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911.
The construction of stable blood vessels is a fundamental challenge for tissue engineering in regenerative medicine. Although certain genes can be introduced into vascular cells to enhance their survival and proliferation, these manipulations may be oncogenic. We show here that a network of long-lasting blood vessels can be formed in mice by co-implantation of vascular endothelial cells and mesenchymal precursor cells, by-passing the need for risky genetic manipulations. These networks are stable and functional for one year in vivo. 相似文献
912.
Whole-genome duplication followed by massive gene loss and specialization has long been postulated as a powerful mechanism of evolutionary innovation. Recently, it has become possible to test this notion by searching complete genome sequence for signs of ancient duplication. Here, we show that the yeast Saccharomyces cerevisiae arose from ancient whole-genome duplication, by sequencing and analysing Kluyveromyces waltii, a related yeast species that diverged before the duplication. The two genomes are related by a 1:2 mapping, with each region of K. waltii corresponding to two regions of S. cerevisiae, as expected for whole-genome duplication. This resolves the long-standing controversy on the ancestry of the yeast genome, and makes it possible to study the fate of duplicated genes directly. Strikingly, 95% of cases of accelerated evolution involve only one member of a gene pair, providing strong support for a specific model of evolution, and allowing us to distinguish ancestral and derived functions. 相似文献
913.
Senescence may result from an optimal balance between current reproductive investment and bodily repair processes required for future reproduction, a theoretical prediction difficult to prove especially in large, long-lived animals. Here we propose that teeth that have fixed dimensions early in life, but that wear during chewing, can be taken as a measure of total lifetime 'repair', and their wear rate as a measure of current expenditure in performance. Our approach also considers the sexual selection process to investigate the advance of senescence in males compared with females, when selection favouring competition over mates reduces the reproductive lifespan of males. We studied carcasses of 2,141 male and 739 female red deer (Cervus elaphus) of different ages, finding that male molariform teeth emerged at a far smaller size than expected from body size dimorphism. This led to higher workload, steeper wear rate and earlier depletion of male teeth than in females, in concordance with sex-specific patterns of lifetime performance and reproduction. These findings provide the empirical support for the disposable-soma hypothesis of senescence, which predicts that investment in bodily repair will decrease when the return from this investment may not be realized as a result of other causes that limit survival or reproduction. 相似文献
914.
915.
Douma S Van Laar T Zevenhoven J Meuwissen R Van Garderen E Peeper DS 《Nature》2004,430(7003):1034-1039
Metastasis is a major factor in the malignancy of cancers, and is often responsible for the failure of cancer treatment. Anoikis (apoptosis resulting from loss of cell-matrix interactions) has been suggested to act as a physiological barrier to metastasis; resistance to anoikis may allow survival of cancer cells during systemic circulation, thereby facilitating secondary tumour formation in distant organs. In an attempt to identify metastasis-associated oncogenes, we designed an unbiased, genome-wide functional screen solely on the basis of anoikis suppression. Here, we report the identification of TrkB, a neurotrophic tyrosine kinase receptor, as a potent and specific suppressor of caspase-associated anoikis of non-malignant epithelial cells. By activating the phosphatidylinositol-3-OH kinase/protein kinase B pathway, TrkB induced the formation of large cellular aggregates that survive and proliferate in suspension. In mice, these cells formed rapidly growing tumours that infiltrated lymphatics and blood vessels to colonize distant organs. Consistent with the ability of TrkB to suppress anoikis, metastases--whether small vessel infiltrates or large tumour nodules--contained very few apoptotic cells. These observations demonstrate the potent oncogenic effects of TrkB and uncover a specific pro-survival function that may contribute to its metastatic capacity, providing a possible explanation for the aggressive nature of human tumours that overexpress TrkB. 相似文献
916.
Expression of lysine-rich protein gene and analysis of lysine content in transgenic wheat 总被引:2,自引:0,他引:2
MENGChaomin CHENXuqing LIANGRongqi YANGFengping ZHANGLiquan ZHANGXiaodong CHENTianyou S.S.M.Sun 《科学通报(英文版)》2004,49(19):2053-2057
Expression vector pBPC102, which carries winged bean lysine-rich protein (wblrp) gene and dihydropicolinate synthase (DHDPS) gene, was transferred into hexaploid winter wheat cv. Jinghua No.l, Jing411, You899 and Yangnongl5 explants of immature inflorescence and immature embryos by particle bombardment. More than 100 transgenic plants were obtained under the selection of s-(2-aminoethyl)-L-cysteine (AEC). Confirmed transgenic plants of To and TI generation by PCR and PCR-Southern blotting analyses showed successful integration of wblrp gene into wheat genome. Analysis of transgenic plant lines of T2 by Northern dot-blotting showed good expression of wblrp gene in offspring seed. The content of free lysine in leaves, contents of bound lysine and total proteins in seeds of T2 transgenie wheat lines were determined and analyzed. Among 34 tested transgenic lines, levels of free lysine content in leaves of 9 transgenic lines are 2~3times higher than un-trans-formed wild-type cultivars. Among 17 analyzed transgenic lines, bound lysine content of 4 transgenic lines is more than 10% higher than that of wild-type cultivars. Our research suggests that introducing wblrp gene into wheat is an effective way to improve its nutrition quality. 相似文献
917.
This article uses data from the 1971 and 2001 Censuses, the 1999-2003 Labour Force Survey and the 1977 to 2002 International Passenger Survey to investigate the migration processes contributing to the age structure and ageing of the UK's overseas-born population. Overall almost half of recent decades' immigrants to the UK emigrate again within five years of arrival, but with large variation by overseas country of birth. Between half and two thirds of the immigrants born in the continental European Union, North America and Oceania emigrate again within five years, while 15 per cent of those born in the Indian subcontinent do so. Significant cumulative emigration more than five years after arrival is seen among earlier immigrants from the Indian subcontinent, the Caribbean Commonwealth and Europe. Large country-of-origin variations in the ratio of pension-age population to working-age population primarily reflect the country composition of immigration streams 30 or more years before. 相似文献
918.
919.
Isolation of human epidermal stem cells by adherence and the reconstruction of skin equivalents 总被引:47,自引:0,他引:47
Kim DS Cho HJ Choi HR Kwon SB Park KC 《Cellular and molecular life sciences : CMLS》2004,61(21):2774-2781
The isolation of human epidermal stem cells is critical for their clinical applications. In the present study, we isolated three populations of epidermal keratinocytes according to their ability to adhere to collagen type IV: i.e., rapidly adhering (RA), slowly adhering (SA), and non-adhering (NA) cells. The aim of this study was to characterize RA cells and to investigate the possibility of using these cells for epidermis reconstruction. To identify RA cells, flow cytometric analysis was performed using anti-6 integrin and anti-CD71 antibodies. RA cells express high levels of 6 integrin and low levels of CD71, which are considered as markers of an epidermal stem cell nature. Furthermore, electron microscopy showed that RA cells are small and have a high nuclear to cytoplasmic ratio, whereas SA and NA cells have well-developed cellular organelles and abundant tonofilaments. Western blot analysis showed that RA cells are slow cycling and express p63, a putative epidermal stem cell marker, whereas SA and NA cells express c-Myc, which is known to regulate stem cell fate. To compare epidermal regenerative abilities, skin equivalents (SEs) were made using RA, SA, and NA cells. The epidermis constructed from RA cells was well formed compared to those formed from SA or NA cells. In addition, only SEs with RA cells expressed 6 integrin and 1 integrin at the basal layer. These results indicate that RA cells represent epidermal stem cells and are predominately comprised of stem cells. Therefore, the isolation of RA cells using a simple technique offers a potential route to their clinical application, because they are easily isolated and provide a high yield of epidermal stem cells.Received 2 July 2004; received after revision 20 August 2004; accepted 10 September 2004 相似文献
920.
Cecchi C Liguri G Fiorillo C Bogani F Gambassi M Giannoni E Cirri P Baglioni S Ramponi G 《Cellular and molecular life sciences : CMLS》2004,61(14):1775-1784
An acylphosphatase (AcPase) overexpression study was carried out on SH-SY5Y neuroblastoma cells, using a
green fluorescent fusion protein (AcP-GFP), with GFP acting as a reporter protein. The cellular proliferation rate
was significantly reduced by overexpression of AcPase by a factor of ten. In contrast, clones transfected with two
inactive AcPase mutants showed a growth rate comparable to control cells. This suggests that AcPase catalyzes the
proliferative down-regulation. AcPase-overexpressing clones showed a physiological mortality rate as assessed by an
MTT reduction test and by evaluation of necrotic markers. DNA fragmentation analysis and assays of caspase-3 and
poly (ADP-ribose) polymerase (PARP)-active fragments showed no evidence of any apoptotic pattern. AcPase
overexpression led to a marked increase in PARP activity as well as Bcl-2 content; these are commonly up-regulated
during differentiative processes in neuronal cells. In fact, the typical differentiation marker,
growth-associated-protein 43, was significantly up-regulated. Microscopic observations also showed a clear
increase in the differentiative phenotype in AcPase-overexpressing cells. Our results clearly show that AcPase
plays a primary causative role in neuronal differentiation.Received 3 May 2004; accepted 25 May 2004 相似文献