Quantitative analysis of 3D extracellular matrix remodelling by pancreatic stellate cells

Extracellular matrix (ECM) remodelling is integral to numerous physiological and pathological processes in biology, such as embryogenesis, wound healing, fibrosis and cancer. Until recently, most cellular studies have been conducted on 2D environments where mechanical cues significantly differ from physiologically relevant 3D environments, impacting cellular behaviour and masking the interpretation of cellular function in health and disease. We present an integrated methodology where cell-ECM interactions can be investigated in 3D environments via ECM remodelling. Monitoring and quantification of collagen-I structure in remodelled matrices, through designated algorithms, show that 3D matrices can be used to correlate remodelling with increased ECM stiffness observed in fibrosis. Pancreatic stellate cells (PSCs) are the key effectors of the stromal fibrosis associated to pancreatic cancer. We use PSCs to implement our methodology and demonstrate that PSC matrix remodelling capabilities depend on their contractile machinery and β1 integrin-mediated cell-ECM attachment

ATRA mechanically reprograms pancreatic stellate cells to suppress matrix remodelling and inhibit cancer cell invasion

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy with a dismal survival rate. Persistent activation of pancreatic stellate cells (PSCs) can perturb the biomechanical homoeostasis of the tumour microenvironment to favour cancer cell invasion. Here we report that ATRA, an active metabolite of vitamin A, restores mechanical quiescence in PSCs via a mechanism involving a retinoic acid receptor beta (RAR-β)-dependent downregulation of actomyosin (MLC-2) contractility. We show that ATRA reduces the ability of PSCs to generate high traction forces and adapt to extracellular mechanical cues (mechanosensing), as well as suppresses force-mediated extracellular matrix remodelling to inhibit local cancer cell invasion in 3D organotypic models. Our findings implicate a RAR-β/MLC-2 pathway in peritumoural stromal remodelling and mechanosensory-driven activation of PSCs, and further suggest that mechanical reprogramming of PSCs with retinoic acid derivatives might be a viable alternative to stromal ablation strategies for the treatment of PDAC

How Big Can Anomalous W Couplings Be?

Conventional wisdom has it that anomalous gauge-boson self-couplings can be at most a percent or so in size. We test this wisdom by computing these couplings at one loop in a generic renormalizable model of new physics. (For technical reasons we consider the CP-violating couplings here, but our results apply more generally.) By surveying the parameter space we find that the largest couplings (several percent) are obtained when the new particles are at the weak scale. For heavy new physics we compare our findings with expectations based on an effective-lagrangian analysis. We find general patterns of induced couplings which robustly reflect the nature of the underlying physics. We build representative models for which the new physics could be first detected in the anomalous gauge couplings.Comment: 40 pages, 11 figures, (dvi file and figures combined into a uuencoded compressed file), (We correct an error in eq. 39 and its associated figure (9). No changes at all to the text.), McGill-93/40, UQAM-PHE-93/03, NEIPH-93-00

Hepatocarcinoma sobre hígado ectópico peritoneal

El hepatocarcinoma (HCC) sobre hígado ectópico es una entidad rara. La mayoría de los casos son asintomáticos y se descubren de manera casual en una autopsia o laparoscopia. En ocasiones producen clínica como dolor abdominal o hemorragia intraabdominal. Se realiza revisión de la literatura y se presenta el caso de una mujer de 68 años diagnosticada de hepatocarcinoma sobre hígado ectópico peritoneal a raíz de un estudio por hipertransaminasemia leve asintomática. Ectopic hepatocellular carcinoma is a rare entity. Most cases are asymptomatic and are occasionally found during autopsy or laparoscopy. They may sometimes cause relevant clinical problems such as abdominal pain or intra-abdominal bleeding. In this clinical case report, we review the literature in order to decipher the case of a 68-year-old female with an ectopic hepatocellular carcinoma that arose from the peritoneum. The patient was diagnosed after being studied due to a mild asymptomatic hypertransaminasemia

SSDSS IV MaNGA - Properties of AGN host galaxies

We present here the characterization of the main properties of a sample of 98 AGN host galaxies, both type-II and type-I, in comparison with those of about 2700 non-active galaxies observed by the MaNGA survey. We found that AGN hosts are morphologically early-type or early-spirals. For a given morphology AGN hosts are, in average, more massive, more compact, more central peaked and rather pressurethan rotational-supported systems. We confirm previous results indicating that AGN hosts are located in the intermediate/transition region between star-forming and non-star-forming galaxies (i.e., the so-called green valley), both in the ColorMagnitude and the star formation main sequence diagrams. Taking into account their relative distribution in terms of the stellar metallicity and oxygen gas abundance and a rough estimation of their molecular gas content, we consider that these galaxies are in the process of halting/quenching the star formation, in an actual transition between both groups. The analysis of the radial distributions of the starformation rate, specific star-formation rate, and molecular gas density shows that the quenching happens from inside-out involving both a decrease of the efficiency of the star formation and a deficit of molecular gas. All the intermediate data-products used to derive the results of our analysis are distributed in a database including the spatial distribution and average properties of the stellar populations and ionized gas, published as a Sloan Digital Sky Survey Value Added Catalog being part of the 14th Data Release: http://www.sdss.org/dr14/manga/manga-data/manga-pipe3d-value-added-catalog/Comment: 48 pages, 14 figures, in press in RMxA

Divergent abiotic spectral pathways unravel pathogen stress signals across species

Abstract: Plant pathogens pose increasing threats to global food security, causing yield losses that exceed 30% in food-deficit regions. Xylella fastidiosa (Xf) represents the major transboundary plant pest and one of the world’s most damaging pathogens in terms of socioeconomic impact. Spectral screening methods are critical to detect non-visual symptoms of early infection and prevent spread. However, the subtle pathogen-induced physiological alterations that are spectrally detectable are entangled with the dynamics of abiotic stresses. Here, using airborne spectroscopy and thermal scanning of areas covering more than one million trees of different species, infections and water stress levels, we reveal the existence of divergent pathogen- and host-specific spectral pathways that can disentangle biotic-induced symptoms. We demonstrate that uncoupling this biotic–abiotic spectral dynamics diminishes the uncertainty in the Xf detection to below 6% across different hosts. Assessing these deviating pathways against another harmful vascular pathogen that produces analogous symptoms, Verticillium dahliae, the divergent routes remained pathogen- and host-specific, revealing detection accuracies exceeding 92% across pathosystems. These urgently needed hyperspectral methods advance early detection of devastating pathogens to reduce the billions in crop losses worldwide

Cover Contact Graphs.

We study problems that arise in the context of covering certain geometric objects (so-called seeds, e.g., points or disks) by a set of other geometric objects (a so-called cover, e.g., a set of disks or homothetic triangles). We insist that the interiors of the seeds and the cover elements are pair wise disjoint, but they can touch. We call the contact graph of a cover a cover contact graph (CCG). We are interested in two types of tasks: (a) deciding whether a given seed set has a connected CCG, and (b) deciding whether a given graph has a realization as a CCG on a given seed set. Concerning task (a) we give efficient algorithms for the case that seeds are points and covers are disks or triangles. We show that the problem becomes NP-hard if seeds and covers are disks. Concerning task (b) we show that it is even NP-hard for point seeds and disk covers (given a fixed correspondence between vertices and seeds)