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V N Danilevich, V V Sorokin, Ya P Moiseev, S V Sizova
The patterns of formation of RNA nanoparticles (NPs) during thermal cycling of bacterial total tRNA in the presence of cations Ca2+ , Mn2+ , Ni2+ , Zn2+ , Co2+ , and Cu2+ were studied. The optimal conditions for the production of NPs were found, and it was revealed that their size depends on the ratio of the concentrations of Me2+ and tRNA. The concentration of reagents for obtaining NPs of small size (from 5 to 100 nm) was selected. It was shown that tRNA-based nanoparticles can comprise short (20-50 nt) ribooligonucleotides, including aptamers and siRNAs...
March 2018: Doklady. Biochemistry and Biophysics
Cornelia Wigger, Luc R Van Loon
The effect of the pore water composition on the diffusive anion transport was studied for two different argillaceous, low permeability sedimentary rocks, Opalinus Clay (OPA) and Helvetic Marl (HM). The samples were saturated with different solutions with varying molar concentration and different main cations in the solution: NaCl based pore solutions and CaCl2 based pore solutions. The total porosity was measured by through-diffusion experiments with the neutral tracer HTO. Experiments performed in NaCl solutions resulted in a porosity of 0...
May 8, 2018: Journal of Contaminant Hydrology
Ying Jiang, Xiaoshu Pan, Jin Chang, Weijia Niu, Weijia Hou, Hailan Kuai, Zilong Zhao, Ji Liu, Ming Wang, Weihong Tan
Circular bivalent aptamers (cb-apt) comprise an emerging class of chemically engineered aptamers with substantially improved stability and molecular recognition ability. Its therapeutic application, however, is challenged by the lack of functional modules to control the interactions of cb-apt with therapeutics. We present the design of a β-cyclodextrin-modified cb-apt (cb-apt-βCD) and its supramolecular interaction with molecular therapeutics via host-guest chemistry for targeted intracellular delivery. The supramolecular ensemble exhibits high serum stability and enhanced intracellular delivery efficiency compared to a monomeric aptamer...
May 17, 2018: Journal of the American Chemical Society
Denise Karaoglu Hanzatian, Annette Schwartz, Farid Gizatullin, Jamie Erickson, Kangwen Deng, Ruth Villanueva, Christopher Stedman, Cristina Harris, Tariq Ghayur, Andrew Goodearl
Therapeutic monoclonal antibodies and endogenous IgG antibodies show limited uptake into the central nervous system (CNS) due to the blood-brain barrier (BBB), which regulates and controls the selective and specific transport of both exogenous and endogenous materials to the brain. The use of natural transport mechanisms, such as receptor-mediated transcytosis (RMT), to deliver antibody therapeutics into the brain have been studied in rodents and monkeys. Recent successful examples include monovalent bispecific antibodies and mono- or bivalent fusion proteins; however, these formats do not have the capability to bind to both the CNS target and the BBB transport receptor in a bivalent fashion as a canonical antibody would...
May 17, 2018: MAbs
Jennifer C Spencer, Noel T Brewer, Justin G Trogdon, Stephanie B Wheeler, Stacie B Dusetzina
OBJECTIVES: To assess predictors of timely human papillomavirus (HPV) vaccine follow-through among privately insured individuals initiating the 3-dose series. METHODS: Using MarketScan Commercial claims data, we identified 1 332 217 privately insured US individuals aged 9 to 26 years who initiated the bivalent or quadrivalent HPV vaccine series from 2006 to 2014, with follow-up data extending through 2015. The study outcome was receipt of third HPV dose within 12 months of the first, compared by year of initiation...
May 17, 2018: American Journal of Public Health
Qayyum Husain
The enzymes proteases have attracted a lot of attention due to their high demand in various industrial and other sectors since past several decades. Nanosupport bound proteases showed high efficiency of binding and yield of immobilization. Enzymes attached to such support were found significantly more resistant to the denaturation mediated by change in pH and temperature, medium particularly in the presence of water miscible and immiscible organic solvents, detergents, and several kinds of other denaturants...
January 1, 2018: Journal of Nanoscience and Nanotechnology
Jan Poolman
Because of diverse sequences and differential expression of surface structures on individual invasive Neisseria meningitidis serogroup B (MenB) strains, predicting the efficacy of MenB vaccines using traditional human serum bactericidal assays (hSBA) is impractical. The meningococcal antigen surface expression (MEASURE) assay uses flow cytometry to quantitate the expression of factor H binding proteins (fHbp) contained in the bivalent rLP2086 MenB vaccine. To date, experience with MEASURE has been lacking, and in a long-awaited article, McNeil et al...
May 15, 2018: MBio
Junwei Ding, Zhiguo Du, Linqing Gu, Bin Li, Lizhen Wang, Shiwen Wang, Yongji Gong, Shubin Yang
Although rechargeable aqueous zinc-ion batteries have attracted extensive interest due to their environmental friendliness and low cost, they still lack suitable cathodes with high rate capabilities, which are hampered by the intense charge repulsion of bivalent Zn2+ . Here, a novel intercalation pseudocapacitance behavior and ultrafast kinetics of Zn2+ into the unique tunnels of VO2 (B) nanofibers in aqueous electrolyte are demonstrated via in situ X-ray diffraction and various electrochemical measurements...
May 15, 2018: Advanced Materials
Sayyed K Zaidi, Andrew Fritz, Kirsten Tracy, Jonathan Gordon, Coralee Tye, Joseph Boyd, Andre Van Wijnen, Jeffrey Nickerson, Anthony Imbalzano, Jane Lian, Janet Stein, Gary Stein
Nuclear organization is functionally linked to genetic and epigenetic regulation of gene expression for biological control and is modified in cancer. Nuclear organization supports cell growth and phenotypic properties of normal and cancer cells by facilitating physiologically responsive interactions of chromosomes, genes and regulatory complexes at dynamic three-dimensional microenvironments. We will review nuclear structure/function relationships that include: 1. Epigenetic bookmarking of genes by phenotypic transcription factors to control fidelity and plasticity of gene expression as cells enter and exit mitosis; 2...
May 9, 2018: Advances in Biological Regulation
Lukas Heger, Silke Balk, Jennifer J Lühr, Gordon F Heidkamp, Christian H K Lehmann, Lukas Hatscher, Ariawan Purbojo, Arndt Hartmann, Fayna Garcia-Martin, Shin-Ichiro Nishimura, Robert Cesnjevar, Falk Nimmerjahn, Diana Dudziak
Dendritic cells (DCs) are major players for the induction of immune responses. Apart from plasmacytoid DCs (pDCs), human DCs can be categorized into two types of conventional DCs: CD141+ DCs (cDC1) and CD1c+ DCs (cDC2). Defining uniquely expressed surface markers on human immune cells is not only important for the identification of DC subpopulations but also a prerequisite for harnessing the DC subset-specific potential in immunomodulatory approaches, such as antibody-mediated antigen targeting. Although others identified CLEC9A as a specific endocytic receptor for CD141+ DCs, such a receptor for CD1c+ DCs has not been discovered, yet...
2018: Frontiers in Immunology
Tess Tsai-Hsiu Lu, Steffen Heyne, Erez Dror, Eduard Casas, Laura Leonhardt, Thorina Boenke, Chih-Hsiang Yang, Sagar, Laura Arrigoni, Kevin Dalgaard, Raffaele Teperino, Lennart Enders, Madhan Selvaraj, Marius Ruf, Sunil J Raja, Huafeng Xie, Ulrike Boenisch, Stuart H Orkin, Francis C Lynn, Brad G Hoffman, Dominic Grün, Tanya Vavouri, Adelheid M Lempradl, J Andrew Pospisilik
To date, it remains largely unclear to what extent chromatin machinery contributes to the susceptibility and progression of complex diseases. Here, we combine deep epigenome mapping with single-cell transcriptomics to mine for evidence of chromatin dysregulation in type 2 diabetes. We find two chromatin-state signatures that track β cell dysfunction in mice and humans: ectopic activation of bivalent Polycomb-silenced domains and loss of expression at an epigenomically unique class of lineage-defining genes...
May 4, 2018: Cell Metabolism
Nina G Schmidt, Anna Żądło-Dobrowolska, Valerie Ruppert, Christian Höflehner, Birgit Wiltschi, Wolfgang Kroutil
The formation of C-C bonds by using CoA independent acyltransferases may have significant impact for novel methods for biotechnology. We report the identification of Pseudomonas strains with CoA-independent acyltransferase activity as well as the heterologous expression of the enzyme in E. coli. The cloning strategies and selected expression studies are discussed. The recombinant acyltransferases were characterized with regard to thermal and storage stability, pH,- and co-solvent tolerance. Moreover, the impact of bivalent metals, inhibitors, and other additives was tested...
May 12, 2018: Applied Microbiology and Biotechnology
S Zhao, F H Zhao
Bivalent and quadrivalent HPV vaccine have been approved by CFDA successively in China. However, currently available prophylactic vaccines have no therapeutic effect for established infection or disease. In recent years, based on the application of genomics and proteomics for interpretation of tumor antigen, animal experiments and clinical trials of vaccines aiming at a wide variety of antigens have been conducted. In this review, we summarize about the preclinical and clinical research status of HPV therapeutic vaccine and find that the efficacy of HPV therapeutic vaccine alone or combined with other conventional cancer treatment is satisfying, which has potential clinical application value...
May 6, 2018: Zhonghua Yu Fang Yi Xue za Zhi [Chinese Journal of Preventive Medicine]
Marc Arbyn, Lan Xu, Cindy Simoens, Pierre Pl Martin-Hirsch
BACKGROUND: Persistent infection with high-risk human papillomaviruses (hrHPV) types is causally linked with the development of cervical precancer and cancer. HPV types 16 and 18 cause approximately 70% of cervical cancers worldwide. OBJECTIVES: To evaluate the harms and protection of prophylactic human papillomaviruses (HPV) vaccines against cervical precancer and HPV16/18 infection in adolescent girls and women. SEARCH METHODS: We searched MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL) and Embase (June 2017) for reports on effects from trials...
May 9, 2018: Cochrane Database of Systematic Reviews
Saugata Majumder, Shreya Das, Vikas Somani, Shivakiran S Makam, Kingston J Joseph, Rakesh Bhatnagar
Anthrax infection is primarily initiated by B. anthracis endospores that on entry into the host germinate to vegetative cells and cause severe bacteremia and toxaemia employing an array of host colonisation factors and the lethal tripartite toxin. The protective efficacy of conventional protective antigen (PA) based anthrax vaccines is improved by co-administration with inactivated spores or its components. In the present study, using structural vaccinology rationale we synthesized a bivalent protein r-PB encompassing toxin (PAIV) and spore components (BclACTD) and characterized its protective efficacy against B...
May 8, 2018: Scientific Reports
Dmitry Borkin, Szymon Klossowski, Jonathan Pollock, Hongzhi Miao, Brian Linhares, Katarzyna Kempinska, Zhuang Jin, Trupta Purohit, Bo Wen, Miao He, Duxin Sun, Tomasz Cierpicki, Jolanta Grembecka
The protein-protein interaction between menin and Mixed Lineage Leukemia 1 (MLL1) plays an important role in development of acute leukemia with translocations of the MLL1 gene and in solid tumors. Here, we report the development of a new generation of menin-MLL1 inhibitors identified by structure-based optimization of the thienopyrimidine class of compounds. This work resulted in compound 28 (MI-1481), which showed very potent inhibition of the menin-MLL1 interaction (IC50 = 3.6 nM), representing the most potent reversible menin-MLL1 inhibitor reported to date...
May 8, 2018: Journal of Medicinal Chemistry
Soumya Chaurasia, Christian F Lehner
Sister kinetochores are connected to the same spindle pole during meiosis I and to opposite poles during meiosis II. The molecular mechanisms controlling the distinct behavior of sister kinetochores during the two meiotic divisions are poorly understood. To study kinetochore behavior during meiosis, we have optimized time lapse imaging with Drosophila spermatocytes, enabling kinetochore tracking with high temporal and spatial resolution through both meiotic divisions. The correct bipolar orientation of chromosomes within the spindle proceeds rapidly during both divisions...
May 7, 2018: PLoS Genetics
Borna Relja, Katharina Mörs, Ingo Marzi
This review summarizes a short list of currently discussed trauma-induced danger-associated molecular patterns (DAMP). Due to the bivalent character and often pleiotropic effects of a DAMP, it is difficult to describe its "friend or foe" role in post-traumatic inflammation and regeneration, both systemically as well locally in tissues. DAMP can be used as biomarkers to indicate or monitor disease or injury severity, but also may serve as clinically applicable parameters for better indication and timing of surgery...
May 4, 2018: European Journal of Trauma and Emergency Surgery: Official Publication of the European Trauma Society
Michael Grasso, Michelle A Estrada, Kiara N Berrios, Jeffrey D Winkler, Ronen Marmorstein
BRAFV600E is the most common activating mutation in melanoma and patients treated with BRAFV600E inhibitors all develop resistance within 1 year. A significant resistance pathway is paradoxical activation (transactivation) involving BRAF dimers, whereby an inhibitor bound protein subunit allosterically activates the other subunit. We recently reported on bivalent BRAFV600E -selective vemurafenib inhibitors that stabilize an inactive αC-out/αC-out homodimeric conformation with improved inhibitor potency and selectivity in vitro...
May 4, 2018: Journal of Medicinal Chemistry
Jeffrey Koury, Mariana Lucero, Caleb Cato, Lawrence Chang, Joseph Geiger, Denise Henry, Jennifer Hernandez, Fion Hung, Preet Kaur, Garrett Teskey, Andrew Tran
Cancer is a condition that has plagued humanity for thousands of years, with the first depictions dating back to ancient Egyptian times. However, not until recent decades have biological therapeutics been developed and refined enough to safely and effectively combat cancer. Three unique immunotherapies have gained traction in recent decades: adoptive T cell transfer, checkpoint inhibitors, and bivalent antibodies. Each has led to clinically approved therapies, as well as to therapies in preclinical and ongoing clinical trials...
2018: Journal of Immunology Research
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