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https://www.readbyqxmd.com/read/28230065/in-vivo-evaluation-of-a-novel-format-of-a-bivalent-her3-targeting-and-albumin-binding-therapeutic-affibody-construct
#1
Tarek Z Bass, Maria Rosestedt, Bogdan Mitran, Fredrik Y Frejd, John Löfblom, Vladimir Tolmachev, Stefan Ståhl, Anna Orlova
Overexpression of human epidermal growth factor receptor 3 (HER3) is involved in resistance to several therapies for malignant tumours. Currently, several anti-HER3 monoclonal antibodies are under clinical development. We introduce an alternative approach to HER3-targeted therapy based on engineered scaffold proteins, i.e. affibody molecules. We designed a small construct (22.5 kDa, denoted 3A3), consisting of two high-affinity anti-HER3 affibody molecules flanking an albumin-binding domain ABD, which was introduced for prolonged residence in circulation...
February 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28223506/intragenic-cpg-islands-play-important-roles-in-bivalent-chromatin-assembly-of-developmental-genes
#2
Sun-Min Lee, Jungwoo Lee, Kyung-Min Noh, Won-Young Choi, Sejin Jeon, Goo Taeg Oh, Jeongsil Kim-Ha, Yoonhee Jin, Seung-Woo Cho, Young-Joon Kim
CpG, 5'-C-phosphate-G-3', islands (CGIs) have long been known for their association with enhancers, silencers, and promoters, and for their epigenetic signatures. They are maintained in embryonic stem cells (ESCs) in a poised but inactive state via the formation of bivalent chromatin containing both active and repressive marks. CGIs also occur within coding sequences, where their functional role has remained obscure. Intragenic CGIs (iCGIs) are largely absent from housekeeping genes, but they are found in all genes associated with organ development and cell lineage control...
February 21, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28219260/automatic-retrieval-of-newly-instructed-cue-task-associations-seen-in-task-conflict-effects-in-the-first-trial-after-cue-task-instructions
#3
Nachshon Meiran, Maayan Pereg
Novel stimulus-response associations are retrieved automatically even without prior practice. Is this true for novel cue-task associations? The experiment involved miniblocks comprising three phases and task switching. In the INSTRUCTION phase, two new stimuli (or familiar cues) were arbitrarily assigned as cues for up-down/right-left tasks performed on placeholder locations. In the UNIVALENT phase, there was no task cue since placeholder's location afforded one task but the placeholders were the stimuli that we assigned as task cues for the following BIVALENT phase (involving target locations affording both tasks)...
January 2017: Experimental Psychology
https://www.readbyqxmd.com/read/28216238/dinitrosyl-iron-complexes-with-natural-thiol-containing-ligands-in-aqueous-solutions-synthesis-and-some-physico-chemical-characteristics-a-methodological-review
#4
REVIEW
Anatoly F Vanin, Rostislav R Borodulin, Vasak D Mikoyan
Two approaches to the synthesis of dinitrosyl iron complexes (DNIC) with glutathione and l-cysteine in aqueous solutions based on the use of gaseous NO and appropriate S-nitrosothiols, viz., S-nitrosoglutathione (GS-NO) or S-nitrosocysteine (Cys-NO), respectively, are considered. A schematic representation of a vacuum unit for generation and accumulation of gaseous NO purified from the NO2 admixture and its application for obtaining aqueous solutions of DNIC in a Thunberg apparatus is given. To achieve this, a solution of bivalent iron in distilled water is loaded into the upper chamber of the Thunberg apparatus, while the thiol solution in an appropriate buffer (рН 7...
February 12, 2017: Nitric Oxide: Biology and Chemistry
https://www.readbyqxmd.com/read/28216094/fusion-of-flagellin-2-with-bivalent-white-spot-syndrome-virus-vaccine-increases-survival-in-freshwater-shrimp
#5
Hansam Cho, Na Hye Park, Yuyeon Jang, Yong-Dae Gwon, Yeondong Cho, Yoon-Ki Heo, Ki-Hoon Park, Hee-Jung Lee, Tae Jin Choi, Young Bong Kim
Despite large economic losses attributable to white spot syndrome virus (WSSV), an infectious pathogen of penaeid shrimp and other crustaceans worldwide, no efficient vaccines or antiviral agents to control the virus are available at present. Here, we designed and constructed baculovirus-based vaccines delivering genes encoding the WSSV envelope proteins, VP28 and VP19. To enhance the immunogenicity of the baculovirus-based vaccine, we fused a Salmonella typhimurium flagellin 2 (FL2) gene with VP28 or VP19 gene...
February 16, 2017: Journal of Invertebrate Pathology
https://www.readbyqxmd.com/read/28213834/molecular-simulation-of-receptor-occupancy-and-tumor-penetration-of-an-antibody-and-smaller-scaffolds-application-to-molecular-imaging
#6
Kelly D Orcutt, Gregory P Adams, Anna M Wu, Matthew D Silva, Catey Harwell, Jack Hoppin, Manabu Matsumura, Masakatsu Kotsuma, Jonathan Greenberg, Andrew M Scott, Robert A Beckman
PURPOSE: Competitive radiolabeled antibody imaging can determine the unlabeled intact antibody dose that fully blocks target binding but may be confounded by heterogeneous tumor penetration. We evaluated the hypothesis that smaller radiolabeled constructs can be used to more accurately evaluate tumor expressed receptors. PROCEDURES: The Krogh cylinder distributed model, including bivalent binding and variable intervessel distances, simulated distribution of smaller constructs in the presence of increasing doses of labeled antibody forms...
February 17, 2017: Molecular Imaging and Biology: MIB: the Official Publication of the Academy of Molecular Imaging
https://www.readbyqxmd.com/read/28211541/antibody-controlled-actuation-of-dna-based-molecular-circuits
#7
Wouter Engelen, Lenny H H Meijer, Bram Somers, Tom F A de Greef, Maarten Merkx
DNA-based molecular circuits allow autonomous signal processing, but their actuation has relied mostly on RNA/DNA-based inputs, limiting their application in synthetic biology, biomedicine and molecular diagnostics. Here we introduce a generic method to translate the presence of an antibody into a unique DNA strand, enabling the use of antibodies as specific inputs for DNA-based molecular computing. Our approach, antibody-templated strand exchange (ATSE), uses the characteristic bivalent architecture of antibodies to promote DNA-strand exchange reactions both thermodynamically and kinetically...
February 17, 2017: Nature Communications
https://www.readbyqxmd.com/read/28208656/primetime-for-learning-genes
#8
REVIEW
Joyce Keifer
Learning genes in mature neurons are uniquely suited to respond rapidly to specific environmental stimuli. Expression of individual learning genes, therefore, requires regulatory mechanisms that have the flexibility to respond with transcriptional activation or repression to select appropriate physiological and behavioral responses. Among the mechanisms that equip genes to respond adaptively are bivalent domains. These are specific histone modifications localized to gene promoters that are characteristic of both gene activation and repression, and have been studied primarily for developmental genes in embryonic stem cells...
February 11, 2017: Genes
https://www.readbyqxmd.com/read/28197308/novel-small-molecule-probes-for-metastatic-melanoma
#9
Anyanee Kamkaew, Nanyan Fu, Weibo Cai, Kevin Burgess
Actively targeting probe 1b, an unsymmetrical bivalent dipeptide mimic, selectively bound melanoma over healthy skin tissue in histological samples from patients and Sinclair swine. Modifications to 1b gave agents 2-4 that contain a near-IR aza-BODIPY fluor. Contrary to our expectations, symmetrical probe 3 gave the highest melanoma-to-healthy skin selectivity in histochemistry and experiments with live cells; this was surprising because 2, not 3, is unsymmetrical like the original lead 1. Optical imaging of 3 in a mouse melanoma model failed to show tumor accumulation in vivo, but the probe did selectively accumulate in the tumor (some in lung and less in the liver) as proven by analysis of the organs post mortem...
February 9, 2017: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28196735/gtl001-and-bivalent-cyaa-based-therapeutic-vaccine-strategies-against-human-papillomavirus-and-other-tumor-associated-antigens-induce-effector-and-memory-t-cell-responses-that-inhibit-tumor-growth
#10
Michaël Esquerré, Marie Momot, Anne Goubier, Christophe Gonindard, Stéphane Leung-Theung-Long, Yolande Misseri, Marie-Christine Bissery
GTL001 is a bivalent therapeutic vaccine containing human papillomavirus (HPV) 16 and HPV18 E7 proteins inserted in the Bordetella pertussis adenylate cyclase (CyaA) vector intended to prevent cervical cancer in HPV-infected women with normal cervical cytology or mild abnormalities. To be effective, therapeutic cervical cancer vaccines should induce both a T cell-mediated effector response against HPV-infected cells and a robust CD8(+) T-cell memory response to prevent potential later infection. We examined the ability of GTL001 and related bivalent CyaA-based vaccines to induce, in parallel, effector and memory CD8(+) T-cell responses to both vaccine antigens...
February 10, 2017: Vaccine
https://www.readbyqxmd.com/read/28196734/bactericidal-activity-of-sera-from-adolescents-vaccinated-with-bivalent-rlp2086-against-meningococcal-serogroup-b-outbreak-strains-from-france
#11
Muhamed-Kheir Taha, Julio Cesar Hawkins, Paul Liberator, Ala-Eddine Deghmane, Lubomira Andrew, Li Hao, Thomas R Jones, Lisa K McNeil, Robert E O'Neill, John L Perez, Kathrin U Jansen, Annaliesa S Anderson
OBJECTIVES: Bivalent rLP2086 (Trumenba®; MenB-FHbp), composed of two factor H binding proteins (FHbps), is a vaccine approved in the United States for prevention of Neisseria meningitidis serogroup B (MnB) invasive meningococcal disease (IMD). Bactericidal activity of sera from subjects vaccinated with bivalent rLP2086 was assessed against MnB isolates from recent disease outbreaks in France. METHODS: MnB isolates from IMD cases were characterized by whole genome sequencing and FHbp expression was assessed using a flow cytometry-based assay...
February 10, 2017: Vaccine
https://www.readbyqxmd.com/read/28194449/comparison-of-ipv-to-topv-week-39-boost-of-primary-opv-vaccination-in-indian-infants-an-open-labelled-randomized-controlled-trial
#12
Suman Kanungo, Deok Ryun Kim, Bisakha Haldar, Cynthia Snider, Uma Nalavade, Soon Ae Kim, Ju Yeon Park, Anuradha Sinha, Aiyel Haque Mallick, Byomkesh Manna, Dipika Sur, Ranjan Kumar Nandy, Jagadish M Deshpande, Cecil Czerkinsky, Thomas F Wierzba, William A Petri Jr, Mohammad Ali, Ayan Dey
BACKGROUND: The final endgame strategy of global polio eradication initiative includes switching from trivalent oral poliovirus vaccines (tOPV) to bivalent oral polio vaccine (bOPV), and introduction of inactivated poliovirus vaccine (IPV). This study compares IPV with tOPV week 39 boost in Indian infants. METHODS: Starting 28 March 2012, we enrolled 372 Indian infant-mother pairs from Kolkata, India in an open-label, block-randomized, controlled trial comparing a 39 week tOPV to an IPV boost among infants immunized with three doses of tOPV...
January 2017: Heliyon
https://www.readbyqxmd.com/read/28186762/synthesis-and-pharmacological-characterization-of-novel-trans-cyclopropylmethyl-linked-bivalent-ligands-that-exhibit-selectivity-and-allosteric-pharmacology-at-the-dopamine-d3-receptor-d3r
#13
Vivek Kumar, Amy E Moritz, Thomas M Keck, Alessandro Bonifazi, Michael P Ellenberger, Christopher D Sibley, R Benjamin Free, Lei Shi, J Robert Lane, David R Sibley, Amy Hauck Newman
The development of bitopic ligands directed toward D2-like receptors has proven to be of particular interest to improve the selectivity and/or affinity of these ligands and as an approach to modulate and bias their efficacies. The structural similarities between dopamine D3 receptor (D3R)-selective molecules that display bitopic or allosteric pharmacology and those that are simply competitive antagonists are subtle and intriguing. Herein we synthesized a series of molecules in which the primary and secondary pharmacophores were derived from the D3R-selective antagonists SB269,652 (1) and SB277011A (2) whose structural similarity and pharmacological disparity provided the perfect templates for SAR investigation...
February 10, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28179535/a-bivalent-heterologous-dna-virus-like-particles-prime-boost-vaccine-elicits-broad-protection-against-both-groups-1-and-2-influenza-a-viruses
#14
Wenbo Jiang, Shuangshuang Wang, Honglin Chen, Huanhuan Ren, Xun Huang, Guiqin Wang, Ze Chen, Ling Chen, Zhiwei Chen, Paul Zhou
Current seasonal influenza vaccines are efficacious when vaccine strains are matched with circulating strains. But they do not protect antigenic variants and newly emerging pandemic and outbreak strains. Thus there is a critical need for developing so-called "universal" vaccines that protect against all influenza viruses. In the present study we developed a bivalent heterologous DNA-virus-like particles (VLP) prime-boost vaccine strategy. We show that mice immunized with this vaccine were broadly protected against lethal challenge of group 1 (H1, H5 and H9) and group 2 (H3 and H7) viruses with 94% aggregate survival...
February 8, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28177840/molecular-cytogenetics-identification-of-a-wheat-leymus-mollis-double-disomic-addition-line-with-stripe-rust-resistance
#15
Aicen Zhang, Wanyue Li, Changyou Wang, Xiaofei Yang, Chunhuan Chen, Chen Zhu, Nana Peng, Zengrong Tian, Yajuan Wang, Hong Zhang, Xinlun Liu, Wanquan Ji
Leymus mollis (Trin.) Pilger (2n = 4x = 28, NsNsXmXm) possesses a number of valuable genes against biotic and abiotic stress, which could be transferred into common wheat background for wheat improvement. In the present study, we determined the karyotypic constitution of a wheat-L. mollis double disomic addition line M11003-4-4-1-1 selected from the F5 progeny of a stable wheat-L. mollis derivative M39 (2n = 56) × Triticum aestivum cv. 7182, by morphological and cytogenetic identification, GISH (genomic in situ hybridization), FISH (fluorescent in situ hybridization), molecular markers analysis and stripe rust resistance evaluation...
November 23, 2016: Genome Génome / Conseil National de Recherches Canada
https://www.readbyqxmd.com/read/28177834/cytogenetic-study-and-stripe-rust-response-of-the-derivatives-from-a-wheat-thinopyrum-intermedium-psathyrostachys-huashanica-trigeneric-hybrid
#16
Kang Houyang, Lin Tang, Daiyan Li, Chengdou Diao, Wei Zhu, Yao Tang, Yi Wang, Xing Fan, Lili Xu, Jian Zeng, Sha Lina, Xiaofang Yu, Zhang Haiqin, Yong-Hong Zhou
In this work, the meiotic behavior, chromosome constitution, and stripe rust resistance of the F5 derivatives from wheat-Th. intermedium-P. huashanica trigeneric hybrid were studied. Cytological analysis indicated that the chromosome number of F5 progenies ranged from 42 to 50. The mean meiotic configuration of F5 lines was 1.28 univalents, 21.74 bivalents, 0.04 trivalents, and 0.02 tetravalents per pollen mother cell (PMC). Among the lines with 2n = 42, the average pairing configuration was 0.05 I + 19.91 II (ring) + 1...
December 10, 2016: Genome Génome / Conseil National de Recherches Canada
https://www.readbyqxmd.com/read/28163600/cytological-characterization-of-an-interspecific-hybrid-in-jatropha-and-its-progeny-reveals-preferential-uniparental-chromosome-transmission-and-interspecific-translocation
#17
Shuto Fukuhara, Narathid Muakrong, Shinji Kikuchi, Patcharin Tanya, Hidenori Sassa, Takato Koba, Peerasak Srinives
Genetic variation in Jatropha curcas, a prospective biodiesel plant, is limited, and interspecific hybridization needed for its genetic improvement. Progeny from interspecific crosses between J. curcas and Jatropha integerrima can be used to improve agronomic characters and to increase oil content and yield. However, these hybrids have not been characterized cytologically. The present study was aimed at the analysis of chromosome behavior during meiosis and chromosome composition of S1 plants derived from an interspecific F1 hybrid using genomic in situ hybridization (GISH) and fluorescence in situ hybridization (FISH)...
December 2016: Breeding Science
https://www.readbyqxmd.com/read/28163157/intranasal-immunization-with-novel-espa-tir-m-fusion-protein-induces-protective-immunity-against-enterohemorrhagic-escherichia-coli-o157-h7-challenge-in-mice
#18
Ruqin Lin, Bo Zhu, Yiduo Zhang, Yang Bai, Fachao Zhi, Beiguo Long, Yawen Li, Yuhua Wu, Xianbo Wu, Hongying Fan
Enterohemorrhagic Escherichia coli (EHEC) O157:H7 causes hemorrhagic colitis and hemolytic uremic syndrome in humans. Due to the risks associated with antibiotic treatment against EHEC O157:H7 infection, vaccines represent a promising method for prevention of EHEC O157:H7 infection. Therefore, we constructed the novel bivalent antigen EspA-Tir-M as a candidate EHEC O157:H7 subunit vaccine. We then evaluated the immunogenicity of this novel EHEC O157:H7 subunit vaccine. Immune responses to the fusion protein administered by intranasal and subcutaneous routes were compared in mice...
February 2, 2017: Microbial Pathogenesis
https://www.readbyqxmd.com/read/28157506/not-all-h3k4-methylations-are-created-equal-mll2-compass-dependency-in-primordial-germ-cell-specification
#19
Deqing Hu, Xin Gao, Kaixiang Cao, Marc A Morgan, Gloria Mas, Edwin R Smith, Andrew G Volk, Elizabeth T Bartom, John D Crispino, Luciano Di Croce, Ali Shilatifard
The spatiotemporal regulation of gene expression is central for cell-lineage specification during embryonic development and is achieved through the combinatorial action of transcription factors/co-factors and epigenetic states at cis-regulatory elements. Here, we show that in addition to implementing H3K4me3 at promoters of bivalent genes, Mll2 (KMT2B)/COMPASS can also implement H3K4me3 at a subset of non-TSS regulatory elements, a subset of which shares epigenetic signatures of active enhancers. Our mechanistic studies reveal that association of Mll2's CXXC domain with CpG-rich regions plays an instrumental role for chromatin targeting and subsequent implementation of H3K4me3...
February 2, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28154855/controlling-and-tuning-the-dynamic-nature-of-supramolecular-polymers-in-aqueous-solutions
#20
Simone I S Hendrikse, Sjors P W Wijnands, René P M Lafleur, Maarten J Pouderoijen, Henk M Janssen, Patricia Y W Dankers, E W Meijer
Structural and kinetic exchange properties of supramolecular polymers composed of mono- and bivalent ureidopyrimidinone-based monomers are investigated in aqueous solutions. It is shown that exchange dynamics can be controlled by mixing different types of monomers. This tunability widens the scope in their design as biomaterials.
February 3, 2017: Chemical Communications: Chem Comm
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