194 resultados para Kohan, Martín


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[EU] Phillips-kurba-k langabezi eta inflazioaren arteko erlazio negatiboa erakusten du. Erlazio hau 1958. urtean aurkeztu zen lehen aldiz eta geroztik hainbat aldaketa, kritika eta eztabaida jasan ditu. Hala ere, honek ez du saihestu hainbat herrialdek politika ekonomiko desberdinak aurrera eraman izana erlazio honetan oinarrituta. Lan honetan Phillips-ek aipaturiko erlazioak jasandako aldaketa desberdinak azalduko ditugu, haren oinarriak eta eraldaketak aztertuz. Espainia eta Euskadiko Phillips kurben egoerak aztertuko ditugu eta Phillips-ek proposaturiko erlazioa betetzen den ala ez konprobatuko dugu.

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Single nucleotide-polymorphisms (SNPs) are a source of diversity among human population, which may be responsible for the different individual susceptibility to diseases and/or response to drugs, among other phenotypic traits. Several low penetrance susceptibility genes associated with malignant melanoma (MM) have been described, including genes related to pigmentation, DNA damage repair and oxidative stress pathways. In the present work, we conducted a candidate gene association study based on proteins and genes whose expression we had detected altered in melanoma cell lines as compared to normal melanocytes. The result was the selection of 88 loci and 384 SNPs, of which 314 fulfilled our quality criteria for a case-control association study. The SNP rs6854854 in ANXA5 was statistically significant after conservative Bonferroni correction when 464 melanoma patients and 400 controls were analyzed in a discovery Phase I. However, this finding could not be replicated in the validation phase, perhaps because the minor allele frequency of SNP rs6854854 varies depending on the geographical region considered. Additionally, a second SNP (rs6431588) located on ILKAP was found to be associated with melanoma after considering a combined set of 1,883 MM cases and 1,358 disease-free controls. The OR was 1.29 (95% CI 1.12-1.48; p-value= 4x10(-4)). Both SNPs, rs6854854 in ANXA5 and rs6431588 in ILKAP, show population structure, which, assuming that the Spanish population is not significantly structured, suggests a role of these loci on a specific genetic adaptation to different environmental conditions. Furthermore, the biological relevance of these genes in MM is supported by in vitro experiments, which show a decrease in the transcription levels of ANXA5 and ILKAP in melanoma cells compared to normal melanocytes.

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Lipoproteins are responsible for cholesterol traffic in humans. Low density lipoprotein (LDL) delivers cholesterol from liver to peripheral tissues. A misleading delivery can lead to the formation of atherosclerotic plaques. LDL has a single protein, apoB-100, that binds to a specific receptor. It is known that the failure associated with a deficient protein-receptor binding leads to plaque formation. ApoB-100 is a large single lipid-associated polypeptide difficulting the study of its structure. IR spectroscopy is a technique suitable to follow the different conformational changes produced in apoB-100 because it is not affected by the size of the protein or the turbidity of the sample. We have analyzed LDL spectra of different individuals and shown that, even if there are not big structural changes, a different pattern in the intensity of the band located around 1617 cm 21 related with strands embedded in the lipid monolayer, can be associated with a different conformational rearrangement that could affect to a protein interacting region with the receptor.

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Homenaje a Ignacio Barandiarán Maestu / coord. por Javier Fernández Eraso, Juan Santos Yanguas.

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Temperature-sensitive poly(N-isopropylacrylamide) (PNIPA) nanohydrogels were synthesized by nanoemulsion polymerization in water-in-oil systems. Several cross-linking degrees and the incorporation of acrylic acid as comonomer at different concentrations were tested to produce nanohydrogels with a wide range of properties. The physicochemical properties of PNIPA nanohydrogels, and their relationship with the swelling-collapse behaviour, were studied to evaluate the suitability of PNIPA nanoparticles as smart delivery systems (for active packaging). The swelling-collapse transition was analyzed by the change in the optical properties of PNIPA nanohydrogels using ultraviolet-visible spectroscopy. The thermodynamic parameters associated with the nanohydrogels collapse were calculated using a mathematical approach based on the van't Hoff analysis, assuming a two-state equilibrium (swollen to collapsed). A mathematical model is proposed to predict both the thermally induced collapse, and the collapse induced by the simultaneous action of two factors (temperature and pH, or temperature and organic solvent concentration). Finally, van't Hoff analysis was compared with differential scanning calorimetry. The results obtained allow us to solve the problem of determining the molecular weight of the structural repeating unit in cross-linked NIPA polymers, which, as we show, can be estimated from the ratio of the molar heat capacity (obtained from the van't Hoff analysis) to the specific heat capacity (obtained from calorimetric measurements).

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V.1. 219 p.; V. 2. 589 p.

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En esta obra aparecen descritos 3.391 mapas y planos, localizados en 76 archivos y bibliotecas anteriores a 1.900. Entre ellos se incluyen también algunos que si bien no han podido ser consultados, el equipo investigador consideró de interés dar a conoce su existencia.

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[ES] La industria ósea postpaleolítica, por lo general, pocas veces ha merecido la atención que se le ha concedido a la fabricada durante el Paleolítico Superior. No obstante una de dichas excepciones serán los denominados ídolos-espátulas con decoración acanalada en su mitad proximal, trabajados sobre tibias de "Capra/Ovis" y procedentes por lo que hasta ahora conocemos de contextos sepulcrales megalíticos. En su morfología deben de señalarse el extremo activo romo, al modo de otras espátulas tan comunes en contextos neolíticos, y el extremo proximal decorado con profundos acanalamientos que conforman motivos geométricos más o menos complejos (espiral, zig-zag, etc.) en unos casos y en menos alguna figura antropomorfa femenina. Los primeros hallazgos se realizaron en la provincia de Álava durante la década de los sesenta, destacando entre ellos los procedentes del sepulcro de corredor de San Martín (Laguardia), a los que se sucedieron otros como los de Kurtzebide, Los Llanos, etc. en el mismo territorio y los importantes conjuntos hallados en distintas provincias de la Meseta Norte y en La Rioja. Todos ellos debido al tipo de contexto del que proceden y las características de los ídolos-espátula ritual dan cierto grado de homogeneidad ideológico o religioso a todo el territorio. No obstante, fuera de este territorio y muy alejados desde el punto de vista geográfico existen otros ejemplares (Tell Halula -Siria-, Sesklo, Agios Petras -Grecia-) que muestran gran similitud tipológica aunque no un nexo de unión entre ambas zonas. Por otra parte, hay que subrayar la notable mayor antigüedad del foco oriental y que el contexto del que proceden no es funerario como en el caso de los ejemplares occidentales.

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[eus] Gaur egungo eskoletan, oraindik ere, zoritxarrez, behar besteko garrantzirik ematen ez zaion eta sendotu behar den ikasleen autoezagutza fisikoaren inguruan, honako landa-lana diseinatu eta ikasleekin burutu egin da, hauengan aldaketa bat sortarazteko asmoarekin. Horretarako, prestatutako ariketa desberdinen bitartez, ikasleen arrazonamendu maila, baita maila emozionala ere landu egin da. Kontuan izanda, autoezagutzan, aldaketak epe luzean ematen direla, esku-hartze honen bidez ez dira aldaketa handirik edo esanguratsurik nabarmendu. Dena den, errespetuaren balorea ikasleengan transmititzea lortu egin da. Hori dela eta, landa lana burutu eta gero, egindakoaren inguruan, autokritika egin da.

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[eus] Lan honen helburua Norvegiako haur eskola baten hezkuntza-praktiken proiektu esku-hartzailea egitea izan da. Horretarako, euren metodologia alternatiboaren ezaugarriak aztertu dira, hezkuntzaren alorrean egin litezkeen ekarpenak hedatzeko. Proiektua garatzeko prozesuan, lehenik eta behin, behaketa parte-hartzailea eta jarraia egin da; ondoren, zentroko hainbat profesional desberdinak elkarrizketatu dira; eta azkenik, esku-hartze berritzaile horiengan eragina duten korronte pedagogikoen azterketa sakona gauzatu da. Burututako lanaren emaitza aztertutako hezkuntza praktiken sintesia web orrialde batean jasotzea izan da, horrela, hezkuntza komunitatea erabili ahal izateko eta aberasteko. Era berean, Norvegiako ekintza pedagogikoa eredu hartuta, euskal eskola batera bideratutako proposamen metodologikoa diseinatu da.

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Current research efforts are focused on the application of growth factors, such as glial cell line-derived neurotrophic factor (GDNF) and vascular endothelial growth factor (VEGF), as neuroregenerative approaches that will prevent the neurodegenerative process in Parkinson's disease. Continuing a previous work published by our research group, and with the aim to overcome different limitations related to growth factor administration, VEGF and GDNF were encapsulated in poly(lactic-co-glycolic acid) nanospheres (NS). This strategy facilitates the combined administration of the VEGF and GDNF into the brain of 6-hydroxydopamine (6-OHDA) partially lesioned rats, resulting in a continuous and simultaneous drug release. The NS particle size was about 200 nm and the simultaneous addition of VEGF NS and GDNF NS resulted in significant protection of the PC-12 cell line against 6-OHDA in vitro. Once the poly(lactic-co-glycolic acid) NS were implanted into the striatum of 6-OHDA partially lesioned rats, the amphetamine rotation behavior test was carried out over 10 weeks, in order to check for in vivo efficacy. The results showed that VEGF NS and GDNF NS significantly decreased the number of amphetamine-induced rotations at the end of the study. In addition, tyrosine hydroxylase immunohistochemical analysis in the striatum and the external substantia nigra confirmed a significant enhancement of neurons in the VEGF NS and GDNF NS treatment group. The synergistic effect of VEGF NS and GDNF NS allows for a reduction of the dose by half, and may be a valuable neurogenerative/neuroreparative approach for treating Parkinson's disease.

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Based on numerous pharmacological studies that have revealed an interaction between cannabinoid and opioid systems at the molecular, neurochemical, and behavioral levels, a new series of hybrid molecules has been prepared by coupling the molecular features of two well-known drugs, ie, rimonabant and fentanyl. The new compounds have been tested for their affinity and functionality regarding CB1 and CB2 cannabinoid and mu opioid receptors. In [S-35]-GTP.S (guanosine 5'-O-[gamma-thio] triphosphate) binding assays from the post-mortem human frontal cortex, they proved to be CB1 cannabinoid antagonists and mu opioid antagonists. Interestingly, in vivo, the new compounds exhibited a significant dual antagonist action on the endocannabinoid and opioid systems.

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Bordetella pertussis causes whooping cough, a respiratory infectious disease that is the fifth largest cause of vaccine-preventable death in infants. Though historically considered an extracellular pathogen, this bacterium has been detected both in vitro and in vivo inside phagocytic and non-phagocytic cells. However the precise mechanism used by B. pertussis for cell entry, or the putative bacterial factors involved, are not fully elucidated. Here we find that adenylate cyclase toxin (ACT), one of the important toxins of B. pertussis, is sufficient to promote bacterial internalisation into non-phagocytic cells. After characterization of the entry route we show that uptake of "toxin-coated bacteria" proceeds via a clathrin-independent, caveolae-dependent entry pathway, allowing the internalised bacteria to survive within the cells. Intracellular bacteria were found inside non-acidic endosomes with high sphingomyelin and cholesterol content, or "free" in the cytosol of the invaded cells, suggesting that the ACT-induced bacterial uptake may not proceed through formation of late endolysosomes. Activation of Tyr kinases and toxin-induced Ca2+-influx are essential for the entry process. We hypothesize that B. pertussis might use ACT to activate the endocytic machinery of non-phagocytic cells and gain entry into these cells, in this way evading the host immune system.

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The purpose of this study was to compare the effects of Small-Sided Games (SSG) vs. Interval Training (IT) in soccer training on aerobic fitness and physical enjoyment in youth elite soccer players during the last 8 weeks of the season. Seventeen U-16 male soccer players (age = 15.5 +/- 0.6 years, and 8.5 years of experience) of a Spanish First Division club academy were randomized to 2 different groups for 6 weeks: SSG group (n = 9) and IT group (n = 8). In addition to the usual technical and tactical sessions and competitive games, the SSG group performed 11 sessions with different SSGs, whereas the IT group performed the same number of sessions of IT. Players were tested before and after the 6-week training intervention with a continuous maximal multistage running field test and the counter movement jump test (CMJ). At the end of the study, players answered the physical activity enjoyment scale (PACES). During the study, heart rate (HR) and session perceived effort (sRPE) were assessed. SSGs were as effective as IT in maintaining the aerobic fitness in elite young soccer players during the last weeks of the season. Players in the SSG group declared a greater physical enjoyment than IT (P = 0.006; ES = 1.86 +/- 1.07). Coaches could use SSG training during the last weeks of the season as an option without fear of losing aerobic fitness while promoting high physical enjoyment.

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Sphingolipids are major constituents of biological membranes of eukaryotic cells. Many studies have shown that sphingomyelin (SM) is a major phospholipid in cell bilayers and is mainly localized to the plasma membrane of cells, where it serves both as a building block for cell architecture and as a precursor of bioactive sphingolipids. In particular, upregulation of (C-type) sphingomyelinases will produce ceramide, which regulates many physiological functions including apoptosis, senescence, or cell differentiation. Interestingly, the venom of some arthropodes including spiders of the genus Loxosceles, or the toxins of some bacteria such as Corynebacterium tuberculosis, or Vibrio damsela possess high levels of D-type sphingomyelinase (SMase D). This enzyme catalyzes the hydrolysis of SM to yield ceramide 1-phosphate (C1P), which promotes cell growth and survival and is a potent pro-inflammatory agent in different cell types. In particular, C1P stimulates cytosolic phospholipase A2 leading to arachidonic acid release and the subsequent formation of eicosanoids, actions that are all associated to the promotion of inflammation. In addition, C1P potently stimulates macrophage migration, which has also been associated to inflammatory responses. Interestingly, this action required the interaction of C1P with a specific plasma membrane receptor, whereas accumulation of intracellular C1P failed to stimulate chemotaxis. The C1P receptor is coupled to Gi proteins and activates of the PI3K/Akt and MEK/ERK1-2 pathways upon ligation with C1P. The proposed review will address novel aspects on the control of inflammatory responses by C1P and will highlight the molecular mechanisms whereby C1P exerts these actions.