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Liang Y.,Sun Yat Sen University | Zhong Z.,Sun Yat Sen University | Huang Y.,Sun Yat Sen University | Deng W.,University of Hong Kong | And 6 more authors.
Journal of Biological Chemistry | Year: 2010

The existence of cancer stem cells (CSCs) or stem-like cancer cells (SLCCs) is regarded as the cause of tumor formation and recurrence. However, the origin of such cells remains controversial with two competing hypotheses:CSCsare either transformed from tissue adult stem cells or dedifferentiated from transformed progenitor cells. Compelling evidence has determined the chromosomal aneuploidy to be one of the hallmarks of cancer cells, indicating genome instability plays an important role in tumorigenesis, for which CSCs are believed to be the initiator. To gain direct evidence that genomic instability is involved in the induction of SLCCs, we utilized multiple approaches to enhance genomic instability and monitored the percentage of SLCC in cultured cancer cells. Using side population (SP) cells as a marker for SLCC in human nasopharyngeal carcinoma (NPC) and CD133 for human neuroblastoma cells,wefound thatDNAdamageinducers,UVand mitomycin C were capable of increasing SP cells in NPCCNE-2 and neuroblastoma SKN-SH cells. Likewise, either overexpression of a key regulator of cell cycle, Mad2, or knock down of Aurora B, an important kinase in mitosis, or Cdh1, a key E3 ligase in cell cycle, resulted in a significant increase of SP cells in CNE-2. More interestingly, enrichment of SP cells was observed in recurrent tumor tissues as compared with the primary tumor in the same NPC patients. Our study thus suggested that, beside transformation of tissue stem cells leading to CSC generation, genomic instability could be another potential mechanism resulting in SLCC formation, especially at tumor recurrence stage. © 2010 by The American Society for Biochemistry and Molecular Biology, Inc.


Wong C.-M.,University of Hong Kong | Wang Y.,University of Hong Kong | Lee J.T.H.,University of Hong Kong | Huang Z.,University of Hong Kong | And 3 more authors.
Journal of Biological Chemistry | Year: 2014

Adropin is a highly conserved polypeptide that has been suggested to act as an endocrine factor that plays important roles in metabolic regulation, insulin sensitivity, and endothelial functions. However, in this study, we provide evidence demonstrating that adropin is a plasma membrane protein expressed abundantly in the brain. Using a yeast two-hybrid screening approach, we identified NB-3/Contactin 6, a brain-specific, non-canonical, membrane-tethered Notch1 ligand, as an interaction partner of adropin. Furthermore, this interaction promotes NB3-induced activation of Notch signaling and the expression of Notch target genes. We also generated and characterized adropin knockout mice to explore the role of adropin in vivo. Adropin knockout mice exhibited decreased locomotor activity and impaired motor coordination coupled with defective synapse formation, a phenotype similar to NB-3 knockout mice. Taken together, our data suggest that adropin is a membrane- bound protein that interacts with the brain-specific Notch1 ligand NB3. It regulates physical activity and motor coordination via the NB-3/Notch signaling pathway and plays an important role in cerebellum development in mice. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.


News Article
Site: www.nature.com

In many cases of prostate cancer, the gene that encodes the androgen receptor becomes overactive and drives tumour progression, leading to fatal tumours that are resistant to castration therapy and contain high levels of ROR-γ. To understand its role, Hong-Wu Chen at the University of California, Davis, Yong Xu at the Guangzhou Institutes of Biomedicine and Health, China, and their team suppressed ROR-γ in cancerous cell lines and in human tumours transplanted into mice. This suppression blocked expression of the androgen-receptor gene and inhibited tumour growth, suggesting that ROR-γ is a crucial component of the castration-resistant tumours. Current therapies target androgen-receptor levels, but mutations in tumours often make them resistant to such treatment. Targeting ROR-γ could help patients to fight advanced prostate cancer.


News Article
Site: www.nature.com

From a slowing economy to geopolitical tensions in the South China Sea, it is a testing time for China’s ruling Communist party. But its science aspirations seem unbridled. On 16 March, China approved its 13th Five-Year Plan. A draft version, as well as statements by key politicians, make it clear that innovation through science and technology is a priority. China also intends for its research expenditure to rise to 2.5% of gross domestic product by 2020, from less than 2.2% over the past five years. Reductions in energy use and the development of low-carbon energy sources feature in the latest five-year plan. For some of the other themes that are set to shape Chinese research over the next five years, Nature spoke to a range of scientists. In 2012, ‘oceanauts’ aboard the research submersible Jiaolong descended more than 7,000 metres beneath the waves, marking China’s entry into an elite club of nations capable of reaching the hadal zone — the deepest part of the ocean, which begins at 6,000 metres below sea level. Over the next five years, Chinese scientists will build one crewed and one uncrewed submersible, according to a plan released by the science ministry in February, each of which can reach depths of 11,000 metres — the very bottom of the hadal zone. "For deep-sea technology, this five years will be a golden period,” says Cui Weicheng of the Hadal Science and Technology Research Center at Shanghai Ocean University. The uncrewed vessel will be similar to Nereus, the advanced US submersible that imploded in 2014 and will not be replaced. The crewed vessel will hold at least two people, more than the Deepsea Challenger, which took film director James Cameron on a solo dive to the deepest point of the Mariana Trench in 2012. The hadal zone is one of the most poorly studied habitats on Earth, and is home to mysterious tube worms, sea cucumbers and jellyfish. Researchers are also interested in its role in the carbon cycle, because the microbes there digest a surprising amount of organic matter. Chinese scientists hope to use both submersibles to explore the zone in more detail than ever before. Independently of the latest five-year plan, Cui has also developed a 'movable laboratory' (W. Cui et al. Meth. Oceanogr. 10, 178–193; 2014) composed of three landers, a robotic submersible and a crewed vehicle.The robotic submersible and first lander were tested down to 4,000 metres last October. A mother ship that controls the robot and landers is due to be launched on 24 March, and the first scientific expedition is planned for August, in the New Britain Trench off Papua New Guinea. Together these projects “could help shorten the gap" between Chinese ocean science and technology and the most advanced capabilities elsewhere, says Cui. The United States, Europe and Japan have each announced their own massive projects to map the brain, and China has had one in the works for several years. The latest five-year plan calls for brain science to be a priority — and most of the resources are expected to be channelled through the China project, which is due to be officially announced shortly, say Chinese researchers. The brain project is expected to focus on brain disease, in particular through studying animal models, as well as artificial intelligence. Scientists in China acknowledge that they are far behind the rest of the world in terms of top-level talent in brain science, but several factors could enable them to catch up. China’s neuroscience community is growing — the Chinese Neuroscience Society now has 6,000 members, compared to just 1,500 ten years ago; the country has tens of millions of patients with psychiatric or degenerative brain disease that will facilitate clinical studies; and it has hundreds of thousands of research monkeys. This last factor has already allowed Chinese researchers to take the lead in using gene-editing technologies to produce models of autism and other conditions. The bounty of research animals is also starting to draw interest from abroad — a new primate research centre in Shenzhen is being jointly established with the Cambridge-based Massachusetts Institute of Technology. With actor Jackie Chan and basketball star Yao Ming involved in campaigns attacking the trade in protected animals such as bears, which are milked for their bile, and elephants, targeted for their ivory, conservation has become a high profile issue in China. The latest five-year plan will launch efforts to protect the giant panda, tiger and Asian elephant in the wild, says Zhang Li, a conservation biologist at Beijing Normal University. "There will be a big budget to restore habitat for these species,” says Zhang. The projects will focus on corridors between protected areas that greatly increase the habitats by letting the animals move from one reserve to another. A biodiversity hotspot between Laos, Myanmar and the southwestern Chinese province of Yunnan requires protection in particular, says Stuart Pimm, a biodiversity specialist at Duke University in Durham, North Carolina. Forest there has been converted into rubber plantations, he says,  “and the level of hunting is worse than any place I’ve ever been”. But a focus on protecting pandas, elephants and tigers could leave other animals at risk, he pointed out in November (B. V. Li and S. L. Pimm Conserv. Biol. 30, 329–339; 2016). In the wake of the five-year plan, China will gain a new funding initiative called 'Stem Cell and Translational Research', according to stem cell researchers Pei Gang, president of Tongji University, and Pei Duanqing, director of the Guangzhou Institutes of Biomedicine and Health. The grants will be awarded under a new competitive review and evaluation process, replacing a system that critics said rewarded scientific and political connections rather than merit. Following the last five year plan, China invested roughly 3 billion yuan (about US$460 million) in stem-cell research. The pair say that there will be a big increase over the next five years but did not give exact figures. “Given the size of its population and the wide spectrum of unmet medical needs, China recognizes the promise of stem-cell and regenerative medicine as one of the key thrusts for modernizing its medical service system,” says Pei Gang. In a country that places great value on social harmony, air and water pollution are the trigger for an increasing number of protests. Under a plan that began in 2012, the government is already trying to reduce the levels of airborne parti­culate matter measuring less than 2.5 micrometres across (PM ), which are small enough to penetrate deep into the respiratory system. By 2017, it wants to achieve reductions of 25% in the Beijing area, 20% in the Yangtze River Delta and greater Shanghai area, and 15% in the Pearl River Delta. Major nationwide environmental initiatives outlined in the latest five-year plan will tackle transportation, clean energy and environmental protection, says Wei-xian Zhang, director of the State Key Lab for Pollution Control at Tongji University in Shanghai. The government will also target pollution black spots, such as smog in Beijing and fertilizer pollution in Lake Tai near Shanghai. Funding to control air pollution alone will increase by at least four times, says Zhang, and several new national laboratories focusing on clean energy and environmental research have also been funded for the next five years. “China is and will continue to be the largest market in air-, soil- and water-pollution control technologies,” says Zhang. “To some degree, the whole country will be a huge laboratory for environmental research, such as smog mitigation.”


Lu Q.,University of Hong Kong | Lu Q.,Hubei University for Nationalities | Yu M.,University of Hong Kong | Shen C.,University of Hong Kong | And 7 more authors.
PLoS ONE | Year: 2014

Human induced pluripotent stem cells (hiPSCs) have potential applications in cell replacement therapy and regenerative medicine. However, limited information is available regarding the immunologic features of iPSCs. In this study, expression of MHC and T cell co-stimulatory molecules in hiPSCs, and the effects on activation, proliferation and cytokine production in allogeneic human peripheral blood mononuclear cells were examined. We found that no-integrate hiPSCs had no MHC-II and T cell co-stimulatory molecules expressions but had moderate level of MHC-I and HLA-G expressions. In contrast to human skin fibroblasts (HSFs) which significantly induced allogeneic T cell activation and proliferation, hiPSCs failed to induce allogeneic CD45+ lymphocyte and CD8+ T cell activation and proliferation but could induce a low level of allogeneic CD4+ T cell proliferation. Unlike HSFs which induced allogeneic lymphocytes to produce high levels of IFN-γ, TNF-α and IL-17, hiPSCs only induced allogeneic lymphocytes to produce IL-2 and IL-10, and promote IL-10-secreting regulatory Tcell (Treg) generation. Our study suggests that the integration-free hiPSCs had low or negligible immunogenicity, which may result from their induction of IL-10-secreting Treg. © 2014 Lu et al.

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