排序方式: 共有63条查询结果,搜索用时 390 毫秒
31.
Gleyzes S Kuhr S Guerlin C Bernu J Deléglise S Busk Hoff U Brune M Raimond JM Haroche S 《Nature》2007,446(7133):297-300
A microscopic quantum system under continuous observation exhibits at random times sudden jumps between its states. The detection of this quantum feature requires a quantum non-demolition (QND) measurement repeated many times during the system's evolution. Whereas quantum jumps of trapped massive particles (electrons, ions or molecules) have been observed, this has proved more challenging for light quanta. Standard photodetectors absorb light and are thus unable to detect the same photon twice. It is therefore necessary to use a transparent counter that can 'see' photons without destroying them. Moreover, the light needs to be stored for durations much longer than the QND detection time. Here we report an experiment in which we fulfil these challenging conditions and observe quantum jumps in the photon number. Microwave photons are stored in a superconducting cavity for times up to half a second, and are repeatedly probed by a stream of non-absorbing atoms. An atom interferometer measures the atomic dipole phase shift induced by the non-resonant cavity field, so that the final atom state reveals directly the presence of a single photon in the cavity. Sequences of hundreds of atoms, highly correlated in the same state, are interrupted by sudden state switchings. These telegraphic signals record the birth, life and death of individual photons. Applying a similar QND procedure to mesoscopic fields with tens of photons should open new perspectives for the exploration of the quantum-to-classical boundary. 相似文献
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Diego Sbardella Grazia R. Tundo Andrea Coletta Julien Marcoux Efthymia Ioanna Koufogeorgou Chiara Ciaccio Anna M. Santoro Danilo Milardi Giuseppe Grasso Paola Cozza Marie-Pierre Bousquet-Dubouch Stefano Marini Massimo Coletta 《Cellular and molecular life sciences : CMLS》2018,75(18):3441-3456
The interaction of insulin-degrading enzyme (IDE) with the main intracellular proteasome assemblies (i.e, 30S, 26S and 20S) was analyzed by enzymatic activity, mass spectrometry and native gel electrophoresis. IDE was mainly detected in association with assemblies with at least one free 20S end and biochemical investigations suggest that IDE competes with the 19S in vitro. IDE directly binds the 20S and affects its proteolytic activities in a bimodal fashion, very similar in human and yeast 20S, inhibiting at (IDE)?≤?30 nM and activating at (IDE)?≥?30 nM. Only an activating effect is observed in a yeast mutant locked in the “open” conformation (i.e., the α-3ΔN 20S), envisaging a possible role of IDE as modulator of the 20S “open”–”closed” allosteric equilibrium. Protein–protein docking in silico proposes that the interaction between IDE and the 20S could involve the C-term helix of the 20S α-3 subunit which regulates the gate opening of the 20S. 相似文献
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Stéphanie?Jouannet Julien?Saint-Pol Laurent?Fernandez Viet?Nguyen Stéphanie?Charrin Claude?Boucheix Christel?Brou Pierre-Emmanuel?Milhiet Eric?RubinsteinEmail author 《Cellular and molecular life sciences : CMLS》2016,73(9):1895-1915
The metalloprotease ADAM10 mediates the shedding of the ectodomain of various cell membrane proteins, including APP, the precursor of the amyloid peptide Aβ, and Notch receptors following ligand binding. ADAM10 associates with the members of an evolutionary conserved subgroup of tetraspanins, referred to as TspanC8, which regulate its exit from the endoplasmic reticulum. Here we show that 4 of these TspanC8 (Tspan5, Tspan14, Tspan15 and Tspan33) which positively regulate ADAM10 surface expression levels differentially impact ADAM10-dependent Notch activation and the cleavage of several ADAM10 substrates, including APP, N-cadherin and CD44. Sucrose gradient fractionation, single molecule tracking and quantitative mass-spectrometry analysis of the repertoire of molecules co-immunoprecipitated with Tspan5, Tspan15 and ADAM10 show that these two tetraspanins differentially regulate ADAM10 membrane compartmentalization. These data represent a unique example where several tetraspanins differentially regulate the function of a common partner protein through a distinct membrane compartmentalization. 相似文献
34.
Julien SG Dubé N Read M Penney J Paquet M Han Y Kennedy BP Muller WJ Tremblay ML 《Nature genetics》2007,39(3):338-346
We investigated the role of protein tyrosine phosphatase 1B (PTP1B) in mammary tumorigenesis using both genetic and pharmacological approaches. It has been previously shown that transgenic mice with a deletion mutation in the region of Erbb2 encoding its extracellular domain (referred to as NDL2 mice, for 'Neu deletion in extracellular domain 2') develop mammary tumors that progress to lung metastasis. However, deletion of PTP1B activity in the NDL2 transgenic mice either by breeding with Ptpn1-deficient mice or by treatment with a specific PTP1B inhibitor results in significant mammary tumor latency and resistance to lung metastasis. In contrast, specific overexpression of PTP1B in the mammary gland leads to spontaneous breast cancer development. The regulation of ErbB2-induced mammary tumorigenesis by PTB1B occurs through the attenuation of both the MAP kinase (MAPK) and Akt pathways. This report provides a rationale for the development of PTP1B as a new therapeutic target in breast cancer. 相似文献
35.
This study is the first to examine the impacts of overnight and intraday oil futures cross-market information on predicting the US stock market volatility the high-frequency data. In-sample estimations present that high overnight oil futures RV can lead to high RV of the S&P 500. Moreover, negative overnight returns are more powerful than positive components, implying the existence of the leverage effect. From statistical and economic perspectives, out-of-sample results indicate that the decompositions of overnight oil futures and intraday RVs, based on signed intraday returns, can significantly increase the models' predictive ability. Finally, when considering the US stock market overnight effect, the decompositions are still useful to predict volatility, especially during high US stock market fluctuations and high and low EPU states. 相似文献
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Kiave-Yune HoWangYin Maria Loustau Juan Wu Estibaliz Alegre Marina Daouya Julien Caumartin Sylvie Sousa Anatolij Horuzsko Edgardo D. Carosella Joel LeMaoult 《Cellular and molecular life sciences : CMLS》2012,69(23):4041-4049
The non-classical Human leukocyte antigen G (HLA-G) differs from classical HLA class I molecules by its low genetic diversity, a tissue-restricted expression, the existence of seven isoforms, and immuno-inhibitory functions. Most of the known functions of HLA-G concern the membrane-bound HLA-G1 and soluble HLA-G5 isoforms, which present the typical structure of classical HLA class I molecule: a heavy chain of three globular domains α1–α2–α3 non-covalently bound to β-2-microglobulin (B2M) and a peptide. Very little is known of the structural features and functions of other HLA-G isoforms or structural conformations other than B2M-associated HLA-G1 and HLA-G5. In the present work, we studied the capability of all isoforms to form homomultimers, and investigated whether they could bind to, and function through, the known HLA-G receptors LILRB1 and LILRB2. We report that all HLA-G isoforms may form homodimers, demonstrating for the first time the existence of HLA-G4 dimers. We also report that the HLA-G α1–α3 structure, which constitutes the extracellular part of HLA-G2 and HLA-G6, binds the LILRB2 receptor but not LILRB1. This is the first report of a receptor for a truncated HLA-G isoform. Following up on this finding, we show that the α1–α3-Fc structure coated on agarose beads is tolerogenic and capable of prolonging the survival of skin allografts in B6-mice and in a LILRB2-transgenic mouse model. This study is the first proof of concept that truncated HLA-G isoforms could be used as therapeutic agents. 相似文献
38.
Enterotypes of the human gut microbiome 总被引:6,自引:0,他引:6
Arumugam M Raes J Pelletier E Le Paslier D Yamada T Mende DR Fernandes GR Tap J Bruls T Batto JM Bertalan M Borruel N Casellas F Fernandez L Gautier L Hansen T Hattori M Hayashi T Kleerebezem M Kurokawa K Leclerc M Levenez F Manichanh C Nielsen HB Nielsen T Pons N Poulain J Qin J Sicheritz-Ponten T Tims S Torrents D Ugarte E Zoetendal EG Wang J Guarner F Pedersen O de Vos WM Brunak S Doré J;MetaHIT Consortium Antolín M Artiguenave F Blottiere HM Almeida M Brechot C Cara C Chervaux C Cultrone A 《Nature》2011,473(7346):174-180
Our knowledge of species and functional composition of the human gut microbiome is rapidly increasing, but it is still based on very few cohorts and little is known about variation across the world. By combining 22 newly sequenced faecal metagenomes of individuals from four countries with previously published data sets, here we identify three robust clusters (referred to as enterotypes hereafter) that are not nation or continent specific. We also confirmed the enterotypes in two published, larger cohorts, indicating that intestinal microbiota variation is generally stratified, not continuous. This indicates further the existence of a limited number of well-balanced host-microbial symbiotic states that might respond differently to diet and drug intake. The enterotypes are mostly driven by species composition, but abundant molecular functions are not necessarily provided by abundant species, highlighting the importance of a functional analysis to understand microbial communities. Although individual host properties such as body mass index, age, or gender cannot explain the observed enterotypes, data-driven marker genes or functional modules can be identified for each of these host properties. For example, twelve genes significantly correlate with age and three functional modules with the body mass index, hinting at a diagnostic potential of microbial markers. 相似文献
39.
McLellan JS Pancera M Carrico C Gorman J Julien JP Khayat R Louder R Pejchal R Sastry M Dai K O'Dell S Patel N Shahzad-ul-Hussan S Yang Y Zhang B Zhou T Zhu J Boyington JC Chuang GY Diwanji D Georgiev I Kwon YD Lee D Louder MK Moquin S Schmidt SD Yang ZY Bonsignori M Crump JA Kapiga SH Sam NE Haynes BF Burton DR Koff WC Walker LM Phogat S Wyatt R Orwenyo J Wang LX Arthos J Bewley CA Mascola JR Nabel GJ Schief WR Ward AB Wilson IA Kwong PD 《Nature》2011,480(7377):336-343
Variable regions 1 and 2 (V1/V2) of human immunodeficiency virus-1 (HIV-1) gp120 envelope glycoprotein are critical for viral evasion of antibody neutralization, and are themselves protected by extraordinary sequence diversity and N-linked glycosylation. Human antibodies such as PG9 nonetheless engage V1/V2 and neutralize 80% of HIV-1 isolates. Here we report the structure of V1/V2 in complex with PG9. V1/V2 forms a four-stranded β-sheet domain, in which sequence diversity and glycosylation are largely segregated to strand-connecting loops. PG9 recognition involves electrostatic, sequence-independent and glycan interactions: the latter account for over half the interactive surface but are of sufficiently weak affinity to avoid autoreactivity. The structures of V1/V2-directed antibodies CH04 and PGT145 indicate that they share a common mode of glycan penetration by extended anionic loops. In addition to structurally defining V1/V2, the results thus identify a paradigm of antibody recognition for highly glycosylated antigens, which-with PG9-involves a site of vulnerability comprising just two glycans and a strand. 相似文献
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