29,164 results match your criteria Combinatorial Chemistry & High Throughput Screening[Journal]


Immediate Neutrophil-Variable-T Cell Receptor Host Response in Bacterial Meningitis.

Front Neurol 2019 2;10:307. Epub 2019 Apr 2.

Bioscientia Institute for Medical Diagnostics, Ingelheim, Germany.

Bacterial meningitis is a life-threatening disease that evokes an intense neutrophil-dominated host response to microbes invading the subarachnoid space. Recent evidence indicates the existence of combinatorial V(D)J immune receptors in neutrophils that are based on the T cell receptor (TCR). Here, we investigated expression of the novel neutrophil TCRαβ-based V(D)J receptors in cerebrospinal fluid (CSF) from human patients with acute-phase bacterial meningitis using immunocytochemical, genetic immunoprofiling, cell biological, and mass spectrometric techniques. Read More

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https://www.frontiersin.org/article/10.3389/fneur.2019.00307
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http://dx.doi.org/10.3389/fneur.2019.00307DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6454057PMC
April 2019
1 Read

Transcriptome and Proteome analysis of steady-state in a perfusion CHO cell culture process.

Biotechnol Bioeng 2019 Apr 18. Epub 2019 Apr 18.

Institute for Chemical and Bioengineering, Department of Chemistry and Applied Biosciences, ETH Zurich, Zurich, Switzerland.

Long-term continuous protein production can be reached by perfusion operation. Through the continuous removal of waste metabolites and supply of nutrients, steady-state (SS) conditions are achieved after a certain transient period, where the conditions inside the reactor are not only uniform in space but also constant in time. Such stable conditions may have beneficial influences on the reduction of product heterogeneities. Read More

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https://onlinelibrary.wiley.com/doi/abs/10.1002/bit.26996
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http://dx.doi.org/10.1002/bit.26996DOI Listing
April 2019
6 Reads

High-throughput combinatorial screening of multi-component electrolyte additives to improve the performance of Li metal secondary batteries.

Sci Rep 2019 Apr 17;9(1):6211. Epub 2019 Apr 17.

Graduate School of Engineering Science, Osaka University, 1-3 Machikaneyama, Toyonaka, Osaka, 560-8531, Japan.

Data-driven material discovery has recently become popular in the field of next-generation secondary batteries. However, it is important to obtain large, high quality data sets to apply data-driven methods such as evolutionary algorithms or Bayesian optimization. Combinatorial high-throughput techniques are an effective approach to obtaining large data sets together with reliable quality. Read More

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http://dx.doi.org/10.1038/s41598-019-42766-xDOI Listing
April 2019
1 Read

Pulsatile MEK Inhibition Improves Anti-tumor Immunity and T Cell Function in Murine Kras Mutant Lung Cancer.

Cell Rep 2019 Apr;27(3):806-819.e5

Ludwig Collaborative and Swim Across America Laboratory, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Parker Institute for Cancer Immunotherapy, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Weill Cornell Medicine, New York, NY 10065, USA. Electronic address:

KRAS is one of the driver oncogenes in non-small-cell lung cancer (NSCLC) but remains refractory to current modalities of targeted pathway inhibition, which include inhibiting downstream kinase MEK to circumvent KRAS activation. Here, we show that pulsatile, rather than continuous, treatment with MEK inhibitors (MEKis) maintains T cell activation and enables their proliferation. Two MEKis, selumetinib and trametinib, induce T cell activation with increased CTLA-4 expression and, to a lesser extent, PD-1 expression on T cells in vivo after cyclical pulsatile MEKi treatment. Read More

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http://dx.doi.org/10.1016/j.celrep.2019.03.066DOI Listing

Construction of second generation protease-deficient hosts of Bacillus subtilis for secretion of foreign proteins.

Biotechnol Bioeng 2019 Apr 16. Epub 2019 Apr 16.

Key Laboratory of Agricultural Environmental Microbiology, Ministry of Agriculture, College of Life Sciences, Nanjing Agricultural University, Nanjing, Jiangsu, People's Republic of China.

Although one of the major factors limiting the application of Bacillus subtilis as an expression host has been its production of at least eight extracellular proteases, researchers have also noticed that some proteases benefited the secretion of foreign proteins at times. Therefore, to maximize the yield of a foreign protein, the proteases should be selectively inactivated. This raises a new question that how to identify the favorable and unfavorable proteases for a target protein. Read More

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http://dx.doi.org/10.1002/bit.26992DOI Listing

Identification of a potent inhibitor of type II secretion system from Pseudomonas aeruginosa.

Biochem Biophys Res Commun 2019 Apr 12. Epub 2019 Apr 12.

Department of Experimental Biology, Wroclaw University of Environmental and Life Sciences, Ul. C. K. Norwida 27B, 50-375, Wroclaw, Poland; Faculty of Veterinary Medicine, Equine Clinic - Equine Surgery, Justus-Liebig-University, 35392, Giessen, Germany.

Pseudomonas aeruginosa is an opportunistic pathogen infecting human population. The pathogen is becoming a serious health problem due to its ability to evade normal immune response of the host and multiple drug resistance to many antibiotics. The pathogen has 2 major virulence systems of which the type III secretion system (T3SS) is of major concern to humans. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S0006291X193068
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http://dx.doi.org/10.1016/j.bbrc.2019.04.055DOI Listing
April 2019
1 Read

A 'sulfonyl-azide-free' (SAFE) aqueous-phase diazo transfer reaction for parallel and diversity-oriented synthesis.

Chem Commun (Camb) 2019 Apr 15. Epub 2019 Apr 15.

Institute of Chemistry, Saint Petersburg State University, Saint Petersburg 199034, Russian Federation.

Diazo transfer reactions are notoriously associated with the use of potentially explosive sulfonyl azides. The first 'sulfonyl-azide-free' (SAFE) protocol for producing diazo compounds from their active-methylene precursors via the Regitz diazo transfer reaction was developed and has displayed a remarkable substrate scope. It can be applied to generating arrays of diazo compounds for further evolution via combinatorial chemistry and a range of scaffold-generating transformations. Read More

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http://dx.doi.org/10.1039/c9cc02042jDOI Listing

Combinatorial effects of radiofrequency hyperthermia and radiotherapy in the presence of magneto-plasmonic nanoparticles on MCF-7 breast cancer cells.

J Cell Physiol 2019 Apr 14. Epub 2019 Apr 14.

Radiation Biology Research Center, Iran University of Medical Science (IUMS), Tehran, Iran.

Here, the effects of combinatorial cancer therapy including radiotherapy (RT) and radiofrequency (RF) hyperthermia in the presence of gold-coated iron oxide nanoparticles (Au@IONPs), as a thermo-radio-sensitizer, are reported. The level of cell death and the ratio of Bax/Bcl2 genes, involved in the pathway of apoptosis, were measured to evaluate the synergistic effect of Au@IONPs-mediated RF hyperthermia and RT. MCF-7 human breast adenocarcinoma cells were treated with different concentrations of Au@IONPs. Read More

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https://onlinelibrary.wiley.com/doi/abs/10.1002/jcp.28599
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http://dx.doi.org/10.1002/jcp.28599DOI Listing
April 2019
1 Read

Methyl ketone production by Pseudomonas putida is enhanced by plant-derived amino acids.

Biotechnol Bioeng 2019 Apr 14. Epub 2019 Apr 14.

Joint BioEnergy Institute, Emeryville, CA.

Plants are an attractive source of renewable carbon for conversion to biofuels and bio-based chemicals. Conversion strategies often use a fraction of the biomass, focusing on sugars from cellulose and hemicellulose. Strategies that use plant components such as aromatics and amino acids may improve the efficiency of biomass conversion. Read More

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https://onlinelibrary.wiley.com/doi/abs/10.1002/bit.26995
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http://dx.doi.org/10.1002/bit.26995DOI Listing
April 2019
1 Read

Sensitive detection of glucagon aggregation using amyloid fibril-specific antibodies.

Biotechnol Bioeng 2019 Apr 14. Epub 2019 Apr 14.

Departments of Pharmaceutical Sciences, Biointerfaces Institute, University of Michigan, Ann Arbor, MI, USA.

Sensitive detection of protein aggregates is important for evaluating the quality of biopharmaceuticals and detecting misfolded proteins in several neurodegenerative diseases. However, it is challenging to detect extremely low concentrations (<10 ppm) of aggregated protein in the presence of high concentrations of natively-folded (soluble) protein. Glucagon, a peptide hormone used in the treatment of extreme hypoglycemia, is aggregation-prone and forms amyloid fibrils. Read More

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https://onlinelibrary.wiley.com/doi/abs/10.1002/bit.26994
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http://dx.doi.org/10.1002/bit.26994DOI Listing
April 2019
2 Reads

Lignocellulose Solubilization and Conversion by Extremely Thermophilic Caldicellulosiruptor bescii Improves by Maintaining Metabolic Activity.

Biotechnol Bioeng 2019 Apr 14. Epub 2019 Apr 14.

Department of Chemical and Biomolecular Engineering North Carolina State University, Raleigh, NC.

The extreme thermophile Caldicellulosiruptor bescii solubilizes and metabolizes the carbohydrate content of lignocellulose, a process that ultimately ceases because of biomass recalcitrance, accumulation of fermentation products, inhibition by lignin moieties, and reduction of metabolic activity. Deconstruction of low loadings of lignocellulose (5 g/l), either natural or transgenic, whether unpretreated or subjected to hydrothermal processing, by C. bescii typically results in less than 40% carbohydrate solubilization. Read More

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http://dx.doi.org/10.1002/bit.26993DOI Listing

New insights into the performance characteristics of the Planova-series hollow-fiber parvovirus filters using confocal and electron microscopy.

Biotechnol Bioeng 2019 Apr 14. Epub 2019 Apr 14.

Department of Chemical Engineering, The Pennsylvania State University, University Park, PA.

Virus filtration remains a critical step in the downstream process for the production of monoclonal antibodies and other mammalian cell-derived biotherapeutics. Recent studies have shown large differences in virus capture behavior of different virus filters, although the origin of these differences is still unclear. The objective of this study was to use confocal and scanning electron microscopy to directly evaluate the capture of virus-size nanoparticles in Planova 20N and BioEX hollow fiber virus filters. Read More

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https://onlinelibrary.wiley.com/doi/abs/10.1002/bit.26991
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http://dx.doi.org/10.1002/bit.26991DOI Listing
April 2019
1 Read

Ultra-high-throughput screening system for directed polymer binding peptide evolution.

Biotechnol Bioeng 2019 Apr 14. Epub 2019 Apr 14.

DWI - Leibniz-Institute for Interactive Materials, Forckenbeckstrasse 50 D-52074, Aachen, Germany.

Accumulation of plastics in the environment became a geological indicator of the Anthropocene era. An effective reduction of long-lasting plastics requires a treatment with microorganisms that release polymer-degrading enzymes. Polymer binding peptides function as adhesion promoters and enable a targeted binding of whole cells to polymer surfaces. Read More

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https://onlinelibrary.wiley.com/doi/abs/10.1002/bit.26990
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http://dx.doi.org/10.1002/bit.26990DOI Listing
April 2019
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Whole-bacterium ribosome display selection for isolation of highly specific anti-Staphyloccocus aureus Affitins for detection- and capture-based biomedical applications.

Biotechnol Bioeng 2019 Apr 14. Epub 2019 Apr 14.

CRCINA, INSERM, CNRS, Université d'Angers, Université de Nantes, Nantes, France.

Detection and capture methods using antibodies have been developed to ensure identification of pathogens in biological samples. Though antibodies have many attractive properties, they also have limitations and there are needs to expand the panel of available affinity proteins with different properties. Affitins, that we developed from the Sul7d proteins, are a solid class of affinity proteins which can be used as substitutes to antibodies or to complement them. Read More

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http://dx.doi.org/10.1002/bit.26989DOI Listing

Machine learning-assisted directed protein evolution with combinatorial libraries.

Proc Natl Acad Sci U S A 2019 Apr 12. Epub 2019 Apr 12.

Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA 91125;

To reduce experimental effort associated with directed protein evolution and to explore the sequence space encoded by mutating multiple positions simultaneously, we incorporate machine learning into the directed evolution workflow. Combinatorial sequence space can be quite expensive to sample experimentally, but machine-learning models trained on tested variants provide a fast method for testing sequence space computationally. We validated this approach on a large published empirical fitness landscape for human GB1 binding protein, demonstrating that machine learning-guided directed evolution finds variants with higher fitness than those found by other directed evolution approaches. Read More

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http://dx.doi.org/10.1073/pnas.1901979116DOI Listing

Current Advances in Studying Clinically Relevant Transporters of the Solute Carrier (SLC) Family by Connecting Computational Modeling and Data Science.

Comput Struct Biotechnol J 2019 8;17:390-405. Epub 2019 Mar 8.

Department of Pharmaceutical Chemistry, Divison of Drug Design and Medicinal Chemistry, University of Vienna, Althanstraße 14, A-1090 Vienna, Austria.

Organic anion and cation transporting proteins (OATs, OATPs, and OCTs), as well as the Multidrug and Toxin Extrusion (MATE) transporters of the Solute Carrier (SLC) family are playing a pivotal role in the discovery and development of new drugs due to their involvement in drug disposition, drug-drug interactions, adverse drug effects and related toxicity. Computational methods to understand and predict clinically relevant transporter interactions can provide useful guidance at early stages in drug discovery and design, especially if they include contemporary data science approaches. In this review, we summarize the current state-of-the-art of computational approaches for exploring ligand interactions and selectivity for these drug (uptake) transporters. Read More

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http://dx.doi.org/10.1016/j.csbj.2019.03.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6438991PMC

Potent and selective caspase-2 inhibitor prevents MDM-2 cleavage in reversine-treated colon cancer cells.

Cell Death Differ 2019 Apr 11. Epub 2019 Apr 11.

NCI Designated Cancer Center, Sanford Burnham Prebys Medical Discovery Institute, 10901 North Torrey Pines Road, La Jolla, CA, 92037, USA.

Most caspases can be positioned unambiguously within the regulated cell death networks of apoptosis and pyroptosis, but the role of caspase-2, a highly conserved protease within the family, remains enigmatic. This is mainly due to lack of selective chemical and biochemical tools for the investigation of this protease. In this study, we used our hybrid combinatorial substrate library (HyCoSuL) approach to broadly profile caspase-2 substrate specificity using peptide scanning libraries. Read More

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http://dx.doi.org/10.1038/s41418-019-0329-2DOI Listing

Staufen2-mediated RNA recognition and localization requires combinatorial action of multiple domains.

Nat Commun 2019 04 10;10(1):1659. Epub 2019 Apr 10.

Institute of Pharmaceutical Biotechnology, 89081 Ulm University, Ulm, Germany.

Throughout metazoans, Staufen (Stau) proteins are core factors of mRNA localization particles. They consist of three to four double-stranded RNA binding domains (dsRBDs) and a C-terminal dsRBD-like domain. Mouse Staufen2 (mStau2)-like Drosophila Stau (dmStau) contains four dsRBDs. Read More

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http://dx.doi.org/10.1038/s41467-019-09655-3DOI Listing

Mixed macrocycles derived from 2,6-diformylpyridine and opposite enantiomers of trans-1,2-diaminocyclopentane and trans-1,2-diaminocyclohexane.

J Org Chem 2019 Apr 9. Epub 2019 Apr 9.

The condensation reaction of 2,6-diformylpyridine with the equimolar mixture of opposite enantiomers of trans-1,2-diaminocyclopentane and trans-1,2-diaminocyclohexane using a dynamic combinatorial chemistry approach has been examined. In nonmetal-templated reactions, depending on reaction conditions mixed 2+1+1 macrocyclic imine or bigger mixed 4+2+2 imine macrocycle are formed selectively. The 2+1+1 imine used as a precursor in the templated by CdII ions produces a library of enlarged chiral mixed imines coordinated with metal cations among which the hexanuclear CdII complex of 6+3+3 imine was isolated and characterized. Read More

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http://dx.doi.org/10.1021/acs.joc.9b00614DOI Listing

Two-in-One Chemogene Assembled from Drug-Integrated Antisense Oligonucleotides To Reverse Chemoresistance.

J Am Chem Soc 2019 Apr 17. Epub 2019 Apr 17.

School of Chemistry and Chemical Engineering, State Key Laboratory of Metal Matrix Composites , Shanghai Jiao Tong University , 800 Dongchuan Road , Shanghai 200240 , China.

Combinatorial chemo and gene therapy provides a promising way to cure drug-resistant cancer, since the codelivered functional nucleic acids can regulate drug resistance genes, thus restoring sensitivity of the cells to chemotherapeutics. However, the dramatic chemical and physical differences between chemotherapeutics and nucleic acids greatly hinder the design and construction of an ideal drug delivery system (DDS) to achieve synergistic antitumor effects. Herein, we report a novel approach to synthesize a nanosized DDS using drug-integrated DNA with antisense sequences (termed "chemogene") to treat drug-resistant cancer. Read More

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http://dx.doi.org/10.1021/jacs.8b13875DOI Listing

EWOD silicon biosensor for multiple nucleic acids analysis.

Biotechnol Bioeng 2019 Apr 9. Epub 2019 Apr 9.

STMicroelectronics, Stradale primosole, Catania.

In this paper, a miniaturized biosensor containing 96 silicon microchambers electroloaded with nano-volumes of liquid (EW-chip) is presented. The liquid electroloading is achieved by the appropriate modulation of interface properties. The surface chemistries have been studied to guarantee effective interface properties for both electrowetting on dielectric actuation and biocompatibility versus biochemical reactions. Read More

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http://dx.doi.org/10.1002/bit.26987DOI Listing

A thermoplastic microfluidic microphysiological system to recapitulate hepatic function and multi-cellular interactions.

Biotechnol Bioeng 2019 Apr 9. Epub 2019 Apr 9.

Draper, 555 Technology Square, Cambridge, MA.

Hepatic in vitro platforms ranging from multi-well cultures to bioreactors and microscale systems have been developed as tools to recapitulate cellular function and responses to aid in drug screening and disease model development. Recent developments in microfabrication techniques and cellular materials enabled fabrication of next-generation, advanced microphysiological systems (MPSs) that aim to capture the cellular complexity and dynamic nature of the organ presenting highly controlled extracellular cues to cells in a physiologically relevant context. Historically, MPSs have heavily relied on elastomeric materials in their manufacture, with unfavorable material characteristics ( such as lack of structural rigidity) limiting their use in high-throughput systems. Read More

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http://dx.doi.org/10.1002/bit.26986DOI Listing

Photosynthetic generation of heterologous terpenoids in cyanobacteria.

Biotechnol Bioeng 2019 Apr 9. Epub 2019 Apr 9.

Department of Plant and Microbial Biology, University of California, Berkeley, California.

The work aims to convert the secondary slow metabolism of the terpenoid biosynthetic pathway into a primary activity in cyanobacteria and to generate heterologous products using these photosynthetic microorganisms as cell factories. Case study is the production of the 10-carbon monoterpene β-phellandrene (PHL) in Synechocystis sp. PCC 6803 (Synechocystis). Read More

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http://dx.doi.org/10.1002/bit.26988DOI Listing
April 2019
1 Read

SNAREs define targeting specificity of trafficking vesicles by combinatorial interaction with tethering factors.

Nat Commun 2019 04 8;10(1):1608. Epub 2019 Apr 8.

Department of Neurobiology, Max Planck Institute for Biophysical Chemistry, Göttingen, 37077, Germany.

Membrane traffic operates by vesicles that bud from precursor organelles and are transported to their target compartment where they dock and fuse. Targeting requires tethering factors recruited by small GTPases and phosphoinositides whereas fusion is carried out by SNARE proteins. Here we report that vesicles containing the Q-SNAREs syntaxin 13 (Stx13) and syntaxin 6 (Stx6) together are targeted to a different endosomal compartment than vesicles containing only Stx6 using injection of artificial vesicles. Read More

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http://dx.doi.org/10.1038/s41467-019-09617-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6453939PMC

Dual Drug Delivery of Sorafenib and Doxorubicin from PLGA and PEG-PLGA Polymeric Nanoparticles.

Polymers (Basel) 2018 Aug 9;10(8). Epub 2018 Aug 9.

Institute of Materials and Environmental Chemistry, Research Centre for Natural Sciences, Hungarian Academy of Sciences, Magyar tudósok körútja 2., H-1117 Budapest, Hungary.

Combinatorial drug delivery is a way of advanced cancer treatment that at present represents a challenge for researchers. Here, we report the efficient entrapment of two clinically used single-agent drugs, doxorubicin and sorafenib, against hepatocellular carcinoma. Biocompatible and biodegradable polymeric nanoparticles provide a promising approach for controlled drug release. Read More

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http://dx.doi.org/10.3390/polym10080895DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6403728PMC

Towards complete polypeptide backbone NH assignment via combinatorial labeling.

J Magn Reson 2019 Mar 29;302:50-63. Epub 2019 Mar 29.

Institute of Biophysical Chemistry & Center for Biomolecular Magnetic Resonance, Goethe University, Max-von-Laue-Str. 9, 60438 Frankfurt, Germany. Electronic address:

Combinatorial selective isotope labeling is a valuable tool to facilitate polypeptide backbone resonance assignment in cases of low sensitivity or extensive chemical shift degeneracy. It involves recording of N-HSQC and 2D HN-projections of triple-resonance spectra on a limited set of samples containing different combinations of labeled and unlabeled amino acid types. Using labeling schemes in which the three backbone heteronuclei (amide nitrogen, α-carbon and carbonyl carbon) are enriched in N or C isotopes - individually as well as simultaneously - usually yields abundant amino-acid type information of consecutive residues i and i - 1. Read More

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http://dx.doi.org/10.1016/j.jmr.2019.03.010DOI Listing

Novel, Linked Bioreactor System for Continuous Production of Biologics.

Biotechnol Bioeng 2019 Apr 5. Epub 2019 Apr 5.

Culture Process Development, Pfizer Inc., 1 Burtt Road, Andover, Massachusetts.

A novel, alternative intensified cell culture process comprised of a linked bioreactor system is presented. An N-1 perfusion bioreactor maintained cells in a highly proliferative state and provided a continuous inoculum source to a second bioreactor operating as a continuous-flow stirred-tank reactor (CSTR). An initial study evaluated multiple system steady-states by varying N-1 steady-state viable cell densities, N-1 to CSTR working volume ratios, and CSTR dilution rates. Read More

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http://dx.doi.org/10.1002/bit.26985DOI Listing
April 2019
2 Reads

Ultra-multiplexed analysis of single-cell dynamics reveals logic rules in differentiation.

Sci Adv 2019 Apr 3;5(4):eaav7959. Epub 2019 Apr 3.

Institute for Molecular Engineering, The University of Chicago, Chicago, IL 60637, USA.

Dynamical control of cellular microenvironments is highly desirable to study complex processes such as stem cell differentiation and immune signaling. We present an ultra-multiplexed microfluidic system for high-throughput single-cell analysis in precisely defined dynamic signaling environments. Our system delivers combinatorial and time-varying signals to 1500 independently programmable culture chambers in week-long live-cell experiments by performing nearly 10 pipetting steps, where single cells, two-dimensional (2D) populations, or 3D neurospheres are chemically stimulated and tracked. Read More

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http://dx.doi.org/10.1126/sciadv.aav7959DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6447378PMC

Targeted delivery of quercetin via pH-responsive zinc oxide nanoparticles for breast cancer therapy.

Mater Sci Eng C Mater Biol Appl 2019 Jul 28;100:129-140. Epub 2019 Feb 28.

Division of Molecular Medicine, Bose Institute, P-1/12, CIT Scheme VII M, Kolkata 700054, India. Electronic address:

Naturally occurring bioactive compounds are gaining much importance as anti-tumor agents in recent times due to their high therapeutic potential and less systemic toxicity. However, different preclinical and clinical studies have noted significant shortcomings, such as nonspecific tumor targeting and low bioavailability which limit their usage in therapeutics. Therefore, a safe and compatible nanoparticle mediated controlled drug delivery system is in high demand to enable effective transport of the drug candidates in the tumor tissue. Read More

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http://dx.doi.org/10.1016/j.msec.2019.02.096DOI Listing
July 2019
1 Read
3.088 Impact Factor

Modeling of Glass Transition Temperatures for Polymeric Coating Materials: Application of QSPR Mixture-based Approach.

Mol Inform 2019 Apr 4. Epub 2019 Apr 4.

Department of Coatings and Polymeric Materials, North Dakota State University, Fargo, ND, 58105, USA.

Cross-linked block copolymers are structurally complex, and utilization of traditional methods of molecular representation in chemoinformatics is only of limited applicability. Therefore, we introduced new techniques of structural representation for block copolymers. We developed additive and combinatorial approaches that treat a copolymer as a mixture system. Read More

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http://dx.doi.org/10.1002/minf.201800150DOI Listing
April 2019
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Emergence of Compartments Formed from Unconventional Surfactants in Dynamic Combinatorial Libraries.

Langmuir 2019 Apr 16. Epub 2019 Apr 16.

Centre for Systems Chemistry, Stratingh Institute , University of Groningen , Nijenborgh 4 , 9747 AG Groningen , The Netherlands.

Assembly processes can drive the selection of self-assembling molecules in dynamic combinatorial libraries, yielding self-synthesizing materials. We now show how such selection in a dynamic combinatorial library made from an amphiphilic building block which, by itself, assembles into micelles, can yield membranous aggregates ranging from vesicles to sponge phases. These aggregates are made from a mixture of unconventional surfactant molecules, showing the power of dynamic combinatorial selection approaches for the discovery of new, not readily predictable, self-assembly motifs. Read More

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http://dx.doi.org/10.1021/acs.langmuir.8b03662DOI Listing
April 2019
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3,5,7-Substituted Pyrazolo[4,3- d]pyrimidine Inhibitors of Cyclin-Dependent Kinases and Their Evaluation in Lymphoma Models.

J Med Chem 2019 Apr 17. Epub 2019 Apr 17.

Laboratory of Growth Regulators , Palacký University and Institute of Experimental Botany, The Czech Academy of Sciences , Šlechtitelů 27 , 783 71 Olomouc , Czech Republic.

Cyclin-dependent kinases are therapeutic targets frequently deregulated in various cancers. By convenient alkylation of the 5-sulfanyl group, we synthesized 3-isopropyl-7-[4-(2-pyridyl)benzyl]amino-1(2) H-pyrazolo[4,3- d]pyrimidines with various substitutions at position 5 with potent antiproliferative activity in non-Hodgkin lymphoma cell lines. The most potent derivative 4. Read More

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http://dx.doi.org/10.1021/acs.jmedchem.9b00189DOI Listing
April 2019
2 Reads

Colorimetric biosensor using dual-amplification of enzyme-free reaction through universal hybridization chain reaction system.

Biotechnol Bioeng 2019 Apr 1. Epub 2019 Apr 1.

Department of Bioengineering and Nano-bioengineering, Incheon National University, Incheon, Korea.

On-site genetic detection needs to develop a sensitive and straightforward biosensor without special equipment, which can detect various genetic biomarkers. Hybridization chain reaction (HCR) amplifying signal isothermally could be considered as a good candidate for on-site detection. Here, we developed a novel genetic biosensor on the basis of enzyme-free dual-amplification of universal hybridization chain reaction (uHCR) and hemin/G-quadruplex horseradish peroxidase (HRP)-mimicking DNAzyme. Read More

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http://dx.doi.org/10.1002/bit.26978DOI Listing

Split-enzyme fragment as a single affinity tag that enables protein expression, purification, and functional assays.

Biotechnol Bioeng 2019 Apr 1. Epub 2019 Apr 1.

Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, Salt Lake City, Utah.

Expressing, isolating, and characterizing recombinant proteins is crucial to many disciplines within the biological sciences. Different molecular tagging technologies have been developed to enable each individual step of protein production, from expression through purification and characterization. Monitoring the entire production process requires multiple tags or molecular interactions, because no individual tag has provided the comprehensive breadth of utility. Read More

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http://dx.doi.org/10.1002/bit.26980DOI Listing
April 2019
1 Read

Improvement of the acid resistance, catalytic efficiency, and thermostability of nattokinase by multisite-directed mutagenesis.

Biotechnol Bioeng 2019 Apr 1. Epub 2019 Apr 1.

Key Laboratory of Industrial Biotechnology, Ministry of Education, School of Biotechnology, Jiangnan University, Wuxi, Jiangsu, China.

Nattokinase (NK) is a serine protease of the subtilisin family; as a potent fibrinolytic enzyme, it is potentially useful for thrombosis therapy. For NK to be applied as an oral medicine for the treatment of cardiovascular diseases, it must overcome the extremely acidic environments of the gastrointestinal tract despite its limited acidic stability. In this study, three strategies were adopted to improve the acid resistance of NK: (a) Surface charge engineering, (b) sequence alignment, and (c) mutation based on the literature. Read More

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http://dx.doi.org/10.1002/bit.26983DOI Listing
April 2019
1 Read

Enhancing 5-aminolevulinic acid tolerance and production by engineering the antioxidant defense system of Escherichia coli.

Biotechnol Bioeng 2019 Apr 1. Epub 2019 Apr 1.

Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin, China.

5-Aminolevulinic acid (ALA) is a value-added compound with potential applications in the fields of agriculture and medicine. Although massive efforts have recently been devoted to building microbial producers of ALA through metabolic engineering, few studies focused on the cellular response and tolerance to ALA. In this study, we demonstrated that ALA caused severe cell damage and morphology change of Escherichia coli via generating reactive oxygen species (ROS), which were further determined to be mainly hydrogen peroxide and superoxide anion radical. Read More

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http://dx.doi.org/10.1002/bit.26981DOI Listing

An engineered mouse embryonic stem cell model with survivin as a molecular marker and EGFP as the reporter for high throughput screening of embryotoxic chemicals in vitro.

Biotechnol Bioeng 2019 Apr 1. Epub 2019 Apr 1.

William G. Lowrie Department of Chemical and Biomolecular Engineering, The Ohio State University, 151 West Woodruff Avenue, Columbus, Ohio.

Embryonic stem cell test (EST) is the only generally accepted in vitro method for assessing embryotoxicity without animal sacrifice. However, the implementation and application of EST for regulatory embryotoxicity screening are impeded by its technical complexity, long testing period, and limited endpoint data. In this study, a high throughput embryotoxicity screening based on mouse embryonic stem cells (mESCs) expressing enhanced green fluorescent protein (EGFP) driven by a human survivin promoter and a human cytomegalovirus promoter, respectively, was developed. Read More

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http://dx.doi.org/10.1002/bit.26977DOI Listing
April 2019
1 Read

Real-time monitoring and model-based prediction of purity and quantity during a chromatographic capture of fibroblast growth factor 2.

Biotechnol Bioeng 2019 Apr 1. Epub 2019 Apr 1.

Austrian Centre of Industrial Biotechnology, Vienna, Austria.

Process analytical technology combines understanding and control of the process with real-time monitoring of critical quality and performance attributes. The goal is to ensure the quality of the final product. Currently, chromatographic processes in biopharmaceutical production are predominantly monitored with UV/Vis absorbance and a direct correlation with purity and quantity is limited. Read More

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http://dx.doi.org/10.1002/bit.26984DOI Listing

Effect of gene copy number and chaperone coexpression on recombinant hydrophobin HFBI biosurfactant production in Pichia pastoris.

Biotechnol Bioeng 2019 Apr 1. Epub 2019 Apr 1.

Department of Biomedical Engineering, University of Virginia, Thornton Hall, Charlottesville, Virginia.

Hydrophobins are small highly surface-active fungal proteins with potential as biosurfactants in a wide array of applications. However, practical implementation of hydrophobins at large scale has been hindered by low recombinant yields. In this study, the effects of increasing hydrophobin gene copy number and overexpressing endoplasmic reticulum resident chaperone proteins Kar2p, Pdi1p, and Ero1p were explored as a means to enhance recombinant yields of the class II hydrophobin HFBI in the eukaryotic expression host Pichia pastoris. Read More

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http://dx.doi.org/10.1002/bit.26982DOI Listing
April 2019
2 Reads
4.126 Impact Factor

Reduction of measurement noise in a continuous glucose monitor by coating the sensor with a zwitterionic polymer.

Nat Biomed Eng 2018 Dec 30;2(12):894-906. Epub 2018 Jul 30.

David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, 500 Main Street, Cambridge, MA, 02139, USA.

Continuous glucose monitors (CGMs), used by patients with diabetes mellitus, can autonomously track fluctuations in blood glucose over time. However, the signal produced by CGMs during the initial recording period following sensor implantation contains substantial noise, requiring frequent recalibration via fingerprick tests. Here, we show that coating the sensor with a zwitterionic polymer, found via a combinatorial-chemistry approach, significantly reduces signal noise and improves CGM performance. Read More

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http://dx.doi.org/10.1038/s41551-018-0273-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6436621PMC
December 2018
1 Read

Genetic and chemical approaches for surface charge engineering of enzymes and their applicability in biocatalysis: A review.

Biotechnol Bioeng 2019 Mar 30. Epub 2019 Mar 30.

Teknologisk institut, Kongsvang Allé 29, Aarhus, DK.

Surface charge engineering has received considerable interest from the scientific and industrial community the last decades. Although it was previously hypothesized that the surface charge-charge interactions were not a fundamental force to determine protein folding and stability, many studies today show that surface charge plays a key role determining protein structure and activity. This review aims to i) highlight the value of surface charged engineering of proteins to improve enzyme stability and activity in aqueous media and in the presence of ionic liquids, and organic solvents, ii) describe the existing approaches (genetic engineering or chemical modifications) for surface charged engineering, and iii) demonstrate the applicability of these surface charged enzymes in biocatalysis. Read More

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http://dx.doi.org/10.1002/bit.26979DOI Listing

Inhibition of Oncogenic Kinases: An In Vitro Validated Computational Approach Identified Potential Multi-Target Anticancer Compounds.

Biomolecules 2019 03 28;9(4). Epub 2019 Mar 28.

Institute of Pharmaceutical Sciences, Riphah University, 54000 Lahore, Pakistan.

Tumorigenesis in humans is a multistep progression that imitates genetic changes leading to cell transformation and malignancy. Oncogenic kinases play a central role in cancer progression, rendering them putative targets for the design of anti-cancer drugs. The presented work aims to identify the potential multi-target inhibitors of oncogenic receptor tyrosine kinases (RTKs) and serine/threonine kinases (STKs). Read More

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http://dx.doi.org/10.3390/biom9040124DOI Listing

Development of Chemical Tools to Monitor Human Kallikrein 13 (KLK13) Activity.

Int J Mol Sci 2019 Mar 28;20(7). Epub 2019 Mar 28.

Faculty of Chemistry, University of Gdansk, 80-308 Gdansk, Poland.

Kallikrein 13 (KLK13) was first identified as an enzyme that is downregulated in a subset of breast tumors. This serine protease has since been implicated in a number of pathological processes including ovarian, lung and gastric cancers. Here we report the design, synthesis and deconvolution of libraries of internally quenched fluorogenic peptide substrates to determine the specificity of substrate binding subsites of KLK13 in prime and non-prime regions (according to the Schechter and Berger convention). Read More

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http://dx.doi.org/10.3390/ijms20071557DOI Listing
March 2019
4 Reads
2.862 Impact Factor

Functionalized graphene oxide as a nanocarrier for dual drug delivery applications: The synergistic effect of quercetin and gefitinib against ovarian cancer cells.

Colloids Surf B Biointerfaces 2019 Mar 18;178:452-459. Epub 2019 Mar 18.

Nanoscience and Nanotechnology Centre, Department of Chemistry, D.S.B. Campus, Kumaun University, Nainital, Uttarakhand, India. Electronic address:

Graphene Oxide (GO) has been extensively studied in the field of biomedical sciences as one of the most promising biomaterials due to its exceptional physiochemical properties. Experts have long favored anticancer drug cocktails over single drugs, given that the former may provide a more balanced molecular basis for novel chemotherapeutic strategies. Here, we investigated a combinatorial anticancer drug treatment involving the well-proven anticancer drugs quercetin and gefitinib and compared it with gefitinib and quercetin loaded separately onto polyvinylpyrrolidone (PVP)-functionalized graphene oxide (GO-PVP). Read More

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http://dx.doi.org/10.1016/j.colsurfb.2019.03.037DOI Listing
March 2019
1 Read

[Baeyer-Villiger monooxygenases in the biosynthesis of microbial secondary metabolites].

Sheng Wu Gong Cheng Xue Bao 2019 Mar;35(3):351-362

Key Laboratory of Combinatorial Biosynthesis and Drug Discovery, Ministry of Education, School of Pharmaceutical Sciences, Wuhan University, Wuhan 430071, Hubei, China.

Baeyer-Villiger monooxygenases, a well-studied class of flavin-dependent enzymes, catalyze the conversion of ketones to lactones or esters and the oxygenation of heteroatoms, which possesses great practical prospect in synthetic chemistry and biocatalysis. In this review, we focus on Baeyer-Villiger oxidations involved in biosynthesis of microbial secondary metabolites and discuss the characteristics of these Baeyer-Villiger oxidations and Baeyer-Villiger monooxygenases, to provide reference for the protein engineering of Baeyer-Villiger monooxygenases. Read More

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http://dx.doi.org/10.13345/j.cjb.180294DOI Listing
March 2019
1 Read

Quantitative Characterization of the Regulation of Iron Metabolism in Glioblastoma Stem-Like Cells using Magnetophoresis.

Biotechnol Bioeng 2019 Mar 24. Epub 2019 Mar 24.

William G. Lowrie Department of Chemical and Biomolecular Engineering, The Ohio State University, 470 CBEC 151 West Woodruff Avenue, Columbus, OH.

This study focuses on different iron regulation mechanisms of glioblastoma (GBM) cancer stem-like cells (CSCs) and non-stem tumor cells (NSTCs) using multiple approaches: cell viability, density and magnetophoresis. GBM CSCs and NSTCs were exposed to elevated iron concentration, and their magnetic susceptibility was measured using Single Cell Magnetophoresis (SCM), which tracks the magnetic and settling velocities of thousands of individual cells passing through the magnetic field with a constant energy gradient. Our results consistently demonstrate that GBM NSTCs have higher magnetic susceptibility distribution at increased iron concentration compared to CSCs, and we speculate that it is because CSCs have the ability to store a high amount of iron in ferritin, whereas the free iron ions inside the NSTCs lead to higher magnetic susceptibility and reduced cell viability and growth. Read More

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http://dx.doi.org/10.1002/bit.26973DOI Listing

Direct capture and conversion of CO from air by growing a cyanobacterial consortium at pH up to 11.2.

Biotechnol Bioeng 2019 Mar 24. Epub 2019 Mar 24.

Department of Geoscience, University of Calgary, Calgary, Alberta, Canada.

Bioenergy with carbon capture and storage (BECCS) is recognized as a potential negative emission technology, needed to keep global warming within safe limits. With current technologies, large-scale implementation of BECCS would compromise food production. Bioenergy derived from phototrophic microorganisms, with direct capture of CO from air, could overcome this challenge and become a sustainable way to realize BECCS. Read More

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http://dx.doi.org/10.1002/bit.26974DOI Listing

Growth factor sustained delivery from poly-lactic-co-glycolic acid microcarriers and its mass transfer modeling by finite element in a dynamic and static three-dimensional environment bioengineered with stem cells.

Biotechnol Bioeng 2019 Mar 24. Epub 2019 Mar 24.

Department of Industrial Engineering, University of Salerno, Fisciano, SA, Italy.

Poly-lactic-co-glycolic acid (PLGA) microcarriers (0.8 ± 0.2 μm) have been fabricated with a load of 20 μg/g by an emulsion-based-proprietary technology to sustained deliver human bone morphogenetic protein 2 (hBMP2), a growth factor largely used for osteogenic induction. Read More

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http://dx.doi.org/10.1002/bit.26975DOI Listing

Synthesis of polyketides from low cost substrates by the thermotolerant yeast Kluyveromyces marxianus.

Biotechnol Bioeng 2019 Mar 24. Epub 2019 Mar 24.

Department of Chemical and Biomolecular Engineering, University of California, Irvine, CA, USA.

Kluyveromyces marxianus is a promising nonconventional yeast for biobased chemical production due to its rapid growth rate, high TCA cycle flux, and tolerance to low pH and high temperature. Unlike S. cerevisiae, K. Read More

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https://onlinelibrary.wiley.com/doi/abs/10.1002/bit.26976
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http://dx.doi.org/10.1002/bit.26976DOI Listing
March 2019
3 Reads

Identification of Bis-Cyclic Guanidines as Antiplasmodial Compounds from Positional Scanning Mixture-Based Libraries.

Molecules 2019 Mar 20;24(6). Epub 2019 Mar 20.

Torrey Pines Institute for Molecular Studies, 11350 SW Village Parkway, Port Saint Lucie, FL 34987, USA.

The screening of more than 30 million compounds derived from 81 small molecule libraries built on 81 distinct scaffolds identified pyrrolidine bis-cyclic guanidine library (TPI-1955) to be one of the most active and selective antiplasmodial libraries. The screening of the positional scanning library TPI-1955 arranged on four sets of sublibraries (26 + 26 + 26 + 40), totaling 120 samples for testing provided information about the most important groups of each variable position in the TPI-1955 library containing 738,192 unique compounds. The parallel synthesis of the individual compounds derived from the deconvolution of the positional scanning library led to the identification of active selective antiplasmodial pyrrolidine bis-cyclic guanidines. Read More

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http://dx.doi.org/10.3390/molecules24061100DOI Listing