Acid ceramidase controls apoptosis and increases autophagy in human melanoma cells treated with doxorubicin

Acid ceramidase (AC) is a lysosomal hydrolase encoded by the ASAH1 gene, which cleaves ceramides into sphingosine and fatty acid. AC is expressed at high levels in most human melanoma cell lines and may confer resistance against chemotherapeutic agents. One such agent, doxorubicin, was shown to increase ceramide levels in melanoma cells. Ceramides contribute to the regulation of autophagy and apoptosis. Here we investigated the impact of AC ablation via CRISPR-Cas9 gene editing on the response of A375 melanoma cells to doxorubicin. We found that doxorubicin activates the autophagic response in wild-type A375 cells, which effectively resist apoptotic cell death. In striking contrast, doxorubicin fails to stimulate autophagy in A375 AC-null cells, which rapidly undergo apoptosis when exposed to the drug. The present work highlights changes that affect melanoma cells during incubation with doxorubicin, in A375 melanoma cells lacking AC. We found that the remarkable reduction in recovery rate after doxorubicin treatment is strictly associated with the impairment of autophagy, that forces the AC-inhibited cells into apoptotic path

Crop changes from the XVI century to the present in a hill/mountain area of eastern Liguria (Italy)

<p>Abstract</p> <p>Background</p> <p>Chronological information on the composition and structure of agrocenoses and detailed features of land cover referring to specific areas are uncommon in ethnobotanical studies, especially for periods before the XIX century. The aim of this study was to analyse the type of crop or the characteristics of soil cover from the XVI century to the present.</p> <p>Methods</p> <p>This diachronic analysis was accomplished through archival research on the inventories of the Parish of St. Mary and those of the Municipality of Pignone and from recent surveys conducted in an area of eastern Liguria (Italy).</p> <p>Results</p> <p>Archival data revealed that in study area the primary means of subsistence during the last five centuries, until the first half of the XX century, was chestnuts. In the XVIII and XIX centuries, crop diversification strongly increased in comparison with previous and subsequent periods. In more recent times, the abandonment of agricultural practices has favoured the re-colonisation of mixed woodland or cluster-pine woodland.</p> <p>Conclusion</p> <p>Ancient documents in the ecclesiastic or municipal inventories can be a very useful tool for enhancing the knowledge of agricultural practice, as well as of subsistence methods favoured by local populations during a particular time and for reconstructing land use change over time.</p

Simulation And Forecasting In

The goal of this paper is to present the first results in the development of a methodology to integrate simulation, forecasting and planning to support day by day and long term decisions for operators working in intermodal container terminals

Error Recovery in Systems of Communicating Processes

This paper deals with some of the relevant problems concerning the backward recovery of autonomous processes. The tools for the description of the past history of the system are formally defined, and an implementation is outlined. 1 Introduction The term &quot;error recovery&quot; is used for the activity which restores to a consistent state a system which is an inconsistent one. Thus, the notion of consistent state is essential to the definition of the methods and purposes of the error recovery. In this introduction we shall give an interpretation of the term &quot;consistency&quot; which should explain its use in different fields of computer science. The attribute of consistency is applied to the information stored in a system (the state of the system), and is strictly bound to the way in which this information is used (according with an algorithm or protocol to produce the expected behavior of the system (described in its specifications): we give the following informal description of consistent state..

Interaction ondes/interfaces en contexte sismique

Many major challenges of the twenty- first century in the economic, social, or environmental fields, require a careful characterization of the geological structures of the Earth. Seismics is probably the most widely used technique to explore the environment at large scales. Imaging and characterizing the subsurface from real seismic data however is a di fficult task, and the di fficulty increases since the wave propagation in complex and heterogeneous natural systems is poorly understood. It is therefore essential to identify the geological features, which signi ficantly in fluence the wave propagation in a given confi guration, and to understand their interaction with the seismic waves. To model the wave characteristics one has to account for the complexity of natural environments through which the waves propagate, but also for the contact laws between the geological media, and for the limitations introduced by the seismic waves themselves. This manuscript summarizes the work I have developed essentially on the understanding and on the modeling of the wave/interface interaction using multidisciplinary approaches. Besides basic knowledge of the physical mechanisms underlying the wave propagation in complex media (e.g., the vertical and the lateral seismic resolutions, the de finition of the 3D seismic refl ector, the interface scattering, and the in fluence of the anisotropy on surface waves), applied works dedicated to the oil and gas exploration or to the monitoring of geological storage of CO2 have also been developed.Certains besoins économiques, sociétaux ou environnementaux nécessitent une caractérisation approfondie des structures géologiques du sous-sol. Parmi les différentes méthodes géophysiques, la sismique est sans doute celle qui est le plus souvent privilégiée. Imager et caractériser le sous-sol à partir de données réelles acquises sur le terrain est cependant un problème inverse généralement di fficile à résoudre. Il l'est d'autant plus si le problème direct associé n'a pas été au préalable "maîtrisé" a minima, c'est-à-dire si l'on ne dispose pas d'une modélisation réaliste de la propagation des ondes. Pour cela, il semble essentiel, pour modéliser les données sismiques synthétiques a fin de les rendre comparables aux données réelles, d'identi fier et de comprendre en premier lieu les facteurs géologiques et/ou physiques de premier ordre qui in fluencent la propagation des ondes dans une con figuration donnée. Cela suppose qu'on prenne en compte à la fois les lois de comportement des couches géologiques traversées et les lois de contact entre ces couches, mais aussi les limitations introduites par le système d'observation constitué par les ondes sismiques. Ce mémoire décrit les travaux que j'ai menés essentiellement sur la compréhension et la modélisation de l'interaction ondes/interfaces en me basant sur des approches pluridisciplinaires. Outre l'aspect fondamental d'une meilleure connaissance des mécanismes physiques sous-jacents à la propagation des ondes dans des milieux complexes (e.g., les résolutions sismiques verticale et latérale, la dé finition du ré flecteur sismique 3D, la diffusion d'interface et l'in fluence de l'anisotropie sur les ondes de surface), des aspects plus appliqués, dédiés notamment à l'exploration de gisements énergétiques ou à la surveillance de réservoirs géologiques de stockage du CO2, ont été également développés

Analysis of the vertical distribution in a model of phytoplankton dynamics

Phytoplankton often faces the dilemma of living in contrasting gradients of two essential resources: the light that comes from above and nutrients that are often supplied from below. In poorly mixed water columns, algae can be heterogeneously distributed, with thin layers of biomass found on the surface, in depth, or on the sediment surface. Here, we show that these patterns can result from intraspecific competition between light and nutrients. First, we present numerical solutions of a reaction-diffusion-taxis model for phytoplankton, nutrients and light. We argue that motile phytoplankton can form a thin layer under poorly mixed conditions. The numerical solution of this model indicates the depth at which phytoplankton is equally limited by both resources. The layer becomes shallower with an increase in the nutrient supply and deeper with an increase in the light supply. These general patterns are in agreement with field observations. Thus, this model can explain many patterns of algal distribution found in poorly mixed aquatic ecosystems

A low-cost simple test for weekly detection of Mycoplasma hyorhinis and arginini contaminations in cell cultures and viral preparations

Mollicutes (Mycoplasma and Acholeplasma) are parasitic bacteria that adhere to cellular surfaces, naturally resistant to many antibiotics and extremely small. They are often found as contaminants in cultured cells, where they go unnoticed. They may be present in viral stocks because they are present in supernatants of cells where cultured viruses are released. The best way to keep laboratories free of Mycoplasma is to discard infected cultures, but, as judged by the very common finding of Mycoplasma-contaminated cultures in many laboratories, this is not done as often as it should be. A possible reason is that most procedures recommended take as long as performing a simple experiment and many laboratories delay testing to save money and time. Indeed, many methods exist to detect Mycoplasma infection of cell lines, but they take at least a couple of hours of hands-on work, if not more. Here we describe a procedure to screen viral stocks and tissue cultures for Mycoplasma presence. It relies on isolation of Mycoplasma on ordinary horse blood agar directly from exhausted tissue culture supernatants and does not require experienced personnel or expensive equipment. It only requires minutes of hands-on work, and, for this, it may be useful for weekly screening of cultures. It yields semiquantitative results in roughly 5 days, which is the time that usually passes between one subculture passage of cells in vitro to another. Because of its simplicity, it may be useful for detecting Mycoplasma in viral stocks and for frequent screening of cultures in research laboratories