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https://www.readbyqxmd.com/read/27913544/treatment-of-rare-factor-deficiencies-in-2016
#1
Flora Peyvandi, Marzia Menegatti
Rare bleeding disorders (RBDs) are a heterogeneous group of coagulation disorders characterized by fibrinogen, prothrombin, factors V, VII, X, XI, or XIII (FV, FVII, FX, FXI, or FXIII, respectively), and the combined factor V + VIII and vitamin K-dependent proteins deficiencies, representing roughly 5% of all bleeding disorders. They are usually transmitted as autosomal, recessive disorders, and the prevalence of the severe forms could range from 1 case in 500 000 for FVII up to 1 in 2-3 million for FXIII in the general population...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27913536/reversal-of-direct-oral-anticoagulants-a-practical-approach
#2
Andrew W Shih, Mark A Crowther
Direct oral anticoagulants (DOACs) have at least noninferior efficacy compared with other oral anticoagulants and have ancillary benefits, including overall better safety profiles, lack of the need for routine monitoring, rapid onset of action, and ease of administration. Reversal of these agents may be indicated in certain situations such as severe bleeding and for perioperative management. DOAC-associated bleeding should be risk stratified: patients with moderate or severe bleeding should have the DOAC discontinued and reversal strategies should be considered...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27913108/chicken-line-dependent-mortality-after-experimental-infection-with-three-type-iixiii-recombinant-toxoplasma-gondii-clones
#3
G Schares, D C Herrmann, P Maksimov, B Matzkeit, F J Conraths, G Moré, R Preisinger, S Weigend
Three genetically different clones of Toxoplasma gondii, also different in mouse virulence, were studied by experimental infection in chickens. For the experiments, four chicken lines were used, which differed in phylogenetic origin and performance level: two white egg layer lines, one with high laying performance (WLA), one with low (R11) and two brown layer lines, also displaying high (BLA) and low (L68) egg number. Chickens were intraperitoneally infected with three different T. gondii isolates representing type IIxIII recombinant clones, i...
November 29, 2016: Experimental Parasitology
https://www.readbyqxmd.com/read/27912985/immunogenicity-and-malaria-transmission-reducing-potency-of-pfs48-45-and-pfs25-encoded-by-dna-vaccines-administered-by-intramuscular-electroporation
#4
Dibyadyuti Datta, Geetha P Bansal, Dietlind L Gerloff, Barry Ellefsen, Drew Hannaman, Nirbhay Kumar
Pfs48/45 and Pfs25 are leading candidates for the development of Plasmodium falciparum transmission blocking vaccines (TBV). Expression of Pfs48/45 in the erythrocytic sexual stages and presentation to the immune system during infection in the human host also makes it ideal for natural boosting. However, it has been challenging to produce a fully folded, functionally active Pfs48/45, using various protein expression platforms. In this study, we demonstrate that full-length Pfs48/45 encoded by DNA plasmids is able to induce significant transmission reducing immune responses...
November 29, 2016: Vaccine
https://www.readbyqxmd.com/read/27911873/interleukin-8-holds-promise-to-serve-as-a-molecular-adjuvant-in-dna-vaccination-model-against-streptococcus-iniae-infection-in-fish
#5
Erlong Wang, Bo Long, Kaiyu Wang, Jun Wang, Yang He, Xingli Wang, Qian Yang, Tao Liu, Defang Chen, Yi Geng, Xiaoli Huang, Ping Ouyang, Weimin Lai
DNA vaccines had been widely used in animal models against various viral infections, while it was not so convincing for many infectious diseases especially bacterial disease in aquaculture. Interleukin-8(IL-8) as one of the CXC chemokines, its immunological role and adjuvant potential which had been proved in mammals were rarely reported in fish species. In this study, recombination plasmid pcDNA3.1/IL-8(pcIL-8) was conducted and the capacity of IL-8 as molecular adjuvant was explored from several aspects by co-injecting with a DNA vaccine encoding α-enolase(pcENO) against Streptococcus iniae infection in channel catfish...
November 30, 2016: Oncotarget
https://www.readbyqxmd.com/read/27908733/sequences-in-linker-1-domain-of-the-multidrug-resistance-associated-protein-mrp1-or-abcc1-bind-to-tubulin-and-their-binding-is-modulated-by-phosphorylation
#6
Raghuram Ambadipudi, Elias Georges
The multidrug resistant associated protein 1 (or MRP1, ABCC1) encodes two cytoplasmic linker domains (L0 and L1) composed of highly charged sequences with multiple protein kinase A/C phosphorylation sites. In this report we made use of the scanning peptide approach to identify MRP1 linker L1 (L1(MRP1)) interacting proteins. Scanning heptapeptides covering L1(MRP1) 126 amino acids (Ile(846)- Leu(972)) were synthesized and used in pull-down assays to isolate proteins from cell extracts (human multidrug resistant SCLC cell line; H69/AR)...
November 28, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27908247/knockdown-of-minichromosome-maintenance-proteins-inhibits-foci-forming-of-mediator-of-dna-damage-checkpoint-1-in-response-to-dna-damage-in-human-esophageal-squamous-cell-carcinoma-te-1-cells
#7
Jinzhong Yu, Ruijie Wang, Jinfeng Wu, Zhongqin Dang, Qinsheng Zhang, Bo Li
Esophageal squamous cell carcinoma (ESCC) has a high morbidity in China and its treatment depends greatly on adjuvant chemotherapy. However, DNA damage repair in cancer cells severely affects the outcome of treatment. This study investigated the potential mechanism regarding mediator of DNA-damage checkpoint 1 (MDC1) and minichromosome maintenance proteins (MCMs) during DNA damage in ESCC. Recombinant vectors of MDC1 and MCMs with tags were constructed and transfected into human ESCC cell line TE-1. Immunoprecipitation and mass spectrometry were performed to screen the MCMs interacting with MDC1, and direct interaction was confirmed by glutathione S-transferase (GST) pull-down assay in vitro...
October 2016: Biochemistry. Biokhimii︠a︡
https://www.readbyqxmd.com/read/27907975/-is-it-necessary-to-revaccinate-against-hepatitis-b-virus-when-the-titer-of-anti-hbs-drops-below-10-iu-l
#8
Pavel Polák, Petr Husa, Petr Smejkal, Jan Kamelander, Gabriela Chlupová, Miroslav Penka
Viral hepatitis B still represents a major epidemiological issue worldwide. After recombinant vaccine administration, a titer of anti-HBs antibodies ≥ 10 IU/L has long been considered to be seroprotective. Persons without this antibody level after complete vaccination are referred to as non-responders. A progressive decline in anti-HBs levels over years is also commonly seen in responders. Recently, there has been increasing evidence that the titer of anti-HBs ≥ 10 IU/L does not provide 100 % protection against infection and clinically manifest illness...
September 2016: Klinická Mikrobiologie a Infekc̆ní Lékar̆ství
https://www.readbyqxmd.com/read/27907066/b-cell-based-seamless-engineering-of-antibody-fc-domains
#9
Koji Hashimoto, Kohei Kurosawa, Akiho Murayama, Hidetaka Seo, Kunihiro Ohta
Engineering of monoclonal antibodies (mAbs) enables us to obtain mAbs with additional functions. In particular, modifications in antibody's Fc (fragment, crystallizable) region can provide multiple benefits such as added toxicity by drug conjugation, higher affinity to Fc receptors on immunocytes, or the addition of functional modules. However, the generation of recombinant antibodies requires multiple laborious bioengineering steps. We previously developed a technology that enables rapid in vitro screening and isolation of specific mAb-expressing cells from the libraries constructed with chicken B-cell line DT40 (referred to as the 'ADLib system')...
2016: PloS One
https://www.readbyqxmd.com/read/27906629/purification-activity-and-expression-levels-of-two-uridine-cytidine-kinase-isoforms-in-neuroblastoma-cell-lines
#10
R Meinsma, A B P van Kuilenburg
Uridine-cytidine kinase (UCK) catalyzes the phosphorylation of uridine, cytidine, and several pyrimidine ribonucleoside analogs. We overexpressed and purified the two known isoforms of human UCK in Escherichia coli, produced a specific antibody against UCK1 and characterized the kinetic properties of UCK1 and 2. The Vmax of purified recombinant UCK2 was 22- and 8-fold higher with uridine and cytidine, respectively, compared to those observed for the purified recombinant UCK1 enzyme. The Km of UCK1 was 39- and 40-fold higher with uridine and cytidine, respectively, compared to those observed for the purified recombinant UCK2 enzyme...
December 2016: Nucleosides, Nucleotides & Nucleic Acids
https://www.readbyqxmd.com/read/27905992/variable-sensitivity-to-complement-dependent-cytotoxicity-in-murine-models-of-neuromyelitis-optica
#11
Yiting Liu, Danielle E Harlow, Katherine S Given, Gregory P Owens, Wendy B Macklin, Jeffrey L Bennett
BACKGROUND: Studies of neuromyelitis optica (NMO), an autoimmune disease of the central nervous system (CNS), have demonstrated that autoantibodies against the water channel aquaporin-4 (AQP4) induce astrocyte damage through complement-dependent cytotoxicity (CDC). In developing experimental models of NMO using cells, tissues or animals from mice, co-administration of AQP4-IgG and normal human serum, which serves as the source of human complement (HC), is required. The sensitivity of mouse CNS cells to HC and CDC in these models is not known...
December 1, 2016: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/27905833/non-conventional-expression-systems-for-the-production-of-vaccine-proteins-and-immunotherapeutic-molecules
#12
Isabelle Legastelois, Sophie Buffin, Isabelle Peubez, Charlotte Mignon, Régis Sodoyer, Bettina Werle
The increasing demand for recombinant vaccine antigens or immunotherapeutic molecules calls into question the universality of current protein expression systems. Vaccine production can require relatively low amounts of expressed materials, but represents an extremely diverse category consisting of different target antigens with marked structural differences. In contrast, monoclonal antibodies, by definition share key molecular characteristics and require a production system capable of very large outputs, which drives the quest for highly efficient and cost-effective systems...
December 1, 2016: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/27904904/clinical-evaluation-of-glycopegylated-recombinant-fviii-efficacy-and-safety-in-severe-haemophilia-a
#13
Paul Giangrande, Tatiana Andreeva, Pratima Chowdary, Silke Ehrenforth, Hideji Hanabusa, Frank W G Leebeek, Steven R Lentz, Laszlo Nemes, Lone Hvitfeldt Poulsen, Elena Santagostino, Chur Woo You, Wan Hui Ong Clausen, Peter G Jönsson, Johannes Oldenburg
Turoctocog alfa pegol (N8-GP) is a novel glycoPEGylated extended half-life recombinant factor VIII (FVIII) product developed for prophylaxis and treatment of bleeds in patients with haemophilia A, to enable higher activity levels with less frequent injections compared with standard FVIII products. This phase III (NCT01480180), multinational, open-label, non-randomised trial evaluated the safety and clinical efficacy of N8-GP when administered for treatment of bleeds and for prophylaxis, in previously treated patients aged ≥12 years with severe haemophilia A...
December 1, 2016: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/27903284/gp50-as-a-promising-early-diagnostic-antigen-for-taenia-multiceps-infection-in-goats-by-indirect-elisa
#14
Xing Huang, Jing Xu, Yu Wang, Cheng Guo, Lin Chen, Xiaobin Gu, Weimin Lai, Xuerong Peng, Guangyou Yang
BACKGROUND: Coenurosis is caused by coenurus, the metacestode of Taenia multiceps, which mainly parasitizes the brain and spinal cord of cattle, sheep and goats. To date, no widely-approved methods are available to identify early coenurus infection. METHODS: In this study, we identified a full-length cDNA that encodes GP50 (TmGP50) from the transcriptome of T. multiceps, and then cloned and expressed in E. coli. The native proteins in adult stage and coenurus were located via immunofluorescence assays, while the potential of recombinant TmGP50 protein (rTmGP50) for indirect ELISA-based serodiagnostics was assessed using native goat sera...
December 1, 2016: Parasites & Vectors
https://www.readbyqxmd.com/read/27903271/differential-humoral-and-cellular-immunity-induced-by-vaccination-using-plasmid-dna-and-protein-recombinant-expressing-the-ns3-protein-of-dengue-virus-type-3
#15
M L Hurtado-Melgoza, A Ramos-Ligonio, L M Álvarez-Rodríguez, T Meza-Menchaca, A López-Monteon
BACKGROUND: The dengue non-structural 3 (NS3) is a multifunctional protein, containing a serine-protease domain, located at the N-terminal portion, and helicase, NTPase and RTPase domains present in the C-terminal region. This protein is considered the main target for CD4+ and CD8+ T cell responses during dengue infection, which may be involved in protection. However, few studies have been undertaken evaluating the use of this protein as a protective antigen against dengue, as well as other flavivirus...
December 1, 2016: Journal of Biomedical Science
https://www.readbyqxmd.com/read/27902904/infection-with-some-infectious-bursal-disease-virus-pathotypes-produces-virus-in-chicken-muscle-tissue-and-the-role-of-humoral-immunity-as-a-mitigation-strategy
#16
Mariana Sá E Silva, Kateri Bertran, Kira Moresco, Daral J Jackwood, David E Swayne
Infectious bursal disease virus (IBDV) causes important economic losses and negatively affects global trade in poultry and poultry products. This study determined the presence of IBDV in primary lymphoid tissues and muscle tissue of infected broilers and the role of vaccination as a mitigation strategy. In the first study, specific-pathogen-free (SPF) broiler chickens were challenged with STC (classical [cIBDV]), Indiana (variant [varIBDV]), rA (very virulent [vvIBDV]), or Ohio (serotype 2, avirulent) IBDV...
December 2016: Avian Diseases
https://www.readbyqxmd.com/read/27902899/endemic-variation-of-h9n2-avian-influenza-virus-in-china
#17
Yu-Fu Liu, Han-Zhang Lai, Lin Li, Yu-Peng Liu, Wen-Yan Zhang, Ren Gao, Wen-Ke Huang, Qin-Fang Luo, Yan Gao, Qiong Luo, Xiao-Yu Xie, Jia-Hua Xu, Rui-Ai Chen
Forty-two H9N2 subtype AIV strains were isolated from vaccinated commercial chickens in China from 2012 to 2015. Their HA genes had nucleotide sequence homology from 86.7% to 99.7%, and similarity to the classic vaccine strain was 88.6%-92.6%. A comparison was carried out with published HA genes (410 H9 strains) and whole genomes (306 strains) isolated in China during 2012-2015. Interestingly, 99.1% (448/452) of Chinese H9N2 AIV belonged to lineage h9.4.2, and 98.5% (445/452) of the viruses belonged to h9.4...
December 2016: Avian Diseases
https://www.readbyqxmd.com/read/27902762/presenting-influenza-a-m2e-antigen-on-recombinant-spores-of-bacillus-subtilis
#18
Tomasz Łęga, Paulina Weiher, Michał Obuchowski, Dawid Nidzworski
Effective vaccination against influenza virus infection is a serious problem mainly due to antigenic variability of the virus. Among many of investigated antigens, the extracellular domain of the M2 protein (M2e) features high homology in all strains of influenza A viruses and antibodies against M2e and is protective in animal models; this makes it a potential candidate for generation of a universal influenza vaccine. However, due to the low immunogenicity of the M2e, formulation of a vaccine based on this antigen requires some modification to induce effective immune responses...
2016: PloS One
https://www.readbyqxmd.com/read/27902430/lateral-typed-flagellin-responsible-for-formation-of-a-polar-flagellum-but-not-of-lateral-flagella-in-sphingomonas-sp-strain-a1
#19
Masahiro Kobayashi, Hidenori Konishi, Yukie Maruyama, Kousaku Murata, Wataru Hashimoto
Alginate-assimilating Sphingomonas sp. strain A1 is the gram-negative bacterium first identified to form a single polar flagellum containing lateral-typed flagellin (p6) in the filament. In addition to the p6 flagellin, two polar-typed flagellins (p5 and p5') are also included in the flagellum. Here we show the significant role of p6 as well as p5/p5' in flagellum formation and cell motility toward alginate. A p6 gene disruptant significantly reduced flagellum formation, and it showed no cell motility, whereas each mutant with a disruption in the p5 or p5' gene exhibited cell motility through the formation of a polar flagellum containing p6...
October 24, 2016: Microbiology
https://www.readbyqxmd.com/read/27902347/the-conserved-n-terminus-of-human-rhinovirus-capsid-protein-vp4-contains-membrane-pore-forming-activity-and-is-a-target-for-neutralising-antibodies
#20
Anusha Panjwani, Amin S Asfor, Tobias J Tuthill
Human rhinovirus is the causative agent of the common cold and belongs to the non-enveloped picornavirus family. A trigger such as receptor binding or low pH initiates conformational changes in the capsid that allow the virus to attach to membranes and form a pore for the translocation of viral RNA into the cytoplasm. We previously showed that recombinant capsid protein VP4 was able to form membrane pores. In this study, we show the N-terminus but not C-terminus of VP4, formed pores with properties similar to full-length VP4 and consistent with the size required for transfer of RNA...
October 11, 2016: Journal of General Virology
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