2011 Vol. 2, No. 3

News and views
An “endocrine function of” bone to pick: starting with males
Allan Z. Zhao, Dongming Su
2011, 2(3): 171-172. doi: 10.1007/s13238-011-1035-0
Formation and regulation of Yersinia biofilms
Dongsheng Zhou, Ruifu Yang
2011, 2(3): 173-179. doi: 10.1007/s13238-011-1024-3
Flea-borne transmission is a recent evolutionary adaptation that distinguishes the deadly Yersinia pestis from its progenitor Y. pseudotuberculosis, a mild pathogen transmitted via the food-borne route. Y. pestis synthesizes biofilms in the flea gut, which is important for fleaborne transmission. Yersinia biofilms are bacterial colonies surrounded by extracellular matrix primarily containing a homopolymer of N-acetyl-D-glucosamine that are synthesized by a set of specific enzymes. Yersinia biofilm production is tightly regulated at both transcriptional and post-transcriptional levels. All the known structural genes responsible for biofilm production are harbored in both Y. pseudotuberculosis and Y. pestis, but Y. pestis has evolved changes in the regulation of biofilm development, thereby acquiring efficient arthropod-borne transmission.
Directed hepatic differentiation from embryonic stem cells
Xuesong Chen, Fanyi Zeng
2011, 2(3): 180-188. doi: 10.1007/s13238-011-1023-4
The liver is the largest internal organ in mammals, and is important for the maintenance of normal physiological functions of other tissues and organs. Hepatitis, cirrhosis, liver cancer and other chronic liver diseases are serious threats to human health, and these problems are compounded by a scarcity of liver donors for transplantation therapies. Directed differentiation of embryonic stem cells to liver cells is a promising strategy for obtaining hepatocytes that can be used for cell transplantation. In vitro hepatocyte differentiation of embryonic stem cells requires a profound understanding of normal development during embryonic hepatogenesis. Here we provide a simple description of hepatogenesis in vivo and discuss directed differentiation of embryonic stem cells into hepatocytes in vitro.
Animal models for the atherosclerosis research: a review
Xiangdong Li, Yuanwu Liu, Hua Zhang, Liming Ren, Qiuyan Li, Ning Li
2011, 2(3): 189-201. doi: 10.1007/s13238-011-1016-3
Atherosclerosis is a leading cause of death worldwide, and its mechanisms are still unclear. However, various animal models have significantly advanced our understanding of the mechanisms involved in atherosclerosis and have allowed the evaluation of therapeutic options. The aim of this paper is to review those animal models (i.e., rabbits, mice, rats, guinea pigs, hamsters, avian, carnivores, swine, and, non-human primates) that have been used to study atherosclerosis. Though there is no single perfect animal model that completely replicates the stages of human atherosclerosis, cholesterol feeding and mechanical endothelial injury are two common features shared by most models of atherosclerosis. Further, with the development of genetically modified animals, these models are significantly broadening our understanding of the pathogenesis of atherosclerosis.
Structure and function of WD40 domain proteins
Chao Xu, Jinrong Min
2011, 2(3): 202-214. doi: 10.1007/s13238-011-1018-1
The WD40 domain exhibits a β-propeller architecture, often comprising seven blades. The WD40 domain is one of the most abundant domains and also among the top interacting domains in eukaryotic genomes. In this review, we will discuss the identification, definition and architecture of the WD40 domains. WD40 domain proteins are involved in a large variety of cellular processes, in which WD40 domains function as a protein-protein or protein-DNA interaction platform. WD40 domain mediates molecular recognition events mainly through the smaller top surface, but also through the bottom surface and sides. So far, no WD40 domain has been found to display enzymatic activity. We will also discuss the different binding modes exhibited by the large versatile family of WD40 domain proteins. In the last part of this review, we will discuss how post-translational modifications are recognized by WD40 domain proteins.
Proteomic and transcriptomic analysis of visual long-term memory in Drosophila melanogaster
Huoqing Jiang, Qinlong Hou, Zhefeng Gong, Li Liu
2011, 2(3): 215-222. doi: 10.1007/s13238-011-1019-0
The fruit fly, Drosophila melanogaster, is able to discriminate visual landmarks and form visual long-term memory in a flight simulator. Studies focused on the molecular mechanism of long-term memory have shown that memory formation requires mRNA transcription and protein synthesis. However, little is known about the molecular mechanisms underlying the visual learning paradigm. The present study demonstrated that both spaced training procedure (STP) and consecutive training procedure (CTP) would induce long-term memory at 12 hour after training, and STP caused significantly higher 12-h memory scores compared with CTP. Labelfree quantification of liquid chromatography-tandem mass spectrometry (LC-MS/MS) and microarray were utilized to analyze proteomic and transcriptomic differences between the STP and CTP groups. Proteomic analysis revealed 30 up-regulated and 27 down-regulated proteins; Transcriptomic analysis revealed 145 up-regulated and 129 down-regulated genes. Among them, five candidate genes were verified by quantitative PCR, which revealed results similar to microarray. These results provide insight into the molecular components influencing visual long-term memory and facilitate further studies on the roles of identified genes in memory formation.
Research articles
FUS/TLS forms cytoplasmic aggregates, inhibits cell growth and interacts with TDP-43 in a yeast model of amyotrophic lateral sclerosis
Dmitry Kryndushkin, Reed B. Wickner, Frank Shewmaker
2011, 2(3): 223-236. doi: 10.1007/s13238-011-1525-0
Amyotrophic lateral sclerosis (ALS) is a fatal disease characterized by the premature loss of motor neurons. While the underlying cellular mechanisms of neuron degeneration are unknown, the cytoplasmic aggregation of several proteins is associated with sporadic and familial forms of the disease. Both wild-type and mutant forms of the RNA-binding proteins FUS and TDP-43 accumulate in cytoplasmic inclusions in the neurons of ALS patients. It is not known if these so-called proteinopathies are due to a loss of function or a gain of toxicity resulting from the formation of cytoplasmic aggregates. Here we present a model of FUS toxicity using the yeast Saccharomyces cerevisiae in which toxicity is associated with greater expression and accumulation of FUS in cytoplasmic aggregates. We find that FUS and TDP-43 have a high propensity for co-aggregation, unlike the aggregation patterns of several other aggregation-prone proteins. Moreover, the biophysical properties of FUS aggregates in yeast are distinctly different from many amyloidogenic proteins, suggesting they are not composed of amyloid.
The tumor suppressor RASSF1A is a novel effector of small G protein Rap1A
Sunil K. Verma, Trivadi S. Ganesan, Uday Kishore, Peter J. Parker
2011, 2(3): 237-249. doi: 10.1007/s13238-011-1028-z
Rap1A is a small G protein implicated in a spectrum of biological processes such as cell proliferation, adhesion, differentiation, and embryogenesis. The downstream effectors through which Rap1A mediates its diverse effects are largely unknown. Here we show that Rap1A, but not the related small G proteins Rap2 or Ras, binds the tumor suppressor Ras association domain family 1A (RASSF1A) in a manner that is regulated by phosphorylation of RASSF1A. Interaction with Rap1A is shown to influence the effect of RASSF1A on microtubule behavior.
An unexpected similarity between antibiotic-resistant NDM-1 and beta-lactamase II from Erythrobacter litoralis
Beiwen Zheng, Shuguang Tan, Jia Gao, Huiming Han, Jun Liu, Guangwen Lu, Di Liu, Yong Yi, Baoli Zhu, George F. Gao
2011, 2(3): 250-258. doi: 10.1007/s13238-011-1027-0
NDM-1 (New Delhi metallo-beta-lactamase) gene encodes a metallo-beta-lactamase (MBL) with high carbapenemase activity, which makes the host bacterial strain easily dispatch the last-resort antibiotics known as carbapenems and cause global concern. Here we present the bioinformatics data showing an unexpected similarity between NDM-1 and beta-lactamase Ⅱ from Erythrobacter litoralis, a marine microbial isolate. We have further expressed these two mature proteins in E. coli cells, both of which present as a monomer with a molecular mass of 25 kDa. Antimicrobial susceptibility assay reveals that they share similar substrate specificities and are sensitive to aztreonam and tigecycline. The conformational change accompanied with the zinc binding visualized by nuclear magnetic resonance, Zn2+-bound NDM-1, adopts at least some stable tertiary structure in contrast to the metal-free protein. Our work implies a close evolutionary relationship between antibiotic resistance genes in environmental reservoir and in the clinic, challenging the antimicrobial resistance monitoring.
An unforgettable debate between descriptive and experimental biology in the 1930s in China
Ming Li, Zonggang Hu, Le Kang
2011, 2(3): 260-260. doi: 10.1007/s13238-011-1031-4