Double non-perturbative gluon exchange: an update on the soft Pomeron contribution to pp scattering

We employ a set of recent, theoretically motivated, fits to non-perturbative unquenched gluon propagators to check in how far double gluon exchange can be used to describe the soft sector of pp scattering data (total and differential cross section). In particular, we use the refined Gribov--Zwanziger gluon propagator (as arising from dealing with the Gribov gauge fixing ambiguity) and the massive Cornwall-type gluon propagator (as motivated from Dyson-Schwinger equations) in conjunction with a perturbative quark-gluon vertex, next to a model based on the non-perturbative quark-gluon Maris-Tandy vertex, popular from Bethe-Salpeter descriptions of hadronic bound states. We compare the cross sections arising from these models with "older" ISR and more recent TOTEM and ATLAS data. The lower the value of total energy \sqrt{s}, the better the results appear to be.Comment: 14 pages, 8 .pdf figures. To appear in Phys.Rev.

Arginine-rich peptides destabilize the plasma membrane, consistent with a pore formation translocation mechanism of cell penetrating peptides

Recent molecular dynamics simulations (Herce and Garcia, PNAS, 104: 20805 (2007)) have suggested that the arginine-rich HIV Tat peptides might be able to translocate by destabilizing and inducing transient pores in phospholipid bilayers. In this pathway for peptide translocation, arginine residues play a fundamental role not only in the binding of the peptide to the surface of the membrane but also in the destabilization and nucleation of transient pores across the bilayer, despite being charged and highly hydrophilic. Here we present a molecular dynamics simulation of a peptide composed of nine arginines (Arg-9) that shows that this peptide follows the same translocation pathway previously found for the Tat peptide. We test this hypothesis experimentally by measuring ionic currents across phospholipid bilayers and cell membranes through the pores induced by Arg-9 peptides. We find that Arg-9 peptides, in the presence of an electrostatic potential gradient, induce ionic currents across planar phospholipid bilayers, as well as in cultured osteosarcoma cells and human smooth muscle cells freshly isolated from the umbilical artery. Our results suggest that the mechanism of action of Arg-9 peptide involves the creation of transient pores in lipid bilayers and cell membranes.Comment: This is an extended version of the published manuscript, which had to be shortened before publication to fit within the number of pages required by the journa

Early alterations in vascular contractility associated to changes in fatty acid composition and oxidative stress markers in perivascular adipose tissue

<p>Abstract</p> <p>Aim</p> <p>To test the early effect of fructose-induced changes in fatty acid composition and oxidative stress markers in perivascular adipose tissue (PVAT) upon vascular contractility.</p> <p>Methods</p> <p>Adult male Wistar rats were fed a commercial diet without (CD) or with 10% fructose (FRD) in the drinking water for 3 weeks. We measured plasma metabolic parameters, lipid composition and oxidative stress markers in aortic PVAT. Vascular contractility was measured in aortic rings sequentially, stimulated with serotonin (5-HT) and high K⁺-induced depolarization using intact and thereafter PVAT-deprived rings.</p> <p>Results</p> <p>Comparable body weights were recorded in both groups. FRD rats had increased plasma triglyceride and fructosamine levels. Their PVAT had an increased saturated to mono- or poly-unsaturated fatty acid ratio, a significant decrease in total superoxide dismutase and glutathione peroxidase activities and in the total content of glutathione. Conversely, lipid peroxidation (TBARS), nitric oxide content, and gluthathione reductase activity were significantly higher, indicating an increase in oxidative stress. In aortic rings, removal of PVAT increased serotonin-induced contractions, but the effect was significantly lower in rings from FRD rats. This effect was no longer observed when the two contractions were performed in PVAT-deprived rings. PVAT did not affect the contractions triggered by high K⁺-induced depolarization either in CD or FRD rats.</p> <p>Conclusions</p> <p>FRD induces multiple metabolic and endocrine systemic alterations which also alter PVAT and the vascular relaxant properties of this tissue. The changes in PVAT would affect its paracrine modulation of vascular function.</p

Cis-regulatory elements are harbored in Intron5 of the RUNX1 gene

BACKGROUND: Human RUNX1 gene is one of the most frequent target for chromosomal translocations associated with acute myeloid leukemia (AML) and acute lymphoid leukemia (ALL). The highest prevalence in AML is noted with (8; 21) translocation; which represents 12 to 15% of all AML cases. Interestingly, all the breakpoints mapped to date in t(8;21) are clustered in intron 5 of the RUNX1 gene and intron 1 of the ETO gene. No homologous sequences have been found at the recombination regions; but DNase I hypersensitive sites (DHS) have been mapped to the areas of the genes involved in t(8;21). Presence of DHS sites is commonly associated with regulatory elements such as promoters, enhancers and silencers, among others. RESULTS: In this study we used a combination of comparative genomics, cloning and transfection assays to evaluate potential regulatory elements located in intron 5 of the RUNX1 gene. Our genomic analysis identified nine conserved non-coding sequences that are evolutionarily conserved among rat, mouse and human. We cloned two of these regions in pGL-3 Promoter plasmid in order to analyze their transcriptional regulatory activity. Our results demonstrate that the identified regions can indeed regulate transcription of a reporter gene in a distance and position independent manner; moreover, their transcriptional effect is cell type specific. CONCLUSIONS: We have identified nine conserved non coding sequence that are harbored in intron 5 of the RUNX1 gene. We have also demonstrated that two of these regions can regulate transcriptional activity in vitro. Taken together our results suggest that intron 5 of the RUNX1 gene contains multiple potential cis-regulatory elements

ALS skeletal muscle shows enhanced TGF-β signaling, fibrosis and induction of fibro/adipogenic progenitor markers

Indexación: Web of Science; Scopus.Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease in which upper and lower motoneurons degenerate leading to muscle wasting, paralysis and eventually death from respiratory failure. Several studies indicate that skeletal muscle contributes to disease progression; however the molecular mechanisms remain elusive. Fibrosis is a common feature in skeletal muscle under chronic damage conditions such as those caused by muscular dystrophies or denervation. However, the exact mechanisms of fibrosis induction and the cellular bases of this pathological response are unknown. We show that extracellular matrix (ECM) components are augmented in skeletal muscles of symptomatic hSOD1G93A mice, a widely used murine model of ALS. These mice also show increased TGF-β1 mRNA levels, total Smad3 protein levels and p-Smad3 positive nuclei. Furthermore, platelet-derived growth factor receptor-α (PDGFRα), Tcf4 and α-smooth muscle actin (α-SMA) levels are augmented in the skeletal muscle of symptomatic hSOD1G93A mice. Additionally, the fibro/adipogenic progenitors (FAPs), which are the main producers of ECM constituents, are also increased in these pathogenic conditions. Therefore, FAPs and ECM components are more abundant in symptomatic stages of the disease than in pre-symptomatic stages. We present evidence that fibrosis observed in skeletal muscle of symptomatic hSOD1G93A mice is accompanied with an induction of TGF-β signaling, and also that FAPs might be involved in triggering a fibrotic response. Co-localization of p-Smad3 positive cells together with PDGFRα was observed in the interstitial cells of skeletal muscles from symptomatic hSOD1G93A mice. Finally, the targeting of pro-fibrotic factors such as TGF-β, CTGF/CCN2 and platelet-derived growth factor (PDGF) signaling pathway might be a suitable therapeutic approach to improve muscle function in several degenerative diseases. © 2017 Gonzalez et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.http://journals.plos.org/plosone/article?id=10.1371/journal.pone.017764

Valor del índice de resistencia arterial medido por Doppler en la función del injerto renal a mediano y largo plazos

Objective: To evaluate the association between the value of the arterial resistance index (RI) measured by Doppler at the month after transplantation, and the loss of graft. Secondary outcomes of loss greater than or equal to 50% of renal function, eath with functioning graft, biopsy findings (inflammation, hyalinosis, rejection, interstitial fibrosis - tubular atrophy, IFTA) are reported. Methods: A cohort study of 66 patients, who underwent renal transplantation at San José Hospital of Bogotá between October 2007 and April 2011. The RI of the hilar artery was measured by Doppler ultrasound at the month post-transplant. Most patients had follow-up until the second year. We describe the cumulative incidence of renal graft loss, loss greater than or equal to 50% of the glomerular filtration rate. At the second year after transplantation, rejection, IFTA, hyalinosis and documented inflammation were reported in protocol biopsies. Association analysis was performed on the histological outcomes. Results: only 2 cases of renal graft loss were reported, belonging to the group with normal RI (3.8%). At 3 years of follow-up, 5 patients had lost more than 50% of GFR compared to baseline, 4 occurred in patients with RI &lt;0.8, 2 of them (3.7%) ocurred in the first year and only one patient with RI&gt; 0.8 ocurred at 3 years. The median GFR at 3 years of follow-up in both groups is greater than 60 ml / min. In the first year of follow-up 22 (47%) patients with normal RI had IFTA, and 7 (54%) with RI&gt; 0.8 had IFTA. Hyalinosis was reported for 23% with RI&gt; 0.8 and 25.5% with RI &lt;0.8. Conclusion: the outcome of the grafts depends not only on RI, but also on factors such as cold ischemia, induction and maintenance immunosuppressive treatment, degree of incompatibility between donor and recipient. Histopathological changes such as IFTA, inflammation, hyalinosis, were observed in both groups, suggesting that there are other factors stronger than the RI, which correlates with the occurrence of these findings.Objetivo: evaluar la asociación entre el valor del índice de resistencia arterial (IR) medido por doppler al&nbsp;mes postrasplante y la pérdida de injerto. Se reportan los desenlaces secundarios de pérdida mayor o igual&nbsp;al 50% de la función renal, muerte con injerto funcionante, hallazgos de la biopsia (inflamación, hialinosis,&nbsp;rechazo, fibrosis intersticial - atrofia tubular, IFTA, por sus siglas en inglés). Métodos: se realizó un estudio de cohorte de 66 pacientes, que recibieron trasplante renal, del Hospital San José de Bogotá, entre octubre de 2007 y abril de 2011; se midió el IR de la arteria hilar por ecografía doppler al mes postrasplante. La mayoría de los pacientes fueron seguidos hasta el segundo año. Se describe la incidencia acumulada de pérdida del injerto renal, pérdida mayor o igual al 50% de la tasa filtración glomerular; al segundo año postrasplante se reporta el rechazo, IFTA, hialinosis e inflamación documentada en las biopsias de protocolo. Se realizó análisis de asociación en los desenlaces histológicos. Resultados: solo se reportaron 2 casos de pérdida del injerto renal, pertenecientes al grupo con IR normal (3.8%). A los 3 años de seguimiento 5 pacientes habían perdido más del 50% de la TFG respecto a la basal, 4 ocurrieron en los pacientes con IR &lt;0.8, 2 de ellos (3.7%) fueron al primer año y solo un paciente con IR &gt;0.8 a los 3 años. La mediana de la TFG a los 3 años de seguimiento en ambos grupos es mayor de 60 ml/ min. En el primer año de seguimiento 22 (47%) pacientes con IR normal presentaron IFTA y 7 (54%) con IR &gt;0.8 presentaron IFTA; la hialinosis con un 23% para IR &gt;0.8 y 25.5% para IR &lt;0.8. Conclusión: los desenlaces de los injertos no solo dependen del IR, hay otros factores que pueden influir como es el tiempo de isquemia fría, esquema de tratamiento inmunosupresor de inducción y mantenimiento, grado de incompatibilidades entre donante, receptor. Cambios histopatológicos como IFTA, inflamación, hialinosis, se observaron en cualquiera de los 2 grupos, lo que sugiere que hay otros factores más fuertes que el IR, que se correlaciona con la aparición de estos hallazgos

Contribución al estudio integral de las laderas del valle, serie: comunidad vegetal sobre suelos erosionados

Se llevó a cabo el inventario florístico en áreas críticas de erosión establecidas según estudios realizados por la Corporación Autónoma Regional del Cauca (CVC), en la vertiente oriental de la Cordillera Occidental, asociaciones de suelos: Dagua, Diamantina y Pescador-Zanjón seco; alturas entre 850 y 1200 m s n m. Se describió los hábitos de las especies inventariadas así como la caracterización morfológica del sistema radical. Las especies se agruparon en seis (6) categorías de acuerdo con el tipo de raíz siguiendo la metodología propuesta por J.E. Weaver (1958) con algunas modificaciones propuestas por los autores de este trabajo. El tipo de raíz que agrupó mayor número de especies es el 111(28) y el de menor número de especies fue, el VI (11). La familia Graminae presentó el mayor número de especies (30) seguida de Leguminosae (18) y Compositae (13) El hábito de crecimiento erecto fue el más característico seguido por los hábitos postrado y decumbente.The blossom inventory was carried out in the critical areas of erosion established by Corporation Autonoma Regional del Cauca (CVC), according to studies developed. This area is placed at the eastern waterfall in the western chain of mountains (Cordillera Occidental). Soil associations are Dagua, Diamantina and Pescador - Zanjon seco. The customs in the species, which were put into an inventory, as well as the morphological eatures of the root system were reviewed. The species were clasified in six (8) groups or types according to the kind of roots, following the methodology proposed by J. E. Weaver (1958) and some modifications proposed by the authors of this thesis. The type of root which grouped together the largest number of species was type 111(28) and the one which grouped the smallest number of species was type VI (11). The Graminea family showed the greatest number of species (30), followed by the Leguminosae and the Compositae (18 and 13 respectively). The erecter growth custom was the most predominant followed by the postrate one and the decumbent one