Identification of human brain tumour initiating cells

The cancer stem cell (CSC) hypothesis suggests that neoplastic clones are maintained exclusively by a rare fraction of cells with stem cell properties. Although the existence of CSCs in human leukaemia is established, little evidence exists for CSCs in solid tumours, except for breast cancer. Recently, we prospectively isolated a CD133+ cell subpopulation from human brain tumours that exhibited stem cell properties in vitro. However, the true measures of CSCs are their capacity for self renewal and exact recapitulation of the original tumour. Here we report the development of a xenograft assay that identified human brain tumour initiating cells that initiate tumours in vivo. Only the CD133+ brain tumour fraction contains cells that are capable of tumour initiation in NOD-SCID (non-obese diabetic, severe combined immunodeficient) mouse brains. Injection of as few as 100 CD133+ cells produced a tumour that could be serially transplanted and was a phenocopy of the patient's original tumour, whereas injection of 10(5) CD133- cells engrafted but did not cause a tumour. Thus, the identification of brain tumour initiating cells provides insights into human brain tumour pathogenesis, giving strong support for the CSC hypothesis as the basis for many solid tumours, and establishes a previously unidentified cellular target for more effective cancer therapies.     

Overproduction of p53 antigen makes established cells highly tumorigenic

The p53 cellular tumour antigen, long known to be overproduced in a variety of neoplastically transformed cells, was recently shown to be directly involved in transformation. Thus, p53 can complement activated Ha-ras in transforming secondary rat embryo fibroblasts into grossly altered, tumorigenic cells. Moreover, p53 can also be shown to possess immortalizing activity. Our previous results indicated, however, that the contribution of p53 to the transformation was not synonymous with immortalization, suggesting that the two activities of the protein are probably separable. We demonstrate here that this is indeed the case, as overproduction of p53 in an established cell line, while not causing gross morphological changes, endows these cells with an overt tumorigenic potential. Furthermore, the tumorigenic efficiency of such cell lines may be correlated with the extent of p53 over-production.     

大肠杆菌表达的成骨蛋白-1的复性研究

带有rhOP-1／pBV221-的E．coli表达得到的rhOP-1以不溶的包涵体形式存在,用高浓度的变性剂溶解后,经过DEAE-FF纯化,得到高纯度的目的蛋白。利用各种不同方法对蛋白质进行复性,并对复性结果进行比较,发现添加氧化还原剂最有助于二聚体的形成,这是由蛋白质分子的结构和理化性质决定的。     

Bone morphogenetic protein 2 improves patellar tendon healing by promoting migration and proliferation of tenocytes

The repair of injured tendons remains a great challenge because of the poor intrinsic healing capacity of tendons. In this study, we examined the spatiotemporal expression pattern of the bone morphogenetic protein 2 (bmp-2) gene in normal and experimentally injured rat patellar tendons. We also investigated the ability of exogenously applied BMP-2 to promote patellar tendon healing. In situ hybridization with bmp-2 and alk-6 (bmp-2 receptor) antisense riboprobes revealed that both genes were normally expressed at low levels in intact rat tendons. However, bmp-2 expression was significantly upregulated in tenocytes found in the wound site at 7 d and later following tendon injury. In addition, it was found that bmp-2 was expressed in cultured patellar tenocytes. Appli- cation of exogenous BMP-2 to the tendon wound site significantly enhanced tendon repair. Moreover, in vitro and in vivo studies further demonstrated that BMP-2 enhanced tenocyte proliferation and migration to the wound site. The detectable amount of BMP-2 in normal tendons suggests that a basal level of bmp-2 expression was likely present to maintain the normal functions of the patellar tendon. Injury to the tendon induced increased bmp-2 expression intrinsically, but the expression level was insufficient for proper tendon repair. Our findings indicate that it is possible to significantly improve tendon healing by applying exogenous BMP-2 to the wound site, inferring that this protein could be developed as a potential therapeutic reagent for the treatment of damaged tendons.     

Bacteriophages inhibit degradation of abnormal proteins in E. coli.

On infection of Escherichia coli cells by bacteriophages T4, T5 or T7, the degradation of E. coli protein fragments and abnormal proteins is inhibited. Normal E. coli proteins, however, continue to be degraded at their usual rates. T4 early proteins (s) is needed to inhibit the turnover of abnormal proteins in T4-infected E. coli cells.     

Bone marrow cells adopt the phenotype of other cells by spontaneous cell fusion

Recent studies have demonstrated that transplanted bone marrow cells can turn into unexpected lineages including myocytes, hepatocytes, neurons and many others. A potential problem, however, is that reports discussing such 'transdifferentiation' in vivo tend to conclude donor origin of transdifferentiated cells on the basis of the existence of donor-specific genes such as Y-chromosome markers. Here we demonstrate that mouse bone marrow cells can fuse spontaneously with embryonic stem cells in culture in vitro that contains interleukin-3. Moreover, spontaneously fused bone marrow cells can subsequently adopt the phenotype of the recipient cells, which, without detailed genetic analysis, might be interpreted as 'dedifferentiation' or transdifferentiation.     

Energetics and the evolution of human brain size

The human brain stands out among mammals by being unusually large. The expensive-tissue hypothesis explains its evolution by proposing a trade-off between the size of the brain and that of the digestive tract, which is smaller than expected for a primate of our body size. Although this hypothesis is widely accepted, empirical support so far has been equivocal. Here we test it in a sample of 100 mammalian species, including 23 primates, by analysing brain size and organ mass data. We found that, controlling for fat-free body mass, brain size is not negatively correlated with the mass of the digestive tract or any other expensive organ, thus refuting the expensive-tissue hypothesis. Nonetheless, consistent with the existence of energy trade-offs with brain size, we find that the size of brains and adipose depots are negatively correlated in mammals, indicating that encephalization and fat storage are compensatory strategies to buffer against starvation. However, these two strategies can be combined if fat storage does not unduly hamper locomotor efficiency. We propose that human encephalization was made possible by a combination of stabilization of energy inputs and a redirection of energy from locomotion, growth and reproduction.     

Transcranial magnetic stimulation and the human brain

Transcranial magnetic stimulation (TMS) is rapidly developing as a powerful, non-invasive tool for studying the human brain. A pulsed magnetic field creates current flow in the brain and can temporarily excite or inhibit specific areas. TMS of motor cortex can produce a muscle twitch or block movement; TMS of occipital cortex can produce visual phosphenes or scotomas. TMS can also alter the functioning of the brain beyond the time of stimulation, offering potential for therapy.     

Unlocking the potential of the human genome with RNA interference

The discovery of RNA interference (RNAi) may well be one of the transforming events in biology in the past decade. RNAi can result in gene silencing or even in the expulsion of sequences from the genome. Harnessed as an experimental tool, RNAi has revolutionized approaches to decoding gene function. It also has the potential to be exploited therapeutically, and clinical trials to test this possibility are already being planned.     

Interactive memory systems in the human brain.

Learning and memory in humans rely upon several memory systems, which appear to have dissociable brain substrates. A fundamental question concerns whether, and how, these memory systems interact. Here we show using functional magnetic resonance imaging (FMRI) that these memory systems may compete with each other during classification learning in humans. The medial temporal lobe and basal ganglia were differently engaged across subjects during classification learning depending upon whether the task emphasized declarative or nondeclarative memory, even when the to-be-learned material and the level of performance did not differ. Consistent with competition between memory systems suggested by animal studies and neuroimaging, activity in these regions was negatively correlated across individuals. Further examination of classification learning using event-related FMRI showed rapid modulation of activity in these regions at the beginning of learning, suggesting that subjects relied upon the medial temporal lobe early in learning. However, this dependence rapidly declined with training, as predicted by previous computational models of associative learning.