Synthesis and Phytotoxicity of 4,5 Functionalized Tetrahydrofuran-2-ones

In this work we report a versatile synthesis of fourteen γ-lactones all structurally related, nine of which are novel compounds, accomplished from the readily available furfural. The phytotoxic activity of the synthesized compounds was evaluated in vitro by the influence on the growth of wheat coleoptiles. The percentages of inhibition were mostly small and not statistically different from control after the third dilution (100 μmol L-1). In general, α,β-unsaturated lactones presented better activities than the saturated ones. The most active compounds presented 51, 68 and 76% of inhibition in 1000 µmol L-1. The results indicate that regardless of saturation, the presence of the γ-lactone moiety is important for the bioactivity, but their presence has no implications with potency

Active faulting and earthquakes in the central Alboran Sea

Central Alboran Sea constitutes a key area to analyze the relationships between active tectonic structures and moderate seismicity. The heterogeneous crustal layered structure and the propagation of the deformation along the fault zones are key features to relate active faults and seismic hazard. The NW-SE oblique convergence between Eurasian and African plates determines the broad band of tectonic deformation and seismicity along the Alboran Sea basin (westernmost Mediterranean). The Betic-Rif Cordilleras are connected through the Gibraltar Arc and surround the Alboran Sea formed by thinned continental crust. This basin is filled since the Neogene by sedimentary and volcanic rocks. Central Alboran Sea is now undergoing shortening and is mainly deformed by a system of conjugated WNW-ESE dextral and NE-SW sinistral faults with recent activity formed by indenter tectonics related to a heterogeneous crustal behavior. In addition a NNW-SSE normal fault set and large ENE-WSW folds deform the central and northern Alboran Sea. These structures support a present-day N160 E maximum compression and orthogonal extension. In this setting, most of the recent seismicity is concentrated along a NNE-SSW zone that extends landward from Campo de Dalias (SE Spain) to Al Hoceima (Morocco). The Campo de Dalias 1993-1994 seismic crisis reached up to magnitudes Mw= 5.3, while the Al Hoceima area was affected by seismic crisis of 1994 (May 26, Mw=5.6) and 2004 (Feb 24, Mw= 6.4). The main active fault related to the 2004 earthquakes, even that it was a vertical NNE-SSW oriented fault and focal depth was 6 km, did not reach the surface probably due to the presence of a mechanically layered crust. The main active surface faults located in Al Hoceima area (the NNE-SSW transtensional sinistral Trougout fault zone) extended northwards towards the NE-SW sinistral Al Idrissi Fault that intersects the Alboran Sea and are connected with the normal NNW-SSE Balanegra Fault zone. Although these active faults determine most of the seismicity of the central Alboran Sea, the seismic crisis that occurred since January 2016, reaching Mw= 6.3 is located in a region westward of Al Idrissi Fault, underlining the relevance of growth of new faults to determine the seismic hazard of the region. Earthquake focal mechanisms support that the main active fault has a NNE-SSW orientation, similar to Al Idrissi Fault zone. Maximum magnitude suggests a surface rupture length of at least 12 km and a subsurface rupture of 20 km. Propagation of a new fault is more efficient to accumulate elastic deformation, and to produce highest magnitude earthquakes than already formed faults. This new fault is connected probably in deep crustal levels with the blind sinistral fault responsible of the 2004 Al Hoceima earthquake. The tsunami hazard of the region should be consequence of both seabottom displacement due to fault activity and co-seismic submarine landslides. The INCRISIS cruise, scheduled by May 2016, will provide evidences of seabottom effects of this seismic crisis

U–Pb SHRIMP zircon dating of Grenvillian metamorphism in Western Sierras Pampeanas (Argentina): Correlation with the Arequipa-Antofalla craton and constraints on the extent of the Precordillera Terrane

Metamorphism of Grenvillian age (ca. 1.2 Ga; U–Pb zircon dating) is recognized for the first time in the Western Sierras Pampeanas (Sierra de Maz). Conditions reached granulite facies (ca. 780 °C and ca. 780 MPa). Comparing geochronological and petrological characteristics with other outcrops of Mesoproterozoic basement, particularly in the northern and central Arequipa-Antofalla craton, we suggest that these regions were part of a single continental crustal block from Mesoproterozoic times, and thus autochthonous or parautochthonous to Gondwana.Facultad de Ciencias Naturales y MuseoCentro de Investigaciones Geológica

Distinct roles for PARP-1 and PARP-2 in c-Myc-driven B-cell lymphoma in mice

Dysregulation of the c-Myc oncogene occurs in a wide variety of hematologic malignancies, and its overexpression has been linked with aggressive tumor progression. Here, we show that poly (ADP-ribose) polymerase 1 (PARP-1) and PARP-2 exert opposing influences on progression of c-Myc-driven B-cell lymphoma. PARP-1 and PARP-2 catalyze the synthesis and transfer of ADP-ribose units onto amino acid residues of acceptor proteins in response to DNA strand breaks, playing a central role in the response to DNA damage. Accordingly, PARP inhibitors have emerged as promising new cancer therapeutics. However, the inhibitors currently available for clinical use are not able to discriminate between individual PARP proteins. We found that genetic deletion of PARP-2 prevents c-Myc-driven B-cell lymphoma, whereas PARP-1 deficiency accelerates lymphomagenesis in the E¿-Myc mouse model of aggressive B-cell lymphoma. Loss of PARP-2 aggravates replication stress in preleukemic E¿-Myc B cells, resulting in accumulation of DNA damage and concomitant cell death that restricts the c-Myc-driven expansion of B cells, thereby providing protection against B-cell lymphoma. In contrast, PARP-1 deficiency induces a proinflammatory response and an increase in regulatory T cells, likely contributing to immune escape of B-cell lymphoma, resulting in an acceleration of lymphomagenesis. These findings pinpoint specific functions for PARP-1 and PARP-2 in c-Myc-driven lymphomagenesis with antagonistic consequences that may help inform the design of new PARP-centered therapeutic strategies, with selective PARP-2 inhibition potentially representing a new therapeutic approach for the treatment of c-Myc-driven tumors.The J.Y. laboratory is funded by the Spanish Ministerio de Economía, Industria y Competitividad (grant SAF2017-83565-R), Spanish Ministerio de Ciencia e Innovación (grant PID2020-112526RB-I00), and Fundación Científica de la Asociación Española Contra el Cáncer (grant PROYEI6018YÉLA). Work in the J.E.S. laboratory is supported by a core grant to the Laboratory of Molecular Biology from the Medical Research Council (U105178808). The F.D. laboratory is supported by a Laboratory of Excellence grant (ANR-10-LABX-0034_Medalis) to Strasbourg University, Centre National de la Recherche Scientifique. The P.N. laboratory is supported by grants from the Spanish Ministry of Economy and Competitiveness/Instituto de Salud Carlos III–Fondo Europeo de Desarrollo Regional (FEDER; PI17/00199 and PI20/00625) and the Generalitat de Catalunya (2017-SGR-225). The P.M. laboratory acknowledges support from Centres de Recerca de Catalunya/Generalitat de Catalunya and Fundació Josep Carreras-Obra Social la Caixa for core support, the Spanish Ministry of Economy and Competitiveness (grant SAF-2019-108160-R), the Fundación Uno entre Cienmil, the Obra Social La Caixa (grant LCF/PR/HR19/52160011), and the German Josep Carreras Leukamie Stiftung. Work at the G.R. and P.M. laboratories are cofinanced by the European Regional Development Fund through the Interreg V-A Spain-France-Andorra Program (project PROTEOblood; grant EFA360/19). The O.F.-C. laboratory is funded by grants from the Spanish Ministry of Science, Innovation and Universities (RTI2018-102204-B-I00; cofinanced with European FEDER funds) and the European Research Council (ERC-617840). T.V.-H. was supported by a Marie Sklodowska Curie fellowship (GA792923). The A.B. laboratory is supported by the Spanish Ministry of Economy and Competitiveness (grant PID2019-104695RB-I00)

Oral vaccination with heat inactivated Mycobacterium bovis activates the complement system to protect against tuberculosis

Tuberculosis (TB) remains a pandemic affecting billions of people worldwide, thus stressing the need for new vaccines. Defining the correlates of vaccine protection is essential to achieve this goal. In this study, we used the wild boar model for mycobacterial infection and TB to characterize the protective mechanisms elicited by a new heat inactivated Mycobacterium bovis vaccine (IV). Oral vaccination with the IV resulted in significantly lower culture and lesion scores, particularly in the thorax, suggesting that the IV might provide a novel vaccine for TB control with special impact on the prevention of pulmonary disease, which is one of the limitations of current vaccines. Oral vaccination with the IV induced an adaptive antibody response and activation of the innate immune response including the complement component C3 and inflammasome. Mycobacterial DNA/RNA was not involved in inflammasome activation but increased C3 production by a still unknown mechanism. The results also suggested a protective mechanism mediated by the activation of IFN-γ producing CD8+ T cells by MHC I antigen presenting dendritic cells (DCs) in response to vaccination with the IV, without a clear role for Th1 CD4+ T cells. These results support a role for DCs in triggering the immune response to the IV through a mechanism similar to the phagocyte response to PAMPs with a central role for C3 in protection against mycobacterial infection. Higher C3 levels may allow increased opsonophagocytosis and effective bacterial clearance, while interfering with CR3-mediated opsonic and nonopsonic phagocytosis of mycobacteria, a process that could be enhanced by specific antibodies against mycobacterial proteins induced by vaccination with the IV. These results suggest that the IV acts through novel mechanisms to protect against TB in wild boar.This research was supported by Plan Nacional I+D+I AGL2011-30041 from Ministerio de Economía y Competitividad (MINECO), Spain and FEDER. This is also a contribution to EU FP7 grant WildTBvac and the EU FP7 ANTIGONE project number 278976. R.C. Galindo was funded by MEC, Spain. B. Beltrán-Beck was supported by MINECO grant BES-2009-017401.Peer Reviewe

O–H–Sr–Nd isotope constraints on the origin of the Famatinian magmatic arc, NW Argentina

We report a study of whole-rock O–H–Sr–Nd isotopes of Ordovician igneous and metamorphic rocks exposed at different crustal palaeodepths along c. 750 km in the Sierras Pampeanas, NW Argentina. The isotope compositions preserved in the intermediate rocks (mostly tonalite) (average δ18O = +8.7 ± 0.5‰, δD = −73 ± 14‰, 87Sr/86Srt = 0.7088 ± 0.0001 and eNdt = −4.5 ± 0.6) show no major difference from those of most of the mafic rocks (average δ18O = +8 ± 0.8‰, δD = −84 ± 18‰, 87Sr/86Srt = 0.7082 ± 0.0016 and eNdt = −4 ± 1.1), suggesting that most of their magmas acquired their crustal characteristics in the mantle. The estimate of assimilation of crustal material (δ18O = +12.2 ± 1.7‰, δD = −89 ± 21‰, 87Sr/86Srt = 0.7146 ± 0.0034 and eNdt = −6.9 ± 0.7) by the tonalite is in most samples within the range 10–20%. Felsic magmas that reached upper crustal levels had isotope values (δ18O = +9.9 ± 1.5‰, δD= −76 ± 5‰, 87Sr/86Srt = 0.7067 ± 0.0010, eNdt = −3.5 ± 1.4) suggesting that they were not derived by fractionation of the contaminated intermediate magmas, but evolved from different magma batches. Some rocks of the arc, both igneous (mostly gabbro and tonalite) and metamorphic, underwent restricted interaction with meteoric fluids. Reported values of δ18O of magmatic zircons from the Famatinian arc rocks (+6 to +9‰) are comparable to our δ18O whole-rock data, indicating that pervasive oxygen isotope exchange in the lower crust was not a major process after zircon crystallization.Centro de Investigaciones Geológica

Understanding the complex geomorphology of a deep sea area affected by continental tectonic indentation: the case of the Gulf of Vera (Western Mediterranean)

We present a multidisciplinary study of morphology, stratigraphy, sedimentology, tectonic structure, and physical oceanography to report that the complex geomorphology of the Palomares continental margin and adjacent Algerian abyssal plain (i.e., Gulf of Vera, Western Mediterranean), is the result of the sedimentary response to the Aguilas Arc continental tectonic indentation in the Eurasian–Africa plate collision. The inden tation is imprinted on the basement of the margin with elongated metamorphic antiforms that are pierced by igneous bodies, and synforms that accommodate the deformation and create a complex physiography. The basement is partially covered by Upper Miocene deposits sealed by the regional Messinian Erosive Surface characterized by palaeocanyons that carve the modern margin. These deposits and outcropping basement highs are then covered and shaped by Plio-Quaternary contourites formed under the action of the Light Intermediate and Dense Deep Mediterranean bottom currents. Even though bottom currents are responsible for the primary sedimentation that shapes the margin, 97% of this region's seafloor is affected by mass-movements that modified contourite sediments by eroding, deforming, faulting, sliding, and depositing sediments. Mass-movement processes have resulted in the formation of recurrent mass-flow deposits, an enlargement of the submarine canyons and gully incisions, and basin-scale gravitational slides spreading above the Messinian Salinity Crisis salt layer. The Polopo, Aguilas and Gata slides are characterized by an extensional upslope domain that shapes the continental margin, and by a downslope contractional domain that shapes the abyssal plain with diapirs piercing (hemi)pelagites/sheet-like turbidites creating a seafloor dotted by numerous crests. The mass movements were mostly triggered by the interplay of the continental tectonic indentation of the Aguilas Arc with sedimentological factors over time. The indentation, which involves the progressively southeastward tectonic tilting of the whole land-sea region, likely generated a quasi-continuous oversteepening of the entire margin, thus reducing the stability of the contourites. In addition, tectonic tilting and subsidence of the abyssal plain favoured the flow of the underlying Messinian Salinity Crisis salt layer, contributing to the gravitational instability of the overlying sediments over large areas of the margin and abyssal plain

Inventory of Geological Sites of Interest in the Canary Islands

En el marco de proyecto de investigación LIGCANARIAS (2018-2021) se ha realizado el Inventario de Lugares de Interés Geológico de las Islas Canarias, que forma parte del Inventario Español de Lugares de Interés Geológico (IELIG) para el dominio de este archipiélago. El inventario ha empleado la metodología del IELIG adaptada a un dominio geológico eminentemente volcánico, partiendo de los contextos geológicos regionales. Consta de 300 LIG: 53 en Gran Canaria, 47 en Tenerife, 54 en Lanzarote y Archipiélago Chinijo, 40 en Fuerteventura, 29 en La Palma, 23 en La Gomera y 21 en El Hierro. La principal novedad con respecto a los inventarios en otros dominios geológicos es la identificación de 33 LIG submarinos.Within the framework of the LIGCANARIAS research project (2018-2021), the Inventory of Geological Sites of Interest of the Canary Islands has been carried out, which is part of the Spanish Inventory of Places of Geological Interest (IELIG) for the domain of this archipelago. The inventory has used the IELIG methodology adapted to an eminently volcanic geological domain, based on regional geological frameworks. It consists of 300 geosites: 53 in Gran Canaria, 47 in Tenerife, 54 in Lanzarote and Chinijo Archipelago, 40 in Fuerteventura, 29 in La Palma, 23 in La Gomera and 21 in El Hierro. The main novelty with respect to the inventories in other geological domains is the identification of 33 submarine geosites.Depto. de Mineralogía y PetrologíaFac. de Ciencias GeológicasTRUEAgencia Canaria de Investigación, Innovación y Sociedad de la Informaciónpu

Conserved expression and functions of PDE4 in rodent and human heart

PDE4 isoenzymes are critical in the control of cAMP signaling in rodent cardiac myocytes. Ablation of PDE4 affects multiple key players in excitation–contraction coupling and predisposes mice to the development of heart failure. As little is known about PDE4 in human heart, we explored to what extent cardiac expression and functions of PDE4 are conserved between rodents and humans. We find considerable similarities including comparable amounts of PDE4 activity expressed, expression of the same PDE4 subtypes and splicing variants, anchoring of PDE4 to the same subcellular compartments and macromolecular signaling complexes, and downregulation of PDE4 activity and protein in heart failure. The major difference between the species is a fivefold higher amount of non-PDE4 activity in human hearts compared to rodents. As a consequence, the effect of PDE4 inactivation is different in rodents and humans. PDE4 inhibition leads to increased phosphorylation of virtually all PKA substrates in mouse cardiomyocytes, but increased phosphorylation of only a restricted number of proteins in human cardiomyocytes. Our findings suggest that PDE4s have a similar role in the local regulation of cAMP signaling in rodent and human heart. However, inhibition of PDE4 has ‘global’ effects on cAMP signaling only in rodent hearts, as PDE4 comprises a large fraction of the total cardiac PDE activity in rodents but not in humans. These differences may explain the distinct pharmacological effects of PDE4 inhibition in rodent and human hearts