排序方式: 共有41条查询结果,搜索用时 31 毫秒
11.
Pepys MB Hirschfield GM Tennent GA Gallimore JR Kahan MC Bellotti V Hawkins PN Myers RM Smith MD Polara A Cobb AJ Ley SV Aquilina JA Robinson CV Sharif I Gray GA Sabin CA Jenvey MC Kolstoe SE Thompson D Wood SP 《Nature》2006,440(7088):1217-1221
Complement-mediated inflammation exacerbates the tissue injury of ischaemic necrosis in heart attacks and strokes, the most common causes of death in developed countries. Large infarct size increases immediate morbidity and mortality and, in survivors of the acute event, larger non-functional scars adversely affect long-term prognosis. There is thus an important unmet medical need for new cardioprotective and neuroprotective treatments. We have previously shown that human C-reactive protein (CRP), the classical acute-phase protein that binds to ligands exposed in damaged tissue and then activates complement, increases myocardial and cerebral infarct size in rats subjected to coronary or cerebral artery ligation, respectively. Rat CRP does not activate rat complement, whereas human CRP activates both rat and human complement. Administration of human CRP to rats is thus an excellent model for the actions of endogenous human CRP. Here we report the design, synthesis and efficacy of 1,6-bis(phosphocholine)-hexane as a specific small-molecule inhibitor of CRP. Five molecules of this palindromic compound are bound by two pentameric CRP molecules, crosslinking and occluding the ligand-binding B-face of CRP and blocking its functions. Administration of 1,6-bis(phosphocholine)-hexane to rats undergoing acute myocardial infarction abrogated the increase in infarct size and cardiac dysfunction produced by injection of human CRP. Therapeutic inhibition of CRP is thus a promising new approach to cardioprotection in acute myocardial infarction, and may also provide neuroprotection in stroke. Potential wider applications include other inflammatory, infective and tissue-damaging conditions characterized by increased CRP production, in which binding of CRP to exposed ligands in damaged cells may lead to complement-mediated exacerbation of tissue injury. 相似文献
12.
Laccases: a never-ending story 总被引:3,自引:0,他引:3
Paola Giardina Vincenza Faraco Cinzia Pezzella Alessandra Piscitelli Sophie Vanhulle Giovanni Sannia 《Cellular and molecular life sciences : CMLS》2010,67(3):369-385
Laccases (benzenediol:oxygen oxidoreductases, EC 1.10.3.2) are blue multicopper oxidases that catalyze the oxidation of an
array of aromatic substrates concomitantly with the reduction of molecular oxygen to water. In fungi, laccases carry out a
variety of physiological roles during their life cycle. These enzymes are being increasingly evaluated for a variety of biotechnological
applications due to their broad substrate range. In this review, the most recent studies on laccase structural features and
catalytic mechanisms along with analyses of their expression are reported and examined with the aim of contributing to the
discussion on their structure–function relationships. Attention has also been paid to the properties of enzymes endowed with
unique characteristics and to fungal laccase multigene families and their organization. 相似文献
13.
Carninci P Sandelin A Lenhard B Katayama S Shimokawa K Ponjavic J Semple CA Taylor MS Engström PG Frith MC Forrest AR Alkema WB Tan SL Plessy C Kodzius R Ravasi T Kasukawa T Fukuda S Kanamori-Katayama M Kitazume Y Kawaji H Kai C Nakamura M Konno H Nakano K Mottagui-Tabar S Arner P Chesi A Gustincich S Persichetti F Suzuki H Grimmond SM Wells CA Orlando V Wahlestedt C Liu ET Harbers M Kawai J Bajic VB Hume DA Hayashizaki Y 《Nature genetics》2006,38(6):626-635
14.
Neutrophils and macrophages are phagocytic cells that cooperate during inflammation and tissue repair. Neutrophils undergo
apoptosis and are engulfed by macrophages. Engulfment modulates macrophage activation and microbicidal activity. Infection
by Leishmania takes place in the context of tissue repair. This article discusses cellular and molecular mechanisms involved in the intimate
cooperation of neutrophils and macrophages in Leishmania infection. 相似文献
15.
Pluchino S Zanotti L Rossi B Brambilla E Ottoboni L Salani G Martinello M Cattalini A Bergami A Furlan R Comi G Constantin G Martino G 《Nature》2005,436(7048):266-271
In degenerative disorders of the central nervous system (CNS), transplantation of neural multipotent (stem) precursor cells (NPCs) is aimed at replacing damaged neural cells. Here we show that in CNS inflammation, NPCs are able to promote neuroprotection by maintaining undifferentiated features and exerting unexpected immune-like functions. In a mouse model of chronic CNS inflammation, systemically injected adult syngeneic NPCs use constitutively activated integrins and functional chemokine receptors to selectively enter the inflamed CNS. These undifferentiated cells survive repeated episodes of CNS inflammation by accumulating within perivascular areas where reactive astrocytes, inflamed endothelial cells and encephalitogenic T cells produce neurogenic and gliogenic regulators. In perivascular CNS areas, surviving adult NPCs induce apoptosis of blood-borne CNS-infiltrating encephalitogenic T cells, thus protecting against chronic neural tissue loss as well as disease-related disability. These results indicate that undifferentiated adult NPCs have relevant therapeutic potential in chronic inflammatory CNS disorders because they display immune-like functions that promote long-lasting neuroprotection. 相似文献
16.
Somatic coding mutations in human induced pluripotent stem cells 总被引:2,自引:0,他引:2
17.
Bowler C Allen AE Badger JH Grimwood J Jabbari K Kuo A Maheswari U Martens C Maumus F Otillar RP Rayko E Salamov A Vandepoele K Beszteri B Gruber A Heijde M Katinka M Mock T Valentin K Verret F Berges JA Brownlee C Cadoret JP Chiovitti A Choi CJ Coesel S De Martino A Detter JC Durkin C Falciatore A Fournet J Haruta M Huysman MJ Jenkins BD Jiroutova K Jorgensen RE Joubert Y Kaplan A Kröger N Kroth PG La Roche J Lindquist E Lommer M Martin-Jézéquel V Lopez PJ Lucas S Mangogna M McGinnis K 《Nature》2008,456(7219):239-244
Diatoms are photosynthetic secondary endosymbionts found throughout marine and freshwater environments, and are believed to be responsible for around one-fifth of the primary productivity on Earth. The genome sequence of the marine centric diatom Thalassiosira pseudonana was recently reported, revealing a wealth of information about diatom biology. Here we report the complete genome sequence of the pennate diatom Phaeodactylum tricornutum and compare it with that of T. pseudonana to clarify evolutionary origins, functional significance and ubiquity of these features throughout diatoms. In spite of the fact that the pennate and centric lineages have only been diverging for 90 million years, their genome structures are dramatically different and a substantial fraction of genes ( approximately 40%) are not shared by these representatives of the two lineages. Analysis of molecular divergence compared with yeasts and metazoans reveals rapid rates of gene diversification in diatoms. Contributing factors include selective gene family expansions, differential losses and gains of genes and introns, and differential mobilization of transposable elements. Most significantly, we document the presence of hundreds of genes from bacteria. More than 300 of these gene transfers are found in both diatoms, attesting to their ancient origins, and many are likely to provide novel possibilities for metabolite management and for perception of environmental signals. These findings go a long way towards explaining the incredible diversity and success of the diatoms in contemporary oceans. 相似文献
18.
Sara Proietti Alessandra Cucina Mirko Minini Mariano Bizzarri 《Cellular and molecular life sciences : CMLS》2017,74(21):4015-4025
The long-recognized fact that oxidative stress within mitochondria is a hallmark of mitochondrial dysfunction has stimulated the development of mitochondria-targeted antioxidant therapies. Melatonin should be included among the pharmacological agents able to modulate mitochondrial functions in cancer, given that a number of relevant melatonin-dependent effects are triggered by targeting mitochondrial functions. Indeed, melatonin may modulate the mitochondrial respiratory chain, thus antagonizing the cancer highly glycolytic bioenergetic pathway of cancer cells. Modulation of the mitochondrial respiratory chain, together with Ca2+ release and mitochondrial apoptotic effectors, may enhance the spontaneous or drug-induced apoptotic processes. Given that melatonin may efficiently counteract the Warburg effect while stimulating mitochondrial differentiation and mitochondrial-based apoptosis, it is argued that the pineal neurohormone could represent a promising new perspective in cancer treatment strategy. 相似文献
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20.
Drossart P Piccioni G Gérard JC Lopez-Valverde MA Sanchez-Lavega A Zasova L Hueso R Taylor FW Bézard B Adriani A Angrilli F Arnold G Baines KH Bellucci G Benkhoff J Bibring JP Blanco A Blecka MI Carlson RW Coradini A Di Lellis A Encrenaz T Erard S Fonti S Formisano V Fouchet T Garcia R Haus R Helbert J Ignatiev NI Irwin P Langevin Y Lebonnois S Luz D Marinangeli L Orofino V Rodin AV Roos-Serote MC Saggin B Stam DM Titov D Visconti G Zambelli M Tsang C;VIRTIS-Venus Express Technical Team 《Nature》2007,450(7170):641-645
The upper atmosphere of a planet is a transition region in which energy is transferred between the deeper atmosphere and outer space. Molecular emissions from the upper atmosphere (90-120 km altitude) of Venus can be used to investigate the energetics and to trace the circulation of this hitherto little-studied region. Previous spacecraft and ground-based observations of infrared emission from CO2, O2 and NO have established that photochemical and dynamic activity controls the structure of the upper atmosphere of Venus. These data, however, have left unresolved the precise altitude of the emission owing to a lack of data and of an adequate observing geometry. Here we report measurements of day-side CO2 non-local thermodynamic equilibrium emission at 4.3 microm, extending from 90 to 120 km altitude, and of night-side O2 emission extending from 95 to 100 km. The CO2 emission peak occurs at approximately 115 km and varies with solar zenith angle over a range of approximately 10 km. This confirms previous modelling, and permits the beginning of a systematic study of the variability of the emission. The O2 peak emission happens at 96 km +/- 1 km, which is consistent with three-body recombination of oxygen atoms transported from the day side by a global thermospheric sub-solar to anti-solar circulation, as previously predicted. 相似文献