Deformation Sequence and Paleofluids in Carbonate Buckle Folds Under Transpression (Pag Anticline, External Dinarides, Croatia)

Contractional deformation structures at the front of transpressional orogens display complex three-dimensional geometries deviating from the interpretative templates commonly applied in thrust belts. Accordingly, detailed constraints on deformation patterns and associated paleofluid circulation are desirable, especially for fracture geometry and permeability predictive purposes. The Pag anticline, which is located in the Dinaric fold and thrust belt, provides an appropriate field site for studying fold- and fault-related deformation structures in a transpressive setting. We performed a multiscale structural analysis together with petrographic and stable isotope characterization of the deformation-related calcite cements. Structural mapping suggests that the Pag anticline is a detachment fold developed mainly by buckling, since large-scale thrust faults are absent. Fold tightening in a transpressive setting produced a complex deformational structure including two sets of N-S right-lateral and E-W left-lateral late-stage strike-slip fault sets trending oblique to the NW-SE fold axis. The pre-folding deformation pattern includes incipient normal faults likely related to the forebulge stage, veins and stylolites coherent with NE-SW layer parallel shortening contraction in a strike-slip regime, and metric to decametric scale conjugate thrusts coherent with layer parallel shortening in a compressive regime. Buckle folding preceded propagation of a series of accommodation structures during fold tightening. Petrographic and isotopic data indicate meteoric alteration of the Cretaceous platform carbonates in the prefolding stage, likely due to forebulge subaerial exposure. Layer parallel shortening and early syn-folding veins involved formational fluids resulting from mixed marine and meteoric fluids during folding at shallow burial conditions. Eventually, meteoric fluid infiltrated again along strike-slip faults, acting as cross-formational conduits in the postfolding stage

Mejora del olmo para resistencia a DED: clones italianos y características de su madera

In Italy, an elm breeding program to develop Dutch elm disease-resistant trees has been established by cross-breeding Asian elms with indigenous species, in order to produce individuals that combine resistance of the first with growth characteristics and higher degree of environmental adaptability of the second. Thus, the favourable adaptation of Ulmus pumila in Italy has been explored: «San Zanobi» and «Plinio» are two recent results of this research and many others promising clones as «FL090», «FL146», «FL441», «FL568», «FL634», are in the final stage of field testing. The resistance levels of all these clones were significantly higher level of resistance than «Lobel» and «Urban» in several assessments during different years. First technological tests indicate that the wood characteristics of «San Zanobi» and «FL090» clones are comparable to those of elm wood traditionally present on the market, thus highlighting that those clones is likely to satisfy the elm wood demand. The present characterisation needs to be confirmed by further evaluations of mature trees having bigger diameters and allowing industrial trials, still not available so far.En Italia, el programa de mejora genética del olmo para la obtención de árboles resistentes a la grafiosis se ha desarrollado a partir del cruzamiento de olmos asiáticos con especies nativas, y tiene por objetivo producir individuos que combinen la resistencia de los primeros con las características vegetativas y el alto grado de adaptación al ambiente de los segundos. Por esta razón, se ha aprovechado la favorable adaptación de Ulmus pumila en Italia: «San Zenobi» y «Plinio » son dos resultados recientes de estas investigaciones, y otros muchos clones prometedores como «FL090», «FL146», «FL441», «FL568» y «FL634» están en las fases finales de las pruebas de campo. Los niveles de resistencia de todos estos clones fueron significativamente mayores, en diferentes ensayos, que los niveles de resistencia de «Lobel» y «Urban ». Los primeros ensayos tecnológicos han mostrado que las características de la madera de los clones «San Zenobi» y «FL090» son comparables a los de las maderas de olmo tradicionalmente presentes en el mercado, indicando que esos clones pueden probablemente satisfacer las demandas de madera. La actual caracterización debe ser confirmada con nuevas evaluaciones en árboles maduros de mayores diámetros y mediante ensayos industriales aún no disponibles

Multidisciplinary investigations of a karst reservoir for managed aquifer recharge applications on the island of Vis (Croatia)

Managed aquifer recharge (MAR) refers to a suite of methods by which excess surface water or non-conventional water is stored underground for subsequent recovery or environmental purposes. MAR solutions have been largely used in unconsolidated aquifers, while their application in karst aquifers is rare. This research presents the first results of a MAR viability study on the island of Vis, a small karstic island in the Adriatic Sea. Favorable geological and hydrogeological conditions enable the formation of karst aquifers, making the island autonomous in terms of water supply. The island's main aquifer, exploited in the Korita well field, is protected from seawater intrusion by several hydrogeological barriers. However, climate change and high seasonal pressures related to tourism pose a threat to the future availability of freshwater. Multidisciplinary field and laboratory investigations were carried out to detail the geological and hydrogeological setting of the island and its groundwater resource. Field analyses consisted of groundwater monitoring and sampling, geophysical investigations (i.e., electrical resistivity tomography), and structural measurements. Laboratory analyses included measurements of principal cations and anions and tritium activity. Despite low precipitation during the observation period (September 2019 - December 2020), the groundwater resource at the Korita site showed stable trends of physico-chemical parameters with a good storage potential and a long-term reserve. Geophysical investigations evidenced a relatively homogeneous sequence of the rock mass at a larger scale, while structural analyses indicated the occurrence of E-W karstified and open fractures that could represent a preferential flow path in the carbonate aquifer. A MAR solution for the Vis island was proposed combining an infiltration pond scheme with the direct injection of the accumulated waters into the aquifer using available wells. The potential water source could be represented by the runoff collected in an old artificial channel and the associated pond system in Korita

Morbid Obesity in Women is Associated to a Lower Prevalence of Thyroid Nodules.

BACKGROUND: Few studies have recently showed functional and morphological changes of the thyroid gland in relation to obesity. To our knowledge, no data are available about the prevalence of thyroid nodules in female obese patients. The aim of this study was to investigate the prevalence of thyroid nodules in morbidly obese women. METHODS: One hundred eight consecutive female obese patients were selected from those referred to our medical and surgery outpatients providing that following criteria were satisfied: (1) affected by morbid obesity (body mass index (BMI) >40 kg/m(2)); (2) no previous diagnosis of thyroid disease; (3) biochemically proven euthyroid state at the time of recruitment. Ninety-seven control subjects, constituted by normo-weight and/or slightly overweight (BMI ≤ 30 kg/m(2)) women, should satisfy the above criteria 2 and 3. All the subjects were submitted to ultrasound investigation. RESULTS: The two groups of patients displayed no differences for age and fT4 levels. Obese patients clearly showed a lower prevalence of thyroid nodules [odds ratio 0.294, 95% confidence interval 0.206-0.382]. A single nodule was found in 23% of obese patients as compared to 65% of control subjects (p < 0.0001). No difference for age (year) was found between obese and non-obese subjects with nodules (40.5 ± 8.2 vs. 44.2 ± 8.9, respectively, p = 0.07). CONCLUSIONS: Our data clearly show a significantly lower prevalence of thyroid nodules in morbidly obese patients. Further studies are needed to confirm and to understand this first observation

Markers for the identification of late breast cancer recurrence

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited

Métodos y progreso de la conservación de los recursos genéticos de los olmos en Europa

The progress made in the conservation of European elm genetic resources since the 1st International Elm Conference is reviewed, and the complementarity of in situ and ex situ methods is discussed. The financial support of the European Union to RESGEN project CT96-78 has permitted to co-ordinate and rationalize the ex situ conservation of elms. The project, which involved 17 partner institutes in nine west European countries, aimed at a better evaluation, conservation and utilisation of the existing collections of native elm clones. Main achievements are: establishing a common database of about 2,000 clones; characterizing over 500 clones through RAPDs and chloroplast DNA PCR-RFLPs molecular markers; completing and rationalizing the existing collections; establishing a long-term core collection of 850 clones; cryo-preserving a subset of 444 clones; and identifying clones of interest for breeding and prudent use in the reconstruction of countryside hedges. The «Noble Hardwoods» network of the pan-European programme EUFORGEN groups members representative of 31 countries, and promotes the dynamic conservation of the genetic resources of several genera of broadleaf forest trees, including Ulmus spp. Strategies for the conservation of the adaptive potential of elm resources were defined and will be disseminated among foresters and conservationists through «Guidelines» leaflets. Some countries have already started implementing conservation measures for U. laevis, associating in situ preservation and the establishment of seed orchards. Others are undertaking inventories, or acquiring genetic knowledge on target populations.Se discute el progreso realizado en la conservaci&oacute;n de los olmos europeos desde la primera conferencia Internacional del Olmo y los m&eacute;todos complementarios de conservaci&oacute;n in situ y ex situ. El apoyo financiero de la Uni&oacute;n Europea al proyecto RESGEN CT96-78 ha permitido coordinar y racionalizar la conservaci&oacute;n ex situ de los olmos. El proyecto, en el cual est&aacute;n involucrados 17 instituciones participantes en nueve pa&iacute;ses de Europa Occidental, tiene por objetivo una mejor evaluaci&oacute;n, conservaci&oacute;n y utilizaci&oacute;n de las colecciones actualmente existentes de clones nativos de olmo. Los principales logros son: el establecimiento de una base de datos com&uacute;n de aproximadamente 2.000 clones; la caracterizaci&oacute;n de m&aacute;s de 500 clones usando RAPD y marcadores moleculares PCR-RFLP de ADN cloropl&aacute;stico; la finalizaci&oacute;n y racionalizaci&oacute;n de las colecciones existentes; el establecimiento a largo plazo de una colecci&oacute;n central con 850 clones; la criopreservaci&oacute;n de un conjunto de 444 clones; y la identificaci&oacute;n de clones de inter&eacute;s para la mejora y para su uso en la restauraci&oacute;n de setos en campo. La red &laquo;Noble Hardwoods&raquo; del programa pan-europeo EUFORGEN agrupa a miembros representantes de 31 pa&iacute;ses, y promueve la conservaci&oacute;n din&aacute;mica de los recursos gen&eacute;ticos de varios g&eacute;neros de &aacute;rboles planifolios, incluido Ulmus spp.. Las estrategias para la conservaci&oacute;n del potencial adaptativo de los recursos de los olmos se definieron y se dieron a conocer entre forestales y conservacionistas a trav&eacute;s de folletos gu&iacute;a. Algunos pa&iacute;ses han comenzado ya a implementar medidas de conservaci&oacute;n para U. laevis mediante el uso de la preservaci&oacute;n in situ y el establecimiento de huertos semilleros. Otros est&aacute;n elaborando inventarios, o adquiriendo informaci&oacute;n gen&eacute;tica de poblaciones de inter&eacute;s

Kinome capture sequencing of high-grade serous ovarian carcinoma reveals novel mutations in theJAK3gene

High-grade serous ovarian carcinoma (HGSOC) remains the deadliest form of epithelial ovarian cancer and despite major efforts little improvement in overall survival has been achieved. Identification of recurring "driver" genetic lesions has the potential to enable design of novel therapies for cancer. Here, we report on a study to find such new therapeutic targets for HGSOC using exome-capture sequencing approach targeting all kinase genes in 127 patient samples. Consistent with previous reports, the most frequently mutated gene wasTP53(97% mutation frequency) followed byBRCA1(10% mutation frequency). The average mutation frequency of the kinase genes mutated from our panel was 1.5%. Intriguingly, afterBRCA1,JAK3was the most frequently mutated gene (4% mutation frequency). We tested the transforming properties of JAK3 mutants using the Ba/F3 cell-basedin vitrofunctional assay and identified a novel gain-of-function mutation in the kinase domain ofJAK3(p.T1022I). Importantly, p.T1022IJAK3mutants displayed higher sensitivity to the JAK3-selective inhibitor Tofacitinib compared to controls. For independent validation, we re-sequenced the entireJAK3coding sequence using tagged amplicon sequencing (TAm-Seq) in 463 HGSOCs resulting in an overall somatic mutation frequency of 1%. TAm-Seq screening ofCDK12in the same population revealed a 7% mutation frequency. Our data confirms that the frequency of mutations in kinase genes in HGSOC is low and provides accurate estimates for the frequency ofJAK3andCDK12mutations in a large well characterized cohort. Although p.T1022IJAK3mutations are rare, our functional validation shows that if detected they should be considered as potentially actionable for therapy. The observation ofCDK12mutations in 7% of HGSOC cases provides a strong rationale for routine somatic testing, although more functional and clinical characterization is required to understand which nonsynonymous mutations alterations are associated with homologous recombination deficiency.ISSN:1932-620

Kinome capture sequencing of high-grade serous ovarian carcinoma reveals novel mutations in the JAK3 gene.

High-grade serous ovarian carcinoma (HGSOC) remains the deadliest form of epithelial ovarian cancer and despite major efforts little improvement in overall survival has been achieved. Identification of recurring "driver" genetic lesions has the potential to enable design of novel therapies for cancer. Here, we report on a study to find such new therapeutic targets for HGSOC using exome-capture sequencing approach targeting all kinase genes in 127 patient samples. Consistent with previous reports, the most frequently mutated gene was TP53 (97% mutation frequency) followed by BRCA1 (10% mutation frequency). The average mutation frequency of the kinase genes mutated from our panel was 1.5%. Intriguingly, after BRCA1, JAK3 was the most frequently mutated gene (4% mutation frequency). We tested the transforming properties of JAK3 mutants using the Ba/F3 cell-based in vitro functional assay and identified a novel gain-of-function mutation in the kinase domain of JAK3 (p.T1022I). Importantly, p.T1022I JAK3 mutants displayed higher sensitivity to the JAK3-selective inhibitor Tofacitinib compared to controls. For independent validation, we re-sequenced the entire JAK3 coding sequence using tagged amplicon sequencing (TAm-Seq) in 463 HGSOCs resulting in an overall somatic mutation frequency of 1%. TAm-Seq screening of CDK12 in the same population revealed a 7% mutation frequency. Our data confirms that the frequency of mutations in kinase genes in HGSOC is low and provides accurate estimates for the frequency of JAK3 and CDK12 mutations in a large well characterized cohort. Although p.T1022I JAK3 mutations are rare, our functional validation shows that if detected they should be considered as potentially actionable for therapy. The observation of CDK12 mutations in 7% of HGSOC cases provides a strong rationale for routine somatic testing, although more functional and clinical characterization is required to understand which nonsynonymous mutations alterations are associated with homologous recombination deficiency

Frictional Melting in Hydrothermal Fluid-Rich Faults: Field and Experimental Evidence From the Bolfin Fault Zone (Chile)

Tectonic pseudotachylytes are thought to be unique to certain water-deficient seismogenic environments and their presence is considered to be rare in the geological record. Here, we present field and experimental evidence that frictional melting can occur in hydrothermal fluid-rich faults hosted in the continental crust. Pseudotachylytes were found in the >40 km-long Bolf\uedn Fault Zone of the Atacama Fault System, within two ca. 1 m-thick (ultra)cataclastic strands hosted in a damage-zone made of chlorite-epidote-rich hydrothermally altered tonalite. This alteration state indicates that hydrothermal fluids were active during the fault development. Pseudotachylytes, characterized by presenting amygdales, cut and are cut by chlorite-, epidote- and calcite-bearing veins. In turn, crosscutting relationship with the hydrothermal veins indicates pseudotachylytes were formed during this period of fluid activity. Rotary shear experiments conducted on bare surfaces of hydrothermally altered rocks at seismic slip velocities (3\ua0m s 121) resulted in the production of vesiculated pseudotachylytes both at dry and water-pressurized conditions, with melt lubrication as the primary mechanism for fault dynamic weakening. The presented evidence challenges the common hypothesis that pseudotachylytes are limited to fluid-deficient environments, and gives insights into the ancient seismic activity of the system. Both field observations and experimental evidence, indicate that pseudotachylytes may easily be produced in hydrothermal environments, and could be a common co-seismic fault product. Consequently, melt lubrication could be considered one of the most efficient seismic dynamic weakening mechanisms in crystalline basement rocks of the continental crust

Investigating the Concordance in molecular subtypes of primary colorectal tumors and their matched synchronous liver metastasis

To date, no systematic analyses are available assessing concordance of molecular classifications between primary tumors (PT) and matched liver metastases (LM) of metastatic colorectal cancer (mCRC). We investigated concordance between PT and LM for four clinically relevant CRC gene signatures. Twenty-seven fresh and 55 formalin-fixed paraffin-embedded pairs of PT and synchronous LM of untreated mCRC patients were retrospectively collected and classified according to the MSI-like, BRAF-like, TGFB activated-like and the Consensus Molecular Subtypes (CMS) classification. We investigated classification concordance between PT and LM and association of TGFBa-like and CMS classification with overall survival. Fifty-one successfully profiled matched pairs were used for analyses. PT and matched LM were highly concordant in terms of BRAF-like and MSI-like signatures, (90.2% and 98% concordance, respectively). In contrast, 40% to 70% of PT that were classified as mesenchymal-like, based on the CMS and the TGFBa-like signature, respectively, lost this phenotype in their matched LM (60.8% and 76.5% concordance, respectively). This molecular switch was independent of the microenvironment composition. In addition, the significant change in subtypes was observed also by using methods developed to detect cancer cell-intrinsic subtypes. More importantly, the molecular switch did not influence the survival. PT classified as mesenchymal had worse survival as compared to nonmesenchymal PT (CMS4 vs CMS2, hazard ratio [HR] = 5.2, 95% CI = 1.5-18.5, P = .0048; TGFBa-like vs TGFBi-like, HR = 2.5, 95% CI = 1.1-5.6, P = .028). The same was not true for LM. Our study highlights that the origin of the tissue may have major consequences for precision medicine in mCRC