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31.
Niikura H Légaré F Hasbani R Bandrauk AD Ivanov MY Villeneuve DM Corkum PB 《Nature》2002,417(6892):917-922
Experience shows that the ability to make measurements in any new time regime opens new areas of science. Currently, experimental probes for the attosecond time regime (10(-18) 10(-15) s) are being established. The leading approach is the generation of attosecond optical pulses by ionizing atoms with intense laser pulses. This nonlinear process leads to the production of high harmonics during collisions between electrons and the ionized atoms. The underlying mechanism implies control of energetic electrons with attosecond precision. We propose that the electrons themselves can be exploited for ultrafast measurements. We use a 'molecular clock', based on a vibrational wave packet in H(2)(+) to show that distinct bunches of electrons appear during electron ion collisions with high current densities, and durations of about 1 femtosecond (10(-15) s). Furthermore, we use the molecular clock to study the dynamics of non-sequential double ionization. 相似文献
32.
We present a system for combining the different types of predictions given by a wide category of mechanical trading rules through statistical learning methods (boosting, and several model averaging methods like Bayesian or simple averaging methods). Statistical learning methods supply better out‐of‐sample results than most of the single moving average rules in the NYSE Composite Index from January 1993 to December 2002. Moreover, using a filter to reduce trading frequency, the filtered boosting model produces a technical strategy which, although it is not able to overcome the returns of the buy‐and‐hold (B&H) strategy during rising periods, it does overcome the B&H during falling periods and is able to absorb a considerable part of falls in the market. Copyright © 2008 John Wiley & Sons, Ltd. 相似文献
33.
Hellgren M Strömberg P Gallego O Martras S Farrés J Persson B Parés X Höög JO 《Cellular and molecular life sciences : CMLS》2007,64(4):498-505
The metabolism of all-trans- and 9-cis-retinol/ retinaldehyde has been investigated with focus on the activities of human, mouse and rat alcohol dehydrogenase 2
(ADH2), an intriguing enzyme with apparently different functions in human and rodents. Kinetic constants were determined with
an HPLC method and a structural approach was implemented by in silico substrate dockings. For human ADH2, the determined Km values ranged from 0.05 to 0.3 μM and kcat values from 2.3 to 17.6 min−1, while the catalytic efficiency for 9-cis-retinol showed the highest value for any substrate. In contrast, poor activities
were detected for the rodent enzymes. A mouse ADH2 mutant (ADH2Pro47His) was studied that resembles the human ADH2 setup.
This mutation increased the retinoid activity up to 100-fold. The Km values of human ADH2 are the lowest among all known human retinol dehydrogenases, which clearly support a role in hepatic
retinol oxidation at physiological concentrations.
Received 12 October 2006; received after revision 6 December 2006; accepted 8 January 2007 相似文献
34.
Dina C Meyre D Gallina S Durand E Körner A Jacobson P Carlsson LM Kiess W Vatin V Lecoeur C Delplanque J Vaillant E Pattou F Ruiz J Weill J Levy-Marchal C Horber F Potoczna N Hercberg S Le Stunff C Bougnères P Kovacs P Marre M Balkau B Cauchi S Chèvre JC Froguel P 《Nature genetics》2007,39(6):724-726
We identified a set of SNPs in the first intron of the FTO (fat mass and obesity associated) gene on chromosome 16q12.2 that is consistently strongly associated with early-onset and severe obesity in both adults and children of European ancestry with an experiment-wise P value of 1.67 x 10(-26) in 2,900 affected individuals and 5,100 controls. The at-risk haplotype yields a proportion of attributable risk of 22% for common obesity. We conclude that FTO contributes to human obesity and hence may be a target for subsequent functional analyses. 相似文献
35.
The Shwachman-Bodian-Diamond syndrome protein mediates translational activation of ribosomes in yeast 总被引:1,自引:0,他引:1
Menne TF Goyenechea B Sánchez-Puig N Wong CC Tonkin LM Ancliff PJ Brost RL Costanzo M Boone C Warren AJ 《Nature genetics》2007,39(4):486-495
The autosomal recessive disorder Shwachman-Diamond syndrome, characterized by bone marrow failure and leukemia predisposition, is caused by deficiency of the highly conserved Shwachman-Bodian-Diamond syndrome (SBDS) protein. Here, we identify the function of the yeast SBDS ortholog Sdo1, showing that it is critical for the release and recycling of the nucleolar shuttling factor Tif6 from pre-60S ribosomes, a key step in 60S maturation and translational activation of ribosomes. Using genome-wide synthetic genetic array mapping, we identified multiple TIF6 gain-of-function alleles that suppressed the pre-60S nuclear export defects and cytoplasmic mislocalization of Tif6 observed in sdo1Delta cells. Sdo1 appears to function within a pathway containing elongation factor-like 1, and together they control translational activation of ribosomes. Thus, our data link defective late 60S ribosomal subunit maturation to an inherited bone marrow failure syndrome associated with leukemia predisposition. 相似文献
36.
Mutations in amphiphysin 2 (BIN1) disrupt interaction with dynamin 2 and cause autosomal recessive centronuclear myopathy 总被引:4,自引:0,他引:4
Nicot AS Toussaint A Tosch V Kretz C Wallgren-Pettersson C Iwarsson E Kingston H Garnier JM Biancalana V Oldfors A Mandel JL Laporte J 《Nature genetics》2007,39(9):1134-1139
Centronuclear myopathies are characterized by muscle weakness and abnormal centralization of nuclei in muscle fibers not secondary to regeneration. The severe neonatal X-linked form (myotubular myopathy) is due to mutations in the phosphoinositide phosphatase myotubularin (MTM1), whereas mutations in dynamin 2 (DNM2) have been found in some autosomal dominant cases. By direct sequencing of functional candidate genes, we identified homozygous mutations in amphiphysin 2 (BIN1) in three families with autosomal recessive inheritance. Two missense mutations affecting the BAR (Bin1/amphiphysin/RVS167) domain disrupt its membrane tubulation properties in transfected cells, and a partial truncation of the C-terminal SH3 domain abrogates the interaction with DNM2 and its recruitment to the membrane tubules. Our results suggest that mutations in BIN1 cause centronuclear myopathy by interfering with remodeling of T tubules and/or endocytic membranes, and that the functional interaction between BIN1 and DNM2 is necessary for normal muscle function and positioning of nuclei. 相似文献
37.
Péterfy M Ben-Zeev O Mao HZ Weissglas-Volkov D Aouizerat BE Pullinger CR Frost PH Kane JP Malloy MJ Reue K Pajukanta P Doolittle MH 《Nature genetics》2007,39(12):1483-1487
Hypertriglyceridemia is a hallmark of many disorders, including metabolic syndrome, diabetes, atherosclerosis and obesity. A well-known cause is the deficiency of lipoprotein lipase (LPL), a key enzyme in plasma triglyceride hydrolysis. Mice carrying the combined lipase deficiency (cld) mutation show severe hypertriglyceridemia owing to a decrease in the activity of LPL and a related enzyme, hepatic lipase (HL), caused by impaired maturation of nascent LPL and hepatic lipase polypeptides in the endoplasmic reticulum (ER). Here we identify the gene containing the cld mutation as Tmem112 and rename it Lmf1 (Lipase maturation factor 1). Lmf1 encodes a transmembrane protein with an evolutionarily conserved domain of unknown function that localizes to the ER. A human subject homozygous for a deleterious mutation in LMF1 also shows combined lipase deficiency with concomitant hypertriglyceridemia and associated disorders. Thus, through its profound effect on lipase activity, LMF1 emerges as an important candidate gene in hypertriglyceridemia. 相似文献
38.
Gout AM;ADPKD Gene Variant Consortium Ravine D Harris PC Rossetti S Peters D Breuning M Henske EP Koizumi A Inoue S Shimizu Y Thongnoppakhun W Yenchitsomanus PT Deltas C Sandford R Torra R Turco AE Jeffery S Fontes M Somlo S Furu LM Smulders YM Mercier B Ferec C Burtey S Pei Y Kalaydjieva L Bogdanova N McCluskey M Geon LJ Wouters CH Reiterova J Stekrová J San Millan JL Aguiari G Del Senno L 《Nature genetics》2007,39(4):427-428
39.
The macromolecular peptide-loading complex in MHC class I-dependent antigen presentation 总被引:5,自引:1,他引:4
A challenging task for the adaptive immune system of vertebrates is to identify and eliminate intracellular antigens. Therefore
a highly specialized antigen presentation machinery has evolved to display fragments of newly synthesized proteins to effector
cells of the immune system at the cell surface. After proteasomal degradation of unwanted proteins or defective ribosome products,
resulting peptides are translocated into the endoplasmic reticulum by the transporter associated with antigen processing and
loaded onto major histocompatibility complex (MHC) class I molecules. Peptide-MHC I complexes are transported via the secretory
pathway to the cell surface where they are then inspected by cytotoxic T lymphocytes, which can trigger an immune response.
This review summarizes the current view of the intracellular machinery of antigen processing and of viral immune escape mechanisms
to circumvent destruction by the host.
Received 4 October 2005; received after revision 19 November 2005; accepted 24 November 2005 相似文献
40.
Kertész A Váradi G Tóth GK Fajka-Boja R Monostori E Sármay G 《Cellular and molecular life sciences : CMLS》2006,63(22):2682-2693
Phosphopeptides interacting with src homology 2 (SH2) domains can activate essential signaling enzymes in vitro. When delivered to cells, they may disrupt protein-protein interactions, thereby influencing intracellular signaling. We
showed earlier that phosphopeptides corresponding to the inhibitory motif of Fcγ receptor IIb and a motif of the Grb2-associated
binder 1 adaptor protein activate SH2-containing tyrosine phosphatase 2 in vitro. To study the ex vivo effects of these peptides, we have now compared different methods for peptide delivery: (i) permeabilization of the target
cells and (ii) the use of cell-permeable vectors, which are potentially able to transport biologically active compounds into
B cells. We found octanoyl-Arg8 to be an optimal carrier for the delivery of phosphopeptides to the cells. With this strategy, the function of cell-permeable
SHP-2-binding phosphopeptides was analyzed. These peptides modulated the protein phosphorylation in B cells in a dose- and
time-dependent manner.
Received 27 July 2006; received after revision 4 September 2006; accepted 18 September 2006 相似文献