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1.
Rodrigo de Balbín Behrmann J.Javier Alcolea GonzálezM. Ángel González Pereda A. Moure Romanillo 《L'Anthropologie》2002,106(4):565
During the year 2002 we have continued the works in the massive of Ardines at Ribadesella, Asturias, and especially in its fundamental cave, Tito Bustillo. Here the prospection has permitted us to find several new elements of great cultural and graphic value. A consistent deposit in four cutted contours in the form of head of hind and also two new galleries, called gallery of the Bisons and gallery of the Anthropomorphes, communicated with the Principal Gallery of the cave and mutually. In this last one exist remains of adaptation of the space, bony remains that we are yet digging and two figures of painted anthropomorphes with an exceptional interest. Finally, in the ensemble N XI, place where it is found the habitation deposit, and where we have found large masses of red colourings prepared for its use, exists a small final cave, where also it has been painted in its interior, and where the mouth is opened among the remains of a great deposit in surface that occupies all its northern part. 相似文献
2.
The first X-ray structures of an intein-DNA complex, that of the two-domain homing endonuclease PI-SceI bound to its 36-base pair DNA substrate, have been determined in the presence and absence of Ca(2+). The DNA shows an asymmetric bending pattern, with a major 50 degree bend in the endonuclease domain and a minor 22 degree bend in the splicing domain region. Distortions of the DNA bound to the endonuclease domain cause the insertion of the two cleavage sites in the catalytic center. DNA binding induces changes in the protein conformation. The two overlapping non-identical active sites in the endonucleolytic center contain two Ca(+2) ions that coordinate to the catalytic Asp residues. Structure analysis indicates that the top strand may be cleaved first. 相似文献
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4.
Crystal structures of I-SceI complexed to nicked DNA substrates: snapshots of intermediates along the DNA cleavage reaction pathway 总被引:2,自引:0,他引:2
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I-SceI is a homing endonuclease that specifically cleaves an 18-bp double-stranded DNA. I-SceI exhibits a strong preference for cleaving the bottom strand DNA. The published structure of I-SceI bound to an uncleaved DNA substrate provided a mechanism for bottom strand cleavage but not for top strand cleavage. To more fully elucidate the I-SceI catalytic mechanism, we determined the X-ray structures of I-SceI in complex with DNA substrates that are nicked in either the top or bottom strands. The structures resemble intermediates along the DNA cleavage reaction. In a structure containing a nick in the top strand, the spatial arrangement of metal ions is similar to that observed in the structure that contains uncleaved DNA, suggesting that cleavage of the bottom strand occurs by a common mechanism regardless of whether this strand is cleaved first or second. In the structure containing a nick in the bottom strand, a new metal binding site is present in the active site that cleaves the top strand. This new metal and a candidate nucleophilic water molecule are correctly positioned to cleave the top strand following bottom strand cleavage, providing a plausible mechanism for top strand cleavage. 相似文献
5.
Aging is associated with increased FGF21 levels but unaltered FGF21 responsiveness in adipose tissue
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Alejando Delgado‐Anglés Montserrat Cairó Ricardo Moure Ma Gracia Mateo Joan C. Domingo Pere Domingo Marta Giralt Francesc Villarroya 《Aging cell》2018,17(5)
Fibroblast growth factor 21 (FGF21) has been proposed to be an antiaging hormone on the basis of experimental studies in rodent models. However, circulating FGF21 levels are increased with aging in rodents and humans. Moreover, despite the metabolic health‐promoting effects of FGF21, the levels of this hormone are increased under conditions such as obesity and diabetes, an apparent incongruity that has been attributed to altered tissue responsiveness to FGF21. Here, we investigated serum FGF21 levels and expression of genes encoding components of the FGF21‐response molecular machinery in adipose tissue from healthy elderly individuals (≥70 years old) and young controls. Serum FGF21 levels were increased in elderly individuals and were positively correlated with insulinemia and HOMA‐IR, indices of mildly deteriorated glucose homeostasis. Levels of β‐Klotho, the coreceptor required for cellular responsiveness to FGF21, were increased in subcutaneous adipose tissue from elderly individuals relative to those from young controls, whereas FGF receptor‐1 levels were unaltered. Moreover, total ERK1/2 protein levels were decreased in elderly individuals in association with an increase in the ERK1/2 phosphorylation ratio relative to young controls. Adipose explants from aged and young mice respond similarly to FGF21 “ex vivo”. Thus, in contrast to what is observed in obesity and diabetes, high levels of FGF21 in healthy aging are not associated with repressed FGF21‐responsiveness machinery in adipose tissue. The lack of evidence for impaired FGF21 responsiveness in adipose tissue establishes a distinction between alterations in the FGF21 endocrine system in aging and chronic metabolic pathologies. 相似文献
6.
Amoeboid cells exhibit a highly dynamic motion that can be directed by external chemical signals, through the process of chemotaxis. Here, we propose a three-dimensional model for chemotactic motion of amoeboid cells. We account for the interactions between the extracellular substances, the membrane-bound proteins, and the cytosolic components involved in the signaling pathway that originates cell motility. We show two- and three-dimensional simulations of cell migration on planar substrates, flat surfaces with obstacles, and fibrous networks. The results show that our model reproduces the main features of chemotactic amoeboid motion. Our simulations unveil a complicated interplay between the geometry of the cell’s environment and the chemoattractant dynamics that tightly regulates cell motion. The model opens new opportunities to simulate the interactions between extra- and intra-cellular compounds mediated by the matrix geometry. 相似文献
7.
Alejandra Moure Mar Orzáez Mónica Sancho Angel Messeguer 《Bioorganic & medicinal chemistry letters》2012,22(23):7097-7099
Apoptosis is the process of programmed cell death and plays a fundamental role in several human diseases. We have previously reported the synthesis of the perhydro-1,4-diazepine-2,5-dione and 1,4-piperazine-2,5-dione derivatives as racemic mixtures. Compounds 1 and 2 showed a potent in vitro and in cellular extracts antiapoptotic activity. In view that the chiral discrimination has been an issue in the development and use of pharmaceutical drugs, the present contribution reports the synthesis of enantiopure peptidomimetics 1 and 2. The biological evaluation of these enantiomers as apoptosis inhibitors is also reported. 相似文献
8.
A chemical inhibitor of Apaf-1 exerts mitochondrioprotective functions and interferes with the intra-S-phase DNA damage checkpoint 总被引:1,自引:0,他引:1
Laura Mondragón Lorenzo Galluzzi Shahul Mouhamad Mar Orzáez José-Miguel Vicencio Ilio Vitale Alejandra Moure Angel Messeguer Enrique Perez-Paya Guido Kroemer 《Apoptosis : an international journal on programmed cell death》2009,14(2):182-190
QM31 represents a new class of cytoprotective agents that inhibit the formation of the apoptosome, the caspase activation
complex composed by Apaf-1, cytochrome c, dATP and caspase-9. Here, we analyzed the cellular effects of QM31, as compared to the prototypic caspase inhibitor Z-VAD-fmk.
QM31 was as efficient as Z-VAD-fmk in suppressing caspase-3 activation, and conferred a similar cytoprotective effect. In
contrast to Z-VAD-fmk, QM31 inhibited the release of cytochrome c from mitochondria, an unforeseen property that may contribute to its pronounced cytoprotective activity. Moreover, QM31 suppressed
the Apaf-1-dependent intra-S-phase DNA damage checkpoint. These results suggest that QM31 can interfere with the two known
functions of Apaf-1, namely apoptosome assembly/activation and intra-S-phase cell cycle arrest. Moreover, QM31 can inhibit
mitochondrial outer membrane permeabilization, an effect that is independent from its action on Apaf-1. 相似文献
9.
Involvement of rabphilin-3A-like (RPH3AL), or Noc2, the potential effector of Ras-associated binding proteins Rab3A and Rab27A in the regulation of exocytotic processes in the endocrine pancreas has been demonstrated in experimental models. Noc2 expression together with other regulatory molecules of the exocytotic machinery in human tissues, however, has not been studied. We evaluated immunohistochemical expression of the key molecules of the exocytotic machinery, Noc2, Rab3A, Rab27A, and RIM2, together with the characteristic islet cell hormones, insulin and glucagon in normal and endocrine tumor tissues of human pancreas. Normal pancreatic islets were stained for all of these proteins and showed strong cytoplasmic localization. A similar pattern of strong cytoplasmic expression of these proteins was observed in the majority of endocrine tumors. By contrast, the exocrine portions of normal appearing pancreas completely lacked Rab27A staining and showed decreased expression of the proteins, Noc2, Rab3A, and RIM2. The staining pattern of Noc2 and Rab27A was similar to the staining pattern of glucagon-producing cells within the islets. The concomitant expression of Noc2 with these molecules suggests that Noc2 may serve as an effector for Rab3A and Rab27A and that it is involved in the regulation of exocytosis of the endocrine pancreas in humans. 相似文献
10.
Molecular phylogeny of Neotropical bioluminescent beetles (Coleoptera: Elateroidea) in southern and central Brazil
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Bioluminescence in beetles is found mainly in the Elateroidea superfamily (Elateridae, Lampyridae and Phengodidae). The Neotropical region accounts for the richest diversity of bioluminescent species in the world with about 500 described species, most occurring in the Amazon, Atlantic rainforest and Cerrado (savanna) ecosystems in Brazil. The origin and evolution of bioluminescence, as well as the taxonomic status of several Neotropical taxa in these families remains unclear. In order to contribute to a better understanding of the phylogeny and evolution of bioluminescent Elateroidea we sequenced and analyzed sequences of mitochondrial NADH2 and the nuclear 28S genes and of the cloned luciferase sequences of Brazilian species belonging to the following genera: (Lampyridae) Macrolampis, Photuris, Amydetes, Bicellonycha, Aspisoma, Lucidota, Cratomorphus; (Elateridae) Conoderus, Pyrophorus, Hapsodrilus, Pyrearinus, Fulgeochlizus; and (Phengodidae) Pseudophengodes, Phrixothrix, Euryopa and Brasilocerus. Our study supports a closer phylogenetic relationship between Elateridae and Phengodidae as other molecular studies, in contrast with previous morphologic and molecular studies that clustered Lampyridae/Phengodidae. Molecular data also supported division of the Phengodinae subfamily into the tribes Phengodini and Mastinocerini. The position of the genus Amydetes supports the status of the Amydetinae as a subfamily. The genus Euryopa is included in the Mastinocerini tribe within the Phengodinae/Phengodidae. Copyright © 2013 John Wiley & Sons, Ltd. 相似文献