2012 Vol. 3, No. 7

Detour and return-Chenfu Wu's interdisciplinary research journey
Ming Li
2012, 3(7): 481-482. doi: 10.1007/s13238-012-2807-x
Higher-order genomic organization in pluripotent stem cells
Ping Wang, Weiqi Zhang, Jiping Yang, Jing Qu, Guang-Hui Liu
2012, 3(7): 483-486. doi: 10.1007/s13238-012-2806-y
Complement genetics, deficiencies, and disease associations
Karine R. Mayilyan
2012, 3(7): 487-496. doi: 10.1007/s13238-012-2924-6
The complement system is a key component of innate immunity. More than 45 genes encoding the proteins of complement components or their isotypes and subunits, receptors, and regulators have been discovered. These genes are distributed throughout different chromosomes, with 19 genes comprising three significant complement gene clusters in the human genome. Genetic deficiency of any early component of the classical pathway (C1q, C1r/s, C2, C4, and C3) is associated with autoimmune diseases due to the failure of clearance of immune complexes (IC) and apoptotic materials, and the impairment of normal humoral response. Deficiencies of mannan-binding lectin (MBL) and the early components of the alternative (factor D, properdin) and terminal pathways (from C3 onward components:C5, C6, C7, C8, C9) increase susceptibility to infections and their recurrence. While the association of MBL deficiency with a number of autoimmune and infectious disorders has been well established, the effects of the deficiency of other lectin pathway components (ficolins, MASPs) have been less extensively investigated due to our incomplete knowledge of the genetic background of such deficiencies and the functional activity of those components. For complement regulators and receptors, the consequences of their genetic deficiency vary depending on their specific involvement in the regulatory or signalling steps within the complement cascade and beyond. This article reviews current knowledge and concepts about the genetic load of complement component deficiencies and their association with diseases. An integrative presentation of genetic data with the latest updates provides a background to further investigations of the disease association investigations of the complement system from the perspective of systems biology and systems genetics.
Functional regulation of monocyte-derived dendritic cells by microRNAs
Yifan Zhan, Li Wu
2012, 3(7): 497-507. doi: 10.1007/s13238-012-0042-0
Dendritic cells (DCs) as a rare type of leukocytes play an important role in bridging the innate and adaptive immune system. A subset of DCs, monocyte-derived dendritic cells (moDCs), exists in very low numbers at steady state but become abundant in inflammatory states. These inflammation-associated DCs are potent producers of pro-inflammatory cytokines and potent inducers of T helper differentiation. They behave as a "double-edge" sword so that they not only mediate protective immunity but also immuno-pathology. It is still incompletely understood how their function is regulated. Emerging evidence indicates that microRNAs (miRNAs), as a new class of gene regulators, potently regulate the function of moDCs. Here we summarize recent progress in this area.
Proteome-wide prediction of protein-protein interactions from high-throughput data
Zhi-Ping Liu, Luonan Chen
2012, 3(7): 508-520. doi: 10.1007/s13238-012-2945-1
In this paper, we present a brief review of the existing computational methods for predicting proteome-wide protein-protein interaction networks from highthroughput data. The availability of various types of omics data provides great opportunity and also unprecedented challenge to infer the interactome in cells. Reconstructing the interactome or interaction network is a crucial step for studying the functional relationship among proteins and the involved biological processes. The protein interaction network will provide valuable resources and alternatives to decipher the mechanisms of these functionally interacting elements as well as the running system of cellular operations. In this paper, we describe the main steps of predicting protein-protein interaction networks and categorize the available approaches to couple the physical and functional linkages. The future topics and the analyses beyond prediction are also discussed and concluded.
Ultra-structural study of insulin granules in pancreatic β-cells of db/db mouse by scanning transmission electron microscopy tomography
Yanhong Xue, Wei Zhao, Wen Du, Xiang Zhang, Gang Ji, Wang Ying, Tao Xu
2012, 3(7): 521-525. doi: 10.1007/s13238-012-2937-1
Insulin granule trafficking is a key step in the secretion of glucose-stimulated insulin from pancreatic β-cells. The main feature of type 2 diabetes (T2D) is the failure of pancreatic β-cells to secrete sufficient amounts of insulin to maintain normal blood glucose levels. In this work, we developed and applied tomography based on scanning transmission electron microscopy (STEM) to image intact insulin granules in the β-cells of mouse pancreatic islets. Using three-dimensional (3D) reconstruction, we found decreases in both the number and the grey level of insulin granules in db/db mouse pancreatic β-cells. Moreover, insulin granules were closer to the plasma membrane in diabetic β-cells than in control cells. Thus, 3D ultra-structural tomography may provide new insights into the pathology of insulin secretion in T2D.
Research article
Prioritization of candidate genes for attention deficit hyperactivity disorder by computational analysis of multiple data sources
Suhua Chang, Weina Zhang, Lei Gao, Jing Wang
2012, 3(7): 526-534. doi: 10.1007/s13238-012-2931-7
Research articles
Curcumin induces differentiation of embryonic stem cells through possible modulation of nitric oxide-cyclic GMP pathway
Kalpana Mujoo, Lubov E. Nikonoff, Vladislav G Sharin, Nathan S. Bryan, Alexander Y. Kots, Ferid Murad
2012, 3(7): 535-544. doi: 10.1007/s13238-012-2053-2
Curcumin, an active ingredient of dietary spice used in curry, has been shown to exhibit anti-oxidant, anti-inflammatory and anti-proliferative properties. Using EB directed differentiation protocol of H-9 human embryonic stem (ES) cells; we evaluated the effect of curcumin (0-20 μmol/L) in enhancing such differentiation. Our results using real time PCR, western blotting and immunostaining demonstrated that curcumin significantly increased the gene expression and protein levels of cardiac specific transcription factor NKx2.5, cardiac troponin I, myosin heavy chain, and endothelial nitric oxide synthase during ES cell differentiation. Furthermore, an NO donor enhanced the curcumin-mediated induction of NKx2.5 and other cardiac specific proteins. Incubation of cells with curcumin led to a dose dependent increase in intracellular nitrite to the same extent as giving an authentic NO donor. Functional assay for second messenger(s) cyclic AMP (cAMP) and cyclic GMP (cGMP) revealed that continuous presence of curcumin in differentiated cells induced a decrease in the baseline levels of cAMP but it significantly elevated baseline contents of cGMP. Curcumin addition to a cell free assay significantly suppressed cAMP and cGMP degradation in the extracts while long term treatment of intact cells with curcumin increased the rates of cAMP and cGMP degradation suggesting that this might be due to direct suppression of some cyclic nucleotide-degrading enzyme (phosphodiesterase) by curcumin. These studies demonstrate that polyphenol curcumin may be involved in differentiation of ES cells partly due to manipulation of nitric oxide signaling.
The growth of B cell receptor microcluster is a universal response of B cells encountering antigens with different motion features
Zhengpeng Wan, Wanli Liu
2012, 3(7): 545-558. doi: 10.1007/s13238-012-2054-1
B lymphocyte cell senses and acquires foreign antigens through clonal distributed B cell receptors (BCRs) expressed on the surface of plasma membrane. The presentation formats of antigens are quite diverse. Based on their Brownian diffusion mobility, there are three forms:free mobile soluble antigens, lateral mobile membrane bound antigens, and fixed immobile antigens. Here, using high resolution high speed live cell imaging approaches, we provide evidence that BCR microclusters are formed on the surface of B cells shortly after B cell's encountering of antigens with each format of motion features. Through high speed live cell imaging, we determine that these BCR microclusters show dynamic growth feature and by doing so function as the basic platforms for B cells to acquire the antigens. We propose that the formation and dynamic growth of BCR microcluster is a universal mechanism for B cell to response to antigens with diverse motion features.
Neural stem cells: mechanisms and modeling
Jun Yao, Yangling Mu, Fred H. Gage
2012, 3(7): 559-559. doi: 10.1007/s13238-012-2808-9