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https://www.readbyqxmd.com/read/28445158/the-hdac-inhibitor-valproate-induces-a-bivalent-status-of-the-cd20-promoter-in-cll-patients-suggesting-distinct-epigenetic-regulation-of-cd20-expression-in-cll-in-vivo
#1
Annarita Scialdone, Muhammad Sharif Hasni, Jesper Kofoed Damm, Andreas Lennartsson, Urban Gullberg, Kristina Drott
Treatment with anti-CD20 antibodies is only moderately efficient in chronic lymphocytic leukemia (CLL), a feature which has been explained by the inherently low CD20 expression in CLL. It has been shown that CD20 is epigenetically regulated and that histone deacetylase inhibitors (HDACis) can increase CD20 expression in vitro in CLL. To assess whether HDACis can upregulate CD20 also in vivo in CLL, the HDACi valproate was given to three del13q/NOTCH1wt CLL patients and CD20 levels were analysed (the PREVAIL study)...
April 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28439030/epithelial-ezh2-serves-as-an-epigenetic-determinant-in-experimental-colitis-by-inhibiting-tnf%C3%AE-mediated-inflammation-and-apoptosis
#2
Yongfeng Liu, Junjie Peng, Tongyu Sun, Ni Li, Le Zhang, Jiale Ren, Huairui Yuan, Shan Kan, Qiang Pan, Xiang Li, Yufeng Ding, Min Jiang, Xiaoji Cong, Minjia Tan, Yushui Ma, Da Fu, Sanjun Cai, Yichuan Xiao, Xiaoming Wang, Jun Qin
Epithelial barrier disruption is a major cause of inflammatory bowel disease (IBD); however, the mechanism through which epigenetic regulation modulates intestinal epithelial integrity remains largely undefined. Here we show that EZH2, the catalytic subunit of polycomb repressive complex (PRC2), is indispensable for maintaining epithelial cell barrier integrity and homeostasis under inflammatory conditions. In accordance with reduced EZH2 expression in patients, the inactivation of EZH2 in IECs sensitizes mice to DSS- and TNBS-induced experimental colitis...
April 24, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28433330/bivalent-rlp2086-trumenba%C3%A2-development-of-a-well-characterized-vaccine-through-commercialization
#3
Khurram Sunasara, John Cundy, Sriram Srinivasan, Brad Evans, Weiqiang Sun, Scott Cook, Eric Bortell, John Farley, Daniel Griffin, Michele Bailey Piatchek, Katherine Arch-Douglas
The phrase "Process is the Product" is often applied to biologics, including multicomponent vaccines composed of complex components that evade complete characterization. Vaccine production processes must be defined and locked early in the development cycle to ensure consistent quality of the vaccine throughout scale-up, clinical studies, and commercialization. This approach of front-loading the development work helped facilitate the accelerated approval of the Biologic License Application for the well-characterized vaccine bivalent rLP2086 (Trumenba®, Pfizer Inc) in 2014 under Breakthrough Therapy Designation...
April 19, 2017: Vaccine
https://www.readbyqxmd.com/read/28421882/inhibition-of-her3-activation-and-tumor-growth-with-a-human-antibody-binding-to-a-conserved-epitope-formed-by-domain-iii-and-iv
#4
Lisa C Schmitt, Alexander Rau, Oliver Seifert, Jonas Honer, Meike Hutt, Simone Schmid, Jonas Zantow, Michael Hust, Stefan Dübel, Monilola A Olayioye, Roland E Kontermann
Human epidermal growth factor receptor 3 (HER3, also known as ErbB3) has emerged as relevant target for antibody-mediated tumor therapy. Here, we describe a novel human antibody, IgG 3-43, recognizing a unique epitope formed by domain III and parts of domain IV of the extracellular region of HER3, conserved between HER3 and mouse ErbB3. An affinity of 11 nM was determined for the monovalent interaction. In the IgG format, the antibody bound recombinant bivalent HER3 with subnanomolar affinity (KD = 220 pM) and HER3-expressing tumor cells with EC50 values in the low picomolar range (27 - 83 pM)...
April 19, 2017: MAbs
https://www.readbyqxmd.com/read/28414915/tethered-fluorogen-assay-to-visualize-membrane-apposition-in-living-cells
#5
Daniel S Ackerman, Kalin V Vasilev, Brigitte F Schmidt, Lianne B Cohen, Jonathan W Jarvik
We describe proof-of-concept for a novel approach for visualizing regions of close apposition between the surfaces of living cells. A membrane-anchored protein with high affinity for a chemical ligand is expressed on the surface of one set of cells, and the cells are co-cultured with a second set of cells that express a membrane-anchored fluorogen-activating protein (FAP). The co-cultured cells are incubated with a bivalent reagent comprised of fluorogen linked to the high-affinity ligand, with the concentration of the bivalent reagent chosen to be less than the binding constant for the FAP/fluorogen pair, but greater than the binding constant for the ligand/high-affinity protein pair...
April 17, 2017: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/28414795/negative-feedback-loop-of-bone-resorption-by-nfatc1-dependent-induction-of-cadm1
#6
Shinya Nakamura, Takuma Koyama, Naohiro Izawa, Seitaro Nomura, Takanori Fujita, Yasunori Omata, Takashi Minami, Morio Matsumoto, Masaya Nakamura, Eriko Fujita-Jimbo, Takashi Momoi, Takeshi Miyamoto, Hiroyuki Aburatani, Sakae Tanaka
Trimethylation of histone H3 lysine 4 and lysine 27 (H3K4me3 and H3K27me3) at gene promoter regions critically regulates gene expression. Key developmental genes tend to exhibit changes in histone modification patterns from the H3K4me3/H3K27me3 bivalent pattern to the H3K4me3 monovalent pattern. Using comprehensive chromatin immunoprecipitation followed by sequencing in bone marrow-derived macrophages (BMMs) and mature osteoclasts, we found that cell surface adhesion molecule 1 (Cadm1) is a direct target of nuclear factor of activated T cells 1 (NFATc1) and exhibits a bivalent histone pattern in BMMs and a monovalent pattern in osteoclasts...
2017: PloS One
https://www.readbyqxmd.com/read/28413500/enhancement-of-humoral-and-cell-mediated-immune-response-to-hpv16-l1-derived-peptides-subsequent-to-vaccination-with-prophylactic-bivalent-hpv-l1-virus-like-particle-vaccine-in-healthy-females
#7
Masato Yokomine, Satoko Matsueda, Kouichiro Kawano, Tetsuro Sasada, Akimasa Fukui, Takuto Yamashita, Nobukazu Komatsu, Shigeki Shichijo, Kazuto Tasaki, Ken Matsukuma, Kyogo Itoh, Toshiharu Kamura, Kimio Ushijima
Currently prophylactic HPV16/18 L1 virus-like particle (VLP) vaccines are employed with great success for the prevention of HPV infection. However, limited information is available regarding the immune responses against human papillomavirus (HPV) 16/18 L1 subsequent to HPV16/18 L1 VLP vaccination, primarily due to the lack of widely used assays for immune monitoring. The aim of the present study was to identify HPV16 L1-derived B and T cell epitopes for monitoring the immune responses after HPV16/18 L1 VLP vaccination in healthy females...
April 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28413051/protective-efficacy-of-a-novel-recombinant-marek-s-disease-virus-vector-vaccine-against-infectious-bursal-disease-in-chickens-with-or-without-maternal-antibodies
#8
Kai Li, Yongzhen Liu, Yanping Zhang, Li Gao, Changjun Liu, Hongyu Cui, Xiaole Qi, Yulong Gao, Li Zhong, Xiaomei Wang
Infectious bursal disease (IBD) causes significant clinical and economic losses to the poultry industry worldwide. Current vaccine programs using live attenuated and inactivated vaccines have numerous drawbacks. As an alternative solution to control IBD, a Marek's disease virus (MDV) vector vaccine (rMDV-VP2) expressing the VP2 gene of infectious bursal disease virus (IBDV) has been developed. In this study, the protective efficacy of rMDV-VP2 was evaluated in a dose-related experiment which showed that a single dose of 1000 PFU was sufficient to fully protect chickens against IBDV infection...
April 2017: Veterinary Immunology and Immunopathology
https://www.readbyqxmd.com/read/28407817/preliminary-study-of-the-ul55-gene-based-on-infectious-chinese-virulent-duck-enteritis-virus-bacterial-artificial-chromosome-clone
#9
Ying Wu, Yangguang Li, Mingshu Wang, Kunfeng Sun, Renyong Jia, Shun Chen, Dekang Zhu, Mafeng Liu, Qiao Yang, Xinxin Zhao, Xiaoyue Chen, Anchun Cheng
BACKGROUND: Lethal Duck Enteritis Virus (DEV) infection can cause high morbidity and mortality of many species of waterfowl within the order Anseriformes. However, little is known about the function of viral genes including the conserved UL55 gene among alpha herpes virus due to the obstacles in maintenance and manipulation of DEV genome in host cells. METHODS: In this paper, we constructed an infectious bacteria artificial chromosome (BAC) clone of the lethal clinical isolate duck enteritis virus Chinese virulent strain (DEV CHv) by inserting a transfer vector containing BAC mini-F sequence and selection marker EGFP into UL23 gene using homologous recombination...
April 13, 2017: Virology Journal
https://www.readbyqxmd.com/read/28405498/cergutuzumab-amunaleukin-cea-il2v-a-cea-targeted-il-2-variant-based-immunocytokine-for-combination-cancer-immunotherapy-overcoming-limitations-of-aldesleukin-and-conventional-il-2-based-immunocytokines
#10
Christian Klein, Inja Waldhauer, Valeria G Nicolini, Anne Freimoser-Grundschober, Tapan Nayak, Danielle J Vugts, Claire Dunn, Marije Bolijn, Jörg Benz, Martine Stihle, Sabine Lang, Michaele Roemmele, Thomas Hofer, Erwin van Puijenbroek, David Wittig, Samuel Moser, Oliver Ast, Peter Brünker, Ingo H Gorr, Sebastian Neumann, Maria Cristina de Vera Mudry, Heather Hinton, Flavio Crameri, Jose Saro, Stefan Evers, Christian Gerdes, Marina Bacac, Guus van Dongen, Ekkehard Moessner, Pablo Umaña
We developed cergutuzumab amunaleukin (CEA-IL2v, RG7813), a novel monomeric CEA-targeted immunocytokine, that comprises a single IL-2 variant (IL2v) moiety with abolished CD25 binding, fused to the C-terminus of a high affinity, bivalent carcinoembryonic antigen (CEA)-specific antibody devoid of Fc-mediated effector functions. Its molecular design aims to (i) avoid preferential activation of regulatory T-cells vs. immune effector cells by removing CD25 binding; (ii) increase the therapeutic index of IL-2 therapy by (a) preferential retention at the tumor by having a lower dissociation rate from CEA-expressing cancer cells vs...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28405459/field-efficacy-of-porcilis%C3%A2-pcv-m-hyo-versus-a-licensed-commercially-available-vaccine-and-placebo-in-the-prevention-of-prdc-in-pigs-on-a-french-farm-a-randomized-controlled-trial
#11
Eric Pagot, Martial Rigaut, David Roudaut, Luca Panzavolta, Rika Jolie, Didier Duivon
BACKGROUND: A controlled, randomised, and blinded trial performed on a conventional French farrow-to-finish farm compared the efficacy of a one-shot bivalent ready to use vaccine, Porcilis® PCV M. Hyo (group PCVM), to that of two commercial vaccines (Ingelvac® Circoflex® + Ingelvac® Mhyo, group ICIM), and to a placebo (group CTL), in preventing the health and economic impacts of Porcine Respiratory Disease Complex (PRDC). MATERIAL & METHODS: In this small-scale clinical study, all piglets in each group were administered the vaccine/placebo at weaning age (27 days old)...
2017: Porcine Health Management
https://www.readbyqxmd.com/read/28390316/dual-targeting-peptide-probe-for-sequence-and-structure-sensitive-sensing-of-serum-albumin
#12
Yang Yu, Yanyan Huang, Yulong Jin, Rui Zhao
Peptide-protein interactions mediate numerous biologic processes and provide great opportunity for developing peptide probes and analytical approaches for detecting and interfering with recognition events. Molecular interactions usually take place on the heterogeneous surface of proteins, and the spatial distribution and arrangement of probes are therefore crucial for achieving high specificity and sensitivity in the bioassays. In this study, small linear peptides, homogenous peptide dimers and hetero bivalent peptides were designed for site-specific recognition of human serum albumin (HSA)...
April 2, 2017: Biosensors & Bioelectronics
https://www.readbyqxmd.com/read/28388624/development-of-a-glycoconjugate-vaccine-to-prevent-invasive-salmonella-typhimurium-infections-in-sub-saharan-africa
#13
Scott M Baliban, Mingjun Yang, Girish Ramachandran, Brittany Curtis, Surekha Shridhar, Rachel S Laufer, Jin Y Wang, John Van Druff, Ellen E Higginson, Nicolas Hegerle, Kristen M Varney, James E Galen, Sharon M Tennant, Andrew Lees, Alexander D MacKerell, Myron M Levine, Raphael Simon
Invasive infections associated with non-typhoidal Salmonella (NTS) serovars Enteritidis (SE), Typhimurium (STm) and monophasic variant 1,4,[5],12:i:- are a major health problem in infants and young children in sub-Saharan Africa, and currently, there are no approved human NTS vaccines. NTS O-polysaccharides and flagellin proteins are protective antigens in animal models of invasive NTS infection. Conjugates of SE core and O-polysaccharide (COPS) chemically linked to SE flagellin have enhanced the anti-COPS immune response and protected mice against fatal challenge with a Malian SE blood isolate...
April 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28387224/multi-scale-chromatin-state-annotation-using-a-hierarchical-hidden-markov-model
#14
Eugenio Marco, Wouter Meuleman, Jialiang Huang, Kimberly Glass, Luca Pinello, Jianrong Wang, Manolis Kellis, Guo-Cheng Yuan
Chromatin-state analysis is widely applied in the studies of development and diseases. However, existing methods operate at a single length scale, and therefore cannot distinguish large domains from isolated elements of the same type. To overcome this limitation, we present a hierarchical hidden Markov model, diHMM, to systematically annotate chromatin states at multiple length scales. We apply diHMM to analyse a public ChIP-seq data set. diHMM not only accurately captures nucleosome-level information, but identifies domain-level states that vary in nucleosome-level state composition, spatial distribution and functionality...
April 7, 2017: Nature Communications
https://www.readbyqxmd.com/read/28384566/impact-of-genetic-changes-pathogenicity-and-antigenicity-on-enterovirus-a71-vaccine-development
#15
REVIEW
Pinn Tsin Isabel Yee, Chit Laa Poh
Enterovirus-A71 (EV-A71) is an etiological agent of the hand, foot and mouth disease (HFMD). EV-A71 infection produces high fever and ulcers in children. Some EV-A71 strains produce severe infections leading to pulmonary edema and death. Although the protective efficacy of the inactivated vaccine (IV) was ≥90% against mild HFMD, there was approximately 80% protection against severe HFMD. The monovalent EV-A71 IV elicits humoral immunity but lacks long-term immunogenicity. Spontaneous mutations of the EV-A71 genome could lead to antigenicity changes and the virus may not be neutralized by antibodies elicited by the IV...
June 2017: Virology
https://www.readbyqxmd.com/read/28376222/optimal-cervical-cancer-screening-in-women-vaccinated-against-human-papillomavirus
#16
Jane J Kim, Emily A Burger, Stephen Sy, Nicole G Campos
Background: Current US cervical cancer screening guidelines do not differentiate recommendations based on a woman's human papillomavirus (HPV) vaccination status. Changes to cervical cancer screening policies in HPV-vaccinated women should be evaluated. Methods: We utilized an individual-based mathematical model of HPV and cervical cancer in US women to project the health benefits, costs, and harms associated with screening strategies in women vaccinated with the bivalent, quadrivalent, or nonavalent vaccine...
February 1, 2017: Journal of the National Cancer Institute
https://www.readbyqxmd.com/read/28369589/bivalent-formation-1-a-plant-conserved-gene-encodes-an-omph-coiled-coil-motif-containing-protein-required-for-meiotic-recombination-in-rice
#17
Lian Zhou, Jingluan Han, Yuanling Chen, Yingxiang Wang, Yao-Guang Liu
Meiosis is essential for eukaryotic sexual reproduction and plant fertility. In comparison with over 80 meiotic genes identified in Arabidopsis, there are only ~30 meiotic genes characterized in rice (Oryza sativa L.). Many genes involved in the regulation of meiotic progression remain to be determined. In this study, we identified a sterile rice mutant and cloned a new meiotic gene, OsBVF1 (Bivalent Formation 1) by map-based cloning. Molecular genetics and cytological approaches were carried out to address the function of OsBVF1 in meiosis...
March 24, 2017: Journal of Experimental Botany
https://www.readbyqxmd.com/read/28367135/age-differences-in-the-transfer-and-maintenance-of-practice-induced-improvements-in-task-switching-the-impact-of-working-memory-and-inhibition-demands
#18
Jutta Kray, Balázs Fehér
Recent aging studies on training in task switching found that older adults showed larger improvements to an untrained switching task as younger adults do. However, less clear is what type of cognitive control processes can explain these training gains as participants were trained with a particular type of switching task including bivalent stimuli, requiring high inhibition demands, and no task cues helping them keeping track of the task sequence, and by this, requiring high working-memory (WM) demands. The aims of this study were first to specify whether inhibition, WM, or switching demands are critical for the occurrence of transfer and whether this transfer depends on the degree of overlap between training and transfer situation; and second to assess whether practiced-induced gains in task switching can be maintained over a longer period of time...
2017: Frontiers in Psychology
https://www.readbyqxmd.com/read/28363699/bench-top-to-clinical-therapies-a-review-of-melanocortin-ligands-from-1954-to-2016
#19
REVIEW
Mark D Ericson, Cody J Lensing, Katlyn A Fleming, Katherine N Schlasner, Skye R Doering, Carrie Haskell-Luevano
The discovery of the endogenous melanocortin agonists in the 1950s have resulted in sixty years of melanocortin ligand research. Early efforts involved truncations or select modifications of the naturally occurring agonists leading to the development of many potent and selective ligands. With the identification and cloning of the five known melanocortin receptors, many ligands were improved upon through bench-top in vitro assays. Optimization of select properties resulted in ligands adopted as clinical candidates...
March 29, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28362135/immunogenicity-and-safety-evaluation-of-bivalent-types-1-and-3-oral-poliovirus-vaccine-by-comparing-different-poliomyelitis-vaccination-schedules-in-china-a-randomized-controlled-non-inferiority-clinical-trial
#20
Jingjun Qiu, Yunkai Yang, Lirong Huang, Ling Wang, Zhiwei Jiang, Jian Gong, Wei Wang, Hongyan Wang, Shaohong Guo, Chanjuan Li, Shuyuan Wei, Zhaojun Mo, Jielai Xia
BACKGROUND: The type 2 component of the oral poliovirus vaccine is targeted for global withdrawal through a switch from the trivalent oral poliovirus vaccine (tOPV) to a bivalent oral poliovirus vaccine (bOPV). The switch is intended to prevent paralytic polio caused by circulating vaccine-derived poliovirus type 2. We aimed to assess the immunogenicity and safety profile of 6 vaccination schedules with different sequential doses of inactivated poliovirus vaccine (IPV), tOPV, or bOPV...
March 1, 2017: Human Vaccines & Immunotherapeutics
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