排序方式: 共有68条查询结果,搜索用时 15 毫秒
11.
Giorgio Cozza Cristina Girardi Alessandro Ranchio Graziano Lolli Stefania Sarno Andrzej Orzeszko Zygmunt Kazimierczuk Roberto Battistutta Maria Ruzzene Lorenzo A. Pinna 《Cellular and molecular life sciences : CMLS》2014,71(16):3173-3185
It has been proposed that dual inhibitors of protein kinases CK2 and PIM-1 are tools particularly valuable to induce apoptosis of cancer cells, a property, however, implying cell permeability, which is lacking in the case of selective CK2/PIM-1 inhibitors developed so far. To fill this gap, we have derivatized the scaffold of the promiscuous CK2 inhibitor TBI with a deoxyribose moiety, generating TDB, a selective, cell-permeable inhibitor of CK2 and PIM-1. Here, we shed light on the structural features underlying the potency and narrow selectivity of TDB by exploiting a number of TDB analogs and by solving the 3D structure of the TDB/CK2 complex at 1.25?Å resolution, one of the highest reported so far for this kinase. We also show that the cytotoxic efficacy of TDB is almost entirely due to apoptosis, is accompanied by parallel inhibition of cellular CK2 and PIM-1, and is superior to both those observed combining individual inhibitors of CK2 and PIM-1 and by treating cells with the CK2 inhibitor CX4945. These data, in conjunction with the observations that cancer cells are more susceptible than non-cancer cells to TDB and that such a sensitivity is maintained in a multi-drug resistance background, highlight the pharmacological potential of this compound. 相似文献
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The post-perovskite phase of (Mg,Fe)SiO3 is believed to be the main mineral phase of the Earth's lowermost mantle (the D' layer). Its properties explain numerous geophysical observations associated with this layer-for example, the D' discontinuity, its topography and seismic anisotropy within the layer. Here we use a novel simulation technique, first-principles metadynamics, to identify a family of low-energy polytypic stacking-fault structures intermediate between the perovskite and post-perovskite phases. Metadynamics trajectories identify plane sliding involving the formation of stacking faults as the most favourable pathway for the phase transition, and as a likely mechanism for plastic deformation of perovskite and post-perovskite. In particular, the predicted slip planes are {010} for perovskite (consistent with experiment) and {110} for post-perovskite (in contrast to the previously expected {010} slip planes). Dominant slip planes define the lattice preferred orientation and elastic anisotropy of the texture. The {110} slip planes in post-perovskite require a much smaller degree of lattice preferred orientation to explain geophysical observations of shear-wave anisotropy in the D' layer. 相似文献
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The Amazon basin in transition 总被引:7,自引:0,他引:7
Davidson EA de Araújo AC Artaxo P Balch JK Brown IF C Bustamante MM Coe MT DeFries RS Keller M Longo M Munger JW Schroeder W Soares-Filho BS Souza CM Wofsy SC 《Nature》2012,481(7381):321-328
Agricultural expansion and climate variability have become important agents of disturbance in the Amazon basin. Recent studies have demonstrated considerable resilience of Amazonian forests to moderate annual drought, but they also show that interactions between deforestation, fire and drought potentially lead to losses of carbon storage and changes in regional precipitation patterns and river discharge. Although the basin-wide impacts of land use and drought may not yet surpass the magnitude of natural variability of hydrologic and biogeochemical cycles, there are some signs of a transition to a disturbance-dominated regime. These signs include changing energy and water cycles in the southern and eastern portions of the Amazon basin. 相似文献
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Bottke WF Vokrouhlický D Minton D Nesvorný D Morbidelli A Brasser R Simonson B Levison HF 《Nature》2012,485(7396):78-81
The barrage of comets and asteroids that produced many young lunar basins (craters over 300 kilometres in diameter) has frequently been called the Late Heavy Bombardment (LHB). Many assume the LHB ended about 3.7 to 3.8 billion years (Gyr) ago with the formation of Orientale basin. Evidence for LHB-sized blasts on Earth, however, extend into the Archaean and early Proterozoic eons, in the form of impact spherule beds: globally distributed ejecta layers created by Chicxulub-sized or larger cratering events4. At least seven spherule beds have been found that formed between 3.23 and 3.47?Gyr ago, four between 2.49 and 2.63?Gyr ago, and one between 1.7 and 2.1?Gyr ago. Here we report that the LHB lasted much longer than previously thought, with most late impactors coming from the E belt, an extended and now largely extinct portion of the asteroid belt between 1.7 and 2.1 astronomical units from Earth. This region was destabilized by late giant planet migration. E-belt survivors now make up the high-inclination Hungaria asteroids. Scaling from the observed Hungaria asteroids, we find that E-belt projectiles made about ten lunar basins between 3.7 and 4.1?Gyr ago. They also produced about 15 terrestrial basins between 2.5 and 3.7?Gyr ago, as well as around 70 and four Chicxulub-sized or larger craters on the Earth and Moon, respectively, between 1.7 and 3.7?Gyr ago. These rates reproduce impact spherule bed and lunar crater constraints. 相似文献
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Alessandro Cocchi Giovanni Semprini 《华南理工大学学报(自然科学版)》2007,35(B10):213-216
目前建筑设计正面临着需要满足某些标准的要求,这看来似乎时建筑师的想象力构成束缚,迫使他进入工程学领域而不仅仅是考虑美观,比如,住宅的声与热舒适对于新建建筑而言是必不可缺的.再者,节能在世界范围内也是强制性的,所有新建建筑均必须考虑此问题,至少应考虑人工照明、热工和空调等方面的低能耗.窗户在建筑设计中成为更重要的细部,必须仔细地加以推敲,使之能吸收能量.在意大利,目前有两种法定的工具来规范隔声和隔热.文中简要地对此加以综合介绍并就如何执行进行了探讨. 相似文献
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Paola Luciani Cristiana Deledda Susanna Benvenuti Ilaria Cellai Roberta Squecco Monica Monici Francesca Cialdai Giorgia Luciani Giovanna Danza Chiara Di Stefano Fabio Francini Alessandro Peri 《Cellular and molecular life sciences : CMLS》2010,67(21):3711-3723
Glucagon-like peptide-1 (GLP-1) is an insulinotropic peptide with neurotrophic properties, as assessed in animal cell models. Exendin-4, a GLP-1 analogue, has been recently approved for the treatment of type 2 diabetes mellitus. The aim of this study was to morphologically, structurally, and functionally characterize the differentiating actions of exendin-4 using a human neuronal cell model (i.e., SH-SY5Y cells). We found that exendin-4 increased the number of neurites paralleled by dramatic changes in intracellular actin and tubulin distribution. Electrophysiological analyses showed an increase in cell membrane surface and in stretch-activated-channels sensitivity, an increased conductance of Na+ channels and amplitude of Ca++ currents (T- and L-type), typical of a more mature neuronal phenotype. To our knowledge, this is the first demonstration that exendin-4 promotes neuronal differentiation in human cells. Noteworthy, our data support the claimed favorable role of exendin-4 against diabetic neuropathy as well as against different neurodegenerative diseases. 相似文献
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Maria Valeria Catani Valeria Gasperi Daniela Evangelista Alessandro Finazzi Agrò Luciana Avigliano Mauro Maccarrone 《Cellular and molecular life sciences : CMLS》2010,67(4):601-610
Platelets are stored at 22°C, since incubation at 37°C results in loss of viability. Nonetheless, in our body (37°C), platelets
survive for 8–10 days. This discrepancy has been explained in terms of deprivation of viability factors or accumulation of
apoptotic factors during storage. We report that the endocannabinoid anandamide (AEA) may be one of the agents allowing platelet
survival. In fact, at 37°C, human platelets enhance the expression of pro-apoptotic proteins (caspases, Bax, Bak) and decrease
the expression of Bcl-xL, thus changing the Bcl-xL/Bak ratio, a key platelet biological clock. AEA or its non-hydrolyzable
analogue, methanandamide, extend platelet life span, without reversing the changes in Bcl-xL/Bak ratio induced by heat stress.
Instead, AEA binding to type-1 cannabinoid receptor activates Akt, which regulates, through phosphorylation of Bad, the interactions
among different Bcl-2 family members. These findings could have implications for platelet collection and, potentially, for
their clinical use. 相似文献
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Vincenzo Luca Annarita Stringaro Marisa Colone Alessandro Pini Maria Luisa Mangoni 《Cellular and molecular life sciences : CMLS》2013,70(15):2773-2786
Pseudomonas aeruginosa is an opportunistic bacterial pathogen that forms sessile communities, named biofilms. The non-motile forms are very difficult to eradicate and are often associated with the establishment of persistent infections, especially in patients with cystic fibrosis. The resistance of P. aeruginosa to conventional antibiotics has become a growing health concern worldwide and has prompted the search for new anti-infective agents with new modes of action. Naturally occurring antimicrobial peptides (AMPs) represent promising future template candidates. Here we report on the potent activity and membrane-perturbing effects of the amphibian AMP esculentin(1-21), on both the free-living and sessile forms of P. aeruginosa, as a possible mechanism for biofilm disruption. Furthermore, the findings that esculentin(1-21) is able to prolong survival of animals in models of sepsis and pulmonary infection indicate that this peptide can be a promising template for the generation of new antibiotic formulations to advance care of infections caused by P. aeruginosa. 相似文献