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https://www.readbyqxmd.com/read/28532097/influence-of-telopeptides-on-the-structural-and-physical-properties-of-polymeric-and-monomeric-acid-soluble-type-i-collagen
#1
Róisín Holmes, Steve Kirk, Giuseppe Tronci, Xuebin Yang, David Wood
Currently two factors hinder the use of collagen as building block of regenerative devices: the limited mechanical strength in aqueous environment, and potential antigenicity. Polymeric collagen is naturally found in the cross-linked state and is mechanically tougher than the monomeric, acid-soluble collagen ex vivo. The antigenicity of collagen, on the other hand, is mainly ascribed to inter-species variations in amino acid sequences of the non-helical terminal telopeptides. These telopeptides can be removed through enzymatic treatment to produce atelocollagen, although the effect of this cleavage on triple helix organization, amino acidic composition and thermal properties is often disregarded...
August 1, 2017: Materials Science & Engineering. C, Materials for Biological Applications
https://www.readbyqxmd.com/read/28531814/targeting-egfr-her2-heterodimerization-with-a-novel-anti-her2-domain-ii-iii-antibody
#2
Xiaojie Yu, Lingfei Wang, Yafeng Shen, Chao Wang, Yajun Zhang, Yanchun Meng, Yang Yang, Beibei Liang, Bo Zhou, Huajing Wang, Huafeng Wei, Changhai Lei, Shi Hu, Bohua Li
HER2, a ligand-free tyrosine kinase receptor of the HER family, is frequently overexpressed in breast cancer. The anti-HER2 antibody trastuzumab has shown significant clinical benefits in metastatic breast cancer. Despite the effectiveness of trastuzumab, its efficacy remains variable and often modest. Thus, there is an urgent need to improve ErbB2-targeting therapy. Here, we describe a novel anti-HER2 antibody, 7C3, which was developed using hybridoma technique. Structural analysis confirms that the epitope of this antibody is in domain II/III of HER2...
May 19, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28531139/dual-component-gelatinous-peptide-reactive-oligomer-formulations-as-conduit-material-and-luminal-filler-for-peripheral-nerve-regeneration
#3
Caroline Kohn-Polster, Divya Bhatnagar, Derek J Woloszyn, Matthew Richtmyer, Annett Starke, Alexandra H Springwald, Sandra Franz, Michaela Schulz-Siegmund, Hilton M Kaplan, Joachim Kohn, Michael C Hacker
Toward the next generation of nerve guidance conduits (NGCs), novel biomaterials and functionalization concepts are required to address clinical demands in peripheral nerve regeneration (PNR). As a biological polymer with bioactive motifs, gelatinous peptides are promising building blocks. In combination with an anhydride-containing oligomer, a dual-component hydrogel system (cGEL) was established. First, hollow cGEL tubes were fabricated by a continuous dosing and templating process. Conduits were characterized concerning their mechanical strength, in vitro and in vivo degradation and biocompatibility...
May 21, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28530710/engineering-protein-stability-with-atomic-precision-in-a-monomeric-miniprotein
#4
Emily G Baker, Christopher Williams, Kieran L Hudson, Gail J Bartlett, Jack W Heal, Kathryn L Porter Goff, Richard B Sessions, Matthew P Crump, Derek N Woolfson
Miniproteins simplify the protein-folding problem, allowing the dissection of forces that stabilize protein structures. Here we describe PPα-Tyr, a designed peptide comprising an α-helix buttressed by a polyproline II helix. PPα-Tyr is water soluble and monomeric, and it unfolds cooperatively with a midpoint unfolding temperature (TM) of 39 °C. NMR structures of PPα-Tyr reveal proline residues docked between tyrosine side chains, as designed. The stability of PPα is sensitive to modifications in the aromatic residues: replacing tyrosine with phenylalanine, i...
May 22, 2017: Nature Chemical Biology
https://www.readbyqxmd.com/read/28530662/pd-l1-inhibits-acute-and-chronic-pain-by-suppressing-nociceptive-neuron-activity-via-pd-1
#5
Gang Chen, Yong Ho Kim, Hui Li, Hao Luo, Da-Lu Liu, Zhi-Jun Zhang, Mark Lay, Wonseok Chang, Yu-Qiu Zhang, Ru-Rong Ji
Programmed cell death ligand-1 (PD-L1) is typically produced by cancer cells and suppresses immunity through the receptor PD-1 expressed on T cells. However, the role of PD-L1 and PD-1 in regulating pain and neuronal function is unclear. Here we report that both melanoma and normal neural tissues including dorsal root ganglion (DRG) produce PD-L1 that can potently inhibit acute and chronic pain. Intraplantar injection of PD-L1 evoked analgesia in naive mice via PD-1, whereas PD-L1 neutralization or PD-1 blockade induced mechanical allodynia...
May 22, 2017: Nature Neuroscience
https://www.readbyqxmd.com/read/28530096/engineering-eschericha-coli-for-enhanced-tyrosol-production
#6
Yuxiang Xue, Xianzhong Chen, Cui Yang, Junzhuang Chang, Wei Shen, You Fan
Tyrosol is a phenolic compound found in olive oil and wines. The health benefits of tyrosol have attracted considerable attention. Because the tyrosol extraction from plants poses a major obstacle, biosynthesizing this compound using microbial hosts is of interest. In this study, the phenylpyruvate decarboxylase gene ARO10 and the aromatic amino acid aminotransferase gene ARO8 were introduced into Escherichia coli to generate two recombinant tyrosol producers. Deleting the prephenate dehydratase pheA and the phenylacetaldehyde dehydrogenase gene feaB improved the tyrosol production...
May 22, 2017: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/28529741/pazopanib-induced-asymptomatic-radiological-acute-pancreatitis-a-case-report
#7
Iosune Baraibar, Almudena Quílez, Diego Salas, Marta Román, Christian Rolfo, José L Pérez-Gracia, Ignacio Gil-Bazo
The universal clinical use of multi-targeted tyrosine kinase inhibitors (TKIs) in patients diagnosed with advanced renal cell carcinoma (RCC) has significantly prolonged their estimated survival times and their quality of life. However, several adverse side-effects associated predominantly with the inhibition of the vascular endothelial growth factor receptor by these drugs may prove to be potentially life-threatening. One adverse event that is only rarely observed with the use of TKIs in this clinical setting is acute pancreatitis...
May 2017: Molecular and Clinical Oncology
https://www.readbyqxmd.com/read/28529699/evolution-immunity-and-the-emergence-of-brain-superautoantigens
#8
Serge Nataf
While some autoimmune disorders remain extremely rare, others largely predominate the epidemiology of human autoimmunity. Notably, these include psoriasis, diabetes, vitiligo, thyroiditis, rheumatoid arthritis and multiple sclerosis. Thus, despite the quasi-infinite number of "self" antigens that could theoretically trigger autoimmune responses, only a limited set of antigens, referred here as superautoantigens, induce pathogenic adaptive responses. Several lines of evidence reviewed in this paper indicate that, irrespective of the targeted organ (e...
2017: F1000Research
https://www.readbyqxmd.com/read/28529640/lung-cancer-targeting-peptides-with-multi-subtype-indication-for-combinational-drug-delivery-and-molecular-imaging
#9
Yi-Hsuan Chi, Jong-Kai Hsiao, Ming-Huang Lin, Chen Chang, Chun-Hsin Lan, Han-Chung Wu
Lung cancer is the leading cause of cancer-related death worldwide. Most targeted drugs approved for lung cancer treatment are tyrosine kinase inhibitors (TKIs) directed against EGFR or ALK, and are used mainly for adenocarcinoma. At present, there is no effective or tailored targeting agent for large cell carcinoma (LCC) or small cell lung cancer (SCLC). Therefore, we aimed to identify targeting peptides with diagnostic and therapeutic utility that possess broad subtype specificity for SCLC and non-small cell lung cancer (NSCLC)...
2017: Theranostics
https://www.readbyqxmd.com/read/28529623/high-expression-of-epha4-predicted-lesser-degree-of-tumor-regression-after-neoadjuvant-chemoradiotherapy-in-rectal-cancer
#10
Ching-Yih Lin, Ying-En Lee, Yu-Feng Tian, Ding-Ping Sun, Ming-Jen Sheu, Chen-Yi Lin, Chien-Feng Li, Sung-Wei Lee, Li-Ching Lin, I-Wei Chang, Chieh-Tien Wang, Hong-Lin He
Background: Numerous transmembrane receptor tyrosine kinase pathways have been found to play an important role in tumor progression in some cancers. This study was aimed to evaluate the clinical impact of Eph receptor A4 (EphA4) in patients with rectal cancer treated with neoadjuvant concurrent chemoradiotherapy (CCRT) combined with mesorectal excision, with special emphasis on tumor regression. Methods: Analysis of the publicly available expression profiling dataset of rectal cancer disclosed that EphA4 was the top-ranking, significantly upregulated, transmembrane receptor tyrosine kinase pathway-associated gene in the non-responders to CCRT, compared with the responders...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28529516/suppression-of-plant-immune-responses-by-the-pseudomonas-savastanoi-pv-savastanoi-ncppb-3335-type-iii-effector-tyrosine-phosphatases-hopao1-and-hopao2
#11
María Pilar Castañeda-Ojeda, Alba Moreno-Pérez, Cayo Ramos, Emilia López-Solanilla
The effector repertoire of the olive pathogen P. savastanoi pv. savastanoi NCPPB 3335 includes two members of the HopAO effector family, one of the most diverse T3E families of the P. syringae complex. The study described here explores the phylogeny of these dissimilar members, HopAO1 and HopAO2, among the complex and reveals their activities as immune defense suppressors. Although HopAO1 is predominantly encoded by phylogroup 3 strains isolated from woody organs of woody hosts, both HopAO1 and HopAO2 are phylogenetically clustered according to the woody/herbaceous nature of their host of isolation, suggesting host specialization of the HopAO family across the P...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/28529483/identification-of-a-novel-allosteric-inhibitory-site-on-tryptophan-hydroxylase-1-enabling-unprecedented-selectivity-over-all-related-hydroxylases
#12
Mike Petrassi, Rob Barber, Celine Be, Sarah Beach, Brian Cox, Anne-Marie D'Souza, Nick Duggan, Martin Hussey, Roy Fox, Peter Hunt, Gabor Jarai, Takatoshi Kosaka, Paul Oakley, Viral Patel, Neil Press, David Rowlands, Clemens Scheufler, Oliver Schmidt, Honnappa Srinivas, Mary Turner, Rob Turner, John Westwick, Alison Wolfreys, Nuzhat Pathan, Simon Watson, Matthew Thomas
Pulmonary arterial hypertension (PAH) has demonstrated multi-serotonin receptor dependent pathologies, characterized by increased tone (5-HT1B receptor) and complex lesions (SERT, 5-HT1B, 5-HT2B receptors) of the pulmonary vasculature together with right ventricular hypertrophy, ischemia and fibrosis (5-HT2B receptor). Selective inhibitors of individual signaling elements - SERT, 5-HT2A, 5HT2B, and combined 5-HT2A/B receptors, have all been tested clinically and failed. Thus, inhibition of tryptophan hydroxylase 1 (TPH1), the rate limiting step in 5-HT synthesis, has been suggested as a more broad, and thereby more effective, mode of 5-HT inhibition...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28529327/metabolite-profiling-of-obese-individuals-before-and-after-a-one-year-weight-loss-program
#13
N Geidenstam, M Al-Majdoub, M Ekman, P Spégel, M Ridderstråle
OBJECTIVE: We and others have previously characterized changes in circulating metabolite levels following diet-induced weight loss. Our aim was to investigate if baseline metabolite levels and weight loss-induced changes in these are predictive of or associated with changes in body mass index (BMI) and metabolic risk traits. METHODS: Serum metabolites were analyzed with gas and liquid chromatography/mass spectrometry in 91 obese individuals at baseline and after participating in a one year non-surgical weight loss program...
May 22, 2017: International Journal of Obesity: Journal of the International Association for the Study of Obesity
https://www.readbyqxmd.com/read/28528977/imatinib-induces-autophagy-via-upregulating-xiap-in-gist882%C3%A2-cells
#14
Qingqing Xie, Qi Lin, Dezhi Li, Jianming Chen
Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasms originating from the gastrointestinal tract with gain of function mutations in receptor tyrosine kinases KIT or platelet-derived growth factor receptor A (PDGFRA). The main effective treatment for GISTs is tyrosine kinase inhibitors, such as imatinib mesylate. However, GISTs respond to imatinib treatment eventually develop acquired resistance, which is a main obstacle for GISTs therapy. Therefore, it's urgent to have a better understanding of the mechanisms underlying the imatinib resistance in GISTs to develop novel therapeutic strategies...
May 18, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28528507/mertk-does-not-mediate-phagocytosis-of-staphylococcus-aureus-but-attenuates-inflammation-induced-by-staphylococcal-lipoteichoic-acid-through-blocking-nf-%C3%AE%C2%BAb-activation
#15
Bing Zhang, Huimei Wu, Lei Fang, Peishan Ding, Ke Xu, Qingbin Yang, Rongyu Liu
Mer receptor tyrosine kinase (MerTK) expressed in macrophages is essential for phagocytosis of apoptotic cells. Here, we investigate whether MerTK is involved in the phagocytosis of Staphylococcus aureus (S. aureus) and regulation of staphylococcal lipoteichoic acid (LTA)-induced inflammatory response in macrophages. We found that stimulating RAW264.7 macrophages with S. aureus activated multiple signaling pathways including toll-like receptor 2 (TLR2), scavenger receptor A (SR-A), and MerTK. Meanwhile, S. aureus stimulation also induced activation of proteins focal adhesion kinase (FAK) and Rac1, which are related to phagocytosis...
May 20, 2017: Inflammation
https://www.readbyqxmd.com/read/28528264/baseline-and-longitudinal-variability-of-normal-tissue-uptake-values-of-18-f-fluorothymidine-pet-images
#16
Matthijs C F Cysouw, Gerbrand M Kramer, Virginie Frings, Adrianus J De Langen, Mariëlle J Wondergem, Laura M Kenny, Eric O Aboagye, Carsten Kobe, Jürgen Wolf, Otto S Hoekstra, Ronald Boellaard
PURPOSE: [(18)F]-fluorothymidine ([(18)F]-FLT) is a PET-tracer enabling in-vivo visualization and quantification of tumor cell proliferation. For qualitative and quantitative analysis, adequate knowledge of normal tissue uptake is indispensable. This study aimed to quantitatively investigate baseline tracer uptake of blood pool, lung, liver and bone marrow and their precision, and to assess the longitudinal effect of systemic treatment on biodistribution. METHODS: (18)F-FLT-PET(/CT) scans (dynamic or static) of 90 treatment-naïve oncological patients were retrospectively evaluated...
May 10, 2017: Nuclear Medicine and Biology
https://www.readbyqxmd.com/read/28527959/systemic-treatment-patterns-with-advanced-or-recurrent-non-small-cell-lung-cancer-in-japan-a-retrospective-hospital-administrative-database-study
#17
Feng Wang, Sari Mishina, Shinji Takai, T Kim Le, Kenya Ochi, Kotaro Funato, Shozo Matsuoka, Yuichiro Ohe
PURPOSE: Data on the treatment of non-small cell lung cancer (NSCLC) in real-world clinical practice in Japan are limited. This large-scale, retrospective cohort study examined data on patients' characteristics and systemic therapies for advanced or recurrent NSCLC in routine practice in Japan. METHODS: This study used an electronic health records-based database of health claims and Diagnosis Procedure Combination data from 215 consenting hospitals in Japan. Records from April 2008 to September 2015 were analyzed...
May 18, 2017: Clinical Therapeutics
https://www.readbyqxmd.com/read/28527958/treadmill-exercise-produces-neuroprotective-effects-in-a-murine-model-of-parkinson-s-disease-by-regulating-the-tlr2-myd88-nf-%C3%AE%C2%BAb-signaling-pathway
#18
Jung-Hoon Koo, Yong-Chul Jang, Dong-Ju Hwang, Hyun-Seob Um, Nam-Hee Lee, Jae-Hoon Jung, Joon-Yong Cho
Parkinson's disease (PD) is characterized by progressive dopamine depletion and a loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc). Treadmill exercise is a promising non-pharmacological approach for reducing the risk of PD and other neuroinflammatory disorders, such as Alzheimer's disease. The goal of this study was to investigate the effects of treadmill exercise on α-synuclein-induced neuroinflammation and neuronal cell death in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model of PD...
May 17, 2017: Neuroscience
https://www.readbyqxmd.com/read/28527899/egfr-mutation-analysis-for-prospective-patient-selection-in-two-phase-ii-registration-studies-of-osimertinib
#19
Suzanne Jenkins, James Chih-Hsin Yang, Pasi A Jänne, Kenneth S Thress, Karen Yu, Rachel Hodge, Susie Weston, Simon Dearden, Sabina Patel, Mireille Cantarini, Frances A Shepherd
INTRODUCTION: Osimertinib is an oral, CNS active, epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) for the treatment of EGFR T790M-positive advanced non-small cell lung cancer (NSCLC). Here we evaluate EGFR mutation frequencies in two Phase II studies of osimertinib (AURA extension and AURA2). METHODS: Patients with EGFR mutation-positive advanced NSCLC provided tumor samples following progression on their latest line of therapy for mandatory central T790M testing for study selection criteria...
May 17, 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/28527703/sperm-oocyte-contact-induces-outside-in-signaling-via-pyk2-activation
#20
Huizhen Wang, Jinping Luo, Carol Carlton, Lynda K McGinnis, William H Kinsey
Fertilization is a multi-step process that begins with plasma membrane interactions that enable sperm - oocyte binding followed by fusion of the sperm and oocyte plasma membranes. Once membrane fusion has occurred, sperm incorporation involves actin remodeling events within the oocyte cortex that allow the sperm head to penetrate the cortical actin layer and gain access to the ooplasm. Despite the significance for reproduction, the control mechanisms involved in gamete binding, fusion, and sperm incorporation are poorly understood...
May 17, 2017: Developmental Biology
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