72 research outputs found

    The Chemical Evolution of the Milky Way

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    The field of chemical evolution modeling of the Galaxy is experiencing in the last years a phase of high activity and important achievements. There are, however, several open questions which still need to be answered. In this review I summarize what have been the most important achievements and what are some of the most urgent questions to be answered.Comment: 10 pages including 3 figs, to appear in "The Chemical Evolution of the Milky Way. Stars vs Clusters", Proceedings of the Sept.1999 Vulcano Workshop, F.Giovannelli and F.Matteucci eds (Kluwer, Dordrecht) in pres

    Autolysosomal Ī²-catenin degradation regulates Wnt-autophagy-p62 crosstalk

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    The Wnt/Ī²-catenin signalling and autophagy pathways each play important roles during development, adult tissue homeostasis and tumorigenesis. Here we identify the Wnt/Ī²-catenin signalling pathway as a negative regulator of both basal and stress-induced autophagy. Manipulation of Ī²-catenin expression levels in vitro and in vivo revealed that Ī²-catenin suppresses autophagosome formation and directly represses p62/SQSTM1 (encoding the autophagy adaptor p62) via TCF4. Furthermore, we show that during nutrient deprivation Ī²-catenin is selectively degraded via the formation of a Ī²-catenin-LC3 complex, attenuating Ī²-catenin/TCF-driven transcription and proliferation to favour adaptation during metabolic stress. Formation of the Ī²-catenin-LC3 complex is mediated by a W/YXXI/L motif and LC3-interacting region (LIR) in Ī²-catenin, which is required for interaction with LC3 and non-proteasomal degradation of Ī²-catenin. Thus, Wnt/Ī²-catenin represses autophagy and p62 expression, while Ī²-catenin is itself targeted for autophagic clearance in autolysosomes upon autophagy induction. These findings reveal a regulatory feedback mechanism that place Ī²-catenin at a key cellular integration point coordinating proliferation with autophagy, with implications for targeting these pathways for cancer therapy. Ā© 2013 European Molecular Biology Organization

    Ī²-catenin negatively regulates expression of the prostaglandin transporter PGT in the normal intestinal epithelium and colorectal tumour cells: A role in the chemopreventive efficacy of aspirin

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    Background: Levels of the pro-tumorigenic prostaglandin PGE 2 are increased in colorectal cancer, previously attributed to increased synthesis through COX-2 upregulation and, more recently, to decreased catabolism. The functionally linked genes 15-prostaglandin dehydrogenase (15-PGDH) and the prostaglandin transporter PGT co-operate in prostaglandin degradation and are downregulated in colorectal cancer. We previously reported repression of 15-PGDH expression by the Wnt/Ī²-catenin pathway, commonly deregulated during early colorectal neoplasia. Here we asked whether Ī²-catenin also regulates PGT expression. Methods: The effect of Ī²-catenin deletion in vivo was addressed by PGT immunostaining of Ī²-catenin/lox-villin-cre-ERT2 mouse tissue. The effect of siRNA-mediated Ī²-catenin knockdown and dnTCF4 induction in vitro was addressed by semi-quantitative and quantitative real-time RT-PCR and immunoblotting. Results: This study shows for the first time that deletion of Ī²-catenin in murine intestinal epithelium in vivo upregulates PGT protein, especially in the crypt epithelium. Furthermore, Ī²-catenin knockdown in vitro increases PGT expression in both colorectal adenoma-and carcinoma-derived cell lines, as does dnTCF4 induction in LS174T cells.Conclusions:These data suggest that Ī²-catenin employs a two-pronged approach to inhibiting prostaglandin turnover during colorectal neoplasia by repressing PGT expression in addition to 15-PGDH. Furthermore, our data highlight a potential mechanism that may contribute to the non-selective NSAID aspirins chemopreventive efficacy. Ā© 2012 Cancer Research UK All rights reserved

    Interacting Supernovae: Types IIn and Ibn

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    Supernovae (SNe) that show evidence of strong shock interaction between their ejecta and pre-existing, slower circumstellar material (CSM) constitute an interesting, diverse, and still poorly understood category of explosive transients. The chief reason that they are extremely interesting is because they tell us that in a subset of stellar deaths, the progenitor star may become wildly unstable in the years, decades, or centuries before explosion. This is something that has not been included in standard stellar evolution models, but may significantly change the end product and yield of that evolution, and complicates our attempts to map SNe to their progenitors. Another reason they are interesting is because CSM interaction is an efficient engine for making bright transients, allowing super-luminous transients to arise from normal SN explosion energies, and allowing transients of normal SN luminosities to arise from sub-energetic explosions or low radioactivity yield. CSM interaction shrouds the fast ejecta in bright shock emission, obscuring our normal view of the underlying explosion, and the radiation hydrodynamics of the interaction is challenging to model. The CSM interaction may also be highly non-spherical, perhaps linked to binary interaction in the progenitor system. In some cases, these complications make it difficult to definitively tell the difference between a core-collapse or thermonuclear explosion, or to discern between a non-terminal eruption, failed SN, or weak SN. Efforts to uncover the physical parameters of individual events and connections to possible progenitor stars make this a rapidly evolving topic that continues to challenge paradigms of stellar evolution.Comment: Final draft of a chapter in the "SN Handbook". Accepted. 25 pages, 3 fig

    Observational and Physical Classification of Supernovae

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    This chapter describes the current classification scheme of supernovae (SNe). This scheme has evolved over many decades and now includes numerous SN Types and sub-types. Many of these are universally recognized, while there are controversies regarding the definitions, membership and even the names of some sub-classes; we will try to review here the commonly-used nomenclature, noting the main variants when possible. SN Types are defined according to observational properties; mostly visible-light spectra near maximum light, as well as according to their photometric properties. However, a long-term goal of SN classification is to associate observationally-defined classes with specific physical explosive phenomena. We show here that this aspiration is now finally coming to fruition, and we establish the SN classification scheme upon direct observational evidence connecting SN groups with specific progenitor stars. Observationally, the broad class of Type II SNe contains objects showing strong spectroscopic signatures of hydrogen, while objects lacking such signatures are of Type I, which is further divided to numerous subclasses. Recently a class of super-luminous SNe (SLSNe, typically 10 times more luminous than standard events) has been identified, and it is discussed. We end this chapter by briefly describing a proposed alternative classification scheme that is inspired by the stellar classification system. This system presents our emerging physical understanding of SN explosions, while clearly separating robust observational properties from physical inferences that can be debated. This new system is quantitative, and naturally deals with events distributed along a continuum, rather than being strictly divided into discrete classes. Thus, it may be more suitable to the coming era where SN numbers will quickly expand from a few thousands to millions of events.Comment: Extended final draft of a chapter in the "SN Handbook". Comments most welcom

    Glutamine synthetase gene expression during the regeneration of the annelid Enchytraeus japonensis

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    Enchytraeus japonensis is a highly regenerative oligochaete annelid that can regenerate a complete individual from a small body fragment in 4ā€“5Ā days. In our previous study, we performed complementary deoxyribonucleic acid subtraction cloning to isolate genes that are upregulated during E. japonensis regeneration and identified glutamine synthetase (gs) as one of the most abundantly expressed genes during this process. In the present study, we show that the full-length sequence of E. japonensis glutamine synthetase (EjGS), which is the first reported annelid glutamine synthetase, is highly similar to other known class II glutamine synthetases. EjGS shows a 61ā€“71% overall amino acid sequence identity with its counterparts in various other animal species, including Drosophila and mouse. We performed detailed expression analysis by in situ hybridization and reveal that strong gs expression occurs in the blastemal regions of regenerating E. japonensis soon after amputation. gs expression was detectable at the cell layer covering the wound and was found to persist in the epidermal cells during the formation and elongation of the blastema. Furthermore, in the elongated blastema, gs expression was detectable also in the presumptive regions of the brain, ventral nerve cord, and stomodeum. In the fully formed intact head, gs expression was also evident in the prostomium, brain, the anterior end of the ventral nerve cord, the epithelium of buccal and pharyngeal cavities, the pharyngeal pad, and in the esophageal appendages. In intact E. japonensis tails, gs expression was found in the growth zone in actively growing worms but not in full-grown individuals. In the nonblastemal regions of regenerating fragments and in intact worms, gs expression was also detected in the nephridia, chloragocytes, gut epithelium, epidermis, spermatids, and oocytes. These results suggest that EjGS may play roles in regeneration, nerve function, cell proliferation, nitrogenous waste excretion, macromolecule synthesis, and gametogenesis

    Identification of several small main-effect QTLs and a large number of epistatic QTLs for drought tolerance related traits in groundnut (Arachishypogaea L.)

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    Cultivated groundnut or peanut (Arachis hypogaea L.), an allotetraploid (2nĀ =Ā 4xĀ =Ā 40), is a self pollinated and widely grown crop in the semi-arid regions of the world. Improvement of drought tolerance is an important area of research for groundnut breeding programmes. Therefore, for the identification of candidate QTLs for drought tolerance, a comprehensive and refined genetic map containing 191 SSR loci based on a single mapping population (TAG 24Ā Ć—Ā ICGV 86031), segregating for drought and surrogate traits was developed. Genotyping data and phenotyping data collected for more than ten drought related traits in 2ā€“3 seasons were analyzed in detail for identification of main effect QTLs (M-QTLs) and epistatic QTLs (E-QTLs) using QTL Cartographer, QTLNetwork and Genotype Matrix Mapping (GMM) programmes. A total of 105 M-QTLs with 3.48ā€“33.36% phenotypic variation explained (PVE) were identified using QTL Cartographer, while only 65 M-QTLs with 1.3ā€“15.01% PVE were identified using QTLNetwork. A total of 53 M-QTLs were such which were identified using both programmes. On the other hand, GMM identified 186 (8.54ā€“44.72% PVE) and 63 (7.11ā€“21.13% PVE), three and two loci interactions, whereas only 8 E-QTL interactions with 1.7ā€“8.34% PVE were identified through QTLNetwork. Interestingly a number of co-localized QTLs controlling 2ā€“9 traits were also identified. The identification of few major, many minor M-QTLs and QTLĀ Ć—Ā QTL interactions during the present study confirmed the complex and quantitative nature of drought tolerance in groundnut. This study suggests deployment of modern approaches like marker-assisted recurrent selection or genomic selection instead of marker-assisted backcrossing approach for breeding for drought tolerance in groundnut

    The Explosion Mechanism of Core-Collapse Supernovae and Its Observational Signatures

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    The death of massive stars is shrouded in many mysteries. One of them is the mechanism that overturns the collapse of the degenerate iron core into an explosion, a process that determines the supernova explosion energy, properties of the surviving compact remnant, and the nucleosynthetic yields. The number of core-collapse supernova observations has been growing with an accelerating pace thanks to modern time-domain astronomical surveys and new tests of the explosion mechanism are becoming possible. We review predictions of parameterized supernova explosion models and compare them with explosion properties inferred from observed light curves, spectra, and neutron star masses.Comment: Reviews in Frontiers of Modern Astrophysics; From Space Debris to Cosmology, edited by Kab\'ath, Petr; Jones, David; Skarka, Marek. ISBN: 978-3-030-38509-5. Cham: Springer International Publishing, 2020, pp. 189-21

    Regional differences in prostaglandin Eā‚‚ metabolism in human colorectal cancer liver metastases

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    Background: Prostaglandin (PG) Eā‚‚ plays a critical role in colorectal cancer (CRC) progression, including epithelial-mesenchymal transition (EMT). Activity of the rate-limiting enzyme for PGEā‚‚ catabolism (15-hydroxyprostaglandin dehydrogenase [15-PGDH]) is dependent on availability of NAD+. We tested the hypothesis that there is intra-tumoral variability in PGEā‚‚ content, as well as in levels and activity of 15-PGDH, in human CRC liver metastases (CRCLM). To understand possible underlying mechanisms, we investigated the relationship between hypoxia, 15-PGDH and PGEā‚‚ in human CRC cells in vitro. Methods: Tissue from the periphery and centre of 20 human CRCLM was analysed for PGEā‚‚ levels, 15-PGDH and cyclooxygenase (COX)-2 expression, 15-PGDH activity, and NAD+/NADH levels. EMT of LIM1863 human CRC cells was induced by transforming growth factor (TGF) Ī². Results: PGEā‚‚ levels were significantly higher in the centre of CRCLM compared with peripheral tissue (P = 0.04). There were increased levels of 15-PGDH protein in the centre of CRCLM associated with reduced 15-PGDH activity and low NAD+/NADH levels. There was no significant heterogeneity in COX-2 protein expression. NAD+ availability controlled 15-PGDH activity in human CRC cells in vitro. Hypoxia induced 15-PGDH expression in human CRC cells and promoted EMT, in a similar manner to PGEā‚‚. Combined 15-PGDH expression and loss of membranous E-cadherin (EMT biomarker) were present in the centre of human CRCLM in vivo.Conclusions: There is significant intra-tumoral heterogeneity in PGEā‚‚ content, 15-PGDH activity and NAD+ availability in human CRCLM. Tumour micro-environment (including hypoxia)-driven differences in PGEā‚‚ metabolism should be targeted for novel treatment of advanced CRC
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