2016 Vol. 7, No. 10

Beyond the classroom lecture: Liang Wang's personal war on tuberculosis in China
Ming Li, Xiaomei Hu, Fuquan Hu, Xiancai Rao
2016, 7(10): 697-698. doi: 10.1007/s13238-016-0304-3
The critical roles of mitophagy in cerebral ischemia
Yan-Cheng Tang, Hong-Xia Tian, Tao Yi, Hu-Biao Chen
2016, 7(10): 699-713. doi: 10.1007/s13238-016-0307-0
Mitochondria play a key role in various cell processes including ATP production, Ca2+ homeostasis, reactive oxygen species (ROS) generation, and apoptosis. The selective removal of impaired mitochondria by autophagosome is known as mitophagy. Cerebral ischemia is a common form of stroke caused by insufficient blood supply to the brain. Emerging evidence suggests that mitophagy plays important roles in the pathophysiological process of cerebral ischemia. This review focuses on the relationship between ischemic brain injury and mitophagy. Based on the latest research, it describes how the signaling pathways of mitophagy appear to be involved in cerebral ischemia.
Research articles
C30F12.4 influences oogenesis, fat metabolism, and lifespan in C. elegans
Lu Wang, Fei Xu, Guishuan Wang, Xiaorong Wang, Ajuan Liang, Hefeng Huang, Fei Sun
2016, 7(10): 714-721. doi: 10.1007/s13238-016-0308-z
Reproduction, fat metabolism, and longevity are intertwined regulatory axes; recent studies in C. elegans have provided evidence that these processes are directly coupled. However, the mechanisms by which they are coupled and the reproductive signals modulating fat metabolism and lifespan are poorly understood. Here, we find that an oogenesis-enriched gene, c30f12.4, is specifically expressed and located in germ cells and early embryos; when the gene is knocked out, oogenesis is disrupted and brood size is decreased. In addition to the reproductive phenotype, we find that the loss of c30f12.4 alters fat metabolism, resulting in decreased fat storage and smaller lipid droplets. Meanwhile, c30f12.4 mutant worms display a shortened lifespan. Our results highlight an important role for c30f12.4 in regulating reproduction, fat homeostasis, and aging in C. elegans, which helps us to better understand the relationship between these processes.
miR-181b functions as an oncomiR in colorectal cancer by targeting PDCD4
Yanqing Liu, Uzair-ur-Rehman, Yu Guo, Hongwei Liang, Rongjie Cheng, Fei Yang, Yeting Hong, Chihao Zhao, Minghui Liu, Mengchao Yu, Xinyan Zhou, Kai Yin, Jiangning Chen, Junfeng Zhang, Chen-Yu Zhang, Feng Zhi, Xi Chen
2016, 7(10): 722-734. doi: 10.1007/s13238-016-0313-2
Programmed cell death 4 (PDCD4) is a RNA-binding protein that acts as a tumor suppressor in many cancer types, including colorectal cancer (CRC). During CRC carcinogenesis, PDCD4 protein levels remarkably decrease, but the underlying molecular mechanism for decreased PDCD4 expression is not fully understood. In this study, we performed bioinformatics analysis to identify miRNAs that potentially target PDCD4. We demonstrated miR-181b as a direct regulator of PDCD4. We further showed that activation of IL6/STAT3 signaling pathway increased miR-181b expression and consequently resulted in downregulation of PDCD4 in CRC cells. In addition, we investigated the biological effects of PDCD4 inhibition by miR-181b both in vitro and in vivo and found that miR-181b could promote cell proliferation and migration and suppress apoptosis in CRC cells and accelerate tumor growth in xenograft mice, potentially through targeting PDCD4. Taken together, this study highlights an oncomiR role for miR-181b in regulating PDCD4 in CRC and suggests that miR-181b may be a novel molecular therapeutic target for CRC.
The superior fault tolerance of artificial neural network training with a fault/noise injectionbased genetic algorithm
Feng Su, Peijiang Yuan, Yangzhen Wang, Chen Zhang
2016, 7(10): 735-748. doi: 10.1007/s13238-016-0302-5
Artificial neural networks (ANNs) are powerful computational tools that are designed to replicate the human brain and adopted to solve a variety of problems in many different fields. Fault tolerance (FT), an important property of ANNs, ensures their reliability when significant portions of a network are lost. In this paper, a fault/noise injection-based (FIB) genetic algorithm (GA) is proposed to construct fault-tolerant ANNs. The FT performance of an FIB-GA was compared with that of a common genetic algorithm, the back-propagation algorithm, and the modification of weights algorithm. The FIB-GA showed a slower fitting speed when solving the exclusive OR (XOR) problem and the overlapping classification problem, but it significantly reduced the errors in cases of single or multiple faults in ANN weights or nodes. Further analysis revealed that the fit weights showed no correlation with the fitting errors in the ANNs constructed with the FIB-GA, suggesting a relatively even distribution of the various fitting parameters. In contrast, the output weights in the training of ANNs implemented with the use the other three algorithms demonstrated a positive correlation with the errors. Our findings therefore indicate that a combination of the fault/noise injection-based method and a GA is capable of introducing FT to ANNs and imply that the distributed ANNs demonstrate superior FT performance.
Human INO80/YY1 chromatin remodeling complex transcriptionally regulates the BRCA2-and CDKN1A-interacting protein (BCCIP) in cells
Jiaming Su, Yi Sui, Jian Ding, Fuqiang Li, Shuang Shen, Yang Yang, Zeming Lu, Fei Wang, Lingling Cao, Xiaoxia Liu, Jingji Jin, Yong Cai
2016, 7(10): 749-760. doi: 10.1007/s13238-016-0306-1
The BCCIP (BRCA2-and CDKN1A-interacting protein) is an important cofactor for BRCA2 in tumor suppression. Although the low expression of BCCIP is observed in multiple clinically diagnosed primary tumor tissues such as ovarian cancer, renal cell carcinoma and colorectal carcinoma, the mechanism of how BCCIP is regulated in cells is still unclear. The human INO80/YY1 chromatin remodeling complex composed of 15 subunits catalyzes ATP-dependent sliding of nucleosomes along DNA. Here, we first report that BCCIP is a novel target gene of the INO80/YY1 complex by presenting a series of experimental evidence. Gene expression studies combined with siRNA knockdown data locked candidate genes including BCCIP of the INO80/YY1 complex. Silencing or over-expressing the subunits of the INO80/YY1 complex regulates the expression level of BCCIP both in mRNA and proteins in cells. Also, the functions of INO80/YY1 complex in regulating the transactivation of BCCIP were confirmed by luciferase reporter assays. Chromatin immunoprecipitation (ChIP) experiments clarify the enrichment of INO80 and YY1 at +0.17 kb downstream of the BCCIP transcriptional start site. However, this enrichment is significantly inhibited by either knocking down INO80 or YY1, suggesting the existence of both INO80 and YY1 is required for recruiting the INO80/YY1 complex to BCCIP promoter region. Our findings strongly indicate that BCCIP is a potential target gene of the INO80/YY1 complex.
Crystal structure of HLA-B*5801, a protective HLA allele for HIV-1 infection
Xiaolong Li, Pedro A. Lamothe, Robert Ng, Shutong Xu, Maikun Teng, Bruce D. Walker, Jia-huai Wang
2016, 7(10): 761-765. doi: 10.1007/s13238-016-0309-y
The PilZ domain of MrkH represents a novel DNA binding motif
Feng Wang, Qing He, Kaixuan Su, Fei Gao, Yan Huang, Zong Lin, Deyu Zhu, Lichuan Gu
2016, 7(10): 766-772. doi: 10.1007/s13238-016-0317-y