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https://www.readbyqxmd.com/read/29777707/functional-analysis-of-juxta-and-intra-membrane-domains-of-murine-app-by-genome-editing-in-neuro2a-cells
#1
Nanaka Kaneshiro, Ryosuke Imaoka, Masato Komai, Taku Kashiyama, Takashi Sakurai, Takashi Uehara, Nobumasa Takasugi
Amyloid-β precursor protein (APP) correlates with the pathogenesis of certain brain diseases, such as Alzheimer disease (AD). APP is cleaved by several enzymes to produce APP metabolites, including the amyloid beta peptide (Aβ), which accumulates in the brain of AD patients. However, the exact functions of APP metabolites remain elusive. In this study, using genome editing technology, we mutated juxta- and intra-membrane domains of murine APP in the mouse neuroblastoma cell line, Neuro2a. We identified several clones that expressed characteristic patterns of APP metabolites...
May 16, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29777059/sequence-diversity-of-tubulin-isotypes-in-regulation-of-the-mitochondrial-voltage-dependent-anion-channel
#2
Tatiana K Rostovtseva, Philip A Gurnev, David P Hoogerheide, Amandine Rovini, Minhajuddin Sirajuddin, Sergey M Bezrukov
The microtubule protein tubulin is a heterodimer comprising α/β subunits, in which each subunit features multiple isotypes in vertebrates. For example, seven α-tubulin and eight β-tubulin isotypes in the human tubulin gene family vary mostly in the length and primary sequence of the disordered anionic C-terminal tails (CTTs). The biological reason for such sequence diversity remains a topic of vigorous enquiry. Here, we demonstrate that it may be a key feature of tubulin's role in regulation of the permeability of the mitochondrial outer membrane voltage-dependent anion channel (VDAC)...
May 18, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29774951/protein-kinase-c%C3%AE-pkc%C3%AE-involved-in-the-regulation-of-pakt1-ser473-on-the-release-of-mouse-oocytes-from-diplotene-arrest
#3
Lingling Liu, Sen Li, Hanwen Li, Dahai Yu, Chunyu Li, Gensong Li, Yu Cao, Chen Feng, Xin Deng
Defects in meiotic maturation may lead to chromosome segregation errors and genomic instability. Previous reports indicated that protein kinase C delta (PKCδ) may interact with microtubule organizing center-associated protein to play a role on meiotic spindle organization of mammalian oocytes. In this study, we explored the potential role of protein kinase B alpha (PKBα/Akt1), PKCδ, and their relationship on meiotic maturation of mouse oocytes. We examined the expression and localization of pAkt1 (Ser473) and/or pPKCδ (Thr505) under the treatment of SH-6 or Sotrastaurin...
May 18, 2018: Cell Biochemistry and Function
https://www.readbyqxmd.com/read/29772274/pharmacodynamic-and-pharmacokinetic-characteristics-of-ymr-65-a-tubulin-inhibitor-in-tumor-bearing-mice
#4
Ali Fan, Jiali Wei, Mengru Yang, Qing Zhang, Yaliang Zhang, Qingwang Liu, Ning Li, Di Zhao, Yang Lu, Junxiu Li, Jie Zhao, Shuhua Deng, Bingjie Zhang, Hailiang Zhu, Xijing Chen
YMR-65, 5-(5-bromo-1-methyl-1H-indol-3-yl)-3-(3-methoxyphenyl)-4, 5-dihydro-1H-pyrazole-1-carboxamide, is a potential tubulin inhibitor exhibiting good anticancer activity. In our study, we illustrated the biological activities in HepG2 cells and the pharmacodynamic and pharmacokinetic profiles were evaluated in murine H22 hepatoma-bearing mice. Molecular docking assay and colchicine competition assay indicated that YMR-65 could bind tightly to the colchicine binding site of tubulin. Further investigation demonstrated that YMR-65 arrested cells in the G2/M phase of cell cycle and induced apoptosis in HepG2 cells...
May 14, 2018: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/29772242/synthesis-molecular-modeling-and-biological-evaluation-of-potent-analogs-of-2-methoxyestradiol
#5
Nora Al-Kazaale, Phuong T Tran, Farhad Haidari, Eirik Johansson Solum, Sandra Liekens, Peter Vervaeke, Ingebrigt Sylte, Jing-Jy Cheng, Anders Vik, Trond Vidar Hansen
The endogenous steroid 2-methoxyestradiol (1) has attracted a great interest as a lead compound towards the development of new anti-cancer drugs. Herein, the synthesis, molecular modeling, anti-proliferative and anti-angiogenic effects of ten 2-ethyl and four 2-methoxy analogs of estradiol are reported. The ethyl group was introduced to the steroid A-ring using a novel Friedel-Crafts alkylation protocol. Several analogs displayed potent anti-proliferative activity with IC50 -values in the submicromolar range towards the CEM human leukemia cancer cell line...
May 14, 2018: Steroids
https://www.readbyqxmd.com/read/29769406/spindle-assembly-disruption-and-cancer-cell-apoptosis-with-a-cltc-binding-compound
#6
Michael J Bond, Marina Bleiler, Lauren E Harrison, Eric W Scocchera, Masako Nakanishi, Narendran G-Dayanandan, Santosh Keshipeddy, Daniel W Rosenberg, Dennis L Wright, Charles Giardina
AK3 compounds are mitotic-arrest agents that induce high levels of γH2AX during mitosis and apoptosis following release from arrest. We synthesized a potent AK3 derivative, AK306, that induced arrest and apoptosis of the HCT116 colon cancer cell line with an EC50 of ~50 nM. AK306 was active on a broad spectrum of cancer cell lines with total growth inhibition values ranging from ~25 nM to 25 µM. Using biotin and BODIPY-linked derivatives of AK306, binding to clathrin heavy chain (CLTC/CHC) was observed, a protein with roles in endocytosis and mitosis...
May 16, 2018: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/29769312/the-chloroplast-division-protein-arc6-acts-to-inhibit-disassembly-of-gdp-bound-ftsz2
#7
Min Woo Sung, Rahamthulla Shaik, Allan D TerBush, Katherine W Osteryoung, Stanislav Vitha, Andreas Holzenburg
Chloroplasts host photosynthesis and fulfill other metabolic functions that are essential to plant life. They have to divide by binary fission to maintain their numbers throughout cycles of cell division. Chloroplast division is achieved by a complex ring-shaped division machinery located on both the inner (stromal) and the outer (cytosolic) side of the chloroplast envelope. The inner division ring (termed the Z ring) is formed by the assembly of tubulin-like FtsZ1 and FtsZ2 proteins. ARC6 is a key chloroplast division protein that interacts with the Z ring...
May 16, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29768039/loss-of-sonic-hedgehog-gene-leads-to-muscle-development-disorder-and-megaesophagus-in-mice
#8
Xueting Jia, Li Min, Shengtao Zhu, Shutian Zhang, Xiaofeng Huang
Sonic hedgehog ( Shh) is crucial for organogenesis in the foregut. This study investigated the function of Shh at the late-gestational stage; during which, the esophagus continues to differentiate. We established cytokeratin 14 ( CK14)-Cre;Shhfl/fl mice in which the down-regulation of Shh in the epithelium occurred at approximately the same time as esophageal muscle conversion. Hematoxylin and eosin and immunohistochemical staining, with antibodies against keratin 14, Shh, patched 1 (Ptch1), Gli1, proliferating cell nuclear antigen (PCNA), α-smooth muscle actin (αSMA), high-molecular-weight caldesmon (hCD), myogenin, paired box 7 (Pax7), β3-tubulin, and protein gene product 9...
May 16, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29768004/effect-of-nucleotide-state-on-the-protofilament-conformation-of-tubulin-octamers
#9
Anjela Manandhar, Myungshim Kang, Kaushik Chakraborty, Sharon M Loverde
At the molecular level, the dynamic instability (random growth and shrinkage) of the microtubule (MT) is driven by the nucleotide state (GTP vs. GDP) in the β subunit of the tubulin dimers at the MT cap. Here, we use large-scale molecular dynamics (MD) simulations and normal mode analysis (NMA) to characterize the effect of a single GTP cap layer on tubulin octamers composed by two neighboring protofilaments (PFs). We utilize recently reported high-resolution structures of dynamic MTs to simulate a GDP octamer both with and without a single GTP cap layer...
May 16, 2018: Journal of Physical Chemistry. B
https://www.readbyqxmd.com/read/29766931/-in-vitro-differentiation-of-neural-cells-from-human-adipose-tissue-derived-stromal-cells
#10
Shruti D Dave, Chetan N Patel, Aruna V Vanikar, Hargovind L Trivedi
Background: Stem cells, including neural stem cells (NSCs), are endowed with self-renewal capability and hence hold great opportunity for the institution of replacement/protective therapy. We propose a method for in vitro generation of stromal cells from human adipose tissue and their differentiation into neural cells. Materials and Methods: Ten grams of donor adipose tissue was surgically resected from the abdominal wall of the human donor after the participants' informed consents...
May 2018: Neurology India
https://www.readbyqxmd.com/read/29764743/design-synthesis-and-evaluation-of-photoactivatable-derivatives-of-microtubule-mt-active-1-2-4-triazolo-1-5-a-pyrimidines
#11
Killian Oukoloff, Jane Kovalevich, Anne-Sophie Cornec, Yuemang Yao, Zachary A Owyang, Michael James, John Q Trojanowski, Virginia M-Y Lee, Amos B Smith, Kurt R Brunden, Carlo Ballatore
The [1,2,4]triazolo[1,5-a]pyrimidines comprise a promising class of non-naturally occurring microtubule (MT)-active compounds. Prior studies revealed that different triazolopyrimidine substitutions can yield molecules that either promote MT stabilization or disrupt MT integrity. These differences can have important ramifications in the therapeutic applications of triazolopyrimidines and suggest that different analogues may exhibit different binding modes within the same site or possibly interact with tubulin/MTs at alternative binding sites...
May 5, 2018: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/29763665/selection-and-paucity-of-phylogenetic-signal-challenge-the-utility-of-alpha-tubulin-in-reconstruction-of-evolutionary-history-of-free-living-litostomateans-protista-ciliophora
#12
Ľubomír Rajter, Peter Vďačný
The class Litostomatea represents a highly diverse but monophyletic group, uniting both free-living and endosymbiotic ciliates. Ribosomal RNA genes and ITS-region sequences helped to recognize and define the main litostomatean lineages, but did not provide enough phylogenetic signal to unambiguously resolve their interrelationships. In this study, we attempted to improve the resolution among main free-living predatory lineages by adding the gene coding for alpha-tubulin. However, our phylogenetic analyses challenged the performance of alpha-tubulin in reconstruction of evolutionary history of free-living litostomateans...
May 12, 2018: Molecular Phylogenetics and Evolution
https://www.readbyqxmd.com/read/29762881/colchicine-a-microtubule-disassembling-drug-in-the-therapy-of-cardiovascular-diseases
#13
George N Chaldakov
Colchicum autumnale, from which colchicine has been isolated more than 100 years ago, has been used as a treatment for pain and swelling for thousands of years. It is one of the few drugs known from that time period whose use has survived to modernity. Over the past decades, advances in the knowledge of (i) cytoskeletal microtubules (МТ), and (ii) anti-inflammatory and anti-fibrotic effects of colchicine, a classical MT-disassembling (tubulin-targeting) agent, have led to potential new uses for this very old drug extended beyond acute gouty arthritis and familial Mediterranean fever...
May 15, 2018: Cell Biology International
https://www.readbyqxmd.com/read/29762666/discovery-and-validation-of-methylation-biomarkers-for-ulcerative-colitis-associated-neoplasia
#14
Andrew D Beggs, Jonathan James, Germaine Caldwell, Toby Prout, Mark P Dilworth, Phillipe Taniere, Tariq Iqbal, Dion G Morton, Glenn Matthews
Background and aims: Ulcerative colitis (UC) is associated with a higher background risk of dysplasia and/or neoplasia due to chronic inflammation. There exist few biomarkers for identification of patients with dysplasia, and targeted biopsies in this group of patients are inaccurate in reliably identifying dysplasia. We aimed to examine the epigenome of UC dysplasia and to identify and validate potential biomarkers. Methods: Colonic samples from patients with UC-associated dysplasia or neoplasia underwent epigenome-wide analysis on the Illumina 450K methylation array...
May 14, 2018: Inflammatory Bowel Diseases
https://www.readbyqxmd.com/read/29761930/multiple-phosphorylation-sites-on-%C3%AE-tubulin-are-essential-and-contribute-to-the-biogenesis-of-basal-bodies-in-tetrahymena
#15
Ewa Joachimiak, Maria Jerka-Dziadosz, Łucja Krzemień-Ojak, Ewa Wacławek, Katarzyna Jedynak, Paulina Urbanska, Wojciech Brutkowski, Hanna Sas-Nowosielska, Hanna Fabczak, Jacek Gaertig, Dorota Wloga
The mechanisms that regulate γ-tubulin, including its post-translational modifications, are poorly understood. γ-Tubulin is important for the duplication of centrioles and structurally similar basal bodies (BBs), organelles which contain a ring of nine triplet microtubules. The ciliate Tetrahymena thermophila carries hundreds of cilia in a single cell and provides an excellent model to specifically address the role of γ-tubulin in the BBs assembly and maintenance. The genome of Tetrahymena contains a single γ-tubulin gene...
May 15, 2018: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29761881/expression-of-stem-cell-markers-nanog-and-nestin-in-lip-squamous-cell-carcinoma-and-actinic-cheilitis
#16
Fernanda M Scotti, Verônica C Mitt, Daniella S C Vieira, Michelle T Biz, Renata G Castro, Filipe Modolo
Cancer stem cells ( CSC ) proteins have been observed in several lesions and are associated with tumor beginning, evolution, and resistance to treatment. OBJECTIVES: to investigate the presence of NANOG, NESTIN, and β-tubulin in lip squamous cell carcinoma (LSCC), actinic cheilitis (AC), and normal epithelium (NE). MATERIALS AND METHODS: thirty cases of LSCC, thirty cases of AC (both analyzed according to the WHO classification and AC according to the binary classification), and twenty cases of NE were submitted to an immunohistochemical study...
May 15, 2018: Oral Diseases
https://www.readbyqxmd.com/read/29757853/multiplex-polymerase-chain-reaction-assay-for-screening-of-mycotoxin-genes-from-ocular-isolates-of-fusarium-species
#17
Orapin Anutarapongpan, Jorge Maestre-Mesa, Eduardo C Alfonso, Terrence P OʼBrien, Darlene Miller
PURPOSE: To identify mycotoxin genes among clinical ocular isolates of Fusarium species and to correlate these with clinical outcomes of Fusarium keratitis. METHODS: Fifty-four clinical isolates of Fusarium were retrieved from the Bascom Palmer Eye Institute Ocular Microbiology Laboratory data bank. Multiplex polymerase chain reactions were run to confirm the identification of Fusarium species [internal transcribed spacer sequence, translation elongation factor 1-α (TEF) and β-tubulin] and to detect the presence of genes encoding production of fumonisin B mycotoxins (FUM1 and FUM8) and trichothecene mycotoxins (deoxynivalenol and nivalenol)...
May 1, 2018: Cornea
https://www.readbyqxmd.com/read/29756010/mitochondrial-protein-sulfenation-during-aging-in-the-rat-brain
#18
Xiaorong Yang, Jinzi Wu, Siqun Jing, Michael J Forster, Liang-Jun Yan
There is accumulating evidence that cysteine sulfenation (cys-SOH) in proteins plays an important role in cellular response to oxidative stress. The purpose of the present study was to identify mitochondrial proteins that undergo changes in cys-SOH during aging. Studies were conducted in rats when they were 5 or 30 months of age. Following blocking of free protein thiols with N -ethylmaleimide, protein sulfenic acids were reduced by arsenite to free thiol groups that were subsequently labeled with biotin-maleimide...
2018: Biophysics Reports
https://www.readbyqxmd.com/read/29755952/a-simple-and-fast-method-for-fixation-of-cultured-cell-lines-that-preserves-cellular-structures-containing-gamma-tubulin
#19
Maria Alvarado-Kristensson
When using fluorescence microscope techniques to study cells, it is essential that the cell structure and contents are preserved after preparation of the samples, and that the preparation method employed does not create artefacts that can be perceived as cellular structure/components. γ-Tubulin forms filaments that in some cases are immunostained with an anti-γ-tubulin antibody, but this immunostaining is not reproducible [[1], [2]]. In addition, the C terminal region of γ-tubulin (green fluorescence protein tagged [GFP]-γ-tubulin334--449 ) forms cytosolic GFP-labeled structures, which can easily be imaged in live cells but are not preserved in fixed cells [[1], [3]]...
2018: MethodsX
https://www.readbyqxmd.com/read/29755347/honokiol-a-polyphenol-natural-compound-attenuates-cisplatin-induced-acute-cytotoxicity-in-renal-epithelial-cells-through-cellular-oxidative-stress-and-cytoskeleton-modulations
#20
Tse-En J Wang, Hung-Ting Liu, Yu-Hua Lai, Tong-Rong Jan, Naohiro Nomura, Hui-Wen Chang, Chi-Chung Chou, Ya-Jane Lee, Pei-Shiue J Tsai
Cisplatin is a potent anti-cancer drug that has been widely used in the treatment of various cancers; however, cisplatin administration results in severe nephrotoxicity and impedes its clinical applications. In this study, we showed that honokiol, a polyphenol constituent extracted from Magnolia officinalis exhibited a short-term protective effect against cisplatin-induced damages in renal epithelial cells in vitro . The protective effects of honokiol were resulted from the combination of (1) reduced cellular oxidative stress ranging from 53 to 32% reduction during a 24-h incubation, (2) the maintenance of cellular antioxidant capacity and (3) the stabilization of cytoskeletal structure of the kidney epithelial cells...
2018: Frontiers in Pharmacology
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