Galanin and galanin receptor expression in neuroblastic tumours: correlation with their differentiation status

Neuroblastoma and its benign differentiated counterpart, ganglioneuroma, are paediatric neuroblastic tumours arising in the sympathetic nervous system. Their broad spectrum of clinical virulence is mainly related to heterogeneous biologic background and tumour differentiation. Neuroblastic tumours synthesize various neuropeptides acting as neuromodulators. Previous studies suggested that galanin plays a role in sympathetic tissue where it could be involved in differentiation and development. We investigated the expression and distribution of galanin and its three known receptors (Gal-R1, Gal-R2, Gal-R3) in 19 samples of neuroblastic tumours tissue by immunohistochemistry, in situ hybridization and fluorescent-ligand binding. This study provides clear evidence for galanin and galanin receptor expression in human neuroblastic tumours. The messengers coding for galanin, Gal-R1 and -R3 were highly expressed in neuroblastoma and their amount dramatically decreased in ganglioneuroma. In contrast, Gal-R2 levels remained unchanged. Double labelling studies showed that galanin was mainly co-expressed with its receptors whatever the differentiation stage. In neuroblastic tumours, galanin might promote cell-survival or counteract neuronal differentiation through the different signalling pathways mediated by galanin receptors. Finally, our results suggest that galanin influences neuroblastoma growth and development as an autocrine/paracrine modulator. These findings suggest potential critical implications for galanin in neuroblastic tumours development

The politics of heroes through the prism of popular heroism

This is the author accepted manuscript. The final version is available from Palgrave Macmillan via the DOI in this record.In modern day Britain, the discourse of national heroification is routinely utilised by politicians, educationalists and cultural industry professionals, whilst also being a popular concept to describe deserving ‘do-gooders’ who contribute to British society in a myriad of ways. We argue that although this heroification discourse is enacted as a discursive device of encouraging politically and morally desirable behaviour, it is dissociated from the largely under-explored facets of contemporary popular heroism. To compensate for this gap, this paper explores public preferences for heroes using survey data representative of British adults. This analysis demonstrates a conceptual stretching in the understanding of heroism, and allows identifying age- and gender-linked dynamics which effect public choices of heroes. In particular, we demonstrate that age above all determines the preference for having a hero, but does not explain preferences for specific hero-types. The focus on gender illustrates that the landscape of popular heroism reproduces a male-dominated bias which exists in the wider political and cultural heroification discourse. Simultaneously, our study shows that if national heroification discourse in Britain remains male-centric, the landscape of popular heroism is characterised by a gendered trend towards privatisation of heroes being particularly prominent amongst women. In the conclusion, this paper argues for a conceptual revision and re-gendering of the national heroification discourse as a step towards both empirically grounded, and age- and gender-sensitive politics of heroes and heroines.AHR

Potassium and Sodium Transport in Yeast

[EN] As the proper maintenance of intracellular potassium and sodium concentrations is vital for cell growth, all living organisms have developed a cohort of strategies to maintain proper monovalent cation homeostasis. In the model yeast Saccharomyces cerevisiae, potassium is accumulated to relatively high concentrations and is required for many aspects of cellular function, whereas high intracellular sodium/potassium ratios are detrimental to cell growth and survival. The fact that S. cerevisiae cells can grow in the presence of a broad range of concentrations of external potassium (10 M–2.5 M) and sodium (up to 1.5 M) indicates the existence of robust mechanisms that have evolved to maintain intracellular concentrations of these cations within appropriate limits. In this review, current knowledge regarding potassium and sodium transporters and their regulation will be summarized. The cellular responses to high sodium and potassium and potassium starvation will also be discussed, as well as applications of this knowledge to diverse fields, including antifungal treatments, bioethanol production and human disease.L.Y. is funded by grant BFU2011-30197-C03-03 from the Spanish Ministry of Science and Innovation (Madrid, Spain) and EUI2009-04147 [Systems Biology of Microorganisms (SysMo2) European Research Area-Network (ERA-NET)].Yenush, L. (2016). Potassium and Sodium Transport in Yeast. Advances in Experimental Medicine and Biology. 892:187-228. https://doi.org/10.1007/978-3-319-25304-6_8S187228892Ahmed A, Sesti F, Ilan N, Shih TM, Sturley SL et al (1999) A molecular target for viral killer toxin: TOK1 potassium channels. Cell 99:283–291Albert A, Yenush L, Gil-Mascarell MR, Rodriguez PL, Patel S et al (2000) X-ray structure of yeast Hal2p, a major target of lithium and sodium toxicity, and identification of framework interactions determining cation sensitivity. J Mol Biol 295:927–938Albertyn J, Hohmann S, Thevelein JM, Prior BA (1994) GPD1, which encodes glycerol-3-phosphate dehydrogenase, is essential for growth under osmotic stress in Saccharomyces cerevisiae, and its expression is regulated by the high-osmolarity glycerol response pathway. Mol Cell Biol 14:4135–4144Alepuz PM, Cunningham KW, Estruch F (1997) Glucose repression affects ion homeostasis in yeast through the regulation of the stress-activated ENA1 gene. Mol Microbiol 26:91–98Ali R, Brett CL, Mukherjee S, Rao R (2004) Inhibition of sodium/proton exchange by a Rab-GTPase-activating protein regulates endosomal traffic in yeast. J Biol Chem 279:4498–4506Alijo R, Ramos J (1993) Several routes of activation of the potassium uptake system of yeast. Biochim Biophys Acta 1179:224–228Anderson JA, Huprikar SS, Kochian LV, Lucas WJ, Gaber RF (1992) Functional expression of a probable Arabidopsis thaliana potassium channel in Saccharomyces cerevisiae. Proc Natl Acad Sci U S A 89:3736–3740Anderson JA, Nakamura RL, Gaber RF (1994) Heterologous expression of K+ channels in Saccharomyces cerevisiae: strategies for molecular analysis of structure and function. Symp Soc Exp Biol 48:85–97André B, Scherens B (1995) The yeast YBR235w gene encodes a homolog of the mammalian electroneutral Na(+)-(K+)-C1- cotransporter family. Biochem Biophys Res Commun 217:150–153Andrés MT, Viejo-Díaz M, Fierro JF (2008) Human lactoferrin induces apoptosis-like cell death in Candida albicans: critical role of K+-channel-mediated K+ efflux. Antimicrob Agents Chemother 52:4081–4088Anemaet IG, van Heusden GP (2014) Transcriptional response of Saccharomyces cerevisiae to potassium starvation. BMC Genomics 15:1040Arino J, Ramos J, Sychrova H (2010) Alkali metal cation transport and homeostasis in yeasts. Microbiol Mol Biol Rev 74:95–120Babazadeh R, Furukawa T, Hohmann S, Furukawa K (2014) Rewiring yeast osmostress signalling through the MAPK network reveals essential and non-essential roles of Hog1 in osmoadaptation. Sci Rep 4:4697Baev D, Rivetta A, Li XS, Vylkova S, Bashi E et al (2003) Killing of Candida albicans by human salivary histatin 5 is modulated, but not determined, by the potassium channel TOK1. Infect Immun 71:3251–3260Baev D, Rivetta A, Vylkova S, Sun JN, Zeng GF et al (2004) The TRK1 potassium transporter is the critical effector for killing of Candida albicans by the cationic protein, Histatin 5. J Biol Chem 279:55060–55072Bagriantsev SN, Ang KH, Gallardo-Godoy A, Clark KA, Arkin MR et al (2013) A high-throughput functional screen identifies small molecule regulators of temperature- and mechano-sensitive K2P channels. ACS Chem Biol 8:1841–1851Bañuelos MA, Sychrová H, Bleykasten-Grosshans C, Souciet JL, Potier S (1998) The Nha1 antiporter of Saccharomyces cerevisiae mediates sodium and potassium efflux. Microbiology 144(Pt 10):2749–2758Bañuelos MA, Ruiz MC, Jiménez A, Souciet JL, Potier S et al (2002) Role of the Nha1 antiporter in regulating K(+) influx in Saccharomyces cerevisiae. Yeast 19:9–15Barnett JA (2008) A history of research on yeasts 13. Active transport and the uptake of various metabolites. Yeast 25:689–731Barreto L, Canadell D, Petrezselyova S, Navarrete C, Maresova L et al (2011) A genomewide screen for tolerance to cationic drugs reveals genes important for potassium homeostasis in Saccharomyces cerevisiae. Eukaryot Cell 10:1241–1250Barreto L, Canadell D, Valverde-Saubí D, Casamayor A, Ariño J (2012) The short-term response of yeast to potassium starvation. Environ Microbiol 14:3026–3042Benito B, Moreno E, Lagunas R (1991) Half-life of the plasma membrane ATPase and its activating system in resting yeast cells. Biochim Biophys Acta 1063:265–268Benito B, Quintero FJ, Rodríguez-Navarro A (1997) Overexpression of the sodium ATPase of Saccharomyces cerevisiae: conditions for phosphorylation from ATP and Pi. Biochim Biophys Acta 1328:214–226Benito B, Garciadeblás B, Rodríguez-Navarro A (2002) Potassium- or sodium-efflux ATPase, a key enzyme in the evolution of fungi. Microbiology 148:933–941Benito B, Garciadeblás B, Schreier P, Rodríguez-Navarro A (2004) Novel p-type ATPases mediate high-affinity potassium or sodium uptake in fungi. Eukaryot Cell 3:359–368Bernardi P (1999) Mitochondrial transport of cations: channels, exchangers, and permeability transition. Physiol Rev 79:1127–1155Bertl A, Slayman CL, Gradmann D (1993) Gating and conductance in an outward-rectifying K+ channel from the plasma membrane of Saccharomyces cerevisiae. J Membr Biol 132:183–199Bertl A, Bihler H, Reid JD, Kettner C, Slayman CL (1998) Physiological characterization of the yeast plasma membrane outward rectifying K+ channel, DUK1 (TOK1), in situ. J Membr Biol 162:67–80Bertl A, Ramos J, Ludwig J, Lichtenberg-Fraté H, Reid J et al (2003) Characterization of potassium transport in wild-type and isogenic yeast strains carrying all combinations of trk1, trk2 and tok1 null mutations. Mol Microbiol 47:767–780Bihler H, Slayman CL, Bertl A (1998) NSC1: a novel high-current inward rectifier for cations in the plasma membrane of Saccharomyces cerevisiae. FEBS Lett 432:59–64Bihler H, Slayman CL, Bertl A (2002) Low-affinity potassium uptake by Saccharomyces cerevisiae is mediated by NSC1, a calcium-blocked non-specific cation channel. Biochim Biophys Acta 1558:109–118Blomberg A (1995) Global changes in protein synthesis during adaptation of the yeast Saccharomyces cerevisiae to 0.7 M NaCl. J Bacteriol 177:3563–3572Blomberg A (2000) Metabolic surprises in Saccharomyces cerevisiae during adaptation to saline conditions: questions, some answers and a model. FEMS Microbiol Lett 182:1–8Borst-Pauwels GW (1981) Ion transport in yeast. Biochim Biophys Acta 650:88–127Botstein D, Fink GR (2011) Yeast: an experimental organism for 21st Century biology. Genetics 189:695–704Bouillet LE, Cardoso AS, Perovano E, Pereira RR, Ribeiro EM et al (2012) The involvement of calcium carriers and of the vacuole in the glucose-induced calcium signaling and activation of the plasma membrane H(+)-ATPase in Saccharomyces cerevisiae cells. Cell Calcium 51:72–81Bowers K, Levi BP, Patel FI, Stevens TH (2000) The sodium/proton exchanger Nhx1p is required for endosomal protein trafficking in the yeast Saccharomyces cerevisiae. Mol Biol Cell 11:4277–4294Breinig F, Tipper DJ, Schmitt MJ (2002) Kre1p, the plasma membrane receptor for the yeast K1 viral toxin. Cell 108:395–405Brett CL, Tukaye DN, Mukherjee S, Rao R (2005) The yeast endosomal Na+K+/H+ exchanger Nhx1 regulates cellular pH to control vesicle trafficking. Mol Biol Cell 16:1396–1405Cagnac O, Leterrier M, Yeager M, Blumwald E (2007) Identification and characterization of Vnx1p, a novel type of vacuolar monovalent cation/H+ antiporter of Saccharomyces cerevisiae. J Biol Chem 282:24284–24293Cagnac O, Aranda-Sicilia MN, Leterrier M, Rodriguez-Rosales MP, Venema K (2010) Vacuolar cation/H+ antiporters of Saccharomyces cerevisiae. J Biol Chem 285:33914–33922Calahorra M, Lozano C, Sánchez NS, Peña A (2011) Ketoconazole and miconazole alter potassium homeostasis in Saccharomyces cerevisiae. Biochim Biophys Acta 1808:433–445Canadell D, González A, Casado C, Ariño J (2015) Functional interactions between potassium and phosphate homeostasis in Saccharomyces cerevisiae. Mol Microbiol 95:555–572Casado C, Yenush L, Melero C, del Carmen Ruiz M, Serrano R et al (2010) Regulation of Trk-dependent potassium transport by the calcineurin pathway involves the Hal5 kinase. FEBS Lett 584:2415–2420Causton HC, Ren B, Koh SS, Harbison CT, Kanin E et al (2001) Remodeling of yeast genome expression in response to environmental changes. Mol Biol Cell 12:323–337Clotet J, Posas F (2007) Control of cell cycle in response to osmostress: lessons from yeast. Methods Enzymol 428:63–76Cornet M, Gaillardin C (2014) pH signaling in human fungal pathogens: a new target for antifungal strategies. Eukaryot Cell 13:342–352Courchesne WE (2002) Characterization of a novel, broad-based fungicidal activity for the antiarrhythmic drug amiodarone. J Pharmacol Exp Ther 300:195–199Courchesne WE, Ozturk S (2003) Amiodarone induces a caffeine-inhibited, MID1-dependent rise in free cytoplasmic calcium in Saccharomyces cerevisiae. Mol Microbiol 47:223–234Crespo JL, Daicho K, Ushimaru T, Hall MN (2001) The GATA transcription factors GLN3 and GAT1 link TOR to salt stress in Saccharomyces cerevisiae. J Biol Chem 276:34441–34444Cunningham KW, Fink GR (1996) Calcineurin inhibits VCX1-dependent H+/Ca2+ exchange and induces Ca2+ ATPases in Saccharomyces cerevisiae. Mol Cell Biol 16:2226–2237Curto M, Valledor L, Navarrete C, Gutiérrez D, Sychrova H et al (2010) 2-DE based proteomic analysis of Saccharomyces cerevisiae wild and K+ transport-affected mutant (trk1,2) strains at the growth exponential and stationary phases. J Proteomics 73:2316–2335D’Avanzo N, Cheng WW, Xia X, Dong L, Savitsky P et al (2010) Expression and purification of recombinant human inward rectifier K+ (KCNJ) channels in Saccharomyces cerevisiae. Protein Expr Purif 71:115–121Daran-Lapujade P, Daran JM, Luttik MA, Almering MJ, Pronk JT et al (2009) An atypical PMR2 locus is responsible for hypersensitivity to sodium and lithium cations in the laboratory strain Saccharomyces cerevisiae CEN.PK113-7D. FEMS Yeast Res 9:789–792Davis DA (2009) How human pathogenic fungi sense and adapt to pH: the link to virulence. Curr Opin Microbiol 12:365–370de Nadal E, Posas F (2011) Elongating under stress. Genet Res Int 2011:326286de Nadal E, Clotet J, Posas F, Serrano R, Gomez N et al (1998) The yeast halotolerance determinant Hal3p is an inhibitory subunit of the Ppz1p Ser/Thr protein phosphatase. Proc Natl Acad Sci U S A 95:7357–7362de Nadal E, Calero F, Ramos J, Ariño J (1999) Biochemical and genetic analyses of the role of yeast casein kinase 2 in salt tolerance. J Bacteriol 181:6456–6462de Nadal E, Alepuz PM, Posas F (2002) Dealing with osmostress through MAP kinase activation. EMBO Rep 3:735–740De Nadal E, Zapater M, Alepuz PM, Sumoy L, Mas G et al (2004) The MAPK Hog1 recruits Rpd3 histone deacetylase to activate osmoresponsive genes. Nature 427:370–374Dimmer KS, Fritz S, Fuchs F, Messerschmitt M, Weinbach N et al (2002) Genetic basis of mitochondrial function and morphology in Saccharomyces cerevisiae. Mol Biol Cell 13:847–853Durell SR, Guy HR (1999) Structural models of the KtrB, TrkH, and Trk1,2 symporters based on the structure of the KcsA K(+) channel. Biophys J 77:789–807Eide DJ, Clark S, Nair TM, Gehl M, Gribskov M et al (2005) Characterization of the yeast ionome: a genome-wide analysis of nutrient mineral and trace element homeostasis in Saccharomyces cerevisiae. Genome Biol 6:R77Elicharova H, Sychrova H (2014) Fluconazole affects the alkali-metal-cation homeostasis and susceptibility to cationic toxic compounds of Candida glabrata. Microbiology 160:1705–1713Endele S, Fuhry M, Pak SJ, Zabel BU, Winterpacht A (1999) LETM1, a novel gene encoding a putative EF-hand Ca(2+)-binding protein, flanks the Wolf-Hirschhorn syndrome (WHS) critical region and is deleted in most WHS patients. Genomics 60:218–225Eraso P, Mazón MJ, Portillo F (2006) Yeast protein kinase Ptk2 localizes at the plasma membrane and phosphorylates in vitro the C-terminal peptide of the H+-ATPase. Biochim Biophys Acta 1758:164–170Erez O, Kahana C (2002) Deletions of SKY1 or PTK2 in the Saccharomyces cerevisiae trk1Deltatrk2Delta mutant cells exert dual effect on ion homeostasis. Biochem Biophys Res Commun 295:1142–1149Estrada E, Agostinis P, Vandenheede JR, Goris J, Merlevede W et al (1996) Phosphorylation of yeast plasma membrane H+-ATPase by casein kinase I. J Biol Chem 271:32064–32072Fairman C, Zhou X, Kung C (1999) Potassium uptake through the TOK1 K+ channel in the budding yeast. J Membr Biol 168:149–157Farnaud S, Evans RW (2003) Lactoferrin – a multifunctional protein with antimicrobial properties. Mol Immunol 40:395–405Fell GL, Munson AM, Croston MA, Rosenwald AG (2011) Identification of yeast genes involved in k homeostasis: loss of membrane traffic genes affects k uptake. G3 (Bethesda) 1:43–56Fernandes AR, Sá-Correia I (2003) Transcription patterns of PMA1 and PMA2 genes and activity of plasma membrane H+-ATPase in Saccharomyces cerevisiae during diauxic growth and stationary phase. Yeast 20:207–219Ferrando A, Kron SJ, Rios G, Fink GR, Serrano R (1995) Regulation of cation transport in Saccharomyces cerevisiae by the salt tolerance gene HAL3. Mol Cell Biol 15:5470–5481Ferrigno P, Posas F, Koepp D, Saito H, Silver PA (1998) Regulated nucleo/cytoplasmic exchange of HOG1 MAPK requires the importin beta homologs NMD5 and XPO1. EMBO J 17:5606–5614Flegelova H, Haguenauer-Tsapis R, Sychrova H (2006) Heterologous expression of mammalian Na/H antiporters in Saccharomyces cerevisiae. Biochim Biophys Acta 1760:504–516Flis K, Hinzpeter A, Edelman A, Kurlandzka A (2005) The functioning of mammalian ClC-2 chloride channel in Saccharomyces cerevisiae cells requires an increased level of Kha1p. Biochem J 390:655–664Forment J, Mulet JM, Vicente O, Serrano R (2002) The yeast SR protein kinase Sky1p modulates salt tolerance, membrane potential and the Trk1,2 potassium transporter. Biochim Biophys Acta 1565:36–40Froschauer E, Nowikovsky K, Schweyen RJ (2005) Electroneutral K+/H+ exchange in mitochondrial membrane vesicles involves Yol027/Letm1 proteins. Biochim Biophys Acta 1711:41–48Fukuda A, Nakamura A, Tagiri A, Tanaka H, Miyao A et al (2004) Function, intracellular localization and the importance in salt tolerance of a vacuolar Na(+)/H(+) antiporter from rice. Plant Cell Physiol 45:146–159Gaber RF (1992) Molecular genetics of yeast ion transport. Int Rev Cytol 137:299–353Gaber RF, Styles CA, Fink GR (1988) TRK1 encodes a plasma membrane protein required for high-affinity potassium transport in Saccharomyces cerevisiae. Mol Cell Biol 8:2848–2859Gaxiola RA, Rao R, Sherman A, Grisafi P, Alper SL et al (1999) The Arabidopsis thaliana proton transporters, AtNhx1 and Avp1, can function in cation detoxification in yeast. Proc Natl Acad Sci U S A 96:1480–1485Gelis S, Curto M, Valledor L, González A, Ariño J et al (2012) Adaptation to potassium starvation of wild-type and K(+)-transport mutant (trk1,2) of Saccharomyces cerevisiae: 2-dimensional gel electrophoresis-based proteomic approach. Microbiologyopen 1:182–193Gómez MJ, Luyten K, Ramos J (1996) The capacity to transport potassium influences sodium tolerance in Saccharomyces cerevisiae. FEMS Microbiol Lett 135:157–160González A, Casado C, Petrezsélyová S, Ruiz A, Ariño J (2013) Molecular analysis of a conditional hal3 vhs3 yeast mutant links potassium homeostasis with flocculation and invasiveness. Fungal Genet Biol 53:1–9Goossens A, de La Fuente N, Forment J, Serrano R, Portillo F (2000) Regulation of yeast H(+)-ATPase by protein kinases belonging to a family dedicated to activation of plasma membrane transporters. Mol Cell Biol 20:7654–7661Gupta SS, Canessa CM (2000) Heterologous expression of a mammalian epithelial sodium channel in yeast. FEBS Lett 481:77–80Gustin MC, Martinac B, Saimi Y, Culbertson MR, Kung C (1986) Ion channels in yeast. Science 233:1195–1197Haass FA, Jonikas M, Walter P, Weissman JS, Jan YN et al (2007) Identification of yeast proteins necessary for cell-surface function of a potassium channel. Proc Natl Acad Sci U S A 104:18079–18084Haro R, Rodríguez-Navarro A (2002) Molecular analysis of the mechanism of potassium uptake through the TRK1 transporter of Saccharomyces cerevisiae. Biochim Biophys Acta 1564:114–122Haro R, Rodríguez-Navarro A (2003) Functional analysis of the M2(D) helix of the TRK1 potassium transporter of Saccharomyces cerevisiae. Biochim Biophys Acta 1613:1–6Haro R, Garciadeblas B, Rodríguez-Navarro A (1991) A novel P-type ATPase from yeast involved in sodium transport. FEBS Lett 291:189–191Hasenbrink G, Schwarzer S, Kolacna L, Ludwig J, Sychrova H et al (2005) Analysis of the mKir2.1 channel activity in potassium influx defective Saccharomyces cerevisiae strains determined as changes in growth characteristics. FEBS Lett 579:1723–1731Herrera R, Álvarez MC, Gelis S, Ramos J (2013) Subcellular potassium and sodium distribution in Saccharomyces cerevisiae wild-type and vacuolar mutants. Biochem J 454:525–532Herrera R, Alvarez MC, Gelis S, Kodedová M, Sychrová H et al (2014) Role of Saccharomyces cerevisiae Trk1 in stabilization of intracellular potassium content upon changes in external potassium levels. Biochim Biophys Acta 1838:127–133Hess DC, Lu W, Rabinowitz JD, Botstein D (2006) Ammonium toxicity and potassium limitation in yeast. PLoS Biol 4:e351Hoeberichts FA, Perez-Valle J, Montesinos C, Mulet JM, Planes MD et al (2010) The role of K+ and H+ transport systems during glucose- and H2O2-induced cell death in Saccharomyces cerevisiae. Yeast 27:713–725Hohmann S (2002) Osmotic stress signaling and osmoadaptation in yeasts. Microbiol Mol Biol Rev 66:300–372Hohmann S, Krantz M, Nordlander B (2007) Yeast osmoregulation. Methods Enzymol 428:29–45Idnurm A, Walton FJ, Floyd A, Reedy JL, Heitman J (2009) Identification of ENA1 as a virulence gene of the human pathogenic fungus Cryptococcus neoformans through signature-tagged insertional mutagenesis. Eukaryot Cell 8:315–326Jung KW, Strain AK, Nielsen K, Jung KH, Bahn YS (2012) Two cation transporters Ena1 and Nha1 cooperatively modulate ion homeostasis, antifungal drug resistance, and virulence of Cryptococcus neoformans via the HOG pathway. Fungal Genet Biol 49:332–345Kafadar KA, Cyert MS (2004) Integration of stress responses: modulation of calcineurin signaling in Saccharomyces cerevisiae by protein kinase A. Eukaryot Cell 3:1147–1153Kahm M, Navarrete C, Llopis-Torregrosa V, Herrera R, Barreto L et al (2012) Potassium starvation in yeast: mechanisms of homeostasis revealed by mathematical modeling. PLoS Comput Biol 8:e1002548Kallay LM, Brett CL, Tukaye DN, Wemmer MA, Chyou A et al (2011) Endosomal Na+(K+)/H+ exchanger Nhx1/Vps44 functions independently and downstream of multivesicular body formation. J Biol Chem 286:44067–44077Kane PM (2007) The long physiological reach of the yeast vacuolar H+-ATPase. J Bioenerg Biomembr 39:415–421Kane PM (2012) Targeting reversible disassembly as a mechanism of controlling V-ATPase activity. Curr Protein Pept Sci 13:117–123Ke R, Ingram PJ, Haynes K (2013) An integrative model of ion regulation in yeast. PLoS Comput Biol 9:e1002879Ketchum KA, Joiner WJ, Sellers AJ, Kaczmarek LK, Goldstein SA (1995) A new family of outwardly rectifying potassium channel proteins with two pore domains in tandem. Nature 376:690–695Kinclová O, Ramos J, Potier S, Sychrová H (2001) Functional study of the Saccharomyces cerevisiae Nha1p C-terminus. Mol Microbiol 40:656–668Kinclova-Zimmermannova O, Sychrova H (2006) Functional study of the Nha1p C-terminus: involvement in cell response to changes in external osmolarity. Curr Genet 49:229–236Kinclová-Zimmermannová O, Flegelová H, Sychrová H (2004) Rice Na+/H+-antiporter Nhx1 partially complements the alkali-metal-cation sensitivity of yeast strains lacking three sodium transporters. Folia Microbiol (Praha) 49:519–525Kinclova-Zimmermannova O, Gaskova D, Sychrova H (2006) The Na+, K+/H+ -antiporter Nha1 influences the plasma membrane potential of Saccharomyces cerevisiae. FEMS Yeast Res 6:792–800Klee CB, Draetta GF, Hubbard MJ (1988) Calcineurin. Adv Enzymol Relat Areas Mol Biol 61:149–200Klipp E, Nordlander B, Krüger R, Gennemark P, Hohmann S (2005) Integrative model of the response of yeast to osmotic shock. Nat Biotechnol 23:975–982Ko CH, Gaber RF (1991) TRK1 and TRK2 encode structurally related K+ transporters in Saccharomyces cerevisiae. Mol Cell Biol 11:4266–4273Ko CH, Buckley AM, Gaber RF (1990) TRK2 is required for low affinity K+ transport in Saccharomyces cerevisiae. Genetics 125:305–312Ko CH, Liang H, Gaber RF (1993) Roles of multiple glucose transporters in Saccharomyces cerevisiae. Mol Cell Biol 13:638–648Kojima A, To

Geolocation with respect to persona privacy for the Allergy Diary app - a MASK study

Background: Collecting data on the localization of users is a key issue for the MASK (Mobile Airways Sentinel network: the Allergy Diary) App. Data anonymization is a method of sanitization for privacy. The European Commission's Article 29 Working Party stated that geolocation information is personal data. To assess geolocation using the MASK method and to compare two anonymization methods in the MASK database to find an optimal privacy method. Methods: Geolocation was studied for all people who used the Allergy Diary App from December 2015 to November 2017 and who reported medical outcomes. Two different anonymization methods have been evaluated: Noise addition (randomization) and k-anonymity (generalization). Results: Ninety-three thousand one hundred and sixteen days of VAS were collected from 8535 users and 54,500 (58. 5%) were geolocalized, corresponding to 5428 users. Noise addition was found to be less accurate than k-anonymity using MASK data to protect the users' life privacy. Discussion: k-anonymity is an acceptable method for the anonymization of MASK data and results can be used for other databases.Peer reviewe

Differential cross section for W boson production as a function of transverse momentum in proton-antiproton collisions at 1.8 TeV

We report a measurement of the differential cross section for W boson production as a function of its transverse momentum in proton-antiproton collisions at sqrt{s} = 1.8 TeV. The data were collected by the D0 experiment at the Fermilab Tevatron Collider during 1994-1995 and correspond to an integrated luminosity of 85 pb^{-1}. The results are in good agreement with quantum chromodynamics over the entire range of transverse momentum.Comment: Accepted by Physics Letters

Measurement of the ratio of differential cross sections for W and Z boson production as a function of transverse momentum in pbar p collisions at sqrt(s)=1.8 TeV

We report on a measurement of the ratio of the differential cross sections for W and Z boson production as a function of transverse momentum in proton-antiproton collisions at sqrt(s) = 1.8 TeV. This measurement uses data recorded by the D0 detector at the Fermilab Tevatron in 1994-1995. It represents the first investigation of a proposal that ratios between W and Z observables can be calculated reliably using perturbative QCD, even when the individual observables are not. Using the ratio of differential cross sections reduces both experimental and theoretical uncertainties, and can therefore provide smaller overall uncertainties in the measured mass and width of the W boson than current methods used at hadron colliders.Comment: 10 pages, 2 figures, to be published in Physics Letters

Performance of missing transverse momentum reconstruction with the ATLAS detector using proton–proton collisions at √s = 13 TeV

The performance of the missing transverse momentum (EmissT) reconstruction with the ATLAS detector is evaluated using data collected in proton–proton collisions at the LHC at a centre-of-mass energy of 13 TeV in 2015. To reconstruct EmissT, fully calibrated electrons, muons, photons, hadronically decaying τ -leptons, and jets reconstructed from calorimeter energy deposits and charged-particle tracks are used. These are combined with the soft hadronic activity measured by reconstructed charged-particle tracks not associated with the hard objects. Possible double counting of contributions from reconstructed charged-particle tracks from the inner detector, energy deposits in the calorimeter, and reconstructed muons from the muon spectrometer is avoided by applying a signal ambiguity resolution procedure which rejects already used signals when combining the various EmissT contributions. The individual terms as well as the overall reconstructed EmissT are evaluated with various performance metrics for scale (linearity), resolution, and sensitivity to the data-taking conditions. The method developed to determine the systematic uncertainties of the EmissT scale and resolution is discussed. Results are shown based on the full 2015 data sample corresponding to an integrated luminosity of 3.2 fb−1

Measurement of the t¯tZ and t¯tW cross sections in proton-proton collisions at √s=13 TeV with the ATLAS detector

A measurement of the associated production of a top-quark pair (t¯t) with a vector boson (W, Z) in proton-proton collisions at a center-of-mass energy of 13 TeV is presented, using 36.1  fb−1 of integrated luminosity collected by the ATLAS detector at the Large Hadron Collider. Events are selected in channels with two same- or opposite-sign leptons (electrons or muons), three leptons or four leptons, and each channel is further divided into multiple regions to maximize the sensitivity of the measurement. The t¯tZ and t¯tW production cross sections are simultaneously measured using a combined fit to all regions. The best-fit values of the production cross sections are σt¯tZ=0.95±0.08stat±0.10syst pb and σt¯tW=0.87±0.13stat±0.14syst pb in agreement with the Standard Model predictions. The measurement of the t¯tZ cross section is used to set constraints on effective field theory operators which modify the t¯tZ vertex

Performance of the upgraded PreProcessor of the ATLAS Level-1 Calorimeter Trigger

The PreProcessor of the ATLAS Level-1 Calorimeter Trigger prepares the analogue trigger signals sent from the ATLAS calorimeters by digitising, synchronising, and calibrating them to reconstruct transverse energy deposits, which are then used in further processing to identify event features. During the first long shutdown of the LHC from 2013 to 2014, the central components of the PreProcessor, the Multichip Modules, were replaced by upgraded versions that feature modern ADC and FPGA technology to ensure optimal performance in the high pile-up environment of LHC Run 2. This paper describes the features of the newMultichip Modules along with the improvements to the signal processing achieved.ANPCyTYerPhI, ArmeniaAustralian Research CouncilBMWFW, AustriaAustrian Science Fund (FWF)Azerbaijan National Academy of Sciences (ANAS)SSTC, BelarusNational Council for Scientific and Technological Development (CNPq)Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)Natural Sciences and Engineering Research Council of CanadaCanada Foundation for InnovationNational Natural Science Foundation of China (NSFC)Departamento Administrativo de Ciencia, Tecnología e Innovación ColcienciasMinistry of Education, Youth & Sports - Czech Republic Czech Republic GovernmentCzech Republic GovernmentDNRF, DenmarkDanish Natural Science Research CouncilCentre National de la Recherche Scientifique (CNRS)CEA-DRF/IRFU, FranceFederal Ministry of Education & Research (BMBF)Max Planck SocietyGreek Ministry of Development-GSRTRGC and Hong Kong SAR, ChinaIsrael Science FoundationBenoziyo Center, IsraelIstituto Nazionale di Fisica Nucleare (INFN)Ministry of Education, Culture, Sports, Science and Technology, Japan (MEXT)Ministry of Education, Culture, Sports, Science and Technology, Japan (MEXT) Japan Society for the Promotion of ScienceCNRST, MoroccoRCN, NorwayPortuguese Foundation for Science and TechnologyMNE/IFA, RomaniaMES of RussiaMESTD, SerbiaMSSR, SlovakiaSlovenian Research Agency - SloveniaMIZS, SloveniaSpanish GovernmentSRC, SwedenWallenberg Foundation, SwedenSNSF Geneva, SwitzerlandMinistry of Science and Technology, TaiwanMinistry of Energy & Natural Resources - TurkeyScience & Technology Facilities Council (STFC)United States Department of Energy (DOE)National Science Foundation (NSF)BCKDF, CanadaCANARIE, CanadaCRC, CanadaEuropean Research Council (ERC)European Union (EU)French National Research Agency (ANR)German Research Foundation (DFG)Alexander von Humboldt FoundationGreek NSRF, GreeceBSF-NSF, IsraelGerman-Israeli Foundation for Scientific Research and DevelopmentLa Caixa Banking Foundation, SpainCERCA Programme Generalitat de Catalunya, SpainPROMETEO, SpainGenT Programmes Generalitat Valenciana, SpainGoran Gustafssons Stiftelse, SwedenRoyal Society of LondonLeverhulme TrustNRC, CanadaCERNANID, ChileChinese Academy of SciencesMinistry of Science and Technology, ChinaSRNSFG, GeorgiaHGF, GermanyNetherlands Organization for Scientific Research (NWO) Netherlands GovernmentMinistry of Science and Higher Education, PolandNCN, PolandNRCKI, Russia FederationJINRDST/NRF, South AfricaSERI, Geneva, SwitzerlandCantons of Bern and Geneva, SwitzerlandCompute Canada, CanadaHorizon 2020Marie Sklodowska-Curie ActionsEuropean Cooperation in Science and Technology (COST)EU-ESF, Greec