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https://www.readbyqxmd.com/read/28441462/transcriptomic-profiling-of-a-chicken-lung-epithelial-cell-line-clec213-reveals-a-mitochondrial-respiratory-chain-activity-boost-during-influenza-virus-infection
#1
Léa Meyer, Olivier Leymarie, Christophe Chevalier, Evelyne Esnault, Marco Moroldo, Bruno Da Costa, Sonia Georgeault, Philippe Roingeard, Bernard Delmas, Pascale Quéré, Ronan Le Goffic
Avian Influenza virus (AIV) is a major concern for the global poultry industry. Since 2012, several countries have reported AIV outbreaks among domestic poultry. These outbreaks had tremendous impact on poultry production and socio-economic repercussion on farmers. In addition, the constant emergence of highly pathogenic AIV also poses a significant risk to human health. In this study, we used a chicken lung epithelial cell line (CLEC213) to gain a better understanding of the molecular consequences of low pathogenic AIV infection in their natural host...
2017: PloS One
https://www.readbyqxmd.com/read/28441076/a-novel-neuroprotective-small-molecule-for-glial-cell-derived-neurotrophic-factor-induction-and-photoreceptor-rescue
#2
Petr Baranov, Hong Lin, Kathryn McCabe, David Gale, Shenshen Cai, Burke Lieppman, Dwight Morrow, Phoebe Lei, Justin Liao, Michael Young
PURPOSE: Degenerative diseases of the retina, such as retinitis pigmentosa and age-related macular degeneration, are characterized by the irreversible loss of photoreceptors. Several growth factors, including glial cell derived neurotrophic factor (GDNF), have been shown to rescue retinal neurons. An alternative strategy to direct GDNF administration is its induction in host retina by small molecules. Here we studied the ability of a novel small molecule GSK812 to induce GDNF in vitro/in vivo and rescue photoreceptors...
April 25, 2017: Journal of Ocular Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28441058/protein-misfolding-diseases
#3
F Ulrich Hartl
The majority of protein molecules must fold into defined three-dimensional structures to acquire functional activity. However, protein chains can adopt a multitude of conformational states, and their biologically active conformation is often only marginally stable. Metastable proteins tend to populate misfolded species that are prone to forming toxic aggregates, including soluble oligomers and fibrillar amyloid deposits, which are linked with neurodegeneration in Alzheimer and Parkinson disease, and many other pathologies...
April 24, 2017: Annual Review of Biochemistry
https://www.readbyqxmd.com/read/28440962/designed-heme-cage-%C3%AE-sheet-miniproteins
#4
Areetha D'Souza, Xiangyang Wu, Edwin Kok Lee Yeow, Surajit Bhattacharjya
The structure and function of naturally occurring proteins are governed by a large number of amino acids (≥100). The design of miniature proteins with desired structures and functions not only substantiates our knowledge about proteins but can also contribute to the development of novel applications. Excellent progress has been made towards the design of helical proteins with diverse functions. However, the development of functional β-sheet proteins remains challenging. Herein, we describe the construction and characterization of four-stranded β-sheet miniproteins made up of about 19 amino acids that bind heme inside a hydrophobic binding pocket or "heme cage" by bis-histidine coordination in an aqueous environment...
April 25, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/28440066/elevated-glypican-1-expression-is-associated-with-an-unfavorable-prognosis-in-pancreatic-ductal-adenocarcinoma
#5
Haizhen Lu, Fangfei Niu, Fang Liu, Jiajia Gao, Yulin Sun, Xiaohang Zhao
Pancreatic ductal adenocarcinoma (PDAC) is the most lethal cancer in humans, with a 5-year survival rate of <5%. Recently, glypican-1 (GPC1)-expressing circulating exosomes were found to be a promising diagnostic tool for PDAC. However, the aberrant expression of GPC1 has not been systematically evaluated in large-scale clinical samples of PDAC. Here, we performed a comprehensive analysis of GPC1 mRNA and protein expression features. Included in this study were 178 PDAC patients from the cancer genome atlas (TCGA) and 186 subjects whose tissues were used in immunohistochemical staining assays...
April 24, 2017: Cancer Medicine
https://www.readbyqxmd.com/read/28440031/production-characterization-and-assessment-of-a-stable-analog-of-the-response-regulator-chey-phosphate-from-thermotoga-maritima
#6
Matthew S Beyersdorf, Ria Sircar, Daniel B Lookadoo, Cory Bottone, Michael J Lynch, Brian R Crane, Christopher J Halkides
Phosphorylation of CheY promotes association with the flagellar motor and ultimately controls the directional bias of the motor. However, biochemical studies of activated CheY-phosphate have been challenging due to the rapid hydrolysis of the aspartyl-phosphate in vitro. An inert analog of Tm CheY-phosphate, phosphono-CheY, was synthesized by chemical modification and purified by cation-exchange chromatography. Changes in HPLC retention times, chemical assays for phosphate and free thiol, and mass spectrometry experiments demonstrate modification of Cys54 with a phosphonomethyl group...
April 25, 2017: Protein Science: a Publication of the Protein Society
https://www.readbyqxmd.com/read/28439766/enhanced-butyric-acid-tolerance-and-production-by-class-i-heat-shock-protein-overproducing-clostridium-tyrobutyricum-atcc-25755
#7
Yukai Suo, Sheng Luo, Yanan Zhang, Zhengping Liao, Jufang Wang
The response of Clostridium tyrobutyricum to butyric acid stress involves various stress-related genes, and therefore overexpression of stress-related genes can improve butyric acid tolerance and yield. Class I heat shock proteins (HSPs) play an important role in the process of protecting bacteria from sudden changes of extracellular stress by assisting protein folding correctly. The results of quantitative real-time PCR indicated that the Class I HSGs grpE, dnaK, dnaJ, groEL, groES, and htpG were significantly upregulated under butyric acid stress, especially the dnaK and groE operons...
April 24, 2017: Journal of Industrial Microbiology & Biotechnology
https://www.readbyqxmd.com/read/28439280/insights-on-structure-and-function-of-a-late-embryogenesis-abundant-protein-from-amaranthus-cruentus-an-intrinsically-disordered-protein-involved-in-protection-against-desiccation-oxidant-conditions-and-osmotic-stress
#8
Alma L Saucedo, Eric E Hernández-Domínguez, Luis A de Luna-Valdez, Angel A Guevara-García, Abraham Escobedo-Moratilla, Esaú Bojorquéz-Velázquez, Federico Del Río-Portilla, Daniel A Fernández-Velasco, Ana P Barba de la Rosa
Late embryogenesis abundant (LEA) proteins are part of a large protein family that protect other proteins from aggregation due to desiccation or osmotic stresses. Recently, the Amaranthus cruentus seed proteome was characterized by 2D-PAGE and one highly accumulated protein spot was identified as a LEA protein and was named AcLEA. In this work, AcLEA cDNA was cloned into an expression vector and the recombinant protein was purified and characterized. AcLEA encodes a 172 amino acid polypeptide with a predicted molecular mass of 18...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/28439240/apolipophorin-iii-acts-as-a-positive-regulator-of-plasmodium-development-in-anopheles-stephensi
#9
Rini Dhawan, Kuldeep Gupta, Mithilesh Kajla, Parik Kakani, Tania P Choudhury, Sanjeev Kumar, Vikas Kumar, Lalita Gupta
Apolipophorin III (ApoLp-III) is a well-known hemolymph protein having a functional role in lipid transport and immune responses of insects. Here we report the molecular and functional characterization of Anopheles stephensi Apolipophorin-III (AsApoLp-III) gene. This gene consists of 679 nucleotides arranged into two exons of 45 and 540 bp that give an ORF encoding 194 amino acid residues. Excluding a putative signal peptide of the first 19 amino acid residues, the 175-residues in mature AsApoLp-III protein has a calculated molecular mass of 22 kDa...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28438781/transporter-mediated-disposition-clinical-pharmacokinetics-and-cholestatic-potential-of-glyburide-and-its-primary-active-metabolites
#10
Rui Li, Yi-An Bi, Anna Vildhede, Renato J Scialis, Sumathy Mathialagan, Xin Yang, Lisa D Marroquin, Jian Lin, Manthena V S Varma
Glyburide is widely used for the treatment of type 2 diabetes mellitus. We studied the mechanisms involved in the disposition of glyburide and its pharmacologically active hydroxy metabolites, M1 and M2b; and evaluated their clinical pharmacokinetics and the potential role in glyburide-induced cholestasis employing physiologically based pharmacokinetic (PBPK) modeling. Transport studies of parent and metabolites in human hepatocytes and transfected cell systems imply hepatic uptake mediated by organic anion transporting polypeptides...
April 24, 2017: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/28438490/acute-nanoparticle-exposure-to-vocal-folds-a-laboratory-study
#11
Xinxin Liu, Tanaya Walimbe, William Pierre Schrock, Wei Zheng, M Preeti Sivasankar
OBJECTIVES: Airway exposure to nanoparticles is common in occupational settings. Inhaled nanoparticles have toxic effects on respiratory tissue. Vocal folds are also at direct risk from inhaled nanoparticles. This study investigated the effects of single-walled carbon nanotubes (SWCNT), a type of nanoparticle, on vocal fold epithelium and fibroblasts. These cell types were selected for study as the epithelium is the outer layer of the vocal folds and fibroblasts are the most common cell type in connective tissue underlying the epithelium...
April 21, 2017: Journal of Voice: Official Journal of the Voice Foundation
https://www.readbyqxmd.com/read/28438458/an-efficient-cumate-inducible-system-for-procyclic-and-bloodstream-form-trypanosoma-brucei
#12
Feng-Jun Li, Zhi-Shen Xu, Htay Mon Aye, Anaïs Brasseur, Zhao-Rong Lun, Kevin S W Tan, Cynthia Y He
In Trypanosoma brucei, the tetracycline-inducible system enables tightly-regulated, highly-efficient expression of recombinant proteins or double-stranded RNA in both procyclic and bloodstream form cells, providing useful molecular genetic tools to study gene functions. An alternative, vanillic acid-inducible system is recently described for procyclic T. brucei, providing ∼18-fold increase in GFP reporter expression upon induction (Sunter JD. Mol Biochem Parasitol. 2016, 207:45-48). Here we describe a cumate-inducible system that allows efficient, tunable gene expression showing >300-fold increase in GFP expression upon induction...
April 21, 2017: Molecular and Biochemical Parasitology
https://www.readbyqxmd.com/read/28437838/prognostic-relevance-of-mir-124-3p-and-its-target-tp53inp1-in-pediatric-ependymoma
#13
Yulia Margolin-Miller, Natalia Yanichkin, Keren Shichrur, Helen Toledano, Anat Ohali, Theophilos Tzaridis, Shalom Michowitz, Suzana Fichman-Horn, Meora Feinmesser, Stefan M Pfister, Hendrik Witt, Uri Tabori, Eric Bouffet, Vijay Ramaswamy, Cynthia Hawkins, Michael D Taylor, Isaac Yaniv, Smadar Avigad
Ependymoma is a malignant pediatric brain tumor, often incurable under the current treatment regimen. We aimed to evaluate the expression of microRNAs (miRs) in pediatric ependymoma tumors in an attempt to identify prognostic molecular markers which would lead to potential therapeutic targets. Following miR-array expression analysis, we focused on 9 miRs that correlated with relapse which were further validated by quantitative real time PCR (qRT-PCR) in a cohort of 67 patients. Western blotting and immunohistochemistry were used to measure target protein expression in 20 and 34 tumor samples, respectively...
April 24, 2017: Genes, Chromosomes & Cancer
https://www.readbyqxmd.com/read/28437613/evaluating-the-role-of-multidrug-resistance-protein-3-mdr3-inhibition-in-predicting-drug-induced-liver-injury-using-125-pharmaceuticals
#14
Michael D Aleo, Falgun Shah, Kan He, Paul D Bonin, A David Rodrigues
The role of bile salt export protein (BSEP) inhibition in drug-induced liver injury (DILI) has been investigated widely, while inhibition of the canalicular multidrug resistant protein 3 (MDR3) has received less attention. This transporter plays a pivotal role in secretion of phospholipids into bile and functions coordinately with BSEP to mediate the formation of bile acid-containing biliary micelles. Therefore, inhibition of MDR3 in human hepatocytes was examined across 125 drugs (70 of Most- and 55 of No-DILI-concern)...
April 24, 2017: Chemical Research in Toxicology
https://www.readbyqxmd.com/read/28437088/hilaq-a-novel-strategy-for-newly-synthesized-protein-quantification
#15
Yuanhui Ma, Daniel B McClatchy, Salim Barkallah, William W Wood, John R Yates Iii
Here we describe a new strategy, HILAQ (Heavy Isotope Labeled Azidohomoalanine Quantification), to rapidly quantify the molecular vulnerability profile to oxytosis, which is an oxidative stress-induced programed cell death pathway that has been reported to be involved in aging and neurodegenerative diseases. HILAQ was able to quantify 1,962 Newly Synthesized Proteins (NSPs) after 1h pulse labeling in HEK293T cell line, while 353 proteins were quantified using the previously published QuaNCAT protocol. HILAQ was successfully applied to the HT22 oxytosis model...
April 24, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/28437072/the-single-disulfide-directed-%C3%AE-hairpin-fold-dynamics-stability-and-engineering
#16
Balasubramanyam Chittoor, Krishnarjuna Bankala, Rodrigo A W Morales, Christopher Andrew MacRaild, Maiada Sadek, Eleanor Ww Leung, Samuel Robinson, Michael Pennington, Raymond S Norton
Grafting bioactive peptide sequences onto small cysteine-rich scaffolds is a promising strategy to enhance their stability and value in novel peptide-based therapeutics. However, correctly folded disulfide-rich peptides can be challenging to produce by either recombinant or synthetic means. The single disulfide-directed β-hairpin (SDH) fold, first observed in contryphan-Vc1, provides a potential alternative to complex disulfide-rich scaffolds. We have undertaken recombinant production of full-length contryphan-Vc1 (rCon-Vc1[Z1Q]) and a truncated analog (rCon-Vc11-22[Z1Q]), analyzed the backbone dynamics of rCon-Vc1[Z1Q], and probed the conformational and proteolytic stability of these peptides to evaluate the potential of contryphan-Vc1 as a molecular scaffold...
April 24, 2017: Biochemistry
https://www.readbyqxmd.com/read/28436469/a-novel-method-to-evaluate-ribosomal-performance-in-cell-free-protein-synthesis-systems
#17
Noémie Kempf, Cristina Remes, Ralph Ledesch, Tina Züchner, Henning Höfig, Ilona Ritter, Alexandros Katranidis, Jörg Fitter
Cell-free protein synthesis (CFPS) systems were designed to produce proteins with a minimal set of purified components, thus offering the possibility to follow translation as well as protein folding. In order to characterize the performance of the ribosomes in such a system, it is crucial to separately quantify the two main components of productivity, namely the fraction of active ribosomes and the number of synthesizing cycles. Here, we provide a direct and highly reliable measure of ribosomal activity in any given CFPS system, introducing an enhanced-arrest peptide variant...
April 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28436203/endoplasmic-reticulum-proteostasis-impairment-in-aging
#18
REVIEW
Gabriela Martínez, Claudia Duran-Aniotz, Felipe Cabral-Miranda, Juan P Vivar, Claudio Hetz
Perturbed neuronal proteostasis is a salient feature shared by both aging and protein misfolding disorders. The proteostasis network controls the health of the proteome by integrating pathways involved in protein synthesis, folding, trafficking, secretion, and their degradation. A reduction in the buffering capacity of the proteostasis network during aging may increase the risk to undergo neurodegeneration by enhancing the accumulation of misfolded proteins. As almost one-third of the proteome is synthetized at the endoplasmic reticulum (ER), maintenance of its proper function is fundamental to sustain neuronal function...
April 23, 2017: Aging Cell
https://www.readbyqxmd.com/read/28435892/dramatic-improvement-of-crispr-cas9-editing-in-candida-albicans-by-increased-single-guide-rna-expression
#19
Henry Ng, Neta Dean
The clustered regularly interspaced short palindromic repeat system with CRISPR-associated protein 9 nuclease (CRISPR/Cas9) has emerged as a versatile tool for genome editing in Candida albicans. Mounting evidence from other model systems suggests that the intracellular levels of single guide RNA (sgRNA) limit the efficiency of Cas9-dependent DNA cleavage. Here, we tested this idea and describe a new means of sgRNA delivery that improves previously described methods by ~10-fold. The efficiency of Cas9/sgRNA-dependent cleavage and repair of a single-copy yeast enhanced monomeric red fluorescent protein (RFP) gene was measured as a function of various parameters that are hypothesized to affect sgRNA accumulation, including transcriptional and posttranscriptional processing...
March 2017: MSphere
https://www.readbyqxmd.com/read/28435458/phosphorylcholine-based-stealthy-nanocapsules-enabling-tumor-microenvironment-responsive-doxorubicin-release-for-tumor-suppression
#20
Gan Liu, Hsiang-I Tsai, Xiaowei Zeng, Yixiong Zuo, Wei Tao, Jun Han, Lin Mei
The efficient delivery of anticancer drugs into tumor tissues to improve therapeutic efficacy remains an urgent demand. To satisfy this demand, a drug delivery system based on a stealthy nanocapsule was developed. This nanocapsule was fabricated by encapsulating stealthy cross-linked poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC) and benzaldehyde groups around the protein bovine serum albumin (BSA) followed by conjugation of doxorubicin (Dox) through a pH-responsive benzoic-imine bond. The in vitro results show that the Dox-conjugated nanocapsule (nBSA-Dox) released the drug under an acidic tumor microenvironment (pH ~6...
2017: Theranostics
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