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https://www.readbyqxmd.com/read/28921913/high-resolution-imaging-of-muscle-attachment-structures-in-c-elegans
#1
Hiroshi Qadota, Yohei Matsunaga, Ken C Q Nguyen, Alexa Mattheyses, David H Hall, Guy M Benian
We used structured illumination microscopy (SIM) to obtain super-resolution images of muscle attachment structures in C. elegans striated muscle. SIM imaging of M-line components revealed two patterns: PAT-3 (β-integrin) and proteins that interact in a complex with the cytoplasmic tail of β-integrin and localize to the basal muscle cell membrane (UNC-112 (kindlin), PAT-4 (ILK), UNC-97 (PINCH), PAT-6 (α-parvin) and UNC-95), are found in discrete, angled segments with gaps. In contrast, proteins localized throughout the depth of the M-line (UNC-89 (obscurin) and UNC-98) are imaged as continuous lines...
September 16, 2017: Cytoskeleton
https://www.readbyqxmd.com/read/28921899/stimulus-induced-conformational-transformation-of-cyclic-peptide-for-selective-cell-targeting-on-off-gatekeeper-of-mesoporous-nanocarrier
#2
Jeonghun Lee, Eun-Taex Oh, Jaehun Song, Ha Gyeong Kim, Heon Joo Park, Chulhee Kim
The αvβ3 integrin is upregulated on many cancer cells. We designed a dual functional cyclic peptide gatekeeper with a capability of stimuli-responsive conformational transformation which could serve as a selective cell targeting on-off gatekeeper for mesoporous nanocarriers. The advantage of employing the motif of stimuli-induced conformational transformation of cyclic peptides is that they could be utilized not only as an on-off gatekeeper for the triggered release of cargo drugs but also as a targeting ligand of the carriers to desired cells with their respective binding receptors...
September 17, 2017: Chemistry, An Asian Journal
https://www.readbyqxmd.com/read/28920441/new-insight-of-common-regulatory-pathways-in-human-trabecular-meshwork-cells-in-response-to-dexamethasone-and-prednisolone-using-an-integrated-quantitative-proteomics-swath-and-mrm-hr-mass-spectrometry
#3
Sze Wan Shan, Chi Wai Do, Thomas Chuen Lam, Ricky Pak Wing Kong, King Kit Li, Ka Man Chun, William Daniel Stamer, Chi Ho To
The molecular pathophysiology of corticosteroid-induced ocular hypertension (CIH) is not well understood. To determine the biological mechanisms of CIH, this study investigated protein expression profiles of human trabecular meshwork (hTM) cells in response to dexamethasone and prednisolone treatment. Both discovery-based Sequential Windowed data independent Acquisition of the Total High-resolution mass spectra (SWATH(TM)-MS) and targeted based high resolution multiple reaction monitoring (MRM-HR) confirmation were applied using a hybrid quadrupole-time-of-flight mass spectrometer...
September 18, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/28920097/acute-cd47-blockade-during-ischemic-myocardial-reperfusion-enhances-phagocytosis-associated-cardiac-repair
#4
Shuang Zhang, Xin-Yi Yeap, Matthew DeBerge, Nivedita K Naresh, Kevin Wang, Zhengxin Jiang, Jane E Wilcox, Steven M White, John P Morrow, Paul W Burridge, Daniel Procissi, Evan A Scott, William Frazier, Edward B Thorp
Our data suggest that, after a myocardial infarction, integrin-associated protein CD47 on cardiac myocytes is elevated. In culture, increased CD47 on the surface of dying cardiomyocytes impairs phagocytic removal by immune cell macrophages. After myocardial ischemia and reperfusion, acute CD47 inhibition with blocking antibodies enhanced dead myocyte clearance by cardiac phagocytes and also improved the resolution of cardiac inflammation, reduced infarct size, and preserved cardiac contractile function. Early targeting of CD47 in the myocardium after reperfusion may be a new strategy to enhance wound repair in the ischemic heart...
August 2017: JACC. Basic to Translational Science
https://www.readbyqxmd.com/read/28919876/peptide-composition-of-stroke-causing-emboli-correlate-with-serum-markers-of-atherosclerosis-and-inflammation
#5
Neal M Rao, Joseph Capri, Whitaker Cohn, Maram Abdaljaleel, Lucas Restrepo, Jeffrey A Gornbein, William H Yong, David S Liebeskind, Julian P Whitelegge
INTRODUCTION: The specific protein composition of stroke-causing emboli is unknown. Because ischemic stroke has a varied etiology, it is possible that the composition of the thrombus from which an embolus originated will have distinctive molecular characteristics reflective of the underlying pathophysiology. We used mass spectrometry to evaluate the protein composition of retrieved emboli from patients with differing stroke etiologies and correlated the protein levels to serum predictors of atherosclerosis...
2017: Frontiers in Neurology
https://www.readbyqxmd.com/read/28919578/selectin-independent-adhesion-during-ovarian-cancer-metastasis
#6
Nadezhda A Khaustova, Diana V Maltseva, Leticia Oliveira-Ferrer, Christine Stürken, Karin Milde-Langosch, Julia A Makarova, Sergey Rodin, Udo Schumacher, Alexander G Tonevitsky
PURPOSE: Ovarian cancer (OvCa) progression mainly takes place by intraperitoneal spread. Adhesion of tumor cells to the mesothelial cells which form the inner surface of the peritoneum is a crucial step in this process. Cancer cells use in principle different molecules of the leukocyte adhesion cascade to facilitate adhesion. This cascade is initiated by selectin-ligand interactions followed by integrin - extracellular matrix protein interactions. Here we address the question whether all tumor cells predominantly employ selectin-dependent leukocyte-like adhesion cascade (SDAC) or whether they use integrin mediated adhesion for OvCa progression as well...
September 14, 2017: Biochimie
https://www.readbyqxmd.com/read/28919512/strontium-and-magnesium-ions-released-from-bioactive-titanium-metal-promote-early-bone-bonding-in-a-rabbit-implant-model
#7
Yaichiro Okuzu, Shunsuke Fujibayashi, Seiji Yamaguchi, Koji Yamamoto, Takayoshi Shimizu, Takashi Sono, Koji Goto, Bungo Otsuki, Tomiharu Matsushita, Tadashi Kokubo, Shuichi Matsuda
We have previously developed the "alkali and heat treatment" method to confer bioactivity (bone-bonding ability) to titanium metal (Ti). As strontium (Sr) and magnesium (Mg) ions reportedly promote osteoblastic cell proliferation and differentiation and accelerate bone formation, we improved this method to induce the release of Sr (Sr-Ti) or Mg (Mg-Ti) ions from Ti in a previous study. Here, we evaluated the bioactivity of these novel surface treatments, Sr-Ti and Mg-Ti. In vitro evaluation of cell viability, expression of integrin β1, β catenin, and cyclin D1, osteogenic gene expression, alkaline phosphatase activity, and extracellular mineralization using MC3T3-E1 cells revealed that Sr-Ti and Mg-Ti enhanced proliferation and osteogenic differentiation...
September 14, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28919443/fv-clasp-an-artificially-designed-small-antibody-fragment-with-improved-production-compatibility-stability-and-crystallizability
#8
Takao Arimori, Yu Kitago, Masataka Umitsu, Yuki Fujii, Ryoko Asaki, Keiko Tamura-Kawakami, Junichi Takagi
Antibody fragments are frequently used as a "crystallization chaperone" to aid structural analysis of complex macromolecules that are otherwise crystallization resistant, but conventional fragment formats have not been designed for this particular application. By fusing an anti-parallel coiled-coil structure derived from the SARAH domain of human Mst1 kinase to the variable region of an antibody, we succeeded in creating a novel chimeric antibody fragment of ∼37 kDa, termed "Fv-clasp," which exhibits excellent crystallization compatibility while maintaining the binding ability of the original IgG molecule...
September 6, 2017: Structure
https://www.readbyqxmd.com/read/28918491/dynamics-of-allosteric-modulation-of%C3%A2-lymphocyte-function-associated-antigen-1-closure-open-switch-unveiling-the-structural-mechanisms-associated-with-outside-in-signaling-activation
#9
Maryam Abdullahi, Fisayo A Olotu, Mahmoud E Soliman
OBJECTIVES: To provide insight into the dynamics of the shape-shifting mechanistic events associated with the opening (activation) of Lymphocyte Function Associated Antigen-1 upon allosteric modulation by an activator, ICAM Binding Enhancer-667 (IBE-667), using molecular dynamics simulation. RESULTS: Various parameters were used to appropriately describe and understand the sequence of events that characterized its activation across the simulation period such as residual distances, TriCα angles; as well as the dihedral angle...
September 16, 2017: Biotechnology Letters
https://www.readbyqxmd.com/read/28918490/notch-signaling-pathway-networks-in-cancer-metastasis-a-new-target-for-cancer-therapy
#10
REVIEW
Li Li, Ping Tang, Shun Li, Xiang Qin, Hong Yang, Chunhui Wu, Yiyao Liu
Notch signaling pathway is evolutionarily conserved in mammals, which plays an important role in cell development and differentiation. In recent years, increasing evidence has shown that aberrant activation of Notch is associated with tumor process. Aberrant activation of Notch signaling pathway has been found in many different solid tumors can induce cell proliferation, metastasis and epithelial-mesenchymal transition. Notch receptor and its ligand are both single transmembrane protein, and Notch is activated when it binds to the Notch ligand of neighbor cells...
September 16, 2017: Medical Oncology
https://www.readbyqxmd.com/read/28917854/tilia-tomentosa-pectins-exhibit-dual-mode-of-action-on-phagocytes-as-%C3%AE-glucuronic-acid-monomers-are-abundant-in-their-rhamnogalacturonans-i
#11
Yordan N Georgiev, Berit S Paulsen, Hiroaki Kiyohara, Milan Ciz, Manol H Ognyanov, Ondrej Vasicek, Frode Rise, Petko N Denev, Antonin Lojek, Tsvetelina G Batsalova, Balik M Dzhambazov, Haruki Yamada, Reidar Lund, Hilde Barsett, Albert I Krastanov, Irina Z Yanakieva, Maria G Kratchanova
Silver linden flowers contain different pectins (PSI-PSIII) with immunomodulating properties. PSI is a low-esterified pectic polysaccharide with predominant homogalacturonan region, followed by rhamnogalacturonan I (RGI) with arabinogalactan II and RGII (traces) domains. PSII and PSIII are unusual glucuronidated RGI polymers. PSIII is a unique high molecular weight RGI, having almost completely O-3 glucuronidated GalA units with >30% O-3 acetylation at the Rha units. Linden pectins induced reactive oxygen species (ROS) and NO generation from non-stimulated whole blood phagocytes and macrophages, resp...
November 1, 2017: Carbohydrate Polymers
https://www.readbyqxmd.com/read/28916665/integrin-%C3%AE-4-overexpression-on-rat-mesenchymal-stem-cells-enhances-transmigration-and-reduces-cerebral-embolism-after-intracarotid-injection
#12
Li-Li Cui, Franziska Nitzsche, Evgeny Pryazhnikov, Marina Tibeykina, Laura Tolppanen, Jussi Rytkönen, Tuulia Huhtala, Jing-Wei Mu, Leonard Khiroug, Johannes Boltze, Jukka Jolkkonen
BACKGROUND AND PURPOSE: Very late antigen-4 (integrin α4β1)/vascular cell adhesion molecule-1 mediates leukocyte trafficking and transendothelial migration after stroke. Mesenchymal stem cells (MSCs) typically express integrin β1 but insufficient ITGA4 (integrin α4), which limits their homing after intravascular transplantation. We tested whether ITGA4 overexpression on MSCs increases cerebral homing after intracarotid transplantation and reduces MSC-borne cerebral embolism. METHODS: Rat MSCs were lentivirally transduced to overexpress ITGA4...
September 15, 2017: Stroke; a Journal of Cerebral Circulation
https://www.readbyqxmd.com/read/28916657/tenascin-c-and-integrin-%C3%AE-9-mediate-interactions-of-prostate-cancer-with-the-bone-microenvironment
#13
Rebeca San Martin, Ravi Pathak, Antrix Jain, Sung Yun Jung, Susan G Hilsenbeck, Maria C Piňa-Barba, Andrew G Sikora, Kenneth J Pienta, David R Rowley
Deposition of the extracellular matrix protein tenascin-C is part of the reactive stroma response, which has a critical role in prostate cancer progression. Here we report that tenascin-C is expressed in the bone endosteum and involved associated with formation of prostate bone metastases. Metastatic cells cultured on osteo-mimetic surfaces coated with tenascin-C exhibited enhanced adhesion and colony formation as mediated by integrin α9β1. Additionally, metastatic cells preferentially migrated and colonized tenascin-C-coated trabecular bone xenografts in a novel system that employed chorioallantoic membranes of fertilized chicken eggs as host...
September 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28916537/reversibility-of-the-effects-of-natalizumab-on-peripheral-immune-cell-dynamics-in-ms-patients
#14
Tatiana Plavina, Kumar Kandadi Muralidharan, Geoffrey Kuesters, Daniel Mikol, Karleyton Evans, Meena Subramanyam, Ivan Nestorov, Yi Chen, Qunming Dong, Pei-Ran Ho, Diogo Amarante, Alison Adams, Jerome De Sèze, Robert Fox, Ralf Gold, Douglas Jeffery, Ludwig Kappos, Xavier Montalban, Bianca Weinstock-Guttman, Hans-Peter Hartung, Bruce A C Cree
OBJECTIVE: To characterize the reversibility of natalizumab-mediated changes in pharmacokinetics/pharmacodynamics in patients with multiple sclerosis (MS) following therapy interruption. METHODS: Pharmacokinetic/pharmacodynamic data were collected in the Safety and Efficacy of Natalizumab in the Treatment of Multiple Sclerosis (AFFIRM) (every 12 weeks for 116 weeks) and Randomized Treatment Interruption of Natalizumab (RESTORE) (every 4 weeks for 28 weeks) studies...
September 15, 2017: Neurology
https://www.readbyqxmd.com/read/28916526/monoclonal-antibodies-directed-against-cadherin-rgd-exhibit-therapeutic-activity-against-melanoma-and-colorectal-cancer-metastasis
#15
Ruben A Bartolomé, Carmen Aizpurua, Marta Jaén, Sofia Torres, Eva Calviño, Juan I Imbaud, J Ignacio Casal
PURPOSE: New targets are required for the control of advanced metastatic disease. We investigated the use of cadherin RGD motifs, which activate the α2β1integrin pathway, as targets for the development of therapeutic monoclonal antibodies (mAbs). EXPERIMENTAL DESIGN: CDH17 fragments and peptides were prepared and used for immunization and antibody development. Antibodies were tested for inhibition of β1 integrin and cell adhesion, proliferation and invasion assays using cell lines from different cancer types: colorectal, pancreatic, melanoma and breast cancer...
September 15, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28915633/selection-of-optimal-molecular-targets-for-tumor-specific-imaging-in-pancreatic-ductal-adenocarcinoma
#16
Willemieke S Tummers, Arantza Farina-Sarasqueta, Martin C Boonstra, Hendrica A Prevoo, Cornelis F Sier, Jan S Mieog, Johannes Morreau, Casper H van Eijck, Peter J Kuppen, Cornelis J van de Velde, Bert A Bonsing, Alexander L Vahrmeijer, Rutger-Jan Swijnenburg
Discrimination of pancreatic ductal adenocarcinoma (PDAC) from chronic pancreatitis (CP) or peritumoral inflammation is challenging, both at preoperative imaging and during surgery, but it is crucial for proper therapy selection. Tumor-specific molecular imaging aims to enhance this discrimination and to help select and stratify patients for resection. We evaluated various biomarkers for the specific identification of PDAC and associated lymph node metastases. Using immunohistochemistry (IHC), expression levels and patterns were investigated of integrin αvβ6, carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5), Cathepsin E (Cath E), epidermal growth factor receptor (EGFR), hepatocyte growth factor receptor (c-MET), thymocyte differentiation antigen 1 (Thy1), and urokinase-type plasminogen activator receptor (uPAR)...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28915447/oxidative-stress-induced-modulation-of-platelet-integrin-%C3%AE-2b%C3%AE-3-expression-and-shedding-may-predict-the-risk-of-major-bleeding-in-heart-failure-patients-supported-by-continuous-flow-left-ventricular-assist-devices
#17
Nandan K Mondal, Zengsheng Chen, Jaimin R Trivedi, Erik N Sorensen, Si M Pham, Mark S Slaughter, Bartley P Griffith, Zhongjun J Wu
INTRODUCTION: Oxidative stress and platelet integrin α2bβ3 plays important role in the process of hemostasis and thrombosis. We hypothesized that device-induced patient specific oxidative stress and integrin α2bβ3 shedding may be linked to major bleeding complication (MBC) in heart failure (HF) patients supported by continuous flow left ventricular assist devices (CF-LVADs). MATERIALS AND METHODS: We recruited 47patients implanted with CF-LVADs and 15 healthy volunteers...
September 8, 2017: Thrombosis Research
https://www.readbyqxmd.com/read/28915383/force-activatable-biosensor-enables-single-platelet-force-mapping-directly-by-fluorescence-imaging
#18
Yongliang Wang, Dana N LeVine, Margaret Gannon, Yuanchang Zhao, Anwesha Sarkar, Bailey Hoch, Xuefeng Wang
Integrin-transmitted cellular forces are critical for platelet adhesion, activation, aggregation and contraction during hemostasis and thrombosis. Measuring and mapping single platelet forces are desired in both research and clinical applications. Conventional force-to-strain based cell traction force microscopies have low resolution which is not ideal for cellular force mapping in small platelets. To enable platelet force mapping with submicron resolution, we developed a force-activatable biosensor named integrative tension sensor (ITS) which directly converts molecular tensions to fluorescent signals, therefore enabling cellular force mapping directly by fluorescence imaging...
September 8, 2017: Biosensors & Bioelectronics
https://www.readbyqxmd.com/read/28913673/multiple-non-catalytic-adams-are-novel-integrin-%C3%AE-4-ligands
#19
Lei Wang, Jason A Hoggard, Erica D Korleski, Gideon V Long, Brandy C Ree, Kenneth Hensley, Stephen R Bond, Tyra G Wolfsberg, JianMing Chen, Tonya N Zeczycki, Lance C Bridges
The ADAM (a disintegrin and metalloprotease) protein family uniquely exhibits both catalytic and adhesive properties. In the well-defined process of ectodomain shedding, ADAMs transform latent, cell-bound substrates into soluble, biologically active derivatives to regulate a spectrum of normal and pathological processes. In contrast, the integrin ligand properties of ADAMs are not fully understood. Emerging models posit that ADAM-integrin interactions regulate shedding activity by localizing or sequestering the ADAM sheddase...
September 14, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28912543/inhibition-of-fucosylation-by-2-fluorofucose-suppresses-human-liver-cancer-hepg2-cell-proliferation-and-migration-as-well-as-tumor-formation
#20
Ying Zhou, Tomohiko Fukuda, Qinglei Hang, Sicong Hou, Tomoya Isaji, Akihiko Kameyama, Jianguo Gu
Core fucosylation is one of the most important glycosylation events in the progression of liver cancer. For this study, we used an easily handled L-fucose analog, 2-fluoro-L-fucose (2FF), which interferes with the normal synthesis of GDP-fucose, and verified its potential roles in regulating core fucosylation and cell behavior in the HepG2 liver cancer cell line. Results obtained from lectin blot and flow cytometry analysis clearly showed that 2FF treatment dramatically inhibited core fucosylation, which was also confirmed via mass spectrometry analysis...
September 14, 2017: Scientific Reports
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