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https://www.readbyqxmd.com/read/28346741/small-molecules-targeting-human-n-acetylmannosamine-kinase
#1
Stephan Hinderlich, Martin Neuenschwander, Paul-Robin Wratil, Andreas Oder, Michael Lisurek, Long D Nguyen, Jens Peter von Kries, Christian Hackenberger
N-Acetylmannosamine kinase (MNK) plays a key role in the biosynthesis of sialic acids and glycosylation of proteins. Sialylated glycoconjugates affect a large number of biological processes, including immune modulation and cancer transformation. For the search of effective inhibitors of MNK we applied high-throughput screening of drug-like small molecules. Applying different orthogonal assays for their validation we identified four potential MNK-specific inhibitors with IC50 values in the low micromolar range...
March 27, 2017: Chembiochem: a European Journal of Chemical Biology
https://www.readbyqxmd.com/read/28345451/the-impact-of-advanced-proteomics-in-the-search-for-markers-and-therapeutic-targets-of-bladder-cancer
#2
Hongshuo Zhang, Yue Fan, Lingling Xia, Chunhui Gao, Xin Tong, Hanfu Wang, Lili Sun, Tuo Ji, Mingyu Jin, Bing Gu, Bo Fan
Bladder cancer is the most common cancer of the urinary tract and can be avoided through proper surveillance and monitoring. Several genetic factors are known to contribute to the progression of bladder cancer, many of which produce molecules that serve as cancer biomarkers. Blood, urine, and tissue are commonly analyzed for the presence of biomarkers, which can be derived from either the nucleus or the mitochondria. Recent advances in proteomics have facilitated the high-throughput profiling of data generated from bladder cancer-related proteins or peptides in parallel with high sensitivity and specificity, providing a wealth of information for biomarker discovery and validation...
March 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28344391/ph-driven-solubilization-and-isoelectric-precipitation-of-proteins-from-the-brown-seaweed-saccharina-latissima-effects-of-osmotic-shock-water-volume-and-temperature
#3
Jenny Veide Vilg, Ingrid Undeland
In the light of the global search for novel and sustainable protein sources, macroalgal proteins are becoming an attractive target. To date, mainly red and green macroalgae have been investigated in this respect, whereas the brown species are less studied, possibly because of the lower content of protein. In a biorefinery context, however, the protein content of brown macroalgae can still be economically interesting due to fast growth and the possibility to co-extract other compounds, such as alginates. The aim of this study was to develop a simple, scalable pH shift-based protein isolation technique applicable on wet Saccharina latissima biomass...
2017: Journal of Applied Phycology
https://www.readbyqxmd.com/read/28343993/discovering-key-residues-of-dengue-virus-ns2b-ns3-protease-new-binding-sites-for-antiviral-inhibitors-design
#4
D Aguilera-Pesantes, L E Robayo, P E Méndez, D Mollocana, Y Marrero-Ponce, F J Torres, M A Méndez
The NS2B-NS3 protease is essential for the Dengue Virus (DENV) replication process. This complex constitutes a target for efficient antiviral discovery because a drug could inhibit the viral polyprotein processing. Furthermore, since the protease is highly conserved between the four Dengue virus serotypes, it is probable that a drug would be equally effective against all of them. In this article, a strategy is reported that allowed us to identify influential residues on the function of the Dengue NS2b-NS3 Protease...
March 23, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28335087/ursolic-acid-and-mechanisms-of-actions-on-adipose-and-muscle-tissue-a-systematic-review
#5
REVIEW
Carlos K Katashima, Vagner R Silva, Tatyanne L Gomes, Claude Pichard, Gustavo D Pimentel
This systematic review aimed at addressing the ursolic acid actions as an adjunctive treatment of the obesity-mediated metabolic abnormalities. To explore our aims, we used the literature search including clinical and animal studies using the Medline and Google Scholar (up to December 2015). Out of 63 screened studies, 17 presented eligibility criteria, such as the use of ursolic acid on adiposity, energy expenditure and skeletal muscle mass in mice and humans. In the literature, we found that several physiological and molecular mechanisms are implicated in the effects of ursolic acid on obesity, energy expenditure, hepatic steatosis, skeletal muscle mass loss and physical fitness, such as (1) increase of thermogenesis by modulation adipocyte transcription factors, activation of 5' adenosine monophosphate-activated protein kinase and overexpression of the uncoupling protein 1 thermogenic marker; (2) enhancement of skeletal muscle mass by activation in bloodstream growth hormone and insulin-like growth factor-1 concentrations secretion, as well as in the activation of mammalian target of rapamycin and inhibition of ring-finger protein-1; and (3) improvement of physical fitness by skeletal muscle proliferator-activated receptor gamma co-activator alpha and sirtuin 1 expression...
March 23, 2017: Obesity Reviews: An Official Journal of the International Association for the Study of Obesity
https://www.readbyqxmd.com/read/28334201/critical-evaluation-of-bioinformatics-tools-for-the-prediction-of-protein-crystallization-propensity
#6
Huilin Wang, Liubin Feng, Geoffrey I Webb, Lukasz Kurgan, Jiangning Song, Donghai Lin
X-ray crystallography is the main tool for structural determination of proteins. Yet, the underlying crystallization process is costly, has a high attrition rate and involves a series of trial-and-error attempts to obtain diffraction-quality crystals. The Structural Genomics Consortium aims to systematically solve representative structures of major protein-fold classes using primarily high-throughput X-ray crystallography. The attrition rate of these efforts can be improved by selection of proteins that are potentially easier to be crystallized...
February 27, 2017: Briefings in Bioinformatics
https://www.readbyqxmd.com/read/28331449/cyclin-d1-in-the-liver-role-of-noncanonical-signaling-in-liver-steatosis-and-hormone-regulation
#7
Kelley G Núñez, Janet Gonzalez-Rosario, Paul T Thevenot, Ari J Cohen
BACKGROUND: Cyclin D1 is an important protein for cell cycle progression; however, functions independent of the cell cycle have been described in the liver. Cyclin D1 is also involved in DNA repair, is overexpressed in many cancers, and functions as a proto-oncogene. The lesser-known roles of Cyclin D1, specifically in hepatocytes, impact liver steatosis and hormone regulation in the liver. METHODS: A comprehensive search of PubMed was conducted using the keywords Cyclin D1, steatosis, lipogenesis, and liver transplantation...
2017: Ochsner Journal
https://www.readbyqxmd.com/read/28328848/clinical-effects-of-p53-overexpression-in-squamous-cell-carcinoma-of-the-sinonasal-tract-a-systematic-meta-analysis-with-prisma-guidelines
#8
Xiaowei Wang, Wei Lv, Fang Qi, Zhiqiang Gao, Hua Yang, Weiqing Wang, Yali Gao
BACKGROUND: The level of p53 protein expression in sinonasal squamous cell carcinoma (SNSCC) has been estimated, but the results remain inconsistent and the point of consensus has not been reached. This study was first determined to evaluate the clinical effects of p53 expression in SCC of the sinonasal tract. METHODS: According to the preferred reporting items for systematic reviews and meta-analyses (PRISMA) statement criteria, the potential literature was searched from diverse databases...
March 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28327523/methodological-challenges-in-protein-microarray-and-immunohistochemistry-for-the-discovery-of-novel-autoantibodies-in-paediatric-acute-disseminated-encephalomyelitis
#9
Patrick Peschl, Melanie Ramberger, Romana Höftberger, Karin Jöhrer, Matthias Baumann, Kevin Rostásy, Markus Reindl
Acute disseminated encephalomyelitis (ADEM) is a rare autoimmune-mediated demyelinating disease affecting mainly children and young adults. Differentiation to multiple sclerosis is not always possible, due to overlapping clinical symptoms and recurrent and multiphasic forms. Until now, immunoglobulins reactive to myelin oligodendrocyte glycoprotein (MOG antibodies) have been found in a subset of patients with ADEM. However, there are still patients lacking autoantibodies, necessitating the identification of new autoantibodies as biomarkers in those patients...
March 22, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28322451/genome-wide-association-studies-with-proteomics-data-reveal-genes-important-for-synthesis-transport-and-packaging-of-globulins-in-legume-seeds
#10
Christine Le Signor, Delphine Aimé, Amandine Bordat, Maya Belghazi, Valérie Labas, Jérôme Gouzy, Nevin D Young, Jean-Marie Prosperi, Olivier Leprince, Richard D Thompson, Julia Buitink, Judith Burstin, Karine Gallardo
Improving nutritional seed quality is an important challenge in grain legume breeding. However, the genes controlling the differential accumulation of globulins, which are major contributors to seed nutritional value in legumes, remain largely unknown. We combined a search for protein quantity loci with genome-wide association studies on the abundance of 7S and 11S globulins in seeds of the model legume species Medicago truncatula. Identified genomic regions and genes carrying polymorphisms linked to globulin variations were then cross-compared with pea (Pisum sativum), leading to the identification of candidate genes for the regulation of globulin abundance in this crop...
March 21, 2017: New Phytologist
https://www.readbyqxmd.com/read/28321130/effective-combinatorial-immunotherapy-for-castration-resistant-prostate-cancer
#11
Xin Lu, James W Horner, Erin Paul, Xiaoying Shang, Patricia Troncoso, Pingna Deng, Shan Jiang, Qing Chang, Denise J Spring, Padmanee Sharma, John A Zebala, Dean Y Maeda, Y Alan Wang, Ronald A DePinho
A significant fraction of patients with advanced prostate cancer treated with androgen deprivation therapy experience relapse with relentless progression to lethal metastatic castration-resistant prostate cancer (mCRPC). Immune checkpoint blockade using antibodies against cytotoxic-T-lymphocyte-associated protein 4 (CTLA4) or programmed cell death 1/programmed cell death 1 ligand 1 (PD1/PD-L1) generates durable therapeutic responses in a significant subset of patients across a variety of cancer types. However, mCRPC showed overwhelming de novo resistance to immune checkpoint blockade, motivating a search for targeted therapies that overcome this resistance...
March 20, 2017: Nature
https://www.readbyqxmd.com/read/28320877/functional-analysis-of-the-alternative-sigma-28-factor-flia-and-its-anti-sigma-factor-flgm-of-the-non-flagellated-legionella-species-l-oakridgensis
#12
Hana Tlapák, Kerstin Rydzewski, Tino Schulz, Dennis Weschka, Eva Schunder, Klaus Heuner
Legionella oakridgensis is causing the Legionnaires' disease but is known to be less virulent than Legionella pneumophilaL. oakridgensis is one of the Legionella species that is non-flagellated. The genes of the flagellar regulon are absent; except the alternative sigma-28 factor (FliA) and its anti-sigma-28 factor (FlgM). Similar to L. oakridgensis, Legionella adelaidensis and Legionella londiniensis, located in the same phylogenetic clade, they have no flagellar regulon, although both are positive for fliA and flgM Herein, we investigated the role and function of both genes to better understand the role of FliA, the positive regulator of flagellin expression, in non-flagellated strains...
March 20, 2017: Journal of Bacteriology
https://www.readbyqxmd.com/read/28319084/structural-and-mechanistic-insights-into-an-archaeal-dna-guided-argonaute-protein
#13
Sarah Willkomm, Christine A Oellig, Adrian Zander, Tobias Restle, Ronan Keegan, Dina Grohmann, Sabine Schneider
Argonaute (Ago) proteins in eukaryotes are known as key players in post-transcriptional gene silencing(1), while recent studies on prokaryotic Agos hint at their role in the protection against invading DNA(2,3). Here, we present crystal structures of the apo enzyme and a binary Ago-guide complex of the archaeal Methanocaldococcus jannaschii (Mj) Ago. Binding of a guide DNA leads to large structural rearrangements. This includes the structural transformation of a hinge region containing a switch helix, which has been shown for human Ago2 to be critical for the dynamic target search process(4-6)...
March 20, 2017: Nature Microbiology
https://www.readbyqxmd.com/read/28317950/in-vivo-identification-of-potential-uranium-protein-targets-in-zebrafish-ovaries-after-chronic-waterborne-exposure
#14
Y Eb-Levadoux, S Frelon, O Simon, C Arnaudguilhem, R Lobinski, S Mounicou
Ecotoxicological studies have indicated the reprotoxicity of uranium (U) in zebrafish, but its molecular mechanisms remain unclear. Due to the non-covalent nature of U-protein complexes, canonical proteomics approaches are often not relevant as they usually use denaturating reagents or solvents. In this study, non-denaturating (ND) methods were used to obtain insight into the nature of U potential targets in ovaries of reproduced and non-reproduced zebrafish after 20 days of exposure to an environmentally relevant U concentration (20 μg L(-1))...
March 20, 2017: Metallomics: Integrated Biometal Science
https://www.readbyqxmd.com/read/28315995/ligand-based-virtual-screening-under-partial-shape-constraints
#15
Mathias M von Behren, Matthias Rarey
Ligand-based virtual screening has proven to be a viable technology during the search for new lead structures in drug discovery. Despite the rapidly increasing number of published methods, meaningful shape matching as well as ligand and target flexibility still remain open challenges. In this work, we analyze the influence of knowledge-based sterical constraints on the performance of the recently published ligand-based virtual screening method mRAISE. We introduce the concept of partial shape matching enabling a more differentiated view on chemical structure...
March 18, 2017: Journal of Computer-aided Molecular Design
https://www.readbyqxmd.com/read/28315215/detection-of-food-allergens-by-phage-displayed-produced-antibodies
#16
Raquel Madrid, Silvia de la Cruz, Aina García, Rosario Martín, Isabel González, Teresa García
Phage display is a powerful tool to produce recombinant antibodies against a given antigen without animal immunization. This technology employs libraries of recombinant bacteriophages that display billions of different functional antibody fragments on their surface. They are selected by panning in vitro against the target antigen in search for specific binders. In this chapter, we describe the selection of single chain variable fragment (scFv) antibodies to be used for detection of allergenic proteins from nuts in food products...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28298637/hybrid-magnetic-dna-directed-immobilisation-approach-for-efficient-protein-capture-and-detection-on-microfluidic-platforms
#17
Elaheh Esmaeili, Mohammad Adel Ghiass, Manouchehr Vossoughi, Masoud Soleimani
In this study, a hybrid magnetic-DNA directed immobilisation approach is presented to enhance protein capture and detection on a microfluidic platform. DNA-modified magnetic nanoparticles are added in a solution to capture fluorescently labelled immunocomplexes to be detected optically. A magnetic set-up composed of cubic permanent magnets and a microchannel was designed and implemented based on finite element analysis results to efficiently concentrate the nanoparticles only over a defined area of the microchannel as the sensing zone...
March 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28298518/evidence-for-ancient-origins-of-bowman-birk-inhibitors-from-selaginella-moellendorffii
#18
Amy Midori James, Achala S Jayasena, Jingjing Zhang, Oliver Berkowitz, David Secco, Gavin J Knott, James Whelan, Charles Bond, Joshua S Mylne
Bowman-Birk Inhibitors (BBIs) are a well-known family of plant protease inhibitors first described 70 years ago. BBIs are known only in the legume (Fabaceae) and cereal (Poaceae) families, but peptides that mimic their trypsin inhibitory loops exist in sunflowers and frogs. The disparate biosynthetic origins and distant phylogenetic distribution implies these loops evolved independently, but their structural similarity suggests a common ancestor. Targeted bioinformatic searches for the BBI inhibitory loop discovered highly divergent BBI like sequences in the seedless, vascular spikemoss Selaginella moellendorffii...
March 14, 2017: Plant Cell
https://www.readbyqxmd.com/read/28295924/flagellin-phase-dependent-swimming-on-epithelial-cell-surfaces-contributes-to-productive-salmonella-gut-colonization
#19
Julia A Horstmann, Erik Zschieschang, Theresa Truschel, Juana de Diego, Michele Lunelli, Manfred Rohde, Tobias May, Till Strowig, Theresia Stradal, Michael Kolbe, Marc Erhardt
The flagellum is a sophisticated nanomachine and an important virulence factor of many pathogenic bacteria. Flagellar motility enables directed movements towards host cells in a chemotactic process and near surface swimming on cell surfaces is crucial for selection of permissive entry sites. The long external flagellar filament is made of tens of thousands subunits of a single protein, flagellin, and many Salmonella serovars alternate expression of antigenically distinct flagellin proteins, FliC and FljB. However, the role of the different flagellin variants during gut colonization and host cell invasion remains elusive...
March 13, 2017: Cellular Microbiology
https://www.readbyqxmd.com/read/28282119/patchsearch-a-fast-computational-method-for-off-target-detection
#20
Inès Rasolohery, Gautier Moroy, Frédéric Guyon
Many therapeutic molecules are known to bind several proteins, which can be different from the initially targeted one. Such unexpected interactions with proteins called off-targets can lead to adverse effects. Potential off-target identification is important to predict to avoid drug side effects or to discover new targets for existing drugs. We propose a new program named PatchSearch that implements local nonsequential searching for similar binding sites on protein surfaces with a controlled amount of flexibility...
March 24, 2017: Journal of Chemical Information and Modeling
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