Biology of pancreatic stellate cells—more than just pancreatic cancer

Pancreatic stellate cells, normally quiescent, are capable of remarkable transition into their activated myofibroblast-like phenotype. It is now commonly accepted that these cells play a pivotal role in the desmoplastic reaction present in severe pancreatic disorders. In recent years, enormous scientific effort has been devoted to understanding their roles in pancreatic cancer, which continues to remain one of the most deadly diseases. Therefore, it is not surprising that considerably less attention has been given to studying physiological functions of pancreatic stellate cells. Here, we review recent advances not only in the field of pancreatic stellate cell pathophysiology but also emphasise their roles in physiological processes

VisGenome: visualization of single and comparative genome representations

VisGenome visualizes single and comparative representations for the rat, the mouse and the human chromosomes at different levels of detail. The tool offers smooth zooming and panning which is more flexible than seen in other browsers. It presents information available in Ensembl for single chromosomes, as well as homologies (orthologue predictions including ortholog one2one, apparent ortholog one2one, ortholog many2many) for any two chromosomes from different species. The application can query supporting data from Ensembl by invoking a link in a browser

The integration of optical interconnections on ceramic substrates

High heat conductivity and high heat capacity make ceramic substrates indispensable to the manufacture of Multi-Chip Modules (MCM) and power electronics. In this paper a detailed description of the integration process of optical lines on to ceramic substrates is presented. The manufacturing of microgrooves in ceramic substrates and the process of integration of optical fibres and active elements is described. Coupling active elements to optical fibre is also presented. Through such an integrated optical line a 4 Gbps signal was transmitted. © 2016 Elsevier B.V. All rights reserved

Gender, media, and mixed martial arts in Poland: the case of Joanna Jędrzejczyk

Recent growth in the media visibility of female combat sport athletes has offered a compelling site for research on gender and sport media, as women in deeply masculinized sports have been increasingly placed in the public spotlight. While scholars in the Anglophone West have offered analyses of the media framing of this phenomenon, little work has been done outside these cultural contexts. Thus, in this paper we offer a qualitative exploration of how Joanna Jędrzejczyk, a Polish champion of the Ultimate Fighting Championship, has been represented in Polish media. Our findings reveal a relatively de-gendered, widely celebratory account, primarily framed by nationalistic discourse–findings we ascribe to both the particularities of the sport of mixed martial arts as well as the historic nature of Jędrzejczyk’s success

Enhanced relativistic-electron beam collimation using two consecutive laser pulses

The double laser pulse approach to relativistic electron beam (REB) collimation has been investigated at the LULI-ELFIE facility. In this scheme, the magnetic field generated by the first laser-driven REB is used to guide a second delayed REB. We show how electron beam collimation can be controlled by properly adjusting laser parameters. By changing the ratio of focus size and the delay time between the two pulses we found a maximum of electron beam collimation clearly dependent on the focal spot size ratio of the two laser pulses and related to the magnetic field dynamics. Cu-K alpha and CTR imaging diagnostics were implemented to evaluate the collimation effects on the respectively low energy ( MeV) components of the REB

Bile acids induce necrosis in pancreatic stellate cells dependent on calcium entry and sodium-driven bile uptake

Acute biliary pancreatitis, caused by bile reflux into the pancreas, is a serious condition characterised by premature activation of digestive enzymes within acinar cells, followed by necrosis and inflammation. Bile acids are known to induce pathological Ca2+ signals and necrosis in acinar cells. However, bile acid-elicited signalling events in stellate cells remain unexplored. This is the first study to demonstrate the pathophysiological effects of bile acids on stellate cells in two experimental models: ex vivo (mouse pancreatic lobules) and in vitro (human cells). Sodium cholate and taurocholate induced cytosolic Ca2+ elevations in stellate cells, larger than those elicited simultaneously in the neighbouring acinar cells. In contrast, taurolithocholic acid 3-sulfate (TLC-S), known to induce Ca2+ oscillations in acinar cells, had only minor effects on stellate cells in lobules. The dependence of the Ca2+ signals on extracellular Na+ and the presence of sodium-taurocholate cotransporting polypeptide (NTCP) indicate a Na+-dependent bile acid uptake mechanism in stellate cells. Bile acid treatment caused necrosis predominantly in stellate cells, which was abolished by removal of extracellular Ca2+ and significantly reduced in the absence of Na+, showing that bile-dependent cell death was a downstream event of Ca2+ signals. Finally, combined application of TLC-S and the inflammatory mediator bradykinin caused more extensive necrosis in both stellate and acinar cells than TLC-S alone. Our findings shed new light on the mechanism by which bile acids promote pancreatic pathology. This involves not only signalling in acinar cells but also in stellate cells

Nitric oxide signals are interlinked with calcium signals in normal pancreatic stellate cells upon oxidative stress and inflammation

The mammalian diffuse stellate cell system comprises retinoid-storing cells capable of remarkable transformations from a quiescent to an activated myofibroblast-like phenotype. Activated pancreatic stellate cells (PSCs) attract attention owing to the pivotal role they play in development of tissue fibrosis in chronic pancreatitis and pancreatic cancer. However, little is known about the actual role of PSCs in the normal pancreas. These enigmatic cells have recently been shown to respond to physiological stimuli in a manner that is markedly different from their neighbouring pancreatic acinar cells (PACs). Here, we demonstrate the capacity of PSCs to generate nitric oxide (NO), a free radical messenger mediating, for example, inflammation and vasodilatation. We show that production of cytosolic NO in PSCs is unambiguously related to cytosolic Ca2+ signals. Only stimuli that evoke Ca2+ signals in the PSCs elicit consequent NO generation. We provide fresh evidence for the striking difference between signalling pathways in PSCs and adjacent PACs, because PSCs, in contrast to PACs, generate substantial Ca2+-mediated and NOS-dependent NO signals. We also show that inhibition of NO generation protects both PSCs and PACs from necrosis. Our results highlight the interplay between Ca2+ and NO signalling pathways in cell–cell communication, and also identify a potential therapeutic target for anti-inflammatory therapies

Characterization of the c.190T>C missense mutation in BRCA1 codon 64 (Cys64Arg).

In the Milan area (Northern Italy), we identified a family characterized by a high prevalence of ovarian and breast cancer cases (5 out of 6 subjects, over 3 generations), and a predominant prevalence of ovarian lesions (4 out of 5 patients). Analysis of BRCA1 and BRCA2 genes allowed the identification of the missense c.190T>C mutation in codon 64 (Cys64Arg) of BRCA1. The aims of the present investigation were to characterize the functional implications of the c.190T>C mutation at the molecular level, and to search whether additional polymorphisms might be linked to the peculiar phenotypic features observed in the Italian pedigree. Molecular modelling studies suggested that substitution of the cysteine 64 with an arginine likely disrupts the architecture of the BRCA1 RING finger domain, responsible for the interaction with BARD1, essential for the tumor-suppressor activity of the BRCA1-BARD1 complex. By splicing site information analysis, exonic splicing enhancer site characterization, and analysis of transcript fragment length and sequence, we showed that the c.190T>C mutation was able to modulate the splicing of exon 5 in a fashion opposite to the c.190T>G transversion, responsible for the functionally-related Cys64Gly amino acid substitution. Genotyping of BRCA1 and BRCA2 in the Italian family revealed the presence of two significant polymorphisms: the cancer-associated c.2612C>T SNP in BRCA1, and the c.-26G>A SNP in the BRCA2 gene, acting as an ovarian cancer risk modifier in carriers of deleterious BRCA1 mutations. Analysis of these SNPs in a genotypically-unrelated Polish family, characterized by prevalent breast neoplasms in carriers of the c.190T>C mutation, revealed a genetic profile consistent with the hypothetic role of both polymorphisms

Physicochemical and Antibacterial Characterisation of a Novel Fluorapatite Coating

Peri-implantitis remains the major impediment to the long-term use of dental implants. With increasing concern over growing antibiotic resistance there is considerable interest in the preparation of antimicrobial dental implant coatings that also induce osseointegration. One such potential coating material is fluorapatite (FA). The aim of this study was to relate the antibacterial effectiveness of FA coatings against pathogens implicated in peri-implantitis to the physicochemical properties of the coating. Ordered and disordered FA coatings were produced on the under and upper surface of stainless steel (SS) discs respectively, using a hydrothermal method. Surface charge, surface roughness, wettability and fluoride release were measured for each coating. Surface chemistry was assessed by X-ray photoelectron spectroscopy and FA crystallinity by X-ray diffraction. Antibacterial activity against periodontopathogens was assessed in vitro using viable counts, confocal and scanning electron (SEM) microscopies. SEM showed that the hydrothermal method produced FA coatings predominately aligned perpendicular to the SS substrate or disordered FA coatings consisting of randomly aligned rod-like crystals. Both FA coatings significantly reduced the growth of all the examined bacterial strains in comparison to the control. The FA coatings, and especially the disordered ones, presented significantly lower charge, higher roughness and area when compared to the control, enhancing bacteria–material interactions and therefore bacterial deactivation by fluoride ions. The ordered FA layer reduced not only bacterial viability but adhesion too. Ordered FA crystals produced as a potential novel implant coating showed significant antibacterial activity against bacteria implicated in peri-implantitis which could be explained by a detailed understanding of their physicochemical properties

O 1s excitation and ionization processes in the CO2 molecule studied via detection of low-energy fluorescence emission

Oxygen 1s excitation and ionization processes in the CO2 molecule have been studied with dispersed and non-dispersed fluorescence spectroscopy as well as with the vacuum ultraviolet (VUV) photon?photoion coincidence technique. The intensity of the neutral O emission line at 845 nm shows particular sensitivity to core-to-Rydberg excitations and core?valence double excitations, while shape resonances are suppressed. In contrast, the partial fluorescence yield in the wavelength window 300?650 nm and the excitation functions of selected O+ and C+ emission lines in the wavelength range 400?500 nm display all of the absorption features. The relative intensity of ionic emission in the visible range increases towards higher photon energies, which is attributed to O 1s shake-off photoionization. VUV photon?photoion coincidence spectra reveal major contributions from the C+ and O+ ions and a minor contribution from C2+. No conclusive changes in the intensity ratios among the different ions are observed above the O 1s threshold. The line shape of the VUV?O+ coincidence peak in the mass spectrum carries some information on the initial core excitatio