2012 Vol. 3, No. 1

News and views
Evolution of iPSC disease models
Weiqi Zhang, Zhichao Ding, Guang-Hui Liu
2012, 3(1): 1-4. doi: 10.1007/s13238-012-2005-x
Evaluating the suitability of essential genes as targets for antibiotic screening assays using proteomics
Ashley Chessher
2012, 3(1): 5-7. doi: 10.1007/s13238-011-1135-x
Zan Ding: founder of medical psychology in China
Ming Li
2012, 3(1): 8-9. doi: 10.1007/s13238-012-2009-6
Emerging role of ER quality control in plant cell signal perception
Hong-Ju Li, Wei-Cai Yang
2012, 3(1): 10-16. doi: 10.1007/s13238-012-2004-y
The endoplasmic reticulum quality control (ER-QC) is a conserved mechanism in surveillance of secreted signaling factors during cell-to-cell communication in eukaryotes. Recent data show that the ER-QC plays important roles in diverse cell-to-cell signaling processes during immune response, vegetative and reproductive development in plants. Pollen tube guidance is a precisely guided cell-cell communication process between the male and female gametophytes during plant reproduction. Recently, the female signal has been identified as small secreted peptides, but how the pollen tube responds to this signal is still unclear. In this review, we intend to summarize the role of ER-QC in plants and discuss the recent advances regarding our understanding of the mechanism of pollen tube response to the female signals.
The crosstalk between autophagy and apoptosis: where does this lead?
Claire Gordy, You-Wen He
2012, 3(1): 17-27. doi: 10.1007/s13238-011-1127-x
Recent advances in the understanding of the molecular processes contributing to autophagy have provided insight into the relationship between autophagy and apoptosis. In contrast to the concept of "autophagic cell death," accumulating evidence suggests that autophagy serves a largely cytoprotective role in physiologically relevant conditions. The cytoprotective function of autophagy is mediated in many circumstances by negative modulation of apoptosis. Apoptotic signaling, in turn, serves to inhibit autophagy. While the mechanisms mediating the complex counter-regulation of apoptosis and autophagy are not yet fully understood, important points of crosstalk include the interactions between Beclin-1 and Bcl-2/Bcl-xL and between FADD and Atg5, caspase-and calpain-mediated cleavage of autophagy-related proteins, and autophagic degradation of caspases. Continued investigation of these and other means of crosstalk between apoptosis and autophagy is necessary to elucidate the mechanisms controlling the balance between survival and death both under normal conditions and in diseases including cancer.
Horizontal transfer of microRNAs: molecular mechanisms and clinical applications
Xi Chen, Hongwei Liang, Junfeng Zhang, Ke Zen, Chen-Yu Zhang
2012, 3(1): 28-37. doi: 10.1007/s13238-012-2003-z
A new class of RNA regulatory genes known as microRNAs (miRNAs) has been found to introduce a whole new layer of gene regulation in eukaryotes. The intensive studies of the past several years have demonstrated that miRNAs are not only found intracellularly, but are also detectable outside cells, including in various body fluids (e.g. serum, plasma, saliva, urine and milk). This phenomenon raises questions about the biological function of such extracellular miRNAs. Substantial amounts of extracellular miRNAs are enclosed in small membranous vesicles (e.g. exosomes, shedding vesicles and apoptotic bodies) or packaged with RNA-binding proteins (e.g. high-density lipoprotein, Argonaute 2 and nucleophosmin 1). These miRNAs may function as secreted signaling molecules to influence the recipient cell phenotypes. Furthermore, secreted extracellular miRNAs may reflect molecular changes in the cells from which they are derived and can therefore potentially serve as diagnostic indicators of disease. Several studies also point to the potential application of siRNA/miRNA delivery as a new therapeutic strategy for treating diseases. In this review, we summarize what is known about the mechanism of miRNA secretion. In addition, we describe the pathophysiological roles of secreted miRNAs and their clinical potential as diagnostic biomarkers and therapeutic drugs. We believe that miRNA transfer between cells will have a significant impact on biological research in the coming years.
SySAP: a system-level predictor of deleterious single amino acid polymorphisms
Tao Huang, Chuan Wang, Guoqing Zhang, Lu Xie, Yixue Li
2012, 3(1): 38-43. doi: 10.1007/s13238-011-1130-2
Single amino acid polymorphisms (SAPs), also known as non-synonymous single nucleotide polymorphisms (nsSNPs), are responsible for most of human genetic diseases. Discriminate the deleterious SAPs from neutral ones can help identify the disease genes and understand the mechanism of diseases. In this work, a method of deleterious SAP prediction at system level was established. Unlike most existing methods, our method not only considers the sequence and structure information, but also the network information. The integration of network information can improve the performance of deleterious SAP prediction. To make our method available to the public, we developed SySAP (a System-level predictor of deleterious Single Amino acid Polymorphisms), an easy-to-use and high accurate web server. SySAP is freely available at http://www.biosino.org/SySAP/and http://lifecenter.sgst.cn/SySAP/.
Research articles
Study on the chaperone properties of conserved GTPases
Xiang Wang, Jiaying Xue, Zhe Sun, Yan Qin, Weimin Gong
2012, 3(1): 44-50. doi: 10.1007/s13238-011-1133-z
As a large family of hydrolases, GTPases are widespread in cells and play the very important biological function of hydrolyzing GTP into GDP and inorganic phosphate through binding with it. GTPases are involved in cell cycle regulation, protein synthesis, and protein transportation. Chaperones can facilitate the folding or refolding of nascent peptides and denatured proteins to their native states. However, chaperones do not occur in the native structures in which they can perform their normal biological functions. In the current study, the chaperone activity of the conserved GTPases of Escherichia coli is tested by the chemical denaturation and chaperone-assisted renaturation of citrate synthase and α-glucosidase. The effects of ribosomes and nucleotides on the chaperone activity are also examined. Our data indicate that these conserved GTPases have chaperone properties, and may be ancestral protein folding factors that have appeared before dedicated chaperones.
A novel xeno-free and feeder-cell-free system for human pluripotent stem cell culture
Qihui Wang, Xiaoning Mou, Henghua Cao, Qingzhang Meng, Yanni Ma, Pengcheng Han, Junjie Jiang, Hao Zhang, Yue Ma
2012, 3(1): 51-59. doi: 10.1007/s13238-012-2002-0
While human induced pluripotent stem cells (hiPSCs) have promising applications in regenerative medicine, most of the hiPSC lines available today are not suitable for clinical applications due to contamination with nonhuman materials, such as sialic acid, and potential pathogens from animal-product-containing cell culture systems. Although several xeno-free cell culture systems have been established recently, their use of human fibroblasts as feeders reduces the clinical potential of hiPSCs due to batch-to-batch variation in the feeders and time-consuming preparation processes. In this study, we have developed a xeno-free and feeder-cell-free human embryonic stem cell (hESC)/hiPSC culture system using human plasma and human placenta extracts. The system maintains the self-renewing capacity and pluripotency of hESCs for more than 40 passages. Human iPSCs were also derived from human dermal fibroblasts using this culture system by overexpressing three transcription factors-Oct4, Sox2 and Nanog. The culture system developed here is inexpensive and suitable for large scale production.
Conservation and divergence of Grb7 family of Ras-binding domains
Raju V. S. Rajala, Ammaji Rajala, Vivek K. Gupta
2012, 3(1): 60-70. doi: 10.1007/s13238-012-2001-1
Ras proteins are signal-transducing GTPases that cycle between inactive GDP-bound and active GTP-bound forms. Ras is a prolific signaling molecule interacting with a spectrum of effector molecules and acting through more than one signaling pathway. The Ras-effector proteins contain a Ras-associating (RA) domain through which these associate with Ras in a GTP-dependent manner. The RA domain is highly conserved among the members of the growth factor receptor-bound (Grb) 7 family of proteins which includes Grb7, Grb10 and Grb14. Our laboratory has reported an unusual observation that RA domain of Grb14 binds to the C-terminal nucleotide binding site of cyclic nucleotide gated channel (CTRCNGA1) and inhibits the channel activity. Molecular modeling of the CTR-CNGA1 displays 50%—70% tertiary structural similarity towards Ras proteins. We named this region as Ras-like domain (RLD). The interaction between RA-Grb14 and RLD-CNGA1 is mediated through a simple protein-protein interaction temporally and spatially regulated by light and cGMP. It is interesting to note that Grb14 binds to GTPase-mutant Rab5, a Ras-related small GTPase whereas Grb10 binds only to GTP-bound form of active Rab5 but not to GTPase-defective mutant Rab5. These results suggest that Grb14 might have been evolved later in the evolution that binds to both Ras and nucleotide binding proteins such as CNGA1. Our studies also suggest that eukaryotic CNG channels could be evolved through a gene fusion between prokaryotic ion channels and cyclic nucleotide binding proteins, both of which might have undergone several sequence variations for functional adaptation during evolution.
Rapid conversion of human ESCs into mouse ESC-like pluripotent state by optimizing culture conditions
Qi Gu, Jie Hao, Xiao-yang Zhao, Wei Li, Lei Liu, Liu Wang, Zhong-hua Liu, Qi Zhou
2012, 3(1): 71-79. doi: 10.1007/s13238-012-2007-8
The pluripotent state between human and mouse embryonic stem cells is different. Pluripotent state of human embryonic stem cells (ESCs) is believed to be primed and is similar with that of mouse epiblast stem cells (EpiSCs), which is different from the naïve state of mouse ESCs. Human ESCs could be converted into a naïve state through exogenous expression of defined transcription factors (Hanna et al., 2010). Here we report a rapid conversion of human ESCs to mouse ESC-like naïve states only by modifying the culture conditions. These converted human ESCs, which we called mhESCs (mouse ESC-like human ESCs), have normal karyotype, allow single cell passage, exhibit domed morphology like mouse ESCs and express some pluripotent markers similar with mouse ESCs. Thus the rapid conversion established a naïve pluripotency in human ESCs like mouse ESCs, and provided a new model to study the regulation of pluripotency.