Quantitative kinematics of a frictional viscous lowangle normal fault on Kea (Western Cyclades, Greece)

Lithospheric extension during the Miocene is well documented in the Aegean. Within theCentral and Western Cyclades extension has been documented in detail by the formation ofMetamorphic Core Complexes and movement along low-angle normal faults (LANFs). Focusing on ahitherto unrecognised main low-angled fault geometry outcropping on northern Kea, this work presentspervasive evidence of top-to-south kinematics

Characteristics of low-angle normal faulting in Serifos (Western Cyclades, Greece)

On the island of Serifos SSW-directed low-angle faults accommodated crustal thinning during Miocene extension. Cross-cutting relationships suggest that the low-angle faults interacted with WNW-ESE striking conjugate high-angle normal faults in both the hanging and the footwall. Although high- and low-angle faults were likely synkinematic, the deformation mechanism differs significantly in both systems. The low-angle faults are characterized by several meters of low-grade, ultrafine grained marble mylonites below several decimetres of ultracataclasites. The high-angle faults represent mainly brittle deformation resulting in slickensides, cataclasites and pseudotachylites. The Ar/Ar mica geochronology yields uniform ages across the low-angle faults suggesting a nearly horizontal detachment at temperatures coincident with the brittle-ductile transition zone

Structural investigations along a low-angle normal fault zone (Kythnos, Greece)

Recent field investigations have revealed a high-strain zone in the south of Kythnos (Greece). Massive layers of ultrafine-grained Mn-rich calcitic mylonitic marbles and several generations of cataclasites hint at a high-strain event in the crust and are associated with a low-angle shear zone. We investigate fold-fault-relationships and deformation events preceding and post-dating normal faulting and compare the tectono-metamorphic history with adjacent islands in the Western Cyclades

Pressure–temperature–time and REE mineral evolution in low- to medium-grade polymetamorphic units (Austroalpine Unit, Eastern Alps)

We investigated rare earth element (REE) minerals in low- to medium-grade metapelites sampled in two nappes of the Austroalpine Unit (Eastern Alps, Austria). Combining microstructural and chemical characterization of the main and REE minerals with thermodynamic forward modeling, Raman spectroscopy on carbonaceous material (RSCM) thermometry and in situ U–Th–Pb dating reveal a polymetamorphic evolution of all samples. In the hanging wall nappe, allanite and REE epidote formed during Permian metamorphism (275–261 Ma, 475–520 °C, 0.3–0.4 GPa). In one sample, Cretaceous (ca. 109 Ma) REE epidote formed at ∼440 °C and 0.4–0.8 GPa at the expense of Permian monazite clusters. In the footwall nappe, large, chemically zoned monazite porphyroblasts record both Permian (283–256 Ma, 560 °C, 0.4 GPa) and Cretaceous (ca. 87 Ma, 550 °C, 1.0–1.1 GPa) metamorphism. Polymetamorphism produced a wide range of complex REE-mineral-phase relationships and microstructures. Despite the complexity, we found that bulk rock Ca, Al and Na contents are the main factor controlling REE mineral stability; variations thereof explain differences in the REE mineral assemblages of samples with identical pressure and temperature (P–T) paths. Therefore, REE minerals are also excellent geochronometers to resolve the metamorphic evolution of low- to medium-grade rocks in complex tectonic settings. The recognition that the main metamorphic signature in the hanging wall is Permian implies a marked P–T difference of ∼250 °C and at least 0.5 GPa, requiring a major normal fault between the two nappes which accommodated the exhumation of the footwall in the Cretaceous. Due to striking similarities in setting and timing, we put this low-angle detachment in context with other Late Cretaceous low-angle detachments from the Austroalpine domain. Together, they form an extensive crustal structure that we tentatively term the “Austroalpine Detachment System”.</p

Characteristics of low-angle normal fault formation on Kea (Western Cyclades, Greece)

The geology of Kea Island shows further evidence for low-angle normal fault (LANF) formation in the Western Cyclades. Structural investigations have demonstrated the existence of a hitherto unrecognised ductile-brittle shear zone with strikingly consistent top-to-SSW extensional kinematics together with a WNW-ESE oriented shortening component. The tectonostratigraphy comprises a &gt;380 m thick, shallowly-dipping schist-calcite marble unit, overlain by ca. 150 m thick fault rocks consisting of cohesive cataclasites, ultramylonitic calcite marbles, brecciated dolostones and protomylonitic calcite marbles. The presence of blueschist-facies lenses and 40Ar/39Ar geochronology point to a significant role of LANFs in exhumation processes and greenschist-facies overprint during Miocene crustal evolution

Genetic architecture of the APM1 gene and its influence on adiponectin plasma levels and parameters of the metabolic syndrome in 1,727 healthy Caucasians

Copyright: Copyright 2008 Elsevier B.V., All rights reserved.The associations of the adiponectin (APM1) gene with parameters of the metabolic syndrome are inconsistent. We performed a systematic investigation based on fine-mapped single nucleotide polymorphisms (SNPs) highlighting the genetic architecture and their role in modulating adiponectin plasma concentrations in a particularly healthy population of 1,727 Caucasians avoiding secondary effects from disease processes. Genotyping 53 SNPs (average spacing of 0.7 kb) in the APM1 gene region in 81 Caucasians revealed a two-block linkage disequilibrium (LD) structure and enabled comprehensive tag SNP selection. We found particularly strong associations with adiponectin concentrations for 11 of the 15 tag SNPs in the 1,727 subjects (five P values <0.0001). Haplotype analysis provided a thorough differentiation of adiponectin concentrations with 9 of 17 haplotypes showing significant associations (three P values <0.0001). No significant association was found for any SNP with the parameters of the metabolic syndrome. We observed a two-block LD structure of APM1 pointing toward at least two independent association signals, one including the promoter SNPs and a second spanning the relevant exons. Our data on a large number of healthy subjects suggest a clear modulation of adiponectin concentrations by variants of APM1, which are not merely a concomitant effect in the course of type 2 diabetes or coronary artery disease.publishersversionPeer reviewe

Mitochondrial DNA haplogroup T is associated with coronary artery disease and diabetic retinopathy: a case control study

<p>Abstract</p> <p>Background</p> <p>There is strong and consistent evidence that oxidative stress is crucially involved in the development of atherosclerotic vascular disease. Overproduction of reactive oxygen species (ROS) in mitochondria is an unifying mechanism that underlies micro- and macrovascular atherosclerotic disease. Given the central role of mitochondria in energy and ROS production, mitochondrial DNA (mtDNA) is an obvious candidate for genetic susceptibility studies on atherosclerotic processes. We therefore examined the association between mtDNA haplogroups and coronary artery disease (CAD) as well as diabetic retinopathy.</p> <p>Methods</p> <p>This study of Middle European Caucasians included patients with angiographically documented CAD (n = 487), subjects with type 2 diabetes mellitus with (n = 149) or without (n = 78) diabetic retinopathy and control subjects without clinical manifestations of atherosclerotic disease (n = 1527). MtDNA haplotyping was performed using multiplex PCR and subsequent multiplex primer extension analysis for determination of the major European haplogroups. Haplogroup frequencies of patients were compared to those of control subjects without clinical manifestations of atherosclerotic disease.</p> <p>Results</p> <p>Haplogroup T was significantly more prevalent among patients with CAD than among control subjects (14.8% vs 8.3%; p = 0.002). In patients with type 2 diabetes, the presence of diabetic retinopathy was also significantly associated with a higher prevalence of haplogroup T (12.1% vs 5.1%; p = 0.046).</p> <p>Conclusion</p> <p>Our data indicate that the mtDNA haplogroup T is associated with CAD and diabetic retinopathy in Middle European Caucasian populations.</p

Fetuin-A Induces Cytokine Expression and Suppresses Adiponectin Production

BACKGROUND: The secreted liver protein fetuin-A (AHSG) is up-regulated in hepatic steatosis and the metabolic syndrome. These states are strongly associated with low-grade inflammation and hypoadiponectinemia. We, therefore, hypothesized that fetuin-A may play a role in the regulation of cytokine expression, the modulation of adipose tissue expression and plasma concentration of the insulin-sensitizing and atheroprotective adipokine adiponectin. METHODOLOGY AND PRINCIPAL FINDINGS: Human monocytic THP1 cells and human in vitro differenttiated adipocytes as well as C57BL/6 mice were treated with fetuin-A. mRNA expression of the genes encoding inflammatory cytokines and the adipokine adiponectin (ADIPOQ) was assessed by real-time RT-PCR. In 122 subjects, plasma levels of fetuin-A, adiponectin and, in a subgroup, the multimeric forms of adiponectin were determined. Fetuin-A treatment induced TNF and IL1B mRNA expression in THP1 cells (p<0.05). Treatment of mice with fetuin-A, analogously, resulted in a marked increase in adipose tissue Tnf mRNA as well as Il6 expression (27- and 174-fold, respectively). These effects were accompanied by a decrease in adipose tissue Adipoq mRNA expression and lower circulating adiponectin levels (p<0.05, both). Furthermore, fetuin-A repressed ADIPOQ mRNA expression of human in vitro differentiated adipocytes (p<0.02) and induced inflammatory cytokine expression. In humans in plasma, fetuin-A correlated positively with high-sensitivity C-reactive protein, a marker of subclinical inflammation (r = 0.26, p = 0.01), and negatively with total- (r = -0.28, p = 0.02) and, particularly, high molecular weight adiponectin (r = -0.36, p = 0.01). CONCLUSIONS AND SIGNIFICANCE: We provide novel evidence that the secreted liver protein fetuin-A induces low-grade inflammation and represses adiponectin production in animals and in humans. These data suggest an important role of fatty liver in the pathophysiology of insulin resistance and atherosclerosis

Unmet need in the hyperlipidaemia population with high risk of cardiovascular disease: a targeted literature review of observational studies

BACKGROUND: The aim of this study was to examine recommended target levels of low-density lipoprotein cholesterol (LDL-C) for hyperlipidaemia patients at high risk (i.e., with two or more risk factors or coronary heart disease or its risk equivalents) for cardiovascular disease (CVD); to determine LDL-C targets recommended by guidelines, and to examine the proportions of patients who do not achieve targeted LDL-C levels in real-world studies. METHODS: Electronic databases were searched: Medline, Medline In-Process, Embase, BIOSIS, and the Cochrane Library (1 January 2005 to 31 December 2013). Guideline searches were limited to publications in the last 5 years. There were no geographical or language restrictions. RESULTS: Seventeen guidelines and 42 observational studies that reported on high-risk hyperlipidaemia patients were identified. The National Cholesterol Education Program–Adult Treatment Panel III’s LDL-C target levels were the most common guidelines used for patients with very high hyperlipidaemia. However, between 68 and 96 % of patients in the studies did not achieve an LDL-C goal <70 mg/dL, except in one study conducted in China (16.9 %). In high-risk patients, 61.8 to 93.8 % did not achieve a target of <100 mg/dL. Regarding common comorbidities, patients with concomitant CVD or diabetes were least likely to reach their target LDL-C goals. CONCLUSION: In patients with high risk for CVD, the majority of patients do not attain recommended LDL-C goals, highlighting worldwide suboptimal hyperlipidaemia management and missed opportunities for reduction of the patients CVD risk. Lipid-modifying management strategies need to be intensified. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12872-016-0241-3) contains supplementary material, which is available to authorized users

Predictive value for cardiovascular events of common carotid intima media thickness and its rate of change in individuals at high cardiovascular risk - Results from the PROG-IMT collaboration.

AIMS: Carotid intima media thickness (CIMT) predicts cardiovascular (CVD) events, but the predictive value of CIMT change is debated. We assessed the relation between CIMT change and events in individuals at high cardiovascular risk. METHODS AND RESULTS: From 31 cohorts with two CIMT scans (total n = 89070) on average 3.6 years apart and clinical follow-up, subcohorts were drawn: (A) individuals with at least 3 cardiovascular risk factors without previous CVD events, (B) individuals with carotid plaques without previous CVD events, and (C) individuals with previous CVD events. Cox regression models were fit to estimate the hazard ratio (HR) of the combined endpoint (myocardial infarction, stroke or vascular death) per standard deviation (SD) of CIMT change, adjusted for CVD risk factors. These HRs were pooled across studies. In groups A, B and C we observed 3483, 2845 and 1165 endpoint events, respectively. Average common CIMT was 0.79mm (SD 0.16mm), and annual common CIMT change was 0.01mm (SD 0.07mm), both in group A. The pooled HR per SD of annual common CIMT change (0.02 to 0.43mm) was 0.99 (95% confidence interval: 0.95-1.02) in group A, 0.98 (0.93-1.04) in group B, and 0.95 (0.89-1.04) in group C. The HR per SD of common CIMT (average of the first and the second CIMT scan, 0.09 to 0.75mm) was 1.15 (1.07-1.23) in group A, 1.13 (1.05-1.22) in group B, and 1.12 (1.05-1.20) in group C. CONCLUSIONS: We confirm that common CIMT is associated with future CVD events in individuals at high risk. CIMT change does not relate to future event risk in high-risk individuals