Foreland Magmatism during the Arabia–Eurasia Collision: Pliocene–Quaternary Activity of the Karacadağ Volcanic Complex, SW Turkey

Pliocene to Quaternary magmatism in the Karacadağ Volcanic Complex in SE Turkey occurred in the foreland region of the Arabia–Eurasia collision and can be divided into two phases. The earlier Karacadağ phase formed a north–south-trending volcanic ridge that erupted three groups of lavas. The same range of mantle sources contributed to the younger Ovabağ phase lavas, which were erupted from monogenetic cones to the east of the Karacadağ fissure. As at several other intraplate localities across the northern Arabian Plate this magmatism represents mixtures of melt from shallow, isotopically enriched mantle and from deeper, more depleted mantle. The deep source is similar to the depleted mantle invoked for other northern Arabian intraplate volcanic fields but at Karacadağ this source contained phlogopite. This source could be located in the shallow convecting mantle or may represent a metasomatic layer in the base of the lithosphere. There is no evidence for a contribution from the Afar mantle plume, as has been proposed elsewhere in northern Arabia. Melting during the Karacadağ and Ovabağ phases could have resulted from a combination of upwelling beneath weak or thinned lithosphere and restricted local extension of that weakened lithosphere as it collided with Eurasia. Tension associated with the collision focused magma of the Karacadağ phase into the elongate shield volcano of Mt. Karacadağ. The northern end of the fissure accommodated more extensive differentiation of magma, with isolated cases of crustal contamination, consistent with greater stress in the lithosphere closest to the collision. Most magma batches of the Karacadağ and Ovabağ phases differentiated by fractional crystallization at ∼5 MPa, near the boundary between the upper and lower crust. Magma batches dominated by melt from garnet lherzolite show evidence for restricted amounts of differentiation at ∼22·5 MPa, which is close to the base of the lithospheric mantle

Geographic variation of mutagenic exposures in kidney cancer genomes

International differences in the incidence of many cancer types indicate the existence of carcinogen exposures that have not yet been identified by conventional epidemiology make a substantial contribution to cancer burden1. In clear cell renal cell carcinoma, obesity, hypertension and tobacco smoking are risk factors, but they do not explain the geographical variation in its incidence2. Underlying causes can be inferred by sequencing the genomes of cancers from populations with different incidence rates and detecting differences in patterns of somatic mutations. Here we sequenced 962 clear cell renal cell carcinomas from 11 countries with varying incidence. The somatic mutation profiles differed between countries. In Romania, Serbia and Thailand, mutational signatures characteristic of aristolochic acid compounds were present in most cases, but these were rare elsewhere. In Japan, a mutational signature of unknown cause was found in more than 70% of cases but in less than 2% elsewhere. A further mutational signature of unknown cause was ubiquitous but exhibited higher mutation loads in countries with higher incidence rates of kidney cancer. Known signatures of tobacco smoking correlated with tobacco consumption, but no signature was associated with obesity or hypertension, suggesting that non-mutagenic mechanisms of action underlie these risk factors. The results of this study indicate the existence of multiple, geographically variable, mutagenic exposures that potentially affect tens of millions of people and illustrate the opportunities for new insights into cancer causation through large-scale global cancer genomics

Uncovering novel mutational signatures by de novo extraction with SigProfilerExtractor

Mutational signature analysis is commonly performed in cancer genomic studies. Here, we present SigProfilerExtractor, an automated tool for de novo extraction of mutational signatures, and benchmark it against another 13 bioinformatics tools by using 34 scenarios encompassing 2,500 simulated signatures found in 60,000 synthetic genomes and 20,000 synthetic exomes. For simulations with 5% noise, reflecting high-quality datasets, SigProfilerExtractor outperforms other approaches by elucidating between 20% and 50% more true-positive signatures while yielding 5-fold less false-positive signatures. Applying SigProfilerExtractor to 4,643 whole-genome- and 19,184 whole-exome-sequenced cancers reveals four novel signatures. Two of the signatures are confirmed in independent cohorts, and one of these signatures is associated with tobacco smoking. In summary, this report provides a reference tool for analysis of mutational signatures, a comprehensive benchmarking of bioinformatics tools for extracting signatures, and several novel mutational signatures, including one putatively attributed to direct tobacco smoking mutagenesis in bladder tissues

Geographic variation of mutagenic exposures in kidney cancer genomes

International differences in the incidence of many cancer types indicate the existence of carcinogen exposures that have not yet been identified by conventional epidemiology make a substantial contribution to cancer burden1. In clear cell renal cell carcinoma, obesity, hypertension and tobacco smoking are risk factors, but they do not explain the geographical variation in its incidence2. Underlying causes can be inferred by sequencing the genomes of cancers from populations with different incidence rates and detecting differences in patterns of somatic mutations. Here we sequenced 962 clear cell renal cell carcinomas from 11 countries with varying incidence. The somatic mutation profiles differed between countries. In Romania, Serbia and Thailand, mutational signatures characteristic of aristolochic acid compounds were present in most cases, but these were rare elsewhere. In Japan, a mutational signature of unknown cause was found in more than 70% of cases but in less than 2% elsewhere. A further mutational signature of unknown cause was ubiquitous but exhibited higher mutation loads in countries with higher incidence rates of kidney cancer. Known signatures of tobacco smoking correlated with tobacco consumption, but no signature was associated with obesity or hypertension, suggesting that non-mutagenic mechanisms of action underlie these risk factors. The results of this study indicate the existence of multiple, geographically variable, mutagenic exposures that potentially affect tens of millions of people and illustrate the opportunities for new insights into cancer causation through large-scale global cancer genomics

Polybaric melting of a single mantle source during the Neogene Siverek phase of the Karacadağ Volcanic Complex, SE Turkey

Siverek plateau basalts represent the Neogene activity of the Karacadağ Volcanic Complex in southeast Turkey and can be divided into two groups based on incompatible element concentrations. Group 1 is largely basaltic, containing some alkali basalts, while Group 2 consists of alkali basalts, trachybasalts and tephrites. The lavas display a range in major element concentrations that are consistent with restricted amounts of differentiation in the crust. Melts from both groups have experienced variable, small amounts of interaction with crustal rocks, which is responsible for most of the isotopic heterogeneity and caused significant Ba-enrichment. Neither fractional crystallisation nor crustal contamination can account for the differences in trace element enrichment observed between the two groups. Group 1 is derived mainly from the spinel lherzolite field by > 1% partial melting. Group 2 lavas were derived from very similar mantle but by smaller degrees of melting and contain a larger relative contribution from garnet-lherzolite. The Siverek plateau lavas are indistinguishable from contemporaneous magmatism in the Karasu Valley of southern Turkey and in northernmost Syria. Together, these plateau basalt fields represent mantle upwelling and melting beneath the thinned and/or weakened Arabian Plate as it migrated northwards during the Neogene

Re-os age and stable isotope (O-h-s-cu) geochemistry of north eastern Turkey’s Kuroko-type volcanogenic massive sulfide deposits: An example from cerattepe-artvin

The eastern Pontide tectonic belt (EPTB) contains greater than 350 identified Kuroko type volcanogenic massive sulfide deposits/mineralization/occurrences (VMSD). The deposits are associated with Late Cretaceous felsic volcanics consisting mainly of dacitic and rhyolitic lavas and py-roclastics that outcrop within a narrow zone running parallel to the eastern Black Sea coast and represent the axial zone of a paleo-magmatic arc. The Cerattepe deposit is the second-largest and is a hybrid VMS system with some epithermal features. To date, no geochemical research constrains the origin and timing of mineralization in the Cerattepe VMS deposit. Here, we provide Cu, O, H and S, isotope analysis of ores and alteration minerals to understand the hydrothermal history of the deposit and date the massive ore with Re-Os geochronology. Secondary weathering mobilized and redistributed metals in the deposit. The copper isotope signatures of shallow ores in the gossan follow patterns resulting from oxidative weathering of copper minerals with gossan Fe oxides of δ65Cu = −2.59‰, enrichment zone copper sulfide of d65Cu = +2.23 and +1.73‰, and primary ores of δ65Cu = +0.71 and +0.41‰. At the boundary of the enrichment zone, further cycling and migration of enrichment zone copper are evidenced by two samples having larger ranges of the δ65Cu = +3.59‰, and −2.93‰. Evidence for a magmatic source for fluids and S are evidenced by the O and H isotope values from quartz veins (δ18O = +7.93‰ to +10.82‰, and δD = −78‰ and −68‰) and sulfides that possess δ34S ratios of –5 and 0‰ from drill core samples.187Os/188Os–187Re/188Os ratios from drill core sulfide samples of Cerattepe VMS deposit yields a 62±3 Ma isochron age and a highly radiogenic Os initial ratio. This age is compatible with silicate alteration ages from a proximal deposit and clearly shows mineralization occurs at a much younger time than previously proposed for VMS mineralization in the eastern Pontides. The new Re-Os age and source of Os imply that mineralization in the area occurs at a distinctly younger interval in the back-arc basin and metals could be sourced from the surrounding host rocks. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.Open access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Serum leptin concentration is increased in patients with Behcet's syndrome and is correlated with disease activity

Background Behcet's syndrome is a systemic, relapsing immuno-inflammatory disease with a generalized vasculitis of the microvasculature endothelial dysfunction. Leptin, a recently discovered neuroendocrine hormone, is a metabolic peptide that appears to be involved. Serum proinflammatory cytokines upregulate leptin levels and leptin itself directly induces nitric oxide production from endothelial cells with its specific receptors