Contribución al conocimiento del género Anthyllis L. (Fabaceae) en la Peninsula Ibérica. A. plumosa sp. nov.

In this paper a morphological, palynologicaland caryologicalstudy of three species of Anthyllis (sect. Oreanthyllis)is included. As a consecuencea newspecies A.plumosa E. Domínguez from the dolomitics sands of Sierra de Almijara (Málaga) is described.Se realiza un estudio morfológico, palinológico y cariológico de tres especies del género Anthyllis (sect. Oreanthyllis), describiéndose una nueva especie, A. plumosa E. Domínguez procedente de las arenas dolomíticas de la Sierra de Almijara (Málaga)

Recent changes of relative humidity: regional connections with land and ocean processes

We analyzed changes in surface relative humidity (RH) at the global scale from 1979 to 2014 using both observations and the ERA-Interim dataset. We compared the variability and trends in RH with those of land evapotranspiration and ocean evaporation in moisture source areas across a range of selected regions worldwide. The sources of moisture for each particular region were identified by integrating different observational data and model outputs into a Lagrangian approach. The aim was to account for the possible role of changes in air temperature over land, in comparison to sea surface temperature (SST), but also the role of land evapotranspiration and the ocean evaporation on RH variability. The results demonstrate that the patterns of the observed trends in RH at the global scale cannot be linked to a particular individual physical mechanism. Our results also stress that the different hypotheses that may explain the decrease in RH under a global warming scenario could act together to explain recent RH trends. Albeit with uncertainty in establishing a direct causality between RH trends and the different empirical moisture sources, we found that the observed decrease in RH in some regions can be linked to lower water supply from land evapotranspiration. In contrast, the empirical relationships also suggest that RH trends in other target regions are mainly explained by the dynamic and thermodynamic mechanisms related to the moisture supply from the oceanic source regions. Overall, while this work gives insights into the connections between RH trends and oceanic and continental processes at the global scale, further investigation is still desired to assess the contribution of both dynamic and thermodynamic factors to the evolution of RH over continental regions.Ministerio de Economía y Competitividad | Ref. PCIN-2015-220Ministerio de Economía y Competitividad | Ref. CGL2014-52135-C03-01Ministerio de Economía y Competitividad | Ref. CGL2014-60849-JINEuropean Commission | Ref. n. 69046

Relaciones filogenéticas en Erysimun (Brassicaceae) de las Cordilleras Béticas (SE Península Ibérica)

The Baetic mountains, located in the southern Iberian Peninsula, is a major hotspot of biodiversity in the Mediterranean Basin, constituting one of the most important glacial refugia for vascular plants in Europe. Despite their relatively limited extension, the Baetic Mountains contain almost 50% of the total endemic Erysimum species in the Iberian Peninsula. The broadly distributed Erysimum genus has diversified profusely in the Mediterranean region, with more than a hundred species described in the area, out of a total of c. 200 species included in the genus. We used two plastid DNA regions (ndhF and trnT-L) and one nuclear DNA region (ITS1-5.8S rDNA-ITS2), with 3,556 bp total length, to carry out phylogenetic analysis by Bayesian inference, maximum likelihood and maximum parsimony, in order to explore the evolutionary relationships between the Erysimum species inhabiting these ranges. Analyses of concatenated sequences from the two genomes identified two main clades with no overlap in species composition so that samples from the same species fell within the same major clade. The phylogenetic relationships depicted by those two clades do not give support to the E. nevadense group, previously proposed on taxonomic grounds. In addition, our results indicated recurrent changes in flower colour in the Baetic Erysimum species although, alternatively, reticulate evolution, which is suggested by incongruent position of taxa in the different trees, may have also affected this trait.Las cordilleras Béticas, localizadas en el sudeste de la Península Ibérica, representan una importante zona para la biodiversidad de la cuenca mediterránea, constituyendo uno de los refugios glaciares más destacados de plantas vasculares en Europa. A pesar de su extensión relativamente limitada, las cordilleras Béticas albergan casi el 50% del total de las especies endémicas de Erysimum de la Península Ibérica. Erysimum es un género ampliamente distribuido, que se ha diversificado profusamente en la región mediterránea, con más de un centenar de especies descritas en dicha área, del total de las alrededor de 200 especies incluidas en el género. Usamos dos regiones de ADN plastidial (ndhF y trnT-L) y una región de ADN nuclear (ITS1-5.8S rDNA-ITS2), con una longitud total de 3.556 pb, para llevar a cabo análisis filogenéticos mediante inferencia bayesiana, máxima verosimilitud y máxima parsimonia, con el fin de explorar las relaciones evolutivas entre las especies de Erysimum que habitan en éstas cordilleras. El análisis de secuencias concatenadas de los dos genomas identifica dos clados principales y las muestras de la misma especie aparecen siempre en un clado o en el otro pero no en ambos. Las relaciones filogenéticas que indican esos dos clados no apoyan la circunscripción del grupo taxonómico E. nevadense, previamente definido en dicho género. Además, los análisis indican cambios recurrentes en el color floral de las especies de Erysimum que habitan los Sistemas Béticos aunque la evolución reticulada, que sugiere la posición de algunos taxones en uno y otro árbol, puede haber también afectado a este rasgo, lo que sería una hipótesis alternativa.This study has been supported by MARM (078/2007), Junta de Andalucía (P07-RNM-02869 and P11-RNM-7676), MONTES Consolider-Ingenio (CSD2008-00040), and Spanish MCyT (CGL2009-07015, and CGL2012-34736) grants. AJMP and MA were supported by Spanish Education and Science grants AP-2006- 00685 and BES-2007-14206, respectively

Computer-Aided Structure-Based Design of Multitarget Leads for Alzheimer’s Disease

Alzheimer’s disease is a neurodegenerative pathology with unmet clinical needs. A highly desirable approach to this syndrome would be to find a single lead that could bind to some or all of the selected biomolecules that participate in the amyloid cascade, the most accepted route for Alzheimer disease genesis. In order to circumvent the challenge posed by the sizable differences in the binding sites of the molecular targets, we propose a computer-assisted protocol based on a pharmacophore and a set of required interactions with the targets that allows for the automated screening of candidates. We used a combination of docking and molecular dynamics protocols in order to discard nonbinders, optimize the best candidates, and provide a rationale for their potential as inhibitors. To provide a proof of concept, we proceeded to screen the literature and databases, a task that allowed us to identify a set of carbazole-containing compounds that initially showed affinity only for the cholinergic targets in our experimental assays. Two cycles of design based on our protocol led to a new set of analogues that were synthesized and assayed. The assay results revealed that the designed inhibitors had improved affinities for BACE-1 by more than 3 orders of magnitude and also displayed amyloid aggregation inhibition and affinity for AChE and BuChE, a result that led us to a group of multitarget amyloid cascade inhibitors that also could have a positive effect at the cholinergic levelFinancial support from the Ministerio de Economia y Competitividad of Spain (Project CTQ2011-22436) and the Xunta de Galicia (CN2011/047 and 10CSA209063PR) is gratefully acknowledgedS

8‐Aminomethyl‐7‐hydroxy‐4‐methylcoumarins as Multitarget Leads for Alzheimer's Disease

This is the peer reviewed version of the following article: Domínguez, J., Fernández-Nieto, F., Brea, J., Catto, M., Paleo, M., & Porto, S. et al. (2016). 8-Aminomethyl-7-hydroxy-4-methylcoumarins as Multitarget Leads for Alzheimer's Disease. Chemistryselect, 1(11), 2742-2749, which has been published in final form at https://doi.org/10.1002/slct.201600735. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived VersionsThis work is part of our ongoing research in the discovery of multitarget therapeutic agents for Alzheimer's disease (AD). A literature screening, based on our recently proposed pharmacophore, led to the identification of 8‐aminomethyl‐7‐hydroxy‐4‐methyl coumarins as potential multitarget leads for AD. The results of a computer‐assisted protocol developed by us to validate multitarget hits for AD indicated that our coumarin candidates were viable leads only for AChE inhibition as later validated by biological assays. The results of BChE binding and propidium displacement assays indicate that our first generation compounds bind to the PAS site in AChE. We designed new generations of coumarin derivatives with a longer substituent at position 8 aimed at leads with more efficient interaction at the catalytic anionic site (CAS). Inhibition data and docking simulations indicated that an anilino‐capping group reached the CAS region of AChE and determined also a higher inhibitory potency towards BChE. The best compound obtained, with a N‐benzylpiperidine fragment, displayed sub‐micromolar affinity for AChE, affinity for BChE, and precluded Aβ‐amyloid aggregation with a potency similar to that of 9,10‐anthraquinone, making it a multitarget lead viable for further improvementFinancial support from the Ministerio de Economia y Competitividad of Spain (Project CTQ2014‐55208‐P) and the Xunta de Galicia (10CSA209063PR and GRC2014/029) is gratefully acknowledged. The Italian authors thank the University of Bari for partial financial support (Fondi di Ateneo 2014–2015)S

MAGIC Upper Limits for two Milagro-detected, Bright Fermi Sources in the Region of SNR G65.1+0.6

We report on the observation of the region around supernova remnant G65.1+0.6 with the stand-alone MAGIC-I telescope. This region hosts the two bright GeV gamma-ray sources 1FGL J1954.3+2836 and 1FGL J1958.6+2845. They are identified as GeV pulsars and both have a possible counterpart detected at about 35 TeV by the Milagro observatory. MAGIC collected 25.5 hours of good quality data, and found no significant emission in the range around 1 TeV. We therefore report differential flux upper limits, assuming the emission to be point-like (<0.1 deg) or within a radius of 0.3 deg. In the point-like scenario, the flux limits around 1 TeV are at the level of 3 % and 2 % of the Crab Nebula flux, for the two sources respectively. This implies that the Milagro emission is either extended over a much larger area than our point spread function, or it must be peaked at energies beyond 1 TeV, resulting in a photon index harder than 2.2 in the TeV band.Comment: 8 pages, 3 figures, 1 tabl

Simultaneous multi-frequency observation of the unknown redshift blazar PG 1553+113 in March-April 2008

The blazar PG 1553+113 is a well known TeV gamma-ray emitter. In this paper, we determine its spectral energy distribution using simultaneous multi-frequency data in order to study its emission processes. An extensive campaign was carried out between March and April 2008, where optical, X-ray, high-energy (HE) gamma-ray, and very-high-energy (VHE) gamma-ray data were obtained with the KVA, Abastumani, REM, RossiXTE/ASM, AGILE and MAGIC telescopes, respectively. This is the first simultaneous broad-band (i.e., HE+VHE) gamma-ray observation, though AGILE did not detect the source. We combine data to derive source's spectral energy distribution and interpret its double peaked shape within the framework of a synchrotron self compton modelComment: 5 pages, 2 figures, publishe

A search for spectral hysteresis and energy-dependent time lags from X-ray and TeV gamma-ray observations of Mrk 421

Blazars are variable emitters across all wavelengths over a wide range of timescales, from months down to minutes. It is therefore essential to observe blazars simultaneously at different wavelengths, especially in the X-ray and gamma-ray bands, where the broadband spectral energy distributions usually peak. In this work, we report on three "target-of-opportunity" (ToO) observations of Mrk 421, one of the brightest TeV blazars, triggered by a strong flaring event at TeV energies in 2014. These observations feature long, continuous, and simultaneous exposures with XMM-Newton (covering X-ray and optical/ultraviolet bands) and VERITAS (covering TeV gamma-ray band), along with contemporaneous observations from other gamma-ray facilities (MAGIC and Fermi-LAT) and a number of radio and optical facilities. Although neither rapid flares nor significant X-ray/TeV correlation are detected, these observations reveal subtle changes in the X-ray spectrum of the source over the course of a few days. We search the simultaneous X-ray and TeV data for spectral hysteresis patterns and time delays, which could provide insight into the emission mechanisms and the source properties (e.g. the radius of the emitting region, the strength of the magnetic field, and related timescales). The observed broadband spectra are consistent with a one-zone synchrotron self-Compton model. We find that the power spectral density distribution at $\gtrsim 4\times 10^{-4}$ Hz from the X-ray data can be described by a power-law model with an index value between 1.2 and 1.8, and do not find evidence for a steepening of the power spectral index (often associated with a characteristic length scale) compared to the previously reported values at lower frequencies.Comment: 45 pages, 15 figure