Novel application assigned to toluquinol: inhibition of lymphangiogenesis by interfering with VEGF-C/VEGFR-3 signalling pathway

BACKGROUND AND PURPOSE Lymphangiogenesis is an important biological process associated with the pathogenesis of several diseases, including metastatic dissemination, graft rejection, lymphoedema and other inflammatory disorders. The development of new drugs that block lymphangiogenesis has become a promising therapeutic strategy. In this study, we investigated the ability of toluquinol, a 2-methyl-hydroquinone isolated from the culture broth of the marine fungus Penicillium sp. HL-85-ALS5-R004, to inhibit lymphangiogenesis in vitro, ex vivo and in vivo. EXPERIMENTAL APPROACH We used human lymphatic endothelial cells (LECs) to analyse the effect of toluquinol in 2D and 3D in vitro cultures and in the ex vivo mouse lymphatic ring assay. For in vivo approaches, the transgenic Fli1:eGFPy1 zebrafish, mouse ear sponges and cornea models were used. Western blotting and apoptosis analyses were carried out to search for drug targets. KEY RESULTS Toluquinol inhibited LEC proliferation,migration, tubulogenesis and sprouting of new lymphatic vessels. Furthermore, toluquinol induced apoptosis of LECs after 14 h of treatment in vitro, blocked the development of the thoracic duct in zebrafish and reduced the VEGF-C-induced lymphatic vessel formation and corneal neovascularization in mice. Mechanistically, we demonstrated that this drug attenuates VEGF-C-induced VEGFR-3 phosphorylation in a dose-dependentmanner and suppresses the phosphorylation of Akt and ERK1/2. CONCLUSIONS AND IMPLICATIONS Based on these findings, we propose toluquinol as a new candidate with pharmacological potential for the treatment of lymphangiogenesis-related pathologies. Notably, its ability to suppress corneal neovascularization paves the way for applications in vascular ocular pathologies.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech. This work has been supported by personal funding by FP7-PEOPLE-2013-IEF Marie Curie Postdoctoral Fellowship (MGC). Acknowledged are the supporting grants from the Action de Recherche Concertée (ARC) (Université de Liège), the Fonds de la Recherche Scientifique-FNRS (F.R.S.-FNRS), the Foundation Against Cancer (foundation of public interest), the Centre Anticancéreux près l’Université de Liège, the Fonds Léon Fredericq (University of Liège), the Interuniversity Attraction Poles Programme-Belgian Science Policy (all from Belgium) and the Plan National Cancer (« Service Public Federal » from Belgium). Research in the lab of A.R.Q. and M.A.M. was supported by grants BIO2014-56092-R (MINECO and FEDER) and P12-CTS-1507 (Andalusian Government and FEDER)

Determinación de la curva de rotación de M31 a lo largo del eje menor

Utilizando datos obtenidos con el radiotelescopio de Westerbork se está construyendo una curva de rotación a lo largo del eje menor. Se comparan los resultados obtenidos con los logrados con otras observaciones a lo largo del eje mayor.Asociación Argentina de Astronomí

Influencia de la turbulencia del gas y geométrica en la curva de rotación básica para la línea de 21 cm

Se ha estudiado el efecto de la turbulencia del gas y de la resolución en velocidades de la antena en la posición y dispersión del pico de acumulación que se observa en los perfiles de la línea de 21 cm mediante la simulación numérica de perfiles teóricos para b=0° y un amplio rango de longitudes. Se encuentra que la turbulencia puede jugar en ciertos casos un papel predominante en la posición en velocidades del pico de acumulación. Este estudio comprende además un análisis paramétrico de la variación de la curva de rotación básica y la posición del pico de acumulación con la turbulencia del gas. Una comparación con perfiles observados permite obtener un orden de magnitud de las perturbaciones en velocidad debido a la presencia de antisimetrías en el potencial (brazos espirales).Asociación Argentina de Astronomí

Estudio de las estructuras exteriores de la galaxia en la zona 310° ≤ l ≤ 33°, 7°≤ b ≤ 3°

En esta región, estudiada por medio de la línea en emisión de 21 cm, se encontraron 5 estructuras bien diferenciadas en velocidades. Se compraron las observaciones con otros relevamientos en el hemisferio Sur, hallándose continuidad en algunas estructuras. Se investigó la existencia de posibles analogías con el hemisferio Norte, encontrándose simetrías respecto del plano galáctico. Se comprobó la inclinación del plano galáctico hacia latitudes negativas en la zona relevada.Asociación Argentina de Astronomí

Effects of acute variation of dialysate calcium concentrations on arterial stiffness and aortic pressure waveform

Background. Abnormal mineral metabolism in chronic kidney disease plays a critical role in vascular calcification and arterial stiffness. The impact of presently used dialysis calcium concentration (DCa) on arterial stiffness and aortic pressure waveform has never been studied. The aim of the present study is to evaluate, in haemodialysis (HD) patients, the impact of acute modification of DCa on arterial stiffness and central pulse wave profile (cPWP)

A supergene-controlling social structure in Alpine ants also affects the dispersal ability and fecundity of each sex.

Social organization, dispersal and fecundity coevolve, but whether they are genetically linked remains little known. Supergenes are prime candidates for coupling adaptive traits and mediating sex-specific trade-offs. Here, we test whether a supergene that controls social structure in Formica selysi also influences dispersal-related traits and fecundity within each sex. In this ant species, single-queen colonies contain only the ancestral supergene haplotype M and produce MM queens and M males, while multi-queen colonies contain the derived haplotype P and produce MP queens, PP queens and P males. By combining multiple experiments, we show that the M haplotype induces phenotypes with higher dispersal potential and higher fecundity in both sexes. Specifically, MM queens, MP queens and M males are more aerodynamic and more fecund than PP queens and P males, respectively. Differences between MP and PP queens from the same colonies reveal a direct genetic effect of the supergene on dispersal-related traits and fecundity. The derived haplotype P, associated with multi-queen colonies, produces queens and males with reduced dispersal abilities and lower fecundity. More broadly, similarities between the Formica and Solenopsis systems reveal that supergenes play a major role in linking behavioural, morphological and physiological traits associated with intraspecific social polymorphisms

Whole Slide Quantification of Stromal Lymphatic Vessel Distribution and Peritumoral Lymphatic Vessel Density in Early Invasive Cervical Cancer: A Method Description

Peritumoral Lymphatic Vessel Density (LVD) is considered to be a predictive marker for the presence of lymph node metastases in cervical cancer. However, when LVD quantification relies on conventional optical microscopy and the hot spot technique, interobserver variability is significant and yields inconsistent conclusions. In this work, we describe an original method that applies computed image analysis to whole slide scanned tissue sections following immunohistochemical lymphatic vessel staining. This procedure allows to determine an objective LVD quantification as well as the lymphatic vessel distribution and its heterogeneity within the stroma surrounding the invasive tumor bundles. The proposed technique can be useful to better characterize lymphatic vessel interactions with tumor cells and could potentially impact on prognosis and therapeutic decisions

Quantum interference in nanofractals and its optical manifestation

We consider quantum interferences of ballistic electrons propagating inside fractal structures with nanometric size of their arms. We use a scaling argument to calculate the density of states of free electrons confined in a simple model fractal. We show how the fractal dimension governs the density of states and optical properties of fractal structures in the RF-IR region. We discuss the effect of disorder on the density of states along with the possibility of experimental observation.Comment: 19 pages, 6 figure

Species recognition limits mating between hybridizing ant species

Identifying mechanisms limiting hybridization is a central goal of speciation research. Here, we studied pre-mating and post-mating barriers to hybridization between two ant species, Formica selysi and Formica cinerea. These species hybridize in the Rhône valley in Switzerland, where they form a mosaic hybrid zone, with limited introgression from F. selysi into F. cinerea. There was no sign of temporal isolation between the two species in the production of queens and males. With choice experiments, we showed that queens and males strongly prefer to mate with conspecifics. Yet, we did not detect post-mating barriers caused by genetic incompatibilities. Specifically, hybrids of all sexes and castes were found in the field and F1 hybrid workers did not show reduced viability compared to non-hybrid workers. To gain insights into the cues involved in species recognition, we analyzed the cuticular hydrocarbons of queens, males and workers and staged dyadic encounters between workers. Cuticular hydrocarbon profiles differed markedly between species, but were similar in F. cinerea and hybrids. Accordingly, workers also discriminated species, but they did not discriminate F. cinerea and hybrids. We discuss how the CHC-based recognition system of ants may facilitate the establishment of pre-mating barriers to hybridization, independent of hybridization costs. This article is protected by copyright. All rights reserved

Assessment of arterial stiffness, oxidative stress and inflammation in acute kidney injury

Background: It is well know that arterial stiffness, oxidative stress and inflammation are features of chronic kidney disease. The arterial changes have a multitude of potential interconnected causes including endothelial dysfunction, oxidative stress, inflammation, atherosclerosis and vascular calcification. There is evidence that arterial stiffness becomes progressively worse as CKD progresses. The contribution of the biochemical changes of uremic toxicity to arterial stiffness is less clear. The aim of this study is to elucidate the vascular changes in acute kidney injury. We hypothesise that arterial stiffness will be increased during acute kidney injury and this will return to normal after kidney function recovers