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In vivo protein protein interaction

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https://www.readbyqxmd.com/read/28528353/adrenomedullin-ameliorates-podocyte-injury-induced-by-puromycin-aminonucleoside-in-vitro-and-in-vivo-through-modulation-of-rho-gtpases
#1
Nan Dong, Lixia Meng, Ruqun Xue, Meng Yu, Zhonghua Zhao, Xueguang Liu
PURPOSE: Podocyte injury is a key event in proteinuric kidney disease and eventually glomerular scarring. While adrenomedullin (AM), a potent vasodilatory peptide, has been reported to confer renoprotection in several experimental models of kidney diseases, its effect on injured podocytes and the related mechanism is still largely unknown. METHODS: Employing Western blotting analysis, immunoprecipitation and immunofluorescence, we investigated the effects of AM on the expressions of podocyte cytoskeletal proteins and Rho-family small GTPases (Rho GTPases) in puromycin aminonucleoside (PAN)-induced podocyte injury, both in cultured podocytes and in PAN nephrosis rats...
May 20, 2017: International Urology and Nephrology
https://www.readbyqxmd.com/read/28526921/glp-1-signalling-compensates-for-impaired-insulin-signalling-in-regulating-beta-cell-proliferation-in-%C3%AE-irko-mice
#2
Dan Kawamori, Jun Shirakawa, Chong Wee Liew, Jiang Hu, Tomoaki Morioka, Alokesh Duttaroy, Bryan Burkey, Rohit N Kulkarni
AIMS/HYPOTHESIS: We aimed to investigate potential interactions between insulin and glucagon-like peptide (GLP)-1 signalling pathways in the regulation of beta cell-cycle dynamics in vivo, in the context of the therapeutic potential of GLP-1 to modulate impaired beta cell function. METHODS: Beta cell-specific insulin receptor knockout (βIRKO) mice, which exhibit beta cell dysfunction and an age-dependent decrease in beta cell mass, were treated with the dipeptidyl peptidase-4 inhibitor vildagliptin...
May 20, 2017: Diabetologia
https://www.readbyqxmd.com/read/28526714/constans-imparts-dna-sequence-specificity-to-the-histone-fold-nf-yb-nf-yc-dimer
#3
Nerina Gnesutta, Roderick W Kumimoto, Swadhin Swain, Matteo Chiara, Chamindika Siriwardana, David Stephen Horner, Ben F Holt, Roberto Mantovani
NF-Y is a heterotrimeric transcription factor that binds CCAAT elements. The NF-Y trimer is composed of a Histone Fold Domain (HFD) dimer (NF-YB/NF-YC) and NF-YA, which confers DNA sequence-specificity. NF-YA shares a conserved domain with the CCT (CONSTANS, CONSTANS-LIKE, TOC1) proteins. We show that CONSTANS (CO/BBX1), a master flowering regulator, forms a trimer with Arabidopsis NF-YB2/NF-YC3 to efficiently bind the CORE element of the FT promoter. We term this complex NF-CO. Using saturation mutagenesis EMSAs and RNA-Seq profiling of co, nf-yb, and nf-yc mutants, we identify CCACA elements as the core NF-CO binding site...
May 19, 2017: Plant Cell
https://www.readbyqxmd.com/read/28525963/the-use-of-transgenic-parasites-in-malaria-vaccine-research
#4
Ahmad Syibli Othman, Catherin Marin-Mogollon, Ahmed M Salman, Blandine M Franke-Fayard, Chris J Janse, Shahid M Khan
Transgenic malaria parasites expressing foreign genes, for example fluorescent and luminescent proteins, are used extensively to interrogate parasite biology and host-parasite interactions associated with malaria pathology. Increasingly transgenic parasites are also exploited to advance malaria vaccine development. Areas Covered: We review how transgenic malaria parasites are used, in vitro and in vivo, to determine protective efficacy of different antigens and vaccination strategies and to determine immunological correlates of protection...
May 19, 2017: Expert Review of Vaccines
https://www.readbyqxmd.com/read/28525741/in%C3%A2-vivo-ubiquitin-linkage-type-analysis-reveals-that-the-cdc48-rad23-dsk2-axis-contributes-to-k48-linked-chain-specificity-of-the-proteasome
#5
Hikaru Tsuchiya, Fumiaki Ohtake, Naoko Arai, Ai Kaiho, Sayaka Yasuda, Keiji Tanaka, Yasushi Saeki
Ubiquitin-binding domain (UBD) proteins regulate numerous cellular processes, but their specificities toward ubiquitin chain types in cells remain obscure. Here, we perform a quantitative proteomic analysis of ubiquitin linkage-type selectivity of 14 UBD proteins and the proteasome in yeast. We find that K48-linked chains are directed to proteasomal degradation through selectivity of the Cdc48 cofactor Npl4. Mutating Cdc48 results in decreased selectivity, and lacking Rad23/Dsk2 abolishes interactions between ubiquitylated substrates and the proteasome...
May 18, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28525313/a-tunable-three-dimensional-in-vitro-culture-model-of-growth-plate-cartilage-using-alginate-hydrogel-scaffolds
#6
Alek G Erickson, Taylor D Laughlin, Sarah M Romereim, Catherine N Sargus-Patino, Angela K Pannier, Andrew T Dudley
Defining the final size and geometry of engineered tissues through precise control of the scalar and vector components of tissue growth is a necessary benchmark for regenerative medicine, but it has proved to be a significant challenge for tissue engineers. The growth plate cartilage that promotes elongation of the long bones is a good model system for studying morphogenetic mechanisms because cartilage is composed of a single cell type, the chondrocyte; chondrocytes are readily maintained in culture; and growth trajectory is predominately in a single vector...
May 18, 2017: Tissue Engineering. Part A
https://www.readbyqxmd.com/read/28524656/multifunctional-and-redox-responsive-self-assembled-magnetic-nanovectors-for-protein-delivery-and-dual-modal-imaging
#7
Hong Yu Yang, Moon-Sun Jang, Yi Li, Jung Hee Lee, Doo Sung Lee
Nanoparticle (NP)-based model carriers present an emerging strategy for protein delivery. However, constructing a multifunctional nanocarrier with high loading capacity, diagnostic imaging capacity and controlled release capability is a tremendous challenge for protein delivery systems. Thus, we herein report on the fabrication of redox-responsive magnetic nanovectors (termed RMNs) through self- assembly of Fe3O4 NPs and redox-responsive polymer ligands, which could effectively transport protein and trigger intracellular protein release...
May 19, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28524160/stroma-regulated-hmga2-is-an-independent-prognostic-marker-in-pdac-and-aac
#8
Carina Strell, Karin Jessica Norberg, Artur Mezheyeuski, Jonas Schnittert, Praneeth R Kuninty, Carlos Fernández Moro, Janna Paulsson, Nicolai Aagaard Schultz, Dan Calatayud, Johannes Matthias Löhr, Oliver Frings, Caroline Sophie Verbeke, Rainer Lothar Heuchel, Jai Prakash, Julia Sidenius Johansen, Arne Östman
BACKGROUND: The HMGA2 protein has experimentally been linked to EMT and cancer stemness. Recent studies imply that tumour-stroma interactions regulate these features and thereby contribute to tumour aggressiveness. METHODS: We analysed 253 cases of pancreatic ductal adenocarcinoma (PDAC) and 155 cases of ampullary adenocarcinoma (AAC) for HMGA2 expression by IHC. The data were correlated with stroma abundance and supplemented by experimental studies. RESULTS: HMGA2 acts as an independent prognostic marker associated with a significantly shorter overall survival in both tumour types...
May 18, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28523625/identification-of-a-novel-putative-inhibitor-of-the-plasmodium-falciparum-purine-nucleoside-phosphorylase-exploring-the-purine-salvage-pathway-to-design-new-antimalarial-drugs
#9
Luciano Porto Kagami, Gustavo Machado das Neves, Ricardo Pereira Rodrigues, Vinicius Barreto da Silva, Vera Lucia Eifler-Lima, Daniel Fábio Kawano
Malaria, a tropical parasitic disease caused by Plasmodium spp., continues to place a heavy social burden, with almost 200 million cases and more than 580,000 deaths per year. Plasmodium falciparum purine nucleoside phosphorylase (PfPNP) can be targeted for antimalarial drug design since its inhibition kills malaria parasites both in vitro and in vivo. Although the currently known inhibitors of PfPNP, immucillins, are orally available and of low toxicity to animals and humans, to the best of our knowledge, none of these compounds has entered clinical trials for the treatment of malaria...
May 18, 2017: Molecular Diversity
https://www.readbyqxmd.com/read/28521777/cip2a-mediates-fibronectin-induced-bladder-cancer-cell-proliferation-by-stabilizing-%C3%AE-catenin
#10
Fengbin Gao, Tianyuan Xu, Xianjin Wang, Shan Zhong, Shanwen Chen, Minguang Zhang, Xiaohua Zhang, Yifan Shen, Xiaojing Wang, Chen Xu, Zhoujun Shen
BACKGROUND: Fibronectin (FN) is associated with tumorigenesis and progression in bladder cancer, however, the underlying mechanisms causing this remain largely unknown. Furthermore, cancerous inhibitor of protein phosphatase 2A (CIP2A) has been shown to play important regulatory roles in cancer proliferation. Here, we investigated whether FN regulates CIP2A expression to promote bladder cancer cell proliferation. METHODS: The correlations of stromal FN with CIP2A and proliferating cell nuclear antigen (PCNA) expression were analyzed in a cohort bladder cancer patients...
May 18, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/28516783/antidiabetic-disruptors-of-the-glucokinase-glucokinase-regulatory-protein-complex-reorganize-a-coulombic-interface
#11
Juliana Martinez, Qing Xiao, Armen Zakarian, Brian G Miller
The glucokinase regulatory protein (GKRP) plays an essential role in glucose homeostasis by acting as a competitive inhibitor of glucokinase (GCK) and triggering its localization to the hepatocyte nucleus upon glucose deprivation. Metabolites such as fructose 6-phosphate and sorbitol 6-phosphate promote assembly of the GCK-GKRP complex, whereas fructose 1-phosphate and functionalized piperazines with potent in vivo antidiabetic activity disrupt the complex. Here, we establish the molecular basis by which these natural and synthetic ligands modulate the GCK-GKRP interaction...
May 18, 2017: Biochemistry
https://www.readbyqxmd.com/read/28516515/interaction-of-lincrna-ror-and-p53-mir-145-correlates-with-lung-cancer-stem-cell-signatures
#12
Fan Xia, Ye Xiong, Qiang Li
ROR is one of large intergenic non-coding RNAs (lincRNAs) and acts as a strong negative regulator of p53 and a sponge for miR-145 to regulate diverse cancer progression. However, the interaction of ROR, p53 and miR-145 in lung cancer and its correlation with lung cancer stem cell (LCSC) signatures were not fully understood. Here, qRT-PCR analysis revealed that p53 and ROR were upregulated while miR-145 was downregulated in non-small cell lung cancer (NSCLC) tissues and LCSCs compared to their paired adjacent normal tissues and lung cancer cells (LCCs)...
May 18, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28516085/analysis-of-septin-reorganization-at-cytokinesis-using-polarized-fluorescence-microscopy
#13
Molly McQuilken, Maximilian S Jentzsch, Amitabh Verma, Shalin B Mehta, Rudolf Oldenbourg, Amy S Gladfelter
Septins are conserved filament-forming proteins that act in diverse cellular processes. They closely associate with membranes and, in some systems, components of the cytoskeleton. It is not well understood how filaments assemble into higher-order structures in vivo or how they are remodeled throughout the cell cycle. In the budding yeast S. cerevisiae, septins are found through most of the cell cycle in an hourglass organization at the mother-bud neck until cytokinesis when the collar splits into two rings that disassemble prior to the next cell cycle...
2017: Frontiers in Cell and Developmental Biology
https://www.readbyqxmd.com/read/28515901/experimental-identification-and-computational-characterization-of-a-novel-extracellular-metalloproteinase-produced-by-clostridium-sordellii
#14
Michael J Aldape, Aoxiang Tao, Dustin D Heeney, Eric R McIndoo, John M French, Dong Xu
Clostridium sordellii is a lethal pathogen for both animals and humans. Severe capillary leakage, toxic shock syndrome, and an extreme leukemoid reaction (LR), are hallmark features of C. sordellii infections and contribute to its high mortality rate. Here we report the discovery of a previously unknown and uncharacterized metalloproteinase of C. sordellii (referred as Mcs1) that cleaves human vascular cell adhesion molecule (VCAM)-1 in vitro, an adhesion molecule critical to hematopoietic precursor retention and leukocyte diapedesis...
March 2, 2017: RSC Advances
https://www.readbyqxmd.com/read/28515487/functional-interaction-between-fus-and-smn-underlies-sma-like-splicing-changes-in-wild-type-hfus-mice
#15
Alessia Mirra, Simona Rossi, Silvia Scaricamazza, Michela Di Salvio, Illari Salvatori, Cristiana Valle, Paola Rusmini, Angelo Poletti, Gianluca Cestra, Maria Teresa Carrì, Maur O Cozzolino
Several of the identified genetic factors in Amyotrophic Lateral Sclerosis (ALS) point to dysfunction in RNA processing as a major pathogenic mechanism. However, whether a precise RNA pathway is particularly affected remains unknown. Evidence suggests that FUS, that is mutated in familial ALS, and SMN, the causative factor in Spinal Muscular Atrophy (SMA), cooperate to the same molecular pathway, i.e. regulation of alternative splicing, and that disturbances in SMN-regulated functions, either caused by depletion of SMN protein (as in the case of SMA) or by pathogenic interactions between FUS and SMN (as in the case of ALS) might be a common theme in both diseases...
May 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28515319/the-h-region-of-twin-arginine-signal-peptides-supports-productive-binding-of-bacterial-tat-precursor-proteins-to-the-tatbc-receptor-complex
#16
Agnes Ulfig, Julia Fröbel, Frank Lausberg, Anne-Sophie Blümmel, Anna Katharina Heide, Matthias Müller, Roland Freudl
The twin arginine translocation (Tat) pathway transports folded proteins across bacterial membranes. Tat precursor proteins possess a conserved twin-arginine (RR) motif in their signal peptides that is involved in their binding to the Tat translocase, but some facets of this interaction remain unclear. Here, we investigated the role of the hydrophobic (h-) region of the Escherichia coli TMAO reductase (TorA) signal peptide in TatBC receptor binding in vivo and in vitro. We show that besides the RR motif, a minimal functional h-region in the signal peptide is required for Tat-dependent export in E...
May 17, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28515087/fxyd5-dysadherin-may-mediate-metastatic-progression-through-regulation-of-the-%C3%AE-na-k-atpase-subunit-in-4t1-mouse-breast-cancer-model
#17
Irina Lubarski-Gotliv, Kuntal Dey, Yuri Kuznetsov, Vecheslav Kalchenco, Carol Asher, Haim Garty
FXYD5 is a Na(+)-K(+)-ATPase regulator, expressed in a variety of normal epithelia. In parallel, it has been found to be associated with several types of cancer and effect lethal outcome by promoting metastasis. However, the molecular mechanism underlying FXYD5 mediated invasion, was has not yet been identified. In this study, using in vivo 4T1 murine breast cancer model, we found that FXYD5 specific shRNA significantly inhibited lung cancer metastasis, without having a substantial effect on primary tumor growth...
May 17, 2017: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/28514441/pd-1-expression-by-tumour-associated-macrophages-inhibits-phagocytosis-and-tumour-immunity
#18
Sydney R Gordon, Roy L Maute, Ben W Dulken, Gregor Hutter, Benson M George, Melissa N McCracken, Rohit Gupta, Jonathan M Tsai, Rahul Sinha, Daniel Corey, Aaron M Ring, Andrew J Connolly, Irving L Weissman
Programmed cell death protein 1 (PD-1) is an immune checkpoint receptor that is upregulated on activated T cells for the induction of immune tolerance. Tumour cells frequently overexpress the ligand for PD-1, programmed cell death ligand 1 (PD-L1), facilitating their escape from the immune system. Monoclonal antibodies that block the interaction between PD-1 and PD-L1, by binding to either the ligand or receptor, have shown notable clinical efficacy in patients with a variety of cancers, including melanoma, colorectal cancer, non-small-cell lung cancer and Hodgkin's lymphoma...
May 17, 2017: Nature
https://www.readbyqxmd.com/read/28512205/phorbol-12-myristate-13-acetate-mediated-stabilization-of-leukemia-inhibitory-factor-lif-mrna-involvement-of-nucleolin-and-pcbp1
#19
Alina Chakraborty, Srimoyee Mukherjee, Sucharita Saha, Soumasree De, Sumita Sengupta Bandyopadhyay
LIF is a potent pleiotropic cytokine involved in diverse biological activities, thereby requiring precise spatial and temporal control of its expression. The present study reveals that enhanced expression of Leukemia Inhibitory Factor in response to PMA (phorbol-12-myristate-13-acetate) in human histiocytic lymphoma cell-line U937 largely happens through stabilization of its mRNA. Functional characterization of the long 3'-untranslated region (3'-UTR) of human lif -mRNA revealed several conserved sequences with conventional cis -acting elements...
May 16, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/28511928/rational-design-of-nanoparticles-towards-targeting-antigen-presenting-cells-and-improved-t-cell-priming
#20
Eva Zupančič, Caterina Curato, Maria Paisana, Catarina Rodrigues, Ziv Porat, Ana S Viana, Carlos A M Afonso, João Pinto, Rogério Gaspar, João N Moreira, Ronit Satchi-Fainaro, Steffen Jung, Helena F Florindo
Vaccination is a promising strategy to trigger and boost immune responses against cancer or infectious disease. We have designed, synthesized and characterized aliphatic-polyester (poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NP) to investigate how the nature of protein association (adsorbed versus entrapped) and polymer/surfactant concentrations impact on the generation and modulation of antigen-specific immune responses. The ability of the NP formulations to target dendritic cells (DC), be internalized and activate the T cells was characterized and optimized in vitro and in vivo using markers of DC activation and co-stimulatory molecules...
May 13, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
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