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https://www.readbyqxmd.com/read/28441714/long-non-coding-rna-hotair-functions-as-mirna-sponge-to-promote-the-epithelial-to-mesenchymal-transition-in-esophageal-cancer
#1
Feng Xu, Jing Zhang
BACKGROUND: Accumulating evidence indicates dysregulated expression of the long non-coding RNA HOTAIR (lncRNA-HOTAIR) may play a significant role in tumor progression. LncRNA-HOTAIR promotes several processes in esophageal cancer (EC), including cell growth, differentiation, invasion and migration. However, the mechanisms by which lncRNA-HOTAIR promotes invasion and migration EC remain unclear. METHODS: LncRNA-HOTAIR and miR-148a expression were quantified in 40 paired human EC and tumor-adjacent tissues and EC cell lines by quantitative real-time PCR (qRT-PCR)...
April 21, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28441648/the-epigenetic-regulation-of-gata4-dependent-brain-natriuretic-peptide-expression-during-alcohol-withdrawal
#2
Alexander Glahn, Mathias Rhein, Annemarie Heberlein, Marc Muschler, Johannes Kornhuber, Helge Frieling, Stefan Bleich, Thomas Hillemacher
OBJECTIVE: Natriuretic peptides participate in the collection of metabolic effects during alcohol withdrawal. Having witnessed modulation of other natriuretic peptides in alcohol-dependent patients during alcohol withdrawal, we were interested in the relation of brain natriuretic peptide (BNP) methylation with protein expression and craving in this longitudinal study. METHODS: Ninety-nine male patients were compared to 101 healthy controls concerning epigenetic regulation and protein expression during detoxification treatment...
April 26, 2017: Neuropsychobiology
https://www.readbyqxmd.com/read/28441623/identification-of-a-macrobrachium-nipponense-c-type-lectin-with-a-close-evolutionary-relationship-to-vertebrate-lectins
#3
Xin Huang, Tingting Li, Min Jin, Shaowu Yin, Wen Wang, Qian Ren
C-type lectins (CTLs) are involved in the innate immune defense of vertebrates and invertebrates against invading pathogens. This study cloned and characterized a novel C-type lectin (MnCTL) of the oriental river prawn, Macrobrachium nipponense. The cloned MnCTL cDNA encompasses an open reading frame of 774 nucleotides and encodes polypeptides of 257 residues. The deduced MnCTL protein contains a single carbohydrate recognition domain (CRD) with an EPN (Glu-Pro-Asn) motif in calcium-binding site 2. Phylogenetic analysis indicated that MnCTL has a closer evolutionary relationship with vertebrate lectins than with invertebrate lectins...
April 22, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28441541/molecular-interaction-of-2-4-diacetylphloroglucinol-dapg-with-human-serum-albumin-hsa-the-spectroscopic-calorimetric-and-computational-investigation
#4
Pragna Lakshmi T, Moumita Mondal, Krishna Ramadas, Sakthivel Natarajan
Drug molecule interaction with human serum albumin (HSA) affects the distribution and elimination of the drug. The compound, 2,4-diacetylphloroglucinol (DAPG) has been known for its antimicrobial, antiviral, antihelminthic and anticancer properties. However, its interaction with HSA is not yet reported. In this study, the interaction between HSA and DAPG was investigated through steady-state fluorescence, time-resolved fluorescence (TRF), circular dichroism (CD), Fourier transform infrared (FT-IR) spectroscopy, isothermal titration calorimetry (ITC), molecular docking and molecular dynamics simulation (MDS)...
April 18, 2017: Spectrochimica Acta. Part A, Molecular and Biomolecular Spectroscopy
https://www.readbyqxmd.com/read/28441533/a-global-view-of-rna-protein-interactions-identifies-post-transcriptional-regulators-of-root-hair-cell-fate
#5
Shawn W Foley, Sager J Gosai, Dongxue Wang, Nur Selamoglu, Amelia C Sollitti, Tino Köster, Alexander Steffen, Eric Lyons, Fevzi Daldal, Benjamin A Garcia, Dorothee Staiger, Roger B Deal, Brian D Gregory
The Arabidopsis thaliana root epidermis is comprised of two cell types, hair and nonhair cells, which differentiate from the same precursor. Although the transcriptional programs regulating these events are well studied, post-transcriptional factors functioning in this cell fate decision are mostly unknown. Here, we globally identify RNA-protein interactions and RNA secondary structure in hair and nonhair cell nuclei. This analysis reveals distinct structural and protein binding patterns across both transcriptomes, allowing identification of differential RNA binding protein (RBP) recognition sites...
April 24, 2017: Developmental Cell
https://www.readbyqxmd.com/read/28441529/mps1-regulates-kinetochore-microtubule-attachment-stability-via-the-ska-complex-to-ensure-error-free-chromosome-segregation
#6
John Maciejowski, Hauke Drechsler, Kathrin Grundner-Culemann, Edward R Ballister, Jose-Antonio Rodriguez-Rodriguez, Veronica Rodriguez-Bravo, Mathew J K Jones, Emily Foley, Michael A Lampson, Henrik Daub, Andrew D McAinsh, Prasad V Jallepalli
The spindle assembly checkpoint kinase Mps1 not only inhibits anaphase but also corrects erroneous attachments that could lead to missegregation and aneuploidy. However, Mps1's error correction-relevant substrates are unknown. Using a chemically tuned kinetochore-targeting assay, we show that Mps1 destabilizes microtubule attachments (K fibers) epistatically to Aurora B, the other major error-correcting kinase. Through quantitative proteomics, we identify multiple sites of Mps1-regulated phosphorylation at the outer kinetochore...
April 24, 2017: Developmental Cell
https://www.readbyqxmd.com/read/28441502/differential-coupling-of-binding-atp-hydrolysis-and-transport-of-fluorescent-probes-with-p-glycoprotein-in-lipid-nanodiscs
#7
Mavis Jiarong Li, Abhinav Nath, William M Atkins
The ATP-binding cassette transporter P-glycoprotein (ABCB1) plays a major role in cellular resistance to drugs, and drug interactions. Experimental studies support a mechanism with nucleotide-dependent fluctuation between inward-facing and outward-facing conformations, which are coupled to nucleotide hydrolysis. However, detailed insight into drug-dependent modulation of these conformational ensembles is lacking. Different drugs likely occupy partially overlapping but distinct sites, and are therefore variably coupled to nucleotide binding and hydrolysis...
April 25, 2017: Biochemistry
https://www.readbyqxmd.com/read/28441481/best-practices-of-computer-aided-drug-discovery-cadd-lessons-learned-from-the-development-of-a-preclinical-candidate-for-prostate-cancer-with-a-new-mechanism-of-action
#8
Fuqiang Ban, Kush Dalal, Huifang Li, Eric LeBlanc, Paul S Rennie, Artem Cherkasov
Small-molecule drug design is a complex and iterative decision-making process relying on pre-existing knowledge and driven by experimental data. Low molecular weight chemicals represent an attractive therapeutic option as they are readily accessible to organic synthesis and can easily be characterized.1 Their potency, as well as pharmacokinetic and pharmacodynamic properties can be systematically and rationally investigated, and ultimately optimized via expert science behind medicinal chemistry and methods of computer-aided drug design (CADD)...
April 25, 2017: Journal of Chemical Information and Modeling
https://www.readbyqxmd.com/read/28441415/pax7-remodels-the-chromatin-landscape-in-skeletal-muscle-stem-cells
#9
Karin C Lilja, Nan Zhang, Alessandro Magli, Volkan Gunduz, Christopher J Bowman, Robert W Arpke, Radbod Darabi, Michael Kyba, Rita Perlingeiro, Brian D Dynlacht
Pluripotent stem cells (PSC) hold great promise for the treatment of human skeletal muscle diseases. However, it remains challenging to convert PSC to skeletal muscle cells, and the mechanisms by which the master regulatory transcription factor, Pax7, promotes muscle stem (satellite) cell identity are not yet understood. We have taken advantage of PSC-derived skeletal muscle precursor cells (iPax7), wherein the induced expression of Pax7 robustly initiates the muscle program and enables the in vitro generation of precursors that seed the satellite cell compartment upon transplantation...
2017: PloS One
https://www.readbyqxmd.com/read/28441351/probing-temperature-and-ph-dependent-binding-between-quantum-dots-and-bovine-serum-albumin-by-fluorescence-correlation-spectroscopy
#10
Zonghua Wang, Qiyan Zhao, Menghua Cui, Shichao Pang, Jingfang Wang, Ying Liu, Liming Xie
Luminescent quantum dots (QDs) with unique optical properties have potential applications in bio-imaging. The interaction between QDs and bio-molecules is important to the biological effect of QDs in vivo. In this paper, we have employed fluorescence correlation spectroscopy (FCS) to probe the temperature- and pH-dependent interactions between CdSe QDs with carboxyl (QDs-COOH) and bovine serum albumin (BSA) in buffer solutions. The results have shown that microscopic dissociation constant K'D is in the range of (1...
April 25, 2017: Nanomaterials
https://www.readbyqxmd.com/read/28441340/selection-characterization-and-interaction-studies-of-a-dna-aptamer-for-the-detection-of-bifidobacterium-bifidum
#11
Lujun Hu, Linlin Wang, Wenwei Lu, Jianxin Zhao, Hao Zhang, Wei Chen
A whole-bacterium-based SELEX (Systematic Evolution of Ligands by Exponential Enrichment) procedure was adopted in this study for the selection of an ssDNA aptamer that binds to Bifidobacterium bifidum. After 12 rounds of selection targeted against B. bifidum, 30 sequences were obtained and divided into seven families according to primary sequence homology and similarity of secondary structure. Four FAM (fluorescein amidite) labeled aptamer sequences from different families were selected for further characterization by flow cytometric analysis...
April 25, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28441135/proteomic-mapping-of-cytosol-facing-outer-mitochondrial-and-er-membranes-in-living-human-cells-by-proximity-biotinylation
#12
Victoria Hung, Stephanie S Lam, Namrata D Udeshi, Tanya Svinkina, Gaelen Guzman, Vamsi K Mootha, Steven A Carr, Alice Y Ting
The cytosol-facing membranes of cellular organelles contain proteins that enable signal transduction, regulation of morphology and trafficking, protein import and export, and other specialized processes. Discovery of these proteins by traditional biochemical fractionation can be plagued with contaminants and loss of key components. Using peroxidase-mediated proximity biotinylation, we captured and identified endogenous proteins on the outer mitochondrial membrane (OMM) and endoplasmic reticulum membrane (ERM) of living human fibroblasts...
April 25, 2017: ELife
https://www.readbyqxmd.com/read/28441004/insights-into-the-mechanisms-by-which-clostridial-neurotoxins-discriminate-between-gangliosides
#13
Joshua R Burns, Gregory S Lambert, Michael R Baldwin
Botulinum neurotoxins (BoNTs) and Tetanus neurotoxin (TeNT) are the causative agents of the paralytic diseases botulism and tetanus, respectively. Entry of toxins into neurons is mediated through initial interactions with gangliosides, followed by binding to a protein co-receptor. Herein we aimed to understand the mechanism through which individual neurotoxins recognize the carbohydrate motif of gangliosides. Using cell-based and in vitro binding assays, in conjunction with structure-driven site directed mutagenesis, a conserved hydrophobic residue within the BoNTs that contributes to both affinity and specificity towards Sia5-containing gangliosides was identified...
April 25, 2017: Biochemistry
https://www.readbyqxmd.com/read/28440827/molecular-dynamics-investigations-of-membrane-bound-cyp2c19-polymorphisms-reveal-distinct-mechanisms-for-peripheral-variants-by-long-range-effects-on-the-enzymatic-activity
#14
Ying-Lu Cui, Rong-Ling Wu
Increasing sophistication in methods used to account for human polymorphisms in susceptibility to drug metabolism has been one of the success stories in the prevention of adverse drug reactions. Genetic polymorphisms in drug-metabolizing enzymes can affect enzyme activity and cause differences in treatment response or drug toxicity. CYP2C19 is one of the most highly polymorphic CYP enzymes and acts on 10-15% of drugs in current clinical use. Despite the number of experimental analyses carried out for this system, the detailed structural basis for altered catalytic properties of polymorphic CYP2C19 variants remains unexplained at the atomic level...
April 25, 2017: Molecular BioSystems
https://www.readbyqxmd.com/read/28440746/dual-interaction-of-scaffold-protein-tim44-of-mitochondrial-import-motor-with-channel-forming-translocase-subunit-tim23
#15
See-Yeun Ting, Nicholas L Yan, Brenda A Schilke, Elizabeth A Craig
Proteins destined for the mitochondrial matrix are targeted to the inner membrane Tim17/23 translocon by their presequences. Inward movement is driven by the matrix-localized, Hsp70-based motor. The scaffold Tim44, interacting with the matrix face of the translocon, recruits other motor subunits and binds incoming presequence. The basis of these interactions and their functional relationships remains unclear. Using site-specific in vivo crosslinking and genetic approaches in Saccharomyces cerevisiae, we found that both domains of Tim44 interact with the major matrix-exposed loop of Tim23, with the C-terminal domain (CTD) binding Tim17 as well...
April 25, 2017: ELife
https://www.readbyqxmd.com/read/28440624/acid-base-catalysis-in-glycosidations-a-nature-derived-alternative-to-the-generally-employed-methodology
#16
Peng Peng, Richard R Schmidt
Inverting glycosyltransferases enforce in the active site an intramolecular, acid-base catalyzed glycosidation that, due to proximity of the donor anomeric carbon and the acceptor hydroxyl group, follows an SN2-type reaction. Spacers, tethering donor and acceptor via nonreacting functional groups, led in intramolecular glycosidations to excellent yields and, independent of the donor anomeric configuration, to either the α- or the β-anomer. The requirement of a demanding protecting group pattern confines the application of this efficient method...
April 25, 2017: Accounts of Chemical Research
https://www.readbyqxmd.com/read/28440622/understanding-carbapenem-translocation-through-occd3-opdp-of-pseudomonas-aeruginosa
#17
Gowrishankar Soundararajan, Satya Prathyusha Bhamidimarri, Mathias Winterhalter
Pseudomonas aeruginosa utilizes a plethora of substrate specific channels for the uptake of small nutrients. OccD3 (OpdP or PA4501) is an OprD like arginine uptake channel of P. aeruginosa whose role has been implicated in carbapenem uptake. To understand the mechanism of selective permeation we reconstituted single OccD3 channels in planar lipid bilayer and characterized the interaction with Imipenem and Meropenem analyzing the ion current fluctuation in presence of substrates. We performed point mutations in the constriction region of OccD3 to understand the binding and translocation of antibiotic in OccD3...
April 25, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28440465/5-furan-2-yl-4-3-4-5-trimethoxyphenyl-3h-1-2-dithiol-3-one-oxime-6f-a-new-synthetic-compound-causes-human-%C3%AF-brosarcoma-ht-1080-cell-apoptosis-by-disrupting-tubulin-polymerisation-and-inducing-g2-m-arrest
#18
Daiying Zuo, Lili Pang, Jiwei Shen, Qi Guan, Zhaoshi Bai, Huijuan Zhang, Yao Li, Guodong Lu, Weige Zhang, Yingliang Wu
In the current study, we synthesized a series of new compounds targeting tubulin and tested their anti-proliferative activities. Among these new synthetic com-pounds, 5-(furan-2-yl)-4-(3,4,5-trimethoxyphenyl)-3H-1,2-dithiol-3-one oxime (6f) exhibited significant anti-proliferative activity against different human cancer cell lines including human gastric adenocarcinoma SGC-7901, human non-small cell lung cancer A549, and human fibrosarcoma HT-1080. As a result, 6f was selected to further test the sensitivity to different cancer cell lines including human cervical cancer cell line HeLa, human breast cancer cell line MCF-7, non-small cell lung cancer cell line A549, human liver carcinoma cell line HepG-2, human oral squamous cell carcinoma cell lines KB, SGC-7901 and HT-1080...
April 18, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28440457/%C3%AE-catenin-induces-expression-of-prohibitin-gene-in-acute-leukemic-cells
#19
Dong Min Kim, Hanbit Jang, Myung Geun Shin, Jeong-Hoon Kim, Sang Mo Shin, Sang-Hyun Min, Il-Chul Kim
Prohibitin (PHB) is a multifunctional protein conserved in eukaryotic systems and shows various expression levels in tumor cells. However, regulation of PHB is not clearly understood. Here, we focused on the regulation of PHB expression by Wnt signaling, one of dominant regulatory signals in various leukemic cells. High mRNA levels of PHB were found in half of clinical leukemia samples. PHB expression was increased by inhibition of the MAPK pathway and decreased by activation of EGF signal. Although cell proliferating signals downregulated the transcription of PHB, treatment with lithium chloride, an analog of the Wnt signal, induced PHB level in various cell types...
April 25, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28440315/tet2-loss-leads-to-hypermutagenicity-in-haematopoietic-stem-progenitor-cells
#20
Feng Pan, Thomas S Wingo, Zhigang Zhao, Rui Gao, Hideki Makishima, Guangbo Qu, Li Lin, Miao Yu, Janice R Ortega, Jiapeng Wang, Aziz Nazha, Li Chen, Bing Yao, Can Liu, Shi Chen, Ophelia Weeks, Hongyu Ni, Brittany Lynn Phillips, Suming Huang, Jianlong Wang, Chuan He, Guo-Min Li, Tomas Radivoyevitch, Iannis Aifantis, Jaroslaw P Maciejewski, Feng-Chun Yang, Peng Jin, Mingjiang Xu
TET2 is a dioxygenase that catalyses multiple steps of 5-methylcytosine oxidation. Although TET2 mutations frequently occur in various types of haematological malignancies, the mechanism by which they increase risk for these cancers remains poorly understood. Here we show that Tet2(-/-) mice develop spontaneous myeloid, T- and B-cell malignancies after long latencies. Exome sequencing of Tet2(-/-) tumours reveals accumulation of numerous mutations, including Apc, Nf1, Flt3, Cbl, Notch1 and Mll2, which are recurrently deleted/mutated in human haematological malignancies...
April 25, 2017: Nature Communications
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