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1.
Christian Dölle Marc Niere Emilia Lohndal Mathias Ziegler 《Cellular and molecular life sciences : CMLS》2010,67(3):433-443
Poly-ADP-ribose polymerases (PARPs) use NAD+ as substrate to generate polymers of ADP-ribose. We targeted the catalytic domain of human PARP1 as molecular NAD+ detector into cellular organelles. Immunochemical detection of polymers demonstrated distinct subcellular NAD+ pools in mitochondria, peroxisomes and, surprisingly, in the endoplasmic reticulum and the Golgi complex. Polymers did not
accumulate within the mitochondrial intermembrane space or the cytosol. We demonstrate the suitability of this compartment-specific
NAD+ and poly-ADP-ribose turnover to establish intra-organellar protein localization. For overexpressed proteins, genetically
endowed with PARP activity, detection of polymers indicates segregation from the cytosol and consequently intra-organellar
residence. In mitochondria, polymer build-up reveals matrix localization of the PARP fusion protein. Compared to presently
used fusion tags for subcellular protein localization, these are substantial improvements in resolution. We thus established
a novel molecular tool applicable for studies of subcellular NAD metabolism and protein localization. 相似文献
2.
Emilia Pedone Danila Limauro Katia D’Ambrosio Giuseppina De Simone Simonetta Bartolucci 《Cellular and molecular life sciences : CMLS》2010,67(22):3797-3814
The Thioredoxin (Trx) fold is a versatile protein scaffold consisting of a four-stranded β-sheet surrounded by three α-helices.
Various insertions are possible on this structural theme originating different proteins, which show a variety of functions
and specificities. During evolution, the assembly of different Trx fold domains has been used many times to build new multi-domain
proteins able to perform a large number of catalytic functions. To clarify the interaction mode of the different Trx domains
within a multi-domain structure and how their combination can affect catalytic performances, in this review, we report on
a structural and functional analysis of the most representative proteins containing more than one catalytically active Trx
domain: the eukaryotic protein disulfide isomerases (PDIs), the thermophilic protein disulfide oxidoreductases (PDOs) and
the hybrid peroxiredoxins (Prxs). 相似文献
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In order to avoid ‘frailty’ in deterministic assumptions concerning survival law, in this paper stochastic volatility in the force of mortality is considered. In particular, mortality rates are studied by means of a stochastic model of CIR type. A method for estimating its parameters is presented and an example of application, based on simulations of the process, is shown. Empirical results and comparison with a traditional model illustrate predictive performance and the flexibility of the model. Copyright © 2006 John Wiley & Sons, Ltd. 相似文献
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Walker LM Huber M Doores KJ Falkowska E Pejchal R Julien JP Wang SK Ramos A Chan-Hui PY Moyle M Mitcham JL Hammond PW Olsen OA Phung P Fling S Wong CH Phogat S Wrin T Simek MD;Protocol G Principal Investigators Koff WC Wilson IA Burton DR Poignard P 《Nature》2011,477(7365):466-470
Broadly neutralizing antibodies against highly variable viral pathogens are much sought after to treat or protect against global circulating viruses. Here we probed the neutralizing antibody repertoires of four human immunodeficiency virus (HIV)-infected donors with remarkably broad and potent neutralizing responses and rescued 17 new monoclonal antibodies that neutralize broadly across clades. Many of the new monoclonal antibodies are almost tenfold more potent than the recently described PG9, PG16 and VRC01 broadly neutralizing monoclonal antibodies and 100-fold more potent than the original prototype HIV broadly neutralizing monoclonal antibodies. The monoclonal antibodies largely recapitulate the neutralization breadth found in the corresponding donor serum and many recognize novel epitopes on envelope (Env) glycoprotein gp120, illuminating new targets for vaccine design. Analysis of neutralization by the full complement of anti-HIV broadly neutralizing monoclonal antibodies now available reveals that certain combinations of antibodies should offer markedly more favourable coverage of the enormous diversity of global circulating viruses than others and these combinations might be sought in active or passive immunization regimes. Overall, the isolation of multiple HIV broadly neutralizing monoclonal antibodies from several donors that, in aggregate, provide broad coverage at low concentrations is a highly positive indicator for the eventual design of an effective antibody-based HIV vaccine. 相似文献
5.
5-Iodo-2-deoxyuridine resistance of vaccinia viruses in cells endowed with thymidine kinase activity
Maria A. Marcialis Emilia Biondi A. Atzeni Maria L. Schivo Paola Uccheddu B. Loddo 《Cellular and molecular life sciences : CMLS》1973,29(6):733-734
Riassunto La IUdR resistenza che alcuni DNA virus manifestano in cellule dotate di timidino-kinasi può essere dovuta ad una accentuata retroinibizione di questo enzima ad opera di TTP.
This work has been supported by a grant of the Consiglio Nazionale delle Ricerche (Roma). 相似文献
This work has been supported by a grant of the Consiglio Nazionale delle Ricerche (Roma). 相似文献
6.
Li Y Vinckenbosch N Tian G Huerta-Sanchez E Jiang T Jiang H Albrechtsen A Andersen G Cao H Korneliussen T Grarup N Guo Y Hellman I Jin X Li Q Liu J Liu X Sparsø T Tang M Wu H Wu R Yu C Zheng H Astrup A Bolund L Holmkvist J Jørgensen T Kristiansen K Schmitz O Schwartz TW Zhang X Li R Yang H Wang J Hansen T Pedersen O Nielsen R Wang J 《Nature genetics》2010,42(11):969-972
Targeted capture combined with massively parallel exome sequencing is a promising approach to identify genetic variants implicated in human traits. We report exome sequencing of 200 individuals from Denmark with targeted capture of 18,654 coding genes and sequence coverage of each individual exome at an average depth of 12-fold. On average, about 95% of the target regions were covered by at least one read. We identified 121,870 SNPs in the sample population, including 53,081 coding SNPs (cSNPs). Using a statistical method for SNP calling and an estimation of allelic frequencies based on our population data, we derived the allele frequency spectrum of cSNPs with a minor allele frequency greater than 0.02. We identified a 1.8-fold excess of deleterious, non-syonomyous cSNPs over synonymous cSNPs in the low-frequency range (minor allele frequencies between 2% and 5%). This excess was more pronounced for X-linked SNPs, suggesting that deleterious substitutions are primarily recessive. 相似文献
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Laura Riboni Hortensia D'Albora Emilia Carlevaro R. Dominguez 《Cellular and molecular life sciences : CMLS》1969,25(7):754-755
Résumé Des greffons d'ovaire de rat impubère placés dans la chambre antérieure de l'il du mâle castré, après traitement avec 0,5 mg de dipropionate d'stradiol ou avec deux doses de 1 mg de progestérone, ont montré une évidente ovulation. On interprète ce fait comme dû á l'action des hormones injectées dans le système nerveux central et qui favorisent le mécanisme de l'ovulation. 相似文献
10.
Carmela Ioppolo Emilia Chiancone L. Forlani 《Cellular and molecular life sciences : CMLS》1968,24(4):328-328
Riassunto Miscele di emoglobina canina e catene isolate di emoglobina umana, tenute a pH neutro e a bassa forza ionica, mostrano la formazione di molecole ibride. La formazione di ibrido in tampone fosfato diluito è minore che in assenza di sali. 相似文献