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Ling Zhao

Bio: Ling Zhao is an academic researcher from Huazhong Agricultural University. The author has contributed to research in topics: Rabies virus & Rabies. The author has an hindex of 32, co-authored 113 publications receiving 6408 citations. Previous affiliations of Ling Zhao include Peking University & Sichuan University.
Topics: Rabies virus, Rabies, Virus, Medicine, Rabies vaccine


Papers
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Journal ArticleDOI
TL;DR: A quantitative model of aging is built using measurements at more than 450,000 CpG markers from the whole blood of 656 human individuals, aged 19 to 101, to measure the rate at which an individual's methylome ages, which is impacted by gender and genetic variants.

2,430 citations

Journal ArticleDOI
Lars G. Fritsche1, Lars G. Fritsche2, Wei Chen2, Wei Chen3  +182 moreInstitutions (60)
TL;DR: A collaborative genome-wide association study, including >17,100 advanced AMD cases and >60,000 controls of European and Asian ancestry, identifies 19 loci associated at P < 5 × 10−8, which show enrichment for genes involved in the regulation of complement activity, lipid metabolism, extracellular matrix remodeling and angiogenesis.
Abstract: Age-related macular degeneration (AMD) is a common cause of blindness in older individuals To accelerate the understanding of AMD biology and help design new therapies, we executed a collaborative genome-wide association study, including >17,100 advanced AMD cases and >60,000 controls of European and Asian ancestry We identified 19 loci associated at P < 5 × 10(-8) These loci show enrichment for genes involved in the regulation of complement activity, lipid metabolism, extracellular matrix remodeling and angiogenesis Our results include seven loci with associations reaching P < 5 × 10(-8) for the first time, near the genes COL8A1-FILIP1L, IER3-DDR1, SLC16A8, TGFBR1, RAD51B, ADAMTS9 and B3GALTL A genetic risk score combining SNP genotypes from all loci showed similar ability to distinguish cases and controls in all samples examined Our findings provide new directions for biological, genetic and therapeutic studies of AMD

745 citations

Journal Article
TL;DR: The hypothesis that circulating IGF-I levels play an important role in tumor development and metastasis in a mouse model of colon cancer is supported.
Abstract: It has been shown previously that slight elevations in serum levels of insulin-like growth factor-I (IGF-I) are correlated with an increased risk for developing prostate, breast, colon, and lung cancer. The aim of this study was to determine the role of serum IGF-I levels in the process of stimulating tumor growth and metastasis in a mouse model of colon cancer. Colon 38 adenocarcinoma tissue fragments were orthotopically transplanted by attachment to the surface of the cecum in control and liver-specific IGF-I-deficient (LID) mice in which serum IGF-I levels are 25% of that in control mice. A total of 156 male mice at 5 weeks of age (74 control mice and 82 LID mice) received tumor transplants. Mice were divided randomly into two groups; one group was injected i.p. with recombinant human IGF-I (2 mg/kg) twice daily for 6 weeks, and the other group received saline injections. IGF-I treatment increased the serum levels of IGF-I and IGFBP-3 in both control and LID mice. In the saline-injected group, the incidence of tumor growth on the cecum as well as the frequency of hepatic metastasis was significantly higher in control mice as compared with LID mice. Both control and LID mice treated with recombinant human IGF-I displayed significantly increased rates of tumor development on the cecum and metastasis to the liver, as compared with saline-injected mice. The number of metastatic nodules in the liver was significantly higher in control mice as compared with LID mice. The expression of vascular epithelial growth factor (VEGF) as well as vessel abundance in the cecum tumors was dependent on the levels of serum IGF-I. This study supports the hypothesis that circulating IGF-I levels play an important role in tumor development and metastasis.

376 citations

Journal ArticleDOI
TL;DR: An essential role of the Hippo-YAP pathway in Gq/11-induced tumorigenesis is revealed and YAP is suggested as a potential drug target for UM patients carrying mutations in GNAQ or GNA11.

364 citations

Journal ArticleDOI
30 Jul 2015-Nature
TL;DR: In this paper, the authors identify two distinct homozygous LSS missense mutations (W581R and G588S) in two families with extensive congenital cataracts.
Abstract: The human lens is comprised largely of crystallin proteins assembled into a highly ordered, interactive macro-structure essential for lens transparency and refractive index. Any disruption of intra- or inter-protein interactions will alter this delicate structure, exposing hydrophobic surfaces, with consequent protein aggregation and cataract formation. Cataracts are the most common cause of blindness worldwide, affecting tens of millions of people1, and currently the only treatment is surgical removal of cataractous lenses. The precise mechanisms by which lens proteins both prevent aggregation and maintain lens transparency are largely unknown. Lanosterol is an amphipathic molecule enriched in the lens. It is synthesized by lanosterol synthase (LSS) in a key cyclization reaction of a cholesterol synthesis pathway. Here we identify two distinct homozygous LSS missense mutations (W581R and G588S) in two families with extensive congenital cataracts. Both of these mutations affect highly conserved amino acid residues and impair key catalytic functions of LSS. Engineered expression of wild-type, but not mutant, LSS prevents intracellular protein aggregation of various cataract-causing mutant crystallins. Treatment by lanosterol, but not cholesterol, significantly decreased preformed protein aggregates both in vitro and in cell-transfection experiments. We further show that lanosterol treatment could reduce cataract severity and increase transparency in dissected rabbit cataractous lenses in vitro and cataract severity in vivo in dogs. Our study identifies lanosterol as a key molecule in the prevention of lens protein aggregation and points to a novel strategy for cataract prevention and treatment.

331 citations


Cited by
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28 Jul 2005
TL;DR: PfPMP1)与感染红细胞、树突状组胞以及胎盘的单个或多个受体作用,在黏附及免疫逃避中起关键的作�ly.
Abstract: 抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1(PfPMP1)与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用,在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员,通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

18,940 citations

01 Jun 2012
TL;DR: SPAdes as mentioned in this paper is a new assembler for both single-cell and standard (multicell) assembly, and demonstrate that it improves on the recently released E+V-SC assembler and on popular assemblers Velvet and SoapDeNovo (for multicell data).
Abstract: The lion's share of bacteria in various environments cannot be cloned in the laboratory and thus cannot be sequenced using existing technologies. A major goal of single-cell genomics is to complement gene-centric metagenomic data with whole-genome assemblies of uncultivated organisms. Assembly of single-cell data is challenging because of highly non-uniform read coverage as well as elevated levels of sequencing errors and chimeric reads. We describe SPAdes, a new assembler for both single-cell and standard (multicell) assembly, and demonstrate that it improves on the recently released E+V-SC assembler (specialized for single-cell data) and on popular assemblers Velvet and SoapDeNovo (for multicell data). SPAdes generates single-cell assemblies, providing information about genomes of uncultivatable bacteria that vastly exceeds what may be obtained via traditional metagenomics studies. SPAdes is available online ( http://bioinf.spbau.ru/spades ). It is distributed as open source software.

10,124 citations

Journal ArticleDOI
Daniel J. Klionsky1, Kotb Abdelmohsen2, Akihisa Abe3, Joynal Abedin4  +2519 moreInstitutions (695)
TL;DR: In this paper, the authors present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macro-autophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes.
Abstract: In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. For example, a key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process versus those that measure flux through the autophagy pathway (i.e., the complete process including the amount and rate of cargo sequestered and degraded). In particular, a block in macroautophagy that results in autophagosome accumulation must be differentiated from stimuli that increase autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. It is worth emphasizing here that lysosomal digestion is a stage of autophagy and evaluating its competence is a crucial part of the evaluation of autophagic flux, or complete autophagy. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. Along these lines, because of the potential for pleiotropic effects due to blocking autophagy through genetic manipulation, it is imperative to target by gene knockout or RNA interference more than one autophagy-related protein. In addition, some individual Atg proteins, or groups of proteins, are involved in other cellular pathways implying that not all Atg proteins can be used as a specific marker for an autophagic process. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular assays, we hope to encourage technical innovation in the field.

5,187 citations

Journal ArticleDOI
TL;DR: It is proposed that DNA methylation age measures the cumulative effect of an epigenetic maintenance system, and can be used to address a host of questions in developmental biology, cancer and aging research.
Abstract: It is not yet known whether DNA methylation levels can be used to accurately predict age across a broad spectrum of human tissues and cell types, nor whether the resulting age prediction is a biologically meaningful measure. I developed a multi-tissue predictor of age that allows one to estimate the DNA methylation age of most tissues and cell types. The predictor, which is freely available, was developed using 8,000 samples from 82 Illumina DNA methylation array datasets, encompassing 51 healthy tissues and cell types. I found that DNA methylation age has the following properties: first, it is close to zero for embryonic and induced pluripotent stem cells; second, it correlates with cell passage number; third, it gives rise to a highly heritable measure of age acceleration; and, fourth, it is applicable to chimpanzee tissues. Analysis of 6,000 cancer samples from 32 datasets showed that all of the considered 20 cancer types exhibit significant age acceleration, with an average of 36 years. Low age-acceleration of cancer tissue is associated with a high number of somatic mutations and TP53 mutations, while mutations in steroid receptors greatly accelerate DNA methylation age in breast cancer. Finally, I characterize the 353 CpG sites that together form an aging clock in terms of chromatin states and tissue variance. I propose that DNA methylation age measures the cumulative effect of an epigenetic maintenance system. This novel epigenetic clock can be used to address a host of questions in developmental biology, cancer and aging research.

4,233 citations

Journal ArticleDOI
TL;DR: A suite of computational tools that incorporate state-of-the-art statistical techniques for the analysis of DNAm data are described that include methods for preprocessing, quality assessment and detection of differentially methylated regions from the kilobase to the megabase scale.
Abstract: Motivation The recently released Infinium HumanMethylation450 array (the '450k' array) provides a high-throughput assay to quantify DNA methylation (DNAm) at ∼450 000 loci across a range of genomic features. Although less comprehensive than high-throughput sequencing-based techniques, this product is more cost-effective and promises to be the most widely used DNAm high-throughput measurement technology over the next several years. Results Here we describe a suite of computational tools that incorporate state-of-the-art statistical techniques for the analysis of DNAm data. The software is structured to easily adapt to future versions of the technology. We include methods for preprocessing, quality assessment and detection of differentially methylated regions from the kilobase to the megabase scale. We show how our software provides a powerful and flexible development platform for future methods. We also illustrate how our methods empower the technology to make discoveries previously thought to be possible only with sequencing-based methods. Availability and implementation http://bioconductor.org/packages/release/bioc/html/minfi.html. Contact khansen@jhsph.edu; rafa@jimmy.harvard.edu Supplementary information Supplementary data are available at Bioinformatics online.

2,961 citations