Antagonistic effects of two novel GIP analogs, (Hyp(3))GIP and (Hyp(3)) GIPLys(16)PAL, on the biological actions of GIP and longer-term effects in diabetic ob/ob mice

This study examines the actions of the novel enzyme- resistant, NH2- terminally modified GIP analog ( Hyp(3)) GIP and its fatty acid- derivatized analog ( Hyp(3)) GIPLys(16)PAL. Acute effects are compared with the established GIP receptor antagonist ( Pro(3)) GIP. All three peptides exhibited DPP IV resistance, and significantly inhibited GIP stimulated cAMP formation and insulin secretion in GIP receptor- transfected fibroblasts and in clonal pancreatic BRIN- BD11 cells, respectively. Likewise, in obese diabetic ob/ob mice, intraperitoneal administration of GIP analogs significantly inhibited the acute antihyperglycemic and insulinreleasing effects of native GIP. Administration of once daily injections of ( Hyp(3)) GIP or ( Hyp(3)) GIPLys(16)PAL for 14 days resulted in significantly lower plasma glucose levels ( P <0.05) after ( Hyp3) GIP on days 12 and 14 and enhanced glucose tolerance ( P <0.05) and insulin sensitivity ( P <0.05 to P <0.001) in both groups by day 14. Both ( Hyp(3)) GIP and ( Hyp(3)) GIPLys(16)PAL treatment also reduced pancreatic insulin ( P <0.05 to P <0.01) without affecting islet number. These data indicate that ( Hyp3) GIP and ( Hyp(3)) GIPLys(16)PAL function as GIP receptor antagonists with potential for ameliorating obesity- related diabetes. Acylation of ( Hyp(3)) GIP to extend bioactivity does not appear to be of any additional benefit.

El pensamiento político de José Ortega y Gasset

Las siguientes páginas versan sobre el pensamiento político de José Ortega y Gasset, mostrando –entre otras cosas– su evolución desde lo que sería el neokantismo de mocedad de Ortega hasta su madurez. Para cumplir con nuestro objetivo se ha recurrido a los escritos de Ortega, así como a autores especializados en su pensamiento. La historia del pensamiento político contemporáneo tiene una deuda contraída con Ortega que desde sus primeros escritos manifestó un claro interés por la política concebida ésta como pedagogía social y cuyo fin debía ser, en primer lugar, solventar los problemas de la vida pública nacional. El pensamiento político de Ortega se define asimismo por la defensa de los valores liberales (liberalismo) compatibles con los principios socialistas (socialismo), que en una primera época de juventud idealista neokantiana adquieren un significado eminentemente cultural aunque también moral, que no se perderá completamente en su madurez o época de plenitud vital, aunque bien es verdad que aquellos dos conceptos (liberalismo y socialismo), así como también su idea de democracia, irán respondiendo a la evolución de su pensamiento.

Rapid ecosystem response to abrupt climate changes during the last glacial period in western Europe, 40-16 ka

We present a high-resolution and independently dated multiproxy lake sediment record from the paleolake at Les Echets in southeastern France that displays synchronous changes in independent limnic and terrestrial ecosystem proxies, in concert with millennial-scale climate oscillations during the last glacial period. Distinct lake-level fluctuations, low lake organic productivity, and open, treeless vegetation indicate cold and dry conditions in response to Heinrich events. Alternating phases of higher and low lake organic productivity, stratified surface waters and long-lasting lake ice cover, decreased or increased catchment erosion, and tree-dominated or herb-dominated vegetation resemble Dansgaard-Oeschger interstadial-stadial variability. Transitions between different ecological states occurred in as little as 40-230 yr and seem to have been controlled by the position of the Polar Front. Ecosystem response after 30 ka suggests that local climate conditions became more important. Our results demonstrate that all parts of the terrestrial system responded to the abrupt and dramatic climatic changes associated with Dansgaard-Oeschger and Heinrich events, and that regional factors modulated ecosystem response.

The persistence of the HgCl2 molecule in five new compounds in the system (NH4)(w)HgxCly(H2O)(z) with w : x : y : z=1 : 5 : 11 : 0, 2 : 3 : 8 : 1, 4 : 3 : 10 : 2, 2 : 1 : 4 : 1, and 10 : 3 : 16 : 0

Five new compounds in the system (NH4)Cl/HgCl2/H2O have been obtained as colourless single crystals, (NH4)Hg5Cl11, (NH4)(2)Hg3Cl8(H2O), (NH4)(4)Hg3Cl10(H2O)(2), (NH4)(2)HgCl4(H2O), and (NH4)(10)Hg3Cl16. In all of these, as in HgCl2 itself, (almost) linear HgCl2 molecules persist with Hg-Cl distances varying from 229 to 236 pm. In (NH4)(10)Hg3Cl16 there are also tetrahedra [HgCl4] with d(Hg-Cl) = 247 pm present. If larger Hg-Cl distances (of up to 340 pm) are considered as belonging to the coordination sphere of Hg-II, the structures may be described as consisting of isolated octahedra and tetrahedra as in (NH4)(10)Hg3Cl16, edge-connected chains as in (NH4)(2)HgCl4(H2O), edge-connected chains and layers of octahedra as in (NH4)(4)Hg3Cl10(H2O)(2), corrugated layers of edge-connected octahedra as in (NH4)(2)Hg3Cl8(H2O), and, finally, a three-dimensional network of connected six- and seven-coordinate Hg-Cl polyhedra as in (NH4)Hg5Cl11. The water molecules are never attached to Hg-II. The (NH4)(+) cations, and sometimes Cl- anions, play a role for electroneutrality only.