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https://www.readbyqxmd.com/read/29775732/il4-10-fusion-protein-has-chondroprotective-anti-inflammatory-and-potentially-analgesic-effects-in-the-treatment-of-osteoarthritis
#1
C Steen-Louws, J Popov-Celeketic, S C Mastbergen, K Coeleveld, C E Hack, N Eijkelkamp, M Tryfonidou, S Spruijt, J A G van Roon, F P J G Lafeber
OBJECTIVE: Effective disease-modifying drugs for osteoarthritis (DMOAD) should preferably have chondroprotective, anti-inflammatory, and analgesic activity combined in a single molecule. We developed a fusion protein of IL4 and IL10 (IL4-10 FP), in which the biological activity of both cytokines is preserved. The present study evaluates the chondroprotective, anti-inflammatory, and analgesic activity of IL4-10 FP in in vitro and in vivo models of osteoarthritis. METHODS: Human osteoarthritic cartilage tissue and synovial tissue were cultured with IL4-10 FP...
May 15, 2018: Osteoarthritis and Cartilage
https://www.readbyqxmd.com/read/29774653/matrix-glycoprotein-interactions-required-for-budding-of-a-plant-nucleorhabdovirus-and-induction-of-inner-nuclear-membrane-invagination
#2
Kai Sun, Xin Zhou, Wenye Lin, Xueping Zhou, Andrew O Jackson, Zhenghe Li
Nucleorhabdoviruses such as Sonchus yellow net virus (SYNV) replicate in the nuclei and undergo morphogenesis at the inner nuclear membrane (IM) in plant cells. Mature particles are presumed to form by budding of the Matrix (M) protein-nucleocapsid complexes through host IMs to acquire host phospholipids and the surface glycoproteins (G). To address mechanisms underlying nucleorhabdovirus budding, we generated recombinant SYNV G mutants containing a truncated amino-terminal (NT) or carboxyl-terminal (CT) domain...
May 18, 2018: Molecular Plant Pathology
https://www.readbyqxmd.com/read/29774349/role-of-arsenic-3-oxidation-state-methyltransferase-in-arsenic-mediated-apl-treatment-an-in-vitro-investigation
#3
Yasen Maimaitiyiming, Chao Wang, Shi Xu, Khairul Islam, Ye Jia Chen, Chang Yang, Qian Qian Wang, Hua Naranmandura
Arsenic (+3 oxidation state) methyltransferase (AS3MT) is a key enzyme responsible for arsenic metabolism in humans, which facilitates conversion of arsenic trioxide (As2O3) to more reactive metabolites such as monomethylarsonous acid (MMAIII) and dimethylarsinous acid (DMAIII). However, it is unclear whether the biotransformation of arsenic by AS3MT contributes to the promotion of acute promyelocytic leukemia (APL) therapy. In order to understand the probable role of AS3MT in APL patients, we evaluated the effects of arsenite (iAsIII) and three mixed arsenicals (i...
May 18, 2018: Metallomics: Integrated Biometal Science
https://www.readbyqxmd.com/read/29774127/paf1-complex-interactions-with-setdb1-mediate-promoter-h3k9-methylation-and-transcriptional-repression-of-hoxa9-and-meis1-in-acute-myeloid-leukemia
#4
James Ropa, Nirmalya Saha, Zhiling Chen, Justin Serio, Wei Chen, Dattatreya Mellacheruvu, Lili Zhao, Venkatesha Basrur, Alexey I Nesvizhskii, Andrew G Muntean
The Polymerase Associated Factor 1 complex (PAF1c) is an epigenetic co-modifying complex that directly contacts RNA polymerase II (RNAPII) and several epigenetic regulating proteins. Mutations, overexpression and loss of expression of subunits of the PAF1c are observed in various forms of cancer suggesting proper regulation is needed for cellular development. However, the biochemical interactions with the PAF1c that allow dynamic gene regulation are unclear. We and others have shown that the PAF1c makes a direct interaction with MLL fusion proteins, which are potent oncogenic drivers of acute myeloid leukemia (AML)...
April 24, 2018: Oncotarget
https://www.readbyqxmd.com/read/29774063/dual-target-gene-therapy-to-eml4-alk-nsclc-by-a-gold-nanoshell-based-system
#5
Siwen Li, Yuxi Liu, Yalan Rui, Liping Tang, Samuel Achilefu, Yueqing Gu
Although EML4-ALK transforming fusion gene is represented in only 8% of non-small cell lung cancer (NSCLC) cases, its expression is partly responsive for the failure of current NSCLC treatments. Preventing secondary mutation of the ALK protein through direct gene manipulation could overcome NSCLC drug resistance. Method: In this study, we developed a gold nanoshell (HAuNs) drug carrier for delivery and selective photo-thermal release of genes that target ALK and microRNA-301 in NSCLC. Additionally, the densely-coated nanoshell adsorbed high amounts of the positively-charged anticancer drug doxorubicin (DOX), generating an exciting multidimensional treatment strategy that includes gene-, thermal- and chemo- therapy...
2018: Theranostics
https://www.readbyqxmd.com/read/29773864/igg-single-chain-trail-fusion-proteins-for-tumour-therapy
#6
Martin Siegemund, Felix Schneider, Meike Hutt, Oliver Seifert, Ines Müller, Dagmar Kulms, Klaus Pfizenmaier, Roland E Kontermann
Single-chain formats of TNF-related apoptosis inducing ligand (scTRAIL) can serve as effector components of tumour-associated antigen-targeted as well as non-targeted fusion proteins, being characterized by high tumour cell-specific induction of apoptosis through death receptor activation. We studied the suitability of immunoglobulin G as a scaffold for oligovalent and bispecific TRAIL fusion proteins. Thus, we developed novel targeted hexa- and dodecavalent IgG-scTRAIL molecules by fusing scTRAIL to the C-terminus of either light (LC-scTRAIL) or heavy immunoglobulin chain (HC-scTRAIL), or to both ends (LC/HC-scTRAIL) of the anti-EGFR IgG antibody hu225...
May 17, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29773600/the-interleukin-3-receptor-cd123-targeted-sl-401-mediates-potent-cytotoxic-activity-against-cd34-cd123-cells-from-acute-myeloid-leukemia-myelodysplastic-syndrome-patients-and-healthy-donors
#7
Rajeswaran Mani, Swagata Goswami, Bhavani Gopalakrishnan, Rahul Ramaswamy, Ronni Wasmuth, Minh Tranh, Xiaokui Mo, Amber Gordon, Donna Bucci, David M Lucas, Alice Mims, Christopher Brooks, Adrienne Dorrance, Alison Walker, William Blum, John C Byrd, Gerard Lozanski, Sumithira Vasu, Natarajan Muthusamy
Diseases with clonal hematopoiesis such as myelodysplastic syndrome and acute myeloid leukemia have high rates of relapse. Only a small subset of acute myeloid leukemia patients are cured with chemotherapy alone. Relapse in these diseases occurs at least in part due to the failure to eradicate leukemic stem cells or hematopoietic stem cells in myelodysplastic syndrome. CD123, the alpha chain of the interleukin-3 receptor heterodimer, is expressed on the majority of leukemic stem cells and myelodysplastic syndrome hematopoietic stem cells and in 80% of acute myeloid leukemia...
May 17, 2018: Haematologica
https://www.readbyqxmd.com/read/29773426/stem-cell-transcription-factor-sox2-in-synovial-sarcoma-and-other-soft-tissue-tumors
#8
Heba Zayed, Iver Petersen
BACKGROUND: SOX2 has gained considerable interest as a pluripotency inducing gene. Co-transfection of SOX2 together with NANOG, KLF4 and c-MYC into adult fibroblasts was able to generate pluripotent stem cells. SOX2 has been reported to be expressed in synovial sarcoma, a tumor being characterized by the SS18-SSX gene fusion forming part of the SWI/SNF chromatin remodeling complex that affects histone methylation. The role of SOX2 in this tumor type as well as other soft tissue tumor entities however is still poorly characterized...
May 4, 2018: Pathology, Research and Practice
https://www.readbyqxmd.com/read/29772656/correction-riedlinger-t-et-al-the-direct-and-indirect-roles-of-nf-%C3%AE%C2%BAb-in-cancer-lessons-from-oncogenic-fusion-proteins-and-knock-in-mice-biomedicines-2018-6-36
#9
Tabea Riedlinger, Jana Haas, Julia Busch, Bart van de Sluis, Michael Kracht, M Lienhard Schmitz
No abstract text is available yet for this article.
May 16, 2018: Biomedicines
https://www.readbyqxmd.com/read/29772060/nucleocytoplasmic-shuttling-the-ins-and-outs-of-quantitative-imaging
#10
Chris Molenaar, Kate L Weeks
Nucleocytoplasmic protein shuttling is integral to the transmission of signals between the nucleus and the cytoplasm. The nuclear/cytoplasmic distribution of proteins of interest can be determined via fluorescence microscopy, following labelling of the target protein with fluorophore-conjugated antibodies (immunofluorescence) or by tagging the target protein with an autofluorescent protein, such as green fluorescent protein (GFP). The latter enables live cell imaging, a powerful approach that precludes many of the artefacts associated with indirect immunofluorescence in fixed cells...
May 17, 2018: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/29771911/asymmetric-polar-localization-dynamics-of-the-serine-chemoreceptor-protein-tsr-in-escherichia-coli
#11
Dongmyung Oh, Yang Yu, Hochan Lee, Jae-Hyung Jeon, Barry L Wanner, Ken Ritchie
The spatial location of proteins in living cells can be critical for their function. For example, the E. coli chemotaxis machinery is localized to the cell poles. Here we describe the polar localization of the serine chemoreceptor Tsr using a strain synthesizing a fluorescent Tsr-Venus fusion at a low level from a single-copy chromosomal construct. Using photobleaching and imaging during recovery by new synthesis, we observed distinct asymmetry between a bright (old) pole and a dim (new) pole. The old pole was shown to be a more stable cluster and to recover after photobleaching faster, which is consistent with the hypothesis that newly synthesized Tsr proteins are inserted directly at or near the old pole...
2018: PloS One
https://www.readbyqxmd.com/read/29771640/phosphorylation-of-snap-23-at-ser95-causes-a-structural-alteration-and-negatively-regulates-fc-receptor-mediated-phagosome-formation-and-maturation-in-macrophages
#12
Chiye Sakurai, Makoto Itakura, Daiki Kinoshita, Seisuke Arai, Hitoshi Hashimoto, Ikuo Wada, Kiyotaka Hatsuzawa
SNAP-23 is a plasma membrane-localized SNARE protein involved in Fc receptor (FcR)-mediated phagocytosis. However, the regulatory mechanism underlying its function remains elusive. Using phosphorylation specific-antibodies, SNAP-23 was found to be phosphorylated at Ser95 in macrophages. To understand the role of this phosphorylation, we established macrophage lines overexpressing the non-phosphorylatable S95A or the phospho-mimicking S95D mutation. The efficiency of phagosome formation and maturation was severely reduced in SNAP-23-S95D-overexpressing cells...
May 17, 2018: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/29771629/brain-uptake-of-multivalent-and-multi-specific-dvd-ig-proteins-after-systemic-administration
#13
Denise Karaoglu Hanzatian, Annette Schwartz, Farid Gizatullin, Jamie Erickson, Kangwen Deng, Ruth Villanueva, Christopher Stedman, Cristina Harris, Tariq Ghayur, Andrew Goodearl
Therapeutic monoclonal antibodies and endogenous IgG antibodies show limited uptake into the central nervous system (CNS) due to the blood-brain barrier (BBB), which regulates and controls the selective and specific transport of both exogenous and endogenous materials to the brain. The use of natural transport mechanisms, such as receptor-mediated transcytosis (RMT), to deliver antibody therapeutics into the brain have been studied in rodents and monkeys. Recent successful examples include monovalent bispecific antibodies and mono- or bivalent fusion proteins; however, these formats do not have the capability to bind to both the CNS target and the BBB transport receptor in a bivalent fashion as a canonical antibody would...
May 17, 2018: MAbs
https://www.readbyqxmd.com/read/29770338/basic-fibroblast-growth-factor-fused-with-tandem-collagen-binding-domains-from-clostridium-histolyticum-collagenase-colg-increases-bone-formation
#14
Hiroyuki Sekiguchi, Kentaro Uchida, Osamu Matsushita, Gen Inoue, Nozomu Nishi, Ryo Masuda, Nana Hamamoto, Takaki Koide, Shintaro Shoji, Masashi Takaso
Basic fibroblast growth factor 2 (bFGF) accelerates bone formation during fracture healing. Because the efficacy of bFGF decreases rapidly following its diffusion from fracture sites, however, repeated dosing is required to ensure a sustained therapeutic effect. We previously developed a fusion protein comprising bFGF, a polycystic kidney disease domain (PKD; s2b), and collagen-binding domain (CBD; s3) sourced from the Clostridium histolyticum class II collagenase, ColH, and reported that the combination of this fusion protein with a collagen-like peptide, poly(Pro-Hyp-Gly)10 , induced mesenchymal cell proliferation and callus formation at fracture sites...
2018: BioMed Research International
https://www.readbyqxmd.com/read/29770142/subcellular-localization-screening-of-colletotrichum-higginsianum-effector-candidates-identifies-fungal-proteins-targeted-to-plant-peroxisomes-golgi-bodies-and-microtubules
#15
Guillaume P Robin, Jochen Kleemann, Ulla Neumann, Lisa Cabre, Jean-Félix Dallery, Nicolas Lapalu, Richard J O'Connell
The genome of the hemibiotrophic anthracnose fungus, Colletotrichum higginsianum , encodes a large inventory of putative secreted effector proteins that are sequentially expressed at different stages of plant infection, namely appressorium-mediated penetration, biotrophy and necrotrophy. However, the destinations to which these proteins are addressed inside plant cells are unknown. In the present study, we selected 61 putative effector genes that are highly induced in appressoria and/or biotrophic hyphae. We then used Agrobacterium -mediated transformation to transiently express them as N -terminal fusions with fluorescent proteins in cells of Nicotiana benthamiana for imaging by confocal microscopy...
2018: Frontiers in Plant Science
https://www.readbyqxmd.com/read/29770128/critical-functions-of-region-1-67-and-helix-xiii-in-retaining-the-active-structure-of-nhad-antiporter-in-halomonas-sp-y2
#16
Zhou Yang, Yiwei Meng, Qi Zhao, Bin Cheng, Ping Xu, Chunyu Yang
NhaD-type antiporters are mainly distributed in various Proteobacteria , especially in marine microorganisms and human pathogens. This distribution as well as the pathogenic properties of these strains suggest that these antiporters contribute to the regulation of high osmoregulation and are potential drug targets. Two NhaD homologs, NhaD1 and NhaD2, from the halotolerant and alkaliphilic Halomonas sp. Y2 exhibits similar, high in vitro activity, but remarkably different in vivo functions. To search for critical domains or residues involved in these differences of physiological functions, various chimeras composed of NhaD1 and NhaD2 segments were generated...
2018: Frontiers in Microbiology
https://www.readbyqxmd.com/read/29769725/mxra8-is-a-receptor-for-multiple-arthritogenic-alphaviruses
#17
Rong Zhang, Arthur S Kim, Julie M Fox, Sharmila Nair, Katherine Basore, William B Klimstra, Rebecca Rimkunas, Rachel H Fong, Hueylie Lin, Subhajit Poddar, James E Crowe, Benjamin J Doranz, Daved H Fremont, Michael S Diamond
Arthritogenic alphaviruses comprise a group of enveloped RNA viruses that are transmitted to humans by mosquitoes and cause debilitating acute and chronic musculoskeletal disease 1 . The host factors required for alphavirus entry remain poorly characterized 2 . Here we use a genome-wide CRISPR-Cas9-based screen to identify the cell adhesion molecule Mxra8 as an entry mediator for multiple emerging arthritogenic alphaviruses, including chikungunya, Ross River, Mayaro and O'nyong nyong viruses. Gene editing of mouse Mxra8 or human MXRA8 resulted in reduced levels of viral infection of cells and, reciprocally, ectopic expression of these genes resulted in increased infection...
May 16, 2018: Nature
https://www.readbyqxmd.com/read/29769533/structure-of-a-cleavage-independent-hiv-env-recapitulates-the-glycoprotein-architecture-of-the-native-cleaved-trimer
#18
Anita Sarkar, Shridhar Bale, Anna-Janina Behrens, Sonu Kumar, Shailendra Kumar Sharma, Natalia de Val, Jesper Pallesen, Adriana Irimia, Devan C Diwanji, Robyn L Stanfield, Andrew B Ward, Max Crispin, Richard T Wyatt, Ian A Wilson
Furin cleavage of the HIV envelope glycoprotein is an essential step for cell entry that enables formation of well-folded, native-like glycosylated trimers, releases constraints on the fusion peptide, and limits enzymatic processing of the N-glycan shield. Here, we show that a cleavage-independent, stabilized, soluble Env trimer mimic (BG505 NFL.664) exhibits a "closed-form", native-like, prefusion conformation akin to furin-cleaved Env trimers. The crystal structure of BG505 NFL.664 at 3.39 Å resolution with two potent bNAbs also identifies the full epitopes of PGV19 and PGT122 that target the receptor binding site and N332 supersite, respectively...
May 16, 2018: Nature Communications
https://www.readbyqxmd.com/read/29769343/glycoprotein-3-of-porcine-reproductive-and-respiratory-syndrome-virus-exhibits-an-unusual-hairpin-like-membrane-topology
#19
Minze Zhang, Ludwig Krabben, Fangkun Wang, Michael Veit
The glycoprotein GP3 of the Arterivirus porcine reproductive and respiratory syndrome virus (PRRSV) consists of a cleaved signal peptide, a highly glycosylated domain, a short hydrophobic region and an unglycosylated C-terminal domain. GP3 is supposed to form a complex with GP2 and GP4 in virus particles, but secretion of GP3 from cells has also been reported.We analyzed the membrane topology of GP3 from various PRRSV strains. A fraction of the protein is secreted from transfected cells; GP3 from PRRSV-1 strains to a greater extent than GP3 from PRRSV-2 strains...
May 16, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29769087/replacement-of-feline-foamy-virus-bet-by-feline-immunodeficiency-virus-vif-yields-replicative-virus-with-novel-vaccine-candidate-potential
#20
Carmen Ledesma-Feliciano, Sarah Hagen, Ryan Troyer, Xin Zheng, Esther Musselman, Dragana Slavkovic Lukic, Ann-Mareen Franke, Daniel Maeda, Jörg Zielonka, Carsten Münk, Guochao Wei, Sue VandeWoude, Martin Löchelt
BACKGROUND: Hosts are able to restrict viral replication to contain virus spread before adaptive immunity is fully initiated. Many viruses have acquired genes directly counteracting intrinsic restriction mechanisms. This phenomenon has led to a co-evolutionary signature for both the virus and host which often provides a barrier against interspecies transmission events. Through different mechanisms of action, but with similar consequences, spumaviral feline foamy virus (FFV) Bet and lentiviral feline immunodeficiency virus (FIV) Vif counteract feline APOBEC3 (feA3) restriction factors that lead to hypermutation and degradation of retroviral DNA genomes...
May 16, 2018: Retrovirology
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