Hypocholesterolemic and Hepatoprotective Effects of “Triguero” Asparagus from Andalusia in Rats Fed a High Cholesterol Diet

The cultivated species of the wild autochthonous Asparagus officinalis in Andalusia in Spain is commonly called “triguero” asparagus. This vegetable has traditionally been very much appreciated for its organoleptic and nutritional characteristics. This study has been designed to evaluate the potential effect of different concentrations of freeze-dried asparagus (500, 250, and 125 mg/Kg of body weight/day) on oxidative status and lipid profile in rats fed a cholesterol-rich diet. After five weeks of treatment, doses of 250 and 500 mg/Kg of asparagus were able to significantly reduce total cholesterol and LDL cholesterol levels. Atherogenic index was also significantly reduced in a dose-dependent manner by administrating freeze-dried asparagus. A beneficial effect was observed in the HDL cholesterol levels in asparagus-fed groups although the increase was not significant. Consumption of asparagus also improved antioxidant status, assayed superoxide dismutase (SOD) and catalase (CAT) enzymes, and protected against lipid peroxidation. These results show that the intake of green asparagus from Andalusia (Spain) helps to regulate plasma lipid levels and prevents oxidative damage in hypercholesterolemic conditions

Superintegrability and higher order polynomial algebras II

In an earlier article, we presented a method to obtain integrals of motion and polynomial algebras for a class of two-dimensional superintegrable systems from creation and annihilation operators. We discuss the general case and present its polynomial algebra. We will show how this polynomial algebra can be directly realized as a deformed oscillator algebra. This particular algebraic structure allows to find the unitary representations and the corresponding energy spectrum. We apply this construction to a family of caged anisotropic oscillators. The method can be used to generate new superintegrable systems with higher order integrals. We obtain new superintegrable systems involving the fourth Painleve transcendent and present their integrals of motion and polynomial algebras.Comment: 11 page

Eficacia y eficiencia de Leader 11 en Andalucía. Aproximación a un índice-resultado en materia de turismo rural

The evaluation has turned into a strategic element of differentiation, into the measurement into that allows to demonstrate his own beneficiaries, that the application of the public or private resources, it is as suitable as possible. To evaluate is necessary a system of indicators, which answer to five big types of which we will centre on two: efficiency (the effort inverted in terms of plysical, human or financial resources and the obtained results) and effectiveness (the impacts or results of the program with regard to his aims). In this article we try to put of manifest as the evaluation of the measurement B.3 (tourist activities) it allows across the analysis of the efficiency (projects) and the effectiveness (investment) in LEADER 11, one approximation in the construction of a proved index.La evaluación se ha convertido en un elemento estratégico de diferenciación, en la medida en que permite demostrar a sus propios beneficiarios, que la aplicación de los recursos públicos o privados, es la más adecuada posible. Para evaluar los programas de desarrollo rural es necesario un sistema de indicadores, que responden a cinco grandes tipos de los que nos centraremos en dos: eficiencia (el esfuerzo invertido en términos de recursos físicos, humanos o financieros y los resultados obtenidos) y eficacia (los impactos o resultados del programa respecto a sus objetivos). En este articulo tratamos de poner de manifiesto como la evaluación de la medida B.3 (actividades turísticas) permite, a través del análisis de la eficacia (proyectos) y la eficiencia (inversión) en LEADER 11, una primera aproximación en la construcción de un índice resultado

Synthesis of Structurally Related Coumarin Derivatives as Antiproliferative Agents

A library of structurally related coumarins was generated through synthesis reactions and chemical modification reactions to obtain derivatives with antiproliferative activity both in vivo and in vitro. Out of a total of 35 structurally related coumarin derivatives, seven of them showed inhibitory activity in in vitro tests against Taq DNA polymerase with IC50 values lower than 250 μM. The derivatives 4-(chloromethyl)-5,7-dihydroxy-2H-chromen-2-one (2d) and 4-((acetylthio)methyl)-2-oxo-2H-chromen-7-yl acetate (3c) showed the most promising anti-polymerase activity with IC50 values of 20.7 ± 2.10 and 48.25 ± 1.20 μM, respectively. Assays with tumor cell lines (HEK 293 and HCT-116) were carried out, and the derivative 4-(chloromethyl)-7,8-dihydroxy-2H-chromen-2-one (2c) was the most promising, with an IC50 value of 8.47 μM and a selectivity index of 1.87. In addition, the derivatives were evaluated against Saccharomyces cerevisiae strains that report about common modes of actions, including DNA damage, that are expected for agents that cause replicative stress. The coumarin derivatives 7-(2-(oxiran-2-yl)ethoxy)-2H-chromen-2-one (5b) and 7-(3-(oxiran-2-yl)propoxy)-2H-chromen-2-one (5c) caused DNA damage in S. cerevisiae. The O-alkenylepoxy group stands out as that with the most important functionality within this family of 35 derivatives, presenting a very good profile as an antiproliferative scaffold. Finally, the in vitro antiretroviral capacity was tested through RT-PCR assays. Derivative 5c showed inhibitory activity below 150 μM with an IC50 value of 134.22 ± 2.37 μM, highlighting the O-butylepoxy group as the functionalization responsible for the activity.This research was supported by CONICET (PIP 11220200101091CO 2021-2023), PICT 2017-0785 Type D of the National Agency for Scientific and Technological Promotion, UNSL (PROICO 02-2620), and RGLP from AvH Foundation. E.F.B.-H. thanks CONICET for doctoral fellowship and specially to Graphic Designer Bruna-Haupt L. for his help. H.A.G. thanks CONICET for belonging to the CIC. We wish thank to Dr. Di Marco N. I. for the genetic material gently provided. C.R.P. thanks CONICET for belonging to the CIC and Alexander von Humboldt Foundation for the different subsidies. We appreciate language revision by staff from the Instituto de Lenguas, UNSL, and specially Mg. Rezzano S.F.M. thanks to the Spanish Ministry of Science (research grant BFU2017-83954-R), ACIISI (research grant ProID2017010167), and FIISC (research grant PIFIIS19/04). C.G. thanks Ministerio de Ciencia, Innovación y Universidades (MCIU) of Spain-European Regional Development Fund (ERDF) (PGC2018-094503-B-C22). This work is a part of the cotutelled (UNSL-ULL) Ph.D. of E.F.B.-H.Peer reviewe

Diffusion of MMPs on the Surface of Collagen Fibrils: The Mobile Cell Surface – Collagen Substratum Interface

Remodeling of the extracellular matrix catalyzed by MMPs is central to morphogenetic phenomena during development and wound healing as well as in numerous pathologic conditions such as fibrosis and cancer. We have previously demonstrated that secreted MMP-2 is tethered to the cell surface and activated by MT1-MMP/TIMP-2-dependent mechanism. The resulting cell-surface collagenolytic complex (MT1-MMP)2/TIMP-2/MMP-2 can initiate (MT1-MMP) and complete (MMP-2) degradation of an underlying collagen fibril. The following question remained: What is the mechanism of substrate recognition involving the two structures of relatively restricted mobility, the cell surface enzymatic complex and a collagen fibril embedded in the ECM? Here we demonstrate that all the components of the complex are capable of processive movement on a surface of the collagen fibril. The mechanism of MT1-MMP movement is a biased diffusion with the bias component dependent on the proteolysis of its substrate, not adenosine triphosphate (ATP) hydrolysis. It is similar to that of the MMP-1 Brownian ratchet we described earlier. In addition, both MMP-2 and MMP-9 as well as their respective complexes with TIMP-1 and -2 are capable of Brownian diffusion on the surface of native collagen fibrils without noticeable dissociation while the dimerization of MMP-9 renders the enzyme immobile. Most instructive is the finding that the inactivation of the enzymatic activity of MT1-MMP has a detectable negative effect on the cell force developed in miniaturized 3D tissue constructs. We propose that the collagenolytic complex (MT1-MMP)2/TIMP-2/MMP-2 represents a Mobile Cell Surface – Collagen Substratum Interface. The biological implications of MT1-MMP acting as a molecular ratchet tethered to the cell surface in complex with MMP-2 suggest a new mechanism for the role of spatially regulated peri-cellular proteolysis in cell-matrix interactions

Rheumatoid arthritis response to treatment across IgG1 allotype - anti-TNF incompatibility: a case-only study.

INTRODUCTION: We have hypothesized that incompatibility between the G1m genotype of the patient and the G1m1 and G1m17 allotypes carried by infliximab (INX) and adalimumab (ADM) could decrease the efficacy of these anti-tumor necrosis factor (anti-TNF) antibodies in the treatment of rheumatoid arthritis (RA). METHODS: The G1m genotypes were analyzed in three collections of patients with RA totaling 1037 subjects. The first, used for discovery, comprised 215 Spanish patients. The second and third were successively used for replication. They included 429 British and Greek patients and 393 Spanish and British patients, respectively. Two outcomes were considered: change in the Disease Activity Score in 28 joint (ΔDAS28) and the European League Against Rheumatism (EULAR) response criteria. RESULTS: An association between less response to INX and incompatibility of the G1m1,17 allotype was found in the discovery collection at 6 months of treatment (P = 0.03). This association was confirmed in the replications (P = 0.02 and 0.08, respectively) leading to a global association (P = 0.001) that involved a mean difference in ΔDAS28 of 0.4 units between compatible and incompatible patients (2.3 ± 1.5 in compatible patients vs. 1.9 ± 1.5 in incompatible patients) and an increase in responders and decrease in non-responders according to the EULAR criteria (P = 0.03). A similar association was suggested for patients treated with ADM in the discovery collection, but it was not supported by replication. CONCLUSIONS: Our results suggest that G1m1,17 allotypes are associated with response to INX and could aid improved therapeutic targeting in RA

Amphioxus functional genomics and the origins of vertebrate gene regulation.

Vertebrates have greatly elaborated the basic chordate body plan and evolved highly distinctive genomes that have been sculpted by two whole-genome duplications. Here we sequence the genome of the Mediterranean amphioxus (Branchiostoma lanceolatum) and characterize DNA methylation, chromatin accessibility, histone modifications and transcriptomes across multiple developmental stages and adult tissues to investigate the evolution of the regulation of the chordate genome. Comparisons with vertebrates identify an intermediate stage in the evolution of differentially methylated enhancers, and a high conservation of gene expression and its cis-regulatory logic between amphioxus and vertebrates that occurs maximally at an earlier mid-embryonic phylotypic period. We analyse regulatory evolution after whole-genome duplications, and find that-in vertebrates-over 80% of broadly expressed gene families with multiple paralogues derived from whole-genome duplications have members that restricted their ancestral expression, and underwent specialization rather than subfunctionalization. Counter-intuitively, paralogues that restricted their expression increased the complexity of their regulatory landscapes. These data pave the way for a better understanding of the regulatory principles that underlie key vertebrate innovations

Search for a vector-like quark T′ → tH via the diphoton decay mode of the Higgs boson in proton-proton collisions at s \sqrt{s} = 13 TeV

A search for the electroweak production of a vector-like quark T′, decaying to a top quark and a Higgs boson is presented. The search is based on a sample of proton-proton collision events recorded at the LHC at = 13 TeV, corresponding to an integrated luminosity of 138 fb−1. This is the first T′ search that exploits the Higgs boson decay to a pair of photons. For narrow isospin singlet T′ states with masses up to 1.1 TeV, the excellent diphoton invariant mass resolution of 1–2% results in an increased sensitivity compared to previous searches based on the same production mechanism. The electroweak production of a T′ quark with mass up to 960 GeV is excluded at 95% confidence level, assuming a coupling strength κT = 0.25 and a relative decay width Γ/MT′ < 5%