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  • Table of Content
      Feb. 2018, Volume 4 Issue 1 Previous Issue    Next Issue
    Cover Story
    Insulin released by pancreatic β cells plays a key role in regulating blood glucose levels in humans,and to understand the mechanism for insulin secretion may reveal therapeutic strategies for diabetes.The authors found that PI4KIIα transgenic (TG) mice have abnormal glucose tolerance and higher serum glucose levels than wild-type mice.Glucose-stimulated insulin secretion was significantly reduced in both PI4KIIα TG mice and PI4KIIa-overexpressing pancreatic β cell lines.A proximity-base [Detail] ...
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    Biophysics Reports. 2018, 4 (1): 0-0.  
    Abstract   HTML   PDF (7596KB) ( 15 )
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    Docking-based inverse virtual screening: methods, applications, and challenges
    Xianjin Xu, Marshal Huang, Xiaoqin Zou
    Biophysics Reports. 2018, 4 (1): 1-16.   DOI: 10.1007/s41048-017-0045-8
    Abstract   HTML   PDF (610KB) ( 137 )
    Identifying potential protein targets for a small-compound ligand query is crucial to the process of drug development. However, there are tens of thousands of proteins in human alone, and it is almost impossible to scan all the existing proteins for a query ligand using current experimental methods. Recently, a computational technology called docking-based inverse virtual screening (IVS) has attracted much attention. In docking-based IVS, a panel of proteins is screened by a molecular docking program to identify potential targets for a query ligand. Ever since the first paper describing a docking-based IVS program was published about a decade ago, the approach has been gradually improved and utilized for a variety of purposes in the field of drug discovery. In this article, the methods employed in dockingbased IVS are reviewed in detail, including target databases, docking engines, and scoring function methodologies. Several web servers developed for non-expert users are also reviewed. Then, a number of applications are presented according to different research purposes, such as target identification, side effects/toxicity, drug repositioning, drug-target network development, and receptor design. The review concludes by discussing the challenges that docking-based IVS needs to overcome to become a robust tool for pharmaceutical engineering.
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    AIM interneurons mediate feeding suppression through the TYRA-2 receptor in C. elegans
    Jiajun Fu, Haining Zhang, Wenming Huang, Xinyu Zhu, Yi Sheng, Eli Song, Tao Xu
    Biophysics Reports. 2018, 4 (1): 17-24.   DOI: 10.1007/s41048-018-0046-2
    Abstract   HTML   PDF (1528KB) ( 129 )
    Feeding behavior is the most fundamental behavior in C. elegans. Our previous results have dissected the central integration circuit for the regulation of feeding, which integrates opposing sensory inputs and regulates feeding behavior in a nonlinear manner. However, the peripheral integration that acts downstream of the central integration circuit to modulate feeding remains largely unknown. Here, we find that a Gai/o-coupled tyramine receptor, TYRA-2, is involved in peripheral feeding suppression. TYRA-2 suppresses feeding behavior via the AIM interneurons, which receive tyramine/octopamine signals from RIM/RIC neurons in the central integration circuit. Our results reveal previously unidentified roles for the receptor TYRA-2 and the AIM interneurons in feeding regulation, providing a further understanding of how biogenic amines tyramine and octopamine regulate feeding behavior.
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    PI4KIIα regulates insulin secretion and glucose homeostasis via a PKD-dependent pathway
    Lunfeng Zhang, Jiangmei Li, Panpan Zhang, Zhen Gao, Yingying Zhao, Xinhua Qiao, Chang Chen
    Biophysics Reports. 2018, 4 (1): 25-38.   DOI: 10.1007/s41048-018-0049-z
    Abstract   HTML   PDF (3634KB) ( 134 )
    Insulin release by pancreatic β cells plays a key role in regulating blood glucose levels in humans, and to understand the mechanism for insulin secretion may reveal therapeutic strategies for diabetes. We found that PI4KⅡα transgenic (TG) mice have abnormal glucose tolerance and higher serum glucose levels than wild-type mice. Glucose-stimulated insulin secretion was significantly reduced in both PI4KⅡα TG mice and PI4KⅡα-overexpressing pancreatic β cell lines. A proximity-based biotin labeling technique, BioID, was used to identify proteins that interact with PI4KⅡα, and the results revealed that PI4KⅡα interacts with PKD and negatively regulates its activity. The effect of PI4KⅡα on insulin secretion was completely rescued by altering PKD activity. PI4KⅡα overexpression also worsened glucose tolerance in streptozotocin/high-fat diet-induced diabetic mice by impairing insulin secretion. Our study has shed new light on PI4KⅡα function and mechanism in diabetes and identified PI4KⅡα as an important regulator of insulin secretion.
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    Identification of small ORF-encoded peptides in mouse serum
    Yaqin Deng, Adekunle Toyin Bamigbade, Mirza Ahmed Hammad, Shimeng Xu, Pingsheng Liu
    Biophysics Reports. 2018, 4 (1): 39-49.   DOI: 10.1007/s41048-018-0048-0
    Abstract   HTML   PDF (4110KB) ( 153 )
    Identification of the coding elements in the genome is fundamental to interpret the development of living systems and species diversity. Small peptides (length <100 amino acids) have played an important role in regulating the biological metabolism, but their identification has been limited by their size and abundance. Serum is the most important body fluid and is full of small peptides. In this study, we have established a small ORF-encoded peptides (SEPs) database from mouse GENCODE release. This database provides about half a million putative translated SEPs in mouse. We also extract serum proteins from wild type and ob/ob mice, and collect the low molecular weight proteins for mass spectrometric analysis. More than 50 novel SEPs have been discovered. Several SEPs are further verified by biochemical method with newly raised antibodies. These novel SEPs enhance the knowledge about the complexity of serum and provide new clues for the annotation and functional analysis of genes, especially the noncoding elements in the genome.
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    Identification of natural products as novel ligands for the human 5-HT2C receptor
    Yao Peng, Simeng Zhao, Yiran Wu, Haijie Cao, Yueming Xu, Xiaoyan Liu, Wenqing Shui, Jianjun Cheng, Suwen Zhao, Ling Shen, Jun Ma, Ronald J. Quinn, Raymond C. Stevens, Guisheng Zhong, Zhi-Jie Liu
    Biophysics Reports. 2018, 4 (1): 50-61.   DOI: 10.1007/s41048-018-0047-1
    Abstract   HTML   PDF (1973KB) ( 187 )
    G protein-coupled receptors (GPCRs) constitute the largest human protein family with over 800 members, which are implicated in many important medical conditions. Serotonin receptors belong to the aminergic GPCR subfamily and play important roles in physiological and psychological activities. Structural biology studies have revealed the structures of many GPCRs in atomic details and provide the basis for the identification and investigation of the potential ligands, which interact with and modulate the receptors. Here, an integrative approach combining a focused target-specific natural compound library, a thermalshift-based screening method, affinity mass spectrometry, molecular docking, and in vitro as well as in vivo functional assay, was applied to identify (-)-crebanine and several other aporphine alkaloids as initial hits for a human serotonin receptor subtype, the 5-HT2C receptor. Further studies illuminated key features of their binding affinity, downstream signaling and tissue reaction, providing a molecular explanation for the interaction between (-)-crebanine and human 5-HT2C receptor.
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ISSN 2364-3439
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