145,358 results match your criteria Chemical biology & drug design[Journal]


Pre-treatment with D942, a furancarboxylic acid derivative, increases desiccation tolerance in an anhydrobiotic tardigrade Hypsibius exemplaris.

FEBS Open Bio 2020 Jul 4. Epub 2020 Jul 4.

Institute for Advanced Biosciences, Keio University, 997-0052, Tsuruoka, Yamagata, Japan.

The tardigrade Hypsibius exemplaris can undergo anhydrobiosis. Several chemicals that inhibit successful anhydrobiosis in H. exemplaris have been identified, and these chemicals inhibit the activity of signaling molecules. Read More

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http://dx.doi.org/10.1002/2211-5463.12926DOI Listing

Gestational bisphenol A exposure induces fatty liver development in male offspring mice through the inhibition of HNF1b and upregulation of PPARγ.

Cell Biol Toxicol 2020 Jul 4. Epub 2020 Jul 4.

Department of Toxicology, Shaanxi Key Lab of Free Radical Biology and Medicine, the Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, School of Public Health, Air Force Medical University (Fourth Military Medical University), Changle West Road 169, Xi'an, 710032, Shaanxi Province, China.

Bisphenol A (BPA) is an endocrine-disrupting chemical (EDC) associated with non-alcoholic fatty liver disease (NAFLD). The effects of gestational BPA exposure on hepatic lipid accumulation in offspring are not fully understood. Here, we investigate the sex-dependent effects of gestational BPA exposure on hepatic lipid and glucose metabolism in the offspring of mice to reveal the mechanisms underlying gestational BPA exposure-associated NAFLD. Read More

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http://dx.doi.org/10.1007/s10565-020-09535-3DOI Listing

Functional wastepaper-montmorillonite composite aerogel for Cd adsorption.

Environ Sci Pollut Res Int 2020 Jul 5. Epub 2020 Jul 5.

College of Environmental Science and Engineering, Hunan University, Changsha, 410082, China.

In this study, a composite aerogel (WP-MMT) composed of wastepaper (WP) and montmorillonite (MMT) was prepared by ambient pressure drying technology to adsorb Cd. The study of compression performance indicated that the composite aerogel had ideal mechanical strength when the mass ratio of WP to MMT was 1:1. The specific surface areas of the aerogels modified by hydrogen peroxide (WP-MMT-HO) and sodium hydroxide (WP-MMT-NaOH) were increased greatly. Read More

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http://dx.doi.org/10.1007/s11356-020-09907-6DOI Listing

Synthetic biology, systems biology, and metabolic engineering of Yarrowia lipolytica toward a sustainable biorefinery platform.

J Ind Microbiol Biotechnol 2020 Jul 4. Epub 2020 Jul 4.

Department of Chemical, Biochemical and Environmental Engineering, University of Maryland, Baltimore County, Baltimore, MD, 21250, USA.

Yarrowia lipolytica is an oleaginous yeast that has been substantially engineered for production of oleochemicals and drop-in transportation fuels. The unique acetyl-CoA/malonyl-CoA supply mode along with the versatile carbon-utilization pathways makes this yeast a superior host to upgrade low-value carbons into high-value secondary metabolites and fatty acid-based chemicals. The expanded synthetic biology toolkits enabled us to explore a large portfolio of specialized metabolism beyond fatty acids and lipid-based chemicals. Read More

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http://dx.doi.org/10.1007/s10295-020-02290-8DOI Listing

Extrahepatic metabolism of ibrutinib.

Invest New Drugs 2020 Jul 4. Epub 2020 Jul 4.

Division of Pharmacoepidemiology & Clinical Pharmacology, Faculty of Science, Department of Pharmaceutical Sciences, Utrecht University, Universiteitsweg 99, 3584 CG, Utrecht, The Netherlands.

Ibrutinib is a first-in-class Bruton's kinase inhibitor used in the treatment of multiple lymphomas. In addition to CYP3A4-mediated metabolism, glutathione conjugation can be observed. Subsequently, metabolism of the conjugates and finally their excretion in feces and urine occurs. Read More

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http://dx.doi.org/10.1007/s10637-020-00970-xDOI Listing

Protein structure analysis of the interactions between SARS-CoV-2 spike protein and the human ACE2 receptor: from conformational changes to novel neutralizing antibodies.

Cell Mol Life Sci 2020 Jul 4. Epub 2020 Jul 4.

Laboratory of Biochemistry, Molecular and Structural Biology, Department of Biosciences, Biotechnologies, Biopharmaceutics, University of Bari, Via E. Orabona, 4, 70125, Bari, Italy.

The recent severe acute respiratory syndrome, known as Coronavirus Disease 2019 (COVID-19) has spread so much rapidly and severely to induce World Health Organization (WHO) to declare a state of emergency over the new coronavirus SARS-CoV-2 pandemic. While several countries have chosen the almost complete lock-down for slowing down SARS-CoV-2 spread, the scientific community is called to respond to the devastating outbreak by identifying new tools for diagnosis and treatment of the dangerous COVID-19. With this aim, we performed an in silico comparative modeling analysis, which allows gaining new insights into the main conformational changes occurring in the SARS-CoV-2 spike protein, at the level of the receptor-binding domain (RBD), along interactions with human cells angiotensin-converting enzyme 2 (ACE2) receptor, that favor human cell invasion. Read More

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http://dx.doi.org/10.1007/s00018-020-03580-1DOI Listing

Interaction of RSC Chromatin Remodeling Complex with Nucleosomes Is Modulated by H3 K14 Acetylation and H2B SUMOylation In Vivo.

iScience 2020 Jun 20;23(7):101292. Epub 2020 Jun 20.

Department of Structural Biochemistry, Max-Planck-Institute of Molecular Physiology, Otto-Hahn-Strasse 11, 44227 Dortmund, Germany; Department of Chemical Engineering and Biotechnology, University of Applied Sciences Darmstadt, Stephanstrasse 7, 64295 Darmstadt, Germany. Electronic address:

Chromatin remodeling complexes are multi-subunit nucleosome translocases that reorganize chromatin in the context of DNA replication, repair, and transcription. To understand how these complexes find their target sites on chromatin, we use genetically encoded photo-cross-linker amino acids to map the footprint of Sth1, the catalytic subunit of the RSC complex, on nucleosomes in living yeast. We find that H3 K14 acetylation induces the interaction of the Sth1 bromodomain with the H3 tail and mediates the interaction of RSC with neighboring nucleosomes rather than recruiting it to chromatin. Read More

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http://dx.doi.org/10.1016/j.isci.2020.101292DOI Listing

Multi-mode fluorescence sensing detection based on one core-shell structure quantum dots via different types of mechanisms.

Spectrochim Acta A Mol Biomol Spectrosc 2020 Jun 19;241:118630. Epub 2020 Jun 19.

Research Center for Analytical Science, State Key Laboratory of Medicinal Chemical Biology and Tianjin Key Laboratory of Biosensing and Molecular Recognition, College of Chemistry, Nankai University, Tianjin 300071, China.

Multi-target sensing completed with single chemosensor is cost-effective and pretty attractive for the analysis of multiple analytes in single sample. CdTe/CdS QDs show high fluorescence quantum yield as a probe for the sensing purpose, but only single target is often detected. Here we proposed that three kinds of different response mechanisms were realized using CdTe/CdS QDs with the simultaneous sensing of Fe, CrO, and IO as model. Read More

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http://dx.doi.org/10.1016/j.saa.2020.118630DOI Listing

Toxicological assessment of seven unregulated drinking water Disinfection By-products (DBPs) using the zebrafish embryo bioassay.

Sci Total Environ 2020 Jun 25;742:140522. Epub 2020 Jun 25.

CIMAR/CIIMAR, LA- Interdisciplinary Centre of Marine and Environmental Research, University of Porto, Matosinhos, Portugal; FCUP - Department of Biology, Faculty of Sciences, University of Porto, Porto, Portugal. Electronic address:

Disinfection By-products (DBPs) are formed during the chemical treatment of water for human consumption, by the reaction of raw water with chemical agents used in the different steps of the process. Disinfection is one of the most important steps, inactivating pathogens and preventing their regrowth during water distribution. However, it is also involved in DBPs formation due to the use of disinfectant agents, such as chlorine, which reacts with dissolved precursors, such as pharmaceuticals, toxins, pesticides, among others. Read More

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http://dx.doi.org/10.1016/j.scitotenv.2020.140522DOI Listing

Pyruvate metabolism redirection for biological production of commodity chemicals in aerobic fungus Aspergillus oryzae.

Metab Eng 2020 Jul 2. Epub 2020 Jul 2.

Graduate School of Science, Technology, and Innovation, Kobe University, 1-1 Rokkodai-cho, Nada-ku, Kobe, Hyogo, 657-8501, Japan; Engineering Biology Research Center, Kobe University, 1-1 Rokkodai, Nada, Kobe, 657-8501, Japan; Biomass Engineering Program, RIKEN, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa, 230-0045, Japan. Electronic address:

Pyruvate is a central metabolite for the biological production of various chemicals. In eukaryotes, pyruvate produced by glycolysis is used in conversion to ethanol and lactate and in anabolic metabolism in the cytosol, or is transported into the mitochondria for use as a substrate in the tricarboxylic acid (TCA) cycle. In this study, we focused on controlling pyruvate metabolism in aerobic microorganisms for the biological production of various chemicals. Read More

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http://dx.doi.org/10.1016/j.ymben.2020.06.010DOI Listing

Structural and chemical changes in glial cells in the rat neocortex induced by constant occlusion of the middle cerebral artery.

Acta Histochem 2020 Jul 13;122(5):151573. Epub 2020 Jun 13.

Laboratory of Physiology, A.V. Zhirmunsky National Scientific Center of Marine Biology, Far Eastern Branch, Russian Academy of Sciences, Vladivostok 690041, Russia. Electronic address:

Stroke-induced changes in neuroglia determine the basic conditions for the survival and damage of neurons in the ischemic core. Here, we studied the immunolocalization of glial cell line-derived neurotrophic factor (GDNF), glial fibrillary acidic protein (GFAP), ionized calcium-binding adaptor molecule 1 (Iba-1), and S-100β in the rat parietal cortex after constant occlusion of the middle cerebral artery. These cytoplasmic proteins are specific for different glial cell types. Read More

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http://dx.doi.org/10.1016/j.acthis.2020.151573DOI Listing

Keratinophilic fungi: Specialized fungal communities in a desert ecosystem identified using cultured-based and Illumina sequencing approaches.

Microbiol Res 2020 Jun 20;239:126530. Epub 2020 Jun 20.

Western Illinois University, Biological Sciences, Macomb, IL, 61455, USA. Electronic address:

Soil fungi in desert ecosystems are adapted to harsh environmental conditions such as high soil surface temperatures and limited organic matter and water. Given limited carbon inputs from plant material, heterotrophic fungi likely use unconventional sources of carbon in these systems. A baiting method was used to culture keratinophilic fungi from biocrust and rhizosphere soils in an arid grassland in Utah, USA. Read More

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http://dx.doi.org/10.1016/j.micres.2020.126530DOI Listing

Lipid nanoparticle technology for therapeutic gene regulation in the liver.

Adv Drug Deliv Rev 2020 Jul 1. Epub 2020 Jul 1.

Laboratory of Chemical Biology, Department of Biomedical Engineering and Institute for Complex Molecular Systems, Eindhoven University of Technology, Eindhoven, The Netherlands.

Hereditary genetic disorders, cancer, and infectious diseases of the liver affect millions of people around the globe and are a major public health burden. Most contemporary treatments offer limited relief as they generally aim to alleviate disease symptoms. Targeting the root cause of diseases originating in the liver by regulating malfunctioning genes with nucleic acid-based drugs s holds great promise as a therapeutic approach. Read More

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http://dx.doi.org/10.1016/j.addr.2020.06.026DOI Listing

Improvising anti-leishmanial activity of Amphotericin B and Paromomycin using co-delivery in D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) tailored Nano-lipid carrier system.

Chem Phys Lipids 2020 Jul 1:104946. Epub 2020 Jul 1.

Infectious Disease Research Laboratory, Department of Medicine, Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh 221005, India. Electronic address:

In the current study, we have focused on the design, development and in-vitro evaluation of D-α-tocopheryl polyethylene glycol 1000 succinate modified amphotericin B (AmB) and paromomycin (PM) loaded solid lipid nanoparticles (TPGS-SLNPs) by emulsion-solvent evaporation method. The optimized TPGS-SLNPs had a mean particle size of 199.4 ± 18. Read More

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http://dx.doi.org/10.1016/j.chemphyslip.2020.104946DOI Listing

Morphological Evidence for an Oral Venom System in Caecilian Amphibians.

iScience 2020 Jun 19:101234. Epub 2020 Jun 19.

Structural Biology Lab, Butantan Institute, São Paulo, Brazil. Electronic address:

Amphibians are known for their skin rich in glands containing toxins employed in passive chemical defense against predators, different from, for example, snakes that have active chemical defense, injecting their venom into the prey. Caecilians (Amphibia, Gymnophiona) are snake-shaped animals with fossorial habits, considered one of the least known vertebrate groups. We show here that amphibian caecilians, including species from the basal groups, besides having cutaneous poisonous glands as other amphibians do, possess specific glands at the base of the teeth that produce enzymes commonly found in venoms. Read More

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http://dx.doi.org/10.1016/j.isci.2020.101234DOI Listing

Type V Collagen in Scar Tissue Regulates the Size of Scar after Heart Injury.

Cell 2020 Jul 2. Epub 2020 Jul 2.

Division of Cardiology, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA; UCLA Cardiovascular Theme, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA; Department of Molecular, Cell and Developmental Biology, College of Letters and Sciences, University of California, Los Angeles, CA 90095, USA; Eli & Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, CA 90095, USA; Molecular Biology Institute, University of California, Los Angeles, CA 90095, USA; California Nanosystems Institute, University of California, Los Angeles, CA 90095, USA. Electronic address:

Scar tissue size following myocardial infarction is an independent predictor of cardiovascular outcomes, yet little is known about factors regulating scar size. We demonstrate that collagen V, a minor constituent of heart scars, regulates the size of heart scars after ischemic injury. Depletion of collagen V led to a paradoxical increase in post-infarction scar size with worsening of heart function. Read More

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http://dx.doi.org/10.1016/j.cell.2020.06.030DOI Listing

A sequential methodology for the rapid identification and characterization of breast cancer-associated functional SNPs.

Nat Commun 2020 Jul 3;11(1):3340. Epub 2020 Jul 3.

Aging Institute, University of Pittsburgh, Pittsburgh, PA, 15219, USA.

GWAS cannot identify functional SNPs (fSNP) from disease-associated SNPs in linkage disequilibrium (LD). Here, we report developing three sequential methodologies including Reel-seq (Regulatory element-sequencing) to identify fSNPs in a high-throughput fashion, SDCP-MS (SNP-specific DNA competition pulldown-mass spectrometry) to identify fSNP-bound proteins and AIDP-Wb (allele-imbalanced DNA pulldown-Western blot) to detect allele-specific protein:fSNP binding. We first apply Reel-seq to screen a library containing 4316 breast cancer-associated SNPs and identify 521 candidate fSNPs. Read More

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http://dx.doi.org/10.1038/s41467-020-17159-8DOI Listing

Self-sustained planar intercalations due to mechanosignaling feedbacks lead to robust axis extension during morphogenesis.

Sci Rep 2020 Jul 3;10(1):10973. Epub 2020 Jul 3.

Chemical and Biomolecular Engineering Department, Lehigh University, Bethlehem, 18015, USA.

Tissue elongation is a necessary process in metazoans to implement their body plans that is not fully understood. Here we propose a mechanism based on the interplay between cellular mechanics and primordia patterning that results in self-sustained planar intercalations. Thus, we show that a location-dependent modulation of the mechanical properties of cells leads to robust axis extension. Read More

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http://dx.doi.org/10.1038/s41598-020-67413-8DOI Listing

Salmonella-based platform for efficient delivery of functional binding proteins to the cytosol.

Commun Biol 2020 Jul 3;3(1):342. Epub 2020 Jul 3.

IMBA, Institute of Molecular Biotechnology of the Austrian Academy of Sciences, Vienna, Austria.

Protein-based affinity reagents (like antibodies or alternative binding scaffolds) offer wide-ranging applications for basic research and therapeutic approaches. However, whereas small chemical molecules efficiently reach intracellular targets, the delivery of macromolecules into the cytosol of cells remains a major challenge; thus cytosolic applications of protein-based reagents are rather limited. Some pathogenic bacteria have evolved a conserved type III secretion system (T3SS) which allows the delivery of effector proteins into eukaryotic cells. Read More

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http://dx.doi.org/10.1038/s42003-020-1072-4DOI Listing

A Keplerian Ag nest of Platonic and Archimedean polyhedra in different symmetry groups.

Nat Commun 2020 Jul 3;11(1):3316. Epub 2020 Jul 3.

Key Laboratory of Colloid and Interface Chemistry, Ministry of Education, School of Chemistry and Chemical Engineering, State Key Laboratory of Crystal Materials, Shandong University, Ji'nan, 250100, People's Republic of China.

Polyhedra are ubiquitous in chemistry, biology, mathematics and other disciplines. Coordination-driven self-assembly has created molecules mimicking Platonic, Archimedean and even Goldberg polyhedra, however, nesting multiple polyhedra in one cluster is challenging, not only for synthesis but also for determining the alignment of the polyhedra. Here, we synthesize a nested Ag nanocluster under solvothermal condition. Read More

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http://dx.doi.org/10.1038/s41467-020-17198-1DOI Listing

Wnt-controlled sphingolipids modulate Anthrax Toxin Receptor palmitoylation to regulate oriented mitosis in zebrafish.

Nat Commun 2020 Jul 3;11(1):3317. Epub 2020 Jul 3.

Department of Biochemistry and NCCR Chemical Biology, 30 Quai Ernest-Ansermet, 1211, Geneva 4, Switzerland.

Oriented cell division is a fundamental mechanism to control asymmetric stem cell division, neural tube elongation and body axis extension, among other processes. During zebrafish gastrulation, when the body axis extends, dorsal epiblast cells display divisions that are robustly oriented along the animal-vegetal embryonic axis. Here, we use a combination of lipidomics, metabolic tracer analysis and quantitative image analysis to show that sphingolipids mediate spindle positioning during oriented division of epiblast cells. Read More

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http://dx.doi.org/10.1038/s41467-020-17196-3DOI Listing

π covalency in the halogen bond.

Nat Commun 2020 Jul 3;11(1):3310. Epub 2020 Jul 3.

Department of Chemistry, The University of British Columbia, 2036 Main Mall, Vancouver, BC, V6T 1Z1, Canada.

Halogen bonds are a highly directional class of intermolecular interactions widely employed in chemistry and chemical biology. This linear interaction is commonly viewed to be analogous to the hydrogen bond because hydrogen bonding models also intuitively describe the σ-symmetric component of halogen bonding. The possibility of π-covalency in a halogen bond is not contemplated in any known models. Read More

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http://dx.doi.org/10.1038/s41467-020-17122-7DOI Listing

Rational flux-tuning of Halomonas bluephagenesis for co-production of bioplastic PHB and ectoine.

Nat Commun 2020 Jul 3;11(1):3313. Epub 2020 Jul 3.

Center for Synthetic and Systems Biology, School of Life Sciences, Tsinghua University, Beijing, 100084, China.

Ectoine, a compatible solute synthesized by many halophiles for hypersalinity resistance, has been successfully produced by metabolically engineered Halomonas bluephagenesis, which is a bioplastic poly(3-hydroxybutyrate) producer allowing open unsterile and continuous conditions. Here we report a de novo synthesis pathway for ectoine constructed into the chromosome of H. bluephagenesis utilizing two inducible systems, which serve to fine-tune the transcription levels of three clusters related to ectoine synthesis, including ectABC, lysC and asd based on a GFP-mediated transcriptional tuning approach. Read More

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http://dx.doi.org/10.1038/s41467-020-17223-3DOI Listing

A yeast platform for high-level synthesis of tetrahydroisoquinoline alkaloids.

Nat Commun 2020 Jul 3;11(1):3337. Epub 2020 Jul 3.

Department of Biology, Concordia University, Montréal, QC, Canada.

The tetrahydroisoquinoline (THIQ) moiety is a privileged substructure of many bioactive natural products and semi-synthetic analogs. Plants manufacture more than 3,000 THIQ alkaloids, including the opioids morphine and codeine. While microbial species have been engineered to synthesize a few compounds from the benzylisoquinoline alkaloid (BIA) family of THIQs, low product titers impede industrial viability and limit access to the full chemical space. Read More

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http://dx.doi.org/10.1038/s41467-020-17172-xDOI Listing

Diamond Blackfan anemia is mediated by hyperactive Nemo-like kinase.

Nat Commun 2020 Jul 3;11(1):3344. Epub 2020 Jul 3.

Division of Hematology/Oncology, Department of Pediatrics, Stanford University, Stanford, CA, 94305, USA.

Diamond Blackfan Anemia (DBA) is a congenital bone marrow failure syndrome associated with ribosomal gene mutations that lead to ribosomal insufficiency. DBA is characterized by anemia, congenital anomalies, and cancer predisposition. Treatment for DBA is associated with significant morbidity. Read More

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http://dx.doi.org/10.1038/s41467-020-17100-zDOI Listing

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Mol Pharmacol 2020 Jul 3. Epub 2020 Jul 3.

Pharmacology and Chemical Biology, Emory University, United States

Human cytochrome P450 (P450) CYP2B6 undergoes nitric oxide (NO)-dependent proteasomal degradation in response to the NO donor dipropylenetriamine NONOate (DPTA) and biological NO in HeLa and HuH7 cell lines. CYP2B6 is also down-regulated by NO in primary human hepatocytes. We hypothesized that NO or derivative reactive nitrogen species may generate adducts of tyrosine and/or cysteine residues, causing CYP2B6 down-regulation, and selected Tyr and Cys residues for mutation based on predicted solvent accessibility. Read More

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http://dx.doi.org/10.1124/molpharm.120.000020DOI Listing

Human antibodies neutralize enterovirus D68 and protect against infection and paralytic disease.

Sci Immunol 2020 Jul;5(49)

Department of Pediatrics (Infectious Diseases), Vanderbilt University Medical Center, Nashville, TN, USA.

Enterovirus D68 (EV-D68) causes outbreaks of respiratory illness, and there is increasing evidence that it causes outbreaks of acute flaccid myelitis (AFM). There are no licensed therapies to prevent or treat EV-D68 infection or AFM disease. We isolated a panel of EV-D68-reactive human monoclonal antibodies that recognize diverse antigenic variants from participants with prior infection. Read More

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http://dx.doi.org/10.1126/sciimmunol.aba4902DOI Listing

Retraction notice to "Direct and simultaneous detection of organic and inorganic ingredients in herbal powder preparations by Fourier transform infrared microspectroscopic imaging" [SAA (2016) 176-182].

Spectrochim Acta A Mol Biomol Spectrosc 2020 Jun 30:118605. Epub 2020 Jun 30.

Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology (Ministry of Education), Department of Chemistry, Tsinghua University, Beijing 100084, China.

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http://dx.doi.org/10.1016/j.saa.2020.118605DOI Listing

New Twists in Detecting mRNA Modification Dynamics.

Trends Biotechnol 2020 Jun 30. Epub 2020 Jun 30.

School of Biosciences, College of Life and Environmental Sciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK. Electronic address:

Modified nucleotides in mRNA are an essential addition to the standard genetic code of four nucleotides in animals, plants, and their viruses. The emerging field of epitranscriptomics examines nucleotide modifications in mRNA and their impact on gene expression. The low abundance of nucleotide modifications and technical limitations, however, have hampered systematic analysis of their occurrence and functions. Read More

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http://dx.doi.org/10.1016/j.tibtech.2020.06.002DOI Listing

Red beet (Beta vulgaris) and amaranth (Amaranthus sp.) microgreens: Effect of storage and in vitro gastrointestinal digestion on the untargeted metabolomic profile.

Food Chem 2020 Jun 27;332:127415. Epub 2020 Jun 27.

Department of Food Engineering, Faculty of Chemical and Metallurgical Engineering, Istanbul Technical University, 34469 Maslak, Istanbul, Turkey.

This study aimed to investigate the combined effect of storage at 4 °C (10-days) and in vitro gastrointestinal digestion on the phytochemical profile of red beet (Beta vulgaris) and amaranth (Amaranthus sp.) microgreens. The untargeted profiling based on UHPLC-QTOF metabolomics allowed annotating 316 compounds, comprising mainly polyphenols and lipids. Read More

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http://dx.doi.org/10.1016/j.foodchem.2020.127415DOI Listing

What is new in the exposome?

Environ Int 2020 Jun 30;143:105887. Epub 2020 Jun 30.

MRC Centre for Environment and Health, School of Public Health, Imperial College London, Norfolk Place, W2 1PG London, UK.

The exposome concept refers to the totality of exposures from a variety of external and internal sources including chemical agents, biological agents, or radiation, from conception onward, over a complete lifetime. It encompasses also "psychosocial components" including the impact of social relations and socio-economic position on health. In this review we provide examples of recent contributions from exposome research, where we believe their application will be of the greatest value for moving forward. Read More

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http://dx.doi.org/10.1016/j.envint.2020.105887DOI Listing

Early-stage dysfunction of hippocampal theta and gamma oscillations and its modulation of neural network in a transgenic 5xFAD mouse model.

Neurobiol Aging 2020 May 12;94:121-129. Epub 2020 May 12.

College of Life Sciences, Key Laboratory of Bioactive Materials, Ministry of Education, Nankai University, Tianjin, PR China. Electronic address:

Alzheimer's disease (AD) is pathologically characterized by amyloid-β (Aβ) accumulation, which induces Aβ-dependent neuronal dysfunctions. We focused on the early-stage disease progression and examined the neuronal network functioning in the 5xFAD mice. The simultaneous intracranial recordings were obtained from the hippocampal perforant path (PP) and the dentate gyrus (DG). Read More

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http://dx.doi.org/10.1016/j.neurobiolaging.2020.05.002DOI Listing

Advances of epigenetic editing.

Curr Opin Chem Biol 2020 Jun 29;57:75-81. Epub 2020 Jun 29.

Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands. Electronic address:

Epigenetic editing refers to the locus-specific targeting of epigenetic enzymes to rewrite the local epigenetic landscape of an endogenous genomic site, often with the aim of transcriptional reprogramming. Implementing clustered regularly interspaced short palindromic repeat-dCas9 greatly accelerated the advancement of epigenetic editing, yielding preclinical therapeutic successes using a variety of epigenetic enzymes. ,CRISPR/dCas9 Here, were review the current applications of these epigenetic editing tools in mammalians and shed light on biochemical improvements that facilitate versatile applications. Read More

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http://dx.doi.org/10.1016/j.cbpa.2020.04.020DOI Listing

Sensitive detection of iron (II) sulfate with a novel reagent using spectrophotometry.

Spectrochim Acta A Mol Biomol Spectrosc 2020 Jun 20;240:118631. Epub 2020 Jun 20.

Istanbul Protein Research Application and Inovation Center (PROMER), Turkey; Department of Molecular Biology and Genetics, Uskudar University, 34662 Uskudar, Istanbul, Turkey. Electronic address:

In this study, a novel reagent was developed for sensitive detection of iron (II) sulfate, spectrophotometrically. A novel thio-anthraquinone derivative, 1-(Dodecylthio)anthracene-9,10-dione (3), was synthesized from the chemical reaction of 1-Chloroanthraquinone (1) and 1-Dodecanethiol (2) by an original reaction method and was used in the preparation of the novel reagent called Catal's reagent. A synthesized thio-anthraquinone analogue (3) was purified by column chromatography, and its chemical structure was characterized by spectroscopic methods such as Fourier-transform infrared spectroscopy (FT-IR), nuclear magnetic resonance (NMR) spectroscopy, mass spectrometry (MS), and ultraviolet (UV)-visible spectrophotometry. Read More

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http://dx.doi.org/10.1016/j.saa.2020.118631DOI Listing

Biosynthesis and tissue-specific partitioning of camphor and eugenol in Ocimum kilimandscharicum.

Phytochemistry 2020 Jun 30;177:112451. Epub 2020 Jun 30.

Division of Biochemical Sciences, CSIR-National Chemical Laboratory, Pune, 411008, Maharashtra, India. Electronic address:

In Ocimum kilimandscharicum, the relative volatile composition of camphor in leaves was as high as 55%, while that of eugenol in roots was 57%. These metabolites were differentially partitioned between the aerial and root tissues. Global metabolomics revealed tissue-specific biochemical specialization, evident by the differential distribution of 2588 putative metabolites across nine tissues. Read More

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http://dx.doi.org/10.1016/j.phytochem.2020.112451DOI Listing

Early Neutrophil Responses to Chemical Carcinogenesis Shape Long-Term Lung Cancer Susceptibility.

iScience 2020 Jun 17;23(7):101277. Epub 2020 Jun 17.

Tumour Host Interaction Laboratory, The Francis Crick Institute, 1 Midland Road, NW1 1AT London, UK. Electronic address:

Neoplastic transformation causing cancer is a key problem in tumor biology and can be triggered by exposure to environmental substances. We investigated whether the cellular composition of a tissue contributes to its predisposition to cancer upon a specific carcinogen. Neutrophils are important immune components involved in cancer progression, but their contribution to generation of transformed cells is elusive. Read More

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http://dx.doi.org/10.1016/j.isci.2020.101277DOI Listing

Agrochemicals and obesity.

Mol Cell Endocrinol 2020 Jun 30:110926. Epub 2020 Jun 30.

Department of Developmental and Cell Biology, University of California, Irvine, CA, 92697-2300, USA; Department of Pharmaceutical Sciences, University of California, Irvine, CA, USA; Department of Biomedical Engineering, University of California, Irvine, CA, USA. Electronic address:

Obesity has become a very large concern worldwide, reaching pandemic proportions over the past several decades. Lifestyle factors, such as excess caloric intake and decreased physical activity, together with genetic predispositions, are well-known factors related to obesity. There is accumulating evidence suggesting that exposure to some environmental chemicals during critical windows of development may contribute to the rapid increase in the incidence of obesity. Read More

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http://dx.doi.org/10.1016/j.mce.2020.110926DOI Listing

Adolescent oxytocin treatment affects resident behavior in aggressive but not tame adult rats.

Physiol Behav 2020 Jun 30:113046. Epub 2020 Jun 30.

Institute of Cytology and Genetics, Novosibirsk, Russia. Electronic address:

There are indications that exposing adolescent rodents to oxytocin (OT) promotes social activity and reduces anxiety in adulthood. Adult male gray rats selected for elimination and enhancement of the aggressive response to humans, when exposed to OT, showed divergent changes in the resident behavior towards the intruder. It could be assumed that adolescent administration of both OT and antagonist of OT receptor (OTR) would also have different long-term effects on resident behavior and startle reflex in adult aggressive and tame rats. Read More

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http://dx.doi.org/10.1016/j.physbeh.2020.113046DOI Listing

Phenformin promotes keratinocyte differentiation via the calcineurin/NFAT pathway.

J Invest Dermatol 2020 Jun 30. Epub 2020 Jun 30.

Department of Tissue Engineering and Regeneration, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration, Jinan, China; Cutaneous Biology Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts. Electronic address:

Phenformin is a drug in the biguanide class that was previously used to treat type 2 diabetes. We have reported the anti-tumor activities of phenformin to enhance the efficacy of BRAF-MEK-ERK pathway inhibition and to inhibit myeloid-derived suppressor cells in various melanoma models. Here we demonstrate that phenformin suppresses tumor growth and promotes keratinocyte differentiation in the DMBA/TPA two stage skin carcinogenesis mouse model. Read More

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http://dx.doi.org/10.1016/j.jid.2020.05.114DOI Listing

Thiosulfinate Tolerance Is a Virulence Strategy of an Atypical Bacterial Pathogen of Onion.

Curr Biol 2020 Jun 26. Epub 2020 Jun 26.

University of Georgia, Department of Plant Biology, Carleton St., Athens, GA 30602, USA; University of Georgia, The Plant Center, Carleton St., Athens, 30602, Athens, GA 30602, USA. Electronic address:

Unlike most characterized bacterial plant pathogens, the broad-host-range plant pathogen Pantoea ananatis lacks both the virulence-associated type III and type II secretion systems. In the absence of these typical pathogenicity factors, P. ananatis induces necrotic symptoms and extensive cell death in onion tissue dependent on the HiVir proposed secondary metabolite synthesis gene cluster. Read More

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http://dx.doi.org/10.1016/j.cub.2020.05.092DOI Listing

Pharmaceutical-Grade Rigosertib Is a Microtubule-Destabilizing Agent.

Mol Cell 2020 Jul;79(1):191-198.e3

Department of Cellular & Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94158, USA; Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, CA 94158, USA; Center for RNA Systems Biology, University of California, San Francisco, San Francisco, CA 94158, USA. Electronic address:

We recently used CRISPRi/a-based chemical-genetic screens and cell biological, biochemical, and structural assays to determine that rigosertib, an anti-cancer agent in phase III clinical trials, kills cancer cells by destabilizing microtubules. Reddy and co-workers (Baker et al., 2020, this issue of Molecular Cell) suggest that a contaminating degradation product in commercial formulations of rigosertib is responsible for the microtubule-destabilizing activity. Read More

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http://dx.doi.org/10.1016/j.molcel.2020.06.008DOI Listing

Differential distribution of characteristic constituents in root, stem and leaf tissues of Salvia miltiorrhiza using MALDI mass spectrometry imaging.

Fitoterapia 2020 Jun 30:104679. Epub 2020 Jun 30.

Natural Product Chemistry Department, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China. Electronic address:

Segmentation-quantification is the most commonly used method for studying the tissue distribution of bioactive constituents in plant, but this method would bring uncontrollable pollution, compound migration and denaturation. Mass spectrometry imaging (MSI), as a new method developed in the past 20 years, has high sensitivity, high spatial resolution, high degree of visualization, and low risk of contamination and degeneration when studying tissue distribution of compounds. For the first time we applied matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) to tissue distribution of characteristic constituents of the medicinal plant Salvia miltiorrhiza. Read More

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http://dx.doi.org/10.1016/j.fitote.2020.104679DOI Listing

A Systematic Analysis of Mosquito-Microbiome Biosynthetic Gene Clusters Reveals Antimalarial Siderophores that Reduce Mosquito Reproduction Capacity.

Cell Chem Biol 2020 Jun 29. Epub 2020 Jun 29.

Department of Chemistry, Duke University, Durham, NC, USA; Department of Molecular Genetics and Microbiology, Duke University, Durham, NC, USA. Electronic address:

Advances in infectious disease control strategies through genetic manipulation of insect microbiomes have heightened interest in microbially produced small molecules within mosquitoes. Herein, 33 mosquito-associated bacterial genomes were mined and over 700 putative biosynthetic gene clusters (BGCs) were identified, 135 of which belong to known classes of BGCs. After an in-depth analysis of the 135 BGCs, iron-binding siderophores were chosen for further investigation due to their high abundance and well-characterized bioactivities. Read More

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http://dx.doi.org/10.1016/j.chembiol.2020.06.004DOI Listing

Profiling Substrate Promiscuity of Wild-Type Sugar Kinases for Multi-fluorinated Monosaccharides.

Cell Chem Biol 2020 Jun 30. Epub 2020 Jun 30.

Department of Chemistry, University of York, Heslington, York YO10 5DD, UK. Electronic address:

Fluorinated sugar-1-phosphates are of emerging importance as intermediates in the chemical and biocatalytic synthesis of modified oligosaccharides, as well as probes for chemical biology. Here we present a systematic study of the activity of a wide range of anomeric sugar kinases (galacto- and N-acetylhexosamine kinases) against a panel of fluorinated monosaccharides, leading to the first examples of polyfluorinated substrates accepted by this class of enzymes. We have discovered four new N-acetylhexosamine kinases with a different substrate scope, thus expanding the number of homologs available in this subclass of kinases. Read More

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http://dx.doi.org/10.1016/j.chembiol.2020.06.005DOI Listing

Convergent Evolution in Breadth of Two V6-1-Encoded Influenza Antibody Clonotypes from a Single Donor.

Cell Host Microbe 2020 Jun 29. Epub 2020 Jun 29.

Department of Integrative Structural and Computational Biology, The Scripps Research Institute, San Diego, CA 92037, USA; The Skaggs Institute for Chemical Biology, The Scripps Research Institute, San Diego, CA 92037, USA. Electronic address:

Understanding how broadly neutralizing antibodies (bnAbs) to influenza hemagglutinin (HA) naturally develop in humans is critical to the design of universal influenza vaccines. Several classes of bnAbs directed to the conserved HA stem were found in multiple individuals, including one encoded by heavy-chain variable domain V6-1. We describe two genetically similar V6-1 bnAb clonotypes from the same individual that exhibit different developmental paths toward broad neutralization activity. Read More

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http://dx.doi.org/10.1016/j.chom.2020.06.003DOI Listing

Charge-Separated and Lewis Paired Metal-Organic Framework for Anion Exchange and CO2 Chemical Fixation.

Chemistry 2020 Jul 3. Epub 2020 Jul 3.

University of New Mexico, Department of Chemistry and Chemical Biology, MSC03 2060, 1 UNM, 87131, Albuquerque, UNITED STATES.

Charge-separated metal-organic frameworks (MOFs) are a unique class of MOFs that can possess added properties originating from the exposed ionic species. We report a new charge-separated MOF, namely UNM-6, synthesized from a tetrahedral borate ligand and Co 2+ cation. UNM-6 crystalizes into the highly symmetric P-43n space group with four-fold interpenetration, despite the stoichiometric imbalance between the B and Co atoms, which also leads to loosely bound NO 3 - anions within the crystal structure. Read More

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http://dx.doi.org/10.1002/chem.202002823DOI Listing

Release Mechanisms and Applications of Drug Delivery Systems for Extended-Release.

Expert Opin Drug Deliv 2020 Jul 3. Epub 2020 Jul 3.

Department of Industrial and Manufacturing Systems Engineering, Biomedical Engineering Programme, Chemical Biology Centre, and Li Ka Shing Faculty of Medicine, The University of Hong Kong , Pokfulam, HKSAR, China.

Introduction: Drug delivery systems with extended-release profiles are ideal in improving patient compliance with enhanced efficacy. To develop devices capable of a prolonged delivery kinetics, it is crucial to understand the various underlying mechanisms contributing to extended drug release and the impact thereof on modulating the long-term performance of such systems in a practical application environment.

Areas Covered: This review article intends to provide a comprehensive summary of release mechanisms in extended-release drug delivery systems, particularly polymer-based systems; however, other material types will also be mentioned. Read More

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http://dx.doi.org/10.1080/17425247.2020.1788541DOI Listing

A mesoporous encapsulated nanozyme for decontaminating two kinds of wastewater and avoiding secondary pollution.

Nanoscale 2020 Jul 3. Epub 2020 Jul 3.

Laboratory of Chemical Biology and State Key Laboratory of Rare Earth Resources Utilization, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, Jilin 130022, China.

Water pollution is becoming a major and serious issue all over the world. However, considering conventional methods for wastewater purification is chemically, energetically and technologically intensive, thus finding a reliable and energy-saving method is still a considerable conundrum. Herein, a mesoporous encapsulated dual-function complex nanozyme consisting of gold, platinum, and cobalt tri-metal is reported, and it not only shows high activity for water purification but also has outstanding resistance to the harsh conditions of the wastewater. Read More

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http://dx.doi.org/10.1039/d0nr03217dDOI Listing

Chemical and structural investigation of the paroxetine-human serotonin transporter complex.

Elife 2020 Jul 3;9. Epub 2020 Jul 3.

Vollum Institute, Oregon Health and Science University, Portland, United States.

Antidepressants target the serotonin transporter (SERT) by inhibiting serotonin reuptake. Structural and biochemical studies aiming to understand binding of small-molecules to conformationally dynamic transporters like SERT often require thermostabilizing mutations and antibodies to stabilize a specific conformation, leading to questions about relationships of these structures to the bonafide conformation and inhibitor binding poses of wild-type transporter. To address these concerns, we determined the structures of ∆N72/∆C13 and ts2-inactive SERT bound to paroxetine analogues using single-particle cryo-EM and x-ray crystallography, respectively. Read More

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http://dx.doi.org/10.7554/eLife.56427DOI Listing

Exploitation of the New Reactivity of Vinylcyclopropanes for Palladium-Catalyzed, Asymmetric [5+2] Dipolar Cycloadditions.

Angew Chem Int Ed Engl 2020 Jul 3. Epub 2020 Jul 3.

Central China Normal University, College of Chemistry, CHINA.

Vinylcyclopropanes (VCPs) are commonly used in transition metal-catalyzed cycloadditions, and the exploitation of their recently realized reactivities to construct new cyclic architectures is of great significance in modern synthetic chemistry. Herein, a palladium-catalyzed, visible light-driven, asymmetric [5+2] cycloaddition of VCPs with α-diazoketones was first accomplished by switching the reactivity of the Pd-containing dipolar intermediates from all-carbon 1,3-dipoles to oxo-1,5-dipoles. Enantioenriched 7-membered lactones were produced with good reaction efficiency and selectivity (23 examples, 52-92% yields with up to 99:1 er and 12. Read More

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http://dx.doi.org/10.1002/anie.202006366DOI Listing