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141.
142.
Du X Shen J Kugan N Furth EE Lombard DB Cheung C Pak S Luo G Pignolo RJ DePinho RA Guarente L Johnson FB 《Molecular and cellular biology》2004,24(19):8437-8446
The Werner and Bloom syndromes are caused by loss-of-function mutations in WRN and BLM, respectively, which encode the RecQ family DNA helicases WRN and BLM, respectively. Persons with Werner syndrome displays premature aging of the skin, vasculature, reproductive system, and bone, and those with Bloom syndrome display more limited features of aging, including premature menopause; both syndromes involve genome instability and increased cancer. The proteins participate in recombinational repair of stalled replication forks or DNA breaks, but the precise functions of the proteins that prevent rapid aging are unknown. Accumulating evidence points to telomeres as targets of WRN and BLM, but the importance in vivo of the proteins in telomere biology has not been tested. We show that Wrn and Blm mutations each accentuate pathology in later-generation mice lacking the telomerase RNA template Terc, including acceleration of phenotypes characteristic of latest-generation Terc mutants. Furthermore, pathology not observed in Terc mutants but similar to that observed in Werner syndrome and Bloom syndrome, such as bone loss, was observed. The pathology was accompanied by enhanced telomere dysfunction, including end-to-end chromosome fusions and greater loss of telomere repeat DNA compared with Terc mutants. These findings indicate that telomere dysfunction may contribute to the pathogenesis of Werner syndrome and Bloom syndrome. 相似文献
143.
144.
Isolation of nuclei from label-retaining cells and measurement of their turnover rates in rat colon 总被引:3,自引:0,他引:3
Kim SJ Cheung S Hellerstein MK 《American journal of physiology. Cell physiology》2004,286(6):C1464-C1473
We describe here a new technique for isolating nuclei from long-term label-retaining cells (LRCs), a subpopulation enriched with stem cells from colon, and for measuring their proliferation rates in vivo. A double-label approach was developed, combining the use of bromodeoxyuridine (BrdU) and 2H2O. Male Fisher 344 rats were administered BrdU in drinking water continuously for 28 wk. BrdU was then discontinued (BrdU washout), and animals (n = 33) were switched to 2H2O in drinking water and killed after 2, 4, and 8 wk. Nuclei from BrdU-positive cells (LRCs) were collected by flow cytometry. The percentages of LRCs were 7 and 3.8% after 4 and 8 wk of BrdU washout, respectively. Turnover rates of LRCs were measured on the basis of deuterium incorporation from 2H2O into DNA of LRC nuclei, as determined by mass spectrometry. The proliferation rate of the LRCs collected was 0.330.90% per day (half-life of 77210 days). Significant contamination from other potentially long-lived colon cells was excluded. In conclusion, this double-labeling method allows both physical isolation of nuclei from colon epithelial LRCs and measurement of their in vivo proliferation rates. Use of this approach may allow better understanding of mechanisms by which agents induce or protect against colon carcinogenesis. carcinogenesis; deuterated water; long-term label-retaining cells; stable isotopes 相似文献
145.
Use of a permanent magnetic field to inhibit the development of canine osteoarthritis 总被引:4,自引:0,他引:4
This study was designed to determine the potential of a permanent magnetic field to inhibit the progression of osteoarthritis (OA) in a canine model. The magnetic field was created by 72 domino-sized ceramic magnets with surface field strength of 1100 G (0.11 T). The magnetic field strength at the surface of the mattress was 450-500 G (45-50 mT) and was equally distributed over the mattress surface. Eighteen animals had closed resection of their right stifle anterior cruciate ligament. Their kennel floors were covered in one of three ways: no floor mattress (OA) (N = 6); a floor mattress with domino-sized ceramic pieces placed between two layers of foam (sham control OA-MAT) (N = 6); or a floor mattress with domino-sized ceramic permanent magnets placed between two layers of foam (OA-MAT-MAG) (N = 6). Animals were kept in their cages except for 4 h of exercise each day. The left stifle of six animals served as the normal control. The stifle joints were examined at 12 weeks for synovial effusion, gross anatomic appearance, microscopic anatomic appearance (Mankin score), and metalloproteinase (MMP)-1 and -3. Macroscopically, the OA-MAT-MAG group appeared to have less synovitis, less synovial effusion, less disruption of the cartilage surface, and less cartilage ulceration than did the OA group or the control mattress group. The mean Mankin score for the OA-MAT-MAG group was less than that for the OA group (4.2 +/- 0.8 vs. 6.7 +/- 0.3; P <.05) and the control mattress group (4.2 +/- 0.8 vs. 5.2 +/- 0.8; P >.05), but greater than that for the normal left group (4.2 +/- 0.8 vs. 1.0 +/- 0.4; P <.05). These scores show a trend of improvement for OA-MAT-MAG group but the difference with the sham control OA-MAT group was not statistically significant. In immunohistochemical studies, the OA-MAT-MAG group cartilage was stained less heavily for MMP-1 and MMP-3 than were the OA group cartilage and the control mattress group cartilage, but did not differ significantly in MMP-1 and MMP-3 from the normal left group cartilage. The OA-MAT-MAG group did not differ from the normal left group in MMP-3 as determined by Western blot analysis. The study suggests that OA of the medial femoral condyle developed in a canine model exposed to a magnetic field may be inhibited beyond the benefit provided by mattress. Further studies are needed to delineate more precisely the effect of the magnetic field in reducing the severity of OA. 相似文献
146.
A common open representation of mass spectrometry data and its application to proteomics research 总被引:12,自引:0,他引:12
Pedrioli PG Eng JK Hubley R Vogelzang M Deutsch EW Raught B Pratt B Nilsson E Angeletti RH Apweiler R Cheung K Costello CE Hermjakob H Huang S Julian RK Kapp E McComb ME Oliver SG Omenn G Paton NW Simpson R Smith R Taylor CF Zhu W Aebersold R 《Nature biotechnology》2004,22(11):1459-1466
A broad range of mass spectrometers are used in mass spectrometry (MS)-based proteomics research. Each type of instrument possesses a unique design, data system and performance specifications, resulting in strengths and weaknesses for different types of experiments. Unfortunately, the native binary data formats produced by each type of mass spectrometer also differ and are usually proprietary. The diverse, nontransparent nature of the data structure complicates the integration of new instruments into preexisting infrastructure, impedes the analysis, exchange, comparison and publication of results from different experiments and laboratories, and prevents the bioinformatics community from accessing data sets required for software development. Here, we introduce the 'mzXML' format, an open, generic XML (extensible markup language) representation of MS data. We have also developed an accompanying suite of supporting programs. We expect that this format will facilitate data management, interpretation and dissemination in proteomics research. 相似文献
147.
Lee HC 《Current molecular medicine》2004,4(3):227-237
It is generally believed that multiple Ca2+ stores are present in cells, a notion that has now been made substantive by the discovery of multiple Ca2+ mobilizing messengers. Cyclic ADP-ribose (cADPR) and nicotinic acid dinucleotide phosphate (NAADP) are two such messengers that are derived from NAD and NADP, respectively. A wide variety of cells, from plants to mammals, including human, have been shown to be responsive to these two novel Ca2+ messengers. Not only are their structures and mechanisms of action different, their targeted Ca2+ stores are also distinct and separable. This article explores the implications of the multiplicity of Ca2+ stores in cellular signaling. Special emphasis will be put on the recent progress in the understanding of the physiological functions of NAADP. 相似文献
148.
Stella?PelengarisEmail author Sylvie?Abouna Linda?Cheung Vasiliki?Ifandi Sevasti?Zervou Michael?Khan 《BMC biology》2004,2(1):26
Background
Tumour regression observed in many conditional mouse models following oncogene inactivation provides the impetus to develop, and a platform to preclinically evaluate, novel therapeutics to inactivate specific oncogenes. Inactivating single oncogenes, such as c-Myc, can reverse even advanced tumours. Intriguingly, transient c-Myc inactivation proved sufficient for sustained osteosarcoma regression; the resulting osteocyte differentiation potentially explaining loss of c-Myc's oncogenic properties. But would this apply to other tumours? 相似文献149.
Remko?de Knikker Youjun?Guo Jin-long?Li Albert?KH?Kwan Kevin?Y?Yip David?W?Cheung Kei-Hoi?CheungEmail author 《BMC bioinformatics》2004,5(1):25
Background
Very often genome-wide data analysis requires the interoperation of multiple databases and analytic tools. A large number of genome databases and bioinformatics applications are available through the web, but it is difficult to automate interoperation because: 1) the platforms on which the applications run are heterogeneous, 2) their web interface is not machine-friendly, 3) they use a non-standard format for data input and output, 4) they do not exploit standards to define application interface and message exchange, and 5) existing protocols for remote messaging are often not firewall-friendly. To overcome these issues, web services have emerged as a standard XML-based model for message exchange between heterogeneous applications. Web services engines have been developed to manage the configuration and execution of a web services workflow. 相似文献150.
A unique set of 11,008 onion expressed sequence tags reveals expressed sequence and genomic differences between the monocot orders Asparagales and Poales
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Kuhl JC Cheung F Yuan Q Martin W Zewdie Y McCallum J Catanach A Rutherford P Sink KC Jenderek M Prince JP Town CD Havey MJ 《The Plant cell》2004,16(1):114-125
Enormous genomic resources have been developed for plants in the monocot order Poales; however, it is not clear how representative the Poales are for the monocots as a whole. The Asparagales are a monophyletic order sister to the lineage carrying the Poales and possess economically important plants such as asparagus, garlic, and onion. To assess the genomic differences between the Asparagales and Poales, we generated 11,008 unique ESTs from a normalized cDNA library of onion. Sequence analyses of these ESTs revealed microsatellite markers, single nucleotide polymorphisms, and homologs of transposable elements. Mean nucleotide similarity between rice and the Asparagales was 78% across coding regions. Expressed sequence and genomic comparisons revealed strong differences between the Asparagales and Poales for codon usage and mean GC content, GC distribution, and relative GC content at each codon position, indicating that genomic characteristics are not uniform across the monocots. The Asparagales were more similar to eudicots than to the Poales for these genomic characteristics. 相似文献