2015 Vol. 6(6)

Vantage points
Small non-coding RNAs transfer through mammalian placenta and directly regulate fetal gene expression
Jing Li, Yujing Zhang, Dameng Li, Yuchen Liu, Danping Chu, Xiaohong Jiang, Dongxia Hou, Ke Zen, Chen-Yu Zhang
2015, 6(6): 391-396. doi: 10.1007/s13238-015-0156-2
NGSmirPlant: comprehensive characterization of the small RNA transcriptomes of plants
Jie Bai, Chen Dan, Yi Zhang, Guoping Zhao, Xiaoming Ding
2015, 6(6): 397-402. doi: 10.1007/s13238-015-0159-z
Leukemia stem cells: the root of chronic myeloid leukemia
Hong Zhou, Rongzhen Xu
2015, 6(6): 403-412. doi: 10.1007/s13238-015-0143-7
Chronic myeloid leukemia (CML) is a clonal myeloproliferative disorder characterized by a chromosome translocation that generates the Bcr-Abl oncogene encoding a constitutive kinase activity. Despite remarkable success in controlling CML at chronic phase by Bcr-Abl tyrosine kinase inhibitors (TKIs), a significant proportion of CML patients treated with TKIs develop drug resistance due to the inability of TKIs to kill leukemia stem cells (LSCs) that are responsible for initiation, drug resistance, and relapse of CML. Therefore, there is an urgent need for more potent and safer therapies against leukemia stem cells for curing CML. A number of LSCassociated targets and corresponding signaling pathways, including CaMKⅡ-γ, a critical molecular switch for co-activating multiple LSC-associated signaling pathways, have been identified over the past decades and various small inhibitors targeting LSC are also under development. Increasing evidence shows that leukemia stem cells are the root of CML and targeting LSC may offer a curable treatment option for CML patients. This review summarizes the molecular biology of LSC and itsassociated targets, and the potential clinical application in chronic myeloid leukemia.
Theoretical and simulation studies on voltage-gated sodium channels
Yang Li, Haipeng Gong
2015, 6(6): 413-422. doi: 10.1007/s13238-015-0152-6
Voltage-gated sodium (Nav) channels are indispensable membrane elements for the generation and propagation of electric signals in excitable cells. The successes in the crystallographic studies on prokaryotic Nav channels in recent years greatly promote the mechanistic investigation of these proteins and their eukaryotic counterparts. In this paper, we mainly review the progress in computational studies, especially the simulation studies, on these proteins in the past years.
Research articles
Molecular dynamics and principal components of potassium binding with human telomeric intra-molecular G-quadruplex
Zhiguo Wang, Ruping Chen, Ling Hou, Jianfeng Li, Jun-Ping Liu
2015, 6(6): 423-433. doi: 10.1007/s13238-015-0155-3
Telomere assumes intra-molecular G-quadruplex that is a significant drug target for inhibiting telomerase maintenance of telomeres in cancer. Metal cations have been recognized as playing important roles in stabilizing G-quadruplex, but their binding processes to human telomeric G-quadruplex remain uncharacterized. To investigate the detailed binding procedures, molecular dynamics simulations were conducted on the hybrid[3 + 1] form-one human telomeric intra-molecular G-quadruplex. We show here that the binding of a potassium ion to a G-tetrad core is mediated by two alternative pathways. Principal component analysis illustrated the dominant concerted motions of G-quadruplex occurred at the loop domains. MM-PBSA calculations revealed that binding was energetically favorable and driven by the electrostatic interactions. The lower binding site was found more constructive favorable for binding. Our data provide useful information on a potassium-mediated stable structure of human telomeric intra-molecular G-quadruplex, implicating in ion disorder associated conformational changes and targeted drug design.
Mitochondrial calcium uniporter protein MCU is involved in oxidative stress-induced cell death
Yajin Liao, Yumin Hao, Hong Chen, Qing He, Zengqiang Yuan, Jinbo Cheng
2015, 6(6): 434-442. doi: 10.1007/s13238-015-0144-6
Mitochondrial calcium uniporter (MCU) is a conserved Ca2+ transporter at mitochondrial in eukaryotic cells. However, the role of MCU protein in oxidative stressinduced cell death remains unclear. Here, we showed that ectopically expressed MCU is mitochondrial localized in both HeLa and primary cerebellar granule neurons (CGNs). Knockdown of endogenous MCU decreases mitochondrial Ca2+ uptake following histamine stimulation and attenuates cell death induced by oxidative stress in both HeLa cells and CGNs. We also found MCU interacts with VDAC1 and mediates VDAC1 overexpression-induced cell death in CGNs. This finding demonstrates that MCU-VDAC1 complex regulates mitochondrial Ca2+ uptake and oxidative stress-induced apoptosis, which might represent therapeutic targets for oxidative stress related diseases.
Scorpion toxin BmK I directly activates Nav1.8 in primary sensory neurons to induce neuronal hyperexcitability in rats
Pin Ye, Yunlu Jiao, Zhenwei Li, Liming Hua, Jin Fu, Feng Jiang, Tong Liu, Yonghua Ji
2015, 6(6): 443-452. doi: 10.1007/s13238-015-0154-4
Voltage-gated sodium channels (VGSCs) in primary sensory neurons play a key role in transmitting pain signals to the central nervous system. BmK I, a site-3 sodium channel-specific toxin from scorpion Buthus martensi Karsch, induces pain behaviors in rats. However, the subtypes of VGSCs targeted by BmK I were not entirely clear. We therefore investigated the effects of BmK I on the current amplitude, gating and kinetic properties of Nav1.8, which is associated with neuronal hyperexcitability in DRG neurons. It was found that BmK I dose-dependently increased Nav1.8 current in smallsized (<25 μm) acutely dissociated DRG neurons, which correlated with its inhibition on both fast and slow inactivation. Moreover, voltage-dependent activation and steady-state inactivation curves of Nav1.8 were shifted in a hyperpolarized direction. Thus, BmK I reduced the threshold of neuronal excitability and increased action potential firing in DRG neurons. In conclusion, our data clearly demonstrated that BmK I modulated Nav1.8 remarkably, suggesting BmK I as a valuable probe for studying Nav1.8. And Nav1.8 is an important target related to BmK I-evoked pain.
Hemagglutinin stem reactive antibody response in individuals immunized with a seasonal influenza trivalent vaccine
Xiaopeng Zhao, Kun Qin, Jinlei Guo, Donghong Wang, Zi Li, Wenfei Zhu, Liqi Liu, Dayan Wang, Yuelong Shu, Jianfang Zhou
2015, 6(6): 453-457. doi: 10.1007/s13238-015-0160-6
Dissection of voltage-gated sodium channels in developing cochlear sensory epithelia
You Zhou, Fang-Hao Fang, Zhi-Rui Liu, Yong-Hua Ji
2015, 6(6): 458-462. doi: 10.1007/s13238-015-0157-1
Targeted disruption of Rab10 causes early embryonic lethality
Pingping Lv, Yi Sheng, Zhenao Zhao, Wei Zhao, Lusheng Gu, Tao Xu, Eli Song
2015, 6(6): 463-467. doi: 10.1007/s13238-015-0150-8

Current Issue

March, 2019

Volume 10, Issue 3

Pages 157-233

About the cover

Metastasis is the leading cause of human cancer deaths.Unfortunately, no approved drugs are available for antimetastatic treatment. In this study, high-throughputsequencing-based high-throughput screening (HTS2) anda breast cancer lung metastasis (BCLM)-associated genesignature were combined to discover anti-metastatic drugs.After screening of thousands of compounds, Shao et al.identifed Ponatinib as a BCLM inhibitor. Ponatinib signifcantlyinhibited the migration and mammosphere formation of breastcancer cells in vitro and blocked BCLM in multiple mousemodels. This study may facilitate the therapeutic treatment ofBCLM as well as other metastases.

Institute of Biophysics, Chinese Academy of Sciences, 15 Datun Road, Chaoyang Beijing 100101, China

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