The Central and Eastern Anatolian plateaus are integral parts of the world's third largest orogenic plateau. In the past decade, geophysical surveys have provided insights into the crust, ...lithosphere, and mantle beneath Eastern Anatolia. These observations are now accompanied by recent surveys in Central Anatolia and new data constraining the timing and magnitude of uplift along its northern and southern margins. Together with predictions from geodynamic models on the effects of various processes on surface deformation and uplift, the observations can be integrated to identify probable mechanisms of Anatolian Plateau growth.
A changeover from shortening to extension along the southern margin of Central Anatolia that is coeval with the start of uplift can be most easily associated with oceanic slab break-off and tearing. This interpretation is supported by tomography, deep seismicity (or lack thereof), and gravity data. Based on the timing of uplift, geophysical and geochemical observations, and model predictions, slab break-off likely occurred first beneath Eastern Anatolia in middle to late Miocene time, and propagated westward toward Cyprus by the latest Miocene. Alternatively, the break-off near Cyprus could have occurred in late Pliocene to early Pleistocene time, in association with collision of the Eratosthenes Seamount (continental fragment) with the subduction zone. Uplift at the northern margin of Central Anatolia appears to result from crustal shortening starting in the late Miocene or early Pliocene, which has been linked to the broad restraining bend of the North Anatolian Fault. The uplift history of the interior of Central Anatolia since the late Miocene is unclear, although shortening there appears to have ended by the late Miocene, followed by NE–SW extension. This change in the deformation style broadly coincides with faster retreat of the Hellenic trench as well as uplift of the northern and southern margins of Central Anatolia.
These different events throughout the plateau may be linked, as faster retreat of the Hellenic trench has been predicted to occur after slab break-off, which could have induced extension of Central Anatolia and helped to form the North Anatolian Fault through accelerated westward movement of Anatolia relative to Eurasia. Correlative geochronologic evidence that we summarize here supports the hypothesis that the geodynamic activity throughout the Aegean–Anatolian domain starting in latest Miocene to early Pliocene time defines a series of events that may all be linked to slab break-off.
Aging is an important determinant of vascular disease. Endothelium-derived nitric oxide (NO) is protective as a vasodilator and inhibitor of platelet function. This study was designed to directly ...measure effects of prolonged aging on endotheliai NO release in isolated blood vessels and to delineate differences between the systemic and pulmonary circulation. Aortas and pulmonary arteries from 5-6-mo-old (young), 18-19-mo-old (middle-aged), and 32-33-mo-old (old) normotensive female rats were used. Blood pressure and plasma estradiol-17beta (E2) remained unchanged. In isolated blood vessels, NO release was induced by the receptor-independent agonist calcium ionophore A23187 (10 micromol/liter) and measured in situ on the endothelial surface of vessels using a porphyrinic microsensor. In vessels suspended in organ chambers isometric tension was recorded. In the aorta, the initial rate of NO release and peak NO concentration were reduced in middle-aged and old rats (P < 0.0006 vs. young rats, n = 6). Furthermore, endothelium-dependent relaxations to calcium ionophore and acetylcholine (both 10(-10) - 10(-5) mol/liter) were also reduced in aortas from old as compared with young rats (n = 6, P < 0.05). The initial rate of NO release and peak NO concentration significantly correlated with maximal relaxation to calcium ionophore A23187 (correlation coefficients r - 0.916, P < 0.0018 and r = 0.961, P < 0.0001, respectively, n = 7). In pulmonary arteries, however, the initial rate of NO release as well as peak NO concentration did not decrease with age (n = 6 for each age group, NS). In both blood vessels, the NO release was unaffected by superoxide dismutase in all age groups (n = 6, NS). Thus, aging specifically reduces initial rate and peak concentrations of endothelial NO release from aorta but not pulmonary artery indicating reduced NO production. As arterial pressure did not change with aging, the chronic exposure of the aorta to higher pressure and/or pulsatility than in the pulmonary artery may be the cause. This appears important as NO plays a protective role by preventing vasoconstriction, thrombosis and atherosclerosis.
El parto prematuro (PP) es la principal afección relacionada con la morbimortalidad perinatal en el mundo. El objetivo de este trabajo exploratorio fue identificar interacciones gen-ambiente ...asociadas al PP espontáneo. Realizamos un estudio retrospectivo de casos y controles que incluyó datos sociodemográficos y obstétricos de gestantes asistidas en una maternidad de Tucumán, Argentina, entre 2005 y 2010. Utilizando la plataforma Ion Torrent S5 secuenciamos los exones de los genes KCNN3, CRHR1, COL4A3, PON1 y F3, de muestras de sangre de 69 recién nacidos pretérmino (casos) y 61 nacidos a término (controles). Identificamos las variantes genéticas y realizamos controles de calidad utilizando el procedimiento de Ion Torrent. Determinamos interacciones gen-ambiente candidatas mediante una regresión logística penalizada estratificando por cada exposición. Las interacciones candidatas fueron analizadas utilizando regresiones logísticas robustas con un modelo genético aditivo, incluyendo covariables relacionadas a la ancestría, sociodemografía, sexo fetal y específicas de cada exposición. De las 57 variantes y 14 exposiciones analizadas se identificó una interacción entre el alelo T de la variante rs705381 (PON1) y el consumo de tabaco antes del embarazo. La razón de probabilidades de la interacción fue 7,62 (IC 95% 1,33-43,54, p=0,02) y del término genético 1,79 (IC 95% 0,39-8,23, p=0,46). La frecuencia de ese alelo en la muestra estudiada fue 18,8%. Los resultados sugieren que la interacción entre la variante del gen PON1 y fumar tabaco aumentaría el riesgo de PP espontáneo.
Tetracycline (TC) and its derivatives have recently been proposed as a new class of antagonists in prion diseases as they prevent the aggregation of prion protein peptides and their acquisition of ...protease resistance in vitro and in vivo. Looking for relationships between conformational flexibility and biological activity, we searched for a geometrical pharmacophore by investigating, in aqueous solution, the conformational behavior of 15 TCs in both the zwitterionic and the anionic forms. For TC similar conformational flexibility was found for the two forms and two main conformational families were detected, an extended and a folded conformation characterized by different intramolecular hydrogen-bond networks. On comparing the Molecular Mechanics results with the ab initio ones and the experimental evidence, it can be seen that the conformational behavior of TC is reasonably well predicted by the MM2 force field, whereas the conformational energies provided by the Amber force field are unreliable. The conformational analysis of the other TC derivatives was then performed by the MM2 force field. As a result, their conformational behavior was similar to that observed for TC itself. Despite the hydronaphthacene moiety's conformational flexibility, no geometrical pharmacophore was found among the TCs, i.e. properties other than geometrical ones should play a crucial role in determining their anti-fibrillogenic ability.
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