排序方式: 共有23条查询结果,搜索用时 15 毫秒
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Julie Lecomte Krystel Louis Benoit Detry Silvia Blacher Vincent Lambert Sandrine Bekaert Carine Munaut Jenny Paupert Pierre Blaise Jean-Michel Foidart Jean-Marie Rakic Stephen M. Krane Agn��s Noel 《Cellular and molecular life sciences : CMLS》2011,68(4):677-686
In this study, we evaluate the potential involvement of collagenase-3 (MMP13), a matrix metalloproteinase (MMP) family member, in the exudative form of age-related macular degeneration characterized by a neovascularisation into the choroid. RT-PCR analysis revealed that human neovascular membranes issued from patients with AMD expressed high levels of Mmp13. The contribution of MMP13 in choroidal neovascularization (CNV) formation was explored by using a murine model of laser-induced CNV and applying it to wild-type mice (WT) and Mmp13-deficient mice (Mmp13 ?/? mice). Angiogenic and inflammatory reactions were explored by immunohistochemistry. The implication of bone marrow (BM)-derived cells was determined by BM engraftment into irradiated mice and by injecting mesenchymal stem cells (MSC) isolated from WT BM. The deficiency of Mmp13 impaired CNV formation which was fully restored by WT BM engraftment and partially rescued by several injections of WT MSC. The present study sheds light on a novel function of MMP13 during BM-dependent choroidal vascularization and provides evidence for a role for MSC in the pathogenesis of CNV. 相似文献
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Caroline Lonez Marc F. Lensink Emilie Kleiren Jean-Marie Vanderwinden Jean-Marie Ruysschaert Michel Vandenbranden 《Cellular and molecular life sciences : CMLS》2010,67(3):483-494
Addition of co-lipids into cationic lipid formulations is considered as promoting cell delivery of DNA by enhancing fusion
processes with cell membranes. Here, by combining FRET and confocal microscopy, we demonstrate that some cationic lipids do
not require a co-lipid to fuse efficiently with cells. These cationic lipids are able to self-organize into bilayers that
are stable enough to form liposomes, while presenting some destabilizing properties reminiscent of the conically shaped fusogenic
co-lipid, DOPE. We therefore analyzed the resident lipid structures in cationic bilayers by molecular dynamics simulations,
clustering the individual lipid structures into populations of similarly shaped molecules, as opposed to the classical approach
of using the static packing parameter to define the lipid shapes. Comparison of fusogenic properties with these lipid populations
suggests that the ratio of cylindrical versus conical lipid populations correlates with the ability to fuse with cell membranes. 相似文献
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Rabia?Sarroukh Emilie?Cerf Sylvie?Derclaye Yves?F.?Dufrêne Erik?Goormaghtigh Jean-Marie?RuysschaertEmail author Vincent?Raussens 《Cellular and molecular life sciences : CMLS》2011,68(8):1429-1438
Alzheimer’s disease (AD) is a neurodegenerative disorder occurring in the elderly. It is widely accepted that the amyloid
beta peptide (Aβ) aggregation and especially the oligomeric states rather than fibrils are involved in AD onset. We used infrared
spectroscopy to provide structural information on the entire aggregation pathway of Aβ(1–40), starting from monomeric Aβ to
the end of the process, fibrils. Our structural study suggests that conversion of oligomers into fibrils results from a transition
from antiparallel to parallel β-sheet. These structural changes are described in terms of H-bonding rupture/formation, β-strands
reorientation and β-sheet elongation. As antiparallel β-sheet structure is also observed for other amyloidogenic proteins
forming oligomers, reorganization of the β-sheet implicating a reorientation of β-strands could be a generic mechanism determining
the kinetics of protein misfolding. Elucidation of the process driving aggregation, including structural transitions, could
be essential in a search for therapies inhibiting aggregation or disrupting aggregates. 相似文献
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Steinberg KM Antonacci F Sudmant PH Kidd JM Campbell CD Vives L Malig M Scheinfeldt L Beggs W Ibrahim M Lema G Nyambo TB Omar SA Bodo JM Froment A Donnelly MP Kidd KK Tishkoff SA Eichler EE 《Nature genetics》2012,44(8):872-880
The 17q21.31 inversion polymorphism exists either as direct (H1) or inverted (H2) haplotypes with differential predispositions to disease and selection. We investigated its genetic diversity in 2,700 individuals, with an emphasis on African populations. We characterize eight structural haplotypes due to complex rearrangements that vary in size from 1.08-1.49 Mb and provide evidence for a 30-kb H1-H2 double recombination event. We show that recurrent partial duplications of the KANSL1 gene have occurred on both the H1 and H2 haplotypes and have risen to high frequency in European populations. We identify a likely ancestral H2 haplotype (H2') lacking these duplications that is enriched among African hunter-gatherer groups yet essentially absent from West African populations. Whereas H1 and H2 segmental duplications arose independently and before human migration out of Africa, they have reached high frequencies recently among Europeans, either because of extraordinary genetic drift or selective sweeps. 相似文献
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Worobey M Gemmel M Teuwen DE Haselkorn T Kunstman K Bunce M Muyembe JJ Kabongo JM Kalengayi RM Van Marck E Gilbert MT Wolinsky SM 《Nature》2008,455(7213):661-664
Human immunodeficiency virus type 1 (HIV-1) sequences that pre-date the recognition of AIDS are critical to defining the time of origin and the timescale of virus evolution. A viral sequence from 1959 (ZR59) is the oldest known HIV-1 infection. Other historically documented sequences, important calibration points to convert evolutionary distance into time, are lacking, however; ZR59 is the only one sampled before 1976. Here we report the amplification and characterization of viral sequences from a Bouin's-fixed paraffin-embedded lymph node biopsy specimen obtained in 1960 from an adult female in Léopoldville, Belgian Congo (now Kinshasa, Democratic Republic of the Congo (DRC)), and we use them to conduct the first comparative evolutionary genetic study of early pre-AIDS epidemic HIV-1 group M viruses. Phylogenetic analyses position this viral sequence (DRC60) closest to the ancestral node of subtype A (excluding A2). Relaxed molecular clock analyses incorporating DRC60 and ZR59 date the most recent common ancestor of the M group to near the beginning of the twentieth century. The sizeable genetic distance between DRC60 and ZR59 directly demonstrates that diversification of HIV-1 in west-central Africa occurred long before the recognized AIDS pandemic. The recovery of viral gene sequences from decades-old paraffin-embedded tissues opens the door to a detailed palaeovirological investigation of the evolutionary history of HIV-1 that is not accessible by other methods. 相似文献
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Jean-Marie LEHN 《复旦学报(自然科学版)》2007,(5)
1 Results Animate as well as inanimate matter,living organisms as well as materials,are formed of molecules and of the organized entities resulting from the interaction of molecules with each other.Chemistry provides the bridge between the molecules of inanimate matter and the highly complex molecular architectures and systems which make up living organisms. Synthetic chemistry has developed a very powerful set of methods for constructing ever more complex molecules.Supramolecular chemistry seeks to con... 相似文献
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Viré E Brenner C Deplus R Blanchon L Fraga M Didelot C Morey L Van Eynde A Bernard D Vanderwinden JM Bollen M Esteller M Di Croce L de Launoit Y Fuks F 《Nature》2006,439(7078):871-874
The establishment and maintenance of epigenetic gene silencing is fundamental to cell determination and function. The essential epigenetic systems involved in heritable repression of gene activity are the Polycomb group (PcG) proteins and the DNA methylation systems. Here we show that the corresponding silencing pathways are mechanistically linked. We find that the PcG protein EZH2 (Enhancer of Zeste homolog 2) interacts-within the context of the Polycomb repressive complexes 2 and 3 (PRC2/3)-with DNA methyltransferases (DNMTs) and associates with DNMT activity in vivo. Chromatin immunoprecipitations indicate that binding of DNMTs to several EZH2-repressed genes depends on the presence of EZH2. Furthermore, we show by bisulphite genomic sequencing that EZH2 is required for DNA methylation of EZH2-target promoters. Our results suggest that EZH2 serves as a recruitment platform for DNA methyltransferases, thus highlighting a previously unrecognized direct connection between two key epigenetic repression systems. 相似文献