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https://www.readbyqxmd.com/read/28214932/theoretical-and-experimental-study-of-polycyclic-aromatic-compounds-as-%C3%AE-tubulin-inhibitors
#1
Fabian E Olazarán, Carlos A García-Pérez, Debasish Bandyopadhyay, Isaias Balderas-Rentería, Angel D Reyes-Figueroa, Lars Henschke, Gildardo Rivera
In this work, through a docking analysis of compounds from the ZINC chemical library on human β-tubulin using high performance computer cluster, we report new polycyclic aromatic compounds that bind with high energy on the colchicine binding site of β-tubulin, suggesting three new key amino acids. However, molecular dynamic analysis showed low stability in the interaction between ligand and receptor. Results were confirmed experimentally in in vitro and in vivo models that suggest that molecular dynamics simulation is the best option to find new potential β-tubulin inhibitors...
March 2017: Journal of Molecular Modeling
https://www.readbyqxmd.com/read/28214891/up-regulated-atf4-expression-increases-cell-sensitivity-to-apoptosis-in-response-to-radiation
#2
Ying Zong, Shijie Feng, Jinwei Cheng, Chenlin Yu, Guocai Lu
BACKGROUND/AIMS: Activating transcription factor 4 (ATF4) is a member of the activating transcription factor family which regulates the expression of genes involved in amino acid metabolism, redox homeostasis and ER stress responses. ATF4 is also over-expressed in human solid tumors, although its effect on responsiveness to radiation is largely unexplored. METHODS: Real-time PCR was used to detect ATF4 mRNA levels in cells treated with different doses of 60Coγ radiation...
February 13, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28214630/ph-and-reduction-dual-responsive-dipeptide-cationic-lipids-with-%C3%AE-tocopherol-hydrophobic-tail-for-efficient-gene-delivery
#3
Qiang Liu, Rong-Chuan Su, Wen-Jing Yi, Li-Ting Zheng, Shan-Shan Lu, Zhi-Gang Zhao
A series of tocopherol-based cationic lipid 3a-3f bearing a pH-sensitive imidazole moiety in the dipeptide headgroup and a reduction-responsive disulfide linkage were designed and synthesized. Acid-base titration of these lipids showed good buffering capacities. The liposomes formed from 3 and co-lipid 1, 2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) could efficiently bind and condense DNA into nanoparticles. Gel binding and HPLC assays confirmed the encapsulated DNA could release from lipoplexes 3 upon addition of 10 mM glutathione (GSH)...
February 12, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28214599/hctoll3-was-involved-in-anti-vibrio-defense-in-freshwater-pearl-mussel-hyriopsis-cumingii
#4
Hong-Wei Zhang, Ying Huang, Xin Man, Yue Wang, Kai-Min Hui, Shao-Wu Yin, Xiao-Wen Zhang
Toll-like receptors (TLRs) play an important role in the activation of innate immune response but their functions in bivalves remain largely unknown. In this study, we identified a TLR from the freshwater pearl mussel Hyriopsis cumingii (HcToll3) and investigated its functions in immunity. The full-length cDNA of HcToll3 is 3852 bp and includes an open reading frame (ORF) of 3228 bp that encodes a polypeptide of 1075 amino acids. The predicted HcToll3 protein shares similar structural characteristics with other known Toll family proteins...
February 15, 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/28214587/paqr3-augments-amino-acid-deprivation-induced-autophagy-by-inhibiting-mtorc1-signaling
#5
Lin Wang, Yi Pan, Meiqin Huang, Xue You, Feifan Guo, Yan Chen
Amino acids are the key activators of the mTOR complex 1 (mTORC1, mainly composed of mTOR, Raptor and mLST8) required for cell growth and proliferation. On the other hand, deprivation of amino acids induces autophagy via inhibition of mTORC1 signaling. We report here that amino acid-induced mTORC1 activity and amino acid deprivation-induced autophagy are regulated by PAQR3, a tumor suppressor. At the cellular level, PAQR3 negatively regulates amino acid-induced activation of mTORC1. The N-terminal end of PAQR3 interacts with the WD domains of Raptor and mLST8 directly...
February 15, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28214369/diagnostic-accuracy-of-history-physical-exam-laboratory-tests-and-point-of-care-ultrasound-for-pediatric-acute-appendicitis-in-the-emergency-department-a-systematic-review-and-meta-analysis
#6
Roshanak Benabbas, Mark Hanna, Jay Shah, Richard Sinert
BACKGROUND: Acute appendicitis (AA) is the most common surgical emergency in children. Accurate and timely diagnosis is crucial but challenging due to atypical presentations and the inherent difficulty of obtaining a reliable history and physical examination in younger children. OBJECTIVES: To determine the utility of history, physical exam, laboratory tests, Pediatric Appendicitis Score (PAS) and Emergency Department-Point-of-Care Ultrasound (ED-POCUS) in the diagnosis of AA in ED pediatric patients...
February 18, 2017: Academic Emergency Medicine: Official Journal of the Society for Academic Emergency Medicine
https://www.readbyqxmd.com/read/28214356/comparative-analysis-of-the-transcriptional-responses-to-low-and-high-temperature-in-three-rice-planthopper-species
#7
Hai-Jian Huang, Jian Xue, Ji-Chong Zhuo, Ruo-Lin Cheng, Hai-Jun Xu, Chuan-Xi Zhang
The brown planthopper (Nilaparvata lugens, BPH), white-backed planthopper (Sogatella furcifera, WBPH), and small brown planthopper (Laodelphax striatellus, SBPH) are important rice pests in Asia. These three species differ in thermal tolerance and exhibit quite different migration and overwintering strategies. To understand the underlying mechanisms, we sequenced and compared the transcriptome of the three species under different temperature treatments. We found that metabolism-, exoskeleton-, and chemosensory-related genes were modulated...
February 18, 2017: Molecular Ecology
https://www.readbyqxmd.com/read/28214241/improvement-of-operational-stability-of-ogataea-minuta-carbonyl-reductase-for-chiral-alcohol-production
#8
Kohsuke Honda, Mizuha Inoue, Tomohiro Ono, Kenji Okano, Yasumasa Dekishima, Hiroshi Kawabata
Directed evolution of enantio-selective carbonyl reductase from Ogataea minuta was conducted to improve the operational stability of the enzyme. A mutant library was constructed by an error-prone PCR and screened using a newly developed colorimetric assay. The stability of a mutant with two amino acid substitutions was significantly higher than that of the wild type at 50°C in the presence of dimethyl sulfoxide. Site-directed mutagenesis analysis showed that the improved stability of the enzyme can be attributed to the amino acid substitution of V166A...
February 14, 2017: Journal of Bioscience and Bioengineering
https://www.readbyqxmd.com/read/28214225/a-relay-pathway-between-arginine-and-tryptophan-metabolism-confers-immunosuppressive-properties-on-dendritic-cells
#9
Giada Mondanelli, Roberta Bianchi, Maria Teresa Pallotta, Ciriana Orabona, Elisa Albini, Alberta Iacono, Maria Laura Belladonna, Carmine Vacca, Francesca Fallarino, Antonio Macchiarulo, Stefano Ugel, Vincenzo Bronte, Federica Gevi, Lello Zolla, Auke Verhaar, Maikel Peppelenbosch, Emilia Maria Cristina Mazza, Silvio Bicciato, Yasmina Laouar, Laura Santambrogio, Paolo Puccetti, Claudia Volpi, Ursula Grohmann
Arginase 1 (Arg1) and indoleamine 2,3-dioxygenase 1 (IDO1) are immunoregulatory enzymes catalyzing the degradation of l-arginine and l-tryptophan, respectively, resulting in local amino acid deprivation. In addition, unlike Arg1, IDO1 is also endowed with non-enzymatic signaling activity in dendritic cells (DCs). Despite considerable knowledge of their individual biology, no integrated functions of Arg1 and IDO1 have been reported yet. We found that IDO1 phosphorylation and consequent activation of IDO1 signaling in DCs was strictly dependent on prior expression of Arg1 and Arg1-dependent production of polyamines...
February 13, 2017: Immunity
https://www.readbyqxmd.com/read/28214203/prognostic-value-of-survivin-and-dna-topoisomerase-ii%C3%AE-in-diffuse-and-anaplastic-astrocytomas
#10
R K Varughese, A J Skjulsvik, S H Torp
Distinguishing WHO grade II astrocytomas from grade III is a difficult task. This study looks into the potential prognostic use of mitotic activity and the proliferation markers Ki67/MiB-1 (Ki67), survivin and DNA topoisomerase IIα (TIIα) in 59 WHO grade II diffuse astrocytomas (DA) and 33 WHO grade III anaplastic astrocytomas (AA), IDH1 R132H-mutated and not otherwise specified (NOS) by means of immunohistochemistry. All proliferation markers showed higher expression in AA compared with DA. Only Ki67 had significantly greater expression in astrocytomas, NOS vs...
January 21, 2017: Pathology, Research and Practice
https://www.readbyqxmd.com/read/28214066/identification-of-g-170g-a-and-g-332g-a-mutations-in-exon-3-of-leptin-gene-bcnl-and-cail-and-their-association-with-semen-quality-and-testicular-dimensions-in-sanjabi-rams
#11
Roya Bakhtiar, Alireza Abdolmohammadi, Hadi Hajarian, Zahra Nikousefat, Davood Kalantar-Neyestanaki
The purpose of this study was to investigate leptin gene polymorphisms and their relationships with the characteristics of sperm quality and testicular dimensions. Semen samples were collected from 96 Sanjabi rams during autumn and spring seasons over two years. Simultaneously, the dimensions of length, width and scrotal circumference were measured. Blood samples were taken from the jugular vein to extract DNA. PCR was performed to amplify a 463bp fragment including exon 3 of leptin gene. PCR products were digested by Bcnl and Cail restriction enzymes to identify 170G>A and 332G>A mutations in exon 3, respectively...
February 4, 2017: Animal Reproduction Science
https://www.readbyqxmd.com/read/28213921/maternal-igf1-and-igf1r-polymorphisms-and-the-risk-of-spontaneous-preterm-birth
#12
Jian-Rong He, Yu-Mian Lai, Hui-Hui Liu, Guang-Jian Liu, Wei-Dong Li, Xue-Jiao Fan, Xue-Ling Wei, Xiao-Yan Xia, Ya-Shu Kuang, Xiao-Dan Liu, Nian-Nian Chen, Jin-Hua Lu, Qiao-Zhu Chen, Wei-Bi Mai, Hui-Min Xia, Xiu Qiu
BACKGROUND: The insulin-like growth factor (IGF) pathway was involved in the occurrence of spontaneous preterm birth (SPTB), but little is known regarding the relationship between genetic variations in IGF pathway and the risk of SPTB. We aimed to investigate the associations of IGF1 rs972936 and IGF1 receptor (IGF1R) rs2229765 polymorphisms with SPTB risk in a Chinese population. METHOD: A total of 114 cases of SPTB and 250 controls of term delivery were included from Guangzhou Women and Children's Medical Center, China...
February 18, 2017: Journal of Clinical Laboratory Analysis
https://www.readbyqxmd.com/read/28213913/application-of-crs-pcr-rflp-to-identify-cyp1a1-gene-polymorphism
#13
Mingcui Ding, Xiaoran Duan, Xiaolei Feng, Pengpeng Wang, Wei Wang
BACKGROUND: Cytochrome P4501A1 (CYP1A1) is a member of the cytochrome P450 gene family and plays an important role in the metabolism of exogenous and endogenous material. In recent research, it has been shown that its genetic polymorphisms are associated with many diseases. But the isoschizomers such as the BsrDI enzyme required for the detection of this polymorphism are expensive. METHODS: The study used an improved PCR-RFLP method with mismatched base for detection of the single-nucleotide polymorphism rs1048943...
February 18, 2017: Journal of Clinical Laboratory Analysis
https://www.readbyqxmd.com/read/28213898/nuclear-localization-of-a-putative-phytophthora-sojae-bzip1-transcription-factor-is-mediated-by-multiple-targeting-motifs
#14
Yufeng Fang, Brett M Tyler
Oomycetes are fungal-like eukaryotic microbes in the kingdom Stramenopila. We recently found that the oomycete plant pathogen Phytophthora sojae uses nuclear localization signals (NLSs) for translocation of proteins into the nucleus that differ from conventional well-characterized NLSs from mammals and yeast. Here we have characterized in depth the nuclear localization signals of a P. sojae basic leucine zipper transcription factor, PsbZIP1. Nuclear localization of PsbZIP1 was determined by a central conserved region overlapping the DNA binding domain...
February 18, 2017: Molecular Microbiology
https://www.readbyqxmd.com/read/28213880/detection-of-digestive-malignancies-and-post-gastrectomy-complications-via-gastrointestinal-fluid-examination
#15
REVIEW
Lei Huang, Aman Xu
To date, gastric carcinoma (GC) is one of the common and fatal digestive malignancies worldwide. The prognosis of GC is not always satisfactory because of late diagnosis. Scholars are keen on discovering novel accurate and economical biomarkers in body liquids for GC screening to detect and evaluate the lesion before the results of imaging techniques are obtained. While traditional serum assays have limited sensitivity and specificity, gastrointestinal juice may provide relevant specific biomarkers because of its close contact with the tumor...
February 17, 2017: Frontiers of Medicine
https://www.readbyqxmd.com/read/28213873/first-isolation-and-genetic-characteristics-of-porcine-sapeloviruses-in-hunan-china
#16
Taotao Yang, Runcheng Li, Wang Peng, Meng Ge, Binyu Luo, Tailong Qu, Xinglong Yu
Outbreaks of diarrhea in piglets cause serious economic consequences in China. Diarrhetic fecal samples from 20 Hunan farm piglets were tested and found to be positive for porcine epidemic diarrhea virus (PEDV) by RT-PCR, although incubation with porcine kidney (PK-15) cells failed to produce infectious PEDV. Four porcine sapelovirus (PSV) strains (designated as PSV-HuNs) were isolated from four of the samples. Genomic sequence analysis revealed open reading frames encoding polyproteins of 2,331 (HuN1, 2 and 3) and 2,332 (HuN4) amino acids...
February 17, 2017: Archives of Virology
https://www.readbyqxmd.com/read/28213870/molecular-characterization-of-bovine-leukemia-virus-from-moldovan-dairy-cattle
#17
Aneta Pluta, Marzena Rola-Łuszczak, Piotr Kubiś, Svetlana Balov, Roman Moskalik, Bhudipa Choudhury, Jacek Kuźmak
Bovine leukemia virus (BLV) is the causative agent of enzootic bovine leukosis (EBL), a disease that has worldwide distribution. Whilst it has been eradicated in most of Western Europe and Scandinavia, it remains a problem in other regions, particularly Eastern Europe and South America. For this study, in 2013, 24 cattle from three farms in three regions of Moldova were screened by ELISA and nested PCR. Of these cattle, 14 which were PCR positive, and these were molecularly characterized based on the nucleotide sequence of the env gene and the deduced amino acid sequence of the encoded gp51 protein...
February 17, 2017: Archives of Virology
https://www.readbyqxmd.com/read/28213519/an-extra-amino-acid-residue-in-transmembrane-domain-10-of-the-gaba-transporter-gat-1-is-required-for-efficient-ion-coupled-transport
#18
Oshrat Dayan, Anu Nagarajan, Raven Shah, Assaf Ben-Yona, Lucy R Forrest, Baruch I Kanner
The GABA transporter GAT-1 mediates electrogenic transport of its substrate together with sodium and chloride. It is a member of the neurotransmitter:sodium:symporters, which are crucial for synaptic transmission. Compared to all other neurotransmitter:sodium:symporters, GAT-1 and the other members of the GABA transporter subfamily, all contain an extra amino acid residue at or near a conserved glycine in transmembrane segment 10. Therefore, we studied the functional impact of deletion and replacement mutants of Gly-457, and its two adjacent residues in GAT-1...
February 17, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28213514/peripheral-membrane-interactions-boost-the-engagement-by-an-anti-hiv-1-broadly-neutralizing-antibody
#19
Edurne Rujas, José M M Caaveiro, Sara Insausti, Miguel García-Porras, Kouhei Tsumoto, José L Nieva
The 4E10 antibody displays an extreme breadth of HIV-1 neutralization and therefore constitutes a suitable model system for structure- guided vaccine design and immunotherapeutics against AIDS. In this regard, the relevance of auto- reactivity with membrane lipids for the biological function of this antibody is still a subject of controversy. To address this dispute, herein we have compared the membrane-partitioning ability of the 4E10 antibody and several of its variants, which were mutated at the region of the paratope surface in contact with the membrane-interface...
February 17, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28213390/epigenetic-patterns-in-blood-associated-with-lipid-traits-predict-incident-coronary-heart-disease-events-and-are-enriched-for-results-from-genome-wide-association-studies
#20
Åsa K Hedman, Michael M Mendelson, Riccardo E Marioni, Stefan Gustafsson, Roby Joehanes, Marguerite R Irvin, Degui Zhi, Johanna K Sandling, Chen Yao, Chunyu Liu, Liming Liang, Tianxiao Huan, Allan F McRae, Serkalem Demissie, Sonia Shah, John M Starr, L Adrienne Cupples, Panos Deloukas, Timothy D Spector, Johan Sundström, Ronald M Krauss, Donna K Arnett, Ian J Deary, Lars Lind, Daniel Levy, Erik Ingelsson
BACKGROUND: Genome-wide association studies have identified loci influencing circulating lipid concentrations in humans; further information on novel contributing genes, pathways, and biology may be gained through studies of epigenetic modifications. METHODS AND RESULTS: To identify epigenetic changes associated with lipid concentrations, we assayed genome-wide DNA methylation at cytosine-guanine dinucleotides (CpGs) in whole blood from 2306 individuals from 2 population-based cohorts, with replication of findings in 2025 additional individuals...
January 2017: Circulation. Cardiovascular Genetics
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