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81.
Lorenz H. Lehmann Barbara C. Worst David A. Stanmore Johannes Backs 《Cellular and molecular life sciences : CMLS》2014,71(9):1673-1690
Cardiovascular disease (CVD) represents a major challenge for health care systems, both in terms of the high mortality associated with it and the huge economic burden of its treatment. Although CVD represents a diverse range of disorders, they share common compensatory changes in the heart at the structural, cellular, and molecular level that, in the long term, can become maladaptive and lead to heart failure. Treatment of adverse cardiac remodeling is therefore an important step in preventing this fatal progression. Although previous efforts have been primarily focused on inhibition of deleterious signaling cascades, the stimulation of endogenous cardioprotective mechanisms offers a potent therapeutic tool. In this review, we discuss class I and class II histone deacetylases, a subset of chromatin-modifying enzymes known to have critical roles in the regulation of cardiac remodeling. In particular, we discuss their molecular modes of action and go on to consider how their inhibition or the stimulation of their intrinsic cardioprotective properties may provide a potential therapeutic route for the clinical treatment of CVD. 相似文献
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Yvonne G. J. van Helden Sandra G. Heil Frederik J. van Schooten Evelien Kramer Susanne Hessel Jaume Amengual Joan Ribot Katja Teerds Adrian Wyss Georg Lietz M. Luisa Bonet Johannes von Lintig Roger W. L. Godschalk Jaap Keijer 《Cellular and molecular life sciences : CMLS》2010,67(12):2039-2056
Beta-carotene 15,15′-monooxygenase 1 knockout (Bcmo1 ?/?) mice accumulate beta-carotene (BC) similarly to humans, whereas wild-type (Bcmo1 +/+) mice efficiently cleave BC. Bcmo1 ?/? mice are therefore suitable to investigate BC-induced alterations in gene expression in lung, assessed by microarray analysis. Bcmo1 ?/? mice receiving control diet had increased expression of inflammatory genes as compared to BC-supplemented Bcmo1 ?/? mice and Bcmo1 +/+ mice that received either control or BC-supplemented diets. Differential gene expression in Bcmo1 ?/? mice was confirmed by real-time quantitative PCR. Histochemical analysis indeed showed an increase in inflammatory cells in lungs of control Bcmo1 ?/? mice. Supported by metabolite and gene-expression data, we hypothesize that the increased inflammatory response is due to an altered BC metabolism, resulting in an increased vitamin A requirement in Bcmo1 ?/? mice. This suggests that effects of BC may depend on inter-individual variations in BC-metabolizing enzymes, such as the frequently occurring human polymorphisms in BCMO1. 相似文献
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Marina Dunaeva Johannes Waltenberger 《Cellular and molecular life sciences : CMLS》2017,74(19):3481-3490
Myocardial infarction (MI) is caused by the occlusion of a coronary artery due to underlying atherosclerosis complicated by localized thrombosis. The blockage of blood flow leads to cardiomyocyte (CM) death in the infarcted area. Adult mammalian cardiomyocytes have little capacity to proliferate in response to injury; however, some pathways active during embryogenesis and silent during adult life are recruited in response to tissue injury. One such example is hedgehog (Hh) signaling. Hh is involved in the embryonic development of the heart and coronary vascular system. Pathological conditions including ischemia activate Hh signaling in adult tissues. This review highlights the involvement of Hh signaling in ischemic tissue regeneration with a particular emphasis on heart regeneration and discusses its potential role as a therapeutic agent. 相似文献
84.
Plant degradation: a nematode expansin acting on plants 总被引:3,自引:0,他引:3
Qin L Kudla U Roze EH Goverse A Popeijus H Nieuwland J Overmars H Jones JT Schots A Smant G Bakker J Helder J 《Nature》2004,427(6969):30
Expansin proteins, which have so far been identified only in plants, rapidly induce extension of plant cell walls by weakening the non-covalent interactions that help to maintain their integrity. Here we show that an animal, the plant-parasitic roundworm Globodera rostochiensis, can also produce a functional expansin, which it uses to loosen cell walls when invading its host plant. As this nematode is known to be able to disrupt covalent bonds in plant cell walls, its accompanying ability to loosen non-covalent bonds challenges the prevailing view that animals are genetically poorly equipped to degrade plant cell walls. 相似文献
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de Lucas M Davière JM Rodríguez-Falcón M Pontin M Iglesias-Pedraz JM Lorrain S Fankhauser C Blázquez MA Titarenko E Prat S 《Nature》2008,451(7177):480-484
88.
Krause J Orlando L Serre D Viola B Prüfer K Richards MP Hublin JJ Hänni C Derevianko AP Pääbo S 《Nature》2007,449(7164):902-904
Morphological traits typical of Neanderthals began to appear in European hominids at least 400,000 years ago and about 150,000 years ago in western Asia. After their initial appearance, such traits increased in frequency and the extent to which they are expressed until they disappeared shortly after 30,000 years ago. However, because most fossil hominid remains are fragmentary, it can be difficult or impossible to determine unambiguously whether a fossil is of Neanderthal origin. This limits the ability to determine when and where Neanderthals lived. To determine how far to the east Neanderthals ranged, we determined mitochondrial DNA (mtDNA) sequences from hominid remains found in Uzbekistan and in the Altai region of southern Siberia. Here we show that the DNA sequences from these fossils fall within the European Neanderthal mtDNA variation. Thus, the geographic range of Neanderthals is likely to have extended at least 2,000 km further to the east than commonly assumed. 相似文献
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Johannes Lenhard 《Foundations of Science》2013,18(3):583-586
In this commentary to Napoletani et al. (Foundations of Science 16:1–20, 2011), we put agnostic science in a wider historical context of philosophy of mathematics. Secondly, the parallel to Tukey’s “exploratory data analysis” will be discussed. Thirdly, it will be argued that what is new is the mutually interdependent dynamics of data (on which Napoletani et al. focus) and of computational modeling—which puts science closer to engineering and vice versa. 相似文献