Potencial Analítico de los Polímeros de Impronta Molecular (MIPs) como Elementos de Reconocimiento Biomimético

Los polímeros de impronta molecular (MIPs) son materiales sintéticos que presentan propiedades de reconocimiento molecular específico hacia determinados compuestos. Estos materiales con “memoria selectiva” presentan un elevado potencial analítico como sustitutos de elementos de reconocimiento de origen biológico para el desarrollo de sensores, como sorbentes en procesos de extracción en fase sólida (SPE) y como fases estacionarias para HPLC y CE. La síntesis de estos materiales se basa en la formación de una estructura polimérica, altamente entrecruzada, alrededor de una molécula que actúa como plantilla que se extrae después de la polimerización. De esta forma, el MIP contendrá sitios de unión que son complementarios a la molécula plantilla en forma, tamaño y distribución de grupos funcionales que permiten su reconocimiento posterior, de forma selectiva Los MIPs suelen presentar ventajas interesantes en comparación con los receptore

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

CIBERER : Spanish national network for research on rare diseases: A highly productive collaborative initiative

Altres ajuts: Instituto de Salud Carlos III (ISCIII); Ministerio de Ciencia e Innovación.CIBER (Center for Biomedical Network Research; Centro de Investigación Biomédica En Red) is a public national consortium created in 2006 under the umbrella of the Spanish National Institute of Health Carlos III (ISCIII). This innovative research structure comprises 11 different specific areas dedicated to the main public health priorities in the National Health System. CIBERER, the thematic area of CIBER focused on rare diseases (RDs) currently consists of 75 research groups belonging to universities, research centers, and hospitals of the entire country. CIBERER's mission is to be a center prioritizing and favoring collaboration and cooperation between biomedical and clinical research groups, with special emphasis on the aspects of genetic, molecular, biochemical, and cellular research of RDs. This research is the basis for providing new tools for the diagnosis and therapy of low-prevalence diseases, in line with the International Rare Diseases Research Consortium (IRDiRC) objectives, thus favoring translational research between the scientific environment of the laboratory and the clinical setting of health centers. In this article, we intend to review CIBERER's 15-year journey and summarize the main results obtained in terms of internationalization, scientific production, contributions toward the discovery of new therapies and novel genes associated to diseases, cooperation with patients' associations and many other topics related to RD research

Early phase of plasticity-related gene regulation and SRF dependent transcription in the hippocampus

Hippocampal organotypic cultures are a highly reliable in vitro model for studying neuroplasticity: in this paper, we analyze the early phase of the transcriptional response induced by a 20 \ub5M gabazine treatment (GabT), a GABA-Ar antagonist, by using Affymetrix oligonucleotide microarray, RT-PCR based time-course and chromatin-immuno-precipitation. The transcriptome profiling revealed that the pool of genes up-regulated by GabT, besides being strongly related to the regulation of growth and synaptic transmission, is also endowed with neuro-protective and pro-survival properties. By using RT-PCR, we quantified a time-course of the transient expression for 33 of the highest up-regulated genes, with an average sampling rate of 10 minutes and covering the time interval [10 3690] minutes. The cluster analysis of the time-course disclosed the existence of three different dynamical patterns, one of which proved, in a statistical analysis based on results from previous works, to be significantly related with SRF-dependent regulation (p-value<0.05). The chromatin immunoprecipitation (chip) assay confirmed the rich presence of working CArG boxes in the genes belonging to the latter dynamical pattern and therefore validated the statistical analysis. Furthermore, an in silico analysis of the promoters revealed the presence of additional conserved CArG boxes upstream of the genes Nr4a1 and Rgs2. The chip assay confirmed a significant SRF signal in the Nr4a1 CArG box but not in the Rgs2 CArG box

Outcomes from elective colorectal cancer surgery during the SARS-CoV-2 pandemic

This study aimed to describe the change in surgical practice and the impact of SARS-CoV-2 on mortality after surgical resection of colorectal cancer during the initial phases of the SARS-CoV-2 pandemic

Role of age and comorbidities in mortality of patients with infective endocarditis

[Purpose]: The aim of this study was to analyse the characteristics of patients with IE in three groups of age and to assess the ability of age and the Charlson Comorbidity Index (CCI) to predict mortality. [Methods]: Prospective cohort study of all patients with IE included in the GAMES Spanish database between 2008 and 2015.Patients were stratified into three age groups:<65 years,65 to 80 years,and ≥ 80 years.The area under the receiver-operating characteristic (AUROC) curve was calculated to quantify the diagnostic accuracy of the CCI to predict mortality risk. [Results]: A total of 3120 patients with IE (1327 < 65 years;1291 65-80 years;502 ≥ 80 years) were enrolled.Fever and heart failure were the most common presentations of IE, with no differences among age groups.Patients ≥80 years who underwent surgery were significantly lower compared with other age groups (14.3%,65 years; 20.5%,65-79 years; 31.3%,≥80 years). In-hospital mortality was lower in the <65-year group (20.3%,<65 years;30.1%,65-79 years;34.7%,≥80 years;p < 0.001) as well as 1-year mortality (3.2%, <65 years; 5.5%, 65-80 years;7.6%,≥80 years; p = 0.003).Independent predictors of mortality were age ≥ 80 years (hazard ratio [HR]:2.78;95% confidence interval [CI]:2.32–3.34), CCI ≥ 3 (HR:1.62; 95% CI:1.39–1.88),and non-performed surgery (HR:1.64;95% CI:11.16–1.58).When the three age groups were compared,the AUROC curve for CCI was significantly larger for patients aged <65 years(p < 0.001) for both in-hospital and 1-year mortality. [Conclusion]: There were no differences in the clinical presentation of IE between the groups. Age ≥ 80 years, high comorbidity (measured by CCI),and non-performance of surgery were independent predictors of mortality in patients with IE.CCI could help to identify those patients with IE and surgical indication who present a lower risk of in-hospital and 1-year mortality after surgery, especially in the <65-year group

Cronoestratigrafía de los registros aluviales del tránsito Pleistoceno superior-Holoceno en la depresión de la Bardena Blanca (Navarra).

In this work, preliminary chronostratigaphic features of the Upper Pleistocene-Holocene morphosedimentary alluvial unit covering the bottom of the Bardena Blanca depression are described. This unit is made up by 1) gravels and sands related to a braided channel system, 2) laminated sands and clays accumulated in distal flats of alluvial fans and 3) clays and gypsums corresponding to a playa-lake environment. According the first chronological data supplied by OSL and 14C the age of this sequence ranges between 18 and 5 ka. The prevailed paleoclimatic conditions were cold and humid during Last Glacial Maximum-Oldest Dryas and arid during Lower Holocene.Este trabajo constituye una contribución del Proyecto BTE2003-01296 del Ministerio de Ciencia y TecnologíaPeer Reviewe

Short-periodic-orbit method for excited chaotic eigenfunctions

An alternative method for the calculation of excited chaotic eigenfunctions in arbitrary energy windows is presented. We demonstrate the feasibility of using wave functions localized on unstable periodic orbits as efficient basis sets for this task in classically chaotic systems. The number of required localized wave functions is only of the order of the ratio tH/tE, with tH the Heisenberg time and tE the Ehrenfest time. As an illustration, we present convincing results for a coupled two-dimensional quartic oscillator with chaotic dynamics