Late cenozoic identation/escape tectonics in the eastern Betic Cordilleras and its consequences on the Iberian foreland

The structuration of the southeastern quarter of the Iberian Peninsula (eastern Betics and Iberian foreland), since Messinian time, was the result of a series of complex deformational events, as related to a major NNE-SSW sinistral shear zone disrupting the southeasternmost part of the Betic cordilleras (Trans-Alborán-Palomares shear zone; TAPSZ). Deformation along this shear zone was characterized by two differentiated and sequential scenarios: 1) periods of stress-build-up associated to momentary slip-obstruction along the TAPSZ, involving NW-directed indentation of the southeastern Iberian domain, and 2) periods of stress-release resulting from the lateral escape of wedge-shaped blocks, thus allowing full-scale strike-slip displacements along the TAPSZ. These events imposed compressional stress fields on the Iberian foreland, with a series of consequences such as alkaline volcanism in Calatrava and Cofrentes, protorift zones, changes in previous structural trends, localized uplift/doming processes, and changes in the sedimentary records of sorne basins.La estructuración del cuadrante SE de la Península Ibérica (Béticas orientales y antepaís Ibérico), desde el Messiniense hasta la actualidad, ha sido el resultado de una serie compleja de eventos deformativos, relacionados con la actividad de una megazona de cizalla NNE-SSO en el SE de las Cordilleras Béticas (zona de cizalla Trans-Alborán-Palomares; TAPSZ). La deformación a lo largo de esta zona de cizalla se caracteriza por dos escenarios secuenciales diferentes: 1) períodos de concentración de esfuerzos, asociados con un frenado momentáneo del movimiento a lo largo de la TAPSZ, y con procesos de identación dirigidos hacia el NO, y 2) períodos de disipación de esfuerzos, que serían el resultado del escape lateral de bloques en forma de cuña, y del movimiento transcurrente renovado a lo largo de la TAPSZ. Estos eventos han generado campos de esfuerzos en el antepaís Ibérico, con una serie de consecuencias tales como el vulcanismo alcalino de Calatrava y Cofrentes, zonas de protorift, modificaciones de directrices estructurales previas, levantamientos/abombamientos localizados, y cambios en el régimen sedimentario de algunas cuencas

Late cenozoic identation/escape tectonics in the eastern Betic Cordilleras and its consequences on the Iberian foreland

13 páginas, 5 figuras.[ES] La estructuración del cuadrante SE de la Península Ibérica (Béticas orientales y antepaís Ibérico), desde el Messiniense hasta la actualidad, ha sido el resultado de una serie compleja de eventos deformativos, relacionados con la actividad de una megazona de cizalla NNE-SSO en el SE de las Cordilleras Béticas (zona de cizalla Trans-Alborán-Palomares; TAPSZ). La deformación a lo largo de esta zona de cizalla se caracteriza por dos escenarios secuenciales diferentes: 1) períodos de concentración de esfuerzos, asociados con un frenado momentáneo del movimiento a lo largo de la TAPSZ, y con procesos de identación dirigidos hacia el NO, y 2) períodos de disipación de esfuerzos, que serían el resultado del escape lateral de bloques en forma de cuña, y del movimiento transcurrente renovado a lo largo de la TAPSZ. Estos eventos han generado campos de esfuerzos en el antepaís Ibérico, con una serie de consecuencias tales como el vulcanismo alcalino de Calatrava y Cofrentes, zonas de protorift, modificaciones de directrices estructurales previas, levantamientos/abombamientos localizados, y cambios en el régimen sedimentario de algunas cuencas.[EN] The structuration of the southeastern quarter of the Iberian Peninsula (eastern Betics and Iberian foreland), since Messinian time, was the result of a series of complex deformational events, as related to a major NNE-SSW sinistral shear zone disrupting the southeasternmost part of the Betic cordilleras (Trans-Alborán-Palomares shear zone; TAPSZ). Deformation along this shear zone was characterized by two differentiated and sequential scenarios: 1) periods of stress-build-up associated to momentary slip-obstruction along the TAPSZ, involving NW-directed indentation of the southeastern Iberian domain, and 2) periods of stress-release resulting from the lateral escape of wedge-shaped blocks, thus allowing full-scale strike-slip displacements along the TAPSZ. These events imposed compressional stress fields on the Iberian foreland, with a series of consequences such as alkaline volcanism in Calatrava and Cofrentes, protorift zones, changes in previous structural trends, localized uplift/doming processes, and changes in the sedimentary records of sorne basins.Financial support was provided by the Dirección General de la Política Científica through Project n.O PB87-0372.Peer reviewe

Immune Checkpoint Inhibitors: The Emerging Cornerstone in Cholangiocarcinoma Therapy?

Background: Cholangiocarcinoma (CCA) encompasses a heterogeneous group of malignant tumors with dismal prognosis and increasing incidence worldwide. Both late diagnosis due to the lack of early symptoms and the refractory nature of these tumors seriously compromise patients' welfare and outcomes. Summary: During the last decade, immunotherapy and, more specifically, modulation of immune checkpoints-mediated signaling pathways have been under the spotlight in the field of oncology, emerging as a potential therapeutic approach for the treatment of several cancers, including CCA. Generally, high expression levels of immune checkpoints in patients with CCA have been associated with worse clinical outcomes, particularly with shorter overall survival and relapse-free survival. Thus, immune checkpoint inhibitors (ICIs), which mainly constitute different monoclonal antibodies, have been developed in order to hamper the immune checkpoint-mediated pathways. Interestingly, chemotherapy may increase the expression of immune checkpoints, while other therapeutic approaches such as ablative and targeted therapies may enhance their antitumor activity. In this sense, several clinical trials evaluated the safety and efficacy of ICIs for CCA, both as a monotherapy and in combination with other ICIs or loco-regional and systemic therapies. Additionally, many other clinical trials are currently ongoing and results are eagerly awaited. Here, we summarize the key aspects of immune checkpoint molecules as prognostic factors and therapeutic targets in CCA, highlighting the most recent advances in the field and future research directions. Key messages: (1) Effective therapeutic approaches for CCA are urgently needed. (2) Expression levels of immune checkpoints in patients with CCA have been proposed to be related with clinical outcomes. (3) Combination of different ICIs may outperform the efficacy of ICI monotherapy for CCA treatment. (4) Recent studies point toward the combination of ICIs and other common therapies, especially chemotherapy, as a promising strategy for treatment of CCA patients

Interstitial Cells of Cajal and Enteric Nervous System in Gastrointestinal and Neurological Pathology, Relation to Oxidative Stress

The enteric nervous system (ENS) is organized into two plexuses-submucosal and myenteric-which regulate smooth muscle contraction, secretion, and blood flow along the gastrointestinal tract under the influence of the rest of the autonomic nervous system (ANS). Interstitial cells of Cajal (ICCs) are mainly located in the submucosa between the two muscle layers and at the intramuscular level. They communicate with neurons of the enteric nerve plexuses and smooth muscle fibers and generate slow waves that contribute to the control of gastrointestinal motility. They are also involved in enteric neurotransmission and exhibit mechanoreceptor activity. A close relationship appears to exist between oxidative stress and gastrointestinal diseases, in which ICCs can play a prominent role. Thus, gastrointestinal motility disorders in patients with neurological diseases may have a common ENS and central nervous system (CNS) nexus. In fact, the deleterious effects of free radicals could affect the fine interactions between ICCs and the ENS, as well as between the ENS and the CNS. In this review, we discuss possible disturbances in enteric neurotransmission and ICC function that may cause anomalous motility in the gut.info:eu-repo/semantics/publishedVersio

Interstitial cells of Cajal and enteric nervous system in gastrointestinal and neurological pathology. Relation to oxidative stress

The enteric nervous system (ENS) is organized into two plexuses—submucosal and myenteric—which regulate smooth muscle contraction, secretion, and blood flow along the gastrointestinal tract under the influence of the rest of the autonomic nervous system (ANS). Interstitial cells of Cajal (ICCs) are mainly located in the submucosa between the two muscle layers and at the intramuscular level. They communicate with neurons of the enteric nerve plexuses and smooth muscle fibers and generate slow waves that contribute to the control of gastrointestinal motility. They are also involved in enteric neurotransmission and exhibit mechanoreceptor activity. A close relationship appears to exist between oxidative stress and gastrointestinal diseases, in which ICCs can play a prominent role. Thus, gastrointestinal motility disorders in patients with neurological diseases may have a common ENS and central nervous system (CNS) nexus. In fact, the deleterious effects of free radicals could affect the fine interactions between ICCs and the ENS, as well as between the ENS and the CNS. In this review, we discuss possible disturbances in enteric neurotransmission and ICC function that may cause anomalous motility in the gut

Proanthocyanidin characterization and bioactivity of extracts from different parts of Uncaria tomentosa L. (cat’s claw)

This article belongs to the Special Issue Dietary Antioxidants and Health Promotion.-- et al.Apart from alkaloids, bioactive properties of Uncaria tomentosa L. have been attributed to its phenolic constituents. Although there are some reports concerning low-molecular-weight polyphenols in U. tomentosa, its polymeric phenolic composition has been scarcely studied. In this study, phenolic-rich extracts from leaves, stems, bark and wood (n = 14) of Uncaria tomentosa plants from several regions of Costa Rica were obtained and analysed in respect to their proanthocyanidin profile determined by a quadrupole-time-of-flight analyser (ESI-QTOF MS). Main structural characteristics found for U. tomentosa proanthocyanidins were: (a) monomer composition, including pure procyanidins (only composed of (epi)catechin units) and propelargonidins (only composed of (epi)afzelechin units) as well as mixed proanthocyanidins; and (b) degree of polymerization, from 3 up to 11 units. In addition, U. tomentosa phenolic extracts were found to exhibit reasonable antioxidant capacity (ORAC (Oxygen Radical Absorbance Capacity) values between 1.5 and 18.8 mmol TE/g) and antimicrobial activity against potential respiratory pathogens (minimum IC of 133 µg/mL). There were also found to be particularly cytotoxic to gastric adenocarcinoma AGS and colon adenocarcinoma SW620 cell lines. The results state the particularities of U. tomentosa proanthocyanidins and suggest the potential value of these extracts with prospective use as functional ingredients.This project was partially funded by grant from the Spanish International Development Cooperation Agency (AECID) (Ref. A/023397/09 and A/030037/10) and a joint grant from the Costa Rica-USA Foundation (CRUSA) and the Spanish Scientific Research Council (CSIC) (Ref. CR0024). Authors also thank financial support from the Comunidad de Madrid (Spain) and European funding from FEDER program (projects AVANSECAL-CM S2013/ABI-3028 and ALIBIRD-CM S2013/ABI-2728) and from the University of Costa Rica. Special thanks are due to Eng. Juan Jose Cordero from Costa Rican National Production Council (CNP).Peer Reviewe

Analysis of Ani s 7 and Ani s 1 allergens as biomarkers of sensitization and allergy severity in human anisakiasis

The high frequency of infection by Anisakis simplex (A. simplex) has led to an increase in IgE sensitization, turning allergy to this parasite a relevant contemporary health problem. Improving the lack of conventional diagnosis test specificity is crucial to better understand these clinical scenarios. Specific IgE (sIgE) to A. simplex extract by ImmunoCAP (Anisakis-sIgE) was determined in sera from 403 blood donors (BD) from Cantabria (North of Spain) of which 51 subjects resulted sensitized. Among these latter, 47 were asymptomatic (sABD). The values of total IgE, prick-test, Anisakis-sIgE, and sIgE to Ani s 1 (anti-rAni s 1) and Ani s 7 (anti-rAni s 7) were compared between 46 sABD and 49 A. simplex allergic patients. The IgE seroprevalence by ImmunoCAP among BD was 12.65%. Allergic patients and sABD showed significant differences in all serum biomarkers evaluated. The area under the curve was assessed for Anisakis-sIgE (0.892), sIgE-rAni s 1 (0.672) and sIgE-rAni s 7 (0.668). After a severe reaction, significantly higher levels of Anisakis-sIgE and sIgE anti-rAni s 1 were detected. Determinations of sIgE by ImmunoCAP, Ani s 1 and Ani s 7 presented different sensitization patterns between allergic and asymptomatic individuals. The Ani s 1 allergen arises as a possible biomarker to detect patients at risk of suffering severe allergic reactions

Fetal undernutrition is associated with perinatal sex-dependent alterations in oxidative status

This is the published version of a work that was accepted for publication in The Journal of Nutritional Biochemestry. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in The Journal of Nutritional Biochemestry 26.12 (2015). DOI: 10.1016/jnubio.2015.09.004Intrauterine growth retardation predisposes to hypertension development, known as fetal programming. Females are less susceptible, which has been mainly attributed to estrogen influence. We hypothesize that perinatal differences in oxidative status might also contribute. We studied 21-day-old (prepuberal) and 6-month-old male and female Intrauterine growth retardation predisposes to hypertension development, known as fetal programming. Females are less susceptible, which has been mainly attributed to estrogen influence. We hypothesize that perinatal differences in oxidative status might also contribute. We studied 21-day-old (prepuberal) and 6-month-old male and female offspring from rats fed ad libitum during gestation (Control) or with 50% of Control daily intake from day 10 to delivery (maternal undernutrition, MUN). We assessed in vivo blood pressure and the following plasma biomarkers of oxidative status: protein carbonyls, thiols, reduced glutathione (GSH), total antioxidant capacity, superoxide anion scavenging activity (SOSA) and catalase activities; we calculated a global score (oxy-score) from them. Estradiol and melatonin concentration was measured in young rats. Prepuberal MUN males were normotensive but already exhibited increased carbonyls and lower thiols, GSH, SOSA and melatonin; oxy-score was significantly lower compared to Control males. Prepuberal MUN females only exhibited reduced SOSA compared to Control females. Adult rats from all experimental groups showed a significant increase in carbonyls and a decrease in antioxidants compared to prepuberal rats; oxy-score was negative in adult rats suggesting the development of a prooxidative status as rat age. Adult MUN males were hypertensive and exhibited the highest increase in carbonyls despite similar or even higher antioxidant levels compared to Controls. Adult MUN females remained normotensive and did not exhibit differences in any of the biomarkers compared to Controls. The better global antioxidant status developed by MUN females during perinatal life could contribute to their protection against hypertension programming.offspring from rats fed ad libitum during gestation (Control) or with 50% of Control daily intake from day 10 to delivery (maternal undernutrition, MUN). We assessed in vivo blood pressure and the following plasma biomarkers of oxidative status: protein carbonyls, thiols, reduced glutathione (GSH), total antioxidant capacity, superoxide anion scavenging activity (SOSA) and catalase activities; we calculated a global score (oxy-score) from them. Estradiol and melatonin concentration was measured in young rats. Prepuberal MUN males were normotensive but already exhibited increased carbonyls and lower thiols, GSH, SOSA and melatonin; oxy-score was significantly lower compared to Control males. Prepuberal MUN females only exhibited reduced SOSA compared to Control females. Adult rats from all experimental groups showed a significant increase in carbonyls and a decrease in antioxidants compared to prepuberal rats; oxy-score was negative in adult rats suggesting the development of a prooxidative status as rat age. Adult MUN males were hypertensive and exhibited the highest increase in carbonyls despite similar or even higher antioxidant levels compared to Controls. Adult MUN females remained normotensive and did not exhibit differences in any of the biomarkers compared to Controls. The better global antioxidant status developed by MUN females during perinatal life could contribute to their protection against hypertension programming.This work was supported by Ministerio de Economía y Competitividad Spain (grant number FEM2012-37634-C03-01 to S. M. Arribas) and Universidad Autónoma de Madrid Banco - Santander (Interuniversity Cooperation Project, Center for Latin American Studies, Santander, USA 2013–2014 to M. A. Martín-Cabrejas)

Approach to the Spanish continental Neogene synthesis and paleoclimatic interpretation

Integrated studies on Neogene geology have been scarce in Spain, but attemps to stratigraphic and sedimentological analysis of continental Tertiary basins have increased considerably lately. The large extent of Neogene basins in Spain, the good quality of the outcrops and the abundance of fossil provide an excellent basis for this kind of studies