic reticulum, and to mediate cell stress from this site. The analysis of Aϐ interaction with RAGE and ABAD, as well as other cofactors, provides insight into new mechanisms and, potentially, identifies therapeutic targets relevant to neuronal dysfunction in AD.
Oxidative signalling and inflammatory pathways in Alzheimer's disease
Authors: Anderson Ian , Adinolfi Christy , Doctrow Susan , Huffman Karl , Joy Ken A. , Malfroy Bernard , Soden Peter , Rupniak H. Tom , Barnes Julie C.
Published: August 2015

It is well established that inflammation and oxidative stress are key components of the pathology of Alzheimer's disease (AD), but how early in the pathological cascade these processes are involved or which specific molecular components are key, has not been fully elucidated. This paper describes the pharmacological approach to understand the molecular components of inflammation and oxidative stress on the activation of microglial cells and neuronal cell viability. We have shown that activation of microglia with the 42-amino-acid form of the ϐ-amyloid peptide (Aϐ42) activates the production of cyclooxygenase-2, the inducible form of nitric oxide synthase and tumour necrosis factor-α and there appears to be little interactive feedback between these three mediators. Moreover, we explore the effects of a series of salen-manganese complexes, EUK-8, -134 and -189, which are known to possess both superoxide and catalase activity. These compounds are able to protect cells from insults produced by hydrogen peroxide or peroxynitrite. Moreover, EUK-134 was also able to limit the output of prostaglandin E2 from activated microglial cells. The mechanisms underlying these effects are discussed. Together, these data support a pivotal role for oxidative stress and inflammation as key mediators of the pathological cascade in AD and provide some ideas about possible therapeutic targets.
How serpins change their fold for better and for worse
Authors: Carrell Robin W. , Huntington James A.
Published: August 2015

The serpins differ from the many other families of serine protease inhibitors in that they undergo a profound change in topology in order to entrap their target protease in an irreversible complex. The solving of the structure of this complex has now provided a video depiction of the changes involved. Cleavage of the exposed reactive centre of the serpin triggers an opening of the five-stranded A-sheet of the molecule, with insertion of the cleaved reactive loop as an additional strand in the centre of the sheet. The drastic displacement of the acyl-linked protease grossly disrupts its active site and gives an overall loss of 40% of ordered structure. This ability to provide effectively irreversible inhibition explains the selection of the serpins to control the proteolytic cascades of higher organisms. The conformational mechanism provides another advantage in its potential to modulate activity. Sequential crystallographic structures now provide clear depictions of the way antithrombin is activated on binding to the heparans of the microcirculation, and how evolution has utilized this mobile mechanism for subtle variations in activity. The complexity of these modulatory mechanisms is exemplified by heparin cofactor II, where the change in fold is seen to trigger multiple allosteric effects. The downside of the mobile mechanism of the serpins is their vulnerability to aberrant intermolecular ϐ-linkages, resulting in various disorders from cirrhosis to thrombosis. These provide a well defined structural prototype for the new entity of the conformational diseases, including the common dementias, as confirmed by the recent identification of the familial neuroserpin dementias.
Cathepsin B and its role(s) in cancer progression
Authors: Podgorski Izabela , Sloane Bonnie F.
Published: August 2015

Experimental and clinical evidence has linked cathepsin B with tumour invasion and metastasis. Cathepsin B expression is increased in many human cancers at the mRNA, protein and activity levels. In addition, cathepsin B is frequently overexpressed in premalignant lesions, an observation that associates this protease with local invasive stages of cancer. Increased expression of cathepsin B in primary cancers, and especially in preneoplastic lesions, suggests that this enzyme might have pro-apoptotic features. Expression of cathepsin B is regulated at many different levels, from gene amplification, use of alternative promoters, increased transcription and alternative splicing, to increased stability and translatability of transcripts. During the transition to malignancy, a change in the localization of cathepsin B occurs, as demonstrated by the presence of cathepsin B-containing vesicles at the cell periphery and at the basal pole of polarized cells. Due to increased expression of cathepsin B and changes in intracellular trafficking, increased secretion of procathepsin B from tumours is observed. Active cathepsin B is also secreted from tumours, a mechanism likely to be facilitated by lysosomal exocytosis or extracellular processing by surface activators. Cathepsin B is localized to caveolae on the tumour surface, where binding to the annexin II heterotetramer occurs. Activation of cathepsin B on the cell surface leads to the regulation of downstream proteolytic cascade(s).
Both normal and polyglutamine- expanded ataxin-7 are components of TFTC-type GCN5 histone acetyltransferase- containing complexes
Authors: Helmlinger Dominique , Hardy Sara , Eberlin Adrien , Devys Didier , Tora Làszlò
Published: August 2015

SCA7 (spinocerebellar ataxia type 7) is a neurodegenerative disorder caused by a CAG repeat expansion in the SCA7 gene that leads to elongation of a polyglutamine tract in ataxin-7, a protein of unknown function. Sgf73, a putative yeast orthologue of ataxin-7, has been identified as a new component of the yeast SAGA (Spt/Ada/Gcn5 acetyltransferase) multisubunit complex, a co-activator required for the transcription of a subset of RNA polymerase II-dependent genes. We show here that ataxin-7 is an integral component of mammalian SAGA-like complexes, i.e. the TFTC [TBP (TATA-binding protein)-free TAF (TBP-associated factor) complex] and the STAGA (SPT3/TAF9/GCN5 acetyltransferase) complex. In agreement with this, immunoprecipitation of ataxin-7 retained a histone acetyltransferase activity characteristic of TFTC-like complexes. Moreover, polyglutamine expansion in ataxin-7 did not affect its incorporation into TFTCs/STAGA complexes purified from cells from a SCA7 patient. We demonstrate here that ataxin-7 is the human orthologue of a the yeast SAGA Sgf73 subunit, and is a bona fide subunit of human TFTC-like transcriptional complexes.
MEMBRANE BOUND AND WATER SOLUBLE CYTOCHROME C1 FROM NEUROSPORA MITOCHONDRIA
Authors: Li Yun , Leonard Kevin , Weiss Hanns
Published: August 2015

Cytochrome c1 is a subunit of ubiquinol: cytochrome c reductase (E.C.1.10.2.2.). In Neurospora grown in the presence of chloramphenicol, the subunit is inserted only into the bilayer of the mitochondrial inner membranes without associating with other proteins. By limited proteolytic digestion of the cytochrome c1-Triton complex with chymotrypsin, a large water soluble monomeric cytochrome c1 fragment was prepared. The 24,000 Mr fragment and the 31,000 Mr cytochrome c1 have the same spectra and cytochrome c binding properties. These results are used to propose a two-part model for cytochrome c1. A large hydrophilic part extends from the mitochondrial inner membrane into the intermembrane space. This part carries the heme and interacts with cytochrome c. A second, smaller hydrophobic part anchors the cytochrome c1 to the bilayer.
‘Folk’ understandings of quality in UK higher hospitality education
Authors: Wood Roy
Published: August 2015

Purpose

– The purpose of this paper is to provide an overview of the evolution of “folk” understandings of quality in higher hospitality education and the consequent implications of these understandings for current quality concerns in the field.

Design/methodology/approach

– The paper combines a historical survey of the stated topic together with an analysis of how the evolution of higher hospitality education provides insight into current issues and problems in the subject area.

Findings

– The paper suggests that only by thoroughly comprehending the past development of higher hospitality education is it possible to accurately map the field’s current travails and diagnose likely future trends.

Practical implications

– The paper outlines the implications of current understandings of quality in hospitality education for its future development and provision.

Originality/value

– The originality and value of this paper lie in its identification of the principal trends that contribute to understanding of current perceptions of the quality of higher hospitality education.
Elemental Characterization and Discrimination of Nontoxic Ammunition Using Scanning Electron Microscopy with Energy Dispersive X‐Ray Analysis and Principal Components Analysis
Authors: Hogg Seth R. , Hunter Brian C. , Waddell Smith Ruth
Published: August 2015

Concerns over the toxic by‐products produced by traditional ammunition have led to an increase in popularity of nontoxic ammunition. In this work, the chemical composition of six brands of nontoxic ammunition was investigated and compared to that of a road flare, which served as an environmental source with similar composition. Five rounds of each brand were fired while a further five were disassembled and the primer alone was fired. Particles collected from all samples, including the road flare, were analyzed by scanning electron microscopy with energy dispersive X‐ray analysis. Common elements among the different ammunition brands included aluminum, potassium, silicon, calcium, and strontium. Spectra were then subjected to principal components analysis in which association of the primer to the intact ammunition sample was generally possible, with distinction among brands and from the road flare sample. Further, PCA loadings plots indicated the elements responsible for the association and discrimination observed.
Surviving in the High Arctic: dental variation in a casually introduced population of Microtus rossiaemeridionalis (Arvicolinae, Rodentia) on Svalbard
Authors: Markova Evgenia , Sibiryakov Petr , Ehrich Dorothee
Published: August 2015

A human‐mediated invasion of a temperate rodent Microtus rossiaemeridionalis on the High Arctic Archipelago of Svalbard in the first half of the 20th century provides an opportunity to explore extent and rate of morphological divergence over decades of isolation. We studied dental size and morphology in 124 voles captured on Svalbard (Spitsbergen) in 1997–2005 and compared the data to mainland conspecific populations across northern Eurasia. Both dental and cranial sizes in the Svalbard population fall within the limits of natural variation of the species. Dental morphology suggests that the population experiences strong effects of isolation as indicated by the significant increase in the frequency of rare dental morphs, possibly caused by inbreeding. No evidence for directional shift towards increased or decreased complexity of the morphotype dental patterns is revealed. Although the population on Svalbard is phenotypically different from the mainland populations (due to increased frequency of rare morphs), those differences are not enough to support the idea of initial rapid evolution related to colonization. The limited spatial extent and environmental homogeneity of suitable habitats on the island allowed the species to initially multiply but not to diversify so that the species exhibits phenotypic conservatism but suffers the consequences of small population size.
Fast and Exact (Poisson) Solvers on Symmetric Geometries
Authors: Kazhdan M.
Published: August 2015

In computer graphics, numerous geometry processing applications reduce to the solution of a Poisson equation. When considering geometries with symmetry, a natural question to consider is whether and how the symmetry can be leveraged to derive an efficient solver for the underlying system of linear equations. In this work we provide a simple representation‐theoretic analysis that demonstrates how symmetries of the geometry translate into block diagonalization of the linear operators and we show how this results in efficient linear solvers for surfaces of revolution with and without angular boundaries.
Risk of cancer in retransplants compared to primary kidney transplants in the United States
Authors: Kalil Roberto S. , Lynch Charles F. , Engels Eric A.
Published: August 2015

Recipients of kidney transplantation have elevated risk of developing cancer. There are limited data on cancer risk in recipients of kidney retransplantation. We used data from the Transplant Cancer Match Study, which links the U.S. transplant registry with 15 cancer registries. Cancer incidence in recipients of kidney retransplantation and primary kidney transplants was compared utilizing Poisson regression, adjusting for demographic and medical characteristics. We assessed 109 224 primary recipients and 6621 retransplants. Compared to primary recipients, retransplants were younger (median age 40 vs. 46 yr), had higher PRA, and more often received induction with polyclonal antibodies (43% vs. 25%). A total of 5757 cancers were observed in primary recipients and 245 in retransplants. Overall cancer risk was similar in retransplants compared with primary recipients (incidence rate ratio [IRR] 1.06, 95% CI 0.93–1.20, adjusted for age, gender, race/ethnicity, PRA, and use of polyclonal induction). However, renal cell carcinoma (RCC) occurred in excess among retransplants (adjusted IRR 2.03, 95% CI 1.45–2.77), based on 514 cases in primary recipients and 43 cases in retransplants. Overall cancer risk did not differ in retransplants compared to primary recipients. Increased risk of RCC may be explained by the presence of acquired cystic kidney disease, which is more likely to develop with additional time with kidney disease and time spent on dialysis waiting for retransplantation.
Should clinical case definitions of influenza in hospitalized older adults include fever?
Authors: Falsey Ann R. , Baran Andrea , Walsh Edward E.
Published: August 2015

Introduction

Influenza is a major cause of morbidity and mortality in elderly persons. Fever is included in all standard definitions of influenza‐like illness (ILI), yet older patients may have diminished febrile response to infection. Therefore, we examined the utility of various thresholds to define fever for case definitions of influenza in persons ≥65 years of age.

Methods

Data from two prospective surveillance studies for respiratory viral infection in adults hospitalized with acute cardiopulmonary illnesses with or without fever were examined. The highest temperature reported prior to admission or measured during the first 24 h after admission was recorded. The diagnosis of influenza was made by a combination of viral culture, reverse‐transcription polymerase chain reaction, antigen testing, and serology.

Results

A total of 2410 subjects (66% ≥65 years of age) were enrolled; 281 had influenza (261 influenza A, 19 influenza B, and one mixed influenza A and B). The commonly used definition of ILI (fever ≥37·8°C and cough) resulted in 57% sensitivity and 71% specificity in older adults. Receiver operating characteristic curves examining the various temperature thresholds combined with cough and/or sore throat showed the optimal balance between sensitivity and specificity to be 37·9°C (AUC 0·71) and 37·3°C (AUC 0·66), in younger and older persons, respectively.

Conclusion

Clinical decision rules using the presence of cough and fever may be helpful when screening for influenza or empiric antiviral treatment when rapid influenza testing is not available; however, lower fever thresholds may be considered for elderly subjects.
New circulating biomarkers for predicting cardiovascular death in healthy population
Authors: Melander Olle , Modrego Javier , Zamorano‐León Jose J. , Santos‐Sancho Juana M. , Lahera Vicente , López‐Farré Antonio J.
Published: August 2015

There is interest to analyse newer biomarkers to identify healthy individuals at risk to develop cardiovascular disease (CVD) incidents and death. To determine in healthy individuals new circulating protein biomarkers, whose systemic levels may be associated with the risk of future development of CVD incidents and death. The study was performed in 82 individuals from the Malmö Diet and Cancer study cohort, free from CVD of whom 41 developed CVD and 41 did not. Plasma proteins related to inflammation and thrombo‐coagulating processes were analysed. α1‐antitrypsin isotype 3 plasma levels were significantly higher while apolipoprotein J plasma levels were lower in participants that developed CVD incidents than those that did not develop acute cardiovascular episode. Of 82 participants, 17 died by CVD causes. There were proteins whose expression in plasma was significantly higher in participants suffering CVD death as compared with those that did not die by CVD. These proteins included: fibrinogen β‐chain isotypes 1 and 3, fibrinogen‐γ‐chain isotype 2, vitamin D‐binding protein isotypes 1, 2 and 3, α1‐antitrypsin isotypes 3 and 6, haptoglobin isotypes 3,4,5 and 5, haemopexin isotypes 1 and 2, and Rho/Rac guanine nucleotide exchange factor 2. Moreover, apolipoprotein J plasma levels were found lower in participants that died by cardiovascular cause. Association between plasma levels of proteins and CVD death was independent of age, gender, conventional risk factors and plasma C‐reactive protein levels. Several protein plasma levels and protein isotypes related to inflammation and thrombo‐coagulating phenomena were independently associated with the risk of future CVD death.
Mass marking of Leuciscus idus larvae using Artemia salina as a vector of fluorescent dyes
Authors: Stańczak K. , Krejszeff S. , Dębowska M. , Mierzejewska K. , Woźniak M. , Hliwa P.
Published: August 2015

A method for the mass marking of ide Leuciscus idus larvae by feeding them Artemia salina nauplii that were immersed in different solutions of alizarin red S, tetracycline hydrochloride and calcein was tested. The best quality marks were obtained after feeding fish for 4 days with nauplii that had been immersed in 200 mg l−1 alizarin red S.
Benchmarking of flood inundation extent using various dynamically linked one‐ and two‐dimensional approaches
Authors: Ahmadian R. , Falconer R. A. , Wicks J.
Published: August 2015

An accurate representation of linking processes between one‐dimensional (1‐D) and two‐dimensional (2‐D) models is of particular importance for many flood‐modelling projects. This paper provides a comparison of 1‐D/2‐D linking methods used to simulate a hypothetical embankment failure. Comparisons were made by implementing 1‐D/2‐D linked models using two different 1‐D/2‐D linking methods, namely water levels and discharges, using both the alternating direction implicit (ADI) and total variation diminishing (TVD) 2‐D numerical schemes widely used in flood models such as Flood Modeller Pro (http://www.floodmodeller.com). The flood inundation levels and extent predicted by each numerical scheme were similar when the discharge method was used to link the models, whereas they were dependent on the numerical scheme when the water‐level method was used. Consequently, where decisions affecting public safety are informed by the modelling, such as evacuation following a breach, it is recommended that the discharge‐linking method should be used for linking models.
Language, multiple authenticities and social media: The online language practices of university students in Mongolia
Authors: Dovchin Sender
Published: August 2015

This paper seeks to contribute to the current discussion of the sociolinguistics of globalization by revealing youth linguistic diversity from the perspective of the online mixed language practices of university students in contemporary post‐socialist Mongolia. Drawing on sets of Facebook data, the paper firstly argues that the online mixed youth language practices should be understood as ‘translingual’ not only due to their varied recombination of linguistic and cultural resources, genres, modes, styles and repertories, but also due to their direct subtextual connections with wider socio‐cultural, historical and ideological meanings. Secondly, online users metalinguistically claim authenticity in terms of their own translingual practices as opposed to other colliding language ideologies such as linguistic dystopia. How they relocalize the notion of authenticity, however, differs profoundly depending on their own often‐diverse criteria, identities, beliefs and ideas. This shows that, with mixing and recombining at its very core, the translingual practices of modern young speakers provide us with a significant insight into the co‐existence of multiple authenticities and origins of authenticity in an increasingly interconnected world.
Portal vein anatomy in the dog: comparison between computed tomographic angiography (CTA) and intraoperative mesenteric portovenography (IOMP)
Authors: Parry A. T. , White R. N.
Published: August 2015

OBJECTIVES

To compare and contrast the findings of intra‐operative mesenteric portovenography (IOMP) and computed tomography angiography (CTA) for the visualisation and identification of the extrahepatic and intrahepatic portal venous system in the normal dog.

METHODS

Retrospective study of dogs with raised post‐prandial bile acids concentrations, normal portal venous pressures and grossly normal portal vasculature that had undergone both CTA and IOMP was performed. Images and video were compared with the published anatomic literature.

RESULTS

Ten dogs met the inclusion criteria. CTA documented the portal vein and its tributaries in all 10 dogs. IOMP documented the portal vein and the cranial mesenteric vein in all 10 dogs and the splenic vein in 1 dog but failed to show the caudal mesenteric and gastroduodenal veins in any dog. CTA documented more extrahepatic portal venous tributaries than IOMP. Both techniques documented the intrahepatic portal vasculature completely with equal clarity.

CLINICAL SIGNIFICANCE

There was a large difference between the ability of the two techniques to delineate the normal portal vasculature; CTA consistently visualised the extrahepatic portal vasculature more completely than the IOMP and, as such, might be considered the modality of choice for imaging the normal portal vasculature in the dog.
Induction and contribution of beta platelet‐derived growth factor signalling by hepatic stellate cells to liver regeneration after partial hepatectomy in mice
Authors: Kocabayoglu Peri , Zhang David Y. , Kojima Kensuke , Hoshida Yujin , Friedman Scott L.
Published: August 2015

Background & Aims

Hepatic stellate cells (HSCs) activate during injury to orchestrate the liver's inflammatory and fibrogenic responses. A critical feature of HSC activation is the rapid induction of beta platelet‐derived growth factor (β‐PDGFR), which drives cellular fibrogenesis and proliferation; in contrast, normal liver has minimal β‐PDGFR expression. While the role of β‐PDGFR is well established in liver injury, its expression and contribution during liver regeneration are unknown. The aim of this study was to determine whether β‐PDGFR is induced during liver regeneration following partial hepatectomy (pHx), and to define its contribution to the regenerative response.

Methods

Control mice or animals with HSC‐specific β‐PDGFR‐depletion underwent two‐thirds pHx followed by assessment of hepatocyte proliferation and expression of β‐PDGFR. RNA‐sequencing from whole liver tissue of both groups after pHx was used to uncover pathways regulated by β‐PDGFR signalling in HSCs.

Results

Beta platelet‐derived growth factor expression on HSCs was up‐regulated within 24 h following pHx in control mice, whereas absence of β‐PDGFR blunted the expansion of HSCs. Mice lacking β‐PDGFR displayed prolonged increases of transaminase levels within 72 h following pHx. Hepatocyte proliferation was impaired within the first 24 h based on Ki‐67 and PCNA expression in β‐PDGFR‐deficient mice. This was associated with dysregulated growth in the β‐PDGFR‐deficient mice based on RNAseq with pathway analysis, and real‐time quantitative PCR, which demonstrated reduced expression of Hgf, Igfbp1, Mapk and Il‐6.

Conclusions

Beta platelet‐derived growth factor is induced in HSCs following surgical pHx and its deletion in HSCs leads to prolonged liver injury. However, there is no significant difference in liver regeneration.
The satisfaction of families in the care of their loved ones in CCUs in Lebanon
Authors: Hajj Madeleine , Gulgulian Taline , Haydar Lili , Saab Amali , Dirany Fatima , Badr Lina Kurdahi
Published: August 2015

Background

The needs of family members vary among cultures and hospitals. Often, these needs remain unmet increasing their stress and anxiety and decreasing their satisfaction with care, which may negatively impact the quality of patient care.

Aims

To assess the satisfaction of families with the care of their loved ones in critical care units (CCUs) in a large university medical centre in Lebanon and to assess the predictors of satisfaction.

Methods

A cross‐sectional descriptive design was conducted using the Critical Care Family Satisfaction Survey (CCFSS). The participants were 123 adult relatives or significant others of patients cared for in both adult and paediatric intensive care units for at least 3 days.

Results

The CCFSS showed acceptable internal reliability and construct validity in a Lebanese population. In general, families were satisfied with the care their loved ones received in the CCUs, and the least satisfaction was in the area of ‘comfort’ and the highest was in ‘assurance’. Younger family members with more education were less satisfied with care and Christian families expressed less satisfaction with informational needs compared with Muslim families. Families of children in the paediatric CCU expressed least satisfaction with care. Gender, residency, relationship to patient, unit, prior experience in a CCU and diagnosis had no effect on satisfaction scores.

Conclusions

Assessment of family satisfaction in different cultures is important as each culture has specific needs that are essential to decipher.

Implications for practice

Patient satisfaction leads to improved quality of care; thus, it behoves nurses to meet the needs of families from different cultures to help them cope and increase their satisfaction, which leads to improve patient outcomes.
The clinical impact of vancomycin‐resistant Enterococcus colonization and bloodstream infection in patients undergoing autologous transplantation
Authors: Ford C.D. , Lopansri B.K. , Gazdik M.A. , Snow G.L. , Webb B.J. , Konopa K.L. , Petersen F.B.
Published: August 2015

Background

Although several studies have documented adverse outcomes for vancomycin‐resistant Enterococcus (VRE) colonization and infection in allogeneic hematopoietic stem cell transplantation (allo‐HSCT) recipients, data are inadequate for patients undergoing autologous (auto‐)HSCT.

Methods

We conducted a retrospective cohort study of 300 consecutive patients receiving an auto‐HSCT between 2006 and 2014. Patients had stool cultures for VRE on admission and weekly during hospitalization.

Results

Thirty‐six percent of patients had VRE gastrointestinal (GI) colonization and 3% developed a VRE bloodstream infection (BSI), all of whom were colonized. VRE strain typing of BSI isolates showed that some patients shared identical patterns. Rates of colonization and BSI in colonized patients were similar to simultaneous patients undergoing allo‐HSCT, except that the latter had a higher rate of colonization at admission. A diagnosis of lymphoma was associated with an increased risk of colonization. VRE BSI was associated with longer lengths of stay and possibly higher costs, but no decrease in overall survival, and colonized patients had no VRE infections during the year following discharge. Repeat stool cultures in patients subsequently undergoing allo‐HSCT suggested that most, if not all, VRE‐positive auto‐HSCT patients lose their detectable GI colonization within a few months of discharge.

Conclusion

VRE colonization is frequent but carries a low risk for infection in patients undergoing auto‐HSCT. However, these patients can serve as reservoirs for transmission to higher risk patients. Moreover, patients may remain colonized if proceeding to an allo‐HSCT shortly after auto‐HSCT, potentially increasing the risk of the allogeneic procedure.