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News Article | March 23, 2016
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.”


HONG KONG, Dec. 21, 2016 /PRNewswire/ -- Hong Kong Science and Technology Parks Corporation ("HKSTP") and Guangzhou Institutes of Biomedicine and Health ("GIBH") cohosted the second Hong Kong and Guangzhou International Conference on Stem Cell & Regenerative Medicine on December 16. During this high-profile event which was attended by HKSAR Chief Executive The Hon CY Leung and a number of major government officials, the Chinese Academy of Science ("CAS"), a research and development authority in Mainland China, announced the setting up of the Guangzhou Hong Kong Stem Cell and Regenerative Medicine Research Centre at Hong Kong Science Park ("HKSP"), under the auspices of its subsidiary GIBH. Remarking on this significant initiative, The Hon. Fanny Law, GBS, JP, Chairperson of HKSTP, said: "We see opportunities for Hong Kong to evolve into a cell therapy centre, capitalising on Hong Kong's world-class medical system, and credible clinical trial centres with data accepted by FDA, EMA as well as CFDA, which is unique to Hong Kong." "Our ambition is to grow an industry in advanced therapy medicinal products, leveraging on the complementary strengths of Hong Kong, Guangzhou and Shenzhen, to form a leading 'Cell Therapy Valley' where the latest technologies are being developed, tested and implemented for the benefit of ethnic Chinese patients who suffer from existing incurable diseases," Mrs Law said. Prof Bai Chunli, President of CAS, said that the proposed research centre "will create the environment for stakeholders to make connections, share information and tap into each other's academic resources for the benefits of the world", and the centre has the potential to mature into a platform that will "strengthen existing partnerships, maximise innovation capacities and reinforce strategic co-operations of the science and technology communities between China and Hong Kong". GIBH is yet another world-renowned biomedicine research authority to set up its base in HKSP, after Karolinska Institutet, which opened the Hong Kong node of its dedicated regenerative medicine facility, the Ming Wai Lau Centre for Reparative Medicine, at HKSP in October 2016. HKSP is also home to 14 other stem cell and cell therapy companies from around the world. At the conference, expert speakers shared their latest research discoveries and insights in stem cell therapy for liver fibrosis, cell therapy for diabetes, and epigenetic fingerprinting and tissue engineering that facilitate pre-clinical drug discovery for Alzheimer's disease, reaffirming stem cell therapy holds great promise in curing debilitating diseases such as Parkinson's, Alzheimer's, spinal cord injury, diabetes and stroke and presenting great potentials for researchers in the field. As HKSTP is stepping up its effort to develop HKSP and Hong Kong as the ideal R&D base and hub for stem cell research and regenerative medicine, Mrs Law pointed out at the conference that a set of clear regulatory guidelines that facilitates clinical translation of advanced cell therapies while safeguarding the interests of patients is fundamental for realising this vision. World stem cell experts from the US, the UK, Mainland China, Europe and Australia attending the Stem Cell Conference joined Hong Kong colleagues in a pre-event round-table discussion to recommend the way forward for the regulatory environment in Hong Kong, referencing the regulatory structures in other countries. Group convenor Prof Marc Turner, who is the Medical Director of Scottish National Blood Transfusion Service, reported at the conference that the group suggested a single stream of legislation covering supply of starting materials, manufacture, administration and follow up. "Since Hong Kong has a relatively clear space, our advice would be to join up tissue and cell legislation with cellular therapy and advanced therapy legislation all in one piece, to be consistent. That would be the most coherent way to do it, therefore in the longer term it will be the most efficient," he said. HKSTP Chief Executive Officer Mr Albert Wong said: "HKSTP has established a strong rapport with the global biomedical community. This is apparent in the sterling speaker lineup of our Stem Cell Conference. Stem cell R&D is a key pillar for supporting healthy ageing, which is one of the key priorities of HKSTP. We will redouble efforts in building the cell therapy ecosystem in Science Park and help the community excel and develop, so that we can ride on the global momentum of stem cell R&D to move forward in the advanced therapy value chain, as Hong Kong endeavours to develop an appropriate regulatory environment for this field." Comprising Science Park, InnoCentre and Industrial Estates, Hong Kong Science & Technology Parks Corporation (HKSTP) is a statutory body dedicated to building a vibrant innovation and technology ecosystem to connect stakeholders, nurture technology talents, facilitate collaboration, and catalyse innovations to deliver social and economic benefits to Hong Kong and the region. Established in May 2001, HKSTP has been driving the development of Hong Kong into a regional hub for innovation and growth in several focused clusters including Electronics, Information & Communications Technology, Green Technology, Biomedical Technology, Materials and Precision Engineering. We enable science and technology companies to nurture ideas, innovate and grow, supported by our R&D facilities, infrastructure, and market-led laboratories and technical centres with professional support services. We also offer value added services and comprehensive incubation programmes for technology start-ups to accelerate their growth. Technology businesses benefit from our specialised services and infrastructure at Science Park for applied research and product development; enterprises can find creative design support at InnoCentre; while skill-intensive businesses are served by our three industrial estates at Tai Po, Tseung Kwan O and Yuen Long. More information about HKSTP is available at www.hkstp.org.


News Article | April 6, 2016
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.


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.


Zhou T.,CAS Guangzhou Institute of Biomedicine and Health | Benda C.,CAS Guangzhou Institute of Biomedicine and Health | Dunzinger S.,University of Natural Resources and Life Sciences, Vienna | Huang Y.,CAS Guangzhou Institute of Biomedicine and Health | And 15 more authors.
Nature Protocols | Year: 2012

Human induced pluripotent stem cells (iPSCs) have been generated with varied efficiencies from multiple tissues. Yet, acquiring donor cells is, in most instances, an invasive procedure that requires laborious isolation. Here we present a detailed protocol for generating human iPSCs from exfoliated renal epithelial cells present in urine. This method is advantageous in many circumstances, as the isolation of urinary cells is simple (30 ml of urine are sufficient), cost-effective and universal (can be applied to any age, gender and race). Moreover, the entire procedure is reasonably quick - around 2 weeks for the urinary cell culture and 3-4 weeks for the reprogramming - and the yield of iPSC colonies is generally high - up to 4% using retroviral delivery of exogenous factors. Urinary iPSCs (UiPSCs) also show excellent differentiation potential, and thus represent a good choice for producing pluripotent cells from normal individuals or patients with genetic diseases, including those affecting the kidney. © 2012 Nature America, Inc.


Wu Q.,University of Minnesota | Wu Q.,Center for Systems Biology | Hwang C.K.,University of Minnesota | Zheng H.,University of Minnesota | And 8 more authors.
FASEB Journal | Year: 2013

μ-Opioid μeceptor (MOR) level is directly related to the function of opioid drugs, such as morphine and fentanyl. Although agonist treatment generally does not affect transcription of mor, previous studies suggest that morphine can affect the translation efficiency of MOR transcript via microRNAs (miRNAs). On the basis of miRNA microarray analyses of the hippocampal total RNA isolated from mice chronically treated with opioid μgonists, we found a miRNA (miR-339-3p) that was consistently and specifically increased by morphine (2-fold) and by fentanyl (3.8- fold). miR-339-3p bound to the MOR 3=-UTR and specifically suppressed reporter activity. Suppression was blunted by adding miR-339-3p inhibitor or mutating the miR-339-3p target site. In cells endogenously expressing MOR, miR-339-3p inhibited the production of MOR protein by destabilizing MOR mRNA. Up-regulation of miR-339-3p by fentanyl (EC50=0.75 nM) resulted from an increase in primary miRNA transcript. Mapping of the miR-339-3p primary RNA and its promoter revealed that the primary miR-339-3p was embedded in a noncoding 3=-UTR region of an unknown host gene and was coregulated by the host promoter. The identified promoter was activated by opioid agonist treatment (10 nM fentanyl or 10 μM morphine), a specific effect blocked by the opioid antagonist naloxone (10 μM). Taken together, these results suggest that miR-339-3p may serve as a negative feedback modulator of MOR signals by regulating intracellular MOR biosynthesis. © FASEB.


PubMed | Johns Hopkins University, Tongji University, Guangzhou Institutes of Biomedicine and Health and CAS Guangzhou Institute of Biomedicine and Health
Type: | Journal: Scientific reports | Year: 2015

Nucleosome positioning and histone modification play a critical role in gene regulation, but their role during reprogramming has not been fully elucidated. Here, we determined the genome-wide nucleosome coverage and histone methylation occupancy in mouse embryonic fibroblasts (MEFs), induced pluripotent stem cells (iPSCs) and pre-iPSCs. We found that nucleosome occupancy increases in promoter regions and decreases in intergenic regions in pre-iPSCs, then recovers to an intermediate level in iPSCs. We also found that nucleosomes in pre-iPSCs are much more phased than those in MEFs and iPSCs. During reprogramming, nucleosome reorganization and histone methylation around transcription start sites (TSSs) are highly coordinated with distinctively transcriptional activities. Bivalent promoters gradually increase, while repressive promoters gradually decrease. High CpG (HCG) promoters of active genes are characterized by nucleosome depletion at TSSs, while low CpG (LCG) promoters exhibit the opposite characteristics. In addition, we show that vitamin C (VC) promotes reorganizations of canonical, H3K4me3- and H3K27me3-modified nucleosomes on specific genes during transition from pre-iPSCs to iPSCs. These data demonstrate that pre-iPSCs have a more open and phased chromatin architecture than that of MEFs and iPSCs. Finally, this study reveals the dynamics and critical roles of nucleosome positioning and chromatin organization in gene regulation during reprogramming.


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.


PubMed | University of Warsaw, Guangzhou Institutes of Biomedicine and Health, Genome Institute of Singapore and University of Hong Kong
Type: | Journal: Scientific reports | Year: 2015

The SOXE transcription factors SOX8, SOX9 and SOX10 are master regulators of mammalian development directing sex determination, gliogenesis, pancreas specification and neural crest development. We identified a set of palindromic SOX binding sites specifically enriched in regulatory regions of melanoma cells. SOXE proteins homodimerize on these sequences with high cooperativity. In contrast to other transcription factor dimers, which are typically rigidly spaced, SOXE group proteins can bind cooperatively at a wide range of dimer spacings. Using truncated forms of SOXE proteins, we show that a single dimerization (DIM) domain, that precedes the DNA binding high mobility group (HMG) domain, is sufficient for dimer formation, suggesting that DIM : HMG rather than DIM:DIM interactions mediate the dimerization. All SOXE members can also heterodimerize in this fashion, whereas SOXE heterodimers with SOX2, SOX4, SOX6 and SOX18 are not supported. We propose a structural model where SOXE-specific intramolecular DIM:HMG interactions are allosterically communicated to the HMG of juxtaposed molecules. Collectively, SOXE factors evolved a unique mode to combinatorially regulate their target genes that relies on a multifaceted interplay between the HMG and DIM domains. This property potentially extends further the diversity of target genes and cell-specific functions that are regulated by SOXE proteins.


Xu L.,CAS South China Botanical Garden | He Z.,Guangzhou Institutes of Biomedicine and Health | Xue J.,CAS South China Botanical Garden | Chen X.,Guangzhou Institutes of Biomedicine and Health | Wei X.,CAS South China Botanical Garden
Journal of Natural Products | Year: 2010

Six new β-resorcylic acid lactones (1-6), named paecilomycins A-F, and five known compounds, aigilomycin B (7), zeaenol (8), aigialomycin D (9), aigialomycin F (10), and aigialospirol, were isolated from the mycelial solid culture of Paecilomyces sp. SC0924. Their structures were elucidated by extensive NMR analysis, single-crystal X-ray study, and chemical correlations. Compounds 5 and 10 exhibited antiplasmodial activity against Plasmodium falciparum line 3D7 with IC50 values of 20.0 and 10.9 nM, respectively, and compounds 5-7 showed moderate activity against the P. falciparum line Dd2. © 2010 The American Chemical Society and American Society of Pharmacognosy.

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