Neuropatía autonómica cardíaca diabética

La neuropatía autonómica cardíaca es una complicación frecuente y subdiagnosticada de la diabetes, se asocia con una mayor mortalidad por causas cardiovasculares e incapacidad física. El tratamiento actual está basado en recomendaciones de expertos y experiencias locales, debido a la falta de estudios de alto peso epidemiológico que orienten el manejo de estos pacientes. Con esta revisión se busca generar conciencia a la comunidad médica acerca de la importancia de esta entidad, de su reconocimiento temprano, formas de diagnóstico y tratamiento disponibles con la evidencia actual

Targeting the Stress-Induced Protein NUPR1 to Treat Pancreatic Adenocarcinoma

Cancer cells activate stress-response mechanisms to adapt themselves to a variety of stressful conditions. Among these protective mechanisms, those controlled by the stress-induced nuclear protein 1 (NUPR1 ) belong to the most conserved ones. NUPR1 is an 82-residue-long, monomeric, basic and intrinsically disordered protein (IDP), which was found to be invariably overexpressed in some, if not all, cancer tissues. Remarkably, we and others have previously showed that genetic inactivation of the Nupr1 gene antagonizes the growth of pancreatic cancer as well as several other tumors. With the use of a multidisciplinary strategy by combining biophysical, biochemical, bioinformatic, and biological approaches, a trifluoperazine-derived compound, named ZZW-115, has been identified as an inhibitor of the NUPR1 functions. The anticancer activity of the ZZW-115 was first validated on a large panel of cancer cells. Furthermore, ZZW-115 produced a dose-dependent tumor regression of the tumor size in xenografted mice. Mechanistically, we have demonstrated that NUPR1 binds to several importins. Because ZZW-115 binds NUPR1 through the region around the amino acid Thr68, which is located into the nuclear location signal (NLS) region of the protein, we demonstrated that treatment with ZZW-115 inhibits completely the translocation of NUPR1 from the cytoplasm to the nucleus by competing with importins

Ácidos grasos y parámetros de calidad del aceite de semilla de uva silvestre (Vitis spp.)

Mexico is one of the centers of origin of the genus Vitis. Most of the native species are in an underutilized or neglected status. Thus, this work was performed aiming the determination of the potential of Mexican native grapes as a source of plant oil. It was determined the amount of oil and its fatty acid composition in seeds of wild grapes (Vitis spp.) in fruits collected in Temascaltepec, Mexico and harvested from a cropped accession growing in Zumpahuacán, Mexico. The average content of oil in seeds was 16.7% presenting four main fatty acids, linoleic, oleic, palmitic and stearic (71.5, 17.2, 6.6 and 4.3%, respectively). In the oil obtained from Temascaltepec grapes, there were determined some oil quality indexes. Possibly, the unsaturated fatty acid content explains the index of iodine (57.9 g/100 g), soapy number (170.7 mg/g), as well as the peroxide value (30 mEq/kg). Nevertheless, the high content of unsaturated fatty acid was not related with the smoking point (211 °C), although this value might be related to the content of palmitic and stearic acid. Oil from wild grape shows similar quality parameters compared with V. vinifera seed oil, thus its culinary, agro-industrial and cosmetic potential is noted.México es centro de origen de varias especies de Vitis. La gran mayoría de ellas no son empleadas en la agricultura e industrias derivadas. Como parte de la exploración de su potencial agroindustrial se identificó y cuantificó a los ácidos grasos del aceite de semilla de vid silvestre (Vitis spp.) de frutos de Temascaltepec, México y de la accesión E-201, cultivada en Zumpahuacán, México. El contenido promedio de aceite en la semilla fue de 16,7%, encontrando ácido linoleico (71,5%), oleico (17,2%), palmítico (6,6%) y esteárico (4,3%). En el aceite obtenido en vides de Temascaltepec se determinó índice de yodo (57,9 g/100 g), índice de saponificación (170,7 mg/g) e índice de peroxidos (30 mEq/kg), valores relacionados posiblemente al contenido de ácidos grasos insaturados. Sin embargo, ese mismo grado de insaturación no concordó con el punto de humeo observado (211 °C), lo cual posiblemente está relacionado con el contenido de ácidos palmítico y esteárico. El aceite de semilla de vid silvestre cumple parcialmente con los estándares establecidos para el aceite de semilla de V. vinifera, lo cual implica su potencial culinario, agroindustrial y cosmetológico

Naturalness and superpartner masses or when to give up on weak scale supersymmetry

Superpartner masses cannot be arbitrarily heavy if supersymmetric extensions of the standard model explain the stability of the gauge hierarchy. This ancient and hallowed motivation for weak scale supersymmetry is often quoted, yet no reliable determination of this upper limit on superpartner masses exists. In this paper we compute upper bounds on superpartner masses in the minimal supersymmetric model, and we identify which values of the superpartner masses correspond to the most natural explanation of the hierarchy stability. We compare the most natural value of these masses and their upper limits to the physics reach of current and future colliders. As a result, we find that supersymmetry could explain weak scale stability naturally even if no superpartners are discovered at LEP II or the Tevatron (even with the Main Injector upgrade). However, we find that supersymmetry cannot provide a complete explanation of weak scale stability, if squarks and gluinos have masses beyond the physics reach of the LHC. Moreover, in the most natural scenarios, many sparticles, for example, charginos, squarks, and gluinos, lie within the physics reach of either LEP II or the Tevatron. Our analysis determines the most natural value of the chargino (squark) ((gluino)) mass consistent with current experimental constraints is $\sim$ 50 (250) ((250)) GeV and the corresponding theoretical upper bound is $\sim$ 250 (700) ((800)) GeV.Comment: 14 pages, LaTex, 17 figures uuencoded, gz-compressed file. Minor revisions bring archived manuscript in line with the published versio

ZZW-115-dependent inhibition of NUPR1 nuclear translocation sensitizes cancer cells to genotoxic agents

Establishing the interactome of the cancer-associated stress protein Nuclear Protein 1 (NUPR1), we found that it binds to several hundreds of proteins, including proteins involved in nuclear translocation, DNA repair, and key factors of the SUMO pathway. We demonstrated that the NUPR1 inhibitor ZZW-115, an organic synthetic molecule, competes with importins for the binding to the NLS region of NUPR1, thereby inhibiting its nuclear translocation. We hypothesized, and then proved, that inhibition of NUPR1 by ZZW-115 sensitizes cancer cells to DNA damage induced by several genotoxic agents. Strikingly, we found that treatment with ZZW-115 reduced SUMOylation of several proteins involved in DNA damage response (DDR). We further report that the presence of recombinant NUPR1 improved the SUMOylation in a cell-free system, indicating that NUPR1 directly stimulates the SUMOylation machinery. We propose that ZZW-115 sensitizes cancer cells to genotoxic agents by inhibiting the nuclear translocation of NUPR1 and thereby decreasing the SUMOylation-dependent functions of key proteins involved in the DDR

Yukawa Unification as a Window into the Soft Supersymmetry Breaking Lagrangian

We study Yukawa unification, including the effects of a physical neutrino mass consistent with the Superkamiokande observations, in a string/$D$-brane inspired Pati-Salam model which allows the most general non-universal scalar and gaugino masses, including the usual $D$-term contributions which arise in SO(10). We investigate how the tight constraints from rare decays such as $b \to s \gamma$ and $\tau \to \mu \gamma$ can provide information about the family dependent supersymmetry breaking soft Lagrangian, for example the trilinears associated with the second and third family. Many of our results also apply to SO(10) to which the model approximately reduces in a limiting case. In both models we find that Yukawa unification is perfectly viable providing the non-universal soft masses have particular patterns. In this sense Yukawa unification acts as a window into the soft supersymmetry breaking Lagrangian.Comment: References added. 82 pages, 57 figures, Late

Aplicación del método de la madurez para la estimación del plazo de descimbrado de forjados construidos con sistemas industrializados

El presente artículo propone una metodología para la estimación del plazo de descimbrado de forjados construidos con sistemas industrializados. Para esto, se realiza un estudio de madurez de hormigones usados en este tipo de construcción. Con el fin de construir la curva de madurez en laboratorio se implementa la metodología descrita en la ASTM C1074, calculando la energía de activación por los tres métodos propuestos y midiendo el historial térmico de las mezclas a una temperatura controlada. Por último, se realiza la instrumentación en obra de una placa donde se estima la edad de descimbrado. Se ha observado que el tiempo de fraguado final no es un parámetro recomendable para descimbrar las placas, como lo recomiendan las productoras de hormigón en Colombia. La edad de descimbrado obtenida es mayor a la del tiempo de fraguado final, habiendo una diferencia de hasta 11 horas en el caso más crítico.Castro-Garrido, M.; López-Garzón, M.; Alvarado Vargas, YA.; Castaño Tabares, JO.; Gasch, I. (2016). Aplicación del método de la madurez para la estimación del plazo de descimbrado de forjados construidos con sistemas industrializados. Informes de la Construcción. 68(541). doi:10.3989/ic.14.105Se1316854

Experimental ovine toxoplasmosis: influence of the gestational stage on the clinical course, lesion development and parasite distribution

P. 1-14The relation between gestational age and foetal death risk in ovine toxoplasmosis is already known, but the mechanisms involved are not yet clear. In order to study how the stage of gestation influences these mechanisms, pregnant sheep of the same age and genetic background were orally dosed with 50 oocysts of Toxoplasma gondii (M4 isolate) at days 40 (G1), 90 (G2) and 120 (G3) of gestation. In each group, four animals were culled on the second, third and fourth week post infection (pi) in order to evaluate parasite load and distribution, and lesions in target organs. Ewes from G1 showed a longer period of hyperthermia than the other groups. Abortions occurred in all groups. While in G2 they were more frequent during the acute phase of the disease, in G3 they mainly occurred after day 20 pi. After challenge, parasite and lesions in the placentas and foetuses were detected from day 19 pi in G3 while in G2 or G1 they were only detected at day 26 pi. However, after initial detection at day 19 pi, parasite burden, measured through RT-PCR, in placenta or foetus of G3 did not increase significantly and, at in the third week pi it was lower than that measured in foetal liver or placenta from G1 to G3 respectively. These results show that the period of gestation clearly influences the parasite multiplication and development of lesions in the placenta and foetus and, as a consequence, the clinical course in ovine toxoplasmosis.S

Star Formation and Dynamics in the Galactic Centre

The centre of our Galaxy is one of the most studied and yet enigmatic places in the Universe. At a distance of about 8 kpc from our Sun, the Galactic centre (GC) is the ideal environment to study the extreme processes that take place in the vicinity of a supermassive black hole (SMBH). Despite the hostile environment, several tens of early-type stars populate the central parsec of our Galaxy. A fraction of them lie in a thin ring with mild eccentricity and inner radius ~0.04 pc, while the S-stars, i.e. the ~30 stars closest to the SMBH (<0.04 pc), have randomly oriented and highly eccentric orbits. The formation of such early-type stars has been a puzzle for a long time: molecular clouds should be tidally disrupted by the SMBH before they can fragment into stars. We review the main scenarios proposed to explain the formation and the dynamical evolution of the early-type stars in the GC. In particular, we discuss the most popular in situ scenarios (accretion disc fragmentation and molecular cloud disruption) and migration scenarios (star cluster inspiral and Hills mechanism). We focus on the most pressing challenges that must be faced to shed light on the process of star formation in the vicinity of a SMBH.Comment: 68 pages, 35 figures; invited review chapter, to be published in expanded form in Haardt, F., Gorini, V., Moschella, U. and Treves, A., 'Astrophysical Black Holes'. Lecture Notes in Physics. Springer 201