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https://www.readbyqxmd.com/read/28726542/generation-and-functional-characterization-of-anti-human-and-anti-mouse-il-36r-antagonist-monoclonal-antibodies
#1
Rajkumar Ganesan, Ernest L Raymond, Detlev Mennerich, Joseph R Woska, Gary Caviness, Christine Grimaldi, Jennifer Ahlberg, Rocio Perez, Simon Roberts, Danlin Yang, Kavita Jerath, Kristopher Truncali, Lee Frego, Eliud Sepulveda, Priyanka Gupta, Su-Ellen Brown, Michael D Howell, Keith A Canada, Rachel Kroe-Barrett, Jay S Fine, Sanjaya Singh, M Lamine Mbow
Deficiency of interleukin (IL)-36 receptor antagonist (DITRA) syndrome is a rare autosomal recessive disease caused by mutations in IL36RN. IL-36R is a cell surface receptor and a member of the IL1R family that is involved in inflammatory responses triggered in skin and other epithelial tissues. Accumulating evidence suggests that IL-36R signaling may play a role in the pathogenesis of psoriasis. Therapeutic intervention of IL-36R signaling offers an innovative treatment paradigm for targeting epithelial cell-mediated inflammatory diseases such as the life-threatening psoriasis variant called generalized pustular psoriasis (GPP)...
July 20, 2017: MAbs
https://www.readbyqxmd.com/read/28708892/cross-recognition-of-a-pit-viper-crotalinae-polyspecific-antivenom-explored-through-high-density-peptide-microarray-epitope-mapping
#2
Mikael Engmark, Bruno Lomonte, José María Gutiérrez, Andreas H Laustsen, Federico De Masi, Mikael R Andersen, Ole Lund
Snakebite antivenom is a 120 years old invention based on polyclonal mixtures of antibodies purified from the blood of hyper-immunized animals. Knowledge on antibody recognition sites (epitopes) on snake venom proteins is limited, but may be used to provide molecular level explanations for antivenom cross-reactivity. In turn, this may help guide antivenom development by elucidating immunological biases in existing antivenoms. In this study, we have identified and characterized linear elements of B-cell epitopes from 870 pit viper venom protein sequences by employing a high-throughput methodology based on custom designed high-density peptide microarrays...
July 14, 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28701401/evaluation-of-the-biological-properties-and-cross-reactive-antibody-response-to-h10-influenza-viruses-in-ferrets
#3
Troy C Sutton, Elaine W Lamirande, Rita Czako, Kanta Subbarao
The recent outbreak of avian origin H10N7 influenza among seals in Northern Europe, and two fatal human infections with an avian H10N8 virus in China, have demonstrated that H10 viruses can spread between mammals and cause severe disease in humans. To gain insight into the potential for H10 viruses to cross the species barrier and identify a candidate vaccine strain, we evaluated the in vitro and in vivo properties and antibody response in ferrets to 20 diverse H10 viruses. H10 virus infection of ferrets caused variable weight loss and all 20 viruses replicated throughout the respiratory tract; however, replication in the lungs was highly variable...
July 12, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28698817/the-fabrication-of-biomimetic-biphasic-can-pac-hydrogel-with-a-seamless-interfacial-layer-applied-in-osteochondral-defect-repair
#4
Jinfeng Liao, Taoran Tian, Sirong Shi, Xueping Xie, Quanquan Ma, Guo Li, Yunfeng Lin
Cartilage tissue engineering based on biomimetic scaffolds has become a rapidly developing strategy for repairing cartilage defects. In this study, a biphasic CAN-PAC hydrogel for osteochondral defect (OCD) regeneration was fabricated based on the density difference between the two layers via a thermally reactive, rapid cross-linking method. The upper hydrogel was cross-linked by CSMA and NIPAm, and the lower hydrogel was composed of PECDA, AAm and PEGDA. The interface between the two layers was first grafted by the physical cross-linking of calcium gluconate and alginate, followed by the chemical cross-linking of the carbon-carbon double bonds in the other components...
2017: Bone Research
https://www.readbyqxmd.com/read/28679758/a-cell-fusion-based-screening-method-identifies-the-gpi-anchored-protein-ly6e-as-the-receptor-for-the-mouse-endogenous-retroviral-envelope-syncytin-a
#5
Agathe Bacquin, Caroline Bireau, Maxime Tanguy, Charlotte Romanet, Cécile Vernochet, Anne Dupressoir, Thierry Heidmann
Syncytins are envelope genes of retroviral origin that have been exapted for a role in placentation. They are involved in the formation of a syncytial structure (the syncytiotrophoblast) at the fetomaternal interface via their fusogenic activity. The mouse placenta is rather unique among placental mammals since the fetomaternal interface comprises two syncytiotrophoblast layers (ST-I and ST-II) instead of one, as observed in humans and all other hemochorial placentae. Each layer specifically expresses a distinct mouse syncytin, namely syncytin-A (SynA) for ST-I and syncytin-B (SynB) for ST-II, which have been shown to be essential to placentogenesis and embryo survival...
July 5, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28664417/epicardial-adipose-tissue-at-the-heart-of-the-obesity-complications
#6
Valeria Guglielmi, Paolo Sbraccia
In recent years, the anatomic and functional contiguity of epicardial adipose tissue (EAT) to myocardium and coronary arteries has gained increasing interest for its potential pathogenetic role in obesity-related cardiac diseases. Besides its known and attributed biochemical cardioprotective properties, it is becoming evident that, in metabolic disease states, EAT-secreted bioactive molecules may play an important role in the pathogenesis of coronary artery disease and cardiac arrhythmias. EAT-derived inflammatory cytokines and reactive oxidative species may, indeed, play a part in the development of a local proatherogenic milieu by paracrine and vasocrine mechanisms of interaction...
June 29, 2017: Acta Diabetologica
https://www.readbyqxmd.com/read/28662190/bone-tissue-blood-lipids-and-inflammatory-profiles-in-adolescent-male-athletes-from-sports-contrasting-in-mechanical-load
#7
Ricardo R Agostinete, João P Duarte, João Valente-Dos-Santos, Manuel J Coelho-E-Silva, Oscar M Tavares, Jorge M Conde, Carlos A Fontes-Ribeiro, Giancarlo Condello, Laura Capranica, Suziane U Caires, Rômulo A Fernandes
Exploring the effect of non-impact and impact sports is particular relevant to understand the interaction between skeletal muscle and bone health during growth. The current study aimed to compare total and regional bone and soft-tissue composition, in parallel to measurements of blood lipid and inflammatory profiles between adolescent athletes and non-athletes. Anthropometry, biological maturity, dual energy X-ray absorptiometry (DXA) scans, training load and lipid and inflammatory profiles were assessed in a cross-sectional sample of 53 male adolescents (20 non-athletes, 15 swimmers and 18 basketball players) aged 12-19 years...
2017: PloS One
https://www.readbyqxmd.com/read/28657332/role-of-hypohalous-acids-in-basement-membrane-homeostasis
#8
Selene Colon, Patrick Page-McCaw, Gautam Bhave
SIGNIFICANCE: Basement membranes (BMs) are sheet-like structures of specialized extracellular matrix that underlie nearly all tissue cell layers including epithelial, endothelial, and muscle cells. BMs not only provide structural support, but are critical for the development, maintenance, and repair of organs. Animal heme peroxidases generate highly reactive hypohalous acids extracellularly and therefore target BMs for oxidative modification. Given the importance of BMs in tissue structure and function, hypohalous acid mediated oxidative modifications of BM proteins represent a key mechanism in normal development and pathogenesis of disease...
June 28, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/28656083/in-vivo-immunotherapy-of-lung-cancer-using-cross-species-reactive-vascular-endothelial-growth-factor-nanobodies
#9
Fatemeh Kazemi-Lomedasht, Kamran Pooshang-Bagheri, Mahdi Habibi-Anbouhi, Ensiyeh Hajizadeh-Safar, Delavar Shahbazzadeh, Hasan Mirzahosseini, Mahdi Behdani
OBJECTIVES: Lung cancer is the main leading cause of cancer death worldwide. Angiogenesis is the main step in proliferation and spreading of tumor cells. Targeting vascular endothelial growth factor (VEGF) is an effective approach for inhibition of cancer angiogenesis. Nanobodies (NBs) are a novel class of antibodies derived from the camel. Unique characteristics of Nbs like their small size and good penetration to tumor tissues makes them promising tools in drug development. Development of NBs targeting both human and mouse VEGF is required for understanding their in vivo functions...
May 2017: Iranian Journal of Basic Medical Sciences
https://www.readbyqxmd.com/read/28647488/autoreactivity-to-malondialdehyde-modifications-in-rheumatoid-arthritis-is-linked-to-disease-activity-and-synovial-pathogenesis
#10
Caroline Grönwall, Khaled Amara, Uta Hardt, Akilan Krishnamurthy, Johanna Steen, Marianne Engström, Meng Sun, A Jimmy Ytterberg, Roman A Zubarev, Dagmar Scheel-Toellner, Jeffrey D Greenberg, Lars Klareskog, Anca I Catrina, Vivianne Malmström, Gregg J Silverman
Oxidation-associated malondialdehyde (MDA) modification of proteins can generate immunogenic neo-epitopes that are recognized by autoantibodies. In health, IgM antibodies to MDA-adducts are part of the natural antibody pool, while elevated levels of IgG anti-MDA antibodies are associated with inflammatory and autoimmune conditions. Yet, in human autoimmune disease IgG anti-MDA responses have not been well characterized and their potential contribution to disease pathogenesis is not known. Here, we investigate MDA-modifications and anti-MDA-modified protein autoreactivity in rheumatoid arthritis (RA)...
June 21, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28645940/t-cell-receptors-for-clinical-therapy-in-vitro-assessment-of-toxicity-risk
#11
Andre Kunert, Matthias Obenaus, Cor Hj Lamers, Thomas Blankenstein, Reno Debets
Adoptive therapy with T cell receptor (TCR)-engineered T cells has shown promising results in the treatment of patients with tumors, and the number of TCRs amenable for clinical testing is expanding rapidly. Notably, adoptive therapy with T cells is challenged by treatment-related side effects, which calls for cautious selection of target antigens and TCRs that goes beyond their mere ability to induce high T cell reactivity. Here, we propose a sequence of in vitro assays to improve selection of TCRs, and exemplify risk assessments of on-target as well as off-target toxicities using TCRs directed against Cancer Germline Antigens...
June 23, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28645930/genomic-and-non-genomic-effects-of-androgens-in-the-cardiovascular-system-clinical-implications
#12
REVIEW
Angela K Lucas-Herald, Rheure Alves-Lopes, Augusto C Montezano, S Faisal Ahmed, Rhian M Touyz
The principle steroidal androgens are testosterone and its metabolite 5α-dihydrotestosterone (DHT), which is converted from testosterone by the enzyme 5α-reductase. Through the classic pathway with androgens crossing the plasma membrane and binding to the androgen receptor (AR) or via mechanisms independent of the ligand-dependent transactivation function of nuclear receptors, testosterone induces genomic and non-genomic effects respectively. AR is widely distributed in several tissues, including vascular endothelial and smooth muscle cells...
July 1, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28639251/regulation-of-the-extracellular-serpina5-protein-c-inhibitor-penetration-through-cellular-membranes
#13
Felix C Wahlmüller, Hanjiang Yang, Margareta Furtmüller, Margarethe Geiger
It is generally accepted that the phospholipid bilayer of the cell membrane is impermeable for proteins and peptides and that these molecules require special mechanisms for their transport from the extra- to the intracellular space. Recently there is increasing evidence that certain proteins/peptides can also directly cross the phospholipid membrane. SERPINA5 (protein C inhibitor) is a secreted protease inhibitor with broad protease reactivity and wide tissue distribution. It binds glycosaminoglycans and certain phospoholipids, which can modulate its inhibitory activity...
June 22, 2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28624515/development-of-selective-androgen-receptor-modulators-sarms
#14
REVIEW
Ramesh Narayanan, Christopher C Coss, James T Dalton
The Androgen Receptor (AR), a member of the steroid hormone receptor family, plays important roles in the physiology and pathology of diverse tissues. AR ligands, which include circulating testosterone and locally synthesized dihydrotestosterone, bind to and activate the AR to elicit their effects. Ubiquitous expression of the AR, metabolism and cross reactivity with other receptors limit broad therapeutic utilization of steroidal androgens. However, the discovery of selective androgen receptor modulators (SARMs) and other tissue-selective nuclear hormone receptor modulators that activate their cognate receptors in a tissue-selective manner provides an opportunity to promote the beneficial effects of androgens and other hormones in target tissues with greatly reduced unwanted side-effects...
June 15, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28613414/the-arg-phe-amide-peptide-26rfa-qrfp-and-its-receptor-iuphar-review
#15
REVIEW
Jérôme Leprince, Didier Bagnol, Ronan Bureau, Shoji Fukusumi, Riccarda Granata, Shuji Hinuma, Dan Larhammar, Stefany Primeaux, Jana Sopkova-de Oliveiras Santos, Kazuyoshi Tsutsui, Kazuyoshi Ukena, Hubert Vaudry
26RFa is an RFamide neuropeptide that was first isolated from the brain of the European green frog on the basis of a cross-reactivity with antibodies raised against bovine NPFF. 26RFa and its N-terminally extended form QRFP have been identified as cognate ligands of the former orphan receptor GPR103, now renamed QRFPR. The 26RFa/QRFP precursor has been characterized in various mammalian and non-mammalian species. In the brain of mammals, including human, 26RFa/QRFP mRNA is almost exclusively expressed in hypothalamic nuclei...
June 14, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28603218/molecular-cloning-of-canine-wilms-tumor-1-for-immunohistochemical-analysis-in-canine-tissues
#16
Osamu Sakai, Masashi Sakurai, Hiroki Sakai, Masahito Kubo, Hiroko Hiraoka, Kenji Baba, Masaru Okuda, Takuya Mizuno
Wilms' tumor 1 (WT1) expression has been investigated in various human cancers as a target molecule for cancer immunotherapy. However, few studies have focused on WT1 expression in dogs. Firstly, cDNA of canine WT1 (cWT1) was molecularly cloned from normal canine kidney. The cross-reactivity of the anti-human WT1 monoclonal antibody (6F-H2) with cWT1 was confirmed via Western blotting using cells overexpressing cWT1. Immunohistochemical staining revealed that cWT1 expression was detected in all canine lymphoma tissues and in some normal canine tissues, including the kidney and lymph node...
June 12, 2017: Journal of Veterinary Medical Science
https://www.readbyqxmd.com/read/28595595/multiplex-detection-in-tonsillar-tissue-of-all-known-human-polyomaviruses
#17
Mohammadreza Sadeghi, Yilin Wang, Torbjörn Ramqvist, Leena-Maija Aaltonen, Lari Pyöriä, Mari Toppinen, Maria Söderlund-Venermo, Klaus Hedman
BACKGROUND: In the past few years, eleven new human viruses have joined the two previously known members JCPyV and BKPyV of the Polyomaviridae family, by virtue of molecular methods. Serology data suggest that infections with human polyomaviruses (HPyVs) occur since childhood and the viruses are widespread in the general population. However, the viral persistence sites and transmission routes are by and large unknown. Our previous studies demonstrated that the four new HPyVs - KIPyV, WUPyV, MCPyV and TSPyV - were present in the tonsils, and suggested lymphoid tissue as a persistent site of these emerging human viruses...
June 8, 2017: BMC Infectious Diseases
https://www.readbyqxmd.com/read/28583232/effect-of-topical-beclomethasone-on-inflammatory-markers-in-adults-with-eosinophilic-esophagitis-a-pilot-study
#18
Neeti Bhardwaj, Faoud Ishmael, Erik Lehman, Deborah Bethards, Francesca Ruggiero, Gisoo Ghaffari
BACKGROUND: Topical corticosteroids have proven efficacy in the treatment of eosinophilic esophagitis (EoE) and are considered the cornerstone of therapy. OBJECTIVE: To evaluate the effect of topical beclomethasone dipropionate (BDP) therapy on clinical outcomes, esophageal eosinophilia, and other markers of inflammation in patients with EoE. METHODS: Nine subjects with a biopsy-proven diagnosis of EoE were enrolled. In a cross-over design, the subjects were randomly assigned to a sequence of BDP and placebo...
June 1, 2017: Allergy & Rhinology
https://www.readbyqxmd.com/read/28535870/age-associated-b-cells-abc-inhibit-b-lymphopoiesis-and-alter-antibody-repertoires-in-old-age
#19
Richard L Riley, Kelly Khomtchouk, Bonnie B Blomberg
With old age (∼2y old), mice show substantial differences in B cell composition within the lymphoid tissues. In particular, a novel subset of IgM(+) CD21/35(lo/-) CD23(-) mature B cells, the age-associated B cells or ABC, increases numerically and proportionately. This occurs at the expense of other B cell subsets, including B2 follicular B cells in spleen and recirculating primary B cells in bone marrow. Our studies suggest that ABC have a distinctive antibody repertoire, as evidenced by relatively high reactivity to the self-antigens phosphorylcholine (PC) and malondialdehyde (MDA)...
April 26, 2017: Cellular Immunology
https://www.readbyqxmd.com/read/28528339/molecular-diagnosis-of-tubercular-lymphadenopathy-from-fine-needle-aspirates-in-pediatric-patients
#20
Vivek Gupta, Arvind Bhake
OBJECTIVES: The diagnosis of peripheral tubercular lymphadenopathy (TBLN) in pediatric patients is often a challenge because features evident on fine-needle aspiration cytology (FNAC) or tissue biopsy can be deceptive for the reason that they result from an immunological response. This study aimed to evaluate polymerase chain reaction (PCR) for Mycobacterium tuberculosis complex (MTBC) in pediatric patients under clinical suspicion for TBLN and to assess its role in the evaluation of cases cytodiagnosed as reactive lymphoid hyperplasia...
2017: Acta Cytologica
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