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Markus Ganter, Jonathan M Goldberg, Jeffrey D Dvorin, Joao A Paulo, Jonas G King, Abhai K Tripathi, Aditya S Paul, Jing Yang, Isabelle Coppens, Rays H Y Jiang, Brendan Elsworth, David A Baker, Rhoel R Dinglasan, Steven P Gygi, Manoj T Duraisingh
Plasmodium parasites, the causative agents of malaria, have evolved a unique cell division cycle in the clinically relevant asexual blood stage of infection(1). DNA replication commences approximately halfway through the intracellular development following invasion and parasite growth. The schizont stage is associated with multiple rounds of DNA replication and nuclear division without cytokinesis, resulting in a multinucleated cell. Nuclei divide asynchronously through schizogony, with only the final round of DNA replication and segregation being synchronous and coordinated with daughter cell assembly(2,3)...
February 17, 2017: Nature Microbiology
Emily Chenette
In this issue, we highlight work from Thorner and colleagues that uncovers how the TORC2 pathway kinase Fpk1 modulates endocytosis, a paper by Rane and colleagues showing that β-cell dysfunction and loss of β-cell mass in diabetes are molecularly linked via a Cdk2-dependent mechanism and a quantitative proteomics study by Norman, Zanivan and colleagues that identifies the key proteins involved in Rab17-mediated anti-invasive effects.
February 2017: FEBS Journal
Namita Kumari, Tatiana Ammosova, Sharmin Diaz, Xionghao Lin, Xiaomei Niu, Andrey Ivanov, Marina Jerebtsova, Subhash Dhawan, Patricia Oneal, Sergei Nekhai
The low incidence of HIV-1 infection in patients with sickle cell disease (SCD) and inhibition of HIV-1 replication in vitro under the conditions of low intracellular iron or heme treatment suggests a potential restriction of HIV-1 infection in SCD. We investigated HIV-1 ex vivo infection of SCD peripheral blood mononuclear cells (PBMCs) and found that HIV-1 replication was inhibited at the level of reverse transcription (RT) and transcription. We observed increased expression of heme and iron-regulated genes, previously shown to inhibit HIV-1, including ferroportin, IKBα, HO-1, p21, and SAM domain and HD domain-containing protein 1 (SAMHD1)...
December 27, 2016: Blood Adv
Sang Mee Park, Hae Ryoun Park, Ji Hye Lee
Proper synaptic function in neural circuits requires precise pairings between correct pre- and post-synaptic partners. Errors in this process may underlie development of neuropsychiatric disorders, such as autism spectrum disorder (ASD). Development of ASD can be influenced by genetic factors, including copy number variations (CNVs). In this study, we focused on a CNV occurring at the 16p11.2 locus in the human genome and investigated potential defects in synaptic connectivity caused by reduced activities of genes located in this region at Drosophila larval neuromuscular junctions, a well-established model synapse with stereotypic synaptic structures...
February 15, 2017: Molecules and Cells
Sonam Gaba, Ram Nageena Singh, Shrutica Abrol, Ajar Nath Yadav, Anil Kumar Saxena, Rajeev Kaushik
Halolamina pelagica strain CDK2, a halophilic archaeon (growth range 1.36 to 5.12 M NaCl), was isolated from rhizosphere of wild grasses of hypersaline soil of the Rann of Kutch, Gujarat, India. Its draft genome contains 2,972,542 bp and 3,485 coding sequences, depicting genes for halophilic serine proteases and trehalose synthesis.
February 9, 2017: Genome Announcements
Qianru Zhang, Hua Yu, Jin Qi, Daisheng Tang, Xiaojia Chen, Jian-Bo Wan, Peng Li, Hao Hu, Yi-Tao Wang, Yuanjia Hu
By comparing the target proteins (TPs) of classic traditional Chinese medicine (TCM) herbal formulas and modern drugs used for treating coronary artery disease (CAD), this study aimed to identify potential therapeutic TPs for treating CAD. Based on the theory of TCM, the Xuefu-Zhuyu decoction (XZD) and Gualou-Xiebai-Banxia decoction (GXBD), both of which are classic herbal formulas, were selected for treating CAD. Data on the chemical ingredients and corresponding TPs of the herbs in these two formulas and data on modern drugs approved for treating CAD and related TPs were retrieved from professional TCM and bioinformatics databases...
2017: PloS One
Peng Zhao, David O Nettleton, Rajeshri G Karki, Frederic J Zecri, Shih-Yuan Liu
The first examples of biologically active monocyclic 1,2- azaborines have been synthesized and demonstrated to exhibit not only improved in vitro aqueous solubility in comparison to the corresponding carbonaceous analogues, but in the context of a CDK2 inhibitor, also improved biological activity and better in vivo oral bioavailability. This proof-of-concept study establishes the viability of monocyclic 1,2-azaborines as a novel pharmacophore with distinct pharmacological profiles that can help address challenges associated with solubility in drug development research...
February 8, 2017: ChemMedChem
Shao-Yan Pu, Qin Yu, Huan Wu, Jian-Jun Jiang, Xiao-Qiong Chen, Yong-Han He, Qing-Peng Kong
By analyzing 4987 cancer transcriptomes from The Cancer Genome Atlas (TCGA), we identified that excision repair cross-complementation group 6 like (ERCC6L), a newly discovered DNA helicase, is highly expressed in 12 solid cancers. However, its role and mechanism in tumorigenesis are largely unknown. In this study, we found that ERCC6L silencing by small interring RNA (siRNA) or short hairpin RNA (shRNA) significantly inhibited the proliferation of breast (MCF-7, MDA-MB-231) and kidney cancer cells (786-0). Furthermore, ERCC6L silencing induced cell cycle arrest at G0/G1 phase without affecting apoptosis...
February 2, 2017: Oncotarget
Seung-Shick Shin, Se Yeon Won, Dae-Hwa Noh, Byungdoo Hwang, Wun-Jae Kim, Sung-Kwon Moon
Preclinical Research Previous studies have shown that morin exerts diverse pharmacological activities. In this study, we investigated the inhibitory activity of morin on bladder cancer EJ cells. Morin significantly inhibited EJ cell proliferation, which was related to the G1-phase cell cycle arrest together with the reduced expression of cyclin D1, cyclin E, CDK2, and CDK4 via increased expression of p21WAF1. Morin also increased ERK1/2 phosphorylation and decreased JNK and AKT phosphorylation without altering the p38MAPK phosphorylation levels...
February 8, 2017: Drug Development Research
S Samarasinghe, H Ling
In this paper, we show how to extend our previously proposed novel continuous time Recurrent Neural Networks (RNN) approach that retains the advantage of continuous dynamics offered by Ordinary Differential Equations (ODE) while enabling parameter estimation through adaptation, to larger signalling networks using a modular approach. Specifically, the signalling network is decomposed into several sub-models based on important temporal events in the network. Each sub-model is represented by the proposed RNN and trained using data generated from the corresponding ODE model...
February 4, 2017: Bio Systems
Xuexiang Chen, Xian Wu, Wen Ouyang, Min Gu, Zili Gao, Mingyue Song, Yunjiao Chen, Yanyin Lin, Yong Cao, Hang Xiao
The tender leaves of Rubus corchorifolius L. f. have been consumed as tea for drinking in China since ancient times. In this study, a novel ent-kaurane diterpenoid was isolated and identified from R. corchorifolius L. f. leaves as ent-kaur-2-one-16β,17-dihydroxy-acetone-ketal (DEK). DEK suppressed the growth of HCT116 human colon cancer cells with an IC50 value of 40 ± 0.21 μM, while it did not cause significant growth inhibition on CCD-18Co human colonic myofibroblasts at up to100 μM. Moreover, DEK induced extensive apoptosis and S phase cell cycle arrest in the colon cancer cells...
February 13, 2017: Journal of Agricultural and Food Chemistry
Quan Xia, Yingli Zhao, Jiali Wang, Wenhao Qiao, Dongling Zhang, Hao Yin, Dujuan Xu, Feihu Chen
PURPOSE: 4-amino-2-trifluoromethyl-phenyl retinate (ATPR) was reported to potentially inhibit proliferation and induce differentiation activity in some tumor cells. In this study, a proteomics approach was used to investigate the possible mechanism by screening the differentially expressed protein profiles of SGC-7901 cells before and after ATPR-treatment in vitro. EXPERIMENTAL DESIGN: Peptides digested from the total cellular proteins were analyzed by reverse phase LC-MS/MS followed by a label-free quantification analysis...
February 6, 2017: Proteomics. Clinical Applications
Mansour Poorebrahim, Ali Salarian, Saeideh Najafi, Mohammad Foad Abazari, Maryam Nouri Aleagha, Mohammad Nasr Dadras, Seyed Mohammad Jazayeri, Atousa Ataei, Vahdat Poortahmasebi
Epstein-Barr virus (EBV) is the most common cause of infectious mononucleosis (IM) and establishes lifetime infection associated with a variety of cancers and autoimmune diseases. The aim of this study was to develop an integrative gene regulatory network (GRN) approach and overlying gene expression data to identify the representative subnetworks for IM and EBV latent infection (LI). After identifying differentially expressed genes (DEGs) in both IM and LI gene expression profiles, functional annotations were applied using gene ontology (GO) and BiNGO tools, and construction of GRNs, topological analysis and identification of modules were carried out using several plugins of Cytoscape...
February 2, 2017: Archives of Virology
Fangfang Xu, Kevin Yueju Wang, Nan Wang, Gangqiang Li, Dehu Liu
Diabetes has become the third largest cause of death in humans worldwide. Therefore, effective treatment for this disease remains a critical issue. Glucagon-like peptide-1 (GLP-1) plays an important role in glucose homeostasis, and therefore represents a promising candidate to use for the treatment of diabetes. Native GLP-1, however, is quickly degraded in in the circulatory system; which limits its clinical application. In the present study, a chemically-synthesized, modified analogue of human GLP-1 (mGLP-1) was designed...
2017: PloS One
Ryan J Davis, Jherek Swanger, Bridget T Hughes, Bruce E Clurman
Cyclin E, in conjunction with its catalytic partner cyclin-dependent kinase 2 (CDK2), regulates cell cycle progression as cells exit quiescence and enter S-phase. Multiple mechanisms control cyclin E periodicity during the cell cycle, including phosphorylation-dependent cyclin E ubiquitylation by the SCF(Fbw7) ubiquitin ligase. Serine 384 (S384) is the critical cyclin E phosphorylation site that stimulates Fbw7 binding and cyclin E ubiquitylation and degradation. Because S384 is autophosphorylated by bound CDK2, this presents a paradox as to how cyclin E can evade autocatalytically induced degradation in order to phosphorylate its other substrates...
January 30, 2017: Molecular and Cellular Biology
Hongmei Chen, Xuexi Tang, Bin Zhou, Ningning Xu, Zhongyuan Zhou, Kuan Fang, You Wang
Cell proliferation is closely related to cell cycle which is strictly regulated by genes and regulatory proteins. In the present study, we comparatively analyzed the toxic effects of BDE-47 and BDE-209 on cell proliferation of Neuro-2a cells, and the possible mechanism was discussed. The results indicated that BDE-47 significantly inhibited the cell proliferation and the cell cycle were arrest at G1 phase, while BDE-209 had little effects on either cell proliferation or cell cycle. qRT-PCR and Western blot assay presented that BDE-47 up-regulated the gene expressions of p53 and p21, which down-regulated the expresseion of cyclinD1 and CDK2, and inhibited retinoblastoma protein (pRb) phosphorylation...
December 21, 2016: Environmental Toxicology and Pharmacology
Xuexiang Chen, Zili Gao, Mingyue Song, Wen Ouyang, Xian Wu, Yunjiao Chen, Liping Zhou, Dixon William, Xiaokun Cai, Yong Cao, Shuangde Zhou, Zhonghai Tang, Hang Xiao
The leaves of Rubus corchorifolius L. f. have been consumed as a herbal tea for a long time. In this study, two novel (1 and 5) and four known (2, 3, 4 and 6) terpenoids were isolated from the leaves of Rubus corchorifolius L. f. Structural analysis was performed using various spectroscopic methods ((1)H NMR, (13)C NMR and MS) to identify the following six compounds: (16α)-16,17,18-trihydroxy-ent-kauran-18-O-β-d-glucoside (1), ent-16β,17-dialkyl-3-oxygen-kaurane (2), ent-kaurane-3α,16β,17-triol (3), ent-kaurane(5R,8S,9R,10R,13R,16R)-2-one-16α,17-diol (4), (16R)-16β,17,19-trihydroxy-ent-kaur-3-one (5) and ent-16α,17-dihydroxy-kauran-19-oic-acid (6)...
January 30, 2017: Food & Function
Aleksander Lenert, David W Fardo
OBJECTIVES: To identify novel risk genes by gene-based association analysis in rheumatoid arthritis (RA). METHODS: We performed gene-based association testing with GATES (Gene-based Association Test using Extended Simes procedure) to augment the power of genomewide-association study (GWAS) results from the largest meta-GWAS by Okada et al. in 14,361 RA cases and 43,923 controls of European ancestry using 8,694,488 SNPs. RESULTS: We identified 115 genes significantly associated with RA by gene-based association testing corresponding to 43 RA risk loci; 23 risk loci contained a single top risk gene, while 20 risk loci contained two or more risk genes...
January 27, 2017: Clinical and Experimental Rheumatology
Michaela Nekardová, Ladislava Vymětalová, Prashant Khirsariya, Silvia Kováčová, Michaela Hylsová, Radek Jorda, Vladimír Kryštof, Jindřich Fanfrlík, Pavel Hobza, Kamil Paruch
The structural basis for the interaction of roscovitine and analogues containing 13 different bioisosteric central heterocycles with the enzyme cyclin-dependent kinase 2 (CDK2) is elucidated. Although all the central scaffolds are very similar to the purine core of roscovitine, the experimentally determined IC50 values of the inhibitors span three orders of magnitude. By using an extensive computational chemistry approach, the affinities of the inhibitors to CDK2 are determined as calculated binding scores of complexes of the inhibitors with the protein...
January 27, 2017: Chemphyschem: a European Journal of Chemical Physics and Physical Chemistry
Xiao Wu, Meng-Yao Wu, Min Jiang, Qiaoming Zhi, Xiaojie Bian, Meng-Dan Xu, Fei-Ran Gong, Juan Hou, Min Tao, Liu-Mei Shou, Weiming Duan, Kai Chen, Meng Shen, Wei Li
PURPOSE: Despite new developments in cancer therapy, chemotherapy and radiotherapy remain the cornerstone of breast cancer treatment. Therefore, finding ways to reduce the toxicity and increase sensitivity is particularly important. Tumor necrosis factor alpha (TNF-α) exerts multiple functions in cell proliferation, differentiation and apoptosis. In the present study, we investigated whether TNF-α could enhance the effect of chemotherapy and radiotherapy against breast cancer cells...
2017: Cancer Cell International
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